GSE135428
Physiomimetic model of the human Gut-Liver axis for studies of inflammatory diseases
Association between the microbiome, IBD and liver diseases are known, yet cause and effect  remain elusive. By connecting human microphysiological systems of the gut, liver and circulating  Treg/Th17 cells, we modeled progression of ulcerative colitis (UC) ex vivo. We show that  microbiome-derived short-chain fatty acids (SCFA) may either improve or worsen disease  severity, depending on the activation state of CD4 T cells. Employing a multiomic approach, we  found SCFA reduced innate activation of the UC gut and increased hepatic metabolism. However,  during acute T cell-mediated inflammation, SCFA exacerbate CD4 T cell effector function leading  to gut barrier disruption and liver damage. These paradoxical findings underscore the emerging  utility of human physiomimetic technology in combination with systems immunology to study  causality and temporal facets of gut-liver axis related diseases where animal models might leave  ambiguity. Overall design: RNA-Seq analyses of tissues from a physiomimetic model of the human gut-liver axis; samples collected and analyzed in triplicates collected under different connectivity patterns.