What Makes Fecal Microbiota Transplant an Effective C Difficile Cure?

With half a million new infections each year, Clostridioides difficile infection (CDI) is the most common hospital acquired infection in the US. The bacterium causes severe diarrhea and colitis, and infection can be recurrent or fatal.

Fecal microbiota transplantation (FMT), the transplant of fecal material from a healthy donor into a C diff patient, is known to effectively treat recurrent CDI. However, there was no consensus of why this therapy is so effective.

Investigators from the University of Virginia (UVA) School of Medicine explored why some microbe combinations work better than others, and why the efficacy of FMT varies from patient to patient.

The investigators previously found that antibiotic-induced dysbiosis reduced colonic expression of interleukin 25 (IL-25) in mice, and FMT helped by restoring IL-25 signaling.

In this study, published in mSphere, the investigators expanded their work to see if FMT induced IL-25 expression in the colons of humans with recurrent CDI.

The investigators collected colonic biopsy specimens and blood samples at the time of each patient’s FMT and then again 60 days later. Specimens were analyzed for IL-25 protein levels, total tissue transcriptome, and epithelium-associated microbiota before and after the patient’s FMT. The investigators also immunophenotyped peripheral immune cells.

The results showed that FMT increased alpha diversity of the colonic microbiota, as well as IL-25 colonic tissue levels. FMT also increased expression of homeostatic genes and repressed inflammatory genes. After successful FMT, circulating Th17 cells significantly decreased.

The increase in cytokine IL-25 levels corresponded with decreased inflammation, an anticipated outcomes that indicates FMT’s ability to restore commensal activation of type 2 immunity and prevent recurrent CDI.

“It is important for us to find out what immune markers change in patients where fecal microbiota transplantation was successful in preventing C difficile re-infections,” said Ning-Jiun Jan, the study’s lead author and a researcher from UVA’s Division of Infectious Disease and International Health.

“Finding that a specific immune-signaling molecule, IL-25, was increased in successful fecal microbiota transplantations indicated that maybe IL-25 can be used as an adjunctive therapy for treating C difficile infection.”