Interplay Between the Intestinal Microbiota and Acute Graft-Versus-Host Disease: Experimental Evidence and Clinical Significance

Abstract

Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is a potentially curative therapy for many hematological disorders and autoimmune diseases, but acute graft-versus-host disease (aGVHD) has remained a major obstacle that limits allo-HSCT and exhibits a daunting mortality rate. The gastrointestinal system is among the most common sites affected by aGVHD. Experimental advances in the field of intestinal microbiota research enhanced our understanding - not only of the quantity and diversity of intestinal microbiota - but also their association with homeostasis of the immune system and disease pathogenesis, including that of aGVHD. Meanwhile, ever-growing clinical evidence suggest that the intestinal microbiota is dysregulated in patients who develop aGVHD and that the imbalance may affect clinical outcomes, indicating a potential predictive role for microbiota dysregulation in aGVHD severity and prognosis. The current animal and human studies investigating the intestinal microbiota in aGVHD and the understanding of the influence and management of the microbiota in the clinic are reviewed herein. Taken together, monitoring and remodeling the intestinal microecology following allo-HSCT may provide us with promising avenues for diagnosing, preventing or treating aGVHD in the clinic.

Gut diversity and the resistome as biomarkers of febrile neutropenia outcome in paediatric oncology patients undergoing hematopoietic stem cell transplantation

“…Moreover, these bacterial families have been identified as reservoirs of antibiotic resistance genes, further complicating their clinical outcome. The members of these bacterial families were often associated with higher mortality after HSCT and FN as well as GvHD development 51 – 53 .…”

Recent advances in ocular graft-versus-host disease

“…However, A prospective study reported a different result in which the microbiome on the ocular surface was characterized by a loss of diversity in ocular GVHD patients ( 79 ). Both investigations indicated that the ocular surface microbial dysbiosis is involved in the underlying microbial mechanism of ocular GVHD, but further investigations are warranted to explore the concrete mechanisms and therapeutic targets ( 80 ). Other less prevalent characteristics include cicatricial conjunctivitis (a kind of chronic conjunctivitis with conjunctival fibrosis and scarring formation), cicatricial entropion(inversion of the eyelids caused by fibrosis and scarring of the eyelid), symblepharon(any adhesion between the palpebral and bulbar conjunctiva), ankyloblepharon (partial or complete adhesion of upper and lower eyelids), and lagophthalmos(an inability to close the eyelids), which could progress to conjunctival keratinization and punctual occlusion ( 26 ).…”

Modulating microbiome-immune axis in the deployment-related chronic diseases of Veterans: report of an expert meeting

“…The outcome of transplantation is adversely affected by graft-versus-host disease (GVHD) after HCT, and organ rejection after SOT. In this context, studies suggest that intestinal microbiota is dysregulated after HCT and in patients who develop GVHD, 1 and monitoring and remodeling of microbiota after HCT can lead to the development of novel diagnostic tools, such as new disease markers or novel therapeutics in the form of elements of gut microbiota. 2 Similarly, dysbiosis occurs after SOT 3 , and it is believed to be caused by immunosuppressive therapy, which while preventing rejection, predisposes the host to various complications, such as life-threatening infections, cancer, or metabolic syndrome.…”