Lactobacillus supports Clostridiales to restrict gut colonization by multidrug-resistant Enterobacteriaceae - mouse data

Infections by multidrug-resistant Enterobacteriaceae (MRE) are life-threatening to patients. The intestinal microbiome protects against MRE colonization, but antibiotics cause collateral damage to commensals and open the way to colonization and subsequent infection. Despite the significance of this problem, the specific commensals and mechanisms that restrict MRE colonization remain largely unknown. Here, by performing a multi-omic prospective study of 133 hospitalized patients combined with mice experiments, we find that Lactobacillus is key, though not sufficient, to restrict MRE gut colonization: Lactobacillus rhamnosus and murinus increase the levels of Clostridiales bacteria, which induces a hostile environment for MRE growth (increased butyrate levels and reduced nutrient sources). This mechanism of colonization resistance, an interaction between Lactobacillus sp. and Clostridiales involving cooperation between microbiota members, is conserved in mice and patients. These results stress the importance of exploiting microbiome interactions, not just single microbes, for developing effective probiotics that prevent infections in hospitalized patients.