Swanson Garth R, Garg Kanika, Shaikh Maliha, Keshavarzian Ali
Department of Internal Medicine, Division of Gastroenterology and Hepatology, Medical University of South Carolina, Charleston, South Carolina, USA.
Rush Center for Integrated Microbiome and Chronobiology, Rush University Medical Center, Chicago, Illinois, USA.
Clin Transl Gastroenterol. 2024 Apr 1;15(4):e00689. 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.
只有20%-30%的酒精使用障碍（AUD）患者会发展为酒精性肝病（ALD）。虽然肠道源性内毒素血症的发展被认为是一个必要的辅助因素，但ALD中肠道通透性增加的情况尚未完全明确。
我们招募了178名受试者——58名健康对照者（HC）、32名患有ALD的患者、53名患有AUD但无肝病的患者（ALC）以及35名患有代谢功能障碍相关脂肪性肝病（MASLD）的患者。通过糖鸡尾酒评估肠道通透性，以口服剂量的百分比表示。在一个亚组中，阿司匹林激发后重复进行通透性测试。
HC、ALC、ALD和MASLD组的5小时尿乳果糖/甘露醇比值（主要代表小肠通透性）在统计学上无差异（P = 0.40）。ALD组的24小时尿三氯蔗糖（代表全肠道通透性）增加（F = 5.3，P < 0.01），且能将ALD与ALC区分开来；24小时三氯蔗糖/乳果糖比值（主要代表结肠通透性）将ALD组（F = 10.2，P < 0.01）与MASLD组区分开来。阿司匹林激发后，所有组的肠道通透性均增加，且ALD组增加幅度最大。
在一组患者中，我们证实：（i）与HC、ALC或MASLD组相比，ALD组的肠道通透性增加。此外，由于小肠通透性（乳果糖/甘露醇比值）正常，肠道屏障的破坏似乎主要发生在大肠；（ii）肠道屏障对损伤性因素（如非甾体抗炎药）的弹性降低可能是发展为ALD的AUD亚组中肠道渗漏的机制。
