title: Host Gut Motility Promotes Competitive Exclusion within a Model Intestinal Microbiota.
abstract: The gut microbiota is a complex consortium of microorganisms with the ability to influence important aspects of host health and development. Harnessing this "microbial organ" for biomedical applications requires clarifying the degree to which host and bacterial factors act alone or in combination to govern the stability of specific lineages. To address this issue, we combined bacteriological manipulation and light sheet fluorescence microscopy to monitor the dynamics of a defined two-species microbiota within a vertebrate gut. We observed that the interplay between each population and the gut environment produces distinct spatiotemporal patterns. As a consequence, one species dominates while the other experiences sudden drops in abundance that are well fit by a stochastic mathematical model. Modeling revealed that direct bacterial competition could only partially explain the observed phenomena, suggesting that a host factor is also important in shaping the community. We hypothesized the host determinant to be gut motility, and tested this mechanism by measuring colonization in hosts with enteric nervous system dysfunction due to a mutation in the ret locus, which in humans is associated with the intestinal motility disorder known as Hirschsprung disease. In mutant hosts we found reduced gut motility and, confirming our hypothesis, robust coexistence of both bacterial species. This study provides evidence that host-mediated spatial structuring and stochastic perturbation of communities can drive bacterial population dynamics within the gut, and it reveals a new facet of the intestinal host-microbe interface by demonstrating the capacity of the enteric nervous system to influence the microbiota. Ultimately, these findings suggest that therapeutic strategies targeting the intestinal ecosystem should consider the dynamic physical nature of the gut environment.
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: Department of Physics, University of Oregon, Eugene, Oregon, United States of America.
authors.forename: Matthew
authors.initials: M
authors.lastname: Jemielita
authors.affiliation: Department of Physics, University of Oregon, Eugene, Oregon, United States of America.
authors.forename: Ryan P
authors.initials: RP
authors.lastname: Baker
authors.affiliation: Department of Physics, University of Oregon, Eugene, Oregon, United States of America.
authors.forename: Brandon H
authors.initials: BH
authors.lastname: Schlomann
authors.affiliation: Department of Physics, University of Oregon, Eugene, Oregon, United States of America.
authors.forename: Savannah L
authors.identifier: 0000-0002-6772-9205
authors.initials: SL
authors.lastname: Logan
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 Neuroscience, University of Oregon, Eugene, Oregon, United States of America.
authors.forename: Ellie
authors.identifier: 0000-0002-1050-8217
authors.initials: E
authors.lastname: Melancon
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.
authors.forename: Karen
authors.initials: K
authors.lastname: Guillemin
authors.affiliation: Department of Physics, University of Oregon, Eugene, Oregon, United States of America.
authors.forename: Raghuveer
authors.initials: R
authors.lastname: Parthasarathy
mesh_terms: D000070079:Aeromonas veronii / Q000502:physiology; D000818:Animals; D000898:Antibiosis / Q000502:physiology; D000069196:Gastrointestinal Microbiome / Q000502:physiology*; D005769:Gastrointestinal Motility / Q000502:physiology*; D041981:Gastrointestinal Tract / Q000382:microbiology*; D007814:Larva / Q000235:genetics / Q000382:microbiology / Q000502:physiology; D064307:Microbiota / Q000502:physiology*; D008856:Microscopy, Fluorescence; D009154:Mutation; D011157:Population Dynamics; D013045:Species Specificity; D014734:Vibrio cholerae / Q000502:physiology; D015027:Zebrafish