Fecal Microbiota Transplantation Can Cure Steroid-Refractory Intestinal Graft-Versus-Host Disease

Abstract

Introduction Enteric dysbiosis has a negative influence on the outcome of allogeneic hematopoietic stem cell transplantation (HSCT) recipients. The presence of an imbalanced microbiome, marked by decreased gut flora diversity and intestinal pathobiont domination, is associated with an increased risk to develop graft-versus-host disease (GvHD). Objectives This prospective, single-arm pilot study tested if donor fecal microbiota transplantation (FMT) is safe and effective to treat intestinal GvHD. Methods Fifteen patients with steroid-refractory or steroid-dependent GvHD received a single FMT via nasoduodenal infusion from an unrelated, healthy donor. Results FMT was well tolerated and there were no serious adverse events observed that could be attributed to FMT. With 6-month follow-up nearly completed for all patients, 11 participants showed a complete response (CR), defined as resolution of all GvHD symptoms four weeks after FMT, without other interventions to alleviate symptoms. In six patients, the normalization of stool frequency and consistency was sustained throughout follow-up and immunosuppressants were tapered successfully. Five other responders initially showed improvement of GvHD after FMT but relapsed upon prednisolone taper (CR/sf; complete responders with secondary failure). A durable response to FMT was associated with a better prognosis (Figure 1). 16S ribosomal RNA sequencing of fecal samples from the first 13 patients revealed overall low alpha diversity in patients pre-FMT (Figure 2). One week after FMT, the fecal microbial composition of CR patients resembled that of the donor the most (Figure 3). Analysis of fecal samples from the other patients will be completed in the near future and will give more insights into the effects on microbial diversity and composition that are introduced by donor FMT. Conclusion The encouraging data from this pilot study show the potential of donor FMT as a safe therapy for steroid-refractory or steroid-dependent GvHD and promote further investigation in larger cohorts.