A Promising Insight: The Potential Influence and Therapeutic Value of the Gut Microbiota in GI GVHD

Abstract

Allogeneic hematopoietic cell transplantation (allo-HSCT) is a reconstruction process of hematopoietic and immune functions that can be curative in patients with hematologic malignancies, but it carries risks of graft-versus-host disease (GVHD), thrombotic microangiopathy (TMA), Epstein–Barr virus (EBV) infection, cytomegalovirus infection, secondary hemophagocytic lymphohistiocytosis (sHLH), macrophage activation syndrome (MAS), bronchiolitis obliterans, and posterior reversible encephalopathy syndrome (PRES). Gastrointestinal graft-versus-host disease (GI GVHD), a common complication of allo-HSCT, is one of the leading causes of transplant-related death because of its high treatment difficulty, which is affected by preimplantation, antibiotic use, dietary changes, and intestinal inflammation. At present, human trials and animal studies have proven that a decrease in intestinal bacterial diversity is associated with the occurrence of GI GVHD. Metabolites produced by intestinal bacteria, such as lipopolysaccharides, short-chain fatty acids, and secondary bile acids, can affect the development of GVHD through direct or indirect interactions with immune cells. The targeted damage of GVHD on intestinal stem cells (ISCs) and Paneth cells results in intestinal dysbiosis or dysbacteriosis. Based on the effect of microbiota metabolites on the gastrointestinal tract, the clinical treatment of GI GVHD can be further optimized. In this review, we describe the mechanisms of GI GVHD and the damage it causes to intestinal cells and we summarize recent studies on the relationship between intestinal microbiota and GVHD in the gastrointestinal tract, highlighting the role of intestinal microbiota metabolites in GI GVHD. We hope to elucidate strategies for immunomodulatory combined microbiota targeting in the clinical treatment of GI GVHD.

Can Cytokine Detection Predict the Occurrence and Outcome of aGVHD after Allo-HCT? A Retrospective Study

“…Diarrhea within 15 days post-transplant is the only independent risk factor for the occurrence of aGVHD and the risk factor for death. Clinical studies supported the association of alterations in the gut microbiome diversity and composition during allo-HSCT, with aGVHD and OS [43,44]. Homeostasis of the immune response in the gut mucosa is maintained by the balance between proinflammatory cells and intestinal microbiota, which also regulate the expression of proinflammatory cytokines and increase T cell proliferation.…”

Multifaceted involvements of Paneth cells in various diseases within intestine and systemically

“…After allogeneic hematopoietic stem cell transplantation, GVHD is a frequent complication due to the immune reaction of allogeneic T cells in transplant against host antigens ( 115 ). The allogeneic T cells instinctively attack host intestinal cells, mainly including ISC, goblet cells and PCs ( 115 ). The reduced PC number in GVHD patients is correlated with clinical severity and nonrelapse mortality ( 21 ).…”

Molecular regulation after mucosal injury and regeneration in ulcerative colitis

“…After ISCs are damaged, Paneth cells replenish ISCs by providing Wnt ligand and Notch stimulation. Thus, Paneth cells are helper cells that maintain the stem cell microenvironment or niche ( Li et al, 2022a ; Mead et al, 2022 ; Ostadmohammadi et al, 2022 ).…”