Commensal Bacterial Expressing Blc^E84 Induces Disruption Of Host Epithelial Barrier And Local Inflammation

Alternation of commensal bacteria composition is strongly associated with diarrhea pathogenesis.However,how intestinal inflammation trigged by specific microbiota remains undefined.We hypothesize that some genes encoded by E.coli may play crucial role to maintain the integrity of host intestinal epithelia and mucosa immunity.By screening 3,983 E.coli mutants,it was found that mutation of bacterial lipocalin(blc)strongly activated innate immunity in C.elegans.Interestingly,blc gene of several diarrhoeagenic E.coli in human gut often encodes a variant protein BlcE84,different from the BlcG84 encoded by blc gene of the nonpathogenic bacteria.This single amino acid change is caused by a G to A transversion at position 251 in blc coding sequence.We found bacteria expressing BlcE84 is significantly enriched in the fecal samples from patients with inflammatory bowel diseases(IBDs)while bacteria expressing BlcG84 is enriched in health control.Exposure of bacteria expression BlcE84 lead to dramatically increased immune response and gut epithelial barrier disruption both in worms and mice.Further studies demonstrated that the BlcE84 displayed decreased binding affinity with lysophosphatidylethanolamine(LPE)compared to BlcG84.Moreover,feeding of LPE reversed the BlcE84 expression E.coli induced disruption of host epithelial barrier and local inflammation.These findings reveal in first time that bacteria genome mutation may regulate the host immunity.