Population-based metaproteomics reveals functional associations between gut microbiota and phenotypes

The association between gut microbiota and physiological disorders underscores the crucial need to understand its largely unexplored biological functions. In this study, we analyzed 86,876 microbial proteins and 1,277 human proteins from 1,967 Chinese stool samples. Our results indicate that metaproteomic data captures the microbial biodiversity of a population more effectively than metagenomic data, displaying greater variability in microbial functions and providing reliable assessments of microbiota stability. We identified crucial functions of core microbes and discovered 10,714 associations between metaproteomic taxon, microbial function, or human proteins with 39 phenotypes, including 1,381 features related to Type 2 Diabetes (T2D). Importantly, Megasphaera elsdeniis conversion of lactate to butyric acid appears to lower blood glucose levels, suggesting a protective mechanism against T2D. Our study underscores the power of population-based metaproteomics to offer unique functional insights into the gut microbiota. Highlights- The first large-scale population-based metaproteomics landscape. - Metaproteomics efficiently maps microbial functions, exposing individual functional variation. - 10,714 associations between metaproteomic taxa, microbial functions, or human proteins with 39 phenotypes. - Megasphaera elsdenii protects against elevated blood glucose levels in the host by degrading lactate to produce butyric acid.