Mechanisms for Selective Modulation of Beneficial Human Gut Microbes by Specific Dietary Plant Polysaccharides

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 DESCRIPTION (provided by applicant): The microbes that reside in the human intestine profoundly influence our ability to extract energy and nutrients from the foods we eat. This influence is increasingly appreciated in the context of obesity, which afflicts over 1/3 of the US population and is associated with serious medical complications. Features of obesity, including increased fat mass and metabolic dysfunction, can be transmitted to germ-free mice colonized with the intestinal microbiota of obese individuals, but not that of lean individuals, providing evidence that differences between gut microbial communities contribute to disease. Diet has a marked impact on the particular bacterial species that are present in the human gut. Dietary plant polysaccharides that cannot be digested by host- derived enzymes become concentrated in the large intestine, where they provide a competitive advantage to microbes that can degrade and consume them. Cultures of individual gut bacterial species grown in the presence of purified carbohydrates have revealed broad capacities for carbohydrate degradation and consumption that do not reflect microbial abundances in vivo. This suggests that undefined mechanisms provide certain microbes with a competitive advantage in metabolizing specific polysaccharides in the gut. At present there is a lack of available tools for determining which dietary interventios can increase the abundance of beneficial bacteria in vivo, where interactions with other microbes influence nutrient acquisition and processing. The following aims will test the hypothesis that dietary plant polysaccharides that selectively increase the abundance of beneficial bacterial species are captured and degraded by those bacterial species in vivo. AIM 1 will identify dietary polysaccharides that increase the abundance of specific bacterial species in vivo. Preliminary results suggest that certain dietary polysaccharides can selectively increase the abundance of beneficial bacterial species. Additional polysaccharides will be screened to identify those with the most potent and selective effects. These polysaccharides will then be fed to mice colonized with microbes from obese human donors to determine which dietary interventions restore physiologic and metabolic health. AIM 2 will determine whether dietary polysaccharides that increase the abundance of beneficial gut microbes are captured and degraded by those microbes in vivo. A novel mass spectrometry-based assay will be used to determine the extent of polysaccharide degradation in the presence and absence of specific microbes. A novel DNA sequencing-based assay will be used to identify bacterial strains that capture specific polysaccharides in the gut. This research will provide a basic understanding of the mechanisms that determine gut microbial community structure and metabolic functions, and may inform the development of novel plant-based dietary interventions for manipulating human microbial communities to promote health.