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The clinical role of the gut microbiome and fecal microbiota transplantation in allogeneic stem cell transplantation
Ferrata Storti Foundation
Haematologica 2021 Volume 106(4):933-946
Israel Henig,1 Dana Yehudai-Ofir1,2 and Tsila Zuckerman1,2
1Department of Hematology and Bone Marrow Transplantation, Rambam Health Care Campus and 2The Ruth and Bruce Rappaport Faculty of Medicine, Technion - Israel Institute of Technology, Haifa, Israel
ABSTRACT
Outcomes of allogeneic hematopoietic stem cell transplantation (allo- HSCT) have improved in the recent decade; however, infections and graft-versus-host disease remain two leading complications signifi- cantly contributing to early transplant-related mortality. In past years, the human intestinal microbial composition (microbiota) has been found to be associated with various disease states, including cancer, response to cancer immunotherapy and to modulate the gut innate and adaptive immune response. In the setting of allo-HSCT, the intestinal microbiota diversity and composition appear to have an impact on infection risk, mortality and over- all survival. Microbial metabolites have been shown to contribute to the health and integrity of intestinal epithelial cells during inflammation, thus mitigating graft-versus-host disease in animal models. While the cause-and- effect relationship between the intestinal microbiota and transplant-associ- ated complications has not yet been fully elucidated, the above findings have already resulted in the implementation of various interventions aiming to restore the intestinal microbiota diversity and composition. Among others, these interventions include the administration of fecal microbiota transplan- tation. The present review, based on published data, is intended to define the role of the latter approach in the setting of allo-HSCT.
Introduction
The past decades have witnessed important advances in the outcome of allogene- ic hematopoietic stem cell transplantation (allo-HSCT),1 mainly attributed to the reduction in non-relapse mortality.2 Yet, the need for further improvement is com- pelling. Acute graft-versus-host disease (aGvHD) and infections are two of the main causes of early transplant-related mortality (TRM), jointly accounting for 36% and 43% of deaths by day 100 in matched related and matched unrelated transplants, respectively.1
One of the emerging and extensively explored allo-HSCT-associated issues is the change in the gut microbial flora, as well as its effect on the pathogenesis of trans- plant-related complications and association with transplant outcomes.
The human body hosts a hundred trillion microbial organisms; the majority of them are bacteria, predominantly colonizing the gut, with the lower intestine being most densely colonized (1011-1012 organisms/g of intestinal content).3 The composi- tion of bacteria in the gut is referred to as the intestinal microbiota and their collec- tive genome is termed the “intestinal microbiome”.3 The two main phyla constitut- ing more than 90% of the gut microbiota are the Firmicutes and Bacteroidetes and among less dominant phyla are Proteobacteria, Actinobacteria, and Verrucomicrobia.4 This composition is relatively flexible and can rapidly change in response to differ- ent environmental factors, adjusting the metabolic and immunologic performance accordingly.5 Intestinal microbiota has been recently found to have a significant impact on both health and disease states. It appears to be crucial for the maturation and education of the immune system and has a role in intestinal cell proliferation, intestine vascularization and endocrine functions. Moreover, it produces energy, synthesizes vitamins, metabolizes bile acids and even inactivates drugs.6-13 The microbiome has been reported to be associated with a variety of disorders such as
Correspondence:
TSILA ZUCKERMAN
t_zuckerman@rambam.health.gov.il
Received: May 23, 2020.
Accepted: August 28, 2020. Pre-published: November 26, 2020.
https://doi.org/10.3324/haematol.2020.247395
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