Resurrecting the intestinal microbiota to combat antibiotic-resistant pathogens

Abstract

The intestinal microbiota, which is composed of diverse populations of commensal bacterial species, provides resistance against colonization and invasion by pathogens. Antibiotic treatment can damage the intestinal microbiota and, paradoxically, increase susceptibility to infections. Reestablishing microbiota-mediated colonization resistance after antibiotic treatment could markedly reduce infections, particularly those caused by antibiotic-resistant bacteria. Ongoing studies are identifying commensal bacterial species that can be developed into next-generation probiotics to reestablish or enhance colonization resistance. These live medicines are at various stages of discovery, testing, and production and are being subjected to existing regulatory gauntlets for eventual introduction into clinical practice. The development of next-generation probiotics to reestablish colonization resistance and eliminate potential pathogens from the gut is warranted and will reduce health care-associated infections caused by highly antibiotic-resistant bacteria.

Fig. 1. The intestinal commensal microbiota provides colonization resistance against a wide range of pathogens by indirect and direct mechanisms

Commensal bacteria activate innate immune defenses in the mucosa, produce or modify host-derived metabolites, deplete nutrients, or produce substances that are directly toxic to competing bacteria. These mechanisms in aggregate can induce a high level of resistance against colonization by exogenous bacteria.

Fig. 2. Antibiotic treatment eliminates many commensal bacterial species from the gut lumen and reduces antimicrobial defenses

Antibiotic-resistant bacterial species can thrive, undergo expansion, and traverse the intestinal epithelial barrier. Antibiotic-induced microbiota defects and the resulting loss of colonization resistance can be corrected by administration of commensal bacterial species.