In a groundbreaking study that uncovered male chromosome genetic material in the intestines of female patients receiving fecal transplants, researchers from Johns Hopkins Medicine believe they have greatly broadened our understanding of how some of these transplants function and succeed.
Fecal microbiota transplant (FMT) is a medical procedure that involves transferring stool from healthy donors into the intestines of individuals suffering from severe and recurring infections caused by a bacteria known as Clostridioides difficile (C. difficile). Numerous prior studies indicate that this fecal material helps restore the balance of beneficial bacteria, which are essential for a healthy gut, in individuals whose C. difficile infections have been treated with potent antibiotics that eliminate both good and bad bacteria.
Recurrent C. difficile infections are often debilitating, characterized by intense diarrhea and colon inflammation. Researchers note that these infections are particularly challenging to manage, as typical antibiotic treatments frequently do not yield long-term improvements or cure the condition.
The recent study, published in the Journal of Gastro Hep Advances on October 18, reveals that the donor’s intestinal cells, alongside the fecal matter, could significantly contribute to better outcomes for certain patients.
“Our research indicates that transferring donor intestinal epithelial cells during fecal microbiota transplant—rather than just bacteria from the fecal samples—could be more advantageous,” states lead author Sudhir Dutta, M.D., a clinical gastroenterologist affiliated with the Division of Gastroenterology and Hepatology at Johns Hopkins University School of Medicine.
Dutta explains that donor intestinal epithelial cells are found in the inner lining of both the colon and the small intestine. These cells are crucial for maintaining the structural integrity and functionality of the intestines, and humans release millions of them daily through their stool.
In this study, researchers identified the SRY gene, associated with male characteristics from Y chromosomes, along with the Y chromosome itself, in the fecal samples of several female patients receiving FMT from male donors.
“The prolonged presence of the Y chromosome indicates that FMT might not only restore the intestinal microbiota but also aid in repairing the gut lining, leading to changes within the intestinal environment. This increases our understanding of the mechanisms behind FMT,” comments Sandeep Verma, M.D., a research fellow with the division of gastroenterology at Johns Hopkins University School of Medicine. “Our findings suggest a much more intricate relationship between the donor microbiome and the recipient’s gut environment than previously recognized.”
Overall, researchers examined fecal samples from 30 healthy male and female donors as well as from 22 patients who had undergone FMT. Over two years, they discovered that female patients who received FMT from male donors contained more than just bacteria in their samples. They found Y chromosomes present in 33% of these females, where normally, Y chromosomes would not be detectable, as they typically do not appear in female fecal samples. “This discovery indicates that stool is much more complex than we had assumed,” Verma notes.
Verma emphasized that further studies are needed with a larger group of female patients receiving FMT from healthy male donors to ascertain the extent of epithelial cell “engraftment” in their intestines.
“Gaining a deeper understanding of how donor-derived cells contribute to gut healing may pave the way for new treatments that extend beyond just restoring microbial balance and focus on the epithelial structure itself,” Verma added.
The U.S. Food and Drug Administration approved FMT in 2022. Although it is not commonly performed, the procedure has shown to be highly effective, with approximately 48,000 procedures conducted annually in the U.S.
This study received funding from 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, with results analyzed at Johns Hopkins University School of Medicine. The authors report no competing interests.
