Intestinal permeability, microbial translocation, changes in duodenal and fecal microbiota, and their associations with alcoholic liver disease progression in humans.
Intestinal permeability, microbial translocation, changes in duodenal and fecal microbiota, and their associations with alcoholic liver disease progression in humans.
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DOI：
10.1080/19490976.2020.1782157
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发表时间：
2020-11-09
期刊：
影响因子：
12.2
通讯作者：
Stärkel P
中科院分区：
文献类型：
--
作者：
Maccioni L;Gao B;Leclercq S;Pirlot B;Horsmans Y;De Timary P;Leclercq I;Fouts D;Schnabl B;Stärkel P
动物数据表明肠-肝轴在酒精性肝病（ALD）进展中的作用，但人类数据很少，特别是对于早期疾病阶段。我们纳入了遵循康复计划的酒精使用障碍（AUD）患者和匹配的健康对照。我们测定了肠上皮和血管通透性（IP）（使用51 Cr-EDTA的尿排泄、粪便白蛋白含量和远端十二指肠活检的免疫组织化学）、上皮损伤（组织学、血清iFABP和肠基因表达）和微生物易位（通过ELISA测定革兰氏和革兰氏+血清标志物）。通过16 S rRNA测序分析十二指肠粘膜相关微生物群和粪便微生物群。通过Fibroscan®（肝硬度，受控衰减参数）结合血清AST、ALT和CK 18-M65对ALD进行分期。只有一部分AUD患者的51 Cr-EDTA和粪便白蛋白增加，同时紧密连接和质膜囊泡相关蛋白-1的血管表达受损。如此定义的肠通透性增加与十二指肠微生物群的变化或肠上皮的改变无关，但与粪便微生物群的组成变化相关。单独的肠漏不能解释AUD患者中微生物易位的增加。相比之下，十二指肠生态失调的优势转向特定的潜在致病菌属（链球菌属，梭菌属，罗氏菌属），IP增加和微生物易位标志物升高的特征是患有进行性ALD（脂肪性肝炎，脂肪性纤维化）的AUD患者。已经处于疾病早期阶段的进行性ALD与十二指肠粘膜相关的生态失调和微生物移位升高相关。令人惊讶的是，这种修饰与IP增加无关。相反，IP增加似乎与粪便微生物群生态失调有关。
Animal data suggest a role of the gut-liver axis in progression of alcoholic liver disease (ALD), but human data are scarce especially for early disease stages. We included patients with alcohol use disorder (AUD) who follow a rehabilitation program and matched healthy controls. We determined intestinal epithelial and vascular permeability (IP) (using urinary excretion of 51Cr-EDTA, fecal albumin content, and immunohistochemistry in distal duodenal biopsies), epithelial damage (histology, serum iFABP, and intestinal gene expression), and microbial translocation (Gram – and Gram + serum markers by ELISA). Duodenal mucosa-associated microbiota and fecal microbiota were analyzed by 16 S rRNA sequencing. ALD was staged by Fibroscan® (liver stiffness, controlled attenuation parameter) in combination with serum AST, ALT, and CK18-M65. Only a subset of AUD patients had increased 51Cr-EDTA and fecal albumin together with disrupted tight junctions and vasculature expression of plasmalemma Vesicle-Associated Protein-1. The so-defined increased intestinal permeability was not related to changes of the duodenal microbiota or alterations of the intestinal epithelium but associated with compositional changes of the fecal microbiota. Leaky gut alone did not explain increased microbial translocation in AUD patients. By contrast, duodenal dysbiosis with a dominance shift toward specific potential pathogenic bacteria genera (Streptococcus, Shuttleworthia, Rothia), increased IP and elevated markers of microbial translocation characterized AUD patients with progressive ALD (steato-hepatitis, steato-fibrosis). Progressive ALD already at early disease stages is associated with duodenal mucosa-associated dysbiosis and elevated microbial translocation. Surprisingly, such modifications were not linked with increased IP. Rather, increased IP appears related to fecal microbiota dysbiosis.
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影响因子：
29.4
作者：
Chen P;Torralba M;Tan J;Embree M;Zengler K;Stärkel P;van Pijkeren JP;DePew J;Loomba R;Ho SB;Bajaj JS;Mutlu EA;Keshavarzian A;Tsukamoto H;Nelson KE;Fouts DE;Schnabl B
通讯作者：
Schnabl B
肠粘膜-2的缺乏可改善小鼠的实验性酒精性肝病。
影响因子：
13.5
作者：
Hartmann, Phillipp;Chen, Peng;Wang, Hui J.;Wang, Lirui;McCole, Declan F.;Brandl, Katharina;Starkel, Peter;Belzer, Clara;Hellerbrand, Claus;Tsukamoto, Hidekazu;Ho, Samuel B.;Schnabl, Bernd
通讯作者：
Schnabl, Bernd
影响因子：
--
作者：
He L;Deng L;Zhang Q;Guo J;Zhou J;Song W;Yuan F
通讯作者：
Yuan F
DOI：
10.1006/clin.1996.0128
发表时间：
1996-09-01
期刊：
CLINICAL IMMUNOLOGY AND IMMUNOPATHOLOGY
影响因子：
--
作者：
Burgmann, H;Winkler, S;Graninger, W
通讯作者：
Graninger, W
影响因子：
3.1
作者：
Gao, Bei;Lang, Sonja;Schnabl, Bernd
通讯作者：
Schnabl, Bernd