A new anchor point for gut microbiome to regulate complications of allogeneic hematopoietic stem cell transplantation: oxidative stress.

Abstract

Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is a cure for many malignant hematologic and metabolic diseases, whose complications are an unignorable cause of long-term prognosis. Pretreatment chemoradiotherapy administered before and after transplantation alters the state of the bone marrow hematopoietic microenvironment. Under the stress of hematopoietic injury, a large number of hematopoietic stem cells (HSCs) proliferate and differentiate, producing large amounts of reactive oxygen species (ROS). In addition, the chemotherapeutic pretreatment drugs also cause oxidative stress (OS) themselves, which can indirectly exacerbate OS of the bone marrow microenvironment. The bone marrow hematopoietic microenvironment and local OS affect the development of infections, relapse, graft-versus-host disease (GVHD), poor graft function (PGF), persistent thrombocytopenia (PT), chronic fatigue syndrome (CFS), bronchiolitis obliterans syndrome (BOS), and transplant-associated thrombotic microangiopathy (TA-TMA). Recent studies have demonstrated that the gut microbiome (GM) and its metabolites such as short-chain fatty acids (SCFAs), secondary bile acids, trimethylamine (TMA) and signaling molecules such as H₂S and NO can enter the bloodstream through the intestinal epithelium and reach all parts of the body. This review describes the impact of OS on the development of allo-HSCT complications. In this article, we will elucidate the mechanism of OS on allo-HSCT complications, summarize the interaction between GM and OS in the body, and highlight the role of GM regulation of OS in allo-HSCT complications to offer new strategies for the prevention and treatment of allo-HSCT complications.