Human Intestinal Organoid as model for Alcohol Use Disorder (AUD)

More than 3 million deaths worldwide are linked to excessive alcohol consumption. Alcohol abuse associated gut barrier dysfunction is thought to play an important role in the development of alcohol-associated liver disease. Although some aspects that contribute to this process have been elucidated, the role of intestinal epithelium, a major component of the gut barrier, and its alterations in gut barrier failure in Alcohol Use Disorder (AUD) remain poorly understood. Our preliminary data on duodenal epithelium in humans showed a disturbed proliferation-differentiation process in AUD patients. In this project, Intestinal Organoids (Enteroids) are used to model this disease. The Enteroids are generated from crypts originating from control and patient’s duodenum biopsies. Interestingly, they are able to growth, differentiate and later display crypt and villi architecture mimicking in vivo condition. In addition, they keep their host phenotype in culture during first passages allowing us to study the different alterations occurring in the host epithelium. Moreover, we could determine the gene expression of differentiated epithelial cells represented in the model.