Transmission and clearance of potential procarcinogenic bacteria during fecal microbiota transplantation for recurrent Clostridioides difficile
Julia L. Drewes, … , Maria Oliva-Hemker, Cynthia L. Sears
Julia L. Drewes, … , Maria Oliva-Hemker, Cynthia L. Sears
Published October 3, 2019
Citation Information: JCI Insight. 2019;4(19):e130848. https://doi.org/10.1172/jci.insight.130848.
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Clinical Medicine Gastroenterology Microbiology

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

Abstract

BACKGROUND Fecal microbiota transplantation (FMT) is an effective treatment for recurrent Clostridioides difficile 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 Bacteroides fragilis, Fusobacterium nucleatum, and Escherichia coli harboring the colibactin toxin) could be durably transmitted from donors to patients during FMT.METHODS 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: Bacteroides fragilis toxin (bft), Fusobacterium adhesin A (fadA), and Escherichia coli colibactin (clbB).RESULTS 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 clbB+ E. coli 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.CONCLUSION 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.FUNDING Crohn’s & 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.

Authors

Julia L. Drewes, Alina Corona, Uriel Sanchez, Yunfan Fan, Suchitra K. Hourigan, Melissa Weidner, Sarah D. Sidhu, Patricia J. Simner, Hao Wang, Winston Timp, Maria Oliva-Hemker, Cynthia L. Sears

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Figure 2

Longitudinal dynamics of bacterial species by 16S qPCR.

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Longitudinal dynamics of bacterial species by 16S qPCR. (A–C) Detection ...
(A–C) Detection of species-specific 16S rRNA–encoding genes in stool DNA by qPCR for FMT donors, patients prior to FMT, and patients at various time points after FMT (2–10 weeks, 10–20 weeks, and >27 weeks) (n = 11 patient/donor pairs). Colors denote the source of the FMT donor stool, with familial donors in shades of blue/purple (P1–P7) and commercial stool bank donors shown in shades of green (P8–P11). The paired-sample Wilcoxon’s test P value shown refers to the levels of the donors compared with the patients prior to FMT. eq., equivalents. (D–F) 16S rRNA–encoding gene levels are divided according to whether the rCDI patient had IBD (red, left panels, n = 6 patient/donor pairs) or not (gray, right panels, n = 5 patient/donor pairs). The final time point available for each patient is presented as the patient’s final post-FMT value, corresponding to either the 10–20 Wks or the 27+ Wks time point. Error bars represent medians with interquartile ranges. For all data, undetectable data points were assigned a value of 1 for display purposes on the log10 scale; statistical analyses (paired-sample Wilcoxon’s test) were performed on the raw data.