Microbiota modulate sympathetic neurons via a gut–brain circuit

Paul A. Muller, Marc Schneeberger, Fanny Matheis, Putianqi Wang, Zachary Kerner, Anoj Ilanges, Kyle Pellegrino, Josefina del Mármol, Tiago B.R. Castro, Munehiro Furuichi, Matthew Perkins, Wenfei Han, Arka Rao, Amanda J. Picard, Justin R. Cross, Kenya Honda, Ivan de Araujo, Daniel Mucida

研究成果: Article査読

18 被引用数 (Scopus)

抄録

Connections between the gut and brain monitor the intestinal tissue and its microbial and dietary content1, regulating both physiological intestinal functions such as nutrient absorption and motility2,3, and brain-wired feeding behaviour2. It is therefore plausible that circuits exist to detect gut microorganisms and relay this information to areas of the central nervous system that, in turn, regulate gut physiology4. Here we characterize the influence of the microbiota on enteric-associated neurons by combining gnotobiotic mouse models with transcriptomics, circuit-tracing methods and functional manipulations. We find that the gut microbiome modulates gut-extrinsic sympathetic neurons: microbiota depletion leads to increased expression of the neuronal transcription factor cFos, and colonization of germ-free mice with bacteria that produce short-chain fatty acids suppresses cFos expression in the gut sympathetic ganglia. Chemogenetic manipulations, translational profiling and anterograde tracing identify a subset of distal intestine-projecting vagal neurons that are positioned to have an afferent role in microbiota-mediated modulation of gut sympathetic neurons. Retrograde polysynaptic neuronal tracing from the intestinal wall identifies brainstem sensory nuclei that are activated during microbial depletion, as well as efferent sympathetic premotor glutamatergic neurons that regulate gastrointestinal transit. These results reveal microbiota-dependent control of gut-extrinsic sympathetic activation through a gut–brain circuit.

本文言語English
ページ(範囲)441-446
ページ数6
ジャーナルNature
583
7816
DOI
出版ステータスPublished - 2020 7 16

ASJC Scopus subject areas

  • General

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