New Methods to Improve Fecal Microbiota Transplantation Discovered

Researchers recently discovered a novel way to improve fecal microbiota transplantation (FMT) in patients with recurrent Clostridium difficile infections.

The study, published by mBio, points to multiple microorganisms that are critical for curing a C. difficile infection with fecal microbiota transplantation.

"This paper provides us data with which microbes to supplement into our preparations," said principal study investigator Michael Sadowsky, PhD.

Of patients who are treated with antibiotics for C. difficile infections, 20% to 30% develop a recurrent infection. This is typically caused by an imbalance of gut bacteria that results from antibiotic treatment that kills healthy bacteria.

Gut microbiota are crucial for human health, but can be changed by treatment with antibiotics, which may result in numerous health problems, including recurrent infections.

FMT is a procedure used to treat patients who develop recurrent C. difficile infections, and is successful in 90% of patients, according to the study. The method involves collecting and purifying microbiota from fecal matter donated by a healthy individual. The microbiota is then mixed with a saline solution that is implanted into the patient, typically via colonoscopy.

Included in the study were 27 patients with recurrent infections who either received a heterologous transplant with fecal microbiota from a donor or an autologous transplant with the patient’s own microbiota. The group that received an autologous transplant was considered the placebo group.

The researchers discovered that 90% of patients who received a heterologous transplant were cured, which was the expected result. However, several patients who received an autologous transplant were also cured, according to the study.

Patients who did not respond to an initial autologous transplant then received a heterologous transplant.

To investigate why this occurred, the researchers used Illumina-based next-generation sequencing to determine the bacterial communities. They discovered that patients who were cured by the autologous transplant had an abundance of Clostridium Xia clade and Holdemania prior to transplantation.

This abundance of microbiota significantly increased after transplantation compared with heterologous transplant and pre-transplant samples, according to the study.

Further analyses showed that the microbiota of patients cured by the autologous transplant was drastically different compared with the patients cured by heterologous transplant.

The investigators also found that the donor’s fecal microbiota did not remain the same, but changed over time.

"As opposed to what we thought, complete engraftment of microbiota is not required to be cured," Dr Sadowsky said. "The study provides insight into which microorganisms are the most important for curing a patient and may allow clinicians to better tailor therapy, by improving the donor material to facilitate a more rapid, effective, and lasting cure."