Study expands understanding of how fecal microbiota transplants may work to restore gut health

Fecal microbiota transplant, or FMT, is a procedure in which stool from healthy donors is transplanted via colonoscopy into the bowels of people with dangerous and recurrent infections caused by a bacterium called Clostridioides difficile (C. difficile). Many previous studies show that the transplanted fecal material from healthy donors restores the balance of good bacteria that are markers of a healthy gut in people whose recurrent C.difficile infections have been treated with heavy duty antibiotics that wipe out "good" bacteria as well as bad.

Recurrent C. difficile infection is an often debilitating condition marked by severe diarrhea and inflammation of the colon. Researchers say the infections are notoriously difficult to treat, with conventional antibiotic therapies often failing to provide long-term relief and cure of the infection.

The new study, described in the Journal of Gastro Hep Advances on October 18, shows that transfer donor cells that line the intestinal tract along with the donor's fecal matter may be responsible for improved outcomes for at least some patients.

"Our study suggests the possibility of donor intestinal epithelial cell transfer during fecal microbiota transplant, rather than the mere transfer of bacteria from donor fecal samples, can be more effective," says lead author Sudhir Dutta, M.D., a clinical gastroenterologist and a researcher with the Division of Gastroenterology and Hepatology at the Johns Hopkins University School of Medicine.

According to Dutta, donor intestinal epithelial cells live in the inner lining of the colon and the small intestine. These cells maintain the intestine's structural integrity and functional capacity. Humans shed millions of these cells into the fecal stream every day.

In the new study, the researchers found that the SRY gene responsible for the male-defining characteristics of Y chromosomes, along with evidence of the Y chromosome itself, was detected in the fecal samples of some female patients receiving FMT from male donors.

"The long-term detection of the Y chromosome suggests that, in addition to the intestinal microbiota restoration, FMT may facilitate epithelial repair in the gut lining resulting in the altered milieu of the intestinal ecosystem. These observations open up a deeper understanding of the mechanism by which FMT works," says Sandeep Verma, M.D., a research and clinical fellow with the division of gastroenterology at the Johns Hopkins University School of Medicine. "Our research points to a much more complex interaction between the donor microbiome and the recipient's gut environment than previously reported."

Overall, the researchers analyzed the fecal samples collected from 30 healthy male and female donors, and 22 patients who had received FMT. Over 24 months, they determined that the female patients who had received the FMT from male donors had something more than bacteria in their samples. They saw that Y chromosomes were present in 33% of the female patients with male donors where, typically, there would be no Y chromosome presence or activity in female fecal samples. "This finding suggests that stool is a much more complex excretion than we thought it was," Verma says.

Verma cautioned that more studies are needed in a larger group of female patients who receive FMT from healthy male donors to determine the extent of epithelial "engraftment" in the intestines of FMT patients.

"Understanding the role of donor-derived cells in gut healing could potentially lead to new treatments that go beyond microbial restoration and target the epithelial structure itself," Verma added.

The U.S. Food and Drug Administration approved FMT in 2022. Although relatively rare, use of the procedure is highly effective. An estimated 48,000 are done in the U.S. annually.

The study was supported by the Harry and Jeanette Weinberg Foundation, the James and Carolyn Frenkil Foundation, the Eric Cowan Fund, and Friedman & Friedman, LLP. It was conducted at Sinai Hospital of Baltimore and results were analyzed at Johns Hopkins University School of Medicine. The authors do not report any competing interests.