Crosstalk Between Intestinal Microbiota Derived Metabolites and Tissues in Allogeneic Hematopoietic Cell Transplantation

Abstract

Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is an evidence based- cellular immunotherapy for hematological malignancies. Immune reactions not only promote graft-versus-tumor effects that kill hematological malignant cells but also graft-versus-host disease (GVHD) that is the primary complication characterized by systemic organ damages consisting of T-cells and antigen presenting cells (APCs) activation. GVHD has long been recognized as an immunological reaction that requires an immunosuppressive treatment targeting immune cells. However immune suppression cannot always prevent GVHD or effectively treat it once it has developed. Recent studies using high-throughput sequencing technology investigated the impact of microbial flora on GVHD and provided profound insights of the mechanism of GVHD other than immune cells. Allo-HSCT affects the intestinal microbiota and microbiome-metabolome axis that can alter intestinal homeostasis and the severity of experimental GVHD. This axis can potentially be manipulated via dietary intervention or metabolites produced by intestinal bacteria affected post-allo-HSCT. In this review, we discuss the mechanism of experimental GVHD regulation by the complex microbial community-metabolites-host tissue axis. Furthermore, we summarize the major findings of microbiome-based immunotherapeutic approaches that protect tissues from experimental GVHD. Understanding the complex relationships between gut microbiota-metabolites-host tissues axis provides crucial insight into the pathogenesis of GVHD and advances the development of new therapeutic approaches.

Klebsiella quasipneumoniae in intestine damages bile acid metabolism in hematopoietic stem cell transplantation patients with bloodstream infection

“…In previous studies, Enterococcus, Streptococcus, and various Proteobacteria were dominant during HSCT. Among them, enterococcal dominance increased vancomycin-resistant Enterococcus bacteremia risk by nine folds, whereas proteobacterial domination increased Gram-negative rod bacteremia risk by five folds [ 13 , 39 ]. Although Enterococcus was not significantly different between the BSI and non-BSI groups in our study, the increased potentially harmful bacteria (especially Enterobacteriaceae reported) and decreased beneficial bacteria under serious disease conditions were proven, and its predictability for BSI was confirmed.…”

“…These findings suggested that HSCT patients with elevated bile acid levels may be related to subsequent BSI onset. Bile acid metabolites could modulate immune cells to regulate host immunity [ 39 , 41 ]. Altered host immunity caused by bile acids might be a possible reason for BSI occurrence in HSCT patients.…”

Analysis of factors associated with hematopoietic stem-cell retransplantation: a case-control study

“…HSCT affects the intestinal microbiota, microbiomemetabolome and liver axis which can alter intestinal homeostasis and the severity of GVHD (20) . The use of ursodeoxycholic acid is considered useful in the prophylaxis and treatment of some liver conditions, especially from DECH for being one of the reasons that Rev.…”

Análise dos fatores associados ao retransplante de células-tronco hematopoiéticas: estudo caso-controle

“…HSCT affects the intestinal microbiota, microbiome-metabolome and liver axis which can alter intestinal homeostasis and the severity of GVHD 20 . The use of ursodeoxycholic acid is considered useful in the prophylaxis and treatment of some liver conditions, especially from DECH for being one of the reasons that may lead to the need for HSCR according to the results presented by this study.…”