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

Walter Spindelboeck; Bettina Halwachs; Nadine Bayer; Bianca Huber-Krassnitzer; Eduard Schulz; Barbara Uhl; Lukas Gaksch; Stefan Hatzl; Victoria Bachmayr; Lisa Kleissl; Patrizia Kump; Alexander Deutsch; Georg Stary; Hildegard Greinix; Gregor Gorkiewicz; Christoph Högenauer; Peter Neumeister

doi:10.1177/20406207211058333

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

Ther Adv Hematol. 2021 Dec 21:12:20406207211058333. doi: 10.1177/20406207211058333. eCollection 2021.

Authors

Walter Spindelboeck¹, Bettina Halwachs¹, Nadine Bayer², Bianca Huber-Krassnitzer³, Eduard Schulz³, Barbara Uhl³, Lukas Gaksch³, Stefan Hatzl³, Victoria Bachmayr², Lisa Kleissl², Patrizia Kump¹, Alexander Deutsch³, Georg Stary², Hildegard Greinix³, Gregor Gorkiewicz⁴, Christoph Högenauer⁵, Peter Neumeister³

Affiliations

¹ Division of Gastroenterology and Hepatology, Department of Internal Medicine, Medical University of Graz, Graz, Austria.
² Department of Dermatology, Medical University of Vienna, Vienna, Austria.
³ Division of Hematology, Department of Internal Medicine, Medical University of Graz, Graz, Austria.
⁴ Institute of Pathology, Medical University of Graz, Graz, Austria.
⁵ Division of Gastroenterology and Hepatology, Department of Internal Medicine, Medical University of Graz, Auenbruggerplatz 15, 8036 Graz, Austria.

Abstract

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.

Keywords: T cells; antibiotics; fecal microbiota transplantation; gastrointestinal graft-versus-host disease; regulatory T cells; type 3 innate lymphoid cells.