Abstract # 1850 Early life stress predisposes to increased sensitivity to inflammatory stimuli through intestinal dysbiosis

Stress, anxiety and depression are considered risk factors for Inflammatory Bowel Disease. We have previously shown in mice that early life stress induced by maternal separation (MS) changes host physiology leading to intestinal dysbiosis, which in turns causes anxiety and depression-like behavior. Using this murine model, we investigated the role of stress and microbiota in susceptibility to intestinal inflammation. Adult MS and control C57Bl/6 mice were used. Experimental colitis was induced by 1.5% or 3.5% dextran sulfate sodium (DSS) in drinking water in germ-free or colonized (ex-germ-free) mice, respectively. After their behavior and clinical scores were assessed, mice were sacrificed and samples collected. Colonized but not germ-free MS mice displayed anxiety and depression-like behavior, higher secretory IgA levels, decreased Paneth cell counts and dysbiosis compared to controls. In colonized mice, DSS colitis clinical scores were higher in MS mice accompanied by marked dysbiosis, lower secretory IgA and increased serum MCP-1 levels compared to controls, although the colonic microscopic scores and inflammatory cytokine levels were similar. In germ-free conditions, no difference in clinical colitis scores, histology or cytokine levels were found. In summary, MS leads to intestinal dysbiosis that sustains and exacerbates an impaired cellular and humoral immunity, leading to increased sensitivity to intestinal injury. Our results further support the role of gut-microbiota-brain axis in the genesis of chronic gastrointestinal inflammatory disorders.