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Woodworth, Michael H.; Conrad, Roth E.; Haldopoulos, Marina; Pouch, Stephanie M.; Babiker, Ahmed; Mehta, Aneesh K.; Sitchenko, Kaitlin L.; Wang, Charlotte H.; Strudwick, Amanda; Ingersoll, Jessica M.; Philippe, Cécile; Lohsen, Sarah; Kocaman, Kumru; Lindner, Blake G.; Hatt, Janet K.; Jones, Rheinallt M.; Miller, Candace; Neish, Andrew S.; Friedman-Moraco, Rachel; Karadkhele, Geeta; Liu, Ken H.; Jones, Dean P.; Mehta, C. Christina; Ziegler, Thomas R.; [...]

Fecal microbiota transplantation promotes reduction of antimicrobial resistance by strain replacement

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  • Media type: E-Article
  • Title: Fecal microbiota transplantation promotes reduction of antimicrobial resistance by strain replacement
  • Contributor: Woodworth, Michael H.; Conrad, Roth E.; Haldopoulos, Marina; Pouch, Stephanie M.; Babiker, Ahmed; Mehta, Aneesh K.; Sitchenko, Kaitlin L.; Wang, Charlotte H.; Strudwick, Amanda; Ingersoll, Jessica M.; Philippe, Cécile; Lohsen, Sarah; Kocaman, Kumru; Lindner, Blake G.; Hatt, Janet K.; Jones, Rheinallt M.; Miller, Candace; Neish, Andrew S.; Friedman-Moraco, Rachel; Karadkhele, Geeta; Liu, Ken H.; Jones, Dean P.; Mehta, C. Christina; Ziegler, Thomas R.; [...]
  • Published: American Association for the Advancement of Science (AAAS), 2023
  • Published in: Science Translational Medicine, 15 (2023) 720
  • Language: English
  • DOI: 10.1126/scitranslmed.abo2750
  • ISSN: 1946-6234; 1946-6242
  • Origination:
  • Footnote:
  • Description: Multidrug-resistant organism (MDRO) colonization is a fundamental challenge in antimicrobial resistance. Limited studies have shown that fecal microbiota transplantation (FMT) can reduce MDRO colonization, but its mechanisms are poorly understood. We conducted a randomized, controlled trial of FMT for MDRO decolonization in renal transplant recipients called PREMIX (NCT02922816). Eleven participants were enrolled and randomized 1:1 to FMT or an observation period followed by delayed FMT if stool cultures were MDRO positive at day 36. Participants who were MDRO positive after one FMT were treated with a second FMT. At last visit, eight of nine patients who completed all treatments were MDRO culture negative. FMT-treated participants had longer time to recurrent MDRO infection versus PREMIX-eligible controls who were not treated with FMT. Key taxa ( Akkermansia muciniphila , Alistipes putredinis , Phocaeicola dorei , Phascolarctobacterium faecium , Alistipes species, Mesosutterella massiliensis , Barnesiella intestinihominis , and Faecalibacterium prausnitzii ) from the single feces donor used in the study that engrafted in recipients and metabolites such as short-chain fatty acids and bile acids in FMT-responding participants uncovered leads for rational microbiome therapeutic and diagnostic development. Metagenomic analyses revealed a previously unobserved mechanism of MDRO eradication by conspecific strain competition in an FMT-treated subset. Susceptible Enterobacterales strains that replaced baseline extended-spectrum β-lactamase–producing strains were not detectable in donor microbiota manufactured as FMT doses but in one case were detectable in the recipient before FMT. These data suggest that FMT may provide a path to exploit strain competition to reduce MDRO colonization.