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Lactose drives Enterococcus expansion to promote graft-versus-host disease.

ABSTRACT: Disruption of intestinal microbial communities appears to underlie many human illnesses, but the mechanisms that promote this dysbiosis and its adverse consequences are poorly understood. In patients who received allogeneic hematopoietic cell transplantation (allo-HCT), we describe a high incidence of enterococcal expansion, which was associated with graft-versus-host disease (GVHD) and mortality. We found that Enterococcus also expands in the mouse gastrointestinal tract after allo-HCT and exacerbates disease severity in gnotobiotic models. Enterococcus growth is dependent on the disaccharide lactose, and dietary lactose depletion attenuates Enterococcus outgrowth and reduces the severity of GVHD in mice. Allo-HCT patients carrying lactose-nonabsorber genotypes showed compromised clearance of postantibiotic Enterococcus domination. We report lactose as a common nutrient that drives expansion of a commensal bacterium that exacerbates an intestinal and systemic inflammatory disease.

SUBMITTER: Stein-Thoeringer CK

PROVIDER: S-EPMC7003985 | biostudies-literature | 2019 Nov

REPOSITORIES: biostudies-literature

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Lactose drives <i>Enterococcus</i> expansion to promote graft-versus-host disease.

Stein-Thoeringer C K CK Nichols K B KB Lazrak A A Docampo M D MD Slingerland A E AE Slingerland J B JB Clurman A G AG Armijo G G Gomes A L C ALC Shono Y Y Staffas A A Burgos da Silva M M Devlin S M SM Markey K A KA Bajic D D Pinedo R R Tsakmaklis A A Littmann E R ER Pastore A A Taur Y Y Monette S S Arcila M E ME Pickard A J AJ Maloy M M Wright R J RJ Amoretti L A LA Fontana E E Pham D D Jamal M A MA Weber D D Sung A D AD Hashimoto D D Scheid C C Xavier J B JB Messina J A JA Romero K K Lew M M Bush A A Bohannon L L Hayasaka K K Hasegawa Y Y Vehreschild M J G T MJGT Cross J R JR Ponce D M DM Perales M A MA Giralt S A SA Jenq R R RR Teshima T T Holler E E Chao N J NJ Pamer E G EG Peled J U JU van den Brink M R M MRM

Science (New York, N.Y.) 20191101 6469

Disruption of intestinal microbial communities appears to underlie many human illnesses, but the mechanisms that promote this dysbiosis and its adverse consequences are poorly understood. In patients who received allogeneic hematopoietic cell transplantation (allo-HCT), we describe a high incidence of enterococcal expansion, which was associated with graft-versus-host disease (GVHD) and mortality. We found that <i>Enterococcus</i> also expands in the mouse gastrointestinal tract after allo-HCT a ...[more]

PMID: 31780560

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Project description:Allogeneic hematopoietic cell transplantation (allo-HCT) is an essential therapeutic modality for patients with hematological malignancies and other blood disorders. Unfortunately, acute graft-versus-host disease (aGVHD) remains a major source of morbidity and mortality following allo-HCT, which limits its use in a broader spectrum of patients. Chronic graft-versus-host disease (cGVHD) also remains the most common long-term complication of allo-HCT, occurring in reportedly 30-70% of patients surviving more than 100 days. Chronic GVHD is also the leading cause of non-relapse mortality (NRM) occurring more than 2 years after HCT for malignant disease. Graft versus tumor (GVT) is a major component of the overall beneficial effects of allogeneic HCT in the treatment of hematological malignancies. Better understanding of GVHD pathogenesis is important to identify new therapeutic targets for GVHD prevention and therapy. Emerging data suggest opposing roles for different T cell subsets, e.g., IFN-γ producing CD4+ and CD8+ T cells (Th1 and Tc1), IL-4 producing T cells (Th2 and Tc2), IL-17 producing T cells (Th17 and Tc17), IL-9 producing T cells (Th9 and Tc9), IL-22 producing T cells (Th22), T follicular helper cells (Tfh), regulatory T-cells (Treg) and tissue resident memory T cells (Trm) in GVHD and GVT etiology. In this review, we first summarize the general description of the cytokine signals that promote the differentiation of T cell subsets and the roles of these T cell subsets in the pathogenesis of GVHD. Next, we extensively explore preclinical findings of T cell subsets in both GVHD/GVT animal models and humans. Finally, we address recent findings about the roles of T-cell subsets in clinical GVHD and current strategies to modulate T-cell differentiation for treating and preventing GVHD in patients. Further exploring and outlining the immune biology of T-cell differentiation in GVHD that will provide more therapeutic options for maintaining success of allo-HCT.

Dataset Information

Lactose drives Enterococcus expansion to promote graft-versus-host disease.

Publications

Lactose drives <i>Enterococcus</i> expansion to promote graft-versus-host disease.

Similar Datasets

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