Fecal microbiota transplantation as safe and successful therapy for intestinal graft-versus-host disease. Fecal microbiota transplantation as safe and successful therapy for intestinal graft-versus-host disease

Gut microbiota can have a major influence on the health of allogeneic hematopoietic stem cell transplantation (HSCT) patients. Damage to the intestinal microbiome occurs in a significant number of allogeneic HSCT recipients and is a risk factor to develop graft-versus-host disease (GvHD) and opportunistic infections. Here, we tested if microbial diversity of intestinal GvHD patients could be restored by fecal microbiota transplantation (FMT) and thereby would alleviate GvHD symptoms. Seven allogeneic HSCT recipients with biopsy-proven, steroid-dependent or steroid-refractory intestinal GvHD received a single FMT via nasoduodenal infusion from an unrelated, healthy donor. The procedure was well tolerated by all patients and no serious adverse events were observed that could be attributed to FMT. Six-months follow-up identified five complete responders (CR), with normalization of defecation frequency and consistency. In three of these patients immunosuppressants were tapered successfully, without relapse of diarrhea. Two other complete responders relapsed upon prednisone taper. Analysis of fecal microbiota composition by 16S ribosomal RNA (rRNA) sequencing revealed overall low alpha diversity in patients pre-FMT, with the lowest diversity observed in non-responding and relapsing patients. This study demonstrates that a single FMT is safe and can be effective in allogeneic HSCT recipients with steroid-refractory or steroid-dependent GvHD.