The Impact of the Microbiome on the Hematologic System: Thrombosis and Graft-Versus-Host Disease

Humans co-exist with trillions of microorganisms, or microbiome. Alterations in the microbiome are associated with several diseases of the hematopoietic system and thrombosis. This session will focus on two recent and compelling mechanistic translational studies that investigate the role of microbial metabolites in health.

Dr. Stanley Hazen will discuss new evidence linking gut microbiota and the trimethylamine N-oxide (TMAO) pathway to platelet hyper-responsiveness and thrombosis potential in vivo. Data shown will span from human clinical association studies to mechanistic studies employing microbial transplantation in germ free mice, demonstrating transmission of diet-dependent platelet hyper-responsiveness and in vivo thrombosis potential. In addition, studies showing use of small molecule non-lethal microbial enzyme inhibitors will be discussed as a new therapeutic approach for the treatment of atherothrombotic heart disease and reduced thrombosis potential without increased bleeding, a limitation of existing anti-platelet therapeutics.

Dr. Pavan Reddy will discuss the role of changes in the gastrointestinal tract microbiome and the related changes in their metabolites in experimental graft-versus-host disease (GVHD). He will discuss the role of microbiome-derived short-chain fatty acids and their effect on GVHD. The mechanisms that are used by the short-chain fatty acids in mitigating GVHD will be presented. In this context, the concept of target tissue tolerance to alloreactive T cell-mediated damage will be discussed. Strategies that can be potentially used for clinical translation of these experimental data will also be discussed.