The bidirectional Gut-Brain Axis is now
identified as a key factor for growth, development and
emotions. In fact, it is the gut microbiome and certain
nutrients that communicate to the brain and direct the brain
in several ways. The gut microbiome also communicates to the
immune system and plays a vital role in maintaining health.
This review article brings out the intricacies of Gut-
Microbiome-Brain Axis, its modulation, and the role of
nutrition interventions for selected Disorders of Gut Brain
Interactions (DGBIs).
Keywords: nutrition,
gut-brain axis, gut brain interaction, gut-microbiome-brain
axis, disorders of gut brain interactions, DGBI
Introduction
"One day the body parts were fighting each other as to which
is the most important organ. Each organ stated its respective
importance. The brain said it controls everything. The heart
said its beating keeps life going. The Lungs said its
breathing brings oxygen. The liver highlighted its synthetic,
secretory and detoxifying functions. Finally, the gut said,
without its digestion, absorption and gut heath, life cannot
be sustained. Every other organ laughed aloud. And the gut got
very angry and shut all its function. In a few days, all
organs agreed to the claim of the Gut". Thus, the story goes.
It is interesting to note that that, Hippocrates, the Father
of Modern Medicine, had endorsed the claim of the gut.
According to him, "All diseases begin in the gut and Health is
determined by the microbiota in the Gut".
Are we Homo sapiens or Micro sapiens?
There are a greater number of microbiomes in the human body,
10
14, which is more than the number of cells in the
body. There are billions of microbes living in the gut, mouth
and skin and we humans depend upon the microbiomes to function
and maintain health and well-being. Microbiomes contribute
about 2 Kg weight and 3 million genes to humans.
Which are the Gut Microbiomes?
Microbes include bacteria, viruses, fungi, algae, and
protozoa. Most bacteria belong to the genera Bacteroides,
Clostridium, Faecalibacterium, Eubacterium, Ruminococcus,
Peptococcus, Peptostreptococcus, and Bifidobacterium. Other
genera, such as Escherichia and Lactobacillus, are present to
a lesser extent. Species from the genus Bacteroides alone
constitute about 30% of all bacteria in the gut, suggesting
that this genus is especially important in the functioning of
the host. These communicate to the brain via Gut Brain Axis.
These also orchestrate the Immune system.
Factors that decide Body and Gut Microbiome [1,2,3]
Factors that influence Gut Bacterial Composition are several
including the environment, diet, infections, medications and
genetics. The home environment, the place of birth, and the
type of delivery are the key factors. Infant feeding,
especially human milk or bovine milk or commercial
preparations is an important factor for establishing the
bacterial community in the gut.
Milk is Species Specific and factors in Breastmilk that
promote favourable microbiota. The early life period is a
"window of opportunity" to program health through microbiota
modulation. Breastmilk is a treasure of Prebiotics, Probiotics
& Postbiotics that modulate gene expression via Epigenetic
mechanisms. Specific human milk oligosaccharide (HMO) promote
Bifidobacterium species that dominate the ecosystem as long as
the infant is primarily breastfed.
Role of Microbiota
There are 3 Major Functions, Protective, Structural and
Metabolic like Fermenting dietary Fibre into short chain fatty
acids (SCFA) and synthesis of Vitamins. These perform
saccharolytic fermentation to short chain fatty acids in the
gut and offer protection against infectious and immune-related
diseases. There is evidence that the composition of the gut
microbiota influences metabolism and can affect energy
balance, gut permeability, and inflammation. These microbial
metabolites act as a messenger in the brain-gut axis and are
correlated with a reduction in anxiety and depression.
Other Specific Factors that influence the gut microbiota of
the infant
Omega 3 Fatty acids have a proven role in restoring and
maintaining healthy intestinal microbiota, and reducing
intestinal inflammation. The major long chain Polyunsaturated
fatty acids (LCPUFAs) that are derived from Omega 3 Linolenic
acid are DHA & EPA, which are brain and heart friendly.
DHA also promotes the development of short-chain fatty
acid-producing bacteria and reduce pro-inflammatory molecules.
In addition to acting on the microbiota, DHA has a potentially
beneficial role in various gut conditions and colon cancer, by
reducing chronic inflammation. Human milk has 30 times more
DHA than Cow's milk.
Breastmilk provides a perfect balance between Omega 6 &
Omega 3 LCPUFAs, of which Omega 3 (Linolenic) leading to DHA
& EPA, which are Anti-inflammatory and Omega 6 (Linoleic)
leading to Arachidonic & Adrenic Acid, which are
Pro-Inflammatory. The desired Omega 6: Omega 3 Ratio (n6: n3)
is <5-10:1)
What is meant by Leaky Gut?
Leaky gut syndrome is based on the theory that intestinal
permeability is not only a symptom of gastrointestinal
disease, but an underlying cause that develops independently.
If the intestinal barrier is impaired or immature, it may be
letting toxins, antigens, proteins and polypeptides into the
bloodstream. Leaky gut, or increased intestinal permeability,
occurs when the tight junctions of intestinal walls loosen.
This may allow harmful substances, such as bacteria, toxins,
and undigested food particles, to pass.
Proponents claim that a "leaky gut" causes chronic
inflammation throughout the body that results in a wide range
of conditions, including chronic fatigue syndrome, rheumatoid
arthritis, lupus, migraines, multiple sclerosis, and autism.
However, till date, this is not convincingly proven.
Bidirectional Gut Brain communication [4,5]
The gut-brain axis is a bidirectional communication system
between the central nervous system (CNS) and the GI tract. Gut
microbes communicate to the CNS through at least Three
parallel and interacting channels involving nervous,
endocrine, and immune signalling mechanisms.
There are many potential direct and indirect pathways through
which the gut microbiota can communicate and modulate the
gut-brain axis. These include endocrine (cortisol), immune
(cytokines), and neural (vagus and enteric nervous system)
pathways.
Communication pathways include sensory neurons, cytokines, gut
hormones and microbial factors, that signal from the gut to
the brain where these can modify cerebral function and
behaviour. There are two pathways, autonomic and
neuroendocrine outputs, that signal from the brain to the gut.
Regulation of the microbiota-brain-gut axis is essential for
maintaining homeostasis, including the CNS. The
microbiota-gut-brain axis leads to communication and
interaction of enteric and central nervous system that decide
emotional and cognitive functions.
The brain-gut-microbiota axis is modulated by the enteric
microbiota.
Thus, Both Microbes & DHA modulate brain function. Both
human and animal studies have highlighted the ability of
omega-3 PUFAs to influence the gut-brain axis, acting through
gut microbiota composition.
How are Neurotransmitters related to Microbiota?
Besides short-chain fatty acids and bile acids, recent studies
show that the metabolites produced by the gut microbiota also
include some neurotransmitters such as glutamate, GABA,
serotonin, and dopamine. GABA is synthesized by Lactobacilli,
Bifidobacterium, Norepinephrine by Escherichia and
Saccharomyces, Acetyl Choline by Lactobacilli and Serotonin by
Candida, Escherichia, Enterococci and Streptococci.
What are the Nutritional Interventions useful for Disorders
of Gut Brain Interaction (DGBIs)?
Emerging evidence suggests that gut microbes play a crucial
role in the brain development and flow of information across
the nervous system. Poor gut health may contribute to the
onset and progression of depression, anxiety, schizophrenia,
autism spectrum disorders, migraine, and epilepsy [6,7].
DGBIs include Irritable bowel syndrome, Reflux
hypersensitivity, Functional dyspepsia and many more. These
are called DGBIs because these are believed to be due to
impaired bidirectional communication between the gut and the
brain.
Glutamatergic signaling is another interesting
and unique factor to treat DGBIs through dietary intervention
via modulation of the gut microbiota.
Autism Spectrum Disorders (ASD) has Gastrointestinal
disturbances as comorbidities that are not only another
symptom of ASD, but also play an expression of social and
behavioral symptoms. Nutritional interventions for ASD,
include the following with varying results [8]:
- Gluten-free and Casein-free diet,
- Ketogenic, and specific Carbohydrate diets,
- Polyunsaturated fatty acids,
- Probiotics,
- Dietary supplements and vitamins A, C, B6, B12, D;
magnesium and folate
ADHD is yet another condition that may benefit the Gut Bain
Interaction. ADHD share symptoms of EFA Deficiency. There are
reports of significantly lower levels of plasma Arachidonic
acid & DHA in subjects with Severe ADHD than controls and
those with fewer symptoms.
Dietary approaches for ADHD include elimination of sugar,
candy and food with red dye. The assumption is that being
sensitive to certain foods may cause or worsen symptoms of
ADHD.
'Nutritional Psychiatry' is an emerging area of
research that has great potential as an adjunctive tool for
the prevention and treatment of diverse neuropsychiatric
disorders.
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