<i>Cosmc</i> is an X-linked inflammatory bowel disease risk gene that spatially regulates gut microbiota and contributes to sex-specific risk

Abstract

Significance Inflammatory bowel disease (IBD) is a devastating illness that affects 1.6 million people in the United States and disproportionately affects males in early onset disease. However, IBD genes that contribute to sex-specific risk are unexplored. The gut microbiota interfaces the host with its environment and exhibits alterations in spatial organization in IBD with dysbiosis in the mucosa but a relatively unaffected lumen. Core 1 β3GalT-specific molecular chaperone ( Cosmc ) was recently identified as an IBD risk gene on the X chromosome by genome-wide association study. We functionally evaluated Cosmc in IBD and discovered that the loss of Cosmc leads to gut inflammation in males but not females and a spatial pattern of dysbiosis resembling IBD. Thus, Cosmc contributes to sex bias in IBD and spatially regulates the gut microbiota.