Sustaining a balanced intestinal microbial community is critical for maintaining intestinal health and preventing chronic inflammation. The gut is a highly dynamic environment, subject to periodic waves of peristaltic activity. We hypothesized that this dynamic environment is a prerequisite for a balanced microbial community and that the enteric nervous system (ENS), a chief regulator of physiological processes within the gut, profoundly influences gut microbiota composition. We found that

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... fish lacking an ENS due to a mutation in the Hirschsprung disease gene, sox10, develop microbiota-dependent inflammation that is transmissible between hosts. Profiling microbial communities across a spectrum of inflammatory phenotypes revealed that increased levels of inflammation were linked to an overabundance of pro-inflammatory bacterial lineages and a lack of anti-inflammatory bacterial lineages. Moreover, either administering a representative anti-inflammatory strain or restoring ENS function corrected the pathology. Thus, we demonstrate that the ENS modulates gut microbiota community membership to maintain intestinal health. Author summary Intestinal health depends on maintaining a balanced microbial community within the highly dynamic environment of the intestine. Every few minutes, this environment is rocked by peristaltic waves of muscular contraction and relaxation through a process regulated by the enteric nervous system (ENS). We hypothesized that normal, healthy intestinal microbial communities are adapted to this dynamic environment, and that their composition would become perturbed without a functional ENS. To test this idea, we used a model organism, the zebrafish, with a genetic mutation that prevents formation of PLOS Biology |