Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2017 Jan 15;595(2):489-503.
doi: 10.1113/JP273106. Epub 2016 Dec 4.

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

Timothy G Dinan  1   2 , John F Cryan  1   3
Affiliations
Review

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

Timothy G Dinan et al. J Physiol. .

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.

Keywords: ageing; gut-brain axis; stress.

PubMed Disclaimer

Figures

Figure 1
Figure 1. We are living in a microbial world throughout our lifespan
A growing body of evidence suggests that gut microbiota is essential to human health and is a key player in the bidirectional communication across the gut–brain axis. The microbiota dynamically changes across the lifespan, establishing its relationship with the host at critical windows during infancy, adolescence and ageing. At these time windows, there is an increased vulnerability to external insults, which may result in enhanced susceptibility to brain disorders. Early life disturbance of the developing gut microbiota has the potential to significantly impact on neurodevelopment and potentially lead to adverse mental health outcomes later in life. Similarly, the microbiota may contribute to the ageing process and the trajectory of neurodegenerative disorders.
See this image and copyright information in PMC

Similar articles

  • The impact of gut microbiota on brain and behaviour: implications for psychiatry.
    Dinan TG, Cryan JF. Dinan TG, et al. Curr Opin Clin Nutr Metab Care. 2015 Nov;18(6):552-8. doi: 10.1097/MCO.0000000000000221. Curr Opin Clin Nutr Metab Care. 2015. PMID: 26372511 Review.
  • Stress & the gut-brain axis: Regulation by the microbiome.
    Foster JA, Rinaman L, Cryan JF. Foster JA, et al. Neurobiol Stress. 2017 Mar 19;7:124-136. doi: 10.1016/j.ynstr.2017.03.001. eCollection 2017 Dec. Neurobiol Stress. 2017. PMID: 29276734 Free PMC article. Review.
  • The Microbiota-Gut-Brain Axis.
    Cryan JF, O'Riordan KJ, Cowan CSM, Sandhu KV, Bastiaanssen TFS, Boehme M, Codagnone MG, Cussotto S, Fulling C, Golubeva AV, Guzzetta KE, Jaggar M, Long-Smith CM, Lyte JM, Martin JA, Molinero-Perez A, Moloney G, Morelli E, Morillas E, O'Connor R, Cruz-Pereira JS, Peterson VL, Rea K, Ritz NL, Sherwin E, Spichak S, Teichman EM, van de Wouw M, Ventura-Silva AP, Wallace-Fitzsimons SE, Hyland N, Clarke G, Dinan TG. Cryan JF, et al. Physiol Rev. 2019 Oct 1;99(4):1877-2013. doi: 10.1152/physrev.00018.2018. Physiol Rev. 2019. PMID: 31460832 Review.
  • Influence of gut microbiota on neuropsychiatric disorders.
    Cenit MC, Sanz Y, Codoñer-Franch P. Cenit MC, et al. World J Gastroenterol. 2017 Aug 14;23(30):5486-5498. doi: 10.3748/wjg.v23.i30.5486. World J Gastroenterol. 2017. PMID: 28852308 Free PMC article. Review.
  • The role of microbiota-gut-brain axis in neuropsychiatric and neurological disorders.
    Socała K, Doboszewska U, Szopa A, Serefko A, Włodarczyk M, Zielińska A, Poleszak E, Fichna J, Wlaź P. Socała K, et al. Pharmacol Res. 2021 Oct;172:105840. doi: 10.1016/j.phrs.2021.105840. Epub 2021 Aug 24. Pharmacol Res. 2021. PMID: 34450312 Review.
See all similar articles

Cited by

See all "Cited by" articles

References

    1. Alam MZ, Alam Q, Kamal MA, Abuzenadah AM & Haque A (2014). A possible link of gut microbiota alteration in type 2 diabetes and Alzheimer's disease pathogenicity: an update. CNS Neurol Disord Drug Targets 13, 383–390. - PubMed
    1. Al‐Asmakh M & Zadjali F (2015). Use of germ‐free animal models in microbiota‐related research. J Microbiol Biotechnol 25, 1583–1588. - PubMed
    1. Allin KH, Nielsen T & Pedersen O (2015). Mechanisms in endocrinology: Gut microbiota in patients with type 2 diabetes mellitus. Eur J Endocrinol 172, R167–R177. - PubMed
    1. Arrieta MC, Walter J, Finlay BB (2016). Human microbiota‐associated mice: a model with challenges. Cell Host Microbe 19, 575–578. - PubMed
    1. Arentsen T, Raith H, Qian Y, Forssberg H & Diaz Heijtz R (2015). Host microbiota modulates development of social preference in mice. Microb Ecol Health Dis 26, 29719. - PMC - PubMed

Publication types

LinkOut - more resources