A placebo-controlled trial may provide a strategy for improving fecal microbiota transplantation (FMT) for patients with recurrent Clostridium difficile infection. The study identified microorganisms that are key for cure with fecal microbiota transplantation.
Approximately 20% to 30% of patients who are treated with antibiotics for C. difficile get a recurrent infection. Typically, this is caused by a dysbiosis or microbial imbalance of the gut. Microbiota are integral to human physiology and health, and exposure to antibiotics can alter the composition and activity of microbiota, sparking many common health problems.
In the last decade, FMT has been increasingly used to treat patients who have recurrent C. difficile infection, with cure rates over 90%. The procedure involves collecting fecal matter from a healthy donor, purifying microbiota from the feces, mixing it with saline solution, and placing it in a patient, usually by colonoscopy. In the new study, principal investigator Michael Sadowsky, PhD, at the University of Minnesota, and colleagues conducted a clinical trial in 27 patients with recurrent C. difficile infection, using fecal microbiota from healthy patients (a heterologous transplant) and, as a placebo, the patient's own stool microbes (an autologous transplant). The cure rate with the transplantation from healthy donors was 90%, which is what the researchers expected, but surprisingly several patients who received the transplant with their own stool were also cured. Those who did not respond to the autologous transplant went on to receive a heterologous transplant.
Using Illumina-based next-generation sequencing to characterize bacterial communities, the researchers found that subjects cured by what was supposed to be the placebo transplantation had a greater abundance of Clostridium Xia clade and Holdemania prior to treatment, and the relative abundance of these microorganisms significantly increased after transplantation, compared to heterologous transplant and pre-transplant samples. Additional analyses showed that the microbiota of patients cured by the autologous transplant remained distinct from that of patients cured by the heterologous transplant.
The researchers also found that once the donor's fecal microbiota became established in the patient, it didn't stay static, but changed over time. Previous studies have shown that a couple weeks after a fecal microbiota transplant from a healthy donor, a patient's microbiota usually looks very similar to the donor's microbiota.