Metagenomic analyses of alcohol induced pathogenic alterations in the intestinal microbiome and the effect of Lactobacillus rhamnosus GG treatment.
Metagenomic analyses of alcohol induced pathogenic alterations in the intestinal microbiome and the effect of Lactobacillus rhamnosus GG treatment.
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DOI：
10.1371/journal.pone.0053028
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Barve S
中科院分区：
文献类型：
--
作者：
Bull-Otterson L;Feng W;Kirpich I;Wang Y;Qin X;Liu Y;Gobejishvili L;Joshi-Barve S;Ayvaz T;Petrosino J;Kong M;Barker D;McClain C;Barve S
肠道生态失调在酒精性肝病（ALD）的发病机制中起重要作用。肠道微生物组改变的详细特征是了解其在ALD中的致病作用和开发使用益生菌补充剂的有效治疗方法所必需的。小鼠分别饲喂不含酒精或含酒精（5% v/v）的Lieber-DeCarli液体饮食6周。一组小鼠从6至8周开始服用益生菌鼠李糖乳杆菌GG （LGG）。评估肠通透性、肝脂肪变性、炎症及损伤等指标。在454 FLX Titanium平台上，通过扩增16S rRNA基因的V3-V5区域和大规模平行焦磷酸测序来分析粪便DNA，对肠道微生物组进行宏基因组分析。慢性乙醇饲养导致细菌门和厚壁菌门的丰度下降，革兰氏阴性变形菌门和革兰氏阳性放线菌门的丰度呈比例增加；扩增最大的细菌属为革兰氏阴性耐碱性碱性菌属和革兰氏阳性棒状杆菌属。与微生物组的定性和定量改变相适应，乙醇引起血浆内毒素、粪便pH值、肝脏炎症和损伤的增加。值得注意的是，添加LGG可以防止乙醇引起的微生物组和肝脏的致病性变化。总的来说，随着时间的推移，肠道微生物群的显著变化是对慢性酒精暴露的反应，并与肠道屏障功能障碍的增加和ALD的发展相对应。此外，肠道细菌群落的改变可能是预防/治疗慢性酒精摄入引起的肠道屏障功能障碍和肝脏疾病的重要治疗靶点。
Enteric dysbiosis plays an essential role in the pathogenesis of alcoholic liver disease (ALD). Detailed characterization of the alterations in the gut microbiome is needed for understanding their pathogenic role in ALD and developing effective therapeutic approaches using probiotic supplementation. Mice were fed liquid Lieber-DeCarli diet without or with alcohol (5% v/v) for 6 weeks. A subset of mice were administered the probiotic Lactobacillus rhamnosus GG (LGG) from 6 to 8 weeks. Indicators of intestinal permeability, hepatic steatosis, inflammation and injury were evaluated. Metagenomic analysis of the gut microbiome was performed by analyzing the fecal DNA by amplification of the V3–V5 regions of the 16S rRNA gene and large-scale parallel pyrosequencing on the 454 FLX Titanium platform. Chronic ethanol feeding caused a decline in the abundance of both Bacteriodetes and Firmicutes phyla, with a proportional increase in the gram negative Proteobacteria and gram positive Actinobacteria phyla; the bacterial genera that showed the biggest expansion were the gram negative alkaline tolerant Alcaligenes and gram positive Corynebacterium. Commensurate with the qualitative and quantitative alterations in the microbiome, ethanol caused an increase in plasma endotoxin, fecal pH, hepatic inflammation and injury. Notably, the ethanol-induced pathogenic changes in the microbiome and the liver were prevented by LGG supplementation. Overall, significant alterations in the gut microbiome over time occur in response to chronic alcohol exposure and correspond to increases in intestinal barrier dysfunction and development of ALD. Moreover, the altered bacterial communities of the gut may serve as significant therapeutic target for the prevention/treatment of chronic alcohol intake induced intestinal barrier dysfunction and 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
DOI：
10.1073/pnas.0504978102
发表时间：
2005-08-02
影响因子：
11.1
作者：
Ley, RE;Bäckhed, F;Gordon, JI
通讯作者：
Gordon, JI
DOI：
10.1152/ajpgi.90232.2008
发表时间：
2008-10-01
影响因子：
4.5
作者：
Gobejishvili, Leila;Barve, Shirish;McClain, Craig
通讯作者：
McClain, Craig
影响因子：
7.1
作者：
Bezkorovainy, A
通讯作者：
Bezkorovainy, A
影响因子：
9.4
作者：
Horz, HP;Vianna, ME;Conrads, G
通讯作者：
Conrads, G