Mapping the gut microbial structural variations in healthy aging within the Chinese population

Highlights•10,367 microbial SVs in 60 gut microbial species are identified from Chinese populations•There is a trend of copy number loss in age-related SVs during the human aging process•Specific microbial SVs could distinguish healthy from unhealthy aging, independent of age•Microbial SVs harboring genes in methionine-homocysteine metabolism are linked to CKDSummaryMapping gut microbial structural variants (SVs) during human aging may provide fundamental knowledge and mechanistic understanding of the gut microbiome's relationship with healthy aging. We characterize gut microbial SVs from 3,230 Chinese participants, identifying key SVs associated with aging, healthy aging, and age-related chronic diseases. Our findings reveal a pattern of copy number loss in aging-related SVs, with 35 core SVs consistently detected. Additionally, eight SVs distinguish healthy from unhealthy aging, regardless of age. Notably, a 3-kbp deletion SV of Bifidobacterium pseudocatenulatum, encoding plant polysaccharide degradation, is regulated by plant-based diet and contributes to healthy aging through bile acid metabolism. Our analysis also connects SVs to age-related diseases, such as chronic kidney disease, via genes in the methionine-homocysteine pathway. This study deepens our understanding of the gut microbiome's role in aging and could inform future efforts to enhance lifespan and healthspan.Graphical abstract