What is a Poo Transplant?
“This paper provides a context for understanding how to make these live biological therapeutics as an alternative to transferring raw fecal matter,” says co-senior author Eric J. Alm, co-director of the Center for Microbiome Informatics and Therapeutics (CMIT) at MIT. “We describe a model focused on three elements, including bacterial engraftment, growth, and mechanism of action, that need to be considered when developing these live therapies targeting the gut microorganisms, or microbiome,” he says.
20 patients with C. diff infection who received therapeutic FMT were examined using high-resolution deep metagenomics genetic sequencing. The scientists thus studied the gut-level microbiota of donors and recipients before and after FMT up to 4 months. Both the strain type and abundance of each strain in donors and recipients was measured, in order to build a predictive model of the presence and the abundance bacterial strains in the recipient after FMT.
It was found that after the FMT process, about 30% of the donor bacteria engrafted in the recipient, and the most abundant strains were more likely to engraft.
“That’s important to know when designing a microbiome-based therapeutic like this,” says the second co-senior author Ramnik J. Xavier, Chief of the Division of Gastroenterology at Massachusetts General Hospital and CMIT co-director. “If a drug only colonises 30 percent of the patients you put it in, then the maximum efficacy of your drug is 30 percent.”
It was also found that 30 percent of the engrafted strains exhibited an unusual “all of nothing” pattern of behaviour. For instance, if the donor had five different strains of a bacterial species, all five strains transferred into the patient. Moreover, if the recipient already had some of the strains found in the donor, the probability of those strains engrafting was higher.
This model has enabled the prediction of the amount of each engrafted strain grown in a recipient.
“Again, that is an essential piece of information because you want to know whether a bacterial strain will be found in trace levels or at high levels so that it can actually produce the metabolite that you want,” adds Xavier.
The team developed and applied this model not only to C. diff patients but in other studies with other diseases, including metabolic syndrome.
“We are in the midst of one of the largest disease therapeutics that are being developed based on a human source—bugs within us,” says Xavier. “These bugs within us, or the microbiome, are going to have a potential impact for many diseases.”