FMT is a promising intervention for immunocompetent patients with recurrent C difficile infection. However, the safety of FMT remains inconclusive due to limited data on serious adverse events and mortality.
Clostridioides difficile (C diff) is a bacterium that can cause severe diarrhea in individuals with dysbiosis of the gut microbiota. Recurrent C diff infection (rCDI) is a common problem, with about 30% of CDI patients experiencing a recurrence.
Traditional treatments with antibiotics may worsen the condition, further killing off “healthy” bacteria that could have competed with the C diff spores. Fecal microbiota transplantation (FMT) is consistently under investigation as a potential solution to correct the underlying gut microbiota imbalance that triggers rCDI.
FMT is a transplant of fecal material from a healthy donor into a C diff patient; it is proven to known to effectively treat rCDI. However, the benefits and risks of FMT for rCDI treatment need to be assessed through randomized controlled trials.
One study, published in the Cochrane Database of Systematic Reviews, aimed to evaluate the benefits and harms of donor-based FMT for treating rCDI in otherwise healthy individuals. The investigators searched medical databases for clinical trials that examined and compared stool transplantation to currently used treatments, such as antibiotics, to treat rCDI.
Randomized trials involving adults or children with rCDI were considered for inclusion. Eligible interventions had to meet the definition of FMT, which was the administration of fecal material containing distal gut microbiota from a healthy donor to the gastrointestinal tract of an individual with rCDI.
The comparison group consisted of participants who did not receive FMT and instead received placebo, autologous FMT, no intervention, or antibiotics targeting C diff.
The primary study outcomes were the proportion of participants with resolution of rCDI and serious adverse events. Secondary outcomes included treatment failure, all-cause mortality, withdrawal from the study, rate of new CDI infection after successful FMT, any adverse event, quality of life, and colectomy.
The final analysis comprised 6 studies involving 320 participants. There were 2 studies conducted in Denmark, and 1 each conducted in the Netherlands, Canada, Italy, and the US. All studies involved adults, and most excluded severely immunocompromised individuals. The time of follow-up after FMT ranged from 8-17 weeks.
The administration of FMT via different routes was evaluated in the studies. The pooled results indicated that FMT in immunocompetent individuals likely resulted in a significant increase in the resolution of rCDI compared to the control group. FMT also showed a slight reduction in serious adverse events and potentially a decrease in all-cause mortality. However, the evidence for these outcomes was of moderate to low certainty.
FMT is likely to be beneficial in resolving recurrent Clostridioides difficile infection in healthy adults compared to alternative treatments such as antibiotics. “We judged the overall certainty of the evidence supporting stool transplants as more effective than other treatments for the resolution of repeated C difficile infection as moderate,” wrote the study authors. “The certainty of evidence for serious side effects was moderate and the certainty of evidence for deaths was low.”
However, the investigators concluded the safety of FMT for rCDI remains inconclusive due to limited data on serious adverse events and all-cause mortality. Further data from large national registry databases are needed to assess any short-term or long-term risks associated with FMT.
Notably, the conclusions hold even when considering the exclusion of immunocompromised individuals, although the study population size was too small to draw definitive conclusions for this group.