Fecal Microbiota Transplantation Influences Procarcinogenic Escherichia coli in Recipient Recurrent Clostridioides difficile Patients

Gastroenterology. 2021 Oct;161(4):1218-1228.e5. doi: 10.1053/j.gastro.2021.06.009. Epub 2021 Jun 11.

Abstract

Background & aims: Patients with multiple recurrent Clostridioides difficile infection (rCDI) have a disturbed gut microbiota that can be restored by fecal microbiota transplantation (FMT). Despite extensive screening, healthy feces donors may carry bacteria in their intestinal tract that could have long-term health effects, such as potentially procarcinogenic polyketide synthase-positive (pks+) Escherichia coli. Here, we aim to determine whether the pks abundance and persistence of pks+E coli is influenced by pks status of the donor feces.

Methods: In a cohort of 49 patients with rCDI treated with FMT and matching donor samples-the largest cohort of its kind, to our knowledge-we retrospectively screened fecal metagenomes for pks+E coli and compared the presence of pks in patients before and after treatment and to their respective donors.

Results: The pks island was more prevalent (P = .026) and abundant (P < .001) in patients with rCDI (pre-FMT, 27 of 49 [55%]; median, 0.46 reads per kilobase per million [RPKM] pks) than in healthy donors (3 of 8 donors [37.5%], 11 of 38 samples [29%]; median, 0.01 RPKM pks). The pks status of patients post-FMT depended on the pks status of the donor suspension with which the patient was treated (P = .046). Particularly, persistence (8 of 9 cases) or clearance (13 of 18) of pks+E coli in pks+ patients was correlated to pks in the donor (P = .004).

Conclusions: We conclude that FMT contributes to pks+E coli persistence or eradication in patients with rCDI but that donor-to-patient transmission of pks+E coli is unlikely.

Keywords: Colibactin; Colorectal Cancer; Genotoxin; Microbiome.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Clostridioides difficile / pathogenicity*
  • Clostridium Infections / diagnosis
  • Clostridium Infections / microbiology
  • Clostridium Infections / therapy*
  • Dysbiosis
  • Escherichia coli / enzymology
  • Escherichia coli / genetics
  • Escherichia coli / growth & development*
  • Escherichia coli Proteins / genetics
  • Escherichia coli Proteins / metabolism
  • Fecal Microbiota Transplantation* / adverse effects
  • Female
  • Gastrointestinal Microbiome*
  • Humans
  • Male
  • Metagenome
  • Metagenomics
  • Middle Aged
  • Polyketide Synthases / genetics
  • Polyketide Synthases / metabolism
  • Reinfection
  • Retrospective Studies
  • Time Factors
  • Treatment Outcome

Substances

  • Escherichia coli Proteins
  • Polyketide Synthases