Gut microbiota regulates maturation of the adult enteric nervous system via enteric serotonin networks.

De Vadder, Filipe; Grasset, Estelle; Mannerås Holm, Louise; Karsenty, Gérard; Macpherson, Andrew; Olofsson, Louise E; Bäckhed, Fredrik (2018). Gut microbiota regulates maturation of the adult enteric nervous system via enteric serotonin networks. Proceedings of the National Academy of Sciences of the United States of America - PNAS, 115(25), pp. 6458-6463. National Academy of Sciences NAS 10.1073/pnas.1720017115

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The enteric nervous system (ENS) is crucial for essential gastrointestinal physiologic functions such as motility, fluid secretion, and blood flow. The gut is colonized by trillions of bacteria that regulate host production of several signaling molecules including serotonin (5-HT) and other hormones and neurotransmitters. Approximately 90% of 5-HT originates from the intestine, and activation of the 5-HT receptor in the ENS has been linked to adult neurogenesis and neuroprotection. Here, we tested the hypothesis that the gut microbiota could induce maturation of the adult ENS through release of 5-HT and activation of 5-HT receptors. Colonization of germ-free mice with a microbiota from conventionally raised mice modified the neuroanatomy of the ENS and increased intestinal transit rates, which was associated with neuronal and mucosal 5-HT production and the proliferation of enteric neuronal progenitors in the adult intestine. Pharmacological modulation of the 5-HT receptor, as well as depletion of endogenous 5-HT, identified a mechanistic link between the gut microbiota and maturation of the adult ENS through the release of 5-HT and activation of the 5-HT receptor. Taken together, these findings show that the microbiota modulates the anatomy of the adult ENS in a 5-HT-dependent fashion with concomitant changes in intestinal transit.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Department of Gastro-intestinal, Liver and Lung Disorders (DMLL) > Clinic of Visceral Surgery and Medicine > Gastroenterology
04 Faculty of Medicine > Pre-clinic Human Medicine > BioMedical Research (DBMR) > DBMR Forschung Mu35 > Forschungsgruppe Gastroenterologie / Mukosale Immunologie
04 Faculty of Medicine > Pre-clinic Human Medicine > BioMedical Research (DBMR) > DBMR Forschung Mu35 > Forschungsgruppe Gastroenterologie / Mukosale Immunologie

UniBE Contributor:

Macpherson, Andrew

Subjects:

600 Technology > 610 Medicine & health

ISSN:

0027-8424

Publisher:

National Academy of Sciences NAS

Language:

English

Submitter:

Thi Thao Anh Pham

Date Deposited:

23 Jan 2019 18:00

Last Modified:

23 Jan 2019 18:00

Publisher DOI:

10.1073/pnas.1720017115

PubMed ID:

29866843

Uncontrolled Keywords:

5-HT4R enteric nervous system microbiota serotonin

BORIS DOI:

10.7892/boris.122383

URI:

https://boris.unibe.ch/id/eprint/122383

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