Antibiotic use and ileocolonic immune cells in patients receiving fecal microbiota transplantation for refractory intestinal GvHD: a prospective cohort study.

Introduction: Treatment-refractory, acute graft- versus -host disease (GvHD) of the lower gastrointestinal tract (GI) after allogeneic hematopoietic stem cell transplantation is life threatening and lacks effective treatment options. While fecal microbiota transplantation (FMT) was shown to ameliorate GI-GvHD, its mechanisms of action and the factors influencing the treatment response in humans remain unclear.The objective of this study is to assess response to FMT treatment, factors influencing response, and to study the mucosal immune cell composition in treatment-refractory GI-GvHD.
Methods: Consecutive patients with treatment-refractory GI-GvHD were treated with up to six endoscopically applied FMTs.
Results: We observed the response to FMT in four out of nine patients with severe, treatment refractory GI-GvHD, associated with a significant survival benefit ( p  = 0.017). The concomitant use of broad-spectrum antibiotics was the main factor associated with FMT failure ( p  = 0.048). In addition, antibiotic administration hindered the establishment of donor microbiota after FMT. Unlike in non-responders, the microbiota characteristics (e.g. α- and β-diversity, abundance of anaerobe butyrate-producers) in responders were more significantly similar to those of FMT donors. During active refractory GI-GvHD, an increased infiltrate of T cells, mainly Th17 and CD8 ⁺ T cells, was observed in the ileocolonic mucosa of patients, while the number of immunomodulatory cells such as regulatory T-cells and type 3 innate lymphoid cells decreased. After FMT, a change in immune cell patterns was induced, depending on the clinical response.
Conclusion: This study increases the knowledge about the crucial effects of antibiotics in patients given FMT for treatment refractory GI-GvHD and defines the characteristic alterations of ileocolonic mucosal immune cells in this setting.
Competing Interests: Conflict of interest statement: The authors declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: W.S. received speakers’ fees from Oesterreichische Gesellschaft fuer Gastroenterologie und Hepatologie, Aerztekammer fuer Steiermark, and AbbVie and received travel support from Boston Scientific. B.H.-K. received support for participation in meetings from Teva Ratiopharm, Novartis, Neovii, Celgene, Takeda, and Gilead. E.S. received Congress support from Amgen, Incyte, Jazz, Janssen, Novartis, Roche, and Takeda; participated in advisory boards of Amgen and Celgene; and received honoraria from Amgen and Novartis. B.U. was supported by a Research Grant of the Austrian Society of Hematology & Medical Oncology and received support for participation in conferences from Neovii, Novartis, Sanofi, Sobi, and Takeda. P.N. participated in advisory boards or had consultancy with and received honoraria from AbbVie, Takeda, BMS/Celgene, and Janssen. P.K. received research funding from Bristol Meyer Squibb and Ipsen and participated in advisory boards and received honoraria from Janssen, Ipsen, Novartis, AbbVie, Takeda, Gebro, Merck Sharp & Dohme (MSD), and Pfizer. H.G. received honoraria for presentations in scientific meetings and consultations from Novartis, Celgene/ Bristol-Myers Squibb (BMS), Janssen, Sanofi, and Therakos. CH received a research grant from Seres Therapeutics. B.H., N.B., V.B., L.K., A.D., L.G., S.H., G.G., and G.S. declare that they have no conflict of interest. The authors declare that none of the mentioned relationships were related to the development and the content of this article.
(© The Author(s), 2021.)