The role of microbiota in allogeneic hematopoietic stem cell transplantation

ABSTRACT

Introduction

Allogeneic hematopoietic stem cell transplantation (Allo-HSCT) is commonly performed to treat a variety of benign and malignant hematological diseases. Acute graft-versus-host disease (GVHD) is a major life-threatening complication that often occurs following allo-HSCT. Recently, improvements in methods to characterize the microbiota have led to a greater appreciation for how frequently and profoundly an alteration in microbial composition, or dysbiosis, can occur in allo-HSCT recipients to better decipher the complex interplay between microbiota and allo-HSCT outcomes.

Areas covered

This article reviews the current knowledge of the microbiota’s impact on allo-HSCT outcomes, including effects of microbiota-derived metabolites, and crosstalk between commensals and the allogeneic immune response. This article also summarizes the effects of HSCT and transplant-related procedures on microbiota, and recent developments in interventional strategies.

Expert opinion

A growing body of literature indicates that the composition of the intestinal microbiota can function as a predictive biomarker for the risk and severity of acute GVHD, as well as overall survival, in patients undergoing allo-HSCT. Mechanisms underpinning these associations, however, are not well understood, and clinical strategies that modulate the microbiome to improve outcomes have yet to be fully developed. There is an unmet need to determine mechanisms to improve the efficacy of allo-HSCT.

KEYWORDS:

• Microbiota
• dysbiosis
• metabolites
• allogeneic hematopoietic stem cell transplantation
• graft-versus-host disease

Article highlights

• Intestinal microbiota has emerged as a novel therapeutic target to potentially improve clinical outcomes of allo-HSCT recipients.

• Changes in metabolomic profiles have been associated with development of acute GVHD in recipients of allo-HSCT.

• Many studies have identified associations between high diversity of the intestinal microbiota and a lower risk of transplant-related mortality.

• Commensal bacteria can modulate immune responses and promote effector T cell responses.

• Strategies to manipulation the microbiome such as FMT have been shown to directly change the recipient’s gut microbiota composition and may mediate clinical benefits.

This box summarizes key points contained in the article.

Declaration of interest

Robert R. Jenq has consulted for Karius, Merck, Microbiome DX, and Prolacta, and is on the scientific advisory boards of Kaleido, Maat Pharma, LISCure Biosciences, and Prolacta Bioscience s, and has received patent royalties licensed to Seres Biosciences. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial relationships or otherwise to disclose.

Additional information

Funding

This work was partially supported by NIH R01 2R01HL124112 and CPRIT Scholar in Cancer Research RR160089 grants.