The emerging roles of the gut microbiome in allogeneic hematopoietic stem cell transplantation

Abstract

Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is used for the treatment of hematologic cancers and disorders. However, graft-versus-host disease (GVHD) in which the donor immune cells attack the genetically-disparate recipient is a significant cause of morbidity. Acute GVHD is an inflammatory condition and the gastrointestinal system is a major organ affected but is also tied to beneficial graft-versus-tumor (GVT) effects. There is increasing interest on the role of the microbiome on immune function as well as on cancer progression and immunotherapy outcomes. However, there are still significant unanswered questions on the role the microbiome plays in GVHD progression or how to exploit the microbiome in GVHD prevention or treatment. In this review, concepts of HSCT with the focus on GVHD pathogenesis as well as issues in preclinical models used to study GVHD will be discussed with an emphasis on the impact of the microbiome. Factors affecting the microbiome and GVHD outcome such as obesity are also examined. The bridging of preclinical models and clinical outcomes in relation to the role of the microbiome will also be discussed along with possibilities for therapeutic exploitation.

Mucositis and Infection in Hematology Patients

“…The microbiome mainly dictates the amplitude of the inflammatory response and its outputs [14]. Intensive chemotherapy [37][38][39] and HCT [40,41] in general, are associated with oral and gut microbial dysbiosis (lower microbial diversity and outgrowth of opportunistic pathogens). Microbial dysbiosis is considered to play a role in severe (post-transplant) complications such as bloodstream infections or bacteremia [37,42] and pulmonary infections [43], graftversus-host disease [44,45], perturbed immune reconstitution [46], even relapse (higher abundance of mostly Eubacterium limosum) [47] and non-relapse mortality [40].…”

Neutropenia and antibiotics: when, what, how and why?

“…Fluoroquinolone prophylaxis has been associated with decreased rates of infection in patients with neutropenia, though most studies do not show an overall survival benefit [2]. However, fluoroquinolone prophylaxis has been associated with the development of drug resistant infections, drug toxicities, adverse changes in the gut microbiome and increased Clostridioides difficile colitis rates, and adverse impacts on graft-versus-host disease (GVHD) and transplant outcomes [3–5]. Balancing infection prevention strategies with benefits and risks of antimicrobial prophylaxis is challenging.…”

Longitudinal dynamics of gut microbiota in the pathogenesis of acute graft‐versus‐host disease

“…Allogeneic hematopoietic stem cell transplantation (allo‐HSCT) remains a curative strategy for a variety of hematologic diseases. During the process, recipients are usually exposed to chemotherapy, broad‐spectrum antibiotics, and immunosuppressive agents, which are all known to affect the dynamic changes in the gut microbiota 1–3 . There is growing evidence that the gut microbiota is linked to the prognosis of patients undergoing allo‐HSCT 4 .…”

“…During the process, recipients are usually exposed to chemotherapy, broad‐spectrum antibiotics, and immunosuppressive agents, which are all known to affect the dynamic changes in the gut microbiota. 1 , 2 , 3 There is growing evidence that the gut microbiota is linked to the prognosis of patients undergoing allo‐HSCT. 4 Published studies on the gut microbiota in allo‐HSCT have indicated that the diversity of the gut microbiota is associated with the incidences of mortality and complications as well as the speed of immune reconstitution.…”