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Linking carbohydrate structure with function in the human gut microbiome using hybrid metagenome assemblies

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Abstract

Abstract Background Complex carbohydrates that escape digestion in the small intestine, are broken down in the large intestine by enzymes encoded by the gut microbiome. This is a symbiotic relationship between particular microbes and the host, resulting in metabolic products that influence host gut health and are exploited by other microbes. However, the role of carbohydrate structure in directing microbiota community composition and the succession of carbohydrate-degrading microbes is not fully understood. Here we take the approach of combining data from long and short read sequencing allowing recovery of large numbers of high quality genomes, from which we can predict carbohydrate degrading functions, and impact of carbohydrate on microbial communities. Results In this study we evaluate species-level compositional variation within a single microbiome in response to six structurally distinct carbohydrates in a controlled model gut using hybrid metagenome assemblies. We identified 509 high-quality metagenome-assembled genomes (MAGs) belonging to ten bacterial classes and 28 bacterial families. We found dynamic variations in the microbiome amongst carbohydrate treatments, and over time. Using these data, the MAGs were characterised as primary (0h to 6h) and secondary degraders (12h to 24h). Annotating the MAG’s with the Carbohydrate Active Enzyme (CAZyme) database we are able to identify species which are enriched through time and have the potential to actively degrade carbohydrate substrates. Conclusions Recent advances in sequencing technology allowed us to identify significant unexplored diversity amongst starch degrading species in the human gut microbiota including CAZyme profiles and complete MAGs. We have identified changes in microbial community composition in response to structurally distinct carbohydrate substrates, which can be directly related to the CAZyme complement of the enriched MAG’s. Through this approach, we have identified a number of species which have not previously been implicated in starch degradation, but which have the potential to play an important role.

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