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.

Fecal microbiota transplantation in cancer management: Current status and perspectives

“…In allogeneic HSCT, donor T cells attack host healthy tissues, resulting in graft‐ vs .‐host disease (GVHD), which is the main cause of mortality associated with HSCT . A clinical study identified intestinal bacterial diversity as a new independent prognostic factor in allogeneic HSCT .…”

Gut dysbiosis during antileukemia chemotherapy versus allogeneic hematopoietic cell transplantation

“…These include colonization resistance against potential pathogens and tonic stimulation to the intestinal epithelium, which facilitates recovery after gut injury . Suppression of the intestinal microbiota and disruptions in its microbial community structure have been associated with complications of intensive antileukemia chemotherapy and allogeneic hematopoietic cell transplantation (allo‐HCT), including infections, mortality, and graft‐versus‐host disease (GVHD) . Because microbiome‐directed interventions are beginning to emerge with the intent of improving the outcomes of curative‐intent therapy, it is important to systematically characterize dysbiosis with respect to the nature of the insults altering the microbiome.…”

Hospital-Level Variability in Broad-Spectrum Antibiotic Use for Children With Acute Leukemia Undergoing Hematopoietic Cell Transplantation

“…This finding is particularly relevant because recent data from adult transplant cohorts have suggested that the risk of noninfectious outcomes, such as mortality, 12,32 GVHD, 12,33 and relapse, 34,35 may be mediated by antibiotic class via the gut microbiota. 36 In addition, specific classes of antibiotics have been associated with an increased risk of C. difficile infection 13 and acute kidney injury 14 in children. If additional research confirms a differential impact of antipseudomonal antibiotics on these secondary outcomes, it will also be important to incorporate this evidence into guidelines for appropriate antibiotic choice.…”