Gut instincts: microbiota as a key regulator of brain development, ageing and neurodegeneration

Dinan, Timothy G.; Cryan, John F.

doi:10.1113/jp273106

Cited by 813Gut microbiota and healthGastrointestinal motility and disordersTryptophan and brain disorders

Gut instincts: microbiota as a key regulator of brain development, ageing and neurodegeneration

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Dinan, Timothy G., Cryan, John F.·2017·The Journal of Physiology

DOI 10.1113/jp273106PMC PMC5233671

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Abstract

There is a growing realisation that the gut-brain axis and its regulation by the microbiota may play a key role in the biological and physiological basis of neurodevelopmental, age-related and neurodegenerative disorders. The routes of communication between the microbiota and brain are being unravelled and include the vagus nerve, gut hormone signalling, the immune system, tryptophan metabolism or by way of microbial metabolites such as short chain fatty acids. The importance of early life gut microbiota in shaping future health outcomes is also emerging. Disturbances of this composition by way of antibiotic exposure, lack of breastfeeding, infection, stress and the environmental influences coupled with the influence of host genetics can result in long-term effects on physiology and behaviour, at least in animal models. It is also worth noting that mode of delivery at birth influences microbiota composition with those born by Caesarean section having a distinctly different microbiota in early life to those born per vaginum. At the other extreme of life, ageing is associated with a narrowing in microbial diversity and healthy ageing correlates with a diverse microbiome. Recently, the gut microbiota has been implicated in a variety of conditions including depression, autism, schizophrenia and Parkinson's disease. There is still considerable debate as to whether or not the gut microbiota changes are core to the pathophysiology of such conditions or are merely epiphenomenal. It is plausible that such neuropsychiatric disorders might be treated in the future by targeting the microbiota either by microbiota transplantation, antibiotics or psychobiotics.

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Short-chain fatty acids that cross into the central nervous system have neuroactive properties.
“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 [100]
The Introduction says SCFAs may exert central effects directly or indirectly, supporting the claim that they can be neuroactive. It does not establish that SCFAs cross into the CNS; its discussion of the blood–brain barrier concerns SCFAs’ role in barrier integrity, not their passage across it. (LLM, conf=0.82)
Experimental — accuracy not yet measured
The GM influences the stress system, behavior, and cognition in animals.
“Studies in animals have demonstrated the effect that the GM has on neural development and neurochemistry in the host, influencing the stress system, behavior, and cognition (42–47).”
From Signalling cognition: The gut microbiota and hypothalamic-pituitary-adrenal axis (2023) · cites this paper as [42]
The HPA axis plays a central role in mediating the stress response and regulating the interaction between the GM, gut, and brain.
“The HPA axis plays a central role in mediating the stress response and regulating the interaction between the GM, gut, and brain (42).”
From Signalling cognition: The gut microbiota and hypothalamic-pituitary-adrenal axis (2023) · cites this paper as [42]
Altered SCFA production is demonstrated in a variety of neuropathologies.
“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 [42]

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Gastrointestinal microbiota in children with autism in Slovakia
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Ly6Chi Monocytes Provide a Link between Antibiotic-Induced Changes in Gut Microbiota and Adult Hippocampal Neurogenesis
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Microbes and the gut‐brain axis
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Bacterial Neuroactive Compounds Produced by Psychobiotics
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Adult microbiota‐deficient mice have distinct dendritic morphological changes: differential effects in the amygdala and hippocampus
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The effect of oxytocin nasal spray on social interaction deficits observed in young children with autism: a randomized clinical crossover trial
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Innate Lymphoid Cell Interactions with Microbiota: Implications for Intestinal Health and Disease
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Microbial ecology and host-microbiota interactions during early life stages
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MECHANISMS IN ENDOCRINOLOGY: Gut microbiota in patients with type 2 diabetes mellitus
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Longitudinal Study of Amygdala Volume and Joint Attention in 2- to 4-Year-Old Children With Autism
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Human Microbiota-Associated Mice: A Model with Challenges
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Gut Microbiota: The Conductor in the Orchestra of Immune–Neuroendocrine Communication
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Review article: small intestinal bacterial overgrowth - prevalence, clinical features, current and developing diagnostic tests, and treatment
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Modulation of Intestinal Microbiota by the Probiotic VSL#3 Resets Brain Gene Expression and Ameliorates the Age-Related Deficit in LTP
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Host microbiota modulates development of social preference in mice
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Gut Microbiota and Brain Function: An Evolving Field in Neuroscience: Table 1.
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Genomics of schizophrenia: time to consider the gut microbiome?
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Immune modulation of the brain-gut-microbe axis
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The effects of gut microbiota on CNS function in humans
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Aging causes morphological alterations in astrocytes and microglia in human substantia nigra pars compacta
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Adding fuel to the fire: the impact of stress on the ageing brain
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Targeting gut microbiota as a possible therapy for diabetes
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Xenobiotics: Interaction with the Intestinal Microflora
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Learning About Oxytocin: Pharmacologic and Behavioral Issues
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Investigating the long-term effect of subchronic phencyclidine-treatment on novel object recognition and the association between the gut microbiota and behavior in the animal model of schizophrenia
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Mother's littlest helpers
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Microbiota diversity and stability of the preterm neonatal ileum and colon of two infants
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Authors: Dinan, T. G., & Cryan, J. F.
Affiliations: University College Cork (IE)
Corresponding author: Cryan, John F.
ORCID: Dinan, Timothy G.
Cryan, John F.
Venue: The Journal of Physiology
Publisher: Wiley
Published: 2016-12-04
Volume: 595
Issue: 2
Pages: 489-503
ISSN: 0022-3751 (ISSN-L)
1469-7793
DOI: 10.1113/jp273106
PMC: PMC5233671
OpenAlex: W2523444109
Cited by: 813
References: 166
Citations by year: 2026: 55 · 2025: 88 · 2024: 96 · 2023: 80 · 2022: 116 · 2021: 115 · 2020: 72 · 2019: 76 · 2018: 56 · 2017: 57 · 2016: 2
FWCI: 5.75
Type: journal article
Language: en
Open access: green
www.ncbi.nlm.nih.gov
Licence: onlinelibrary.wiley.com/termsAndConditions#vor (vor)
Locations: The Journal of Physiology (publishedVersion)
PubMed Central (publishedVersion)
PubMed (publishedVersion)
Funders: Science Foundation Ireland (SFI/12/RC/2273)
Health Research Board (HRA_POR/2011/23, HRA_POR/2012/32)
Seventh Framework Programme (FP7/2007–2013)
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, gut-brain axis, brain development, brain aging, neurodegeneration, vagus nerve, immune system, tryptophan metabolism, short-chain fatty acids, early-life microbiota, mode of delivery, cesarean section, microbial diversity, depression, autism spectrum disorder, schizophrenia, Parkinson's disease, microbiota transplantation, psychobiotics, antibiotics
MeSH terms: Gastrointestinal Microbiome, Aging, Animals, Mental Disorders, Brain, Humans, Neurodegenerative Diseases

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Gut instincts: microbiota as a key regulator of brain development, ageing and neurodegeneration

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