2 December 2020
Researchers in the Netherlands have found a potential treatment for graft rejection in an unlikely place, the gut bacteria found in faeces.
Patients with blood diseases such as leukaemia are often treated with transplants of blood stem cells from donors, which sometimes stimulate devastating graft versus host disease (GvHD) — an immune attack initiated by donor cells against those of the patient. Now, research shows that transplanting faecal matter from healthy donors directly into a patient’s gut can lead to a successful transplant. “We were able to cure some patients who had a really grim outlook,” says Mette Hazenberg of the Amsterdam University Medical Centre, who led the research team.
Using stem cells to treat blood diseases such as leukaemia relies on balancing the benefits and risks of the donor cells. The diseased stem cells in the patient are mostly destroyed by drug treatment prior to the transplant, but some can remain. The donor cells can help eradicate any residual malignant host cells. However, the benefit of this attack on diseased cells can be negated if the donated cells also stimulate an immune attack against the patient’s healthy cells. Resistance to drug therapies used to treat GvHD can leave some patients with no treatment options.
The researchers turned to the microbes in the gut because research is steadily revealing that these microbes play a significant role in mediating our immune system. Recipients of blood stem cell transplants are known to have disrupted populations of gut bacteria, which seem to predispose them to GvHD.
“To give these patients trillions of bacteria from an unrelated person was quite nerve-wracking, as they already had suppressed immune systems” says Hazenberg. But the patients’ desperate situation made it worthwhile to try, and they readily agreed.
In patients who responded well, a single transplant of donor faecal matter was sufficient to cure the GvHD. Ten of the 15 patients exhibited a good initial response, and six of them were apparently cured long-term.
All of the patients who did not respond died from GvHD within six months of the trial.
These initial results suggest the treatment could offer a dramatic benefit to a significant proportion of patients, but Hazenberg cautions that the team have only completed a single, small-scale pilot study. This will need to be followed up with larger randomized and controlled clinical trials to see if the initial promise is borne out sufficiently to establish this as a new routine treatment.
- van Lier, Y. F., Davids, M., Haverkate, N. J. E., de Groot, P. F., Donker, M. L., et al. Donor fecal microbiota transplantation ameliorates intestinal graft-versus-host disease in allogeneic hematopoietic cell transplant recipients. Science Translational Medicine12, eaaz8926 (2020). | article