Transmission and clearance of potential procarcinogenic bacteria during fecal microbiota transplantation for recurrent Clostridioides difficile

Abstract

<div class="section"> <a class="named-anchor" id="d2809027e254"> <!-- named anchor --> </a> <h5 class="section-title" id="d2809027e255">BACKGROUND</h5> <p id="d2809027e257">Fecal microbiota transplantation (FMT) is an effective treatment for recurrent <i>Clostridioides difficile</i> infection (rCDI) in adults and children, but donor stool samples are currently screened for only a limited number of potential pathogens. We sought to determine whether putative procarcinogenic bacteria (enterotoxigenic <i>Bacteroides fragilis</i>, <i>Fusobacterium nucleatum</i>, and <i>Escherichia coli</i> harboring the colibactin toxin) could be durably transmitted from donors to patients during FMT. </p> </div><div class="section"> <a class="named-anchor" id="d2809027e271"> <!-- named anchor --> </a> <h5 class="section-title" id="d2809027e272">METHODS</h5> <p id="d2809027e274">Stool samples were collected from 11 pediatric rCDI patients and their respective FMT donors prior to FMT as well as from the patients at 2–10 weeks, 10–20 weeks, and 6 months after FMT. Bacterial virulence factors in stool DNA extracts and stool cultures were measured by quantitative PCR: <i>Bacteroides fragilis</i> toxin ( <i>bft</i>), <i>Fusobacterium</i> adhesin A ( <i>fadA</i>), and <i>Escherichia coli</i> colibactin ( <i>clbB</i>). </p> </div><div class="section"> <a class="named-anchor" id="d2809027e295"> <!-- named anchor --> </a> <h5 class="section-title" id="d2809027e296">RESULTS</h5> <p id="d2809027e298">Four of 11 patients demonstrated sustained acquisition of a procarcinogenic bacteria. Whole genome sequencing was performed on colony isolates from one of these donor/recipient pairs and demonstrated that <i>clbB ⁺ </i> <i>E</i>. <i>coli</i> strains present in the recipient after FMT were identical to a strain present in the donor, confirming strain transmission. Conversely, 2 patients exhibited clearance of procarcinogenic bacteria following FMT from a negative donor. </p> </div><div class="section"> <a class="named-anchor" id="d2809027e312"> <!-- named anchor --> </a> <h5 class="section-title" id="d2809027e313">CONCLUSION</h5> <p id="d2809027e315">Both durable transmission and clearance of procarcinogenic bacteria occurred following FMT, suggesting that additional studies on appropriate screening measures for FMT donors and the long-term consequences and/or benefits of FMT are warranted. </p> </div><div class="section"> <a class="named-anchor" id="d2809027e317"> <!-- named anchor --> </a> <h5 class="section-title" id="d2809027e318">FUNDING</h5> <p id="d2809027e320">Crohn’s &amp; Colitis Foundation, the Bloomberg~Kimmel Institute for Cancer Immunotherapy at Johns Hopkins University School of Medicine, the National Cancer Institute, and the Canadian Institutes of Health Research. </p> </div><p class="first" id="d2809027e323"> <div class="figure-container so-text-align-c"> <img alt="" class="figure" src="/document_file/8e5815f3-4139-42af-ba9c-2b18678c5fe5/PubMedCentral/image/jciinsight-4-130848-g081.jpg"/> </div> </p><p class="first" id="d2809027e328">Transmission and/or clearance of putative procarcinogenic bacteria may be a frequent, unintended consequence of fecal microbiota transplantation in pediatric patients with recurrent <i>Clostridioides difficile</i> infection. </p>