Gut Microbiome and Modulation of CNS Function
Abstract
Preclinical evidence strongly suggests a role for the gut microbiome in modulating the host central nervous system function and behavior. Several communication channels have been identified that enable microbial signals to reach the brain and that enable the brain to influence gut microbial composition and function. In rodent models, endocrine, neural, and inflammatory signals generated by gut microbes can alter brain structure and function, while autonomic nervous system activity can affect the microbiome by modulating the intestinal environment and by directly regulating microbial behavior. The amount of information that reaches the brain is dynamically regulated by the blood-brain barrier and the intestinal barrier. In humans, associations between gut microbial composition and function and several brain disorders have been reported, and fecal microbial transplants from patient populations into gnotobiotic mice have resulted in the reproduction of homologous features in the recipient mice. However, in contrast to preclinical findings, there is little information about a causal role of the gut microbiome in modulating human central nervous system function and behavior. Longitudinal studies in large patient populations with therapeutic interventions are required to demonstrate such causality, which will provide the basis for future clinical trials. © 2020 American Physiological Society. Compr Physiol 10:57-72, 2020.
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Enteroendocrine cells contain signaling molecules including ghrelin, NPY, PYY which can act locally on the vagus nerve or reach the CNS via systemic circulation.
“Enteroendocrine cells (EECs) are interspersed in the gut epithelium and contain important signaling molecules, including key orexigenic (ghrelin) and anorexigenic (NPY, PYY) hormones which can act locally on the vagus nerve as neurotransmitters, or reach the CNS via the systemic circulation in an endocrine fashion [12].”
From Role of diet and its effects on the gut microbiome in the pathophysiology of mental disorders (2022) · cites this paper as [12]
The gut microbiome interacts with the brain primarily through three interacting pathways: neuronal, endocrine, and immunoregulatory.
“The gut microbiome has been shown to interact with the brain primarily through three interacting pathways, namely neuronal, endocrine, and immunoregulatory [12, 16].”
From Role of diet and its effects on the gut microbiome in the pathophysiology of mental disorders (2022) · cites this paper as [12]
Indoxyl sulfate may play part in the pathophysiology of several brain disorders, including ASD, AD, and depression.
“One such metabolite, indoxyl sulfate, may play part in the pathophysiology of several brain disorders, including ASD, AD, and depression [12].”
From Role of diet and its effects on the gut microbiome in the pathophysiology of mental disorders (2022) · cites this paper as [12]
Metabolic endotoxemia results from a compromised gut barrier, allowing contacts between gut microbial cell wall components and Toll-like receptors on dendritic cells, or after translocation of intact microbes and activation of other cells in the gut-associated immune system.
“As reviewed elsewhere [12], metabolic endotoxemia results from a compromised gut barrier (“leaky gut”), allowing contacts between gut microbial cell wall components and Toll-like receptors on dendritic cells, or after translocation of intact microbes and activation of other cells in the gut-associated immune system.”
From Role of diet and its effects on the gut microbiome in the pathophysiology of mental disorders (2022) · cites this paper as [12]
The gut microbiome interacts with the brain in bidirectional ways using neural, inflammatory, and hormonal signalling pathways.
“The gut microbiome interacts with the brain in bidirectional ways using neural, inflammatory, and hormonal signalling pathways.23”
From Food and mood: How do diet and nutrition affect mental wellbeing? (2020) · cites this paper as [23]
The neurocognitive effects of the Western diet, and the possible mediating role of low grade systemic immune activation, may result from a compromised mucus layer with or without increased epithelial permeability.
“For instance, the neurocognitive effects of the Western diet, and the possible mediating role of low grade systemic immune activation (as discussed above) may result from a compromised mucus layer with or without increased epithelial permeability.”
From Food and mood: How do diet and nutrition affect mental wellbeing? (2020) · cites this paper as [23]
A decrease in the function of the gut barrier, sometimes referred to as leaky gut, has been linked to an unhealthy gut microbiome resulting from a diet low in fibre and high in saturated fats, refined sugars, and artificial sweeteners.
“Such a decrease in the function of the gut barrier is sometimes referred to as a “leaky gut” and has been linked to an “unhealthy” gut microbiome resulting from a diet low in fibre and high in saturated fats, refined sugars, and artificial sweeteners.15 23 27”
From Food and mood: How do diet and nutrition affect mental wellbeing? (2020) · cites this paper as [23]
Diet is a potentially modifiable determinant of the diversity, relative abundance, and functionality of the gut microbiome throughout life.
“In addition to genetic factors and exposure to antibiotics, diet is a potentially modifiable determinant of the diversity, relative abundance, and functionality of the gut microbiome throughout life.”
From Food and mood: How do diet and nutrition affect mental wellbeing? (2020) · cites this paper as [23]
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The microbiota-gut-brain axis: from motility to mood
Margolis, K. G., Cryan, J. F., & Mayer, E. A. (2021) · Gastroenterology · doi:10.1053/j.gastro.2020.10.066 · Cited by 999 · see citing works
Gut microbiota and dysbiosis in Alzheimer's disease: Implications for pathogenesis and treatment
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Food and mood: How do diet and nutrition affect mental wellbeing?
Firth, J., Gangwisch, J. E., Borsini, A., Wootton, R. E., & Mayer, E. A. (2020) · BMJ · doi:10.1136/bmj.m2382 · Cited by 475 · see citing works
Self-citationRole of diet and its effects on the gut microbiome in the pathophysiology of mental disorders
Horn, J., Mayer, D. E., Chen, S., & Mayer, E. A. (2022) · Translational Psychiatry · doi:10.1038/s41398-022-01922-0 · Cited by 193 · see citing works
Self-citation
- Authors
- Osadchiy, V., Martin, C. R., & Mayer, E. A.
- Affiliations
- University of California, Los Angeles (US)
- Corresponding author
- Mayer, Emeran A.
- Venue
- Comprehensive Physiology
- Publisher
- Wiley
- Published
- 2019-12-18
- Volume
- 10
- Issue
- 1
- Pages
- 57-72
- ISSN
- 2040-4603 (ISSN-L)
- OpenAlex
- W2996661506
- Cited by
- 53
- References
- 191
- Citations by year
- 2026: 1 · 2025: 3 · 2024: 10 · 2023: 13 · 2022: 10 · 2021: 10 · 2020: 6
- Type
- other
- Language
- en
- Open access
- closed
- Locations
- Comprehensive physiology (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gut microbiota and health
- Health Sciences › Medicine › Gastroenterology › Gastrointestinal motility and disorders
- Life Sciences › Neuroscience › Biological Psychiatry › Tryptophan and brain disorders
- Keywords
- gut microbiota, central nervous system, gut-brain axis, neurobehavior, hormone signaling, neuronal signaling, inflammatory signaling, autonomic nervous system, blood-brain barrier, intestinal barrier, fecal microbiota transplantation, gnotobiotic mice, brain disorders, causality
- MeSH terms
- Gastrointestinal Microbiome, Animals, Autonomic Nervous System, Brain, Feeding Behavior, Gastrointestinal Motility, Humans, Obesity
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