title: The enteric nervous system promotes intestinal health by constraining microbiota composition.
abstract: 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.
authors.affiliation: Institute of Molecular Biology, University of Oregon, Eugene, Oregon, United States of America.
authors.forename: Annah S
authors.identifier: 0000-0001-7080-4352
authors.initials: AS
authors.lastname: Rolig
authors.affiliation: Institute of Molecular Biology, University of Oregon, Eugene, Oregon, United States of America.
authors.forename: Erika K
authors.initials: EK
authors.lastname: Mittge
authors.affiliation: Institute of Neuroscience, University of Oregon, Eugene, Oregon, United States of America.
authors.forename: Julia
authors.initials: J
authors.lastname: Ganz
authors.affiliation: Institute of Molecular Biology, University of Oregon, Eugene, Oregon, United States of America.
authors.forename: Josh V
authors.initials: JV
authors.lastname: Troll
authors.affiliation: Institute of Neuroscience, University of Oregon, Eugene, Oregon, United States of America.
authors.forename: Ellie
authors.initials: E
authors.lastname: Melancon
authors.affiliation: Institute of Molecular Biology, University of Oregon, Eugene, Oregon, United States of America.
authors.forename: Travis J
authors.initials: TJ
authors.lastname: Wiles
authors.affiliation: Institute of Neuroscience, University of Oregon, Eugene, Oregon, United States of America.
authors.forename: Kristin
authors.initials: K
authors.lastname: Alligood
authors.affiliation: Institute of Molecular Biology, University of Oregon, Eugene, Oregon, United States of America.
authors.forename: W Zac
authors.initials: WZ
authors.lastname: Stephens
authors.affiliation: Institute of Neuroscience, University of Oregon, Eugene, Oregon, United States of America.
authors.forename: Judith S
authors.initials: JS
authors.lastname: Eisen
authors.affiliation: Institute of Molecular Biology, University of Oregon, Eugene, Oregon, United States of America.|Humans and the Microbiome Program, Canadian Institute for Advanced Research, Toronto, Ontario, Canada.
authors.forename: Karen
authors.initials: K
authors.lastname: Guillemin
mesh_terms: D000818:Animals; D001419:Bacteria / Q000254:growth & development / Q000302:isolation & purification; D002452:Cell Count; D015169:Colony Count, Microbial; D064806:Dysbiosis / Q000235:genetics / Q000382:microbiology / Q000473:pathology; D017615:Enteric Nervous System / Q000166:cytology / Q000502:physiology*; D000069196:Gastrointestinal Microbiome; D005786:Gene Expression Regulation; D007249:Inflammation / Q000235:genetics / Q000473:pathology; D007422:Intestines / Q000382:microbiology* / Q000473:pathology; D007958:Leukocyte Count; D008954:Models, Biological; D009154:Mutation / Q000235:genetics; D009504:Neutrophils / Q000378:metabolism; D010802:Phylogeny; D055757:SOXE Transcription Factors / Q000378:metabolism; D033581:Stem Cell Transplantation; D015027:Zebrafish; D029961:Zebrafish Proteins / Q000378:metabolism
chemical_list: D055757:SOXE Transcription Factors; D029961:Zebrafish Proteins; C442229:sox10 protein, zebrafish