SRA

Human genetic variation influences the composition of the gut microbiome. Studies have focused on associations between components of the microbiome and single nucleotide polymorphisms in genes, but their copy number (CN) can also vary. Here, we relate oral and gut microbiome to CN variation at the AMY1 locus, encoding the salivary amylase gene active in starch degradation, in a study of human subjects including a 2-week standard diet. We show that diet standardization drove gut microbiome convergence, yet AMY1-CN influenced oral and gut microbiome composition and function. Low-AMY1-subject gut microbiomes showed an enhanced capacity for breakdown of complex carbohydrates, and high-AMY1 an enrichment of microbiota linked to resistant starch fermentation. High-AMY1-subject microbiomes were associated with higher fecal SCFAs, and drove higher adiposity when transferred to germfree mice. This study establishes AMY1-CN as a significant genetic factor patterning microbiome composition and function, with implications for personalized nutrition targeting microbiomes.