Host Gut Motility Promotes Competitive Exclusion within a Model Intestinal Microbiota

摘要

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. Live imaging of a model intestinal microbiota reveals that enteric neural function and peristalsis, combined with the spatial structure of microbial communities, can drive competition between bacterial species. Author Summary Hundreds of microbial species thrive within the gut of humans and other animals, where they can influence the health of their host in profound ways. The factors that shape the composition of the resident gut microbiota are not well understood, but identifying them represents an important step toward developing treatments for diseases associated with microbial imbalances. Current experimental approaches poorly capture spatial and temporal aspects of microbial interactions within the gut, and yet these features may hold clues to what determines the composition of the microbiota. To address this issue, we used state-of-the-art live imaging to track two bacterial species within the intestine of a model vertebrate host, the zebrafish. We observed strikingly different interplay between the spatial organization of each population and the intestine’s peristaltic activity. As a result, one species dominates while the other experiences sudden drops in abundance, the dynamics of which are predicted by a stochastic mathematical model. From this work, we conclude that the composition of indigenous microbial communities may, in part, be shaped by a combination of the physical intestinal environment and the spatial structure of bacterial populations.