A consortium of seven commensal bacteria promotes gut microbiota recovery and strengthens ecological barrier against Vancomycin-Resistant Enterococci

Background Vancomycin-resistant enterococci (VRE) often originate from the gastrointestinal tract, where their proliferation precedes dissemination into the bloodstream, and can lead to systemic infection. Understanding the mechanisms responsible for resistance to intestinal colonisation by VRE is essential for infection control. We aimed to identify commensal bacteria that enhance resistance to colonisation or act as an ecological barrier against VRE. Results We performed a longitudinal analysis of the gut microbiota composition and VRE carriage levels in mice colonised with VRE after antibiotic-induced dysbiosis. By combining biological data and mathematical modelling, we identified 15 molecular species (OTUs) that negatively correlated with VRE overgrowth. Six strains representative of these OTUs were used in mixture with a seventh strain (Mix7) in two different mouse lines challenged with VRE. Of the seven strains, three belonged to Lachnospiraceae, one to Muribaculaceae ( Muribaculum intestinale YL27), one to Ruminococcaceae and two to Lactobacillaceae. We found that Mix7 led to a better recovery of the gut microbiota and reduced VRE carriage. Differences in the effect of Mix7 were observed between responder and non-responder mice. These differences were associated with variations in composition during recovery and initial microbiota, and represent potential biomarkers for predicting response to Mix7. In a mouse model of alternative stable state of dysbiosis, response to Mix7 was associated with higher concentrations of short-chain fatty acids and a range of metabolites, reflecting the recovery of the microbiota back to initial state. Furthermore, M. intestinale YL27 was required for the Mix7 effect in vivo with at least one of the other six strains. None of the supernatant of the 7 strains, alone or in combination, inhibited VRE growth in vitro . Interestingly, 5 strains belong to species shared between humans and mice, and the other two have human functional equivalents. Conclusions We show that supplementation with a mixture of commensal strains, identified by mathematical modelling, improves the ecological barrier effect against VRE through mechanisms dependent on recovery and initial composition of the microbiota. Ultimately, this work will enable a move towards a personalised medicine by targeting patients at risk and likely to respond to supplementation with commensal strains.