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.
Highlights
Trillions of microbial cells representing hundreds of species make up the human intestinal microbiota
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
One species dominates while the other experiences sudden drops in abundance, the dynamics of which are predicted by a stochastic mathematical model
Summary
Trillions of microbial cells representing hundreds of species make up the human intestinal microbiota. A major goal of host–microbe systems biology is to clarify the ecological factors that determine microbiota integrity by meshing experimental techniques and quantitative modeling Insights derived from such efforts will inspire the design of novel therapeutic strategies for microbiota-associated diseases. An unresolved question is whether the host and microbiota function independently or together to govern the dynamics and stability of individual bacterial lineages Addressing this question requires identifying the interactions that arise within the spatially complex and heterogeneous environment of the vertebrate gut. Typical interrogation of vertebrate intestinal microbiota involves phylogenetic profiling of fecal material using high-throughput sequencing of 16S ribosomal RNA (rRNA) genes This technique is blind to the spatial structure of microbial communities, which is known in general to strongly influence interactions [8,9,10] and has recently been predicted to be important for microbiota stability [11]. Such methods to date have employed deterministic Lotka-Volterra models [12,14,15] that, even with noise terms representing measurement error, neglect the possibility of fundamentally stochastic or discontinuous interactions among constituents
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