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

ABSTRACT: 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 ?-defensins, the most abundant AMPs of intestine, in regulating microbial ecology remains inconclusive. Here, we report that ?-defensins promote commensal Bacteroides colonization by enhancing bacterial adhesion to the mucosal reservoir. Experiments utilizing mice deficient in matrix metalloproteinase 7 (MMP7), the ?-defensin-activating enzyme, with rigorous littermate controls showed that ?-defensin deficiency did not significantly influence steady-state intestinal microbiota. In contrast, ?-defensins are essential for replenishment of commensal Bacteroides from the mucosal reservoir following antibiotics-induced dysbiosis, shown by markedly compromised recovery of Bacteroides in Mmp7 -/- animals. Mechanistically, ?-defensins promote Bacteroides colonization on epithelial surfaces in vivo and adhesion to epithelial cells in vitro. Moreover, ?-defensins unexpectedly does not show any microbicidal activities against Bacteroides. Together, we propose that ?-defensins promote commensal bacterial colonization and recovery to maintain microbial diversity upon environmental challenges.

SUBMITTER: Ou J 

PROVIDER: S-EPMC7509133 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature