Commensal consortia decolonize Enterobacteriaceae via ecological control

Abstract

Persistent colonization and outgrowth of potentially pathogenic organisms in the intestine can result from long-term antibiotic use or inflammatory conditions, and may perpetuate dysregulated immunity and tissue damage1,2. Gram-negative Enterobacteriaceae gut pathobionts are particularly recalcitrant to conventional antibiotic treatment3,4, although an emerging body of evidence suggests that manipulation of the commensal microbiota may be a practical alternative therapeutic strategy5–7. Here we isolated and down-selected commensal bacterial consortia from stool samples from healthy humans that could strongly and specifically suppress intestinal Enterobacteriaceae. One of the elaborated consortia, comprising 18 commensal strains, effectively controlled ecological niches by regulating gluconate availability, thereby re-establishing colonization resistance and alleviating Klebsiella- and Escherichia-driven intestinal inflammation in mice. Harnessing these activities in the form of live bacterial therapies may represent a promising solution to combat the growing threat of proinflammatory, antimicrobial-resistant Enterobacteriaceae infection. Transplants of consortia with limited numbers of strains of commensal bacteria derived from healthy human stool samples are able to suppress intestinal Enterobacteriaceae by regulating gluconate availability, suggesting potential therapies for infectious and inflammatory diseases.