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Prevension of Acute Graft-Versus-Host Disease and Restoration of Gut Microbiome Diversity Via Butyrate Administration in Allogeneic Hematopoietic Stem Cell Transplantation

Year: 2025

Type: article

Abstract: Acute graft-versus-host disease (aGVHD) is a significant cause of morbidity and mortality in patients undergoing allogeneic hematopoietic stem cell transplantation (allo-HSCT). The diversity of the gut microbiota declines during allo-HSCT due to conditioning chemotherapy, prophylactic or therapeutic antibiotics, and dietary alterations. According to numerous reports, as the diversity of the microbiome decreases further during the engraftment period in the transplantation process, the incidence of GVHD and the mortality rate increase. Emerging evidence suggests that interventions aimed at restoring gut microbiota diversity may significantly mitigate the risk of aGVHD. Postbiotics—bioactive metabolites produced by probiotic bacteria—have garnered considerable interest as potential therapeutic agents. Among these, butyrate , a short-chain fatty acid, has shown profound immunomodulatory properties, making it a promising candidate for promoting intestinal epithelial health and modulating systemic immune responses. The study aims to evaluate the clinical efficacy of butyrate administration in allo-HSCT recipients, focusing on its potential to support microbiota diversity and reduce the incidence of aGVHD. A prospective study was conducted to evaluate the clinical effects and microbial changes in postbiotics intake in allo-HSCT recipients. Twenty individuals who underwent allo-HSCT at Soonchunhyang University Seoul Hospital from September 2022 through December 2023 were enrolled in the study (the postbiotics group). The patients ingested sodium butyrate (600 mg × 2 capsules per day) from engraftment (day +14 to +21) until days +90 to +100. The historical control group consisting of eighteen patients who received allo-HSCT between March 2021 and June 2022 was also included. Stool samples were collected at three key points: start of allo-HSCT, during the engraftment period, and 100 days post-transplant. Clinical data of the historical control group were collected from the medical records . Metagemoic analysis was performed on collected stool samples. By day 180, the cumulative incidence of aGVHD of all grades showed lower tendency in the postbiotics group than in the historical control group. The incidence of grade 3 to 4 aGVHD was significantly lower in the postbiotics group. Notably, the cumulative incidence of lower gastrointestinal aGVHD was very significantly lower in the postbiotics group (40.42% vs 5%, P = 0.008) (Figure). The diversity of the microbiome decreased throughout the transplantation process, and a more rapid recovery of microbiome diversity was seen with the administration of butyrate. In conclusion, the administration of butyrate is anticipated to prevent aGVHD. However, more larger cohort of patients is needed to define the role of butyrate in allo-HSCT. ClinicalTrials.gov as #NCT05808985.

Source: Transplantation and Cellular Therapy

DOI: 10.1016/j.jtct.2025.01.430

Authors: Kyoung Ha Kim, Seug Yun Yoon, Jong-Ho Won

Institutions: Soonchunhyang University, Soonchunhyang University Hospital Seoul

Language: English

Topic: Hematopoietic Stem Cell Transplantation

Subfield: Hematology

Field: Medicine

Domain: Health Sciences

SDG: Good health and well-being

Open Access status: hybrid

Estimated APC paid: $3,650