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

• Published in: Clinical and translational gastroenterology Vol. 15; no. 4; p. e00689
• Main Authors: Swanson, Garth R, Garg, Kanika, Shaikh, Maliha, Keshavarzian, Ali
• Format: Journal Article
• Language: English
• Published: United States Wolters Kluwer 01-04-2024
• Subjects: Adult; Aged; Alcoholism - complications; Alcoholism - metabolism; Aspirin - administration & dosage; Case-Control Studies; Colon; Female; Humans; Intestinal Absorption - drug effects; Intestinal Barrier Function; Intestinal Mucosa - metabolism; Intestinal Mucosa - pathology; Lactulose - administration & dosage; Lactulose - urine; Liver Diseases, Alcoholic - metabolism; Male; Mannitol - administration & dosage; Mannitol - urine; Middle Aged; Permeability; Sucrose - administration & dosage; Sucrose - analogs & derivatives
• ISSN: 2155-384X; 2155-384X
• DOI: 10.14309/ctg.0000000000000689

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 cofactor, increased intestinal permeability in ALD is not completely understood.
We recruited 178 subjects-58 healthy controls (HCs), 32 with ALD, 53 with AUD but no liver disease (ALC), and 35 with metabolic dysfunction-associated steatotic liver disease (MASLD). 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.
Five-hour urinary lactulose/mannitol ratio (primarily representing small intestinal permeability) was not statistically different in HC, ALC, ALD, and MASLD groups ( P = 0.40). Twenty-four-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 ratio (primarily representing colon permeability) separated the ALD group ( F = 10.2, P < 0.01) from the MASLD group. After aspirin challenge, intestinal permeability increased in all groups and ALD had the largest increase.
In a group of patients, we confirmed that (i) the ALD group has increased intestinal permeability compared with the HC, ALC, or MASLD group. In addition, because small bowel permeability (lactulose/mannitol ratio) is normal, the disruption of intestinal barrier seems to be primarily in the large intestine; (ii) decreased resiliency of intestinal barrier to injurious agents (such as NSAID) might be the mechanism for gut leak in subset of AUD who develop ALD.