A Consortium of Fecal Microbes that Decolonizes Antibiotic-resistant Enteric Pathogens: A Potential Alternative to Fecal Microbiota Transplantation

Abstract Fecal microbiota transplantation (FMT) has proven effective in decolonizing carbapenemase-producing Enterobacteriaceae (CPE) and vancomycin-resistant Enterococci (VRE). However, its efficacy varies among patients, and frequent implementation poses challenges. Through microbiome analysis of fecal samples from both FMT responders and non-responders, we identified a consortium of four gut commensal species, termed BM111. In an antibiotic-pretreated mouse infection model, BM111 effectively decolonized a VRE strain, demonstrating its therapeutic potential. Additionally, in a humanized mouse model with feces from CPE-infected patients transplanted into germ-free mice, BM111 significantly cleared CPE strains. In animals treated with the BM111 consortium, their microbiome diversity increased post-treatment, correlating with BM111-induced positive outcomes. Further informatic analysis of cohorts from 11 countries confirmed the high prevalence and abundance of these four species in healthy individuals, supporting their potential to restore microbiome balance in patients with infection-induced dysbiosis. The BM111 consortium presents a promising, safe, and effective alternative to FMT for combating antibiotic-resistant enteric infections, warranting further clinical research and development.