The Association between Gut Microbiota and Osteoporosis was Mediated by Amino Acid Metabolism: Multi-omics Integration in a Large Adult Cohort

Several small studies suggested gut microbiome might influence osteoporosis, but rare metabolomics evidence from human study had explained the link. This study examined the association of gut microbiome dysbiosis with osteoporosis and explored the potential pathways by using fecal and serum metabolomics.We analyzed gut microbiota compositions by 16S rRNA profiling and bone density (BMD) using a dual-energy X-ray absorptiometry in 1776 community-based adults. Targeted metabolomics in feces (15 categories) and serum (12 categories) were further analyzed in 971 participants with ultra-performance liquid chromatography coupled to tandem mass spectrometry.This study showed osteoporosis was related to gut microbiota beta diversity, taxonomy and functional composition. The relative abundance of Actinobacillus, Blautia, Oscillospira, Bacteroides and Phascolarctobacterium was positively, while Veillonellaceae other, Collinsella and Ruminococcaceae other were inversely, associated with the presence of osteoporosis, which related to higher levels of peptidases and transcription machinery in microbial function. Fecal and serum metabolomics analyses suggested that the tyrosine metabolism and the tryptophan metabolism in feces and the valine, leucine and isoleucine degradation in serum were significantly linked to the identified microbiota biomarkers and osteoporosis.This large population-based study provided the robust evidence connecting gut dysbiosis, fecal and serum metabolomics with osteoporosis. Our results suggested that gut dysbiosis and amino acid metabolism could be potential targets for the intervention of osteoporosis.