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Fecal microbiota transplantation promotes reduction of antimicrobial resistance by strain replacement

作者:Michael H. Woodworth, Roth E. Conrad, Marina E Haldopoulos, Stephanie Marie Pouch, Ahmed Yahia Mahadi Babiker, Aneesh K. Mehta, Kaitlin L. Sitchenko, Charlotte H. Wang, Amanda F Strudwick, Jessica Mae Ingersoll, Cécile Philippe, Sarah Lohsen, Kumru Kocaman, Blake G. Lindner, Janet K. Hatt, Rheinallt M. Jones, Candace R. Miller, Andrew Scott Neish, Rachel Friedman‐Moraco, Geeta M. Karadkhele, Ken Liu, Dean P. Jones, C. Christina Mehta, Thomas R. Ziegler, David S. Weiss, Christian P. Larsen, Konstantinos T. Konstantinidis, Colleen S. Kraft · 发表于:Science Translational Medicine · 年份:2023 · DOI:10.1126/scitranslmed.abo2750 · 被引用次数:118 · 研究领域:Clostridium difficile and Clostridium perfringens research、Gut microbiota and health、Mycobacterium research and diagnosis

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 st...