Fecal microbial (FMTs) can be traced back to the 4th Century, but it is only since their approval by the US Food and Drug Administration in past decade that the procedure has entered wide practice.
They have been hailed as a treatment for Clostridium difficile or C.diff, a common 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 think FMTs may also be an option for treating — a chronic autoimmune condition — ulcerative colitis and irritable bowel disorder.
But researchers warned in a study published June 6, 2025, that FMTs may introduce microbes that could hijack the host environment to suit their needs and thrive, potentially introducing new health risks.
The study, which was performed in mice, human tissue samples and with a small volunteer group, found “mismatches” between the donor fecal matter and destination could have unintended consequences on the recipient’s and metabolic function.
“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,” said Eugene Chang, the study’s senior author and a professor of medicine at the University of Chicago, US, in a press statement.
How does a fecal transplant work?
Every human has a unique mix of microbes in their gastrointestinal tract — the gut. This includes trillions of bacteria, fungi, viruses and other microorganisms that perform biological duties within the body. Collectively, this collection of microbes is called gut flora.
For some people, this ecosystem of microbes is disrupted by infections, autoimmune issues and other problems. This disrupted state is called gut dysbiosis.
FMT donors need to meet a range of requirements: For instance, they must be free of blood-related infections, such as hepatitis and HIV, and they cannot have gut issues themselves.
Doctors usually perform a colonoscopy to extract the donor’s stool and, after further preparation, insert the donor microbes via a long tube into the recipient’s gut.
Colonizing the colon
In the study, microbes were taken from three separate regions of the small and large intensities and implanted into mice recipients.
Each batch of newly introduced gut flora appeared to take over — or, as described by the researchers, “terraform” — 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 — even at a microbial level, these introduced species appeared to thrive.
An assessment in seven human volunteers over a month also found high levels of microbe colonization in the small intestine.
Because this caused modifications to immune and metabolic functions, the researchers say greater care should be given to that use specific, targeted microbes for the intestines.
A ‘wake-up call’ for the FMT field
The study’s lead author, Orlando DeLeon, University of Chicago, said it was 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.”
OMT — omni microbial transplantation — administers a batch of good gut flora as a pill or through endoscopy, targeting specific intestinal regions with “matched” microbes. DeLeon said it’s a better way forward for fecal transplants.
“The microbes that were supposed to be there are better suited for it,” said DeLeon, “so they’re more naturally going to fill it even in the presence of other microbes.”
DW approached the research group for further comment but did not receive a response in time for publication.
Ed Kuijper, an expert at the Leiden University Medical Centre, Netherlands, who was not involved in the study, told DW via email that the research “clearly demonstrates that FMT […] affects the microbiota composition throughout the entire intestinal tract, in both humans and mice.”
But Kuijper said he had concerns with the conclusion that FMT leads to “microbiota mismatches” and “unintended consequences” in various regions of the intestinal tract.
Just as the research team acknowledged the limitations of only investigating seven human subjects over a month, Kuijper said a more extensive assessment in patients would be important to conclusively assess the potential negative health outcomes of fecal transplants.
“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.”
In Europe, an inter-organization group called EurFMT exchanges research and information, and maintains a continental registry for patient follow-up.
Edited by: Zulfikar Abbany
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