Novel microbiota-related gene set enrichment analysis identified osteoporosis associated gut microbiota from autoimmune diseases

Introduction Gut microbiota is now considered to be a hidden organ that interacts bidirectionally with cellular responses in numerous organs belonged to the immune, bone, and nervous systems. Here, we aimed to investigate the relationships between gut microbiota and complex diseases by utilizing multiple publicly available genome-wide association. Materials and methods We applied a novel microbiota-related gene set enrichment analysis approach to detect the associations between gut microbiota and complex diseases by processing genome-wide association studies (GWASs) data sets of six autoimmune diseases (including celiac disease (CeD), inflammatory bowel diseases (IBD), multiple sclerosis (MS), primary biliary cirrhosis (PBC), type 1 diabetes (T1D) and primary sclerosing cholangitis (PSC)) and osteoporosis (OP). Results The family Oxalobacteraceae and genus Candidatus_Soleaferrea were found to be correlated with all of the six autoimmune diseases (FDR adjusted P < 0.05). Moreover, we observed that the six autoimmune diseases except PBC shared 3 overlapping features (including family Peptostreptococcaceae, order Gastranaerophilales and genus Romboutsia). For all of the six autoimmune diseases and BMDs (LS-BMD and TB-BMD), an association signal was observed for genus Candidatus_Soleaferrea (FDR adjusted P < 0.05). Notably, FA / FN-BMD shared the maximum number of overlapping microbial features (e.g., genus Ruminococcaceae_UCG009, Erysipelatoclostridium and Ruminococcaceae_UCG013). Conclusion Our study found that part of the gut microbiota could be novel regulators of BMDs and autoimmune diseases via the effects of its metabolites and may lead to a better understanding of the role played by gut microbiota in the communication of the microbiota-skeletal/immune-gut axis.