A statistical model named ‘Strain Finder’ was developed by a research team led by the Broad Institute of Massachusetts Institute of Technology (MIT) and Harvard.
The model predicts bacterial genotypes and tracks them over time, enabling researchers to identify the likelihood of whether particular bacterial strains would attach or engraft to a recipient’s gut following FMT.
In the study, scientists also discovered the presence of bacteria in the patient after FMT that had been previously undetected in either donor or recipient. The finding suggests that environment may help determine the post-FMT microbiome composition as well as the strains originally present in donor and recipient, explained the researchers.
Engraftment of the donor bacteria into the recipient’s gut is critical to the success of the FMT, emphasised the scientists. The strongest determinants of engraftment were found to be bacterial abundance of species and their phylogeny (the historical pattern of relationships among bacterial strains) in the donor and the recipient prior to the transfer.
“We find that engraftment can be predicted largely from the abundance and phylogeny of bacteria in the donor and the pre-FMT patient,” commented co-senior author Eric J .Alm, co-director of the Centre for Microbiome Informatics and Therapeutics (CMIT) at MIT.
All or nothing
Interestungly, at the strain level, bacteria engrafted in an ‘all- or-nothing’ manner. In other words, if a donor had multiple strains of a given species, either all or none of them transplanted successfully. The likelihood of success also increased if the patient already possessed some of these strains.
“Donor strains within a species engraft in an all-or-nothing manner and previously undetected strains frequently colonise patients receiving FMT,” said Alm.
This finding adds to an increasing body of research suggesting that bacteria may not act singly, but may co-operate.
This finding adds to an increasing body of research suggesting that bacteria may not act singly, but may co-operate. This type of interaction has been previously identified in species of ‘superbugs’, which may form antibiotic-resistant ecosystems.
Initial research was carried out in 20 patients who received FMT for resistant Clostridium difficile infections. The scientists used high-resolution metagenomic sequencing to analyse the microbiome composition of donors and patients before and after FMT.
They monitored the abundance of each strain for 4 months after the transfer and used this data to build the predictive Strain Finder model.
The researchers also applied the model to metabolic syndrome, and proposed that it may have applications for numerous other diseases.
“We validated these findings for metabolic syndrome, suggesting that the same principles of engraftment extend to other indications,” commented Alm.
"This paper provides a context for understanding how to make these live biological therapeutics as an alternative to transferring raw faecal matter," he added.
"We are in the midst of one of the largest disease therapeutics that are being developed based on a human source--bugs within us," added second co-senior author Ramnik J. Xavier, Chief of the Division of Gastroenterology at Massachusetts General Hospital and CMIT co-director. "These bugs within us, or the microbiome, are going to have a potential impact for many diseases."
Source: Cell Host and Microbe
Volume 23, pp 1-12, doi: 10.1016/j.chom.2018.01.003
“Strain Tracking Reveals the Determinants of Bacterial Engraftment in the Human Gut Following Fecal Microbiota Transplantation”
Authors: Christopher S. Smillie, Ramnik J. Xavier, Eric J. Alm et al