Impact of Alcohol on Intestinal Homeostasis

Chronic heavy alcohol consumption results in intestinal injury characterized by increased permeability, dysbiosis, nutrient malabsorption, increased risk of colorectal cancer, and functional alterations in mucosal immune cells. Studies have implicated dysregulation of tight junction proteins as well as quantitative and qualitative changes in gut microbiota as key contributors to gut injury. Recently, we showed using a macaque model of voluntary ethanol self-administration that moderate consumption resulted in a more robust T-cell and antibody vaccine response to Modified Vaccinia Ankara (MVA), while heavy drinkers generated blunted T-cell and antibody response compared to controls. First, we show that chronic alcohol consumption modulates host defense and response to booster vaccination by altering gene expression in circulating leukocytes. Using this model, we previously examined the effect of chronic ethanol consumption on cytokine production using intracellular cytokine staining, and found that colonic T cells exhibited a disruption of inflammatory cytokine production. Next, we show the modulation of transcriptome and microbiota profiles by chronic alcohol consumption within the different segments of the gastrointestinal tract. Lastly, we report alterations in the transcriptional profiles of intestinal lamina propria lymphocytes following chronic alcohol consumption. Since our animals lack overt organ damage, the alterations in gene expression and microbial composition precede clinical disease and could potentially serve as early biomarkers before detrimental effects occur. These findings provide novel insight into the mechanisms of ethanol-induced mucosal damage and lay the foundation for follow up studies to develop new interventions to reverse mucosal damage and improve immunity in heavy alcohol abusers