Role of the intestinal mucosa in acute gastrointestinal GVHD

Abstract

Intestinal graft-versus-host disease remains a significant obstacle to the success of allogeneic hematopoietic cell transplantation. The intestinal mucosa comprises the inner lining of the intestinal tract and maintains close proximity with commensal microbes residing within the intestinal lumen. Recent advances have significantly improved our understanding of the interactions between the intestinal mucosa and the enteric microbiota. Changes in host mucosal tissue and commensals post-transplant have been actively investigated, and provocative insights into mucosal immunity and the enteric microbiota are now being translated into clinical trials of novel approaches for preventing and treating acute graft-versus-host disease. In this review, we summarize recent findings related to aspects of the intestinal mucosa during acute graft-versus-host disease.

Cannabidiol Enhances Intestinal Cannabinoid Receptor Type 2 Receptor Expression and Activation Increasing Regulatory T Cells and Reduces Murine Acute Graft-versus-Host Disease without Interfering with the Graft-versus-Leukemia Response

“…In this regard, we attested that CBD treatment does not reduce the migration of CD4 + or CD8 + cells to lymphoid and target organs. In our study, the main organ evaluated was the intestine, which is a major target organ of aGVHD and is regarded as one of the main environments for antigen presentation, acting as a barrier against commensal microbiota (Peled et al, 2016). CBD protected the intestinal barriers by preventing the migration of bacteria into the peritoneal cavity, while in the vehicle group, the intestinal barrier was inefficient in preventing this translocation; owing to intestinal damage, bacteria were found in the peritoneal cavity (Figure 3 E).…”

Fecal Microbiota Transplantation: Restoring the Injured Microbiome after Allogeneic Hematopoietic Cell Transplantation

“…Continuous signaling from native microbiota is required to maintain the optimal structure and function of the intestinal mucosal barrier, which serves to prevent autoimmunity and exclude pathogens [18]. Numerous important epithelial cell populations located in the intestinal mucosa (eg, enterocytes, goblet cells, Paneth cells, intestinal stem cells) can be adversely affected by the conditioning regimen and/or acute GVHD [3]. Furthermore, regulatory T cells and innate lymphoid cells (ILCs), which produce Th17 family cytokines, including IL-22, are abundant within the intestinal tract.…”

“…Decades after early studies identified a potential association between the microbiome and graft-versus-host disease (GVHD) [1,2], the composition of the recipient microbiome has reemerged as a possible contributor to allo-HCT outcomes. With significant advances in sequencing techniques, we are beginning to better understand the composition of the host intestinal microbiome and how it changes after receipt of allo-HCT [3].…”

Fecal microbiota diversity disruption and clinical outcomes after auto-HCT: a multicenter observational study

“…[17][18][19] We and others have described that patients undergoing allogeneic hematopoietic cell transplantation (allo-HCT) exhibit loss of fecal diversity and anaerobic commensal taxa, and domination by potentially pathogenic organisms. [20][21][22][23][24] Loss of fecal diversity, as well as increased abundance of members of genus Enterococcus have been associated with graft-vs-host disease (GVHD), [20][21][22][23] bloodstream infections, 25 and shorter OS after allo-HCT. 24,26 Increased abundance of a cluster of related bacteria including Eubacterium limosum was associated with decreased risk of relapse or POD.…”