A deeper understanding of the mechanisms underlying the success of fecal microbiota transplantation (FMT) is needed to further improve its effectiveness, according to two recent reviews published in Cell Host and Microbe.
how closely the donor’s microbial composition matches the patient’s existing microbiome, and the presence of nonbacterial gut inhabitants like viruses and fungi – affect FMT success, according to a press release.
FMT is most often used to treat recurrent Clostridioides difficile infections, which don’t always respond to antibiotics. Success rates range from 60% to 90%, depending on the administration route and study design, notes an international research team led by Abbas Yadegar, PhD, a medical bacteriologist at the Shahid Beheshti University of Medical Sciences in Tehran, Iran.
The understanding of how FMT works is incomplete, however, and the reasons some patients fail to benefit is unclear, note Dr. Yadegar and colleagues. Little attention has been paid to the role that other components of the patient’s microbiome, along with outside factors, play in the treatment’s success, they add.
“We wanted other researchers to look beyond changes in stool microbial composition and function, which have been the focus of research in the past few years,” Dr. Yadegar’s team said in a statement provided to this news organization.
Dr. Yadegar and colleagues’ review of more than 130 studies summarizes recent evidence on the mechanisms contributing to FMT success against recurrent C. difficile infection, highlights knowledge gaps, and proposes future research directions in the field.
Factors that influence FMT’s effectiveness and the potential the procedure holds for treatment of other diseases associated with gut dysbiosis are the subject of a review of 149 studies by a team of researchers led by Serena Porcari, MD, a gastroenterologist at the Fondazione Policlinico Universitario Gemelli and Università Cattolica del Sacro Cuore, in Rome.
“Our main goal was not only to unravel the different mechanisms of FMT efficacy but also to introduce some mindset shifts that are needed to bring FMT forward, mainly covering the gap that exists between basic scientists and clinicians,” Gianluca Ianiro, MD, PhD, a senior researcher in digestive diseases who works with Dr. Porcari and is the review’s lead author, told this news organization.
Engraftment may influence success
Engraftment of donor microbial strains in recipients appears to be key to the therapeutic success of FMT, both reviews note.
Three factors influence engraftment: the donor’s bacteria fitness relative to the recipient, the bacteria already present in the recipient, and whether antibiotics are used prior to FMT to open a niche for the incoming donor microbes, according to Dr. Yadegar and colleagues.
How to calculate strain engraftment has not yet been standardized in the field, and the number of strains detected in the recipient’s fecal sample is dependent on the depth of sequencing techniques, Dr. Porcari and colleagues note.
The use of whole-genome sequencing has enabled more precise evaluation of engraftment, they add.
“With this approach, microbial engraftment has been associated with clinical success, regardless of the disease, in a large metagenomic metanalysis of 24 FMT trials and almost 1,400 fecal samples,” Dr. Porcari and colleagues write. However, these results have not been replicated, likely because of differences between the studies.
More study on the topic is needed, both articles note.
“Because the recent metagenomics studies compared pre- and post-FMT only in cases with successful treatment outcomes, it is not possible to link engraftment to clinical outcomes,” Dr. Yadegar and colleagues write in their statement to this news organization.