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以蛋鸡为模型研究盲肠微生物群与非酒精性脂肪性肝炎的相互作用。

Interactions between the cecal microbiota and non-alcoholic steatohepatitis using laying hens as the model.

机构信息

State Key Laboratory of Animal Nutrition, College of Animal Science and Technology, China Agricultural University, Beijing 100193, P. R. China.

Key Laboratory of Biomass Energy and Materials of Jiangsu Province, Nanjing 210042, China.

出版信息

Poult Sci. 2019 Jun 1;98(6):2509-2521. doi: 10.3382/ps/pey596.

DOI:10.3382/ps/pey596
PMID:30690636
Abstract

Chronic liver disease has caused increasing numbers of deaths worldwide. Fatty liver hemorrhagic syndrome, one of the chronic liver diseases in laying hens, has great similarity to non-alcoholic fatty liver disease (NAFLD) in humans. It is characterized by the pathological accumulation of liver fat. Non-invasive techniques are needed for early identification of fibrosis. As primary de novo lipogenesis in the liver of chicken is similar to that of humans, mature chicken is an ideal animal model for the understanding of NAFLD. This study was aimed to evaluate the relationships between gut microbiota and natural chronic liver disease (i.e., non-alcoholic steatohepatitis [NASH] and fibrosis stages) in a well-characterized laying hen population. One hundred 20-wk-old Hy-Line Brown laying hens were used and fed with basal diets until 52 wk of age. At the end of the experiment, birds were killed for sampling blood, liver, and cecal contents, and then classified by liver histology measurement into different groups. We investigated microbial community structure of cecum using 16S rRNA gene sequencing. Subjects in stage 0 fibrosis without NASH were classified as low NAFLD (Group A), subjects in stage 1-2 fibrosis with mild to moderate NASH were defined as low NASH (Group B), and subjects in stage 3 fibrosis were defined as severe NASH (Group C). The abundance of Firmicutes was reduced in Groups B and C (P < 0.001), whereas opposite results were observed for the abundance of Bacteroidetes. Additionally, the families Bacteroidaceae, Ruminococcaceae Lachnospiraceae, and lactobacillae were significantly different between groups of differing fibrosis stages (P < 0.001), driven entirely by alterations of Bacteroides and lactobacillus and lachnospiraceae genera (P < 0.001), were observed. Results indicated that cecal dysbiosis was linked with the severity of fibrosis and NASH; importantly, increased levels of serum AST, alkaline phosphatase, and uric acid were accompanied with liver fibrosis and NASH severity. Collectively, these data highlight the role of gut-liver axis and associations between the gut microbiota and fibrosis and NASH severity.

摘要

慢性肝病在全球范围内导致的死亡人数不断增加。脂肪肝出血综合征是蛋鸡的慢性肝病之一,与人非酒精性脂肪性肝病(NAFLD)有很大的相似性。它的特征是肝脏脂肪病理性积累。需要非侵入性技术来早期识别纤维化。由于鸡的肝内原发性从头合成脂肪与人类相似,成熟的鸡是理解 NAFLD 的理想动物模型。本研究旨在评估肠道微生物群与一种特征明确的蛋鸡群体中自然发生的慢性肝病(即非酒精性脂肪性肝炎[NASH]和纤维化阶段)之间的关系。使用 100 只 20 周龄的海兰褐蛋鸡,用基础日粮喂养至 52 周龄。实验结束时,处死鸟类进行采样血、肝和盲肠内容物,然后根据肝组织学测量将鸟类分为不同的组。我们使用 16S rRNA 基因测序研究了盲肠的微生物群落结构。无 NASH 纤维化阶段 0 的研究对象被归类为低 NAFLD(A 组),纤维化阶段 1-2 且有轻度至中度 NASH 的研究对象被定义为低 NASH(B 组),纤维化阶段 3 的研究对象被定义为严重 NASH(C 组)。Firmicutes 的丰度在 B 组和 C 组中减少(P < 0.001),而 Bacteroidetes 的丰度则相反。此外,在不同纤维化阶段的组之间,科 Bacteroidaceae、Ruminococcaceae 和 Lachnospiraceae 以及乳杆菌科的丰度存在显著差异(P < 0.001),这完全是由 Bacteroides 和乳杆菌属以及lachnospiraceae 属的变化引起的(P < 0.001)。结果表明,盲肠菌群失调与纤维化和 NASH 的严重程度有关;重要的是,血清 AST、碱性磷酸酶和尿酸水平的升高伴随着肝纤维化和 NASH 的严重程度。总之,这些数据强调了肠道-肝脏轴的作用以及肠道微生物群与纤维化和 NASH 严重程度之间的关联。

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