Fecal Transplants Safe Long Term for Recurrent C. Diff

More evidence has emerged for fecal microbiota transplantation (FMT) as a safe option for treating recurrent Clostridioides difficile infection (CDI), according to a survey-based study.

FMT was safe in both the short and long term with little risk of infection transmission, according to Sahil Khanna, MBBS, and colleagues, of the Mayo Clinic in Rochester, Minnesota.

However, several new medical conditions were seen in patients after FMT, in particular weight gain and irritable bowel syndrome (IBS), and “These should be explored further in future prospective studies,” they wrote in Gastroenterology.

CDI is the leading cause of gastroenteritis-related death in North America, and FMT is increasingly showing promise as a second-line or add-on therapy in conjunction with antibiotics for recurrent CDI.

In a separate study in Gastroenterology, researchers at the University British Columbia in Vancouver reported that one therapeutic mechanism behind FMT’s efficacy is that it appears to boost acquired immunity.

Khanna’s group conducted the prospective, single-center study from September 2012 to June 2018 in patients undergoing FMT at the clinic for recurrent CDI.

Data on demographics and comorbidities were abstracted from electronic health records and participants were surveyed at 1 week, 1 month, 6 months, 1 year (short-term), and ≥2 years post-FMT (long-term).

Overall, 609 patients (64.8% female; 95.6% white; median age 56) underwent FMT. Just over 20% were overweight or obese, and 22.8% had inflammatory bowel disease (IBD).

Recurrent CDI was diagnosed when watery diarrhea occurred within 8 weeks of a previous CDI episode with a positive stool assay and interim symptom resolution. FMT was performed using fresh or freeze-thawed stool product from a known or standard universal donor. Most patients received the product by colonoscopy.

In short-term follow-up, >60% of all patients had diarrhea, <33% had constipation, and 9.5% reported additional CDI episodes at 1 year.

On multivariable analysis, patients with IBD, dialysis-dependent kidney disease, and multiple FMTs had a higher risk of urgency and diarrhea. The risk of constipation also increased with time, with susceptibility peaking at 1 year, and was higher in females and lower in IBD patients (P<0.05 for all). Also, patients with depression had lower risk. The risk of cramping decreased with age and time (6 month vs 1 week), and increased with pre-existing IBS.

In long-term follow-up post-FMT (median time 3.7 years), 73 new diagnoses among 477 patients were reported, 13% had gastrointestinal problems, 10% had weight gain, and 11.8% had new infections (unrelated to FMT), with a median time to infection of 29 months.

More than 60% reported short-lived diarrhea at some point, and by 1 year post-FMT, the cumulative incidence of IBS was 16.9% (59/348 patients), with 8.5% having IBS mixed type, 7.2% IBS diarrhea, and, 2.0% IBS constipation.

The authors noted that randomized clinical trials have provided short-term safety data usually limited to a few weeks or months post-FMT, while a few observational studies have reported on long-term safety of FMT in patients with recurrent CDI.

Current study limitations included the survey-based design, which could not assess severity of adverse events (AEs) and their relation to FMT treatment. Also, questionnaires were administered at the 1-month, 6-month, and 1-year time points only to those participants with IBD or FMT failures so the study likely overestimated the overall proportion of patients with symptoms, the authors noted.

Furthermore, estimates of post-FMT IBS should be interpreted with caution as the study did not use a validated questionnaire specifically designed for IBS. A lack of a control group made it difficult to assess if FMT was associated with a higher risk of certain AEs, they stated. Finally, Khanna’s group did not analyze the microbiota of donors or recipients, which could have helped explain the association between FMT and AEs.

In a recent multicenter, retrospective study with data from 207 patients, 143 new diagnoses were reported post-FMT within an average follow-up of 34 months. The most frequently reported conditions were new infections (n=84), followed by gastrointestinal conditions (n=26). No clustering of diagnoses associated with dysbiosis was found.

In the second study, the positive effects of FMT in recurrent CDI patients may be due to beneficial changes in the microbiome, and to improvements in CD4+ T cell and antibody-mediated immunity to C. difficile toxins such as TcdB, according to Theodore S. Steiner, MD, and colleagues.

“These results are important for the design of disease monitoring strategies and highlight that future study of how FMT influences pathogen specific immunity is warranted: specifically, determining if effectively restoring the TcdB specific cellular repertoire to healthy control proportions contributes to treatment success of FMT,” they wrote.

Steiner and colleagues added that understanding how FMT affects immune memory responses will enable its fine-tuning and wider application.

The current studies add to previous research showing that adding FMT to antibiotic therapy can effectively curb CDI recurrence.