RT Journal Article SR Electronic T1 Host Gut Motility and Bacterial Competition Drive Instability in a Model Intestinal Microbiota JF bioRxiv FD Cold Spring Harbor Laboratory SP 052985 DO 10.1101/052985 A1 Travis J. Wiles A1 Matthew L. Jemielita A1 Ryan P. Baker A1 Brandon H. Schlomann A1 Savannah L. Logan A1 Julia Ganz A1 Ellie Melancon A1 Judith S. Eisen A1 Karen Guillemin A1 Raghuveer Parthasarathy YR 2016 UL http://biorxiv.org/content/early/2016/05/12/052985.abstract AB 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 we combined bacteriological manipulation and light sheet fluorescence microscopy to monitor the dynamics of a defined two-species microbiota within the vertebrate gut. We observed that the interplay between each population and the gut environment produced distinct spatiotemporal patterns. Consequently, one species dominates while the other experiences dramatic collapses that are well fit by a stochastic mathematical model. Modeling revealed that 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 mutation in the Hirschsprung disease locus ret. 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 along with bacterial competition drives population dynamics within the gut. In addition, this work highlights the capacity of the enteric nervous system to affect stability of gut microbiota constituents, demonstrating that the ‘gut-brain axis’ is bidirectional. Ultimately, these findings will help inform disease mitigation strategies focused on engineering the intestinal ecosystem.