A microbial consortium alters intestinal Pseudomonadota and antimicrobial resistance genes in individuals with recurrent Clostridioides difficile infection.

Intestinal colonization with pathogens and antimicrobial-resistant organisms (AROs) is associated with increased risk of infection. Fecal microbiota transplant (FMT) has successfully been used to cure recurrent Clostridioides difficile infection (rCDI) and to decolonize intestinal AROs. However, FMT has significant practical barriers to safe and broad implementation. Microbial consortia represent a novel strategy for ARO and pathogen decolonization, with practical and safety advantages over FMT. We undertook an investigator-initiated analysis of stool samples collected from previous interventional studies of a microbial consortium, microbial ecosystem therapeutic (MET-2), and FMT for rCDI before and after treatment. Our aim was to assess whether MET-2 was associated with decreased Pseudomonadota (Proteobacteria ) and antimicrobial resistance gene (ARG) burden with similar effects to FMT. Participants were selected for inclusion if baseline stool had Pseudomonadota relative abundance ≥10%. Pre- and post-treatment Pseudomonadota relative abundance, total ARGs, and obligate anaerobe and butyrate-producer relative abundances were determined by shotgun metagenomic sequencing. MET-2 administration had similar effects to FMT on microbiome outcomes. The median Pseudomonadota relative abundance decreased by four logs after MET-2 treatment, a greater decrease than that observed after FMT. Total ARGs decreased, while beneficial obligate anaerobe and butyrate-producer relative abundances increased. The observed microbiome response remained stable over 4 months post-administration for all outcomes. IMPORTANCE Overgrowth of intestinal pathogens and AROs is associated with increased risk of infection. With the rise in antimicrobial resistance, new therapeutic strategies that decrease pathogen and ARO colonization in the gut are needed. We evaluated whether a microbial consortium had similar effects to FMT on Pseudomonadota abundances and ARGs as well as obligate anaerobes and beneficial butyrate producers in individuals with high Pseudomonadota relative abundance at baseline. This study provides support for a randomized, controlled clinical trial of microbial consortia (such as MET-2) for ARO decolonization and anaerobe repletion.
Competing Interests: The authors declare a conflict of interest. E.A.V. is a cofounder of Nubiyota and K.C. is employed by Nubiyota. S.H. was an investigator in a clinical trial by Finch Therapeutics, for which she received a research grant. NuBiyota manufactured MET-2 and funded the original trial. No funding was received from NuBiyota for the current study.