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 α-defensins, the most abundant AMPs of intestine, in regulating microbial ecology remains inconclusive. Here, we report that α-defensins promote commensal Bacteroides 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 Bacteroides from the mucosal reservoir following antibiotics-induced dysbiosis, shown by markedly compromised recovery of Bacteroides in Mmp7−/− animals. Mechanistically, α-defensins promote Bacteroides colonization on epithelial surfaces in vivo and adhesion to epithelial cells in vitro. Moreover, α-defensins unexpectedly does not show any microbicidal activities against Bacteroides. Together, we propose that α-defensins promote commensal bacterial colonization and recovery to maintain microbial diversity upon environmental challenges.
Highlights
The mammalian gastrointestinal tract is under continuous exposure to trillions of microorganisms that play fundamental roles in maintenance of gut homeostasis, modulation of the immune system, facilitation of digestion, and regulation of distant organ functions in physiology and disease [1, 2]
The mucus layers α-Defensins Promote Bacteroides Colonization serve as nutrients for bacteria and provide attachment sites that are protected from the fecal streams [8]
Data from microbial analyses and functional studies demonstrated lack of significant differences in the fecal or terminal ileum microbiota of Mmp7+/+ and Mmp7−/− littermates at homeostasis, yet revealed a previously unappreciated role of α-defensins in facilitating microbiota recovery from antibiotics-induced dysbiosis by promoting bacterial colonization on the mucosal reservoirs such as epithelial surfaces
Summary
The mammalian gastrointestinal tract is under continuous exposure to trillions of microorganisms (microbiota) that play fundamental roles in maintenance of gut homeostasis, modulation of the immune system, facilitation of digestion, and regulation of distant organ functions in physiology and disease [1, 2]. Antimicrobial proteins (AMPs) secreted by intestinal epithelia cells help maintain proper segregation of microbiota from the epithelial surfaces [9]. Besides their protective functions, several recent studies imply that AMPs could be detrimental to host defense by promoting colonization of certain enteric pathogens [10, 11]. Data from microbial analyses and functional studies demonstrated lack of significant differences in the fecal or terminal ileum microbiota of Mmp7+/+ and Mmp7−/− littermates at homeostasis, yet revealed a previously unappreciated role of α-defensins in facilitating microbiota recovery from antibiotics-induced dysbiosis by promoting bacterial colonization on the mucosal reservoirs such as epithelial surfaces
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
