A closer look at donor-recipient pairings
Clinicians usually enlist healthy, carefully screened individuals as FMT donors.
However, both research groups conclude that fine-scale taxonomic and metabolic analyses of donor and recipient microbiomes would better inform clinical decisions, especially when treating diseases other than C. difficile.
This may call for a more personalized approach to choosing donor-recipient pairings. Investigators should assess the patient’s diet and genetic background and how closely the donor’s microbiome matches that of the patient.
“Most studies focused on profiling stool samples before and after FMT without also including functional analyses; therefore, there are still a lot of aspects of host microbial interactions that remain unknown,” write Dr. Yadegar and colleagues in their statement.
Ecologic factors, including diet and host genetics, are often not included in clinical studies of C. difficile, but they “may potentially be the missing links” to treatment failure in the small portion of patients whose condition doesn’t respond to FMT, they write.
Pairing donor-recipient combinations on the basis of dietary patterns and preferences could improve FMT efficacy because the donor microbiota would be preadapted to the recipient’s diet, Dr. Yadegar and colleagues write. The team is examining how donor and recipient diet may affect outcomes.
Dr. Porcari and colleagues add that while some studies support the existence of shared characteristics that make up super-donors, others found that the optimal donor is more patient specific. They call for personalized selection strategies that employ microbiome sequencing tools rather than a “one stool fits all” approach.
Currently, many clinicians aren’t familiar with microbiome sequencing and analysis, but they’ll need to be in the near future, note Dr. Porcari and colleagues.
“Identifying microbiome characteristics that maximize strain engraftment in the FMT will allow clinicians to select the best donor for each single patient,” they write.
The possible role of viruses and fungi
In FMT research, investigators tend to focus on the bacteria in the human microbiome. However, viruses and fungi also appear to play a role, both articles note.
“Other microbial kingdoms that inhabit the intestine should be taken into account when considering predictors of post-FMT microbial transfer,” write Dr. Porcari and colleagues.
Although few studies have examined the gut virome’s impact on FMT effectiveness against C. difficile, the existing research, although limited, indicates that bacteriophage viruses could play a role, Dr. Yadegar and colleagues note. For example, high levels of donor-derived Caudoviralesbacteriophages in recipients were associated with FMT efficacy in one preliminary study, they write.
In a small human study, fecal filtrate from healthy donors who had bacteriophages but no live bacteria successfully treated five patients with recurrent C. difficile infection, Dr. Yadegar and colleagues write.
“Therefore, the idea that viruses may play a role is very provocative,” write Dr. Yadegar’s team in their statement.
It’s important to note that these studies are associative, which means they can’t definitively answer the question of how or whether viruses play a role, Dr. Yadegar’s team added.
Researchers “know even less about how fungi may or may not play a role,” write Dr. Yadegar and colleagues. However, in early research that involved patients who had successfully undergone FMT for C. difficile, there was higher relative abundance of Saccharomyces and Aspergillus, whereas Candida, if prominent, may impede response, they write in their article.
Additionally, to explore whether live bacteria are necessary for FMT to work, Dr. Yadegar and colleagues informed this news organization that they are conducting a study “comparing traditional FMT to a fecal filtrate that contains no live bacteria, but has all other components, to see if we can achieve similar success rates in recurrent C. difficile infection.”