Increased Intestinal Permeability and Decreased Resiliency of the Intestinal Barrier in Alcoholic Liver Disease

Objectives: Only 20- 30% of individuals with Alcohol Use Disorder (AUD) develop Alcoholic Liver Disease (ALD). While the development of gut-derived endotoxemia is understood to be a required co-factor, increased intestinal permeability in ALD is not completely understood. Methods: We recruited 178 subjects – 58 healthy controls (HC), 32 with ALD, 53 with AUD but no liver disease (ALC), and 35 with nonalcoholic fatty liver disease (NAFLD). Intestinal permeability was assessed by a sugar cocktail as a percentage of oral dose. The permeability test was repeated after an aspirin challenge in a subset. Results: 5 hour urinary Lactulose/Mannitol (L/M) Ratio (primarily representing small intestinal permeability) was not statistically different in HC, ALC, ALD, and NAFLD (p=0.40). 24 hour urinary Sucralose (representing whole gut permeability) was increased in ALD (F= 5.3, p < 0.01) and distinguished ALD from ALC; 24 hour sucralose/lactulose (S/L) ratio (primarily representing colon permeability) separated the ALD group (F= 10.2, p<0.01) from NAFLD. After aspirin challenge, intestinal permeability increased in all groups and ALD had the largest increase. Conclusions: In a cohort of patients, we confirmed that (1) ALD has increased intestinal permeability compared to HC, ALC, or NAFLD. In addition, since small bowel permeability (L/M ratio) is normal, the disruption of intestinal barrier appears to be primarily in the large intestine.; (2) Decreased resiliency of intestinal barrier to injurious agents (like NSAID) might be the mechanism for gut leak in subset of AUD who develop ALD.