Monday, 15th August, 2022

DAILY ANALYST
Monday, 15th August, 2022 Page 9
How Intestinal Bacteria Help
Humans to Stay Healthy
Gut microbiota refers
to a diverse
community of
microorganisms
that colonize the
gut mucosa.
Humans are seeded with
their first microbes at birth,
both on the skin and in the
gut.
The initial seeding sets
the stage for a person’s
developing immune system,
influencing the risk for future
diseases.
SYMBIOSIS.
The gut microbiome
exists in a state of mutual
symbiosis with the human
host.
The microbes benefit
from the stable and nutrient-rich
environment of the
gut.
Humans do not possess
all the requisite genetic
codes for optimal metabolic
health promotion.
There are over 100
trillion bacteria in the gut
(belonging to about 400
bacterial species). The gut
microbiota encodes over
three million genes (far
greater than the genome in
humans) that can produce
various metabolites essential
for human health.
So, the gut microbiota
provides the human host
with metabolites that are
naturally not produced by
humans, but essential for
optimal human health.
Metabolites from the gut
microbiota:
• Help human host
to develop their immune
system.
• Help regulate host
metabolism
• Modulate host brain
functions.
• GUT DYSBIOSIS AND
SYSTEMIC DISEASES.
Dysbiosis is the alteration
of the composition of
human microbiota at given
site. Gut dysbiosis can lead
to alteration of the host
physiology resulting in the
pathogenic processes of
different diseases.
Gut dysbiosis leads to
poor gut-health. There is
loss of gut integrity and
immunity.
There is upregulation of
proinflammatory cytokines
and chemokines (due to loss
of Regulatory T cell anti-inflammatory
activities associated
with Gut dysbiosis).
Gram negative bacteria
generate lipopolysaccharides
(LPS), a marker of inflammation.
Overproduction
or abundance of gram-negative
bacteria in the gut can
cause inflammation
A Gut dysbiosis induces
a chronic state of systemic
low-grade inflammation
that plays a crucial role
in the pathophysiology of
chronic diseases. Gut dysbiosis
is associated with the
following:
. Cardiovascular diseases
(Atherosclerosis, HTN);
Metabolic disorders (Type 2
diabetes, Obesity); chronic
kidney diseases; Autoimmune
disorders, Neurological
disorders.
Association does not
mean causality; causality,
however, has been demonstrated
in rodent models.
THE SHORY CHAIN FAT-
TY ACIDS (SCFAs)
The 2- to 4- short chain
fatty acids (SCFAs), mainly,
Acetate, Propionate and
Butyrate, are generated by
bacterial fermentation of
dietary fibers and non-digestible
carbohydrates.
The SCFAs are readily absorbed
from the large intestines
into the bloodstream
to reach distant tissues like
liver, kidneys, fatty tissues.
Acetate readily crosses the
Blood-Brain Barrier to reach
the brain tissue.
The production of SCFA
is influenced by the pattern
of food intake and diet
mediated changes in the gut
microbiota.
The SCFAs are involved
in cellular energy production
and are known to affect
Lipids, Glucose, Cholesterol
metabolism.
The SCFAs improve insulin
sensitivity and therefore,
support the role of the
gut microbiota in glycemic
control.
About 90-95% of the
short chain fatty acids are
absorbed from the colon
into the systemic circulation
(only 5-10% of the short
chain fatty acids are lost in
stools).
SCFAs-MECHANISM OF
ACTIONS
SCFAs switch gene-expression
on and off by inhibiting
histone deacetylase
(HDAC).
By so doing, the SCFAs
upregulate anti-inflammatory
cytokines/chemokines;
down-regulate proinflammatory
cytokines.
SCFAs AND METABOLIC
SYNDROME
SCFAs not only protect
against diet-induced obesity,
but also inhibit insulin
resistance (Lin et al., 2012)
The SCFAs switch on the
genetic codes that help to
burn body fat as fuel for energy
production in the cells.
SCFAs AND INFLAMMA-
TIONS
SCFAs promote Regulatory
T (Treg) cells formation.
It is the Tregs that
suppress the production of
inflammatory cytokines by
inflammatory T-cells. So, the
SCFAs could be described as
Anti-inflammatory agents;
they help the human body
to control inflammations.
SCFAs AND ATHEROGEN-
ESIS
The SCFAs exert regulatory
control over the
production of enzymes
involved in cholesterol
generation, and those that
promote plaque-formation
in blood vessels.
Butyric acid downregulates
de novo lipogenesis,
ameliorate lipo-toxicity,
slows down atherosclerosis
progression, and stimulate
the burning of fats as fuel
for energy production in the
body cells.
GUT MICROBIOTA, AND
BRAIN HEALTH
SCFAs modulate brain
and behavioral health; they
influence maturation and
functions of microglia.
Altered SCFA production
has been implicated in a
variety of neurobehavioral
diseases including Autistic
spectrum disorder, and neurodegenerative
diseases like
Parkinson diseases.
Gram negative bacteria
generate Lipopolysaccharides
(LPS). On brain tissue,
LPS may activate immune
cells to induce inflammatory
cytokines that cause lowgrade
neuroinflammation.
SCFAs generate anti-inflammatory
cytokines that
prevent neuroinflammation.
Elderly persons have impaired
barrier functions of
both the intestinal wall and
the Blood-Brain Barrier.
Bacterial amyloid and
LPS may escape from intestine,
into the circulation;
enter the brain tissue to
promote neuroinflammation
that lead to neurodegenerative
diseases like
Parkinsons diseases, Multiple
sclerosis, Dementia.
GUT MICROBIOTA AND
HYPERTENSION
A healthy gut microbiome
generates the SCFAs.
SCFAs affect epithelial-,
immune-, nervous-, and vascular
functions to modulate
blood pressure
Studies indicate that gut
dysbiosis is associated with
hypertension:
. in hypertensive Rats
there is a reduction in microbial
richness and diversity
. There is a reduction in
butyrate- and acetate-producing
bacteria in hypertensives
. There is an increase in
Firmicutes bacteria phyla
relative to Bacteroidetes in
the gut
SCFA-receptors are
expressed in renal tissues;
intestinal dysbiosis activates
the renin-angiotensin
system (RAS) which contributes
to chronic kidney
diseases (CKD)
SCFAs affect blood pressure
by modulating local
RAS in the kidneys. Butyrate
inhibits Ang II-induced hypertension
by suppressing
the (pro)renin receptor and
intrarenal RAS
SCFA receptors (i.e.,
Gpr41, Olfr78) in the renal
Juxtaglomerular apparatus
mediate renin secretion in
response from gut microbiota
signals to lower baseline
blood pressure.
WESTERN DIETS
Western diets (high-protein,
high-fat, low-fiber
components) and the commercially
processed foods
promote Gut Dysbiosis and
decreased microbial diversity
in the gut.
Western diets, therefore,
promote obesity, metabolic
syndrome, chronic diseases
like cardiovascular diseases,
hypertension, and cancers
The high fructose sugary
drinks made from corn syrups
promote Gut dysbiosis
and, metabolic syndrome.
FOOD AS MEDICINE
High fiber diet serves as
fuel for gut microbiome. Gut
metabolome including the
SCFAs are essential products
for optimal gut function.
(High protein diets could
promote the formation of
harmful products in the
gut).
Therefore, a healthy
dietary pattern should include
high-fiber vegetables
like broccoli, spinach (and
other green-leafy vegetables),
nuts, seeds and whole
grains, and fresh farm produce
to help maintain gut
health.
Diets high in fiber (low in
animal proteins and animal
fats) that have been minimally
processed are good
for gut health. A healthy gut
promotes good health and
prevents the chronic diseases.
Indeed, you are what you
eat.
ALEX SARKODIE, MD