Treat. The. Gut.

Treat.The.Gut.Addressing CDI, UC, IBS and more withFecal Microbiota Transplantation (FMT)Mark Davis, ND

Treat.The.Gut.Addressing CDI, UC, IBS and more withFecal Microbiota Transplantation (FMT)Mark Davis, ND2013 AANP convention in the licensed state of Colorado!

introduction• Mark Davis, ND• NCNM class of 2011, honors in research• Private practice, Bright Medicine Clinic: Portland, OR

introduction• Mark Davis, ND• NCNM class of 2011, honors in research• Private practice, Bright Medicine Clinic: Portland, OR• I’ve used FMT with sixty patients, about half of whom haveinflammatory bowel disease (IBD)• Remote consults with dozens more, but no doctor/patientrelationship, generally little follow-up, and no data collection

introduction• Mark Davis, ND• NCNM class of 2011, honors in research• Private practice, Bright Medicine Clinic: Portland, OR• I’ve used FMT with sixty patients, about half of whom haveinflammatory bowel disease (IBD)• Remote consults with dozens more, but no doctor/patientrelationship, generally little follow-up, and no data collection• Was only physician in North America offering donor-bank drivenFMT for conditions outside of C difficile infection (CDI)• FecalMicrobiotaTransplantation.com, probioticinfusion.com

Acknowledgements andconflict of interestThanksImages and quotesCOI

Room surveyRaise your hand if you’ve ever prepared or administeredfecal slurry for therapeutic benefit

Room surveyRaise your hand if you’ve ever prepared or administeredfecal slurry for therapeutic benefitRaise your hand if you’ve recommended FMT to apatient, referred for FMT, or walked a patient throughhow to prepare and self-administer FMT at home

Overview• Nomenclature and history• Micro/gastro review (with fun quizzes!)• Nuts and bolts of FMT• Current legal status• Cost and the yuck factor• In the literature: Safety and efficacy of FMT for CDI, IBD,IBS, and more• Case series and case

FMT, aka…

FMT, aka…Fecal transplant

FMT, aka…Fecal transplantFecal bacteriotherapy

FMT, aka…Fecal transplantFecal bacteriotherapyHuman probiotic infusion

FMT, aka…Fecal transplantFecal bacteriotherapyHuman probiotic infusionFecal slurry

FMT, aka…Fecal transplantFecal bacteriotherapyHuman probiotic infusionFecal slurryGut flora rehabilitation

FMT, aka…Fecal transplantFecal bacteriotherapyHuman probiotic infusionFecal slurryGut flora rehabilitationIntestinal microbiota transplantation

FMT, aka…Fecal transplantFecal bacteriotherapyHuman probiotic infusionFecal slurryGut flora rehabilitationIntestinal microbiota transplantationFecal microbiota transplantation

HistoryGe Hong, 4th century CE

HistoryGe Hong, 4th century CEPO fecal suspension for food poisoning or severe diarrhea

HistoryGe Hong, 4th century CEPO fecal suspension for food poisoning or severe diarrheaLi Shizhen, 16th century CE

HistoryGe Hong, 4th century CEPO fecal suspension for food poisoning or severe diarrheaLi Shizhen, 16th century CEFermented, fresh, dried, or infant feces (“yellow soup” ) forsevere diarrhea, vomiting, and constipation

HistoryFabricius Aquapendente(1537-1619)Transfaunation

HistoryJournal of AdvancedTherapeutics, Jan 1910

• Ben Eiseman, MDHistory

History• Ben Eiseman, MDBen Eiseman, MD

History• Ben Eiseman, MDBen Eiseman, MDWilliam Silen, MD

HistoryClostridium difficile discovered in 1935, but link betweenC diff and pseudomembranous colitis not elucidateduntil 1978.

History

History• 11 years of UC• 7 years of severe symptoms if he dropped below 30 mg/dprednisone• 3 months post-FMT no symptoms, no prednisone, colonoscopyreveals no active inflammation

History

History

History

History

History

History

History

History

Micro/gastro Review

Micro/gastro ReviewWhat percent ofa human beingconsists ofmicrobes??

Micro/gastro ReviewMicrobes make up:A. 1-3% of the total human

Micro/gastro ReviewMicrobes make up:A. 1-3% of the total humanB. 90% of the total human

Micro/gastro ReviewMicrobes make up:A. 1-3% of the total humanB. 90% of the total humanC. 99% of the total human

Micro/gastro ReviewMicrobes make up:A. 1-3% of the total humanB. 90% of the total humanC. 99% of the total humanD. All of the above

Micro/gastro ReviewIn which of the following areas do microbes live?(please cheer for microbe-containing areas as Iread them)

Micro/gastro ReviewIn which of the following areas do microbes live?The adult colon

Micro/gastro ReviewIn which of the following areas do microbes live?The adult colonThe lungs

Micro/gastro ReviewIn which of the following areas do microbes live?The adult colonThe lungsThe bladder

Micro/gastro ReviewIn which of the following areas do microbes live?The adult colonThe lungsThe bladderThe GI tract of a fetus

Micro/gastro ReviewIn which of the following areas do microbes live?The adult colonThe lungsThe bladderThe GI tract of a fetus

Micro/gastro ReviewIn which of the following areas do microbes live?The adult colonThe lungsThe bladderThe GI tract of a fetus

Micro/gastro ReviewIn which of the following areas do microbes live?The adult colonThe lungsThe bladderThe GI tract of a fetus

The gut microbiome

The gut microbiomeConcentration of bacteria per mL:• Duodenum: 10-1,000• Jejunum & ileum: 10,000-one million• Colon: 10-100 billion

The gut microbiome

The gut microbiome

The gut microbiomePatients often report that the consistency and odor of their bowel movements becomesidentical to that of their donor.

OK, but what is it?

OK, but what is it?Fecal microbiota transplantationconsists of collecting stool from ahealthy donor, diluting, blending,and filtering it, and delivering it tothe patient, usually via enema

OK, but what is it?Fecal microbiota transplantationconsists of collecting stool from ahealthy donor, diluting, blending,and filtering it, and delivering it tothe patient, usually via enema

OK, but what is it?Fecal microbiota transplantationconsists of collecting stool from ahealthy donor, diluting, blending,and filtering it, and delivering it tothe patient, usually via enema

OK, but what is it?Fecal microbiota transplantationconsists of collecting stool from ahealthy donor, diluting, blending,and filtering it, and delivering it tothe patient, usually via enema

FMT Working GroupScreening protocolsSerologic testing• HIV 1 and 2• Rapid plasma reagin andfluorescent treponemalantibody-absorbed•Viral hepatitis panel

FMT Working GroupScreening protocolsSerologic testing• HIV 1 and 2• Rapid plasma reagin andfluorescent treponemalantibody-absorbed•Viral hepatitis panelStool testing• C difficile toxin B by PCR• Routine bacterial culture forenteric pathogens• Fecal Giardia antigen• Fecal Cryptosporidium antigen• Acid-fast stain for Cyclospora andIsospora• Microscopy for ova and parasites

FMT Working GroupScreening protocolsSerologic testing• HIV 1 and 2• Rapid plasma reagin andfluorescent treponemalantibody-absorbed•Viral hepatitis panelI add:•PCR stool screening test to look atrelative abundances of somenormal stool flora as well as screenin a more sensitive way for somepathogens or borderline pathogensStool testing• C difficile toxin B by PCR• Routine bacterial culture forenteric pathogens• Fecal Giardia antigen• Fecal Cryptosporidium antigen• Acid-fast stain for Cyclospora andIsospora• Microscopy for ova and parasites

FMT Working GroupScreening protocols• The eligible donor is a healthy individual withoutcommunicable disease or risk factors, with no history ofIBD, IBS, or GI malignancy, no antibiotic, majorimmunosuppressive or systemic antineoplastic use in thepast three months, who does not have autoimmune, atopicor chronic pain disease, food or respiratory allergies,metabolic syndrome or mood disorders, and has notrecently ingested any potential allergens.

FMT Working GroupScreening protocols• The eligible donor is a healthy individual withoutcommunicable disease or risk factors, with no history ofIBD, IBS, or GI malignancy, no antibiotic, majorimmunosuppressive or systemic antineoplastic use in thepast three months, who does not have autoimmune, atopicor chronic pain disease, food or respiratory allergies,metabolic syndrome or mood disorders, and has notrecently ingested any potential allergens.• I also consider: was the donor breastfed, vaginally delivered?Willing and able to stay well-hydrated and eat a diet rich infibrous whole foods? Has a 3-4 on the Bristol stool scale onmost days? Skin health? Mental clarity? Adult vs.pediatric? Blood type? Gender? Strong vis?

How to perform FMT:Utilize the healing power of nature

How to perform FMT:Utilize the healing power of natureTreat the cause (patient screening)

How to perform FMT:Utilize the healing power of natureTreat the cause (patient screening)Do no harm (donor screening)

How to perform FMT:

How to perform FMT:

How to perform FMT:

How to perform FMT:

How to perform FMT:

How to perform FMT:

How to perform FMT:x1

How to perform FMT:x1x10

Current legal status

Current legal status• Long history of naturopathic doctors being jailed orprosecuted for practicing ways not approved bycontemporary legislators.

Current legal status• Long history of naturopathic doctors being jailed orprosecuted for practicing ways not approved bycontemporary legislators.• FMT had long been in legislative limbo

Current legal status• Long history of naturopathic doctors being jailed orprosecuted for practicing ways not approved bycontemporary legislators.• FMT had long been in legislative limbo• Different legal opinions:

Current legal status• “Since the FDA regulates interstate commerce inmedicine, if you’re using stool from Oregon anddiluent from Oregon, I don’t really see how it’s theFDA’s business what you do.”

Current legal status• “You really don’t want to get in a pissing match withthe FDA.”

Current legal status• “You really don’t want to get in a pissing match withthe FDA.”

Current legal status• “You really don’t want to get in a pissing match withthe FDA.”

Current legal status• “You really don’t want to get in a pissing match withthe FDA.”Conversations around FMT?

Current legal status• “You really don’t want to get in a pissing match withthe FDA.”Conversations around FMT?“The FDA is allowing it’s regulatory policies toevolve”

Current legal status“The FDA is allowing it’s regulatory policies toevolve”

Current legal status“The FDA is allowing it’s regulatory policies toevolve”

Current legal status“The FDA is allowing it’s regulatory policies toevolve”

Current legal status

Current legal status

Cost• Centre for Digestive Diseases: US patients estimatespending $10,000-$20,000 counting travel and lodging costs(10 days?)• Rogue Valley: $2,000 + donor screening (single infusion)• Bright Medicine: $800 donor screening fee plus $400 perpreparation & administration ($1200 for a single infusion)• DIY with a trusted, symptom-free related donor (e.g. a childor parent): $2 for an enema bag, plus $15 for a blender ($17for a single infusion).

The “yuck” factor• Not so yucky after all:• Khan SA, Gorawara-Bhat R, Rubin D. Fecalbacteriotherapy forulcerative colitis:patients are ready, arewe? Inflamm BowelDis 2011

Causes of CDI, IBD, IBS

Causes of CDI, IBD, IBS

FMT for CDI• CDI is Clostridium difficile infection: spore former,commonly overgrows after clindamycin, penicillin,floroquinalones, cephalosporins

FMT for CDI• CDI is Clostridium difficile infection: spore former,commonly overgrows after clindamycin, penicillin,floroquinalones, cephalosporins• Detected using PCR for toxin B

FMT for CDI• CDI is Clostridium difficile infection: spore former,commonly overgrows after clindamycin, penicillin,floroquinalones, cephalosporins• Detected using PCR for toxin B• Detected in 0.26% of hospitalized patients in 1993,and 0.54% of hospitalized patients in 2003

FMT for CDI• CDI is Clostridium difficile infection: spore former,commonly overgrows after clindamycin, penicillin,floroquinalones, cephalosporins• Detected using PCR for toxin B• Detected in 0.26% of hospitalized patients in 1993,and 0.54% of hospitalized patients in 2003• In 2010, the annual incidence of CDI was estimated at500,000 and mortality at 15,000–20,000

FMT for CDI• Conventional Rx:• Vancocin (or compounded vancomycin, FDA approvedtreatment): 85-96% effective, 20-25%% recurrence. (31% relapsewith tapered, 14% with pulsed) Takes 3-8 days. Small caseseries: 8/9 cases cured with enema delivery.• Metronidazole: 74-87% effective, 20-30% recurrence ratewithin 60 days. Takes 8-16 days to work. Long courses canlead to neuropathies.• Rifaximin, nitazoxinide may help.• Dificid (fidaxomicin): FDA approved in May 2011.• 85% effective, 15% relapse• Sach boulardii decreases relapse rate if given with >2gvancomycin, caution with fungemia in immunosuppressedpatients.

FMT for CDI• Conventional Rx:• Vancocin (or compounded vancomycin, FDA approvedtreatment): 85-96% effective, 20-25%% recurrence. (31% relapsewith tapered, 14% with pulsed) Takes 3-8 days. Small caseseries: 8/9 cases cured with enema delivery.• Metronidazole: 74-87% effective, 20-30% recurrence ratewithin 60 days. Takes 8-16 days to work. Long courses canlead to neuropathies.• Rifaximin, nitazoxinide may help.• Dificid (fidaxomicin): FDA approved in May 2011.• 85% effective, 15% relapse• Sach boulardii decreases relapse rate if given with >2gvancomycin, caution with fungemia in immunosuppressedpatients.

FMT for CDI• Up to 65% of patients who have experienced onerecurrence will experience another

FMT for CDI• Up to 65% of patients who have experienced onerecurrence will experience another• About 1/3 of recurrences are new strain

FMT for CDI• Up to 65% of patients who have experienced onerecurrence will experience another• About 1/3 of recurrences are new strain• If resistant to all antibiotics, colectomy (0.25-1% ofpatients with C diff diagnosis)

FMT for CDI• Up to 65% of patients who have experienced onerecurrence will experience another• About 1/3 of recurrences are new strain• If resistant to all antibiotics, colectomy (0.25-1% ofpatients with C diff diagnosis)• CDI was 7.8% fatal in 1993, 9.3% fatal in 2003

FMT for CDI• Up to 65% of patients who have experienced onerecurrence will experience another.• About 1/3 of recurrences are new strain.• If resistant to all antibiotics, colectomy (0.25-1% ofpatients with C diff diagnosis).• CDI was 7.8% fatal in 1993, 9.3% fatal in 2003.

FMT for CDI

FMT for CDI

• 92% successfulFMT for CDI

FMT for CDI• 92% successful• Therapeutic response in hours to days

FMT for CDI• 92% successful• Therapeutic response in hours to days• If delivered by enema, only noted S/E is transientabdominal tenderness

FMT for CDI• 92% successful• Therapeutic response in hours to days• If delivered by enema, only noted S/E is transientabdominal tenderness• If delivered via colonoscope, could include perforation,risks of anesthesia

FMT for CDI

FMT for CDI• Reviewed 317 patients treated for CDI with FMT

FMT for CDI• Reviewed 317 patients treated for CDI with FMT• 92% experienced resolution, 4% relapse rate.

FMT for CDIBest guesses for best care:Up to 3 infusions (96% effective)vs.1 infusion (88%)

FMT for CDIBest guesses for best care:Enema or rectal catheter delivery (95% effective)vs.colonoscopic (88%)

FMT for CDIBest guesses for best care:Related donor, counting spouses (93% effective)vs.unrelated (84%) or mixed (79%)

FMT for CDIBest guesses for best care:Water as diluent (95% effective)vs.N saline (86%)

FMT for CDIBest guesses for best care:>500 mL suspension (97% effective)vs.200-500 mL (86%)or

FMT for CDI

FMT for CDI

FMT for CDI

FMT for CDI

FMT for CDIMy limited results: less durable

FMT for CDIQuestions about FMT for CDI?

FMT for IBD and IBS

FMT for IBD and IBS

FMT for IBD and IBS

FMT for IBD and IBS

FMT for IBD and IBS

FMT for IBD and IBS

FMT for IBD and IBS

FMT for IBD and IBS

FMT for IBD and IBS

FMT for IBD and IBS

FMT for IBD and IBSQuestions about FMT for IBD andIBS?

FMT for otherconditions

FMT for otherconditions

FMT for otherconditions

FMT for otherconditions

FMT for otherconditions

FMT for otherconditions

FMT for otherconditions

Case series

Case series

Case series

Case #1• 51yo M with 36y hx of IBD sxs, UC dx for 15y

Case #1• 51yo M with 36y hx of IBD sxs, UC dx for 15y• Managed on asacol 1600 mg qid, 6mp 50mg/d,remicade q 6 weeks, cortenema 2-3x/week

Case #1• 49yo M with 34y hx of IBD sxs, UC dx for 13y• Managed on asacol 1600 mg qid, 6mp 50mg/d,remicade q 6 weeks, cortenema 2-3x/week• 3-4 urgent BMs/d, no blood or mucous as long as heavoids certain fiber foods (esp lettuce)

Case #1• 49yo M with 34y hx of IBD sxs, UC dx for 13y• Managed on asacol 1600 mg qid, 6mp 50mg/d,remicade q 6 weeks, cortenema 2-3x/week• 3-4 urgent BMs/d, no blood or mucous as long as heavoids certain fiber foods (esp lettuce)• Colonoscopy 5 months previous reveals L sided colitis

Case #1

Case #1• Daily fecal slurry retention enemas, M-F x 3 weeks

Case #1• Daily fecal slurry retention enemas, M-F x 3 weeks• Followed by 1-2x/week for 4 weeks

Case #1• Daily fecal slurry retention enemas, M-F x 3 weeks• Followed by 1-2x/week for 4 weeks• Moved from 3-4 BM/d to 1-2, D/C’d hydrocortisoneenemas

Case #1• Daily fecal slurry retention enemas, M-F x 3 weeks• Followed by 1-2x/week for 4 weeks• Moved from 3-4 BM/d to 1-2, D/C’d hydrocortisoneenemas• Challenged with lettuce:

Case #1• Daily fecal slurry retention enemas, M-F x 3 weeks• Followed by 1-2x/week for 4 weeks• Moved from 3-4 BM/d to 1-2, D/C’d hydrocortisoneenemas• Challenged with lettuce: blood/mucus in stool

Case #1• Vancomycin 500 mg bid, metronidazole 500 mg bid,rifampicin 150 mg bid, all po x 7

Case #1• Vancomycin 500 mg bid, metronidazole 500 mg bid,rifampicin 150 mg bid, all po x 7• Oral lacto/bifido probiotic 50b CFU/d x 7d

Case #1• Vancomycin 500 mg bid, metronidazole 500 mg bid,rifampicin 150 mg bid, all po x 7• Oral lacto/bifido probiotic 50b CFU/d x 7• Interphase (+) 2 caps bid x 7d

Case #1• Vancomycin 500 mg bid, metronidazole 500 mg bid,rifampicin 150 mg bid, all po x 7• Oral lacto/bifido probiotic 50b CFU/d x 7• Interphase (+) 2 caps bid x 7d• 10 mg prednisone taper c 50 mg DHEA

Case #1• Vancomycin 500 mg bid, metronidazole 500 mg bid,rifampicin 150 mg bid, all po x 7• Oral lacto/bifido probiotic 50b CFU/d x 7• Interphase (+) 2 caps bid x 7d• 10 mg prednisone taper c 50 mg DHEA• Day 8: PEG bowel lavage, only H2O po

Case #1• Daily fecal slurry retention enemas, M-F x 3 weeks• Followed by 1-2x/week for (6?) weeks

Case #1• Daily fecal slurry retention enemas, M-F x 3 weeks• Followed by 1-2x/week for (6?) weeks• No blood, no mucus, 1-2 formed BM/d

Case #1• Daily fecal slurry retention enemas, M-F x 3 weeks• Followed by 1-2x/week for (6?) weeks• No blood, no mucus, 1-2 formed BM/d• Gradually D/C’d all meds, remained aymptomatic

Case #1• Daily fecal slurry retention enemas, M-F x 3 weeks• Followed by 1-2x/week for (6?) weeks• No blood, no mucus, 1-2 formed BM/d• Gradually D/C’d all meds, remained aymptomatic• Lettuce challenge:

Case #1• Daily fecal slurry retention enemas, M-F x 3 weeks• Followed by 1-2x/week for (6?) weeks• No blood, no mucus, 1-2 formed BM/d• Gradually D/C’d all meds, remained aymptomatic• Lettuce challenge: no symptoms!

Case #1• Daily fecal slurry retention enemas, M-F x 3 weeks• Followed by 1-2x/week for (6?) weeks• No blood, no mucus, 1-2 formed BM/d• Gradually D/C’d all meds, remained aymptomatic• Lettuce challenge: no symptoms!• 14 months aymptomatic with no meds, varied diet

Case #2• Warning: graphic images including stool and blood

Case #2• 22-month-old M with six month history of blood instool leading to hospitalization and diagnosis ofulcerative pancolitis three months previously (& VRE)

Case #2• 22-month-old M with six month history of blood instool leading to hospitalization and diagnosis ofulcerative pancolitis three months previously (& VRE)• 5 (+?) blood transfusions in previous three months, anda couple weeks of parenteral nutrition

Case #2• 22-month-old M with six month history of blood instool leading to hospitalization and diagnosis ofulcerative pancolitis three months previously (& VRE)• 5 (+?) blood transfusions in previous three months, anda couple weeks of parenteral nutrition• Prednisone taper (currently 7.5 mg), low fiber diet,Sach boulardii bid, iron suppls

Case #2• 22-month-old M with six month history of blood instool leading to hospitalization and diagnosis ofulcerative pancolitis three months previously (& VRE)• 5 (+?) blood transfusions in previous three months, anda couple weeks of parenteral nutrition• Prednisone taper (currently 7.5 mg), low fiber diet,Sach boulardii bid, iron suppls• 5-10 bloody BMs/d, three diaper changes during ourfirst (1h) office visit:

Case #2

Case #2

Case #2

• Day 1, sample diaper:Case #2

Case #2• Day 1, sample diaper:• Eve 1, 80 mL night-time infusion

Case #2• Days 2-6, gradual decrease in frequency, bleeding

Case #2• Days 2-6, gradual decrease in frequency, bleeding• Day 7, first day of no blood, formed stool

Case #2• Days 2-6, gradual decrease in frequency, bleeding• Day 7, first day of no blood, formed stool• Day 8, only 2 BMs, small amount blood in one

Case #2• Days 2-6, gradual decrease in frequency, bleeding• Day 7, first day of no blood, formed stool• Day 8, only 2 BMs, small amount blood in one• Days 9-10, no blood, formed stool**This is ten consecutive infusions, and I instruct movingto q other day evening infusions

Case #2• Days 2-6, gradual decrease in frequency, bleeding• Day 7, first day of no blood, formed stool• Day 8, only 2 BMs, small amount blood in one• Days 9-10, no blood, formed stool**This is ten consecutive infusions, and I instruct movingto q other day evening infusions• Day 11, mom frustrated with mood swings, stopsprednisone 3 days early (skips infusion)

• Day 12 sample diaper:Case #2

Case #2• Day 12 sample diaper:(cold or flu in household?)(evening FMT infusion)

Case #2• Day 12 sample diaper:(cold or flu in household?)(evening FMT infusion)• Day 13 sample diaper:(Mom has cold, no FMT)

Case #2• Over the next week, no FMT and patient starts todecline

Case #2• Over the next week, no FMT and patient starts todecline• Emergent care, infliximab started. Pediatric gastroasks for no outside interventions during this time

Case #2• Over the next week, no FMT and patient starts todecline• Emergent care, infliximab started. Pediatric gastroasks for no outside interventions during this time• Infliximab q 6 weeks, breakthrough sx in 2 weeks preinfliximabover the course of three rounds (4 months)

Case #2• Over the next week, no FMT and patient starts todecline• Emergent care, infliximab started. Pediatric gastroasks for no outside interventions during this time• Infliximab q 6 weeks, breakthrough sx in 2 weeks preinfliximabover the course of three rounds (4 months)• Evening FMT infusions q 2 nights for one month—nobreakthrough symptoms

Case #2• Currently still on infliximab q 8 weeks withoutbreakthrough symptoms

Case #3• 30yo F with ulcerative proctitis (20 cm from rectum) x6 months

Case #3• 30yo F with ulcerative proctitis (20 cm from rectum) x6 months• Well-managed on curcumin 1 g bid, boswellia 1g/d,fish oil (8-10 g/d EPA/DHA), lacto/bifido probiotic4b CFUs/d

Case #3• 30yo F with ulcerative proctitis (20 cm from rectum) x6 months• Well-managed on curcumin 1 g bid, boswellia 1g/d,fish oil (8-10 g/d EPA/DHA), lacto/bifido probiotic4b CFUs/d• S boulardii and LDN added after three months, addedbenefit for atopic derm

Case #3• 30yo F with ulcerative proctitis (20 cm from rectum) x6 months• Well-managed on curcumin 1 g bid, boswellia 1g/d,fish oil (8-10 g/d EPA/DHA), lacto/bifido probiotic4b CFUs/d• S boulardii and LDN added after three months, addedbenefit for atopic derm• Mesalamine enemas added after another three monthsduring stress of family travel

Case #3• Another three months, UP flare not responsive to anyof above therapies or dietary restrictions

Case #3• Another three months, UP flare not responsive to anyof above therapies or dietary restrictions• Emotionally unable to complete 24-hour water fast

Case #3• Another three months, UP flare not responsive to anyof above therapies or dietary restrictions• Emotionally unable to complete 24-hour water fast• 10 FMT home infusions with child donor: no benefit

Case #3• Another three months, UP flare not responsive to anyof above therapies or dietary restrictions• Emotionally unable to complete 24-hour water fast• 10 FMT home infusions with child donor: no benefit• 3 months later, still not well-managed, another 10infusions from different donor: seems to be improvingsxs during the 10 days—acute rhinosinusitis on day 10,flares UC, no durable benefit apparent from FMT

Case #3• Another three months, UP flare not responsive to anyof above therapies or dietary restrictions• Emotionally unable to complete 24-hour water fast• 10 FMT home infusions with child donor: no benefit• 3 months later, still not well-managed, another 10infusions from different donor: seems to be improvingsxs during the 10 days—acute rhinosinusitis on day 10,flares UC, no durable benefit apparent from FMT

Troubleshooting• Viscosity• Enema tubing• Stopping meds• Donor issues• Oral lab-cultured probiotics?• FMT-refractory/relapsing cases—biofilms? MAP?

Q & Amark@brightmedicineclinic.com