Alterations in intestinal Proteobacteria and antimicrobial resistance gene burden in individuals administered microbial ecosystem therapeutic (MET-2) for recurrentClostridioides difficileinfection

Abstract

Intestinal colonisation 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 decolonise intestinal AROs. However, FMT has significant practical barriers to implementation. A microbial consortium, microbial ecosystem therapeutic (MET)-2, is an alternative to FMT for the treatment of rCDI. It is unknown whether MET-2 is associated with decreases in pathogens and antimicrobial resistance genes (ARGs). We conducted a post-hoc metagenomic analysis of stool collected from two interventional studies of MET-2 (published) and FMT (unpublished) for rCDI treatment to understand if MET-2 had similar effects to FMT for decreasing pathogens and ARGs as well as increasing anaerobes. Patients were included in the current study if baseline stool had Proteobacteria relative abundance greater than or equal to 10% by metagenomic sequencing. We assessed pre- and post-treatment Proteobacteria, obligate anaerobe and butyrate-producer relative abundances and total ARGs. MET-2 and FMT were associated with decreases in Proteobacteria relative abundance as well as increases in obligate anaerobe and butyrate-producer relative abundances. The microbiota response remained stable over 4 or 6 months for MET-2 and FMT, respectively. MET-2, but not FMT, was associated with a decrease in the total number of ARGs. MET-2 is a potential therapeutic strategy for ARO/ARG decolonisation and anaerobe repletion.

Antimicrobial Resistant Organism Decolonization After Microbiome Perturbation (ARO-DECAMP): protocol for a multi-centre, randomized, placebo-controlled feasibility pilot trial

“…In a Phase 1a clinical trial in 19 patients with rCDI, MET-2 was safe and well tolerated among patients (31). In a post-hoc analysis of stool from participants in this study, MET-2 exposure was associated with signi cant decreases in the relative abundance of potential pathogens and antimicrobial resistance genes at a level similar to or greater than FMT (32).…”