Experts Identify Why Fecal Transplants Are Effective Treatments for C. difficile

Investigators from the University of Nottingham and Nottingham Trent University have identified a new molecular reason why fecal transplants are highly effective in treating infections such as Clostridium difficile (C.diff), which could potentially lead to more targeted treatments for this and other similar diseases.

C. diff, a bacterium that can infect the bowel and cause severe diarrhea, most commonly affects people who have recently been treated with antibiotics. A fecal microbiota transplant (FMT) works by repopulating the patient’s gut with the microbes from a healthy person, making it an effective therapy against C. diff.

An FMT, which is only considered if the patient suffers recurring bouts of the infection or has not responded to traditional treatments, is effective in at least 80% of cases, according to the study.

After the fecal sample is produced, it is mixed with water. Patients can either receive it orally or through a colonoscopy in order to get the sample into the required location in the bowel. Whilst the technique is highly effective, researchers still know relatively little information about how it works. In the new study, investigators aimed to understand the molecular workings of the treatment.

“It is not fully understood how an FMT works at a molecular level,” explained Tanya Monaghan, a clinical associate professor at the University of Nottingham and co-lead author of the project, in a press release. “That is a problem because if we know how it worked at this level, then we could refine the treatment, which would mean a full transplant may not be needed.”

The investigators used blood samples from 2 clinical FMT trials, which were undertaken in Canada. From these data, they could see that following successful FMTs, patients had altered microRNAs in the blood. MicroRNAs are a class of short non-coding RNA molecules and there are more than 2000 microRNAs discovered in humans to date, many of which have already been implicated in common human disorders.

“MicroRNAs are characterized as master regulators of gene expression,” said study co-author Christos Polytarchou, an associate professor at Nottingham Trent University, in the press release. “A single microRNA can modulate multiple RNA and protein molecules, affecting a vast array of cell functions.”

The researchers discovered that following successful transplant, specific microRNAs in the blood were increased, resembling similar changes seen in both human and mouse intestine. Polytarchou added that C. diff utilizes its toxins to highjack the molecular mechanism important to microRNA maturation.

The investigators then looked at whether or not the combination of specific microRNAs could protect bowel cells from the damage that is induced by toxins from the bacteria, and they found that they could.

“We have discovered a new mechanism by which the transplants work, which will now help us to develop a new method of therapeutics, which specifically target microRNAs,” Monaghan said in the press release. “MicroRNA-based drugs are already being investigated to treat cancers, heart abnormalities, and kidney disease, but this is the first time microRNAs have been looked at as a means to treat C. diff infections. If used with antimicrobials, microRNA drugs could be extremely effective in treating C. diff and potentially other diseases.”

REFERENCES

New research on why ‘poo’ transplants effectively treat C. diff could lead to more treatments for similar conditions [news release]. University of Nottingham; April 9, 2021. https://www.nottingham.ac.uk/news/poo-transplants. Accessed April 16, 2021.