Abstract
There is mounting evidence for the emerging role of gut microbiota (GM) and its metabolites in profoundly impacting allogenic hematopoietic stem cell transplantation (allo-HSCT) and its subsequent complications, mainly infections and graft versus host-disease (GvHD). The present study was performed in order to investigate changes in GM composition and fecal metabolic signature between transplant patients (n = 15) and healthy controls (n = 18). The intestinal microbiota was characterized by NGS and gas chromatography–mass spectrometry was employed to perform untargeted analysis of fecal metabolites. We found lower relative abundances of Actinobacteria, Firmicutes, and Bacteroidetes and a higher abundance of Proteobacteria phylum after allo-HSCT. Particularly, the GvHD microbiota was characterized by a lower relative abundance of the short-chain fatty acid-producing bacteria, namely, the Feacalibacterium, Akkermansia, and Veillonella genera and the Lachnospiraceae family, and an enrichment in multidrug-resistant bacteria belonging to Escherichia, Shigella, and Bacteroides. Moreover, network analysis showed that GvHD was linked to a higher number of positive interactions of Blautia and a significant mutual-exclusion rate of Citrobacter. The fecal metabolome was dominated by lipids in the transplant group when compared with the healthy individuals (p < 0.05). Overall, 76 metabolites were significantly altered within transplant recipients, of which 24 were selected as potential biomarkers. Furthermore, the most notable altered metabolic pathways included the TCA cycle; butanoate, propanoate, and pyruvate metabolisms; steroid biosynthesis; and glycolysis/gluconeogenesis. Specific biomarkers and altered metabolic pathways were correlated to GvHD onset. Our results showed significant shifts in gut microbiota structure and fecal metabolites characterizing allo-HSCT.
Highlights
IntroductionHematopoietic stem cell transplantation (HSCT) is considered to be the most effective form of tumor immunotherapy for many hematologic malignancies and disorders
We subdivided our patient cohort into subgroups according to the presence or absence of graft-versus-host disease (GvHD and no-GvHD groups, respectively)
We found five main phyla that were abundant in the study groups, namely, Bacteroidetes, Firmicutes, Proteobacteria, Verrucomicrobia, and Actinobacteria
Summary
Hematopoietic stem cell transplantation (HSCT) is considered to be the most effective form of tumor immunotherapy for many hematologic malignancies and disorders. Microorganisms 2021, 9, 1845 available to date [1]. Advances in transplant management have greatly improved outcomes, patients, especially those receiving allogeneic hematopoietic stem cell transplantation (allo-HSCT), are at high risk for several complications, such as intestinal inflammation, bloodstream infections (BSI), sepsis, and graft-versus-host disease (GvHD) [2]. Early diagnostic tests and biomarkers for prediction remain limited. GvHD, which is a multisystem disorder, remains the major source of morbidity and non-relapse mortality occurring in patients undergoing allo-HSCT [3,4]. Several studies highlighted the mechanisms of GvHD development, including alloreactive immune cells and pronounced gut microbiota perturbations [5]
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