In a groundbreaking advancement for microbiome science, researchers at the Icahn School of Medicine at Mount Sinai have unveiled a revolutionary technology enabling precise tracking of beneficial bacteria following fecal microbiota transplants (FMT). This sophisticated approach provides an unprecedented window into the intricate dynamics of how donor microbes colonize and persist within the patient’s gut environment, mapping not only their initial success but also how their genetic makeup evolves across extended periods. This breakthrough could redefine the future landscape of microbiome-based therapies, offering safer, more targeted interventions with enhanced efficacy.
FMT, the practice of transferring stool from a healthy donor to a patient’s intestinal tract, has gained widespread recognition for its remarkable effectiveness in combatting Clostridioides difficile infections. Beyond this, it holds promise for treating a host of conditions including inflammatory bowel disease (IBD) and certain forms of cancer. Yet a significant knowledge gap has persisted: which bacterial strains are the true champions of colonization and therapeutic benefit, and how they evolve within their new hosts has remained elusive.
The new method pioneered by Mount Sinai researchers cleverly combines state-of-the-art long-read DNA sequencing with an innovative computational algorithm termed LongTrack. Unlike traditional short-read sequencing that processes fragmented pieces of microbial genomes, long-read sequencing decodes extended DNA sequences, providing a continuous genetic narrative of each bacterium. When paired with LongTrack, this enables strain-level resolution — distinguishing even the most closely related bacterial strains by their unique genetic fingerprints. The synergy of these technologies allows scientists to monitor individual donor bacteria from the instant of transplant and track their genetic adaptation for up to five years post-treatment.
Professor Gang Fang, the senior researcher and corresponding author of the study, emphasizes the transformative potential of this method. He explains, “Our ability to reliably follow donor bacterial strains over long durations was previously limited by the short-read sequencing technology. With LongTrack and long-read metagenomics, we achieve unprecedented scale and specificity, revealing the complex evolutionary pathways bacteria undertake to survive and thrive in diverse patients’ gastrointestinal environments.” This level of detail lays the foundation for designing microbiome therapies that are precise, reproducible, and personalized.
Collaborating closely with co-author Dr. Jeremiah Faith, specialists in immunology and immunotherapy at the Icahn School of Medicine, the research team applied this approach to analyze stool samples from both FMT donors and recipients. Their cohort included individuals treated for recurring C. difficile infections and those battling IBD. Samples were collected across multiple time points, with some extending up to five years after transplantation. The results were illuminating: numerous donor-derived bacterial strains successfully colonized the recipients’ guts, maintaining their presence long term. Intriguingly, genetic mutations observed in certain strains strongly suggested active adaptation to the recipient’s unique gut ecosystem, highlighting the dynamic interplay between host environment and microbial evolution.
This study delivers a blueprint for systematically identifying and selecting beneficial bacterial mixtures, streamlining the development of novel microbiome-based interventions that could serve as safer, more controllable alternatives compared to whole-stool FMT. By pinpointing which microbial strains persist and adapt effectively, therapeutic formulations can be tailored with greater predictability and safety, potentially minimizing risks associated with donor variability and pathogen transmission currently observed in conventional FMT.
In practical terms, the implications for precision medicine are profound. Dr. Fang states, “This technology does not merely enable us to track bacterial survival; it sheds light on the exact genetic shifts that facilitate their long-term adaptation. Such insights are critical for engineering microbial therapeutics that consistently deliver beneficial outcomes without unintended consequences.” This capability opens doors to next-generation, strain-specific treatments for microbiome-related diseases that transcend the one-size-fits-all model.
Looking ahead, the research team plans to harness this technology in larger clinical studies involving diverse patient populations and a broader array of diseases where the gut microbiome influences health outcomes. Their goal is to leverage LongTrack’s capacity to identify functionally advantageous bacterial strains that can be developed into bespoke microbial therapeutics, ushering in a new era of microbiome science where treatments are personalized at the genetic level.
Published in the October 22, 2025 issue of Nature Microbiology, this landmark study, titled “Long-read metagenomics for strain tracking after faecal microbiota transplant,” was authored by Yu Fan, Mi Ni, Varun Aggarwala, Edward A. Mead, Magdalena Ksiezarek, Lei Cao, Michael A. Kamm, Thomas J. Borody, Sudarshan Paramsothy, Nadeem O. Kaakoush, Ari Grinspan, Jeremiah J. Faith, and Gang Fang. Their work was funded by the National Institutes of Health under grant number R35 GM139655.
This development marks a significant stride toward unlocking the full therapeutic potential of the human microbiome. By enabling direct observation of beneficial microbes in action over extended periods, this research not only advances scientific understanding but also promises to accelerate the translation of microbiome science into precision interventions that could transform medicine for patients worldwide.
Subject of Research: People
Article Title: Long-read metagenomics for strain tracking after faecal microbiota transplant
News Publication Date: October 22, 2025
Web References:
https://doi.org/10.1038/s41564-025-02164-8
References:
Fan Y, Ni M, Aggarwala V, Mead EA, Ksiezarek M, Cao L, Kamm MA, Borody TJ, Paramsothy S, Kaakoush NO, Grinspan A, Faith JJ, Fang G. Long-read metagenomics for strain tracking after faecal microbiota transplant. Nature Microbiology. 2025 Oct 22. doi:10.1038/s41564-025-02164-8.
Keywords: Microbial infections, Fecal microbiota transplant, Long-read sequencing, Gut microbiome, Clostridioides difficile, Inflammatory bowel disease, Microbial therapeutics, Genetic adaptation, Precision medicine, Metagenomics, Microbiome therapy, Strain tracking
