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The Central Nervous System and the Gut Microbiome
Open accessAbstract
Summary Neurodevelopment is a complex process governed by both intrinsic and extrinsic signals. While historically studied by researching the brain, inputs from the periphery impact many neurological conditions. Indeed, emerging data suggests communication between the gut and the brain in anxiety, depression, cognition and autism spectrum disorder (ASD). The development of a healthy, functional brain depends on key pre- and post-natal events that integrate environmental cues, such as molecular signals from the gut. These cues largely originate from the microbiome, the consortium of symbiotic bacteria that reside within all animals. Research over the past few years reveals that the gut microbiome plays a role in basic neurogenerative processes such as the formation of the blood-brain-barrier, myelination, neurogenesis, and microglia maturation, and also modulates many aspects of animal behavior. Herein, we discuss the biological intersection of neurodevelopment and the microbiome, and explore the hypothesis that gut bacteria are integral contributors to development and function of the nervous system, and the balance between mental health and disease.
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“delivery mode (47) and early-life occurrences such as feeding changes, infection, and antibiotics treatment (48, 49) have a huge effect on the gut microbiota composition with a long-term impact on brain and behavior (9, 29).”
From The Role of Short-Chain Fatty Acids From Gut Microbiota in Gut-Brain Communication (2020) · cites this paper as [29]
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“The modulation of gut physiology by the CNS and its effects on gut function such as motility, secretion, blood flow, nociception, and immune function during neurological stressors are well-documented (17, 29, 30).”
From The Role of Short-Chain Fatty Acids From Gut Microbiota in Gut-Brain Communication (2020) · cites this paper as [29]
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“Accumulating evidence suggests that SCFAs that cross into the CNS have neuroactive properties.”
From The Role of Short-Chain Fatty Acids From Gut Microbiota in Gut-Brain Communication (2020) · cites this paper as [29]
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
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“The central hypothesis is supported by experimental and clinical evidence that the microbiota is altered in such diseases, which aggravates the condition, and/or its modulation might prevent or improve the development and progression of CNS pathologies (17, 19, 29, 33–37).”
From The Role of Short-Chain Fatty Acids From Gut Microbiota in Gut-Brain Communication (2020) · cites this paper as [29]
Experimental — accuracy not yet measuredThe cited source says what the claim attributes to it.
In the citing paper
“several brain disorders have been linked to imbalances in the microbial composition of the gut (17, 19, 29, 33–37)”
From The Role of Short-Chain Fatty Acids From Gut Microbiota in Gut-Brain Communication (2020) · cites this paper as [29]
In the citing paper
“Through SCFAs, the gut microbiota actively communicates with host cells to regulate neurotrophic factors, neurotransmitters, and levels of neuroinflammation by affecting glial cell morphology and function, mitochondrial function, immune activation, lipid metabolism, and gene expression, thereby influencing CNS functions.”
From Modulation of the gut–brain axis via the gut microbiota: a new era in treatment of amyotrophic lateral sclerosis (2023) · cites this paper as [54]
In the citing paper
“The maturation and function of CNS-resident macrophages and microglia are controlled by the gut microbiota (54).”
From Modulation of the gut–brain axis via the gut microbiota: a new era in treatment of amyotrophic lateral sclerosis (2023) · cites this paper as [54]
In the citing paper
“Animal studies suggest that the GM plays a crucial role in regulating early brain development (19, 45, 60, 114–117).”
From Signalling cognition: The gut microbiota and hypothalamic-pituitary-adrenal axis (2023) · cites this paper as [116]
In the citing paper
“Altered SCFA production has also been demonstrated in a variety of neuropathologies (42, 116, 127, 130, 132, 292–295).”
From Signalling cognition: The gut microbiota and hypothalamic-pituitary-adrenal axis (2023) · cites this paper as [116]
In the citing paper
“A large body of preclinical literature supports the notion of a bidirectional communication system linking the gut and the brain, known as the gut-microbiota-brain axis (Borre et al., 2014; Sharon et al., 2016; Vuong et al., 2017).”
From Mechanisms underlying microbial-mediated changes in social behavior in mouse models of autism spectrum disorder (2019) · cites this paper as Sharon et al., 2016
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Citations
Cites
Diet rapidly and reproducibly alters the human gut microbiome
David, L. A., Maurice, C. F., Carmody, R. N., Gootenberg, D. B., Button, J. E., Wolfe, B. E., Ling, A. V., Devlin, A. S., Varma, Y., Fischbach, M. A., et al. (2014) · Nature · doi:10.1038/nature12820 · Cited by 10,100
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The gut microbiota shapes intestinal immune responses during health and disease
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Self-citationDominguez-Bello, M. G., Costello, E. K., Contreras, M., Magris, M., Hidalgo, G., Fierer, N., & Knight, R. (2010) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1002601107 · Cited by 4,774
Induction of Intestinal Th17 Cells by Segmented Filamentous Bacteria
Ivanov, I. I., Atarashi, K., Manel, N., Brodie, E. L., Shima, T., Karaoz, U., Wei, D., Goldfarb, K. C., Santee, C. A., Lynch, S. V., et al. (2009) · Cell · doi:10.1016/j.cell.2009.09.033 · Cited by 4,554
Structural and functional features of central nervous system lymphatic vessels
Louveau, A., Smirnov, I., Keyes, T. J., Eccles, J. D., Rouhani, S. J., Peske, J. D., Derecki, N. C., Castle, D., Mandell, J. W., Lee, K. S., et al. (2015) · Nature · doi:10.1038/nature14432 · Cited by 4,413
Synaptic Pruning by Microglia Is Necessary for Normal Brain Development
Paolicelli, R. C., Bolasco, G., Pagani, F., Maggi, L., Scianni, M., Panzanelli, P., Giustetto, M., Ferreira, T. A., Guiducci, E., Dumas, L., et al. (2011) · Science · doi:10.1126/science.1202529 · Cited by 4,244
Microglia Sculpt Postnatal Neural Circuits in an Activity and Complement-Dependent Manner
Schafer, D. P., Lehrman, E. K., Kautzman, A. G., Koyama, R., Mardinly, A. R., Yamasaki, R., Ransohoff, R. M., Greenberg, M. E., Barres, B. A., & Stevens, B. (2012) · Neuron · doi:10.1016/j.neuron.2012.03.026 · Cited by 4,089 · cited 1×
“Microglia produce copious amounts of C1q, the first protein in the complement activation cascade, and express various complement receptors (Schafer et al., 2012; Stephan et al., 2012).”
Background
Cited by
Sorted by citations
Interaction between microbiota and immunity in health and disease
Zheng, D., Liwinski, T., & Elinav, E. (2020) · Cell Research · doi:10.1038/s41422-020-0332-7 · Cited by 3,947
Gut microbiota regulate motor deficits and neuroinflammation in a model of Parkinson's disease
Sampson, T. R., Debelius, J. W., Thron, T., Janssen, S., Shastri, G. G., Ilhan, Z. E., Challis, C., Schretter, C. E., Rocha, S., Gradinaru, V., et al. (2016) · Cell · doi:10.1016/j.cell.2016.11.018 · Cited by 3,622
Self-citationThe Role of Short-Chain Fatty Acids From Gut Microbiota in Gut-Brain Communication
Silva, Y. P., Bernardi, A., & Frozza, R. L. (2020) · Frontiers in Endocrinology · doi:10.3389/fendo.2020.00025 · Cited by 3,043
Gut microbiota in colorectal cancer: mechanisms of action and clinical applications
Wong, S. H., & Yu, J. (2019) · Nature Reviews Gastroenterology & Hepatology · doi:10.1038/s41575-019-0209-8 · Cited by 1,392
Martin, C. R., Osadchiy, V., Kalani, A., & Mayer, E. A. (2018) · Cellular and Molecular Gastroenterology and Hepatology · doi:10.1016/j.jcmgh.2018.04.003 · Cited by 1,284
Metadata
- Authors
- Sharon, G., Sampson, T. R., Geschwind, D. H., & Mazmanian, S. K.
- Affiliations
- California Institute of Technology (US)
- University of California, Los Angeles (US)
- Corresponding author
- Sharon, Gil
- Mazmanian, Sarkis K.
- Venue
- Cell
- Publisher
- Elsevier BV
- Published
- 2016-11
- Volume
- 167
- Issue
- 4
- Pages
- 915-932
- ISSN
- 0092-8674 (ISSN-L)
- PMC
- PMC5127403
- OpenAlex
- W2548933161
- Semantic Scholar
- 7bb11be31e7f534cb591760aeb939cd84b4b45ac
- Cited by
- 1,513
- References
- 190
- Citations by year
- 2026: 140 · 2025: 157 · 2024: 198 · 2023: 186 · 2022: 175 · 2021: 211 · 2020: 160 · 2019: 128 · 2018: 95 · 2017: 60 · 2016: 2
- FWCI
- 8.63
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Cell (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- eScholarship (California Digital Library) (submittedVersion)
- CaltechAUTHORS (California Institute of Technology) (submittedVersion)
- Funders
- Meixner Postdoctoral Fellowship in Translational Research
- Larry L. Hillblom Foundation Postdoctoral Fellowship
- NIH (MH100556, DK078938, GM099535, NS085910)
- Department of Defense
- Heritage Medical Research Institute
- Simons Foundation
- NIMH (HD055784, MH100027, MH110927, MH1064382)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gut microbiota and health
- Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
- Life Sciences › Neuroscience › Biological Psychiatry › Tryptophan and brain disorders
- Keywords
- gut microbiota, central nervous system, brain development, gut-brain axis, anxiety, depression, autism spectrum disorder, blood-brain barrier, myelination, neurogenesis, behavior, mental health
- MeSH terms
- Gastrointestinal Microbiome, Animals, Behavior, Brain, Female, Humans, Pregnancy, Vagina, Neurodevelopmental Disorders
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