The intestinal microbiota in allogeneic hematopoietic cell transplant and graft-versus-host disease

Abstract

Hematopoietic cell transplantation (HCT) is a critical treatment of patients with high-risk hematopoietic malignancies, hematological deficiencies, and other immune diseases. In allogeneic HCT (allo-HCT), donor-derived T cells recognize host tissues as foreign, causing graft-versus-host disease (GVHD) which is a main contributor to morbidity and mortality. The intestine is one of the organs most severely affected by GVHD and research has recently highlighted the importance of bacteria, particularly the gut microbiota, in HCT outcome and in GVHD development. Loss of intestinal bacterial diversity is common during the course of HCT and is associated with GVHD development and treatment with broad-spectrum antibiotics. Loss of intestinal diversity and outgrowth of opportunistic pathogens belonging to the phylum Proteobacteria and Enterococcus genus have also been linked to increased treatment-related mortality including GVHD, infections, and organ failure after allo-HCT. Experimental studies in allo-HCT animal models have shown some promising results for prebiotic and probiotic strategies as prophylaxis or treatment of GVHD. Continuous research will be important to define the relation of cause and effect for these associations between microbiota features and HCT outcomes. Importantly, studies focused on geographic and cultural differences in intestinal microbiota are necessary to define applicability of new strategies targeting the intestinal microbiota.

Figure 1.

Intestinal damage and dysbiosis linked to GVHD. Upon HCT, multiple factors such as conditioning toxicity, antibiotic treatment, and immune activation mediate GVHD. GVHD progression associates with injury to stem cell compartments along with Paneth cells (small intestine) and goblet cells. This leads to increased intestinal permeability, inflammation, and reduction of the mucus layer and antimicrobial products (eg, defensins). Antibiotic treatment and a limited amount of nutrients in the gut also promote gut dysbiosis, furthering gastrointestinal damage and disease. DC, dendritic cell; IgA, immunoglobulin A.