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Improving microbe-based therapy for C. diff infections

New research has uncovered details of what happens during fecal microbiota transplantation (FMT) when it is used as a treatment for Clostridium difficile (C. diff) infections, offering insight into potentially safer and improved microbe-based therapies. Changes or disruptions in the gut’s microbiome—the diverse community of bacteria, viruses, and fungi that naturally inhabit the intestines—are associated with C. diff bacterial infections, a disease that causes severe diarrhea and colitis. One treatment proven to be successful is FMT, whereby gut microbes from a healthy donor’s stool sample are introduced into the recipient’s large intestine to help reestablish a more functional gut microbiome. Despite a success rate of over 90 percent of people cured after a single treatment, many questions remain about how FMT works. For example, it is unclear how long the donor bacterial strains remain in the recipient following transplantation. Knowing whether the donated microbiota persist could help predict whether the C. diff infection is likely to return. It would also be important to know which donated strains are necessary for clearing the infection so a more defined therapeutic cocktail can be designed that avoids the transfer of unnecessary strains or disease-causing bacteria.

To address these questions, researchers supported by NIDDK and the Crohn’s and Colitis Foundation analyzed gut microbiomes and identified bacterial strains from 13 people before and after undergoing FMT as a treatment for recurrent C. diff infections. They also analyzed the microbiomes from the seven healthy donors who provided the FMT samples and developed a new statistical method to track the transfer of strains from donors to recipients during the study period of up to 5 years after FMT. This enabled the researchers to determine which strains successfully colonized and persisted in the recipients following transplantation, and which strains correlated with successful outcomes (i.e., no relapses of C. diff infections). They found that, in people who experienced no relapses, over two-thirds of donor strains were retained for at least 5 years following FMT, while less than one-quarter of the recipient strains were retained (some additional strains were derived from food or the environment). The researchers also identified the bacterial strains that appear to be necessary for such a long-term engraftment. This suggests that a stable, near-permanent colonization of donor microbiota from FMT, driven by certain bacterial strains, is a reliable predictor for a successful outcome.

This research underscores the value of microbe-based therapy as an effective and potentially long-term treatment for C. diff infections. It also paves the way for the design of streamlined, synthetic therapies that consist only of certain bacterial strains and avoid the transfer of unnecessary microbes, thereby providing an attractive and safer alternative to FMT.

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