The enteric nervous system promotes intestinal health by constraining microbiota composition

• Published in: PLoS biology Vol. 15; no. 2; p. e2000689
• Main Authors: Rolig, Annah S., Mittge, Erika K., Ganz, Julia, Troll, Josh V., Melancon, Ellie, Wiles, Travis J., Alligood, Kristin, Stephens, W. Zac, Eisen, Judith S., Guillemin, Karen
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 16.02.2017; Public Library of Science (PLoS)
• Subjects: Animals; Bacteria - growth & development; Bacteria - isolation & purification; Biology and Life Sciences; Cell Count; Colleges & universities; Colony Count, Microbial; Danio rerio; Data collection; Dysbiosis - genetics; Dysbiosis - microbiology; Dysbiosis - pathology; E coli; Editing; Enteric Nervous System - cytology; Enteric Nervous System - physiology; Experiments; Funding; Gastrointestinal Microbiome; Gene Expression Regulation; Health aspects; Inflammation; Inflammation - genetics; Inflammation - pathology; Intestine, Small; Intestines; Intestines - microbiology; Intestines - pathology; Leukocyte Count; Medicine and Health Sciences; Microbial activity; Microbiota (Symbiotic organisms); Models, Biological; Molecular biology; Mutation; Mutation - genetics; Nervous system; Nervous system, Autonomic; Neurosciences; Neutrophils; Neutrophils - metabolism; Phylogeny; Research and Analysis Methods; Roles; SOXE Transcription Factors - metabolism; Stem Cell Transplantation; Writing; Zebrafish; Zebrafish Proteins - metabolism; Oregon; United States > US
• ISSN: 1545-7885; 1544-9173; 1545-7885
• DOI: 10.1371/journal.pbio.2000689

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 zebrafish 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.