α-Defensins Promote Colonization on Mucosal Reservoir to Prevent Antibiotic-Induced Dysbiosis.

In addition to their established functions in host defense, accumulating evidence has suggested an emerging role for antimicrobial proteins (AMPs) in shaping commensal microbiota. However, the role of α-defensins, the most abundant AMPs of intestine, in regulating microbial ecology remains inconclusive. Here, we report that α-defensins promote commensal colonization by enhancing bacterial adhesion to the mucosal reservoir. Experiments utilizing mice deficient in matrix metalloproteinase 7 (MMP7), the α-defensin-activating enzyme, with rigorous littermate controls showed that α-defensin deficiency did not significantly influence steady-state intestinal microbiota. In contrast, α-defensins are essential for replenishment of commensal from the mucosal reservoir following antibiotics-induced dysbiosis, shown by markedly compromised recovery of in animals. Mechanistically, α-defensins promote colonization on epithelial surfaces and adhesion to epithelial cells . Moreover, α-defensins unexpectedly does not show any microbicidal activities against . Together, we propose that α-defensins promote commensal bacterial colonization and recovery to maintain microbial diversity upon environmental challenges.