Fecal microbiota transplantation for patients with steroid-resistant acute graft-versus-host disease of the gut.

Increasing evidence indicates that the gut microbiota is closely associated with acute graft-versus-host disease (aGVHD) in stem cell transplantation (SCT). Fecal microbiota transplantation (FMT) could represent an alternative treatment option for aGVHD. However, FMT for SCT patients carries a potential risk of infection by infused microbiota because of the severely immunosuppressed status. We therefore conducted a pilot study to evaluate the safety of FMT in SCT. A total of 4 patients with steroid-resistant (n = 3) or steroid-dependent gut aGVHD (n = 1) received FMT. No severe adverse events attributed to FMT were observed. All patients responded to FMT, with 3 complete responses and 1 partial response. Temporal dynamics of microbiota seemed to be linked to the gut condition of patients and peripheral effector regulatory T cells also increased during response to FMT. FMT was safely performed in our patients and might offer a novel therapeutic option for aGVHD. This trial was registered at the University Hospital Medical Information Network (https://upload.umin.ac.jp/cgi-open-bin/icdr_e/ctr_view.cgi?recptno=R000017575) as #UMIN000015115.

[1]  Daniel Wolff,et al.  Low urinary indoxyl sulfate levels early after transplantation reflect a disrupted microbiome and are associated with poor outcome. , 2015, Blood.

[2]  Y. Taur,et al.  Intestinal Blautia Is Associated with Reduced Death from Graft-versus-Host Disease. , 2015, Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation.

[3]  S. Rampelli,et al.  Gut microbiota trajectory in pediatric patients undergoing hematopoietic SCT , 2015, Bone Marrow Transplantation.

[4]  T. Gouliouris,et al.  Fecal microbiota transplantation (FMT) for Clostridium difficile infection: focus on immunocompromised patients. , 2015, Journal of infection and chemotherapy : official journal of the Japan Society of Chemotherapy.

[5]  R. Ganc,et al.  Fecal microbiota transplant after hematopoietic SCT: report of a successful case , 2015, Bone Marrow Transplantation.

[6]  K. Honda,et al.  Treatment with Antibiotics Containing Activity Against Obligate Anaerobes Worsens GVHD Survival in Mice and Humans after Allogeneic BMT , 2014 .

[7]  A. Viale,et al.  The effects of intestinal tract bacterial diversity on mortality following allogeneic hematopoietic stem cell transplantation. , 2014, Blood.

[8]  Daniel Wolff,et al.  Metagenomic analysis of the stool microbiome in patients receiving allogeneic stem cell transplantation: loss of diversity is associated with use of systemic antibiotics and more pronounced in gastrointestinal graft-versus-host disease. , 2014, Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation.

[9]  A. Rudensky,et al.  Metabolites produced by commensal bacteria promote peripheral regulatory T cell generation , 2013, Nature.

[10]  J. Karbach,et al.  Anti-CCR4 mAb selectively depletes effector-type FoxP3+CD4+ regulatory T cells, evoking antitumor immune responses in humans , 2013, Proceedings of the National Academy of Sciences.

[11]  M. Hattori,et al.  Treg induction by a rationally selected mixture of Clostridia strains from the human microbiota , 2013, Nature.

[12]  Emma Allen-Vercoe,et al.  Toward an Understanding of Changes in Diversity Associated with Fecal Microbiome Transplantation Based on 16S rRNA Gene Deep Sequencing , 2012, mBio.

[13]  K. Akashi,et al.  Graft-versus-host disease disrupts intestinal microbial ecology by inhibiting Paneth cell production of α-defensins. , 2012, Blood.

[14]  R. Khanin,et al.  Regulation of intestinal inflammation by microbiota following allogeneic bone marrow transplantation , 2012, The Journal of experimental medicine.

[15]  T. Braun,et al.  Frequency of CD4(+)CD25(hi)FOXP3(+) regulatory T cells has diagnostic and prognostic value as a biomarker for acute graft-versus-host-disease. , 2010, Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation.

[16]  T. Nomura,et al.  Functional delineation and differentiation dynamics of human CD4+ T cells expressing the FoxP3 transcription factor. , 2009, Immunity.

[17]  J. Doré,et al.  Faecalibacterium prausnitzii is an anti-inflammatory commensal bacterium identified by gut microbiota analysis of Crohn disease patients , 2008, Proceedings of the National Academy of Sciences.

[18]  H. Deeg,et al.  How I treat refractory acute GVHD. , 2007, Blood.

[19]  R. Soiffer,et al.  Blood and marrow transplant clinical trials network toxicity committee consensus summary: thrombotic microangiopathy after hematopoietic stem cell transplantation. , 2005, Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation.

[20]  C. Thoburn,et al.  Association of Foxp3 regulatory gene expression with graft-versus-host disease. , 2004, Blood.