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

De Vadder, FilipeGothenburg University,Göteborgs universitet,Wallenberglaboratoriet,Wallenberg Laboratory (författare)

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.

Grasset, EstelleGothenburg University,Göteborgs universitet,Wallenberglaboratoriet,Wallenberg Laboratory(Swepub:gu)xgraes (författare)
Mannerås Holm, Louise,1980Gothenburg University,Göteborgs universitet,Wallenberglaboratoriet,Wallenberg Laboratory(Swepub:gu)xmanlo (författare)
Karsenty, G. (författare)
Macpherson, A. J. (författare)
Olofsson, Louise,1977Gothenburg University,Göteborgs universitet,Wallenberglaboratoriet,Wallenberg Laboratory(Swepub:gu)xolofl (författare)
Bäckhed, Fredrik,1973Gothenburg University,Göteborgs universitet,Wallenberglaboratoriet,Wallenberg Laboratory(Swepub:gu)xbafre (författare)
Göteborgs universitetWallenberglaboratoriet (creator_code:org_t)

Ingår i:Proceedings of the National Academy of Sciences of the United States of America: Proceedings of the National Academy of Sciences115:25, s. 6458-64630027-8424
Ingår i:Proceedings of the National Academy of Sciences: Proceedings of the National Academy of Sciences115:25, s. 6458-64631091-6490

Av författaren/redakt...: De Vadder, Filip ...; Grasset, Estelle; Mannerås Holm, L ...; Karsenty, G.; Macpherson, A. J ...; Olofsson, Louise ...; visa fler...; Bäckhed, Fredrik ...; visa färre...

Om ämnet

MEDICIN OCH HÄLSOVETENSKAP: MEDICIN OCH HÄLS ...; och Klinisk medicin; och Neurologi

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