Supplementation of saturated long-chain fatty acids maintains intestinal eubiosis and reduces ethanol-induced liver injury in mice.
Supplementation of saturated long-chain fatty acids maintains intestinal eubiosis and reduces ethanol-induced liver injury in mice.
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DOI：
10.1053/j.gastro.2014.09.014
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发表时间：
2015-01
期刊：
影响因子：
29.4
通讯作者：
Schnabl B
中科院分区：
文献类型：
--
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
酒精性肝病是导致死亡的主要原因。长期饮酒伴随着肠道生态失调，酒精性肝病的发展需要肠道衍生的细菌产物。然而，关于微生物组的改变如何有助于酒精性肝病的发病机制知之甚少。我们使用Tsukamoto-French小鼠模型，该模型包括连续胃内喂养等热量饮食或酒精3周。从盲肠提取细菌DNA用于深度宏基因组测序。靶向代谢组学评估盲肠内容物中饱和脂肪酸的浓度。为了维持肠道代谢稳态，乙醇喂养和对照小鼠的饮食中补充了饱和长链脂肪酸（LCFA）。参与脂肪酸生物合成的细菌基因，乳酸杆菌的数量和饱和LCFA在非酒精性个人和活跃的酒精滥用患者的粪便样本中进行了测量。对小鼠肠道内容物的分析显示，肠道宏基因组和代谢组发生了与酒精相关的变化，其特征在于饱和LCFA的合成减少。维持小鼠肠道内饱和脂肪酸的水平，可使机体保持良好的生态状态，稳定肠道屏障，并减少乙醇引起的肝损伤。饱和的LCFA被乳酸菌代谢并促进其生长。参与脂肪酸生物合成的细菌基因的比例在酒精滥用患者的粪便中低于对照组。LCFA的总水平与活跃的酒精滥用患者粪便样本中的乳酸杆菌相关，但在对照组中不相关。在人类和小鼠中，酒精会导致肠道生态失调，降低微生物组合成饱和LCFA的能力和乳酸杆菌的比例。恢复肠道饱和脂肪酸水平的饮食方法可能会减少酒精性肝病患者乙醇引起的肝损伤。
Alcoholic liver disease is a leading cause of mortality. Chronic alcohol consumption is accompanied by intestinal dysbiosis, and development of alcoholic liver disease requires gut-derived bacterial products. However, little is known about how alterations to the microbiome contribute to pathogenesis of alcoholic liver disease. We used the Tsukamoto-French mouse model which involves continuous intragastric feeding of isocaloric diet or alcohol for 3 weeks. Bacterial DNA from the cecum was extracted for deep metagenomic sequencing. Targeted metabolomics assessed concentrations of saturated fatty acids in cecal contents. To maintain intestinal metabolic homeostasis, diets of ethanol-fed and control mice were supplemented with saturated long-chain fatty acids (LCFA). Bacterial genes involved in fatty acid biosynthesis, amounts of lactobacilli, and saturated LCFA were measured in fecal samples of non-alcoholic individuals and patients with active alcohol abuse. Analyses of intestinal contents from mice revealed alcohol-associated changes to the intestinal metagenome and metabolome, characterized by reduced synthesis of saturated LCFA. Maintaining intestinal levels of saturated fatty acids in mice resulted in eubiosis, stabilized the intestinal gut barrier and reduced ethanol-induced liver injury. Saturated LCFA are metabolized by commensal Lactobacillus and promote their growth. Proportions of bacterial genes involved in fatty acid biosynthesis were lower in feces from patients with active alcohol abuse than controls. Total levels of LCFA correlated with those of lactobacilli in fecal samples from patients with active alcohol abuse but not in controls. In humans and mice, alcohol causes intestinal dysbiosis, reducing the capacity of the microbiome to synthesize saturated LCFA and the proportion of Lactobacillus species. Dietary approaches to restore levels of saturated fatty acids in the intestine might reduce ethanol-induced liver injury in patients with alcoholic liver disease.
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DOI：
10.1016/j.alcohol.2008.12.009
发表时间：
2009-03
期刊：
Alcohol (Fayetteville, N.Y.)
影响因子：
--
作者：
Forsyth CB;Farhadi A;Jakate SM;Tang Y;Shaikh M;Keshavarzian A
通讯作者：
Keshavarzian A
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：
2.3
作者：
Kirpich, Irina A.;Feng, Wenke;Wang, Yuhua;Liu, Yanlong;Beier, Juliane I.;Arteel, Gavin E.;Falkner, K. Cameron;Barve, Shirish S.;McClain, Craig J.
通讯作者：
McClain, Craig J.
影响因子：
2.1
作者：
Bergstrom, Anders;Licht, Tine R.;Bahl, Martin I.
通讯作者：
Bahl, Martin I.
影响因子：
7.4
作者：
Fouts DE;Pieper R;Szpakowski S;Pohl H;Knoblach S;Suh MJ;Huang ST;Ljungberg I;Sprague BM;Lucas SK;Torralba M;Nelson KE;Groah SL
通讯作者：
Groah SL