OBJECTIVES Chronic liver disease (CLD) is associated with both alterations of the stool microbiota and increased small intestinal permeability. However, little is known about the role of the small intestinal mucosa-associated microbiota (MAM) in CLD. The aim of this study was to evaluate the relationship between the duodenal MAM and both small intestinal permeability and liver disease severity in CLD. METHODS Subjects with CLD and a disease-free control group undergoing routine endoscopy underwent duodenal biopsy to assess duodenal MAM by 16S rRNA gene sequencing. Small intestinal permeability was assessed by a dual sugar (lactulose: rhamnose) assay. Other assessments included transient elastography, endotoxemia, serum markers of hepatic inflammation, dietary intake, and anthropometric measurements. RESULTS Forty-six subjects (35 with CLD and 11 controls) were assessed. In subjects with CLD, the composition (P = 0.02) and diversity (P < 0.01) of the duodenal MAM differed to controls. Constrained multivariate analysis and linear discriminate effect size showed this was due to Streptococcus-affiliated lineages. Small intestinal permeability was significantly higher in CLD subjects compared to controls. In CLD, there were inverse correlations between microbial diversity and both increased small intestinal permeability (r = -0.41, P = 0.02) and serum alanine aminotransferase (r = -0.35, P = 0.04). Hepatic stiffness was not associated with the MAM. DISCUSSION In CLD, there is dysbiosis of the duodenal MAM and an inverse correlation between microbial diversity and small intestinal permeability. TRANSLATIONAL IMPACT Strategies to ameliorate duodenal MAM dysbiosis may ameliorate intestinal barrier dysfunction and liver injury in CLD.

中文翻译：

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慢性肝病中十二指肠粘膜微生物群的营养不良与小肠通透性增加有关。

目的慢性肝病（CLD）与粪便微生物群的改变和小肠通透性的增加有关。然而，关于小肠粘膜相关微生物群（MAM）在CLD中的作用知之甚少。这项研究的目的是评估CLD中十二指肠MAM与小肠通透性和肝病严重程度之间的关系。方法接受常规内镜检查的CLD患者和无病对照组进行十二指肠活检，以通过16S rRNA基因测序评估十二指肠MAM。小肠通透性通过双重糖（乳果糖：鼠李糖）测定法评估。其他评估包括瞬时弹性成像，内毒素血症，肝炎的血清标志物，饮食摄入和人体测量。结果对46名受试者（35名CLD和11名对照）进行了评估。在患有CLD的受试者中，十二指肠MAM的组成（P = 0.02）和多样性（P <0.01）与对照组不同。受约束的多元分析和线性区分效应大小表明，这是由于链球菌相关谱系所致。与对照组相比，CLD受试者的小肠通透性显着更高。在CLD中，微生物多样性与小肠通透性增加（r = -0.41，P = 0.02）和血清丙氨酸转氨酶（r = -0.35，P = 0.04）之间呈负相关。肝硬度与MAM无关。讨论在CLD中，十二指肠MAM存在生物功能异常，并且微生物多样性与小肠通透性之间呈负相关。