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Currently, there are no effective modalities for decreasing or preventing colonization by antibiotic-resistant bacteria. Intestinal microbiota restoration can prevent\n                      <jats:italic>Clostridioides difficile<\/jats:italic>\n                      infection (CDI) recurrences. Another potential application of microbiota restoration is suppression of non-\n                      <jats:italic>C. difficile<\/jats:italic>\n                      multidrug-resistant bacteria and overall decrease in the abundance of antibiotic resistance genes (the resistome) within the gut microbiota. This study characterizes the effects of RBX2660, a microbiota-based investigational therapeutic, on the composition and abundance of the gut microbiota and resistome, as well as multidrug-resistant organism carriage, after delivery to patients suffering from recurrent CDI.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      An open-label, multi-center clinical trial in 11 centers in the USA for the safety and efficacy of RBX2660 on recurrent CDI was conducted. Fecal specimens from 29 of these subjects with recurrent CDI who received either one (\n                      <jats:italic>N<\/jats:italic>\n                      \u2009=\u200916) or two doses of RBX2660 (\n                      <jats:italic>N<\/jats:italic>\n                      \u2009=\u200913) were analyzed secondarily. Stool samples were collected prior to and at intervals up to 6\u2009months post-therapy and analyzed in three ways: (1) 16S rRNA gene sequencing for microbiota taxonomic composition, (2) whole metagenome shotgun sequencing for functional pathways and antibiotic resistome content, and (3) selective and differential bacterial culturing followed by isolate genome sequencing to longitudinally track multidrug-resistant organisms.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Successful prevention of CDI recurrence with RBX2660 correlated with taxonomic convergence of patient microbiota to the donor microbiota as measured by weighted UniFrac distance. RBX2660 dramatically reduced the abundance of antibiotic-resistant Enterobacteriaceae in the 2 months after administration. Fecal antibiotic resistance gene carriage decreased in direct relationship to the degree to which donor microbiota engrafted.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Microbiota-based therapeutics reduce resistance gene abundance and resistant organisms in the recipient gut microbiome. This approach could potentially reduce the risk of infections caused by resistant organisms within the patient and the transfer of resistance genes or pathogens to others.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Trial registration<\/jats:title>\n                    <jats:p>\n                      ClinicalTrials.gov,\n                      <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"uri\" xlink:href=\"https:\/\/clinicaltrials.gov\/ct2\/show\/NCT01925417\">NCT01925417<\/jats:ext-link>\n                      ; registered on August 19, 2013.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1186\/s13073-021-00843-9","type":"journal-article","created":{"date-parts":[[2021,2,18]],"date-time":"2021-02-18T03:18:11Z","timestamp":1613618291000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":82,"title":["Microbiota restoration reduces antibiotic-resistant bacteria gut colonization in patients with recurrent Clostridioides difficile infection from the open-label PUNCH CD study"],"prefix":"10.1186","volume":"13","author":[{"name":"for the CDC Prevention Epicenter Program","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amy","family":"Langdon","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1568-7733","authenticated-orcid":false,"given":"Drew J.","family":"Schwartz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher","family":"Bulow","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoqing","family":"Sun","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tiffany","family":"Hink","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kimberly A.","family":"Reske","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Courtney","family":"Jones","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carey-Ann D.","family":"Burnham","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Erik R.","family":"Dubberke","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gautam","family":"Dantas","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2021,2,16]]},"reference":[{"key":"843_CR1","volume-title":"Tackling drug-resistant infections globally: final report and recommendations","author":"J O'Neill","year":"2016","unstructured":"O'Neill J. 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Institutional review boards at each center approved the study protocol, and all patients provided informed consent. Secondary microbiome analysis of de-identified fecal samples presented here was deemed non-human subjects research by the Washington University in St. Louis Human Rights Protection Office (HRPO 201409079). Both the clinical trial and this study conformed to the principles of the Helsinki Declaration.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"Not applicable","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"Rebiotix, Inc. provided access to study specimens and data and reviewed the manuscript prior to submission, but was not involved in this study\u2019s design, specimen processing, data analysis, or interpretation. Washington University investigators had the final say on published content. Erik R. Dubberke is a consultant for Sanofi, Pfizer, Synthetic Biologics, BioK+, and Rebiotix with grants from Pfizer. The remaining authors declare no other competing interests.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"28"}}