Abstract
Over the past decades, hematopoietic stem cell transplantation (HSCT) has been evolving as specific treatment for patients with severe and refractory autoimmune diseases (ADs), where mechanistic studies have provided evidence for a profound immune renewal facilitating the observed beneficial responses. The intestinal microbiome plays an important role in host physiology including shaping the immune repertoire. The relationships between intestinal microbiota composition and outcomes after HSCT for hematologic diseases have been identified, particularly for predicting the mortality from infectious and non-infectious causes. Furthermore, therapeutic manipulations of the gut microbiota, such as fecal microbiota transplant (FMT), have emerged as promising therapeutic approaches for restoring the functional and anatomical integrity of the intestinal microbiota post-transplantation. Although changes in the intestinal microbiome have been linked to various ADs, studies investigating the effect of intestinal dysbiosis on HSCT outcomes for ADs are scarce and require further attention. Herein, we describe some of the landmark microbiome studies in HSCT recipients and patients with chronic ADs, and discuss the challenges and opportunities of microbiome research for diagnostic and therapeutic purposes in the context of HSCT for ADs.
Highlights
Intestinal microbiota may positively affect many aspects of the host physiology, including absorption of nutrients, prevention of overgrowth by potential pathogens, maintenance of epithelial barrier function, and shaping the immune system [1]
We have summarized the current evidence supporting the relationship between the microbiome, hematopoietic stem cell transplantation (HSCT) and autoimmune diseases (ADs), and speculated on the potential impact of the microbiome on clinical outcomes and immune reconstitution following HSCT for severe, resistant ADs
All co-authors were involved in drafting the paper, revising it critically, and approval of the submitted and final versions
Summary
Intestinal microbiota may positively affect many aspects of the host physiology, including absorption of nutrients, prevention of overgrowth by potential pathogens, maintenance of epithelial barrier function, and shaping the immune system [1]. Studies of the microbiome in the setting of hematopoietic stem cell transplantation (HSCT) demonstrated that intestinal flora are of particular importance in determining treatment outcomes, influencing immune reconstitution, and impacting complications such as infections or graft-versus-host disease (GvHD) [2, 3]. Increased abundance of a cluster of related bacteria including Eubacterium limosum was associated with decreased risk of relapse or disease-progression [67] These results indicate that the intestinal microbiota represent a potentially important factor in the success or failure of HSCT. A small cohort study recently reported a complete response in 10 out of 14 patients (71%) with steroidrefractory or steroid-dependent acute GvHD 28 days after FMT [101] This response was accompanied by an increase in microbial a-diversity, a partial engraftment of donor bacterial species, and increased abundance of butyrate-producing bacteria, including groups in the order Clostridiales, namely Blautia species. Additional studies are warranted to confirm that restoration of gut microbiota dysbiosis after FMT translates into clinical improvement after allogeneic HSCT, in particular a lower incidence of acute GvHD [96]
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