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.