Disease trends in a young Chinese cohort according to fecal metagenome and plasma metabolites

Abstract

Most of the disease studies for the gut microbiome have collected cases and control samples from the elderly or the middle-aged. Despite general interest in microbiome health, it is not known how microbial biomarkers from metagenome-wide association studies (MWAS) would perform in a cohort of young individuals, who would be largely free of chronic diseases, as well as medication. Here we analyze high-depth fecal metagenomic shotgun sequencing for 2183 healthy adults with clinical parameters, diet, lifestyle, and metabolite measurements. We provide the first set of large-scale evidence for gut microbiome dysbiosis in hyperuricemia, which relates to meat intake. We build a cardiometabolic disease risk model based on gut microbes for initial screening in a young population and confirm the validity using external cohorts. Fecal bacteria that have been reported to be enriched in colorectal cancer (CRC) are found to correlate with methylhistidines, branched-chain amino acids (BCAA), aromatic amino acids and glutamic acid in these young individuals, which were validated by an additional cohort of 1404 individuals. Our comprehensive data suggest that the gut microbiome could show trends towards diseases years before onset, and the results lay the foundation for the design of larger screens for cardiometabolic diseases and CRC with clinically meaningful cutoffs.