Uncovering the molecular strategies that allow human gut symbionts to degrade insoluble dietary and host glycans

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The supply of glycans from the diet and the host is the most important factor that determines microbial populations and metabolism within the large intestine. Recent evidences indicate that Ruminococcus play ‘keystone’ roles in initiating the degradation of insoluble substrates, whereas human colonic Bacteroides tend to favour soluble carbohydrates. This proposal will therefore investigate for the first time the molecular mechanisms that enable human colonic species of Ruminococcus to degrade particulate resistant starch, cereal bran rich in plant cell wall polysaccharides and insoluble mucin. The work will exploit the available genome sequences to enable functional studies on extracellular enzymes, enzyme complexes and substrate attachment mechanisms. A second main element of the proposal will examine interactions of these primary degraders with other species that are likely to compete for solubilized products of insoluble substrates, or to modify metabolism by utilizing fermentation products. These interactions will then be explored in vitro and also in vivo by using gnotobiotic animal models (colonised by single, or combinations of, Ruminococcus strains). Results from this work will help us understand how to keep a beneficial relationship with our gut bacteria and should lead to the development of novel strategies for designing health-promoting foods and improving health via the diet

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