Department of Gastroenterology and Hepatology, Princess Alexandra Hospital, Woolloongabba, Queensland, Australia.
School of Medicine, Faculty of Medicine and Biomedical Sciences, the University of Queensland, and Translational Research Institute, Woolloongabba, Queensland, Australia.
Clin Transl Gastroenterol. 2019 Aug;10(8):e00068. doi: 10.14309/ctg.0000000000000068.
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.
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.
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.
In CLD, there is dysbiosis of the duodenal MAM and an inverse correlation between microbial diversity and small intestinal permeability.
Strategies to ameliorate duodenal MAM dysbiosis may ameliorate intestinal barrier dysfunction and liver injury in CLD.
慢性肝病（CLD）与粪便微生物群的改变和小肠通透性增加有关。然而，人们对 CLD 中小肠黏膜相关微生物群（MAM）的作用知之甚少。本研究旨在评估十二指肠 MAM 与 CLD 中小肠通透性和肝病严重程度的关系。
接受常规内镜检查的 CLD 患者和无疾病对照组接受十二指肠活检，通过 16S rRNA 基因测序评估十二指肠 MAM。通过双糖（乳果糖：鼠李糖）测定法评估小肠通透性。其他评估包括瞬时弹性成像、内毒素血症、肝炎症血清标志物、饮食摄入和人体测量。
共评估了 46 名受试者（35 名 CLD 患者和 11 名对照组）。CLD 患者的十二指肠 MAM 组成（P = 0.02）和多样性（P < 0.01）与对照组不同。受约束的多变量分析和线性判别效应大小表明，这是由于链球菌相关谱系。CLD 患者的小肠通透性明显高于对照组。在 CLD 中，微生物多样性与增加的小肠通透性（r = -0.41，P = 0.02）和血清丙氨酸氨基转移酶（r = -0.35，P = 0.04）呈负相关。肝硬度与 MAM 无关。
在 CLD 中，十二指肠 MAM 存在失调，微生物多样性与小肠通透性呈负相关。
改善十二指肠 MAM 失调的策略可能改善 CLD 中的肠道屏障功能障碍和肝损伤。
