Exploiting commensal bacteria to strengthen host immunity and treat infections

Abstract

Abstract As the rise of microbial resistance to antibiotics continues, there is a pressing need for new therapeutic strategies. One method includes augmenting host immunity and subsequent defense molecules to protect against pathogenic organisms. Antimicrobial peptides (AMPs) represent an ancient arm of the innate immune system that is critical for maintaining host–microbiome interactions. We previously identified that the commensal bacteria Ruminococcus gnavus and Lactobacillus reuteri induce ileal expression of Reg3γ, an AMP with bactericidal activity against gram-positive bacteria. We now find that R. gnavus and L. reuteri induced expression of these AMPs requires Myd88 and group 3 innate lymphoid cells but, interestingly, does not require persistent probiotic colonization. Consistent with this increase in AMP expression, R. gnavus- and L. reuteri-treated mice were protected against intestinal colonization by vancomycin-resistant enterococci (VRE). Finally, patients at high-risk for VRE domination were >4 times less likely to have Enterococcus in their fecal microbiota if they also had Ruminococcus present, a finding that demonstrates the clinical translatability of R. gnavus mediated protection. Taken together, these results spotlight the potential for probiotic based therapies to combat antimicrobial resistant organisms. Supported by grants from NIH (1F31AI161989-01)