CLRs function as an interface among microbiota, intestinal epithelial barrier and immune system, so we firstly discussed the relationship between dysbiosis caused by microbiota alteration and inflammatory bowel disease (IBD), then focused on the role of CLRs signaling in pathogenesis of IBD (including Mincle, Dectin-3, Dectin-1, DCIR, DC-SIGN, LOX-1 and their downstream CARD9). The gene discussed is CLEC4A; the disease is inflammatory bowel disease.