Fecal microbiota transplants (FMTs) have been explored as a treatment for various conditions, including inflammatory bowel diseases and obesity. However, new research from the University of Chicago indicates that the most commonly used FMT technique may lead to unintended long-term health consequences.
The process involves transferring microbes from a healthy individual's stool to a sick person, aiming to restore gut microbiome balance. Yet, the digestive system comprises different environments with specific needs, and this method might introduce microbes into unsuitable areas.
In studies involving mice and human tissue samples, researchers found that transplanted colon microbes also colonized recipients' small bowels after one transplant and persisted for months. These microbes altered their new environments to benefit themselves, impacting metabolism, behavior, and energy balance in recipients.
Orlando "Landon" DeLeon, a postdoctoral researcher at UChicago and lead author of the study published in Cell, stated: “I think it's a bit of a wakeup 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.” He emphasized matching regional microbiota to their proper environments for better health outcomes.
Currently approved by the Food and Drug Administration only for treating repeated Clostridium difficile infections, FMT has shown success in these cases. This success has led some physicians to consider its use for other digestive conditions. However, each gut region hosts distinct microbial ecosystems tailored for specific functions vital to host health.
DeLeon worked with Prof. Eugene B. Chang and others on experiments with mice receiving transplants from different intestinal regions. They observed that transplanted microbes could colonize entire intestinal tracts rather than just their native niches, causing regional mismatches lasting up to three months post-transplant.
These mismatches altered metabolite production in each intestinal region, affecting host health by changing liver metabolism and immune function-related gene activity. Changes were also noted in eating behaviors and energy expenditure among mice after transplants.
Chang highlighted the need for caution with FMT due to potential long-term effects: “We have absolutely no idea what’s in FMT... But even a single FMT will cause a change in the host-microbe relationships.”
Both DeLeon and Chang propose "omni-microbial transplants" (OMT), using microbes from all intestinal regions instead of primarily those from the colon. This approach would help ensure that microbes naturally settle where they are best suited.
DeLeon plans further research on how different microbes influence various intestinal parts using methods like single-cell sequencing. Understanding these dynamics could improve microbial transplant applications significantly.
Additional contributors include Mora Mocanu et al., from UChicago; Julia Moore et al., from Midwestern University; Zhilu Xu et al., from the Chinese University of Hong Kong.
Citation: “Regional microbiota mismatches from fecal microbiota transplants promote persistent, off-target consequences to the host.” DeLeon et al., Cell, June 6, 2025.
Funding was provided by National Institutes of Health/National Institute of Diabetes and Digestive and Kidney Diseases and UChicago GI Research Foundation.