Gut Microbiota Regulates Maturation of the Adult Enteric Nervous System Via Enteric Serotonin Networks

Overview

Journal Proc Natl Acad Sci U S A

Specialty Science

Date 2018 Jun 6

PMID 29866843

Citations 229

Authors

Filipe De Vadder

Estelle Grasset

Louise Manneras Holm

Gerard Karsenty

Andrew J Macpherson

Louise E Olofsson

Fredrik Backhed

Affiliations

Soon will be listed here.

Abstract

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.

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