Scientists develop tracking technology for donor bacteria in fecal transplants

A team at the Icahn School of Medicine at Mount Sinai has cracked open a longstanding puzzle in microbiome medicine: which bacteria from a donor's stool actually take root in a patient's gut after transplant, and what happens to them over time. The breakthrough hinges on a combination of long-read DNA sequencing—a technique that reads much longer stretches of genetic code than older methods—paired with a computational tool called LongTrack, developed at Mount Sinai itself. Together, they allow researchers to identify individual bacterial strains with precision, tracking each one's unique genetic signature through years of adaptation in a new host.

Fecal microbiota transplants, or FMT, involve transferring stool from a healthy donor directly into a patient's intestine. The procedure has proven remarkably effective for treating Clostridioides difficile infection, a serious gut pathogen, and researchers are now testing it for inflammatory bowel disease and even cancer. Yet the field has operated largely in the dark about which specific bacterial strains drive recovery and how those strains change once they settle into their new environment. The new tracking technology answers both questions.

Gang Fang, a professor of genetics and genomic sciences at Mount Sinai and senior author of the study published in Nature Microbiology, explains that the approach offers something previous short-read sequencing could not: the ability to follow donor bacteria strain by strain with reliability and at scale. The team analyzed stool samples collected from both FMT donors and recipients before and after treatment for C. difficile and inflammatory bowel disease, with some samples taken as long as five years after transplant. The data revealed that many donor bacteria not only survived but persisted in the recipients' microbiome. More striking still, some strains showed genetic mutations that suggested they had adapted to their new hosts—evidence that different gut environments can actually shape how bacteria evolve from one person to another.

This capacity to pinpoint which bacteria successfully colonize opens a new path forward for microbiome medicine. Rather than transplanting whole stool, which contains hundreds of bacterial species and is difficult to standardize or regulate, researchers could now design targeted mixtures of beneficial microbes chosen specifically for their ability to establish and persist. Such treatments would be safer, more predictable, and far easier for regulators to evaluate than the current whole-stool approach. Fang describes the work as a step toward precision medicine for the microbiome—the ability to track beneficial bacteria reliably over time, understand the genetic mutations involved in their adaptation, and use that knowledge to design treatments that are both effective and consistent.

The implications extend beyond C. difficile and inflammatory bowel disease. As researchers continue to explore FMT for other conditions, the ability to monitor which strains thrive and how they change will become increasingly valuable. The technology essentially provides a detailed map of bacterial colonization and evolution, information that was simply unavailable before. For patients, the promise is treatments that work more reliably and carry fewer unknowns. For the field, it represents a shift from trial-and-error transplantation toward rational design of microbiome interventions.