Eco-evolutionary processes in gut Bacteroides

The human intestine harbors a rich microbial ecosystem with a tremendous number and density of microorganisms collectively referred to as the gut microbiota. These organisms perform important services such as breakdown of refractory dietary polysaccharides and production of vitamins. The gut microbiota of each person has a distinct composition that is relatively stable over time, but how the microbiota is assembled is not well understood. This project explores a fundamentally new perspective on assembly and interactions of the gut microbiota based on the idea that microbial populations undergo rapid evolution due to competition for niche space in an environment with diverse substrates. Co-evolution therefore occurs on ecologically meaningful time scales, and the resulting adaptation plays a key role in fine tuning populations to their environment and to other populations. The resulting community is thus shaped by the interplay of ecological and evolutionary processes. Adaptation and diversification affect community-level properties such as ecosystem productivity, stability, and invasibility by other microbes (pathogens or commensals). This idea and specific questions related to it will be addressed using an experimental evolution approach that explores a key process in the gut: polysaccharide degradation by members of the genus Bacteroides. Experimental evolution-based approaches will allow us to explore fundamental questions about adaptation, diversification, and community assembly under controlled environments with well-defined niche spaces and a manageable (though not trivial) level of complexity. Bacteroides degradation of polysaccharides is not only an important process mediated by an abundant group of microorganisms, but also a well studied subject with a wealth of useful genetic and biochemical knowledge as well as developed genetic tools. The project examines model systems at varying levels of complexity as well as real gut microbial communities. These studies will provide a clearer picture of the interplay of ecological and evolutionary processes in the gut microbiota and hold the potential to provide a new conceptual understanding of how communities assemble that may be more broadly applicable to our understanding of a diversity of important natural and engineered microbial ecosystems. This research may not only have widespread implications for our understanding of intestinal function, health, and nutrition, but also, over a longer horizon, may inform novel therapeutic strategies for gut-associated diseases such as enteric infections, inflammatory bowel diseases, and colorectal cancer.

The human intestine harbors a rich microbial ecosystem with a tremendous number and density of microorganisms collectively referred to as the gut microbiota. The microbiota performs important services such as breakdown of refractory dietary polysaccharides and production of vitamins. We have recently discovered that the gut microbiota of each person has a distinct composition that is relatively stable over time. However, a conceptual understanding is still lacking in regards to basic questions about how this complex ecosystem functions and the strength and types of interactions between members of the microbiota. This project addressed two important and foundational questions in gut microbiology: What processes govern gut microbial community assembly, and why is the gut microbiota relatively stable within an individual but different between individuals? This project explored a new perspective on assembly and interactions of the gut microbiota based on the idea that microbial populations undergo rapid and ecologically important evolution due to competition for niche space and the presence of a diverse substrate environment. Using experimental evolution approach, we found that the gut commensal Bacteroides thetaiotaomicron rapidly evolves in response to its nutrient environment as well as in response to the part of the intestines in which it colonizes. These results suggest that rapid genetic diversification occurs by members of the gut microbiota and that this diversification can contribute to increased fitness, and thereby enhance the stability of resident members of the gut microbiota. This has implications for designing strategies to modulate gut microbiota composition for health, such as prebiotic and probiotic treatments.