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Complete FMT engraftment may be unnecessary for treating C. diff
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Complete transfer of donor microbiota is not necessary for fecal microbiota transplantation to effectively treat recurrent Clostridium difficile infection, according to the results of a randomized controlled trial.
Further, these results suggest that certain bacteria — specifically, those associated with secondary bile acid metabolism — could be most effective for achieving CDI cure, which could help clinicians improve FMT in the future, Michael J. Sadowsky, PhD, director of the BioTechnology Institute at the University of Minnesota in St. Paul, and colleagues wrote.
Colleen R. Kelly
“As opposed to what we thought, complete engraftment of microbiota is not required to cure a patient,” Sadowsky said in a press release. “The study provides insight into which microorganisms are the most important for curing C. difficile and may allow clinicians to better tailor therapy, by improving the donor material to facilitate a more rapid, effective, and lasting cure.”
Sadowsky and colleagues, including Colleen R. Kelly, MD, a gastroenterologist at the Women’s Medicine Collaborative and assistant professor of medicine at the Warren Alpert Medical School of Brown University, randomly assigned 27 patients with recurrent CDI to receive heterologous FMT from healthy donors or autologous FMT using their own stool microbiota as placebo. The researchers previously reported the expected superiority of the heterologous FMT (90% vs. 43%; P = .019) and significant differences in microbial composition between groups after FMT (P < .001).
However, several patients who received autologous FMT also achieved CDI cure.
They therefore characterized patients’ intestinal bacterial communities using Illumina next-generation sequencing, which showed the patients who achieved CDI cure after autologous FMT tended to have an increased abundance of Clostridium XIVa clade and Holdemania bacteria before treatment, as well as an increased relative abundance of these bacterial communities after FMT compared with the heterologous group and specimens collected before FMT.
Moreover, the autologous group did not show high relative abundances of genera within the Bacteroidetes and Firmicutes phyla, as is typical of patients who receive donor FMT, the researchers wrote. The autologous patients had significantly different bacterial composition compared with the heterologous group and donors (P < .001).
Finally, the heterologous group showed significantly greater microbiota engraftment after FMT, with a mean of 74% similarity to donor microbial communities, vs. 1% among autologous FMT patients who experienced CDI recurrence (P .013).
“The findings of this study suggest that complete donor engraftment may not be necessary if functionally critical taxa are present in subjects following antibiotic therapy,” and also suggest “that bacteria associated with secondary bile acid metabolism could potentially provide resistance to infection,” the researchers concluded. – by Adam Leitenberger
Disclosures: Sadowsky reports he has received research funding and has served as a consultant for CIPAC (now Crestovo). Kelly reports she has served as a consultant for Summit Therapeutics, served as a site investigator for Seres Health, and has received research support from Assembly Biosciences. Please see the study for a full list of all other researchers’ relevant financial disclosures.
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