Lantibiotic-producing bacteria impact microbiome resilience and colonization resistance.

A subset of commensal bacterial strains secretes bacteriocins, such as lantibiotics, to inhibit or kill neighboring bacteria, thereby protecting their niche in the gut. The antimicrobial spectrum of lantibiotics includes pathogens, offering a potential therapeutic approach for antibiotic-resistant infections. However, the impact of lantibiotic-producing bacteria on the microbiome remains poorly defined. We find that bacterial species encoding lanthipeptide genes in hospitalized patients are present in greater abundance than lantibiotic-deficient strains of the same species. Among the lanthipeptide sequences, some overlapped with the lantibiotic genes of Blautia pseudococcoides SCSK (BpSCSK). In mice, BpSCSK administration prevents intestinal recolonization by a wide range of commensal species following antibiotic-induced dysbiosis and markedly reduces fecal concentrations of microbiota-derived metabolites. Lantibiotic-mediated dysbiosis results in sustained loss of colonization resistance against Klebsiella pneumoniae and Clostridioides difficile infection. Our findings reveal the impact of lantibiotic-producing bacterial species on microbiome resilience and susceptibility to infection following antibiotic treatment.