Changes in the microbiota following allogeneic hematopoietic stem cell transplantation: A potential bioguide for clinical outcome?

Abstract

Introduction: This study aims to support our hypothesis regarding compositional changes in the intestinal microbiota by characterizing these changes through pre- and post-transplantation analyses. Additionally, it seeks to determine whether monitoring the intestinal flora could provide predictive or therapeutic insights into graft versus host disease. Methods: This study included adult patients who underwent allogeneic hematopoietic stem cell transplantation. Microbiota assessments were performed through stool analyses. Stool samples were collected twice: once before transplantation and once after engraftment. Following nucleic acid isolation, the samples were processed using New Generation Sequencing. Microbiota-associated pathways were examined using the Kyoto Encyclopedia of Genes and Genomes (KEGG) database. Statistical analyses were performed using R statistical software. In addition to microbiota analysis, resistance genes common in Gram-negative bacteria in the region (such as OXA-48-like, KPC-like, NDM-like, and CTX-M-like) were identified via classical polymerase chain reaction in stool samples collected after transplantation. The pathways were analyzed using the KEGG database. Results: Fifteen transplant recipients participated in the study. The Proteobacteria phylum increased in patients who tested positive for the CTXM-1 group and OXA-48-like resistance genes. Blautia caecimuris and Enterococcus exhibited significant changes following transplantation, while Tyzzerella spp. and Dialister spp. showed significant alterations after the onset of graft-versus-host disease. A marked change in Eubacterium spp. was also noted in patients with disease relapse. Two key metabolic pathways-acridone alkaloid biosynthesis and the D-arginine and D-ornithine metabolism-were associated with clini-cal outcomes. Conclusions: This study demonstrates that allogeneic hematopoietic stem cell transplants lead to significant alterations in intestinal microbiota composition, including increased pathogenic bacteria associated with graft-versus-host disease exacerbation. These findings suggest that microbiota monitoring may be a promising strategy for the prevention and treatment of graft-versus-host disease. Moreover, modulation of specific microbial meta-bolic pathways may influence disease clinical outcomes. As the first study of its kind con-ducted within the Turkish population, this research contributes novel insights to the existing literature and highlights the potential of microbiota-based approaches in post-transplant patient management. (c) 2025 Associa & ccedil;& atilde;o Brasileira de Hematologia, Hemoterapia e Terapia Celular. Published by Elsevier Espa & ntilde;a, S.L.U. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).