Gastroenterology Today Summer 2023
Gastroenterology Today Summer 2023
Gastroenterology Today Summer 2023
Create successful ePaper yourself
Turn your PDF publications into a flip-book with our unique Google optimized e-Paper software.
Volume 33 No. 2<br />
<strong>Summer</strong> <strong>2023</strong><br />
Passionate about Endoscopy?<br />
We are clearing NHS trust waiting lists<br />
one weekend at a time, and<br />
we need your help<br />
18 Week Support <strong>Gastroenterology</strong>:<br />
Building Expert Teams
Better Resource<br />
Management<br />
for Digestive<br />
Disease Pathways<br />
Quantum Blue ® for Point of<br />
Care helps triage patients<br />
in clinic giving results in a<br />
rapid time frame (15 mins)<br />
Calprotectin Testing<br />
Make more informed<br />
clinical decisions without<br />
waiting for lab results.<br />
IBDoc ® Home Tests. Supporting<br />
remote patient monitoring and<br />
virtual clinics<br />
Faecal Immunochemical Testing<br />
Complete bespoke solutions to triage patients<br />
within the colorectal cancer pathway.<br />
New kit ordering portal for<br />
convenient logistics<br />
Customised FIT Kits delivered to patient<br />
‘ready to use’ – everything the patient<br />
requires to take their sample safely at<br />
home for return to a laboratory<br />
19 TH – 22 ND JUNE<br />
COME AND<br />
SEE US ON<br />
STAND B17<br />
Supplied by<br />
For more information, to discuss your requirements or organise an<br />
evaluation please contact: digestivedx@alphalabs.co.uk<br />
T: +44 (0)23 8048 3000<br />
E: sales@alphalabs.co.uk<br />
W: www.alphalabs.co.uk<br />
02380 483000 • sales@alphalabs.co.uk • www.alphalabs.co.uk
CONTENTS<br />
CONTENTS<br />
4 EDITORS COMMENT<br />
6 FEATURE Evaluation of non-gastric upper gastrointestinal<br />
system polyps: an epidemiological assessment<br />
13 FEATURE Evaluation of gut microbiota of Iranian patients<br />
with celiac disease, non-celiac wheat sensitivity,<br />
and irritable bowel syndrome: are there any<br />
similarities?<br />
29 COMPANY NEWS<br />
COVER STORY<br />
18 Week Support is the leading insourcing provider in the UK, partnering with<br />
trusts to address their waiting lists by optimising the utilisation of their theatres<br />
and clinics. Although we cover a wide range of specialties, our emphasis lies in<br />
Endoscopy and <strong>Gastroenterology</strong>, where we strive to ensure the highest quality<br />
of care for our patients.<br />
After Covid 19, the number of patients waiting more than 6 weeks for<br />
endoscopies, gastroscopies and flexible sigmoidoscopies rose dramatically,<br />
from 9.3% in February 2020 to 67.6% in May 2020. Since then, the NHS has<br />
been working tirelessly to address the influx of patients waiting for procedures,<br />
although this has not been easy. In March <strong>2023</strong>, the percentage of patients<br />
waiting more than 6 weeks for this procedure was 37.5%; still far greater than<br />
the 5% aim set out by the NHS <strong>2023</strong>/2024 Operating Plan.<br />
This issue edited by:<br />
Andrew Poullis<br />
c/o Media Publishing Company<br />
Greenoaks<br />
Lockhill<br />
Upper Sapey, Worcester, WR6 6XR<br />
ADVERTISING & CIRCULATION:<br />
Media Publishing Company<br />
Greenoaks, Lockhill<br />
Upper Sapey, Worcester, WR6 6XR<br />
Tel: 01886 853715<br />
E: info@mediapublishingcompany.com<br />
www.MediaPublishingCompany.com<br />
PUBLISHING DATES:<br />
March, June, September and December.<br />
COPYRIGHT:<br />
Media Publishing Company<br />
Greenoaks<br />
Lockhill<br />
Upper Sapey, Worcester, WR6 6XR<br />
PUBLISHERS STATEMENT:<br />
The views and opinions expressed in<br />
this issue are not necessarily those of<br />
the Publisher, the Editors or Media<br />
Publishing Company.<br />
Next Issue Autumn <strong>2023</strong><br />
Designed in the UK by me&you creative<br />
While progress has been made since Covid 19, recent data points to a<br />
potential increase in patients waiting more than 6 weeks for these procedures.<br />
We believe that the solution to this problem lies in maximising the use of<br />
existing capacity in addition to the new capacity created by the government as<br />
it continues to invest in community diagnostics centres.<br />
We need to support the NHS in transforming its model to a seven-day<br />
service to tackle this problem thereby making full use of the existing capacity.<br />
Insourcing can achieve this by providing flexible workforce models and making<br />
better use of the capacity already available within the NHS.<br />
GASTROENTEROLOGY TODAY - SUMMER <strong>2023</strong><br />
3
EDITORS COMMENT<br />
EDITORS COMMENT<br />
GASTROENTEROLOGY TODAY - SUMMER <strong>2023</strong><br />
“Over the<br />
years a<br />
number<br />
of Nobel<br />
prize<br />
winners<br />
for<br />
medicine<br />
have<br />
originated<br />
in<br />
Liverpool<br />
or carried<br />
out their<br />
early<br />
works in<br />
this city.”<br />
Liverpool <strong>2023</strong><br />
Eurovision and BSG! Liverpool is having a busy <strong>2023</strong>. Although no home grown success<br />
in the Eurovision this year Liverpool is a city with a long history of awards and international<br />
successes. Ignoring the obvious footballing awards, in the field of science and medicine<br />
Liverpool has a long history.<br />
Over the years a number of Nobel prize winners for medicine have originated in Liverpool or<br />
carried out their early works in this city.<br />
Sir Ronald Ross in 1902 was recognised for his work on transmission of malaria.<br />
In 1932 Sir Charles Scott Sherrington was recognised as he defined the spinal reflex and<br />
defined synapses.<br />
More pertinent to gastroenterology was Professor Rodney Porter, who started his studies in<br />
Liverpool, and was awarded Nobel prize in 1972 determining the chemical structure of an<br />
antibody - an important first step in the field of biologic drug therapies which have become<br />
the cornerstone of IBD management.<br />
The BSG conference will showcase national and international work in its annual meeting in<br />
Liverpool.<br />
Andrew Poullis<br />
St George’s Hospital<br />
4
FEATURE<br />
EVALUATION OF NON-GASTRIC UPPER<br />
GASTROINTESTINAL SYSTEM POLYPS:<br />
AN EPIDEMIOLOGICAL ASSESSMENT<br />
Çağdaş Erdoğan*, Derya Arı, Bayram Yeşil, Kenan Koşar, Orhan Coşkun, İlyas Tenlik, Hasan Tankut Köseoğlu & Mahmut Yüksel<br />
Department of <strong>Gastroenterology</strong>, Ankara City Hospital, University of Health Sciences, Bilkent Avenue, Çankaya, 06800 Ankara, Turkey. *email: cagdas.erdogan@saglik.gov.tr;<br />
cagdas_edogan@hotmail.com Scientific Reports | (<strong>2023</strong>) 13:6168 https://doi.org/10.1038/s41598-023-33451-1<br />
Abstract<br />
Non-gastric upper gastrointestinal system polyps are detected rarely<br />
and mostly incidentally during upper gastrointestinal endoscopy. While<br />
the majority of lesions are asymptomatic and benign, some lesions<br />
have the potential to become malignant, and may be associated with<br />
other malignancies. Between May 2010 and June 2022, a total of<br />
127,493 patients who underwent upper gastrointestinal endoscopy<br />
were retrospectively screened. Among these patients, those who had<br />
polyps in the esophagus and duodenum and biopsied were included in<br />
the study. A total of 248 patients with non-gastric polyps were included<br />
in this study. The esophageal polyp detection rate was 80.00/100,000,<br />
while the duodenal polyp detection rate was 114.52/100,000. In<br />
102 patients (41.1%) with esophageal polyps, the mean age was<br />
50.6 ± 15.1, and 44.1% (n = 45) were male. The most common type<br />
of polyps was squamous papilloma (n = 61, 59.8%), followed by<br />
inflammatory papilloma (n = 18, 17.6%). In 146 patients (58.9%) with<br />
duodenal polyps, the mean age of patients was 58.3 ± 16.5, and 69.8%<br />
(n = 102) were male. Brunner’s gland hyperplasia, inflammatory polyp,<br />
ectopic gastric mucosa, and adenomatous polyp were reported to be<br />
the most prevalent types of polyps in the duodenum overall (28.1%,<br />
27.4%, 14.4%, and 13.7%, respectively). It is crucial to identify rare nongastric<br />
polyps and create an effective follow-up and treatment plan in<br />
the era of frequently performed upper gastrointestinal endoscopies. The<br />
epidemiological assessment of non-gastric polyps, as well as a followup<br />
and treatment strategy, are presented in this study.<br />
some lesions can be considered as premalignant. Since glycogenic<br />
acanthosis, the most prevalent polypoid lesion in the esophagus, has a<br />
frequency of 3.5–15%, a characteristic structure, and a benign nature,<br />
these lesions are simple to identify and don’t need to be biopsied or<br />
evaluated pathologically 3-5 . With a rate between 0.01% and 0.45%,<br />
esophageal squamous papilloma (Fig. 1) are relatively the most prevalent<br />
polypoid lesions in the esophagus 6,7 . It is mostly seen in patients<br />
around 50 years of age, in the distal esophagus and as a single lesion 8 .<br />
Although most papilloma are asymptomatic, dysphagia due to large<br />
papilloma has been reported rarely 9 . Esophageal papillomas are followed<br />
in incidence by inflammatory polyps 10 , esophageal parakeratosis 11 ,<br />
and esophageal adenomas 12-14 that develop on the basis of Barrett’s<br />
esophagus and carry malignant potential.<br />
Lymphangiomas 15 and neuroendocrine tumors that originate from the<br />
submucosa are other esophageal lesions that can come across. These<br />
lesions can, however, only be found extremely rare. Neuroendocrine<br />
tumors can be seen in the pancreas or tubular organs of the GI<br />
system and show neuroendocrine differentiation. Endoscopically,<br />
neuroendocrine tumors of the digestive tract can present as polypoid<br />
forms, nodules, masses, ulcers, or stenosis, and they can be single or<br />
multiple and range in size from a few millimeters to several centimeters.<br />
These tumors, which are rare in the esophagus (only 50 cases have<br />
been documented), typically form sessile polypoid structures in the<br />
lower third 16 .<br />
GASTROENTEROLOGY TODAY - SUMMER <strong>2023</strong><br />
6<br />
Introduction<br />
Upper gastrointestinal endoscopy (esophagogastroduodenoscopy,<br />
EGD) includes evaluation of the oropharynx, esophagus, stomach, and<br />
proximal duodenum. EGD can be performed with indications such as<br />
dyspeptic complaints unresponsive to medical treatment, presence<br />
of alarm symptoms, upper gastrointestinal symptoms after the age of<br />
50, dysphagia, persistent vomiting, or upper gastrointestinal bleeding.<br />
Polyps are mostly detected incidentally during upper gastrointestinal<br />
endoscopy. However, management and appropriate pathological<br />
evaluation of polyps are very important 1,2 .<br />
Many benign lesions can be encountered during the endoscopic<br />
evaluation of the esophagus. Most lesions are rare and asymptomatic.<br />
Although most of these lesions do not have malignant potential,<br />
Duodenal polyps are generally quite rare and can be classified as nonneoplastic<br />
and neoplastic. Based on the respective incidence, nonneoplastic<br />
lesions include ectopic gastric mucosa, inflammatory polyps,<br />
Brunner’s gland hyperplasia, peutz-jeghers polyps, and hyperplastic<br />
polyps. Whereas, neoplastic lesions include adenomas, gastrointestinal<br />
stromal tumors, Brunner’s gland adenoma, carcinoid tumors,<br />
leiomyoma, lipoma, schwannoma can be counted. Duodenal adenomas<br />
(Figs. 2, 3) have three major types: villous adenomas, tubular adenomas,<br />
and Brunner’s gland adenomas. Villous adenomas carry a significant<br />
risk of malignancy. Since the incidence of colon adenomas increases in<br />
patients with duodenal polyps, colonoscopy should be performed when<br />
these polyps are detected 17 .<br />
Tubular adenomas are more common in the duodenum, are mostly<br />
asymptomatic and have less malignant potential. Brunner’s gland<br />
adenomas are rare small intestinal polyps that are more common,
FEATURE<br />
In this study we aimed to evaluate the epidemiological distribution of<br />
polyps detected during EGD and submitted to pathological assessment<br />
by biopsy, as well as the follow-up and treatment strategy in polyps with<br />
malignant potential or symptomatic.<br />
Patients/material and methods<br />
Figure 1. Esophageal squamous papilloma.<br />
Our study was approved by Ankara City Hospital Scientific Research<br />
Evaluation and Ethics Committee (Approval No: E1-22-2328). The<br />
procedures implemented until February 2019 were carried out at Ankara<br />
Turkey Yüksek İhtisas Training and Research Hospital. Since Ankara<br />
Turkey Yüksek İhtisas Training and Research Hospital joined the Ankara<br />
City Hospital after February 2019, the patients included in the study after<br />
this date were selected among the patients followed up and treated at<br />
Ankara City Hospital.<br />
Between May 2010 and June 2022, a total of 127,493 patients who<br />
underwent upper gastrointestinal endoscopy with indications such as<br />
dyspepsia, dysphagia, and iron deficiency anemia were retrospectively<br />
screened. Among these patients, those who had polyps in the<br />
esophagus and duodenum and biopsied were included in the study.<br />
Figure 2. Duodenal adenomatous polyp.<br />
In patients who underwent EGD, biopsy or excision was performed on<br />
all polyps detected in the esophagus that were solitary or larger than<br />
1 cm. All patients with Barrett’s esophagus discovered to have polyps<br />
underwent biopsies. When dysplasia clusters are observed rather<br />
than a single polyp formation in Barrett’s esophagus, which is where<br />
the majority of esophageal adenomas arise from, the vascular pattern<br />
was assessed with NBI endoscopy, and a biopsy was collected for<br />
esophageal adenoma. In addition, biopsies or excisions were performed<br />
on hyperemic polyps, polyps with aberrant vascular patterns on narrowband<br />
imaging (NBI) endoscopy, and ulcerated polyps. However, no<br />
biopsy was performed when multiple instances of glycogenic acanthosis<br />
were found. In case of detection of polyps in the duodenum, polyps<br />
were biopsied or excised from all patients.<br />
Figure 3. Duodenal adenomatous polyp magnified.<br />
accounting for 10.6% of duodenal tumors 18 . Ectopic gastric mucosa may<br />
present as polypoid lesions which are rare congenital disorders and are<br />
detected incidentally during upper GI endoscopy. It has been reported<br />
in the literature that heterotopic gastric mucosa may be associated with<br />
duodenal ulcers 19 . Gastrointestinal stromal tumors (GIST) are mostly<br />
encountered in the stomach, they can also be seen in the esophagus<br />
(< 1%) and duodenum (5%) 20 . Tumors originating from the upper GI may<br />
present with dysphagia, GI bleeding, or obstructive jaundice.<br />
Duodenal or ampullary NETs are extremely rare and account for<br />
approximately 2.6% of all NETs 21 . These tumors are of clinical<br />
importance as most of them are asymptomatic and potentially<br />
malignant. They typically occur in the I and II duodenal sections,<br />
preferring the peripapillary region, and under endoscopic vision, they<br />
show as a single, small lesion (frequently less than 1 cm in size).<br />
Additionally, they may exist in groups or be linked to neuroendocrine<br />
tumors in other organs 16 .<br />
Patients who had polyps but could not be biopsied due to<br />
antiaggregant/anticoagulant use, hemodynamic instability, and patient<br />
intolerance were excluded from the study. In addition, patients with<br />
gastric polyps were also excluded. Additionally, patients with esophageal<br />
polyps who underwent biopsies and who, upon pathologic inspection,<br />
revealed to have glycogenic acanthosis were removed from the study.<br />
Patients’ demographic characteristics such as age, gender, smoking,<br />
history of comorbid diseases and drug use were recorded. Polyp sizes,<br />
polyp types, number of polyps and histopathological findings were<br />
recorded in patients who were found to have esophageal and duodenal<br />
polyps and biopsied. Additionally, antrum biopsies were performed to check<br />
for H. pylori in patients with polyps. The pathologists stained the tissue<br />
samples with Giemsa and tested for the presence of H. pylori. Patients<br />
with helicobacter pylori positivity as a result of pathology were separately<br />
identified. According to the pathology results, whether the patients<br />
had reflux findings in their histories, whether they had a history of head<br />
and neck cancer, and previous endoscopic and colonoscopy findings,<br />
if any, were evaluated. The frequency per 100,000 of esophageal and<br />
duodenal polyps detected in the patients was reported. The pathological<br />
distributions of the polyps were also displayed as a rate per 100,000.<br />
GASTROENTEROLOGY TODAY - SUMMER <strong>2023</strong><br />
7
FEATURE<br />
In patients undergoing colonoscopy the cleanliness of the colonoscopy<br />
was evaluated using the Boston Bowel Preparation Scale (BBPS).<br />
Following colonoscopy cleaning, patients with BBPS 0 or 1 were taken<br />
for another colonoscopy. Colonoscopy cleanliness scores BBPS 2 and 3<br />
were used to assess all study participants who had non-gastric polyps.<br />
Withdrawal from the colonoscopy took at least 10 min.<br />
Endoscopic evaluation was performed with Olympus brand GIF-Q260<br />
model gastroscopes. Before the procedure, patients were given<br />
sedo-analgesia or topical anesthetic containing 10% lidocaine to the<br />
oropharynx, accompanied by an anesthesiologist. The lesions were<br />
removed with forceps or snare. The biopsy material was fixed with 10%<br />
formaldehyde solution and sent for pathological evaluation.<br />
Statistical analysis<br />
All statistical analyzes were performed using SPSS software (SPSS<br />
for Windows, version 25.0, IBM. Corp., Armonk, NY, USA). The<br />
Kolmogorov–Smirnov test was used to determine the normality of the<br />
continuous variables. Normally distributed variables were expressed<br />
as mean ± standard deviation and non-normally distributed variables<br />
as median and interquartile range. Normally distributed variables<br />
were compared using the student t test and non-normally distributed<br />
variables using the Mann–Whitney U test. Chi-square (χ 2 ) test and<br />
Fisher’s Exact test were used for group comparisons (cross tables)<br />
of nominal variables. Two-tailed p values < 0.05 were considered<br />
statistically significant.<br />
Ethics committee approval<br />
This study was complied with the ethical guidelines of the 1975 Helsinki<br />
Declaration that was then modified in 2008. The study protocol was<br />
approved by Ankara City Hospital ethics committee (Approval No: E1-<br />
22-2328).<br />
Informed consent<br />
Informed consent was obtained from all patients participating in the<br />
study.<br />
All patients (n = 102)<br />
Age, years 50.6 ± 15.1 –<br />
Gender, male, n (%) 45 (44.1) –<br />
Smoking, n (%) 56 (54.9) –<br />
Polyp size, mm 5.0 (4.0–7.0) –<br />
Number of polyps 1.0 (1.0–1.0) –<br />
Polyp type, n (%)<br />
Pedunculated 65 (63.7) –<br />
Sessile 37 (36.3) –<br />
Pathology, n (%)<br />
Squamous papilloma 65 (63.7) 50.98<br />
Inflammatory polyp 21 (20.7) 16.47<br />
Hyperplastic polyp 3 (2.9) 2.35<br />
Lymphangioma 3 (2.9) 2.35<br />
Esophageal parakeratosis 6 (5.9) 4.70<br />
Esophageal adenoma 4 (3.9) 3.14<br />
Helicobacter pylori, n (%) 26 (25.5) –<br />
Reflux esophagitis, n (%) 17 (16.7) –<br />
Other endoscopic findings, n (%)<br />
Normal 8 (7.8) –<br />
Antral gastritis 31 (30.4) –<br />
Bulbitis 3 (2.9) –<br />
Pangastritis 49 (48.0) –<br />
Antral gastritis + bulbitis 9 (8.9) –<br />
Gastric lymphoma 2 (2.0) –<br />
Colonoscopy, n (%) 76 (74.5) –<br />
Colon polyp localization, n (%)<br />
Transverse + ascending + sigmoid 3 (2.9) –<br />
Transverse + ascending + rectum 3 (2.9) –<br />
Descending + transverse 4 (3.9) –<br />
Rectum 5 (4.9) –<br />
Colon polyp pathology, n (%)<br />
Adenomatous 15 (14.7) –<br />
Rate per 100,000 patients<br />
Table Table 1. 1. Demographic characteristics, endoscopic endoscopic and and colonoscopy colonoscopy findings, and pa<br />
of patients findings, with and esophageal pathological polyps, evaluations pathologic of patients findings with as esophageal rate per 100,000 patients. D<br />
median polyps, ± SD pathologic or median findings (IQR) or as frequency rate per 100,000 (%). SD patients. standard Data deviation. are<br />
expressed as median ± SD or median (IQR) or frequency (%).<br />
SD standard deviation.<br />
GASTROENTEROLOGY TODAY - SUMMER <strong>2023</strong><br />
Results<br />
Vol:.(1234567890)<br />
A total of 248 patients who were evaluated for non-gastric polyps<br />
were included in this study. Total evaluation revealed a detection rate<br />
of 194.52 non-gastric polyps per 100,000 patients. In this context,<br />
the esophageal polyp detection rate was 80.00 per 100,000, while<br />
the duodenal polyp detection rate was 114.52 per 100,000.<br />
One hundred and two (41.1%) of the included patients were those<br />
with esophageal polyps. The mean age of patients with esophageal<br />
polyps was 50.6 ± 15.1, and 44.1% (n = 45) were male. The median<br />
size of esophageal polyps was 5.0 (4.0–7.0) mm. Pedunculated<br />
polyps were seen in 63.7% of cases (n = 65), while sessile polyps<br />
were found in 36.3% of cases (n = 37). The most common type<br />
of polyps was squamous papilloma (n = 65, 63.7%), followed by<br />
inflammatory papilloma (n = 18, 17.6%). Helicobacter pylori was<br />
found in 26 (25.5%) and reflux esophagitis in 21 (20.7%) patients.<br />
The most common endoscopic gastric finding was pangastritis<br />
(n = 49, %48.0) followed by antral gastritis (n = 31, %30.4).<br />
Adenomatous polyps were detected in 15 of 76 patients with<br />
esophageal polyps who underwent colonoscopy. Table 1 includes<br />
demographic information as well as endoscopic and colonoscopic<br />
findings, pathology results, and epidemiological rates of patients<br />
with esophageal polyps.<br />
When patients with duodenal polyps were evaluated (n = 146),<br />
polyps were observed in the duodenal bulb in 91 patients (62.3%)<br />
and in the second part of the duodenum (D2) in 55 patients (37.7%).<br />
The mean age of patients with duodenal polyps was 58.3 ± 16.5,<br />
and 69.8% (n = 102) were male. The median size of duodenal polyps<br />
was 7.0 (3.5–15.0) mm. Brunner’s gland hyperplasia, inflammatory<br />
polyp, ectopic gastric mucosa, and adenomatous polyp were<br />
reported to be the most prevalent types of polyps in the duodenum<br />
overall (28.1%, 27.4%, 14.4%, and 13.7%, respectively). In<br />
subgroup analysis Brunner’s gland hyperplasia was most common<br />
in bulbus (36%), while adenomatous polyp was most common in D2<br />
(bulbus vs. D2; 2 vs. 18; p < 0.001). All polyps with adenomatous<br />
pathology were detected in the second continent of the duodenum,<br />
whereas individuals with ectopic gastric mucosa as a result of<br />
pathology had polyp localization in the first continent (p0.00.1 for<br />
both findings). The presence of antral gastritis, bulbitis, duodenitis,<br />
8
FEATURE<br />
pangastritis, pangastritis + bulbitis, atrophic gastritis, FAP, gastric<br />
cancer and peutz-jeghers syndrome was at similar rates between<br />
both groups. In addition, colonoscopy was performed in 88 (%60.3)<br />
patients with polyps in the duodenum, and polyps were detected in<br />
the colon in 35 (%24) of them. While hyperplastic polyp was found<br />
in the colon in two patients with polyp in the bulbus, adenomatous<br />
polyp was detected in the colon in the 33 patients and in all patients<br />
with polyps in the second part of the duodenum. Table 2 includes<br />
demographic information as well as endoscopic and colonoscopic<br />
findings, pathology results, and epidemiological rates of patients<br />
with duodenal polyps.<br />
All patients (n = 146)<br />
Age, years 58.3 ± 16.5 –<br />
Gender, male, n (%) 102 (69.8) –<br />
Smoking, n (%) 81 (55.5) –<br />
Polyp size, mm 7.0 (3.5–15.0) –<br />
Number of polyps 1.0 (1.0–2.5) –<br />
Polyp localization, n (%)<br />
Duodenal bulb 91 (62.3) 71.38<br />
Second part of the duodenum (D2) 55 (37.7) 43.14<br />
Pathology, n (%)<br />
Brunner gland hyperplasia 41 (28.1) 32.16<br />
Ectopic gastric mucosa 21 (14.4) 16.47<br />
Inflammatory polyp 40 (27.4) 31.37<br />
Villous adenoma 4 (2.7) 3.14<br />
Neuroendocrine tumor 3 (2.1) 2.35<br />
Tubular adenoma 4 (2.7) 3.14<br />
Hyperplastic polyp 7 (4.8) 5.49<br />
Adenomatous polyp 20 (13.7) 15.69<br />
Hamartomatous polyp 6 (4.1) 4.71<br />
Helicobacter pylori, n (%) 14 (9.6) –<br />
Other endoscopic findings, n (%)<br />
Antral gastritis 50 (34.2) –<br />
Duodenal ulcer 13 (8.8) –<br />
Duodenitis 3 (2.1) –<br />
Pangastritis 64 (43.8) –<br />
Pangastritis + bulbitis 5 (3.4) –<br />
Atrophic gastritis 3 (2.1) –<br />
FAP 3 (2.1) –<br />
Gastric CA 3 (2.1) –<br />
Peutz-jeger 2 (1.4) –<br />
Colonoscopy, n (%) 88 (60.3)<br />
Detection of polyps in colonoscopy, n (%) 35 (24.0) –<br />
Colon polyp localization, n (%)<br />
Rectosigmoid 22 (15.1) –<br />
Other colonic parts 13 (8.9) –<br />
Polyp type, n (%)<br />
Rate per 100,000 patients<br />
In our study, esophageal adenocarcinoma was diagnosed in 6<br />
individuals who underwent biopsies following the discovery of an<br />
esophageal polypoid lesion. Two of the individuals who were found<br />
to have duodenal polypoid lesions had a biopsy, which revealed<br />
duodenal adenocarcinoma. All malignant esophageal and duodenal<br />
lesions were ulcero-vegetative and fragile in appearance, and they<br />
were all assessed separately from benign esophageal lesions.<br />
Discussion<br />
As the frequency of performing upper GI endoscopy increases in<br />
the world, the detection of non-gastric polyps has also increased.<br />
Although gastric polyps can be assessed more easily due to their<br />
frequency, non-gastric polyps cannot be recognized adequately<br />
due to their rarity. These polyps may be benign, as well as they<br />
may carry the risk of malignancy, and may be an indicator of an<br />
accompanying malignancy. In this study we sought to assess the<br />
prevalence of non-gastric polyps in the general population, their<br />
distribution by localization, their clinical significance, and follow-up<br />
and treatment approaches. Our research revealed that 194.52 out of<br />
100,000 upper GI endoscopies discovered non-gastric polyps. When<br />
assessed according to polyp localization, the rate of esophageal<br />
polyp identification was 80.00 per 100,000, whereas the rate of<br />
duodenal polyp detection was 114.52 per 100,000. Squamous<br />
papilloma, inflammatory papilloma, and esophageal parakeratosis are<br />
the most frequently detected esophageal polyps (50.98, 16.47, and<br />
4.70 per 100,000, respectively), whereas Brunner gland hyperplasia,<br />
inflammatory polyp, ectopic gastric mucosa, and adenomatous polyp<br />
are the most frequently detected duodenal polyps (32.16, 31.37,<br />
16.47, and 15.69 per 100,000, respectively,).<br />
Bulur et al. 22 evaluated 19,560 patients and found non-gastric polyps<br />
in 38 of them. In our study, 127,493 patients were evaluated, and<br />
248 non-gastric polyps were detected. Total evaluation revealed a<br />
detection rate of 194.52 non-gastric polyps per 100,000 patients.<br />
We were able to report the incidence rate in 100,000 patients as an<br />
epidemiological data for rare non-gastric polyps as a result of our<br />
study because of the large patient group we screened.<br />
Hyperplastic 2 (1.4) –<br />
Adenomatous 33 (22.6) –<br />
In the series of Szanto et al. 7 evaluating 35-year upper gastrointestinal<br />
endoscopies, nearly 60,000 upper GI endoscopy was performed,<br />
Table Table 2. 2. Demographic characteristics, characteristics, endoscopic endoscopic and colonoscopy and colonoscopy findings, and pathological and squamous evaluations papilloma was detected in 155 patients. None of<br />
of patients findings, with and duodenal pathological polyps, evaluations pathologic findings of patients as rate with per duodenal 100,000 patients. Data are expressed as<br />
median polyps, ± SD pathologic or median (IQR) findings or frequency as rate per (%). 100,000 SD standard patients. deviation. Data are<br />
expressed as median ± SD or median (IQR) or frequency (%).<br />
SD standard deviation.<br />
these have turned into malignancies. Mosca et al. 9 examined 7618<br />
upper GI endoscopy procedures and detected squamous papilloma<br />
in 9 patients. In our study, squamous papilloma was detected in 65<br />
of 127,493 patients evaluated over a 12-year period. Looking at the<br />
studies in the literature, the rate of detecting squamous papilloma<br />
in upper GIS endoscopy has been reported between 0.045 and<br />
0.26% 6,7,9 . Consistently with the literature, this rate was found 50.98<br />
per 100,000 patients in our study. None of the patients developed<br />
malignancy during their mean follow-up of 3.2 years. In a case<br />
presented by Kostiainen et al. 23 , the patient had the symptoms<br />
of dysphagia and vomiting due to large squamous papilloma.<br />
In our study, 63 of 65 patients with squamous papillomas were<br />
asymptomatic, while squamous papilloma larger then 20 mm was<br />
detected in two patient who had intermittent nausea and vomiting.<br />
Mandard et al. 24 found accompanying esophageal parakeratosis in<br />
approximately 40% of 400 patients, newly diagnosed with head and<br />
neck squamous cell carcinoma. However, no malignancy was found to<br />
originate from the parakeratotic area in the esophagus. In our study, 4<br />
Vol.:(0123456789)<br />
of 6 patients (66.6%) with esophageal parakeratosis had a history of<br />
squamous cell head and neck cancer (larynx and hypopharynx). In the<br />
light of these findings, it would be appropriate to screen the patients<br />
for possible head and neck malignancies in the case of esophageal<br />
parakeratosis detected incidentally in upper GI endoscopy.<br />
GASTROENTEROLOGY TODAY - SUMMER <strong>2023</strong><br />
9
FEATURE<br />
Esophageal adenomas typically present as wide islets of dysplasia rather<br />
than a single polyp and typically develop in the presence of Barrett’s<br />
esophagus. In a case series presented by Wong et al. 13 , polypoid<br />
lesions developing on the ground of Barrett’s esophagus, with dysplastic<br />
adenomas and adenocarcinomas found in the pathology were evaluated.<br />
In our study, esophageal adenoma was detected in four patients and all<br />
four also had Barrett’s esophagus. These patients underwent surgical<br />
esophagectomy afterward. The risk of adenocarcinoma is quite high<br />
in patients with Barrett’s esophagus and accompanying adenoma in<br />
the esophagus, and these patients should be evaluated further, and<br />
the lesion should be removed endoscopically or surgically. Due to the<br />
presence of Barrett’s esophagus in these patients, mucosectomy or<br />
ablation procedures for the disease should be integrated into endoscopic<br />
treatment strategies in addition to polyp excision. An esophagectomy is a<br />
surgical option in which the patient’s polyp and esophagus segment are<br />
removed together, and the small intestine or stomach is anastomosed.<br />
Europe. In addition to being an epidemiological study with a large<br />
patient group to evaluate, our study also offers suggestions for the best<br />
examination and treatment approaches to use when non-gastric polyps<br />
are found. The epidemiological study we conducted is the largest on<br />
non-gastric polyps ever published in the world’s literature.<br />
In conclusion, nowadays, with the widespread utilization upper GI<br />
system endoscopy, it is critical to recognize, monitor, and treat common<br />
lesions as well as less frequent but clinically significant lesions. Our<br />
study is not only the broadest evaluation of non-gastric polyps, but it<br />
also provides clinical approach recommendations for these polyps and<br />
discloses the prevalence of these polyps in the general population.<br />
Data availability<br />
The datasets used and/or analyzed during the current study available<br />
from the corresponding author on reasonable request.<br />
GASTROENTEROLOGY TODAY - SUMMER <strong>2023</strong><br />
Levine et al. 25 evaluated 27 patients with Brunner gland hyperplasia<br />
detected in the duodenum, and GIS bleeding was found in 10 of the<br />
patients, obstruction in 10, and incidentally in 7 patients. In our study,<br />
Brunner’s gland hyperplasia was detected in the duodenum in 41<br />
patients with 21 of them having GI bleeding and 9 signs of obstruction.<br />
It was detected incidentally in 11 of them. Although Brunner’s gland<br />
hyperplasia are benign lesions, they should be treated as they may have<br />
clinical symptoms. We treated all patients endoscopically, except for one<br />
patient with obstruction. In the long-term follow-up, the patients were<br />
observed up as stable.<br />
Ectopic gastric mucosa are benign lesions that can be detected incidentally<br />
in the duodenum. Naguchi et al. 19 found ectopic gastric mucosa in 76 (55%)<br />
of 137 patients with duodenal ulcer, and Helicobacter pylori was detected in<br />
59% (45/76) of the biopsies taken from them. In our study, duodenal ulcer<br />
was detected in 12 (57.1%) of 21 patients with ectopic gastric mucosa, and<br />
HP positivity was observed in 13 (61.9%) of them.<br />
Sporadic duodenal adenomas are very rare and have the potential to<br />
transform into adenocarcinoma by showing similar morphological and<br />
molecular features with colorectal adenomas. The majority of sporadic<br />
duodenal adenomas are flat or sessile solitary lesions with pearly villi<br />
surfaces that develop on the descending duodenum’s posterior or lateral<br />
walls 26 . Witterman et al. 17 showed that 42% of patients with duodenal<br />
villous adenoma had malignant cells. In addition, it was shown that the<br />
rate of detecting concomitant colon adenoma is increased in these<br />
patients. In our study, all 20 adenomas detected in the duodenum<br />
originated from the second part of the duodenum, and malignant cells<br />
were detected in 1 of 4 villous adenomas. Again, 17 (85.0%) of these<br />
patients had adenomatous polyps in the colon. When polyps are found<br />
in the duodenum, they should be removed via snare polypectomy,<br />
endoscopic mucosal resection (EMR), endoscopic submucosal<br />
dissection (ESD), or argon plasma coagulation (APC) ablation due to<br />
their potential for malignancy. Then again, based on these findings, it<br />
would be a reasonable approach to be careful in terms of malignancy<br />
in patients with adenomatous polyps in the duodenum and to perform<br />
colon screening in these patients.<br />
With a bed capacity of 3600 patients and more than 300 endoscopic<br />
procedures carried out each day, our center has the title of largest<br />
institution in Turkey and one of the three largest institutes in all of<br />
Received: 20 December 2022; Accepted: 13 April <strong>2023</strong><br />
Published online: 15 April <strong>2023</strong><br />
References<br />
1. Hirota, W. K. et al. ASGE guideline: The role of endoscopy in<br />
the surveillance of premalignant conditions of the upper GI tract.<br />
Gastrointest. Endosc. 63, 570 (2006).<br />
2. ASGE Standards of Practice Committee et al. Endoscopic mucosal<br />
tissue sampling. Gastrointest. Endosc. 78, 216 (2013).<br />
3. Vadva, M. D. & Triadafilopoulos, G. Glycogenic acanthosis of the<br />
esophagus and gastroesophageal reflux. J. Clin. Gastroenterol. 17,<br />
79 (1993).<br />
4. Ghahremani, G. G. & Rushovich, A. M. Glycogenic acanthosis of<br />
the esophagus: Radiographic and pathologic features. Gastrointest.<br />
Radiol. 9, 93 (1984).<br />
5. Stern, Z. et al. Glycogenic acanthosis of the esophagus. A benign<br />
but confusing endoscopic lesion. Am. J. Gastroenterol. 74, 261<br />
(1980).<br />
6. Sablich, R., Benedetti, G., Bignucolo, S. & Serraino, D. Squamous<br />
cell papilloma of the esophagus. Report on 35 endoscopic cases.<br />
Endoscopy 20, 5 (1988).<br />
7. Szántó, I. et al. Squamous papilloma of the esophagus. Clinical and<br />
pathological observations based on 172 papillomas in 155 patients.<br />
Orv. Hetil. 146, 547 (2005).<br />
8. Carr, N. J., Monihan, J. M. & Sobin, L. H. Squamous cell papilloma<br />
of the esophagus: A clinicopathologic and follow-up study of 25<br />
cases. Am. J. Gastroenterol. 89, 245 (1994).<br />
9. Mosca, S. et al. Squamous papilloma of the esophagus: Long-term<br />
follow up. J. Gastroenterol. Hepatol. 16, 857 (2001).<br />
10. LiVolsi, V. A. & Perzin, K. H. Inflammatory pseudotumors<br />
(inflammatory fibrous polyps) of the esophagus. A clinicopathologic<br />
study. Am. J. Dig. Dis. 20, 475 (1975).<br />
11. Guelrud, M., Herrera, I. & Eggenfeld, H. Compact parakeratosis of<br />
esophageal mucosa. Gastrointest. Endosc. 51, 329 (2000).<br />
12. Lee, R. G. Adenomas arising in Barrett’s esophagus. Am. J. Clin.<br />
Pathol. 85, 629 (1986).<br />
13. Wong, R. S. et al. Multiple polyposis and adenocarcinoma arising in<br />
Barrett’s esophagus. Ann. Thorac. Surg. 61, 216 (1996).<br />
14. Adoke, K. U. et al. Hyperplastic polyps of the esophagus and<br />
esophagogastric junction with esophageal constriction—a<br />
case report. Pathology 46(Supplement 2), S81. https://doi.<br />
org/10.1097/01.PAT.0000454378.95070.60 (2014).<br />
15. Saers, T., Parusel, M., Brockmann, M. & Krakamp, B.<br />
Lymphangioma of the esophagus. Gastrointest. Endosc. 62, 181<br />
(2005).<br />
10
FEATURE<br />
16. Sivero, L. et al. Endoscopic diagnosis and treatment of<br />
neuroendocrine tumors of the digestive system. Open Med. 11(1),<br />
369–373. https://doi.org/10.1515/med-2016-0067 (2016).<br />
17. Witteman, B. J., Janssens, A. R., Griffioen, G. & Lamers, C. B.<br />
Villous tumours of the duodenum. An analysis of the literature with<br />
emphasis on malignant transformation. Neth. J. Med. 42, 5 (1993).<br />
18. Levine, J. A., Burgart, L. J., Batts, K. P. & Wang, K. K. Brunner’s<br />
gland hamartomas: Clinical presentation and pathological features<br />
of 27 cases. Am. J. Gastroenterol. 90, 290–294 (1995).<br />
19. Noguchi, H. et al. Prevalence of Helicobacter pylori infection rate<br />
in heterotopic gastric mucosa in histological analysis of duodenal<br />
specimens from patients with duodenal ulcer. Histol. Histopathol.<br />
35(2), 169–176. https://doi.org/10.14670/HH-18-142 (2020)<br />
(Epub 2019 Jul 2).<br />
20. Singhal, S. et al. Anorectal gastrointestinal stromal tumor: A case<br />
report and literature review. Case Rep. Gastrointest. Med. 2013,<br />
934875 (2013).<br />
21. Modlin, I. M., Lye, K. D. & Kidd, M. A 5-decade analysis of 13,715<br />
carcinoid tumors. Cancer 97, 934–959 (2003).<br />
22. Bulur, A. et al. Polypoid lesions detected in the upper<br />
gastrointestinal endoscopy: A retrospective analysis in 19560<br />
patients, a single-center study of a 5-year experience in Turkey.<br />
N. Clin. Istanb. 8(2), 178–185. https://doi.org/10.14744/<br />
nci.2020.16779 (2020).<br />
23. Kostiainen, S., Teppo, L. & Virkkula, L. Papilloma of the<br />
oesophagus. Report of a case. Scand. J. Thorac. Cardiovasc.<br />
Surg. 7(1), 95–97. https://doi.org/10.3109/14017437309139176<br />
(1973).<br />
24. Mandard, A. M. et al. Cancer of the esophagus and associated<br />
lesions: Detailed pathologic study of 100 esophagectomy<br />
specimens. Hum. Pathol. 15, 660 (1984).<br />
25. Levine, J. A., Burgart, L. J., Batts, K. P. & Wang, K. K. Brunner’s<br />
gland hamartomas: Clinical presentation and pathological features<br />
of 27 cases. Am. J. Gastroenterol. 90(2), 290–294 (1995).<br />
26. Ma, M. X. & Bourke, M. J. Management of duodenal polyps. Best<br />
Pract. Res. Clin. Gastroenterol. 31(4), 389–399 (2017).<br />
Author contributions<br />
Ç.E., M.Y.: conception, design, supervision, materials, data collection<br />
and processing, analysis and interpretation, literature review, writer<br />
and critical review. D.A., B.Y., K.K. O.C., İ.T., H.T.K.: materials, data<br />
collection and processing, analysis and interpretation, literature review<br />
and manuscript supervision.<br />
Competing interests<br />
The authors declare no competing interests.<br />
Additional information<br />
Correspondence and requests for materials should be addressed to Ç.E.<br />
Reprints and permissions information is available at<br />
www.nature.com/reprints.<br />
Publisher’s note Springer Nature remains neutral with regard to<br />
jurisdictional claims in published maps and institutional affiliations.<br />
Open Access This article is licensed under a Creative Commons<br />
Attribution 4.0 International License, which permits use, sharing,<br />
adaptation, distribution and reproduction in any medium or format, as<br />
long as you give appropriate credit to the original author(s) and the source,<br />
provide a link to the Creative Commons licence, and indicate if changes<br />
were made. The images or other third party material in this article are<br />
included in the article’s Creative Commons licence, unless indicated<br />
otherwise in a credit line to the material. If material is not included in the<br />
article’s Creative Commons licence and your intended use is not permitted<br />
by statutory regulation or exceeds the permitted use, you will need to<br />
obtain permission directly from the copyright holder. To view a copy of this<br />
licence, visit http:// creat iveco mmons. org/ licen ses/ by/4. 0/.<br />
© The Author(s) <strong>2023</strong><br />
WHY NOT WRITE FOR US?<br />
<strong>Gastroenterology</strong> <strong>Today</strong> welcomes the submission of<br />
clinical papers and case reports or news that<br />
you feel will be of interest to your colleagues.<br />
Material submitted will be seen by those working within all<br />
UK gastroenterology departments and endoscopy units.<br />
All submissions should be forwarded to info@mediapublishingcompany.com<br />
If you have any queries please contact the publisher Terry Gardner via:<br />
info@mediapublishingcompany.com<br />
GASTROENTEROLOGY TODAY - SUMMER <strong>2023</strong><br />
11
FEATURE<br />
Stronger Together<br />
Cantel, Key Surgical and Diagmed are now part of STERIS.<br />
Our companies share a commitment to provide the very best<br />
solutions for our Customers and we are excited to bring the<br />
power of our teams together, and to provide a more extensive<br />
and innovative suite of offerings to new and existing<br />
Customers around the world.<br />
The unique strength of our collective organisation will continue<br />
to uphold our mission of HELPING OUR CUSTOMERS CREATE<br />
A HEALTHIER AND SAFER WORLD.<br />
GASTROENTEROLOGY TODAY - SUMMER <strong>2023</strong><br />
Come join us<br />
at BSG!<br />
Stand A26<br />
The Arena<br />
12<br />
www.steris.com
FEATURE<br />
EVALUATION OF GUT MICROBIOTA OF IRANIAN<br />
PATIENTS WITH CELIAC DISEASE, NON-CELIAC WHEAT<br />
SENSITIVITY, AND IRRITABLE BOWEL SYNDROME:<br />
ARE THERE ANY SIMILARITIES?<br />
Kaveh Naseri 1 , Hossein Dabiri 2 , Meysam Olfatifar 3 , Mohammad Amin Shahrbaf 4 , Abbas Yadegar 5 , Mona Soheilian‐Khorzoghi 4 ,<br />
Amir Sadeghi 4 , Saeede Saadati 4 , Mohammad Rostami‐Nejad 4* , Anil K. Verma 6 and Mohammad Reza Zali 4<br />
Naseri et al. BMC <strong>Gastroenterology</strong> (<strong>2023</strong>) 23:15 https://doi.org/10.1186/s12876-023-02649-y<br />
Abstract<br />
Introduction<br />
Background and aims<br />
Individuals with celiac disease (CD), non-celiac wheat sensitivity<br />
(NCWS), and irritable bowel syndrome (IBS), show overlapping clinical<br />
symptoms and experience gut dysbiosis. A limited number of studies so<br />
far compared the gut microbiota among these intestinal conditions. This<br />
study aimed to investigate the similarities in the gut microbiota among<br />
patients with CD, NCWS, and IBS in comparison to healthy controls<br />
(HC).<br />
Materials and methods<br />
In this prospective study, in total 72 adult subjects, including CD (n = 15),<br />
NCWS (n = 12), IBS (n = 30), and HC (n = 15) were recruited. Fecal<br />
samples were collected from each individual. A quantitative real-time<br />
PCR (qPCR) test using 16S ribosomal RNA was conducted on stool<br />
samples to assess the relative abundance of Firmicutes, Bacteroidetes,<br />
Bifidobacterium spp., and Lactobacillus spp.<br />
Results<br />
In all groups, Firmicutes and Lactobacillus spp. had the highest and<br />
lowest relative abundance respectively. The phylum Firmicutes had<br />
a higher relative abundance in CD patients than other groups. On<br />
the other hand, the phylum Bacteroidetes had the highest relative<br />
abundance among healthy subjects but the lowest in patients with<br />
NCWS. The relative abundance of Bifidobacterium spp. was lower in<br />
subjects with CD (P = 0.035) and IBS (P = 0.001) compared to the HCs.<br />
Also, the alteration of Firmicutes to Bacteroidetes ratio (F/B ratio) was<br />
statistically significant in NCWS and CD patients compared to the HCs<br />
(P = 0.05).<br />
Conclusion<br />
The principal coordinate analysis (PCoA), as a powerful multivariate<br />
analysis, suggested that the investigated gut microbial profile of patients<br />
with IBS and NCWS share more similarities to the HCs. In contrast,<br />
patients with CD had the most dissimilarity compared to the other<br />
groups in the context of the studied gut microbiota.<br />
Keywords<br />
Celiac disease, Irritable bowel syndrome, Non-celiac wheat sensitivity,<br />
Gut microbiota, Dysbiosis<br />
The human gastrointestinal (GI) tract harbors an incredibly complex<br />
and abundant ensemble of microbes referred to as gut microbiota<br />
[1]. Gut microbiota plays a pivotal role in human health and<br />
diseases [2–4] and its composition depends on various factors,<br />
including age [5], diet [6], geography [7], malnourishment [8], race,<br />
ethnicity [9], and socioeconomic status [10]. Balance in the gut<br />
microbiota composition and the presence or absence of critical<br />
species capable of causing specific responses contribute to<br />
ensuring homeostasis in the intestinal mucosa and other organs<br />
[11–14]. An imbalanced or disturbed composition and quantity<br />
of the gut microbiota, known as dysbiosis [15], can affect the<br />
bacterial function and is associated with a variety of GI disorders<br />
[16–20]. Celiac disease (CD), non-celiac wheat sensitivity (NCWS),<br />
and irritable bowel syndrome (IBS), have intestinal dysbiosis as<br />
a causative factor in the initiation of their symptoms [21–24].<br />
CD is a chronic small intestinal inflammation, triggered by the<br />
consumption of gluten, resulting in villous atrophy in genetically<br />
susceptible individuals [25]. IBS is a functional gastrointestinal<br />
disorder that afflicts nearly 15% of the population worldwide,<br />
characterized by recurrent abdominal pain or discomfort, and<br />
changes in bowel habits, in the absence of any other disease to<br />
cause these symptoms [26, 27]. NCWS is still an unclear diagnosis,<br />
characterized by a combination of CD-like or IBS-like symptoms<br />
(e.g., diarrhea, abdominal pain, bloating), behavior disturbances,<br />
and systemic manifestations, related to the ingestion of gluten in<br />
subjects who are not affected by either CD or wheat allergy [28,<br />
29]. Therefore, since these three disorders are related to dysbiosis<br />
in gut microbiota and share similarities in their symptoms, these<br />
data form a hypothesis regarding the possible similarities in the<br />
alterations of the gut microbiota in subjects with the aforementioned<br />
disorders. Although the findings are inconsistent, previous<br />
studies mainly reported decreased levels of fecal Lactobacilli and<br />
Bifidobacteria, and increased ratios of Firmicutes to Bacteroidetes<br />
in patients with IBS when compared to healthy individuals [21, 30–<br />
32]. According to most studies conducted on the gut microbiota of<br />
CD patients, Bifidobacteria and Lactobacilli levels are decreased in<br />
comparison to healthy controls [22, 33, 34]. Due to NCWS being a<br />
relatively new diagnosis, few studies have examined gut microbiota<br />
in this group.<br />
GASTROENTEROLOGY TODAY - SUMMER <strong>2023</strong><br />
* Correspondence: Mohammad Rostami‐Nejad<br />
m.rostamii@gmail.com<br />
© The Author(s) <strong>2023</strong>.<br />
13
FEATURE<br />
GASTROENTEROLOGY TODAY - SUMMER <strong>2023</strong><br />
14<br />
To the best of our knowledge, no previous studies have investigated<br />
the possible similarities in the gut microbiota profile of patients with CD,<br />
NCWS, and IBS compared to healthy control. Hence, we designed this<br />
monocentric prospective observational study to compare the relative<br />
abundance of Firmicutes and Bacteroidetes, as the two most dominant<br />
phyla [35–38], and Bifidobacterium and Lactobacillus, as two highly<br />
controversial genera of fecal microbial communities, among Iranian<br />
subjects with CD, NCWS, and IBS compared to HCs.<br />
Materials and methods<br />
Study population<br />
From March 2020 to November 2020, consecutive newly diagnosed<br />
CD, NCWS, and IBS patients were recruited from an outpatient<br />
gastroenterology clinic in Taleghani Hospital, Tehran, Iran. Convenience<br />
sampling was used for participants’ selection. Subjects who had<br />
recently been diagnosed with CD, NCWS, and IBS, and were not<br />
on therapeutic diets such as gluten-free or low-FODMAP diets or<br />
taking supplements such as probiotics, prebiotics, or synbiotics were<br />
considered as patients groups. CD diagnosis was established according<br />
to the “4 out of 5” rule and four of the following criteria were considered<br />
sufficient for disease diagnosis: typical CD related symptoms, positivity<br />
of CD-specific antibodies, HLA-DQ2 or 8 genotypes, intestinal damages<br />
at duodenal biopsy and clinical response to GFD [39]. Twelve patients<br />
with NCWS that fulfilled the Salerno consensus criteria [40] were<br />
included. All NCWS subjects demonstrated negative serology results for<br />
tissue-transglutaminase IgA antibodies, and the duodenal biopsy results<br />
were normal [41].<br />
IBS diagnosis was based on fulfilling the ROME-IV criteria [27], including<br />
recurrent abdominal pain at least one day per week over the previous<br />
3 months, along with two or more of the following criteria: (a) changes<br />
in defecation, (b) changes in frequency, and (c) changes in the form of<br />
stool, with no medication to alleviate symptoms in the last 3 months.<br />
Anti-Tissue Trans-glutaminase (Anti-tTG) and/or endomysial antibodies<br />
(EMA), histological findings compatible with atrophy (according to the<br />
Marsh classification), and wheat-specific Immunoglobulin E (IgE) levels<br />
were negative in all thirty patients with IBS. Apart from these, fifteen<br />
healthy volunteers, with no history of digestive pathologies lacking<br />
CD-specific antibodies, were enrolled in the healthy control (HC)<br />
group. These HCs had normal bowel movements without abdominal<br />
symptoms, coronary artery disease, inflammatory conditions, IBS,<br />
NCWS, and diabetes mellitus.<br />
Pregnant and lactating women, individuals with any systemic<br />
inflammatory diseases like autoimmune conditions, gastrointestinal<br />
diseases (i.e. inflammatory bowel disease (IBD)) or any other acute<br />
or chronic diseases, gastrointestinal surgery, cancer, and those who<br />
were not willing to participate in the study were excluded from all<br />
study groups. Non-steroidal anti-inflammatory drugs (NSAIDs) usage,<br />
excessive alcohol consumption, systemic use of immunosuppressive<br />
agents, poorly controlled psychiatric diseases and the history of broadspectrum<br />
antibiotics and probiotics consumption were also considered<br />
as exclusion criteria. Participants were also asked not to take any<br />
antibiotics, eat spicy food, and smoke four weeks prior to sample<br />
collection.<br />
Fecal samples collection and homogenization<br />
Fresh early-morning fecal samples, representative of whole gut<br />
microbiome, were collected from each participant in sterile fecal<br />
specimen containers at the study’s baseline. A water ban was also<br />
required after midnight and before collecting the samples in the morning.<br />
Stool specimens were collected and handled by experienced clinicians<br />
and trained technicians. Homogenization of the stool samples was<br />
conducted through agitation by using a vortex. Afterward, stool samples<br />
were divided into three aliquots within 3 h of defecation. Using screwcapped<br />
cryovial containers, the aliquots were immediately frozen and<br />
stored at − 80 °C until used for DNA extraction [42].<br />
DNA extraction from fecal samples<br />
QIAamp ® DNA Stool Mini Kit (Qiagen Retsch GmbH, Hannover,<br />
Germany) was used for DNA extraction [43]. DNA concentration was<br />
quantified by NanoDrop ND-2000 Spectrophotometer (NanoDrop<br />
products, Wilmington, DE, USA). In addition, Nanodrop (DeNovix<br />
Inc., USA) was used for assessing the concentration and purity of the<br />
extracted DNA. Extracted DNA samples were stored at − 20 °C until<br />
further analysis.<br />
Microbiota analysis by quantitative real-time PCR (qPCR)<br />
We performed qPCR assay to evaluate the relative abundance of two<br />
bacterial phyla, including Firmicutes and Bacteroidetes, and two genera,<br />
including Bifidobacterium spp. and Lactobacillus spp. The qPCR was<br />
conducted by SYBR Green chemistry using universal and group-specific<br />
primers based on the bacterial 16S rRNA sequences presented in<br />
Additional file 1: Table S1. All PCRs were performed in a volume of 25<br />
μL, comprising 12.5 μL of SYBR green PCR master mix (Ampliqon,<br />
Odense, Denmark), 1 μL of 10 pmol of forward, and reverse primers,<br />
and 100 ng of the DNA template.<br />
Rotor-Gene ® Q (Qiagen, Germany) real-time PCR system was used<br />
for the PCR amplification. The amplification reaction parameters were<br />
assumed as 95 °C for 10 min and 40 cycles at 95 °C for 20 and 30 s for<br />
each primer (Additional file 1: Table S1) and 72 °C for the 20 s. Melting<br />
curve analysis was conducted to assess the amplification accuracy by<br />
increasing temperature from 60 to 95 °C (0.5 °C increase in every 5 s).<br />
The relative abundance of studied taxa was evaluated based on the ratio<br />
of the 16S rRNA copy number of the specific bacteria to the total 16S<br />
rRNA copy number of all bacteria using the previously described method<br />
[32]. Accordingly, the average Ct value for primers was reported as the<br />
percentage values using the following formula:<br />
univ<br />
(Eff. Univ)Ct<br />
Χ =<br />
(Eff. Spec)<br />
Ct spec<br />
×100<br />
The percentage of 16S taxon-specific copy numbers was indicated by<br />
“X”. Furthermore, “Eff. Univ” and “Eff. Spec” represents the efficiency<br />
of the universal primers (2 = 100% and 1 = 0%) and the efficiency of the<br />
taxon-specific primers respectively. The threshold cycles registered by<br />
the thermocycler were indicated by “Ct univ” and “Ct spec”.<br />
Statistical analysis<br />
Analysis of collected data was performed using Statistical Package<br />
for the Social Sciences (SPSS) version 25.0, SPSS Inc., Chicago, IL,<br />
USA. Figures were drawn using GRAPHPAD Prism 8.4.0 (GraphPad<br />
Software, Inc, San Diego, CA). Quantitative variables were reported as
FEATURE<br />
Table 1 Baseline characteristics of study participants at enrollment<br />
Variables HC (n = 15) IBS (n = 30) NCWS (n = 12) CD (n = 15) Total (n = 72) P‐value*<br />
Table Age (years) 1 Baseline characteristics 32.8 ± 12.2 of study 37.8 participants ± 10.7 at enrollment 31.8 ± 6.4 40.1 ± 8.2 35.5 ± 6.4 0.76<br />
Variables<br />
Males (n%)<br />
HC<br />
7 (46.7%)<br />
(n = 15) IBS<br />
15 (50%)<br />
(n = 30) NCWS<br />
5 (41.7%)<br />
(n = 12) CD<br />
6 (50%)<br />
(n = 15) Total<br />
33 (45.8%)<br />
(n = 72) P‐value*<br />
0.83<br />
Females (n%) 8 (53.3%) 15 (50%) 7 (58.3%) 6 (50%) 39 (54.2%) 0.45<br />
Age Smoking (years) (n%) 32.8 4 (26.6%) ± 12.2 37.8 9 (30%) ± 10.7 31.8 4 (33.3%) ± 6.4 40.1 2 (13.3%) ± 8.2 35.5 19 (26.4%) ± 0.76 0.65<br />
Males (n%) 7 (46.7%) 15 (50%) 5 (41.7%) 6 (50%) 33 (45.8%) 0.83<br />
HC, healthy control; IBS, irritable bowel syndrome; NCWS, non-celiac wheat sensitivity; CD, celiac disease<br />
Females (n%) 8 (53.3%) 15 (50%) 7 (58.3%) 6 (50%) 39 (54.2%) 0.45<br />
*P-values obtained by Kruskal–Wallis test<br />
Smoking (n%) 4 (26.6%) 9 (30%) 4 (33.3%) 2 (13.3%) 19 (26.4%) 0.65<br />
HC, healthy control; IBS, irritable bowel syndrome; NCWS, non-celiac wheat sensitivity; CD, celiac disease<br />
*P-values obtained by Kruskal–Wallis test<br />
mean ± standard deviation (SD) and qualitative variables were reported statistically significant (p = 0.002). Whereas the phylum Bacteroidetes<br />
as numerical (%) data. ANOVA test was used for the assessment of the was significantly lower in patients with IBS (P = 0.049) and NCWS<br />
relative abundance differences between the two phyla. In addition, we (P = 0.006). This phylum had the lowest relative abundance in the<br />
used R software and Principal Coordinate Analysis (PCoA) method to NCWS group (7.3 ± 4.0%). In addition, the relative abundance of<br />
assess dissimilarities in this study. The PCoA was calculated based on Bifidobacterium spp. was statistically lower in subjects with CD<br />
the Bray Curtis dissimilarity method [44].<br />
(P = 0.022) and IBS (P = 0.001); with the lowest percentage in the IBS<br />
group (0.5 ± 0.5). Moreover, Lactobacillus spp. was significantly lower<br />
Results<br />
in subjects with CD (P = 0.022) and IBS (P = 0.007) compared to the<br />
HCs. The relative abundance of this genus was also lower in subjects<br />
with NCWS, though not statistically significant (P = 0.12). The results<br />
Demographics<br />
Seventy-two samples from adult participants were enrolled in this<br />
study. Due to age-related changes in the gut microbiota, the study<br />
groups were adjusted according to their age so as not to have<br />
for the relative abundance are presented in Table 2 and Fig. 1. As<br />
shown in Table 2 the results obtained from the Kruskal–Wallis test also<br />
revealed significant inter-groups differences for all the studied bacteria<br />
(p
FEATURE<br />
Fig. 1 Box plot for the distribution of the selected bacterial taxa by the median abundance that constitutes the fecal microbiota in each group of<br />
the study population. Differences in each group of the patients were compared to the healthy control (HC) and were considered to be statistically<br />
significant when *P < 0.05, **P < 0.01, and ***P < 0.001<br />
GASTROENTEROLOGY TODAY - SUMMER <strong>2023</strong><br />
16<br />
Discussion<br />
The current study examined fecal samples from adult participants<br />
with three GI disorders, including CD, NCWS, and IBS. Comparing<br />
gut dysbiosis to healthy controls, the microbiota analysis interestingly<br />
showed a significant difference in the relative abundance of Firmicutes,<br />
Bacteroidetes, Bifidobacterium spp., and Lactobacillus spp. in<br />
CD patients. In addition, the analysis of the relative abundance of<br />
Bifidobacterium spp. and Lactobacillus spp. in IBS patients and<br />
Bacteroidetes in NCWS revealed a statistically significant decrease<br />
compared to the HC group. Furthermore, Firmicutes to Bacteroidetes<br />
ratio (F/B ratio) assessment, as a valuable index for detecting the<br />
alterations in gut microbiota, was another aim of the current study.<br />
Changes in the F/B ratio could be particularly important. Firmicutes and<br />
Bacteroidetes are two predominant phyla accounting for up to 90%<br />
of the total gut microbiota composition [45]. The F/B ratio has been<br />
suggested as an important index of gut microbiota health. [46]. This<br />
ratio is associated with different pathological states [47]. For instance,<br />
the association of a high F/B ratio with several conditions including<br />
GI disorders has been observed repeatedly [48–50]. Particularly, it<br />
is associated with the production of short-chain fatty acids such as<br />
butyrate and propionate [51]. Short-chain fatty acids generated by<br />
microbiota can have a significant influence on human health. The antiinflammatory<br />
molecule butyrate, in particular, acts both on enterocytes<br />
and circulating immune cells, regulating gut barrier integrity. Additionally,<br />
propionate production plays a crucial role in human health since it<br />
promotes satiety and prevents hepatic lipogenesis, which in turn lowers<br />
cholesterol production [52, 53]. Moreover, the increased F/B ratio is<br />
associated with an increased energy harvest from colonic fermentation<br />
[54]. According to our analysis, the F/B ratio was significantly higher in<br />
the subjects with CD and NCWS than in the HCs. In contrast, it was<br />
not statistically significant in subjects with IBS, suggesting a higher level<br />
of alteration in the gut microbiota of individuals with CD and NCWS<br />
than in the IBS compared to the HCs. Recent studies suggested that<br />
the alteration of gut microbiota composition is associated with CD<br />
pathogenesis [55–57]. In the study of Golfetto et al., the concentration<br />
of Bifidobacterium spp. in CD patients was significantly lower compared<br />
to the HCs [58]. Another study conducted by Bodkhe et al., reported<br />
that Firmicutes and Bacteroidetes were the major phyla in the duodenal<br />
microbiota of subjects with CD [59]. Several other studies have<br />
demonstrated that Bifidobacterium spp. and Lactobacillus spp. protect<br />
the intestinal epithelial cells from gliadin damage [60,61,62]. Accordingly,<br />
it has been suggested that the fecal transplant which can cause an<br />
increment in Bifidobacterium spp. could reverse the inflammatory<br />
pathway in CD patients [63]. Among all the groups we studied,<br />
Firmicutes predominated the gut microbiota. In addition, Bacteroidetes,
FEATURE<br />
Bifidobacterium spp., and Lactobacillus spp. had significantly lower<br />
abundance in subjects with CD compared to the HCs. In terms of the<br />
alteration and relative abundance of the studied bacterial groups, the<br />
current study’s results were largely consistent with the previous reports.<br />
Fig. 2 Box plots showing the Firmicutes to Bacteroidetes (F/B) I each<br />
group of participants. This ratio was significantly (*P = 0.05) increased<br />
in the NCWS and CD patients but non‐significant in the IBS patients<br />
compared with the healthy controls (HC)<br />
Gut microbiota dysbiosis in individuals with IBS has been reported<br />
in several studies [64–66]. In fact, gastrointestinal dysbiosis in these<br />
patients is associated with intestinal hypersensitivity, mucosal immune<br />
activation, and chronic inflammation, which are the three important<br />
pathophysiological factors in this disease [67, 68]. A number of studies<br />
have reported lower amounts of Bacteroidetes and higher amounts of<br />
Firmicutes in subjects with IBS compared to HCs [32, 69, 70]. In the<br />
current study, both of these phyla had lower relative abundances than<br />
those of HCs, although their differences were not statistically significant.<br />
Furthermore, it has been suggested that IBS is associated with the<br />
lower relative abundance of Bifidobacterium spp. and Lactobacillus<br />
spp. [71, 72] which is in accordance with the current study. However, it<br />
is noteworthy that Maccaferri et al. observed an increase in the relative<br />
abundance of Bifidobacterium spp. and Lactobacillus among subjects<br />
with IBS [73]. It seems that further evidence is needed to confirm<br />
these results. As for NCWS, dysbiosis in these individuals is one of<br />
the important issues which can cause constipation, diarrhea, chronic<br />
inflammation, intestinal hypersensitivity, and immune dysfunction [74].<br />
Fig. 3 Shepherd plot showing the correlation between the distance from the dissimilarity matrix and the coordination distance for NMDS analysis<br />
GASTROENTEROLOGY TODAY - SUMMER <strong>2023</strong><br />
17
FEATURE<br />
Fig. 4 Bray–Curtis dissimilarity metric plotted in PCoA space comparing the microbial communities from different patient groups (CD, NCWS, IBS,<br />
and HC). Each circle representing a participant colored according to the studied group<br />
GASTROENTEROLOGY TODAY - SUMMER <strong>2023</strong><br />
18<br />
Garcia-Mazcorro et al. reported a high relative abundance of Firmicutes<br />
and a low relative abundance of Bacteroidetes in the fecal microbiota<br />
of the individuals with NCWS [75]. According to the current study,<br />
the Phylum Bacteroidetes was significantly lower in NCWS patients<br />
compared to HCs, in agreement with the previous study.<br />
Analysis of the dissimilarity and PCoA in this study suggests that<br />
individuals with CD experience a higher level of dysbiosis compared to<br />
the other subjects with microbiota-related GI disorders. In fact, fewer<br />
similarities were observed in the studied bacterial profile of subjects<br />
with IBS and those with NCWS. Overall, it may explain why this<br />
disorder exhibits more severe symptoms when compared to the other<br />
GI disorders, suggesting that the recovery of gut microbiota should be<br />
emphasized more in the treatment of this disease. According to these<br />
analyses, the composition of the gut microbiota in the subjects with IBS<br />
and NCWS is more similar to that of the HCs’, which may suggest a<br />
more favorable outcome for IBS and NCWS than for CD.<br />
The present study had some limitations. First, the sample size is not<br />
large enough to extrapolate the results. Actually, the present study has<br />
monocentric nature that was conducted in a limited population with<br />
specific features. Even if this matter has been addressed with bigger<br />
sample sizes, the results cannot be generalized from one population<br />
to others. Second, based on the meta-genomic data, the human gut<br />
microbiome may contain more than 1000 bacterial species. Although<br />
the studied bacterial phyla and genera are the most dominant and<br />
critical taxonomical groups, there are other groups that should be taken<br />
into consideration. Third, alimentary habits of the included subjects,<br />
which can consistently modify gut microbiota, were not assessed in the<br />
current study. Considering the fact that, eating habits such as using fiber<br />
sub-types, food additives, ultra-processed foods and etc. can affect the<br />
gut bacteria composition, performing further similar microbiota studies<br />
evaluating patients’ dietary pattern is highly recommended. Moreover,<br />
the lack of a follow-up of patients and comparison of results before and<br />
after receiving treatment is another important limitation.<br />
To our knowledge, no previous publication has compared the gut<br />
microbiota profile of subjects with CD, NCWS, and IBS. In fact,<br />
the potential overlap between NCWS and IBS diagnosis and the<br />
unavailability of gluten challenge tests in many medical centers make it<br />
difficult to explore the gut microbiota among these groups. Thus, this<br />
study represents promising findings for future research. Additionally,<br />
investigating all components of the gut microbiota including bacteria,<br />
viruses, fungi, and archaea in order to identify microbial patterns,
FEATURE<br />
conducting multi-centric studies, and examining the fecal microbiome<br />
and mucosal microbiome simultaneously to have a better perspective on<br />
the differences between the mucosal microbiome and fecal microbiome<br />
would have been of great importance.<br />
Consent for publication<br />
Not applicable.<br />
Competing interests<br />
The authors declare that they have no competing interests.<br />
Conclusion<br />
Results of our study indicate that the human intestinal microbiota<br />
composition differs across the studied groups with different microbiotarelated<br />
GI disorders. Specifically, patients with CD had the highest<br />
level of dissimilarity compared to the other studied groups with GI<br />
disorders and HCs. In contrast, those with IBS had the lowest level of<br />
dissimilarity with HCs. This study found some microbial changes that<br />
were inconsistent with the previous results, possibly due to genetics,<br />
geographical pattern, ethnicity, or diet.<br />
Supplementary Information<br />
The online version contains supplementary material available at<br />
https://doi.org/10.1186/s12876-023-02649-y.<br />
Additional file 1: Supplementary Table 1. The taxon-specific primers<br />
used in this study.<br />
Acknowledgements<br />
The authors wish to thank the laboratory staffs of the Foodborne<br />
and Waterborne Diseases Research Center, Research Institute for<br />
<strong>Gastroenterology</strong> and Liver Diseases, Shahid Beheshti University of<br />
Medical Sciences, Tehran, Iran, specially Ms. Masoumeh Azimirad and<br />
Ms. Nastaran Asri for their sincere assistance.<br />
Author contributions<br />
KN, SS, and MSK collected the samples and KN performed the<br />
real-time PCR analysis; MRN and HD designed and supervised the<br />
study; KN and MO participated in data analysis; KN, and MAS wrote<br />
the manuscript; MRN, AY, AS, HD, AKV, and MRZ critically revised the<br />
manuscript. All authors approved the final version of the manuscript.<br />
Funding<br />
<strong>Gastroenterology</strong> and Liver Diseases Research Center, Research<br />
Institute for <strong>Gastroenterology</strong> and Liver Diseases, Shahid Beheshti<br />
University of Medical Sciences, Tehran, Iran, supported the study.<br />
Availability of data and materials<br />
The datasets used and/or analysed during the current study available<br />
from the corresponding author on reasonable request.<br />
Declarations<br />
Ethics approval and consent to participate<br />
The study protocol was submitted for evaluation and approval to the Ethical<br />
Review Committee of the Research Institute for <strong>Gastroenterology</strong> and Liver<br />
Diseases, Shahid Beheshti University of Medical Sciences to ensure that it<br />
meets ethical standards and guidelines. The present study was approved<br />
by mentioned Ethical Review Committee under the number IR.SBMU.<br />
RIGLD. REC.1396.154. The study was performed according to the revised<br />
Declaration of Helsinki 2013 [39] and informed consent was obtained from<br />
all subjects and/or their legal guardians prior to sample collection.<br />
Author details<br />
1<br />
School of Health and Biomedical Sciences, RMIT University, Melbourne,<br />
VIC, Australia. 2 Department of Microbiology, School of Medicine, Shahid<br />
Beheshti University of Medical Sciences, Tehran, Iran. 3 <strong>Gastroenterology</strong><br />
and Hepatology Diseases Research Center, Qom University of Medical<br />
Sciences, Qom, Iran. 4 Celiac Disease Department, <strong>Gastroenterology</strong> and<br />
Liver Diseases Research Center, Research Institute for <strong>Gastroenterology</strong><br />
and Liver Diseases, Shahid Beheshti University of Medical Sciences,<br />
Tehran, Iran. 5 Foodborne and Waterborne Diseases Research Center,<br />
Research Institute for <strong>Gastroenterology</strong> and Liver Diseases, Shahid<br />
Beheshti University of Medical Sciences, Tehran, Iran. 6 Celiac Disease<br />
Research Laboratory, Department of Pediatrics, Università Politecnica<br />
Delle Marche, 60123 Ancona, Italy.<br />
Received: 2 June 2022 Accepted: 11 January <strong>2023</strong><br />
Published online: 16 January <strong>2023</strong><br />
References<br />
1. Hooper LV, Wong MH, Thelin A, et al. Molecular analysis of<br />
commensal host-microbial relationships in the intestine. Science.<br />
2001;291(5505):881–4.<br />
2. Altveş S, Yildiz HK, Vural HC. Interaction of the microbiota with the<br />
human body in health and diseases. Biosci Microbiota Food Health.<br />
2019;39:19–023.<br />
3. Clemente JC, Ursell LK, Parfrey LW, et al. The impact of the<br />
gut microbiota on human health: an integrative view. Cell.<br />
2012;148(6):1258–70.<br />
4. Ogunrinola GA, Oyewale JO, Oshamika OO, et al. The human<br />
microbiome and its impacts on health. Int J Microbiol. 2020;2020.<br />
5. Teng F, Felix KM, Bradley CP, et al. The impact of age and gut<br />
microbiota on Th17 and Tfh cells in K/BxN autoimmune arthritis.<br />
Arthritis Res Ther. 2017;19(1):1–13.<br />
6. David LA, Maurice CF, Carmody RN, et al. Diet rapidly and<br />
reproducibly alters the human gut microbiome. Nature.<br />
2014;505(7484):559–63.<br />
7. Prideaux L, Kang S, Wagner J, et al. Impact of ethnicity, geography,<br />
and disease on the microbiota in health and inflammatory bowel<br />
disease. Inflamm Bowel Dis. 2013;19(13):2906–18.<br />
8. Million M, Diallo A, Raoult D. Gut microbiota and malnutrition.<br />
Microb Pathog. 2017;106:127–38.<br />
9. Renson A, Herd P, Dowd JB. Sick individuals and sick (microbial)<br />
populations: challenges in epidemiology and the microbiome. Annu<br />
Rev Public Health. 2020;2(41):63–80.<br />
10. Chong CW, Ahmad AF, Lim YAL, et al. Effect of ethnicity and<br />
socioeconomic variation to the gut microbiota composition among<br />
pre-adolescent in Malaysia. Sci Rep. 2015;5(1):1–12.<br />
GASTROENTEROLOGY TODAY - SUMMER <strong>2023</strong><br />
19
FEATURE<br />
GASTROENTEROLOGY TODAY - SUMMER <strong>2023</strong><br />
20<br />
11. Lin L, Zhang J. Role of intestinal microbiota and metabolites on gut<br />
homeostasis and human diseases. BMC Immunol. 2017;18(1):1–<br />
25.<br />
12. Takiishi T, Fenero CIM, Câmara NOS. Intestinal barrier and gut<br />
microbiota: shaping our immune responses throughout life. Tissue<br />
barriers. 2017;5(4): e1373208.<br />
13. Thursby E, Juge N. Introduction to the human gut microbiota.<br />
Biochem J. 2017;474(11):1823–36.<br />
14. Wu H-J, Wu E. The role of gut microbiota in immune homeostasis<br />
and autoimmunity. Gut Microb. 2012;3(1):4–14.<br />
15. Belizário JE, Faintuch J. Microbiome and gut dysbiosis. Metabolic<br />
interaction in infection. Springer; 2018. p. 459–76.<br />
16. Chang C, Lin H. Dysbiosis in gastrointestinal disorders. Best Pract<br />
Res Clin Gastroenterol. 2016;30(1):3–15.<br />
17. Fukui H, Xu X, Miwa H. Role of gut microbiota-gut hormone axis<br />
in the pathophysiology of functional gastrointestinal disorders. J<br />
Neurogastroenterol Motil. 2018;24(3):367.<br />
18. Lopetuso LR, Petito V, Graziani C, et al. Gut microbiota in health,<br />
diverticular disease, irritable bowel syndrome, and inflammatory<br />
bowel diseases: time for microbial marker of gastrointestinal<br />
disorders. Dig Dis. 2018;36(1):56–65.<br />
19. Malikowski T, Khanna S, Pardi DS. Fecal microbiota transplantation<br />
for gastrointestinal disorders. Curr Opin Gastroenterol.<br />
2017;33(1):8–13.<br />
20. Ostadmohammadi S, Azimirad M, Houri H, et al. Characterization<br />
of the gut microbiota in patients with primary sclerosing cholangitis<br />
compared to inflammatory bowel disease and healthy controls. Mol<br />
Biol Rep. 2021;48(7):5519–29.<br />
21. Bhattarai Y, Muniz Pedrogo DA, Kashyap PC. Irritable bowel<br />
syndrome: a gut microbiota-related disorder? Am J Physiol<br />
Gastrointestinal Liver Physiol. 2017;312(1):52–62.<br />
22. Marasco G, Di Biase AR, Schiumerini R, et al. Gut microbiota and<br />
celiac disease. Dig Dis Sci. 2016;61(6):1461–72.<br />
23. Igbinedion SO, Ansari J, Vasikaran A, et al. Non-celiac gluten<br />
sensitivity: all wheat attack is not celiac. World J Gastroenterol.<br />
2017;23(40):7201.<br />
24. Leccioli V, Oliveri M, Romeo M, et al. A new proposal for the<br />
pathogenic mechanism of non-coeliac/non-allergic gluten/wheat<br />
sensitivity: piecing together the puzzle of recent scientific evidence.<br />
Nutrients. 2017;9(11):1203.<br />
25. Shannahan S, Leffler DA. Diagnosis and updates in celiac disease.<br />
Gastrointestinal Endosc Clin. 2017;27(1):79–92.<br />
26. Buono JL, Carson RT, Flores NM. Health-related quality of life, work<br />
productivity, and indirect costs among patients with irritable bowel<br />
syndrome with diarrhea. Health Qual Life Outcomes. 2017;15(1):1–8.<br />
27. Lacy BE, Patel NK. Rome criteria and a diagnostic approach to<br />
irritable bowel syndrome. J Clin Med. 2017;6(11):99.<br />
28. Barbaro MR, Cremon C, Stanghellini V, et al. Recent advances<br />
in understanding non-celiac gluten sensitivity. F1000Research.<br />
2018;7.<br />
29. Catassi C, Bai JC, Bonaz B, et al. Non-celiac gluten sensitivity:<br />
the new frontier of gluten related disorders. Nutrients.<br />
2013;5(10):3839–53.<br />
30. Hills RD Jr, Pontefract BA, Mishcon HR, et al. Gut Microbiome:<br />
profound implications for diet and disease. Nutrients.<br />
2019;11(7):1613.<br />
31. Salem AE, Singh R, Ayoub YK, et al. The gut microbiome and<br />
irritable bowel syndrome: state of art review. Arab J Gastroenterol.<br />
2018;19(3):136–41.<br />
32. Naseri K, Dabiri H, Rostami-Nejad M, et al. Influence of low<br />
FODMAP-gluten free diet on gut microbiota alterations and<br />
symptom severity in Iranian patients with irritable bowel syndrome.<br />
BMC Gastroenterol. 2021;21(1):1–14.<br />
33. Chander AM, Yadav H, Jain S, et al. Cross-talk between gluten,<br />
intestinal microbiota and intestinal mucosa in celiac disease: recent<br />
advances and basis of autoimmunity. Front Microbiol. 2018;9:2597.<br />
34. Losurdo G, Principi M, Iannone A, et al. The interaction between<br />
celiac disease and intestinal microbiota. J Clin Gastroenterol.<br />
2016;50:S145–7.<br />
35. Khanna S, Tosh PK. A clinician’s primer on the role of the<br />
microbiome in human health and disease. Mayo Clin Proc.<br />
2014;89(1):107–14.<br />
36. Johnson EL, Heaver SL, Walters WA, et al. Microbiome and<br />
metabolic disease: revisiting the bacterial phylum Bacteroidetes. J<br />
Mol Med. 2017;95(1):1–8.<br />
37. Kumar H, Lund R, Laiho A, et al. Gut microbiota as an epigenetic<br />
regulator: pilot study based on whole-genome methylation analysis.<br />
MBio. 2014;5(6):e02113-e2114.<br />
38. Mahowald MA, Rey FE, Seedorf H, et al. Characterizing a model<br />
human gut microbiota composed of members of its two dominant<br />
bacterial phyla. Proc Natl Acad Sci. 2009;106(14):5859–64.<br />
39. Raiteri A, Granito A, Giamperoli A, et al. Current guidelines for<br />
the management of celiac disease: a systematic review with<br />
comparative analysis. World J Gastroenterol. 2022;28(1):154–75.<br />
40. Catassi C, Elli L, Bonaz B, et al. Diagnosis of non-celiac gluten<br />
sensitivity (NCGS): the Salerno experts’ criteria. Nutrients.<br />
2015;7(6):4966–77.<br />
41. Taraghikhah N, Ashtari S, Asri N, et al. An updated overview<br />
of spectrum of gluten-related disorders: clinical and diagnostic<br />
aspects. BMC Gastroenterol. 2020;20(1):258.<br />
42. Soheilian-Khorzoghi M, Rezasoltani S, Moheb-Alian A, Yadegar A,<br />
Rostami-Nejad M, Azizmohammad-Looha M, Verma AK, Haddadi<br />
A, Dabiri H. Impact of nutritional profile on gut microbiota diversity<br />
in patients with celiac disease. Curr Microbiol. 2022;79(5):129.<br />
https://doi.org/10.1007/s00284-022-02820-w.<br />
43. Mirsepasi H, Persson S, Struve C, et al. Microbial diversity in fecal<br />
samples depends on DNA extraction method: easyMag DNA<br />
extraction compared to QIAamp DNA stool mini kit extraction. BMC<br />
Res Notes. 2014;21(7):50.<br />
44. Bray JR, Curtis JT. An ordination of the upland forest communities<br />
of southern Wisconsin. Ecol Monogr. 1957;27(4):326–49.
Distal<br />
ulcerative colitis:<br />
Together we know more.<br />
Together we do more.<br />
FEATURE<br />
Real<br />
challenges<br />
When you’ve just been diagnosed with ulcerative colitis,<br />
rectal therapy isn’t always the most welcome prospect<br />
Real<br />
solution<br />
Salofalk Granules are a simple oral treatment providing the<br />
once-daily dosing that patients prefer, along with the efficacy<br />
that patients need – even for those with distal disease 1-3<br />
Salofalk Granules have a clever delivery mechanism providing prolonged<br />
release throughout the colon, shown using gamma-scintigraphy 1,4<br />
4 h 6 h 8 h 10 h 12 h<br />
Mesalazine, the Dr Falk way<br />
Prescribing Information (refer to full SPC before prescribing):<br />
Presentation: Salofalk 250mg gastro-resistant tablets: gastro-resistant tablet<br />
Prescribing containing 250mg Information mesalazine. (refer Salofalk to full 500mg SPC and before 1g gastro-resistant prescribing): tablet (UK<br />
Salofalk ONLY) containing gastro-resistant 500mg prolonged-release and 1g mesalazine granules respectively. Salofalk<br />
Presentation: 500mg/1000mg/1500mg/3000mg Stick-formed or prolonged-release round, greyish granules: white prolonged-release<br />
gastro-resistant<br />
granules containing 500mg,1000mg, 1500mg or 3000mg mesalazine per sachet.<br />
prolonged-release granules in sachets containing 500mg, 1000mg,<br />
Indications: Salofalk 250mg tablets (UK): treatment and maintenance of remission<br />
1.5g of mild/moderate or 3g mesalazine ulcerative per colitis. sachet. Salofalk Indications: 250mg tablets Treatment (Ireland): as of an acute antiinflammatory<br />
and in the management maintenance of ulcerative of remission colitis and of in ulcerative the treatment colitis. of<br />
episodes<br />
Dosage: Crohn’s disease. Adults: Salofalk Once daily 500mg 1 tablets sachet (UK): of 3g treatment granules, and 1 or maintenance 2 sachets of of<br />
1.5g remission granules of ulcerative or 3 sachets colitis. Salofalk 1000mg 1g tablets or 500mg (UK): treatment granules of (equivalent acute episodes to<br />
of mild/moderate ulcerative colitis. Salofalk granules: treatment of acute episodes<br />
1.5 – 3.0g mesalazine daily) preferably taken in the morning, according<br />
and the maintenance of remission of mild to moderate ulcerative colitis. Dosage:<br />
to Salofalk individual 250mg clinical tablets - requirement. Adults and elderly: May acute be treatment taken in 6 three -12 tablets divided daily doses in 3<br />
(1 divided sachet doses. of 500mg Maintenance granules treatment three 6 tablets times daily in or 3 divided 1 sachet doses. of 1000mg Salofalk<br />
granules 500mg tablets three (UK times only): 1 daily) or 2 tablets if more 3 times convenient. daily. Maintenance: Maintenance: 1 tablet 3 times 0.5g<br />
mesalazine daily. Salofalk 1g three tablets times (UK only): daily 1 tablet (morning, three times midday daily. Salofalk and granules evening) –<br />
corresponding<br />
adults: acute treatment<br />
to a<br />
–<br />
total<br />
once<br />
dose<br />
daily 1<br />
of<br />
sachet<br />
1.5g<br />
of<br />
mesalazine<br />
3g granules, 1<br />
per<br />
or 2<br />
day.<br />
sachets<br />
For<br />
of<br />
patients<br />
Salofalk<br />
1.5g granules, 3 sachets of 500mg granules or 3 sachets of 1000mg granules<br />
known (equivalent to be to at 1.5 increased – 3.0g mesalazine risk for relapse daily), preferably for medical taken reasons in the or morning. due to<br />
difficulties Alternatively, the to dose adhere can to be taken three divided daily doses, in three doses. give 3.0g Maintenance mesalazine treatment as a<br />
single – 1 sachet daily of 500mg dose, granules preferably 3 times in daily the (1.5g morning. mesalazine Children: daily). Where There needed, is only<br />
limited 3.0g per day documentation in a single morning for dose an may effect be taken. in children Method of administration: (age 6-18 years). oral.<br />
Children<br />
Tablets - taken<br />
6 years<br />
whole without<br />
of age<br />
chewing,<br />
and older:<br />
with<br />
Active<br />
liquid, one<br />
disease:<br />
hour before<br />
To be<br />
meals.<br />
determined<br />
Granules<br />
- taken on the tongue and swallowed, without chewing, with plenty of liquid.<br />
individually, Duration of treatment starting is with usually 30-50mg/kg/day 8 weeks. To be determined once daily by physician. preferably Children in the<br />
morning (all formulations): in divided there is only doses. limited Maximum documentation dose: for 75mg/kg/day. an effect in children The (age total<br />
dose 6-18 years). should Children not 6 exceed years and the older: maximum active disease adult – on individual dose. Maintenance<br />
basis starting<br />
treatment: with 30-50mg/kg/day To be determined either once daily individually, (granules) starting or divided with doses 15-30mg/kg/day (tablets and<br />
in granules). divided Maximum doses. The 75mg/kg/day. total dose Total should dose not should exceed not exceed the recommended<br />
adult dose. Maintenance - on individual basis starting with 15-30mg/kg/day in<br />
adult<br />
divided<br />
dose.<br />
doses.<br />
It<br />
Total<br />
is generally<br />
dose should<br />
recommended<br />
not exceed recommended<br />
that half the<br />
adult<br />
adult<br />
dose.<br />
dose<br />
Generally<br />
may<br />
be recommended given to children that half the up adult to a body dose may weight be given of 40kg; to children and up the to normal a body weight adult<br />
dose of 40kg to and those the above normal 40kg. adult dose Method to those of administration: above 40kg. Contra-indications:<br />
Taken the<br />
tongue Hypersensitivity and swallowed, to salicylates without or any of chewing, the excipients. with Severe plenty impairment of liquid. of Contraindications:<br />
hepatic function. Hypersensitivity Warnings/Precautions: to salicylates Blood tests and or any urinary of status the excipients. (dip sticks)<br />
renal or<br />
should be determined prior to and during treatment. Caution is recommended in<br />
Severe impairment of renal or hepatic function. Warnings/Precautions:<br />
patients with impaired hepatic function. Should not be used in patients with<br />
Blood impaired tests renal and function. urinary Mesalazine-induced status (dip sticks) renal should toxicity should be determined be considered prior if<br />
to renal and function during deteriorates treatment. during Caution treatment is - recommended stop treatment immediately in patients in such with<br />
impaired cases. Cases hepatic of nephrolithiasis function. reported; Should ensure not good be used hydration. in patients Serious blood with<br />
impaired dyscrasias renal have been function. reported Mesalazine-induced very rarely with mesalazine. renal toxicity Hematological should be<br />
investigations should be performed if patients suffer from unexplained<br />
considered if renal function deteriorates during treatment. Cases of<br />
haemorrhages, bruises, purpura, anaemia, fever or pharyngolaryngeal pain. Salofalk<br />
should be discontinued in case of suspected or confirmed blood dyscrasia. Cardiac<br />
hypersensitivity reactions (myocarditis, and pericarditis) induced by mesalazine<br />
nephrolithiasis have been rarely reported. reported; Salofalk ensure should good then be hydration. discontinued Patients immediately. with<br />
pulmonary Patients with disease, pulmonary in disease, particular in particular asthma, asthma, should should be be carefully<br />
monitored. Severe Patients cutaneous with adverse a history reactions of (SCARs), adverse including drug reactions drug reaction to<br />
with eosinophilia and systemic symptoms (DRESS), Stevens-Johnson syndrome<br />
preparations<br />
(SJS) and toxic<br />
containing<br />
epidermal necrolysis<br />
sulphasalazine<br />
(TEN), have<br />
should<br />
been<br />
be<br />
reported.<br />
kept under<br />
Discontinue<br />
close<br />
medical treatment surveillance. at the first appearance If acute of signs intolerance and symptoms reactions of severe e.g., skin abdominal reactions,<br />
cramps, such as skin acute rash, abdominal mucosal lesions, pain, or fever, any severe other sign headache of hypersensitivity. and rash, Patients occur,<br />
stop with a treatment history of adverse immediately. drug reactions Severe to preparations cutaneous containing adverse sulphasalazine reactions<br />
(SCARs), should be kept including under close Stevens-Johnson medical surveillance. syndrome If acute intolerance (SJS) reactions and toxic e.g.,<br />
abdominal cramps, acute abdominal pain, fever, severe headache and rash occur,<br />
epidermal<br />
stop treatment<br />
necrolysis<br />
immediately.<br />
(TEN),<br />
Tablets may<br />
have<br />
be excreted<br />
been<br />
undissolved<br />
reported.<br />
in<br />
Discontinue<br />
patients with<br />
treatment the ileocecal at valve the first removed. appearance Salofalk of granules: signs and contain symptoms aspartame, of severe a source skin of<br />
reactions, phenylalanine. such May as be skin harmful rash, to patients mucosal with lesions, phenylketonuria. or any other Granules sign also of<br />
hypersensitivity. contain sucrose: 0.04mg, Salofalk 0.08mg, granules 0.12mg, contain 0.24mg aspartame, (500mg/1g/1.5g a source and 3g of<br />
phenylalanine granules respectively). that Salofalk may be tablets: harmful For patients for patients on a sodium-controlled with phenylketonuria. diet: the<br />
250mg and 500mg tablets contain 48mg and 49mg of sodium, equivalent to 2.4%<br />
Salofalk granules contain sucrose: 0.02mg, 0.04mg, 0.06mg and<br />
and 2.5% of the recommended maximum daily intake for sodium. Urine may be<br />
0.12mg discoloured (500mg/1g/1.5g red-brown after and contact 3g with granules sodium respectively). hypochlorite bleach Interactions: used in<br />
Specific toilets. Interactions: interaction Specific studies interaction have not studies been have performed. not been performed. Lactulose With or<br />
similar concomitant preparations treatment with that azathioprine, lower stool 6-mercaptopurine pH: possible or reduction thioguanine, of<br />
mesalazine consider a possible release increase from granules in their myelosuppressive due to decreased effects. pH There caused is weak by<br />
bacterial<br />
evidence that<br />
metabolism<br />
mesalazine<br />
of<br />
might<br />
lactulose.<br />
decrease<br />
With<br />
the<br />
concomitant<br />
anticoagulant effect<br />
treatment<br />
of warfarin.<br />
with<br />
Salofalk granules (additionally): lactulose, or similar preparations which lower stool<br />
azathioprine, pH: possible reduction 6-mercaptopurine of mesalazine release or thioguanine from granules consider due to decreased a possible pH<br />
increase caused by in bacterial their myelosuppressive metabolism of lactulose. effects. Use in There pregnancy is weak and lactation: evidence do that not<br />
mesalazine use Salofalk during might pregnancy decrease unless the anticoagulant the potential benefit effect outweighs of warfarin. the possible Use in<br />
pregnancy risks. Limited and experience lactation: in the lactation There are period. no Salofalk adequate should data. only be Do used not during use<br />
during<br />
breast-feeding<br />
pregnancy<br />
if the potential<br />
unless<br />
benefit<br />
the potential<br />
outweighs<br />
benefit<br />
the possible<br />
outweighs<br />
risks; if<br />
the breast-fed<br />
possible<br />
infant develops diarrhoea, breast-feeding should be discontinued. Undesirable<br />
risks. effects: Limited altered blood experience counts in (aplastic the lactation anaemia, period. agranulocytosis, Use during pancytopenia, breastfeeding<br />
neutropenia, only leukopenia, if the potential thrombocytopenia), benefit outweighs hypersensitivity the possible reactions risks; such if the as<br />
infant allergic develops exanthema, diarrhoea, drug fever, breast-feeding lupus erythematosus should syndrome, be discontinued. pancolitis,<br />
Undesirable headache, dizziness, effects: peripheral Headache, neuropathy, dizziness, peri- and peri- myo-carditis, and myocarditis, allergic and<br />
abdominal fibrotic lung pain, reactions diarrhoea, (including dyspepsia, dyspnoea, cough, flatulence, bronchospasm, nausea, vomiting, alveolitis,<br />
pulmonary eosinophilia, lung infiltration, pneumonitis), abdominal pain, diarrhoea,<br />
aplastic<br />
dyspepsia, flatulence,<br />
anaemia,<br />
nausea,<br />
agranulocytosis,<br />
vomiting, acute<br />
pancytopenia,<br />
pancreatitis, cholestatic<br />
neutropenia,<br />
hepatitis,<br />
leukopenia, hepatitis, rash, thrombocytopenia, pruritus, photosensitivity peripheral – especially neuropathy, with pre-existing allergic skin and<br />
fibrotic conditions, lung alopecia, reactions severe (including cutaneous adverse dyspnoea, reactions cough, (SCARs) bronchospasm,<br />
including drug<br />
alveolitis, reaction with pulmonary eosinophilia eosinophilia, and systemic symptoms lung infiltration, (DRESS), Stevens-Johnson<br />
pneumonitis),<br />
acute syndrome pancreatitis, (SJS), toxic epidermal impairment necrolysis of renal (TEN), function arthralgia, including myalgia, impairment acute and<br />
of renal function including acute and chronic interstitial nephritis and renal<br />
chronic interstitial nephritis and renal insufficiency, nephrolithiasis,<br />
insufficiency, nephrolithiasis, asthenia, fatigue, oligospermia (reversible), changes<br />
in hepatic function parameters, changes in pancreatic enzymes, eosinophil count<br />
increased. Legal category: POM. Cost (UK - basic NHS price; Ireland - PtW): Salofalk<br />
photosensitivity 250mg tablets (100s) especially £16.19; with €13.48. pre-existing Salofalk 500mg skin conditions, tablets (100s) alopecia, £32.38.<br />
Stevens-Johnson Salofalk 1g tablets (90s) syndrome £58.50. (SJS), Salofalk toxic 500mg epidermal granules (100 necrolysis sachets) (TEN), £28.74;<br />
myalgia,<br />
€27.93. Salofalk<br />
arthralgia,<br />
1000mg granules<br />
hypersensitivity<br />
(50 sachets)<br />
reactions<br />
£28.74; €32.87.<br />
such<br />
Salofalk<br />
as allergic<br />
1500mg<br />
granules (60 sachets) £48.85; €49.66. Salofalk 3g granules (60 sachets) £97.70;<br />
exanthema,<br />
€101.64. Product<br />
drug<br />
licence<br />
fever, lupus<br />
number:<br />
erythematosus<br />
Salofalk 250mg<br />
syndrome,<br />
tablets: PL10341/0004;<br />
pancolitis,<br />
changes PA573/4/3. in hepatic Salofalk function 500mg parameters, tablets: PL08637/0019. hepatitis, cholestatic Salofalk 1g hepatitis tablets:<br />
and PL08637/0027. oligospermia Salofalk (reversible), 500mg granules: asthenia, PL08637/0007; fatigue, changes PA573/3/1. in pancreatic Salofalk<br />
enzymes, 1000mg granules: eosinophil PL08637/0008; count increased. PA573/3/2. Legal Salofalk category: 1500mg POM. granules: Basic<br />
cost: PL08637/0016; Salofalk 500mg PA573/3/7. granules, Salofalk pack 3g size granules: 100 sachets PL08637/0025; - £28.74; PA573/3/6. €30.39.<br />
Product licence holder: Salofalk 250mg tablets in the UK: Dr Falk Pharma UK Ltd,<br />
Salofalk<br />
Bourne End<br />
1000mg<br />
Business<br />
granules,<br />
Park, Cores<br />
pack<br />
End Road,<br />
size<br />
Bourne<br />
50 sachets<br />
End, SL8<br />
–<br />
5AS.<br />
£28.74;<br />
Salofalk<br />
32.87€.<br />
500mg<br />
Salofalk and 1g tablets 1.5g Granules, and all granules: pack Dr size Falk 60 Pharma sachets GmbH, - £48.85; Leinenweberstr.5, €50.02. Salofalk D-79108<br />
3g Freiburg, Granules Germany. pack Date size of 60 preparation: sachets - January £97.70; <strong>2023</strong> €102.62 (UK- NHS price; IE<br />
- PtW). Product licence number: Salofalk 500mg granules –<br />
Further information is available on request.<br />
PL08637/0007; PA573/3/1. Salofalk 1000mg granules – PL08637/0008;<br />
PA573/3/2. Salofalk 1.5g granules PL08637/0016; PA573/3/7. Salofalk<br />
Adverse events should be reported. In the UK: Reporting forms<br />
3g<br />
and<br />
granules<br />
information<br />
PL08637/0025;<br />
can be<br />
PA573/3/6.Product<br />
found at https://yellowcard.mhra.gov.<br />
licence holder: Dr Falk<br />
Pharma uk/ In GmbH, Ireland: Leinenweberstr.5, Reporting forms D-79108 and information Freiburg, Germany. can be found Date of<br />
preparation: at https://www.hpra.ie/homepage/about-us/report-an-issue/<br />
January 2022.<br />
Further human-adverse-reaction-form information is available on Adverse request. events should also be<br />
reported to Dr Falk Pharma UK Ltd at PV@drfalkpharma.co.uk.<br />
GASTROENTEROLOGY TODAY - SUMMER <strong>2023</strong><br />
Adverse events should be reported. Reporting forms and information<br />
References:<br />
can be found at https://yellowcard.mhra.gov.uk/ (UK residents) or in<br />
1. Ireland Salofalk at Granules. https://www.hpra.ie/homepage/about-us/report-anissue/human-adverse-reaction-form<br />
Kruis W et al. Gut 2009; 58(2): Adverse 233-40. events should also be<br />
Summary of Product Characteristics.<br />
2.<br />
3.<br />
reported<br />
Leifeld<br />
to<br />
L<br />
Dr<br />
et<br />
Falk<br />
al. Aliment<br />
Pharma<br />
Pharmacol<br />
UK Ltd at PV@drfalkpharma.co.uk<br />
Ther 2011; 34(9): 1115-22.<br />
4. Data on file, Dr Falk Pharma.<br />
References: UC: ulcerative colitis<br />
1. Salofalk Granules. Summary of Product Characteristics.<br />
2. Date Kruis of W preparation: et al. Gut 2009; March 58(2): <strong>2023</strong> 233-40.<br />
3. UI--2300071<br />
Leifeld L et al. Aliment Pharmacol Ther 2011; 34(9): 1115-22.<br />
4. Data on file, Dr Falk Pharma.<br />
Date of preparation: To March find out 2022more about Salofalk Granules<br />
UI--2200080 watch this 60s animation<br />
21
FEATURE<br />
GASTROENTEROLOGY TODAY - SUMMER <strong>2023</strong><br />
45. Consortium HMP. Structure, function and diversity of the healthy<br />
human microbiome. Nature. 2012;486(7402):207.<br />
46. Li W, Ma ZS. FBA ecological guild: trio of firmicutesbacteroidetes<br />
alliance against actinobacteria in human oral<br />
microbiome. Sci Rep. 2020;10(1):1–11.<br />
47. Liang D, Leung RKK, Guan W, et al. Involvement of gut<br />
microbiome in human health and disease: brief overview,<br />
knowledge gaps and research opportunities. Gut Pathogens.<br />
2018;10(1):1–9.<br />
48. Rowin J, Xia Y, Jung B, et al. Gut inflammation and dysbiosis in<br />
human motor neuron disease. Physiol Rep. 2017;5(18): e13443.<br />
49. Stojanov S, Berlec A, Štrukelj B. The influence of probiotics on<br />
the firmicutes/bacteroidetes ratio in the treatment of obesity and<br />
inflammatory bowel disease. Microorganisms. 2020;8(11):1715.<br />
50. Woting A, Blaut M. The intestinal microbiota in metabolic<br />
disease. Nutrients. 2016;8(4):202.<br />
51. Fernandes J, Su W, Rahat-Rozenbloom S, et al. Adiposity, gut<br />
microbiota and faecal short chain fatty acids are linked in adult<br />
humans. Nutr Diabetes. 2014;4(6):e121–e121.<br />
52. Bifari F, Ruocco C, Decimo I, et al. Amino acid supplements<br />
and metabolic health: a potential interplay between intestinal<br />
microbiota and systems control. Genes Nutr. 2017;12(1):1–12.<br />
53. Chambers ES, Preston T, Frost G, et al. Role of gut<br />
microbiota-generated short-chain fatty acids in metabolic and<br />
cardiovascular health. Curr Nutr Rep. 2018;7(4):198–206.<br />
54. Turnbaugh PJ, Ley RE, Mahowald MA, et al. An obesityassociated<br />
gut microbiome with increased capacity for energy<br />
harvest. Nature. 2006;444(7122):1027–31.<br />
55. Akobeng AK, Singh P, Kumar M, et al. Role of the gut microbiota<br />
in the pathogenesis of coeliac disease and potential therapeutic<br />
implications. Eur J Nutr. 2020;59:1–22.<br />
56. Caio G, Lungaro L, Segata N, et al. Effect of gluten-free diet on<br />
gut microbiota composition in patients with celiac disease and<br />
non-celiac gluten/wheat sensitivity. Nutrients. 2020;12(6):1832.<br />
57. Schiepatti A, Bacchi S, Biagi F, et al. Relationship between<br />
duodenal microbiota composition, clinical features at diagnosis,<br />
and persistent symptoms in adult Coeliac disease. Dig Liver Dis.<br />
2021;53:972–9.<br />
58. Golfetto L, de Senna FD, Hermes J, et al. Lower bifidobacteria<br />
counts in adult patients with celiac disease on a gluten-free diet.<br />
Arq Gastroenterol. 2014;51(2):139–43.<br />
59. Bodkhe R, Shetty SA, Dhotre DP, et al. Comparison of small<br />
gut and whole gut microbiota of first-degree relatives with<br />
adult celiac disease patients and controls. Front Microbiol.<br />
2019;10:164–164.<br />
60. de Sousa Moraes LF, Grzeskowiak LM, de Sales Teixeira TF, et<br />
al. Intestinal microbiota and probiotics in celiac disease. Clin<br />
Microbiol Rev. 2014;27(3):482–9.<br />
61. Ghodsi A, Sarabi M, Ranjbar G, et al. The gut microbiota and<br />
probiotics in celiac disease. J Nutr Fast Health. 2021;9(2):105–12.<br />
62. Norouzbeigi S, Vahid-Dastjerdi L, Yekta R, et al. Celiac therapy<br />
by administration of probiotics in food products: a review. Curr<br />
Opin Food Sci. 2020;32:58–66.<br />
63. Medina M, De Palma G, Ribes-Koninckx C, et al.<br />
Bifidobacterium strains suppress in vitro the pro-inflammatory<br />
milieu triggered by the large intestinal microbiota of coeliac<br />
patients. J Inflamm. 2008;5(1):1–13.<br />
64. Javanmard A, Ashtari S, Sabet B, et al. Probiotics and their<br />
role in gastrointestinal cancers prevention and treatment; an<br />
overview. Gastroenterol Hepatol Bed Bench. 2018;11(4):284.<br />
65. Chey WD, Kurlander J, Eswaran S. Irritable bowel syndrome: a<br />
clinical review. JAMA. 2015;313(9):949–58.<br />
66. Wang Z, Xu C-M, Liu Y-X, et al. Characteristic dysbiosis of<br />
gut microbiota of Chinese patients with diarrhea-predominant<br />
irritable bowel syndrome by an insight into the pan-microbiome.<br />
Chin Med J. 2019;132(8):889.<br />
67. Wang L, Alammar N, Singh R, et al. Gut microbial dysbiosis<br />
in the irritable bowel syndrome: a systematic review and<br />
meta-analysis of case-control studies. J Acad Nutr Diet.<br />
2020;120(4):565–86.<br />
68. Chong PP, Chin VK, Looi CY, et al. The microbiome and irritable<br />
bowel syndrome—a review on the pathophysiology, current<br />
research and future therapy. Front Microbiol. 2019;10:1136.<br />
69. Labus JS, Hollister EB, Jacobs J, et al. Differences in gut<br />
microbial composition correlate with regional brain volumes in<br />
irritable bowel syndrome. Microbiome. 2017;5(1):49.<br />
70. Duan R, Zhu S, Wang B, et al. Alterations of gut microbiota<br />
in patients with irritable bowel syndrome based on 16S<br />
rRNA-targeted sequencing: a systematic review. Clin Transl<br />
Gastroenterol. 2019;10:2.<br />
71. Lee BJ, Bak Y-T. Irritable bowel syndrome, gut microbiota and<br />
probiotics. J Neurogastroenterol Motil. 2011;17(3):252.<br />
72. Bellini M, Gambaccini D, Stasi C, et al. Irritable bowel syndrome:<br />
a disease still searching for pathogenesis, diagnosis and<br />
therapy. World J Gastroenterol. 2014;20(27):8807.<br />
73. Maccaferri S, Candela M, Turroni S, et al. IBS-associated<br />
phylogenetic unbalances of the intestinal microbiota are<br />
not reverted by probiotic supplementation. Gut Microb.<br />
2012;3(5):406–13.<br />
74. Daulatzai MA. Non-celiac gluten sensitivity triggers gut<br />
dysbiosis, neuroinflammation, gut-brain axis dysfunction, and<br />
vulnerability for dementia. CNS Neurol Disord Drug Targets.<br />
2015;14(1):110–31.<br />
75. Garcia-Mazcorro JF, Rivera-Gutierrez X, Cobos-Quevedo OJ,<br />
et al. First insights into the gut microbiota of Mexican patients<br />
with celiac disease and non-celiac gluten sensitivity. Nutrients.<br />
2018;10(11):1641.<br />
Publisher’s Note<br />
Springer Nature remains neutral with regard to jurisdictional claims in<br />
published maps and institutional affiliations.<br />
22
We get the gut<br />
JOIN OUR BSG LIVE ‘23<br />
SYMPOSIUM<br />
FEATURE<br />
Manipulation of the gut microbiome<br />
in gastrointestinal health<br />
WEDNESDAY 21ST JUNE<br />
13.00-13.40pm<br />
Stay on tract.<br />
Go further.<br />
A healthy microbiome is vital for a balanced<br />
digestive system.<br />
Delivering 450 billion bacteria across 8 diverse strains,<br />
VSL#3 is one of the most powerful polybiotics available<br />
to help enrich your patients’ gut microbiome. 1 Proven<br />
to survive the harsh stomach conditions 2 , VSL#3<br />
contributes to the diversity of good gut bacteria. 3<br />
Help to enrich your patient’s gut microbiome;<br />
Help them stay on track, with VSL # 3 ® .<br />
For information and samples, visit www.vsl3.co.uk<br />
Sign up to our NEW healthcare<br />
professional newsletter for the<br />
latest updates and research on<br />
gut health and probiotics.<br />
GASTROENTEROLOGY TODAY - SUMMER <strong>2023</strong><br />
VSL-23-001. Date of Preparation: April <strong>2023</strong>.<br />
1. Cancello R, et al. Nutrients 2019, 11, 3011.<br />
2. Vecchione A, et al. Front Med. 2018;5(59). doi: 10.3389/fmed.2018.00059.<br />
3. Singh G, et al. 2021 Clinical Nutrition ESPEN 47 (2022) 70-77.<br />
23
FEATURE<br />
TRIAGE GASTROSCOPY<br />
REFERRALS WITH<br />
A first-line test for the stomach<br />
BIOHIT HealthCare’s GastroPanel® is a simple<br />
and effective non-invasive test to diagnose<br />
advanced atrophic gastritis and Helicobacter<br />
pylori (H. pylori) in patients presenting with<br />
dyspepsia and upper abdominal symptoms.<br />
Where endoscopy resources and capacity are stretched,<br />
GastroPanel helps select cases for gastroscopy.<br />
GastroPanel measures three stomach-specific biomarkers,<br />
enabling a thorough and objective investigation of the whole<br />
gastric mucosa, non-invasively, and offers clinicians more<br />
confidence in their diagnoses or referrals.<br />
Atrophic gastritis – a chronic condition of the gastric mucosa,<br />
is considered to be the greatest independent risk factor for<br />
developing gastric cancer and current guidance recommends<br />
that individuals with extensive gastric atrophy undergo<br />
regular endoscopic surveillance to closely monitor their<br />
disease progression. Early detection of those individuals<br />
with a significant risk of developing gastric cancer is the<br />
key to effective patient management, helping to reduce<br />
unnecessary referrals, and improving survival rates through<br />
earlier diagnoses.<br />
Figure 1.<br />
GastroPanel measures<br />
plasma concentrations of<br />
Pepsinogen I, Pepsinogen II,<br />
Gastrin-17 and H. pylori IgG.<br />
GASTROENTEROLOGY TODAY - SUMMER <strong>2023</strong><br />
GastroPanel is a simple, effective and low cost blood test This patient-friendly blood test can help transform the<br />
that, through extensive validation, has consistently proven referral pathway for upper GI investigations by identifying<br />
to be effective in the determination of chronic atrophic<br />
those who need enhanced endoscopy with biopsies.<br />
gastritis, acid output disorders, and other diseases of<br />
Implementing GastroPanel could help to relieve the<br />
the gastric mucosa resulting from a H. pylori infection.<br />
burden on overstretched gastroscopy services, streamline<br />
When GastroPanel is positive, it helps direct appropriate and referrals for higher-risk patients, and effectively rule-out<br />
effective treatment plans, including, eradication therapy,<br />
atrophic gastritis for others.<br />
surveillance gastroscopy, and antacid prescription.<br />
Scan to find out more or visit www.biohithealthcare.co.uk<br />
24<br />
BIOHIT HealthCare Ltd<br />
Pioneer House, Pioneer Business Park, North Road,<br />
Ellesmere Port, Cheshire, United Kingdom CH65 1AD<br />
Tel. +44 151 550 4 550<br />
info@biohithealthcare.co.uk<br />
www.biohithealthcare.co.uk
ADVERTORIAL FEATURE<br />
THE NEXT, BRUSHLESS STEP IN<br />
ENDOSCOPE REPROCESSING<br />
Endoscopy continues to witness a number of important innovations that<br />
contribute to even better clinical outcomes. At the same time, there are still<br />
significant opportunities for further improving patient safety and infection<br />
prevention in the field. Given the constantly changing environment of medical<br />
device reprocessing, which is marked by a heightened consciousness of the<br />
overall environmental impact of healthcare and endoscopy, coupled with a<br />
shortage of hospital staff following Covid-19, improving the decontamination<br />
of endoscopes has become increasingly critical. Market feedback shows<br />
that there is a need for an automated and standardized process to clean<br />
endoscopes to ensure all steps are carried out in a uniform manner.<br />
Paul Caesar, Head of Hygiene, Infection Control and Reprocessing at<br />
PENTAX Medical EMEA, explains: “PENTAX Medical is launching the<br />
AquaTYPHOON to do just that. It is a new brushless solution for the<br />
automated pre-cleaning of endoscopes. The device was developed in<br />
association with PlasmaBiotics and offers an alternative to the manual<br />
pre-cleaning step in endoscope reprocessing without the need for brushes<br />
or detergent, addressing hygiene and sustainability challenges faced by<br />
healthcare providers in daily clinical practice.”<br />
Daniel Vinteler CEO of PlasmaBiotics, explains: “Thanks to its patented<br />
technology, the AquaTYPHOON disperses millions of water droplets in the<br />
endoscope channels through a compressed air flow at up to 200 kilometres<br />
per hour. Such high velocity creates a high shear stress which eliminates the<br />
residues from the endoscope channels walls.”<br />
Vinteler pursues: “Moreover, as this new technology replaces the mechanical<br />
brushing of the endoscope channels, wrist injuries are prevented. The<br />
reprocessing staff can work more comfortably with the height-adjustable<br />
AquaBOX which prevents splashing of the operator and the surrounding<br />
environment or uncomfortable positions.”<br />
Caesar continues: “The AquaTYPHOON offers a completely standardized,<br />
controlled and validated process, thus optimizing the pre-cleaning phase.<br />
No steps can be skipped any more so the results are more constant. I truly<br />
believe this new cutting-edge solution offers more balance between patient<br />
safety and staff productivity along with their well-being as the process is<br />
automated, lowering the risk of contamination.”<br />
PENTAX Medical AquaTYPHOON system with the AquaBOX<br />
The automated solution has built-in validation and safety features that help<br />
preventing human errors. The automated routine, unlike manual pre-cleaning,<br />
is always fully in line with the protocol and the full pre-cleaning procedure is<br />
documented. The system also offers full traceability and can be connected to<br />
hospital networks.<br />
Reprocessing staff member using the PENTAX Medical AquaTYPHOON<br />
Enhancing hygiene with automated pre-cleaning<br />
As an alternative to the manual pre-cleaning phase, the AquaTYPHOON<br />
improves hygiene and patient safety by further enhancing reprocessing<br />
of reusable endoscopes, through developing new ways of pre-cleaning<br />
to reduce the risk of infection. It automatically cleans all endoscope<br />
channels, including the non-brushable ones, removing organic residues<br />
very effectively, supporting the automated endoscope reprocessing (AER)<br />
process following the pre-cleaning.<br />
Supporting reprocessing staff for increased<br />
efficiency and ergonomics<br />
Focusing on efficiency, the AquaTYPHOON was designed to offer a<br />
solution to limits faced by staff, such as time constraints, heavy workloads,<br />
and ergonomic issues. It requires between two and five times less labour<br />
time , which reduces the daily workload for staff and increases productivity.<br />
Depending on the endoscope type being used, the device reduces channel<br />
pre-cleaning time to just 2-7 minutes.<br />
Balancing patient safety, productivity and sustainability<br />
As the AquaTYPHOON combines only water and air, waste generation<br />
due to consumables and/or chemicals is avoided. This solution reduces<br />
significantly water consumption, using this natural resource between six<br />
and ten times less than manual pre-cleaning . By optimizing efficiency but<br />
also reducing waste generation, it not only yields cost benefits but also has<br />
a positive environmental impact - making it an ideal solution for endoscopy<br />
departments looking to minimize their environmental footprint.<br />
By offering a reliable solution which enhances the reprocessing of reusable<br />
and semi-reusables endoscopes like the AquaTYPHOON, PENTAX Medical<br />
removes setbacks physicians might have when considering these devices,<br />
allowing them the highest possible freedom to pick the right equipment for<br />
their procedure. Paul Caesar concludes: “In the reprocessing process of<br />
endoscopes, stringent endoscope pre-cleaning is vital. However, it is much<br />
more than just a flush and a brush. As the industry seeks ways to optimize<br />
endoscope reprocessing, PENTAX Medical is turning to automated precleaning<br />
devices with this cutting-edge solution. Not only does it improve<br />
patient safety, but it also addresses the productivity challenges faced by staff<br />
along with hospitals’ sustainability and costs concerns.”<br />
Join our Digital<br />
Hygiene Event<br />
to learn more about<br />
sustainability in endoscopy.<br />
1<br />
Depending on the local guidelines, AquaTYPHOON requires between 2 and 5 times less labour time compared with today’s manual pre-cleaning solutions.<br />
2<br />
Depending on the endoscope type, AquaTYPHOON requires between 6 and 10 times less water compared with today’s manual pre-cleaning solutions.<br />
GASTROENTEROLOGY TODAY - SUMMER <strong>2023</strong><br />
25
ADVERTORIAL FEATURE<br />
FAECAL CALPROTECTIN<br />
ASK TWICE<br />
Dr Peter Rimmer, The Queen Elizabeth Hospital, Birmingham and Amanda Appleton, Senior Product Manager, Alpha Laboratories Ltd.<br />
We are all very familiar with the use of faecal calprotectin testing to help<br />
distinguish inflammatory bowel disease (IBD) from functional disorders,<br />
and it has become a staple tool to support the clinical teams in their<br />
diagnosis and management of patients. If a negative faecal calprotectin<br />
result is obtained the cause of a patient’s symptoms is unlikely to be<br />
IBD, however, calprotectin is a non-specific marker for inflammation, and<br />
so a high result may be due to something other than IBD.<br />
There was a significant difference in the median initial calprotectin which<br />
was 949µg/g for patients who were subsequently diagnosed with IBD<br />
compared to 353µg/g for those who didn’t have IBD. If two results were<br />
available, then the difference was even more pronounced with 749µg/g<br />
for those with IBD compared to 34µg/g for those without. This data is<br />
presented in the graphs below:<br />
The literature highlights numerous other situations that can cause<br />
(usually transient) increases in the calprotectin concentration found in<br />
stool samples, for example:<br />
• Use of certain medication e.g. NSAIDs, proton pump inhibitors<br />
• Diverticulitis<br />
• Infections e.g. Salmonella, Campylobacter<br />
• Stomach/duodenal ulcers<br />
• Excessive alcohol<br />
• Cancer<br />
Basically, anything that causes an irritation/ inflammatory response in the<br />
digestive system (mouth to anus) can cause an increase in calprotectin<br />
concentrations. Whereas a negative calprotectin is a good rule out for<br />
IBD, a positive calprotectin result isn’t necessarily a cause for instant<br />
referral to secondary care.<br />
The Queen Elizabeth Hospital in Birmingham introduced a rapid<br />
access ‘Inception IBD’ clinic based on symptoms and a raised faecal<br />
calprotectin test, Dr Peter Rimmer presented their findings and some<br />
proposed changes to the pathway at the European Crohn’s and Colitis<br />
Organisation (ECCO) conference in Copenhagen earlier this year (P126<br />
Ask Twice: The importance of a repeated faecal calprotectin testing prior<br />
to diagnostic colonoscopy in an adult inception cohort).<br />
The importance of repeated testing prior to diagnostic colonoscopy in<br />
an adult inception cohort - Comparison of first and second testing<br />
Supplementary graphs not presented on the poster show that 88.6%<br />
of calprotectin results fell between the first and second result in patients<br />
that subsequently had IBD excluded:<br />
GASTROENTEROLOGY TODAY - SUMMER <strong>2023</strong><br />
26<br />
“During the triaging process (for the Rapid Access clinic) it became<br />
apparent that the majority of patients only had one result at the point<br />
of referral, so patients were sent a sample pot in the post and asked to<br />
bring the sample back with them to their first outpatient appointment. The<br />
median time between the GP referral and this second result was 34 days.<br />
During this project, we did not reject referrals due to the lack of a<br />
second test, but we did delay the request for a colonoscopy until the<br />
second test was available in those with a borderline initial result or the<br />
clinical history was not strongly suggestive of IBD. This was only a few<br />
days as most brought the sample along to the appointment.”<br />
The data presented in the ECCO poster showed that there were 425 patients<br />
with a single calprotectin result and 185 patients who had two calprotectin<br />
results (using BÜHLMANN fCAL turbo on Abbott Alinity analysers) and a<br />
final diagnosis between January 2021 and November 2022.
ADVERTORIAL FEATURE<br />
It also demonstrates that 83% of patients with an increase<br />
between their first and second calprotectin test were subsequently<br />
found to have IBD.Although the overall statistics are compelling,<br />
interpretation is not always straightforward as Dr Rimmer explains:<br />
The poster concluded that the data, in general, supports repeat<br />
FCP testing to avoid unnecessary investigations adding to post<br />
COVID endoscopy backlogs. A cut-off of two values >200µg/g<br />
had the best overall performance but can miss a small number of<br />
IBD cases, particularly those with isolated ileitis or more indolent<br />
disease course. This cut-off should not be used in those with a<br />
marked increase between the 1st and 2nd result, where IBD is<br />
likely.<br />
Modifications to the local referral pathway are currently being<br />
determined, taking into account the data generated in the study.<br />
This will hopefully enable better use of over stretched resources<br />
which should in turn result in quicker access to those with most<br />
need.<br />
For more information on Faecal Calprotectin Testing visit:<br />
www.calprotectin.co.uk<br />
“We certainly feel that the faecal calprotectin (FCAL) is a highly<br />
accurate test, but there are some inconsistencies and pitfalls, which<br />
to an extent the graph represents:<br />
• The FCAL is just a snapshot from a single time point. In acute<br />
infection it will be high but if symptoms improve and FCAL<br />
normalises then investigation isn’t needed – post infective IBS is<br />
common in this patient group.<br />
• However, IBD is also characterised by periods of relapse and<br />
remission and FCAL will fluctuate alongside this, occasionally<br />
by the time we come to investigate they may have entered a<br />
milder phase of the disease. The clinical history and duration of<br />
symptoms in these patients is important, particularly with Crohn’s<br />
disease where the symptoms can be more insidious.<br />
We also had a handful of patients with mild proctitis in our<br />
cohort would not have been picked up with FCAL alone as<br />
their inflammation had largely resolved by the time we saw<br />
them.<br />
• FCAL will on rare occasions fail to correlate with disease severity,<br />
in the majority of our patients that was in ileal Crohn’s disease.<br />
Again, careful attention to the clinical history is necessary and<br />
investigation required regardless of the FCAL result in those with<br />
progressive symptoms or concerning features such as weight<br />
loss.”<br />
A variety of cut-off values were assessed on the poster, and two<br />
results of >200µg/g gave the best performance overall with a 85.7<br />
PPV% , 86.2 NPV% and a specificity of 89.5% but the sensitivity<br />
was lower than other cut-off values at 81.5%.<br />
SCOPE EVENTS FOR <strong>2023</strong>-24<br />
Scope Health UK<br />
Best Health Care Training & Education Courses Provider 2022<br />
from Northern Enterprise Awards 2022<br />
THERAPEUTIC ENDOSCOPY COURSE FOR ENDOSCOPY<br />
NURSE ASSISTANTS AND NURSE CONSULTANTS<br />
28th TECNA COURSE 17th JUNE SAT <strong>2023</strong> MANCHESTER<br />
29th TECNA COURSE 4th NOV SAT <strong>2023</strong> BRISTOL<br />
GASTROENTEROLOGY COURSE FOR GENERAL PRACTITIONERS<br />
1st GCGP COURSE 9th Sept <strong>2023</strong> MANCHESTER<br />
ENDOSCOPIC LESION RECOGNITION & IMAGING COURSE<br />
1st ELRIC COURSE 9th March 2024 MANCHESTER<br />
REGISTER AS EXHIBITORS/SPONSORS FOR <strong>2023</strong>/2024<br />
https://scopehealthuk.com/<br />
SCOPE HEALTH UK is Registered in England and Wales. Registration No 8170455<br />
TECNA : “A COURSE WITH VISION & MISSION TO EDUCATE”<br />
We look forward to meeting you at the course.<br />
GASTROENTEROLOGY TODAY - SUMMER <strong>2023</strong><br />
27
NEWS<br />
GASTROENTEROLOGY TODAY - SUMMER <strong>2023</strong><br />
28
COMPANY NEWS<br />
TAILOR-MADE INSOURCING/OUTSOURCING<br />
GASTROENTEROLOGY AND ENDOSCOPY CLINICAL SERVICES<br />
From delivering a full patient pathway, to building services based<br />
on individual requirements, ID Medical’s gastroenterology and<br />
endoscopy clinical services significantly reduce wait times, improve<br />
patient access, and increase outpatients and diagnostic capacity.<br />
ID Medical Clinical Services is a CQC-registered provider already helping<br />
many NHS trusts manage their patients’ healthcare pathways and<br />
improve patient outcomes. All while delivering millions of pounds worth<br />
of savings against NHS Tariffs.<br />
Our <strong>Gastroenterology</strong> Clinical Services are delivered by experienced NHS<br />
Consultants and nursing healthcare professionals. They work alongside our<br />
Senior Operations team, <strong>Gastroenterology</strong> Clinical Lead and Medical Director.<br />
We appreciate how important it is to comply with local service protocols,<br />
policies and processes which is why, whether insourcing or outsourcing<br />
is chosen, we are able to seamlessly integrate within existing services,<br />
working in full partnership with hospitals/trusts as an extension of the<br />
gastroenterology department.<br />
The service can be up and running in as little as two weeks and set up<br />
to meet exacting requirements: a 24/7 elective care service, weekends,<br />
during the week and/or evenings.<br />
More key benefits of IDM Clinical Services include:<br />
• National coverage<br />
• Insourcing/outsourcing options: fixed premises or mobile units to suit<br />
your requirements<br />
• No extra work for staff – from queries to admin, we take care of<br />
everything<br />
• Capacity to flex up or down based on demand<br />
• All Major Framework(s) approved, providing simple contractual<br />
engagement<br />
For further information, please visit id-medical.com/clinical-services,<br />
email clinicalservices@id-medical.com or call 01908 525 756.<br />
CONSTIPATION AFFECTS 14% OF OTHERWISE<br />
HEALTHY PEOPLE<br />
For the 1 in 7 people in the UK struggling with constipation, 1<br />
VSL# Fibre offers a unique combination of fibre, poly-biotics and<br />
hibiscus extract, to help maintain a healthy bowel and facilitate<br />
intestinal transit. These natural ingredients are designed to gently<br />
relieve symptoms of constipation, replenish the gut microbiota, and<br />
naturally restore a healthy toilet routine.<br />
Relieve: Psyllium Husk is recommended by NICE for the selfmanagement<br />
of constipation, as it’s over three times more effective than<br />
wheat bran at increasing stool output 2 . Psyllium Husk swells to form a<br />
gel-like substance when in contact with water, helping to ease bowel<br />
movements. It has also been associated with significant changes in gut<br />
microbiota in both healthy adults and people with constipation 3 .<br />
Replenish: Osmotic laxative use has been shown to destroy the<br />
gastrointestinal mucous barrier and alter gut microbial composition, with<br />
long-lasting effect 4 . VSL# Fibre contains the same 8 strains of bacteria<br />
found in VSL#3, offering 30 Billion CFU per serving. These strains<br />
have been proven to survive the harsh conditions of the stomach 5 and<br />
contribute to the diversity of good gut bacteria 6 .<br />
Restore: Alongside lifestyle management, VSL# Fibre could help<br />
restore a healthy toilet routine, facilitating intestinal transit and helping<br />
to maintain a healthy bowel. It can easily slot into your patients’ daily<br />
routine, by mixing it with 200ml water for a delicious fruity drink.<br />
VSL# Fibre is available to order through AAH, or can be purchased by<br />
patients directly from www.vsl3.co.uk<br />
1. Guts UK Charity. https://gutscharity.org.uk/advice-and-information/<br />
symptoms/constipation/<br />
2. NICE Clinical Knowledge Summary: Constipation in Adults. https://<br />
cks.nice.org.uk/ topics/constipation/management/adults/#initial-selfmanagement<br />
3. Jalanka et al. Int. J. Mol. Sci 2019, 20(2) 433<br />
4. Tropini et al. Cell. 2018 June 14; 173(7): 1742–1754<br />
5. Vecchione et al. Front Med. 2018;5(59)<br />
6. Kubacher et al Gut. 2006: 55(6): 833-841<br />
GASTROENTEROLOGY TODAY - SUMMER <strong>2023</strong><br />
29
COMPANY NEWS<br />
MICROBIOME CHARACTERISATION ENSURES SUCCESS<br />
IN FAECAL MICROBIOTA TRANSPLANTATION<br />
Graham Johnson, Managing Director, BIOHIT Healthcare<br />
GASTROENTEROLOGY TODAY - SUMMER <strong>2023</strong><br />
Faecal microbiota transplantation (FMT) is becoming a more widespread<br />
treatment for dysbiosis-associated conditions, in particular, for<br />
gastrointestinal disorders, and its use was further endorsed recently<br />
when, in 2022, the National Institute for Health and Care Excellence<br />
(NICE) approved it for treating recurrent Clostridium difficile infections.<br />
[1] However, several randomized controlled trials investigating FMT in<br />
irritable bowel syndrome (IBS) patients have revealed huge variability in<br />
treatment response.[2] These contradictory findings may be attributable<br />
to a lack of standardisation in various aspects of the trial protocol<br />
design, one of which is donor selection criteria.[3] At the same time,<br />
there has been a rising tendency to recruit ‘super-donors’ – favourable<br />
both in terms of their microbial diversity and stool composition – with<br />
the aim of ensuring positive outcomes for recipient patients.[4, 5] The<br />
gut microbiota of these donors is currently not always characterised,<br />
but some advocates of FMT are beginning to suggest that this may be<br />
more valuable than simple clinical screening when it comes to matching<br />
recipients to donors, especially with the innovative diagnostic tools<br />
that are now available.[6] Microbial profiling undoubtedly provides key<br />
information, such as the abundance and diversity of bacteria in the<br />
gut – as well as a measure of dysbiosis in patients – and applying this<br />
approach across the board as a measure of standardisation could help<br />
to refine therapeutic FMT strategies and lead to more consistent study<br />
results with favourable patient outcomes.[7]<br />
Purposeful protocol design<br />
This is certainly the strategy chosen by Magdy El-Salhy, Professor of<br />
<strong>Gastroenterology</strong> and Hepatology at the University of Bergen, whose<br />
research team recently conducted a clinical trial to determine the efficacy<br />
of FMT for IBS patients.[8] The study found that FMT is an effective<br />
therapy for IBS, with up to 89.1 % of patients responding to treatment,<br />
and around half of all patients experiencing clinical improvements in<br />
abdominal symptoms, fatigue and quality of life. However, Magdy is<br />
convinced that protocol design was key to ensuring the validity of the<br />
study results. There were five important factors: the super-donors<br />
were screened against set criteria; there was frequent faecal analysis<br />
of the donor to monitor microbiome stability; the fresh donor faeces<br />
were immediately frozen; the sample was mixed manually prior to<br />
administration; and the donor material was administered by gastroscope<br />
directly into the recipient’s duodenum.<br />
The right tool for the job<br />
On top of this, the GA-map ® Dysbiosis Test (GA-map ® Test) – a gut<br />
microbiota DNA-based platform that identifies and characterises<br />
dysbiosis – was used throughout the trial, as Magdy explained: “The<br />
GA map ® Test was fundamental to the analytical element of our trial;<br />
we used it to profile the faecal samples from the donor and to evaluate<br />
the intestinal bacterial profiles of patients following transplantation.”<br />
GA-map ® Test assigns each sample with an index that ranges from 1<br />
for ‘normobiosis’ to any score greater than 2 to represent an increasing<br />
degree of dysbiosis. Samples are then cross-indexed with an additional<br />
value that represents the abundance of present species compared to<br />
the reference population. Indexing in this manner refines the definition of<br />
dysbiosis and multiple FMT studies have correlated the GA-map ® Test<br />
index with effectiveness of therapeutic intervention.[9-12]<br />
Standardisation for success<br />
The trial protocol included faecal analysis of the super-donor at the<br />
start of the study to ensure that they had normal gut microbiota, and<br />
then at three monthly intervals throughout the year to confirm stability<br />
of their microbiome. Christina Casèn, Senior Vice President, Clinical<br />
and Medical Affairs at Genetic Analysis AS, said: “A standardised and<br />
validated test that could be conducted in situ was vital for this study as it<br />
involved repeated sampling and measurements of the donor. Performing<br />
analyses with the GA-map ® Test allowed the trial clinicians to compare<br />
results from different time periods instantaneously and evaluate FMT<br />
efficacy on site.”<br />
Characterisation to further understanding<br />
The study conducted by Magdy and his team confirmed that the<br />
outcome of FMT in IBS patients is donor dependent, and demonstrated<br />
that standardisation of key aspects of the trial protocol is critical. A<br />
donor needs to be well defined with both a normal dysbiosis index and<br />
a favourable specific microbial signature, and using dysbiosis testing<br />
platforms for characterisation can reduce variability in clinical response<br />
and ultimately ensure success of the FMT method. When clinicians are<br />
able to perform DNA-based faecal analysis themselves during trials –<br />
without needing to send samples to an external sequencing laboratory<br />
– they benefit from instantaneous information that guides FMT as an<br />
effective therapeutic intervention.<br />
References<br />
[1] NICE recommends transplant with good bacteria taken from poo to resolve recurrent Clostridium<br />
difficile infections | News | News | NICE, https://www.nice.org.uk/news/nice-recommends-faecalmicrobiota-transplant-for-recurrent-clostridioides-difficile-infection<br />
(accessed 16 January <strong>2023</strong>).<br />
[2] Cammarota G, Ianiro G, Tilg H, et al. European consensus conference on faecal microbiota<br />
transplantation in clinical practice. Gut 2017; 66: 569–580.<br />
[3] El-Salhy M, Hausken T, Hatlebakk JG. Current status of fecal microbiota transplantation for<br />
irritable bowel syndrome. Neurogastroenterology and Motility; 33. Epub ahead of print 1<br />
November 2021. DOI: 10.1111/NMO.14157.<br />
[4] Koren O, Fiorucci S, O’sullivan JM, et al. The Super-Donor Phenomenon in Fecal Microbiota<br />
Transplantation. Frontiers in Cellular and Infection Microbiology | www.frontiersin.org; 1. Epub<br />
ahead of print 2019. DOI: 10.3389/fcimb.2019.00002.<br />
[5] Moayyedi P, Surette MG, Kim PT, et al. Fecal Microbiota Transplantation Induces Remission in<br />
Patients With Active Ulcerative Colitis in a Randomized Controlled Trial. <strong>Gastroenterology</strong> 2015;<br />
149: 102-109.e6.<br />
[6] Allegretti JR, Mullish BH, Kelly C, et al. The evolution of the use of faecal microbiota<br />
transplantation and emerging therapeutic indications. The Lancet 2019; 394: 420–431.<br />
[7] Ianiro G, Punčochář M, Karcher N, et al. Variability of strain engraftment and predictability of<br />
microbiome composition after fecal microbiota transplantation across different diseases. Nature<br />
Medicine 2022 28:9 2022; 28: 1913–1923.<br />
[8] El-Salhy M, Gunnar Hatlebakk J, Kristoffersen AB, et al. Gut microbiota Efficacy of faecal<br />
microbiota transplantation for patients with irritable bowel syndrome in a randomised, doubleblind,<br />
placebo-controlled study. Gut 2020; 69: 859–867.<br />
[9] Wei S, Bahl MI, Dahl Baunwall SM, et al. Determining Gut Microbial Dysbiosis: a Review of Applied<br />
Indexes for Assessment of Intestinal Microbiota Imbalances. Epub ahead of print 2021. DOI:<br />
10.1128/AEM.00395-21.<br />
[10] El-Salhy M, Hausken T, Hatlebakk JG. Increasing the Dose and/or Repeating Faecal Microbiota<br />
Transplantation (FMT) Increases the Response in Patients with Irritable Bowel Syndrome (IBS).<br />
DOI: 10.3390/nu11061415.<br />
[11] Mazzawi T, Lied GA, Sangnes DA, et al. The kinetics of gut microbial community composition in<br />
patients with irritable bowel syndrome following fecal microbiota transplantation. PLoS One 2018;<br />
13: e0194904.<br />
[12] El-Salhy M, Hatlebakk JG, Gilja OH, et al. Efficacy of faecal microbiota transplantation for patients<br />
with irritable bowel syndrome in a randomised, double-blind, placebo-controlled study. Gut 2020;<br />
69: 859–867.<br />
30
COMPANY NEWS<br />
PENTAX MEDICAL’S NEW PREMIUM VIDEO PROCESSOR<br />
AND ENDOSCOPE SERIES NOW LAUNCHED<br />
See the future of endoscopy with the PENTAX Medical INSPIRA video processor (EPK-i8020c) and i20c endoscope series<br />
HAMBURG, 19 April <strong>2023</strong> – PENTAX Medical, a division of HOYA<br />
Group, has launched its two newest innovations: the PENTAX<br />
Medical INSPIRA premium video processor, and the i20c video<br />
endoscope series. The video processor acts as the bridge for<br />
legacy endoscopes 1 , bringing them to next level image quality,<br />
whilst the i20c video endoscope series supports procedures with<br />
superior vision and ergonomics.<br />
Improved clinical outcomes<br />
Boosting diagnostic and therapeutic capabilities is a core consideration<br />
in the development of all PENTAX Medical products. The new<br />
PENTAX Medical INSPIRA video processor aims to improve clinical<br />
outcomes by providing optimum image quality for all PENTAX Medical<br />
endoscopes, including legacy endoscopes 1 . When this processor is<br />
combined with the new i20c endoscope series, visualization is further<br />
enhanced by providing highly detailed images to show vessels and<br />
structures in the best possible clarity. Its ergonomic control body and<br />
steering wheels allow for improved maneuverability. The new platform is<br />
designed to support healthcare professionals in detection, diagnosis and<br />
therapy better than ever.<br />
Maximized value<br />
The PENTAX Medical INSPIRA video processor and i20c video<br />
endoscope series are designed to maximize the value of the endoscopy<br />
suite. The new video processor upgrades legacy endoscope portfolios<br />
to the latest imaging standards 1 , allowing current endoscope<br />
generations to meet high-class clinical needs for an extended duration<br />
of time. By providing an LED light source and smart image processing<br />
to a wide range of compatible endoscopes, it extends the lifecycle of<br />
each endoscope for greater sustainability. The processor’s dual port<br />
is compatible with two connection types, which makes this solution<br />
a gateway to the future of endoscopes. This i20c endoscope series<br />
consists of a unique control body and lightweight connector to enhance<br />
the user experience.<br />
Rainer Burkard, Global President at PENTAX Medical, comments:<br />
“At PENTAX Medical we care about providing the best possible<br />
support for health care professionals. We are very excited about our<br />
new premium platform INSPIRA setting new standards in endoscopy:<br />
the INSPIRA video processor allows physicians to upgrade legacy<br />
endoscopes, whilst being future-proof for the next generation, like<br />
the new i20c video endoscopes. Physicians benefit from optimized<br />
endoscopic workflows, improved imaging, and visualization, while<br />
extending lifecycles and experiencing superior ergonomics.”<br />
Enhanced experience and satisfaction<br />
PENTAX Medical is committed to continuously developing innovative<br />
products in accordance with physicians’ needs, as they spend countless<br />
hours working with these instruments. The unique 7-inch touchscreen<br />
with intuitive plug-and-play features of the new video processor,<br />
alongside the customizable graphical user interface, means that they<br />
can truly focus on their patient.<br />
Dr. Marc Giovannini, Chief of the Department of Medico-surgical<br />
Digestive Oncology, Institut Paoli-Calmettes, France, shares: “This<br />
new processor improves dramatically the quality of the endoscopic<br />
image, especially with the 4K screen.” The i20c endoscope series<br />
features improved ergonomics and adjustable stiffness, significantly<br />
improving the user experience for all physicians. This new generation of<br />
endoscopes offers richly detailed imaging, and the Auto-HDR feature<br />
provides true colors and high contrasts. Healthcare professionals can<br />
enjoy outstanding maneuverability, angulation and handling, combined<br />
with further improved vision.<br />
After receiving CE marks in January, these solutions are commercially<br />
available from April 19th, <strong>2023</strong>. Launch dates may vary between global<br />
regions, please contact your local PENTAX Medical sales representative<br />
for further information.<br />
Join PENTAX Medical at the ESGE Days <strong>2023</strong>, in Dublin, for the official<br />
launch event. A team of experts will be there to showcase how these<br />
new innovations help any department meet its goals for patient safety,<br />
productivity, and sustainability. If you are interested in attending this<br />
event in-person or online, or in an interview with an executive, please<br />
contact Charlotte Hérault (charlotte.herault@omnicomprgroup.com).<br />
1<br />
90i, i10, J10, 90K and i10c series endoscopes. Not all models are<br />
compatible. For details, contact your local PENTAX Medical service<br />
facility.<br />
GASTROENTEROLOGY TODAY - SUMMER <strong>2023</strong><br />
PENTAX Medical INSPIRA video processor (EPK-i8020c) and i20c endoscope series<br />
31
Helicobacter Test INFAI ®<br />
One of the most used<br />
13<br />
C-urea breath tests for the diagnosis<br />
of Hp-infections worldwide<br />
• New line of INFAI packaging and serialization according the EU’s Falsified Medicines Directive<br />
• More than 7.0 million Helicobacter Test INFAI performed worldwide<br />
• Registered in more than 40 countries worldwide<br />
• First approved Hp test for children from the ages of 3 to 11<br />
• Modified Hp test for patients taking PPIs (REFEX)<br />
• Modified Hp test for patients with atrophic gastritis<br />
• Cost-effective CliniPac Basic for hospital and GPs use<br />
INFAI UK Ltd<br />
Innovation Centre, York Science Park<br />
University Road, Heslington<br />
York YO10 5DG UK<br />
Phone: +44 1904 435 228<br />
Fax: +44 1904 435 229<br />
E-Mail: mail@infai.co.uk<br />
Web: www.infai1.com