Complex Substrates and Microbial Interactions: Does Substrate Chemical Structure Dictate Microbial Diversity and Function?
Abstract
Though much work has been done describing how microbes compete for consumption of simple substrates, relatively little is known regarding how consumption of complex substrates affects the ecology of microbial communities. Prior work suggests that microbes in mixed culture exhibit increasingly cooperative behavior in degrading some complex substrates (e.g., polysaccharides) compared with growth on simple substrates. Theoretically, substrates with increasingly complex chemical structures may sustain a greater diversity of organisms by minimizing competition among them, as each organism may be able to ÒspecializeÓ in degrading a certain portion of the substrate; this may result in each organism non-competitively occupying a distinct niche in the community. Because diversity in microbial communities is important to the functioning and stability of many microbial ecosystem, such as animal and plant microbiomes, mechanisms to maintain diversity in these environments are important. This is especially true in the human gut microbiome, as low diversity of gut microbiota is linked to multiple acute and chronic disease states, such as metabolic syndrome, type 2 diabetes, inflammatory bowel diseases, and colorectal cancer. However, it remains unclear to what degree the chemical structure of a substrate influences the composition of the microbial community consuming it and, in turn, its metabolic fate. We here propose to test the hypothesis that increasing complexity of a substrate will sustain increased microbial diversity by allowing niche partitioning of organisms around degrading specific structural motifs. Determining the contribution of a complex substrateÕs structural properties to microbial ecology requires examining responses of microbiota to substrates with equivalent compositions, but in a range of different structural arrangements. Specifically, here we propose to examine the compositional and metabolic responses of gut microbiota to structurally-distinct dextrins, which are breakdown products of starches and composed entirely of glucose. In Objective I, we investigate the degree to which the response of the gut microbiota depends upon dextrin structure and whether gut microbiota adapt to specific structures using an in vitro evolutionary approach. We monitor microbiota community structure over their evolutionary trajectory by 16S rRNA amplicon sequencing and metabolic outputs (gases and short-chain fatty acids produced), and at interval determine whether adaptation is specific to a single dextrin structure using high-throughput cultivation. We use metagenomics and metabolomics techniques to reconstruct individual speciesÕ genomes and link them with metabolic outcomes. In Objective II, we identify the degree to which dextrin structure governs gut microbiota function in vivo by examining the microbiota composition, metabolic output, and gut permeability of mice fed alternate dextrin structures. Using computational modeling approaches, we further combine these in vivo and in vitro data with detailed information on dextrin chemical structure, to predict interactions among members and determine which structural properties of dextrins are most important for driving microbial ecology. This work aims to contribute generalizable principles describing the effects of complex substrate structure on microbial ecology and may provide insight into rational strategies to modulate the gut microbiomes of soldiers to improve health and/or performance.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Feb 14, 2019
- Source ID
- W911NF1810161
Entities
People
- Stephen R Lindemann
Organizations
- Army Contracting Command
- United States Army
- University of Virginia