Metagenomic Characterization of Gut Microbiota of Carriers of Extended-Spectrum Beta-Lactamase or Carbapenemase-Producing Enterobacteriaceae Following Treatment with Oral Antibiotics and Fecal Microbiota Transplantation: Results from a Multicenter Randomized Trial

• Main Authors: Stefano Leo, Vladimir Lazarevic, Myriam Girard, Nadia Gaïa, Jacques Schrenzel, Victoire de Lastours, Bruno Fantin, Marc Bonten, Yehuda Carmeli, Emilie Rondinaud, Stephan Harbarth, Benedikt D. Huttner
• Format: Article
• Language: English
• Published: MDPI AG 2020-06-01
• Series: Microorganisms
• Subjects: Fecal microbiota transplantation; extended-spectrum beta-lactamase-producing Enterobacteriaceae; carbapenemase-producing Enterobacteriaceae; microbiome; whole metagenome shotgun sequencing
• Online Access: https://www.mdpi.com/2076-2607/8/6/941

<strong>Background:</strong> The R-GNOSIS (Resistance in Gram-Negative Organisms: Studying Intervention Strategies) WP3 study was the first multicenter randomized clinical trial systematically investigating fecal microbiota transplantation (FMT) for intestinal decolonization of extended-spectrum beta-lactamase-producing Enterobacteriaceae (ESBL-E) or carbapenemase-producing Enterobacteriaceae (CPE). Here, we characterized the temporal dynamics of fecal microbiota changes in a sub-cohort of the R-GNOSIS WP3 participants before and after antibiotics/FMT using whole metagenome shotgun sequencing. <strong>Methods:</strong> We sequenced fecal DNA obtained from 16 ESBL-E/CPE carriers having received oral colistin/neomycin followed by FMT and their corresponding seven donors. Ten treatment-naïve controls from the same trial were included. Fecal samples were collected at baseline (V0), after antibiotics but before FMT (V2) and three times after FMT (V3, V4 and V5). <strong>Results:</strong> Antibiotic treatment transiently decreased species richness and diversity and increased the abundance of antibiotic resistance determinants (ARDs). <em>Bifidobacterium</em> species, together with butyrate- and propionate-producing species from Lachnospiraceae and Ruminococcaceae families were significantly enriched in post-FMT microbiota of treated carriers. After FMT, the proportion of Enterobacteriaceae was lower compared to baseline but without statistical significance. <strong>Conclusions:</strong> Combined antibiotic and FMT treatment resulted in enrichment of species that are likely to limit the gut colonization by ESBL-E/CPE.