Gut microbiota of carriers of extended-spectrum beta-lactamase or carbapenemase-producing Enterobacteriaceae following treatment with oral antibiotics and fecal microbiota transplantation

Objective Fecal microbiota transplantation (FMT) has been recently suggested for decolonization of extended-spectrum beta-lactamase (ESBL-E) or carbapenemase-producing (CPE) Enterobacteriaceae from the gut. We aimed to explore which microbiota signatures of the donor and recipient influence successful decolonization by analyzing a cohort of FMT-treated carriers and corresponding donors. Design We used whole-metagenome shotgun sequencing to characterize fecal microbiota obtained from a nested cohort of 16 ESBL-E/CPE carriers having received oral colistin/neomycin followed by FMT and their corresponding 7 donors in the context of a randomized trial (NCT02472600). Ten treatment-naïve controls from the same trial were also included. Fecal samples were collected at baseline (V0), after antibiotics but before FMT (V2) and three times after FMT (a median of 3.7 weeks [V3], 6.7 weeks [V4] and 24.1 weeks [V5] from V0). Decolonization was defined as stool culture negative for ESBL-E/CPE at V4.Results Antibiotic treatment resulted in transient changes characterized by decreased species richness and diversity and increased abundance of antibiotic resistance determinants. Plasmid-borne resistance to colistin was not detected. After FMT, propionate and butyrate producers were increased in successfully decolonized carriers. Conclusions Our findings provide a basis for future studies that should explore whether the microbiota profiles identified in this study might potentially allow targeted selection of ESBL-E carriers with a higher likelihood of successful ESBL-E/CPE decolonization through FMT.