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
Leo, Stefano; Lazarevic, Vladimir; Girard, Myriam; Gaïa, Nadia; Schrenzel, Jacques; de Lastours, Victoire; Fantin, Bruno; Bonten, Marc; Carmeli, Yehuda; Rondinaud, Emilie; Harbarth, Stephan; Huttner, Benedikt D
(2020) Microorganisms, volume 8, issue 6, pp. 1 - 15
(Article)
Abstract
Background: 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
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of the R-GNOSIS WP3 participants before and after antibiotics/FMT using whole metagenome shotgun sequencing. Methods: 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). Results: Antibiotic treatment transiently decreased species richness and diversity and increased the abundance of antibiotic resistance determinants (ARDs). Bifidobacterium 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. Conclusions: Combined antibiotic and FMT treatment resulted in enrichment of species that are likely to limit the gut colonization by ESBL-E/CPE.
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Keywords: Carbapenemase-producing Enterobacteriaceae, Extended-spectrum Enterobacteriaceae, Fecal microbiota transplantation, Metagenome shotgun sequencing, Microbiology (medical), Virology, Microbiology, Journal Article
ISSN: 2076-2607
Publisher: MDPI AG
Note: Funding Information: Funding: The present study was part of the European R-GNOSIS (Resistance in Gram-Negative Organisms: Studying Intervention Strategies) collaborative research project funded by the European Commission under the Seventh Framework Programme (FP7/2007) for Research and Technology (Grant Agreement no. 282512). Funding Information: The present study was part of the European R-GNOSIS (Resistance in Gram-Negative Organisms: Studying Intervention Strategies) collaborative research project funded by the European Commission under the Seventh Framework Programme (FP7/2007) for Research and Technology (Grant Agreement no. 282512). Acknowledgments: We would like to thank all the patients, donors and medical personnel involved in the study. This study has also received contributions from the Clinical Research Centre, Geneva University Hospitals and Faculty of Medicine, Geneva (special thanks to Serenella Ferro Rojas and Khaled Mostaguir). Furthermore, we would like to thank the following colleagues, M. Wassenberg, N. Maharshak, A. Mauris, T. Galperine, V. Zanichelli, N. Kapel, A. Bellanger, F. Olearo, X. Duval, L. Armand-Lefevre, F. Jantarada, D. Schaerrer, I. U?kay, K. Berrouane, E. Marcault, I. Vivaldo, L. Alavoine and M. Benhayoun. Publisher Copyright: © 2020 by the authors. Licensee MDPI, Basel, Switzerland.
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