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

Journal article
Authors Filipe De Vadder
Estelle Grasset
Louise Mannerås Holm
G. Karsenty
A. J. Macpherson
Louise Olofsson
Fredrik Bäckhed
Published in Proceedings of the National Academy of Sciences of the United States of America
Volume 115
Issue 25
Pages 6458-6463
ISSN 0027-8424
Publication year 2018
Published at Wallenberg Laboratory
Pages 6458-6463
Language en
Keywords microbiota, enteric nervous system, serotonin, 5-HT4R, neuronal serotonin, glial-cells, gastrointestinal motility, intestinal-mucosa, expressing cells, 5-ht4 receptors, mouse, mice, inflammation, neuroprotection, Science & Technology - Other Topics
Subject categories Neurology


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-HT4 receptor in the ENS has been linked to adult neurogenesis and neuroprotection. Here, we tested the hypothesis that the gut micro-biota could induce maturation of the adult ENS through release of 5-HT and activation of 5-HT4 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-HT4 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-HT4 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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