A groundbreaking study published June 6, 2025, has raised significant safety concerns about fecal microbiota transplants (FMTs), warning that the procedure may introduce microbes that could hijack the host environment and create new health risks. The research, conducted by scientists at the University of Chicago, challenges current practices in a field that has gained widespread acceptance since FDA approval in 2013.
Microbes "Terraform" Entire Intestinal Tract
The study, which examined mice, human tissue samples, and seven human volunteers, revealed that transplanted microbes don't simply occupy their original regions but instead "terraform" the entire intestinal tract of recipients. Eugene Chang, the study's senior author and professor of medicine at the University of Chicago, warned that "even a single FMT will cause a change in the host-microbe relationships in these very different regions of the bowel that may be very difficult to reverse."
In the research, microbes were taken from three separate regions of the small and large intestines and implanted into mice recipients. Each batch of newly introduced gut flora appeared to take over the entire intestinal tract of each mouse, rather than simply occupying the same region they originated from in the donor's gut. The colonizing microbes also transformed genes and proteins in the tissues of the recipient mice to make a more accommodating environment.
Human Data Confirms Widespread Colonization
The assessment of seven human volunteers over a month found high levels of microbe colonization in the small intestine, confirming that the phenomenon observed in mice also occurs in humans. This widespread colonization caused modifications to immune and metabolic functions, leading researchers to call for greater care in designing fecal transplants.
Current Treatment Landscape and Regulatory Status
FMTs have been hailed as a treatment for Clostridium difficile (C.diff), a common bacterial infection that can cause inflammation and gastrointestinal issues. The FDA first approved FMTs as a treatment for C.diff in 2013 and approved the first drug for FMT treatment in 2022. Some researchers also consider FMTs as potential treatments for Crohn's disease, ulcerative colitis, and irritable bowel disorder.
Proposed Solution: Targeted Microbial Transplantation
Lead author Orlando DeLeon described the findings as a "wake-up call to the field that maybe we shouldn't willy-nilly put large bowel microbes into different parts of the intestine that shouldn't be there." The researchers propose omni microbial transplantation (OMT) as a safer alternative, which administers targeted gut flora as a pill or through endoscopy, targeting specific intestinal regions with "matched" microbes.
"The microbes that were supposed to be there are better suited for it," DeLeon explained, "so they're more naturally going to fill it even in the presence of other microbes."
Expert Commentary and Study Limitations
Ed Kuijper, an expert at the Leiden University Medical Centre in the Netherlands who was not involved in the study, acknowledged that the research "clearly demonstrates that FMT affects the microbiota composition throughout the entire intestinal tract, in both humans and mice." However, Kuijper expressed concerns about the conclusions regarding "microbiota mismatches" and "unintended consequences."
Kuijper noted that the research team acknowledged limitations of investigating only seven human subjects over a month, suggesting that "a more extensive assessment in patients would be important to conclusively assess the potential negative health outcomes of fecal transplants." He proposed that "a more appropriate conclusion would be that FMT induces changes in both the small and large intestines in mice, with systemic effects that vary depending on the region affected. It remains unclear if these changes persist in humans."
Implications for Clinical Practice
The study's findings suggest that current FMT practices may need significant refinement to ensure patient safety. The research indicates that the procedure's effects extend far beyond the intended treatment area, potentially altering the recipient's entire gut ecosystem in ways that may be difficult to reverse.
In Europe, an inter-organization group called EurFMT exchanges research and information and maintains a continental registry for patient follow-up, providing a framework for monitoring long-term outcomes of FMT procedures.
