Alleviation of colonic inflammation by Lypd8 in a mouse model of inflammatory bowel diseases (IBD)

Dysfunction of the intestinal mucosal barrier causes inflammatory bowel diseases (IBD). Indeed, mucosal barrier impairment in the gut of IBD patients results from decreased expression of barrier molecules. Lypd8 segregates microbiota from the colonic epithelial layer. In this study, we found that Lypd8-/- mice, in which flagellated bacteria invaded the mucosal surface of the colon, developed spontaneous colitis when dysbiosis was induced by a high-fat diet (HFD). Based on this finding, we assessed whether the application of human LYPD8 (hLYPD8) protein exhibiting the glycan-dependent inhibition of bacterial motility is effective in a colitis model. Oral and anal treatment with hLYPD8 protein ameliorates dextran sulfate sodium-induced colitis and HFD-induced colitis in Lypd8-/- mice. These results indicate a therapeutic potential of hLYPD8 protein supplementation for IBD.