Links of gut microbiota composition with alcohol dependence syndrome and alcoholic liver disease.
Links of gut microbiota composition with alcohol dependence syndrome and alcoholic liver disease.
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DOI：
10.1186/s40168-017-0359-2
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发表时间：
2017-10-17
期刊：
影响因子：
15.5
通讯作者：
Govorun VM
中科院分区：
文献类型：
--
作者：
Dubinkina VB;Tyakht AV;Odintsova VY;Yarygin KS;Kovarsky BA;Pavlenko AV;Ischenko DS;Popenko AS;Alexeev DG;Taraskina AY;Nasyrova RF;Krupitsky EM;Shalikiani NV;Bakulin IG;Shcherbakov PL;Skorodumova LO;Larin AK;Kostryukova ES;Abdulkhakov RA;Abdulkhakov SR;Malanin SY;Ismagilova RK;Grigoryeva TV;Ilina EN;Govorun VM
酒精滥用会破坏许多器官和系统的功能，从而对人体健康产生有害影响。肠道微生物群与酒精相关肝病的发病机制有关，其组成在酒精依赖患者中表现出表达的生态失调。肠道菌群由于其固有的可塑性，是预防和治疗这些疾病的重要靶点。确定酒精滥用与相关精神症状对肠道群落结构的影响与肝功能障碍相混淆。为了区分这两个因素的影响，我们对99例酒精依赖综合征患者进行了一项比较的“散弹枪”宏基因组调查，这些患者分为肝硬化和非肝硬化两组。肠道微生物群的分类和功能组成进行了多因素分析，包括与外部对照组的比较。酒精依赖和肝硬化与患者肠道群落结构和代谢潜力的深刻变化有关。在有肝硬化和没有肝硬化的队列中，对物种水平群落组成的具体影响有显著差异。在这两种情况下，发现共生微生物群都被耗尽了。酒精依赖与产丁酸的梭状芽孢杆菌的水平呈负相关，而肝硬化与多个拟杆菌的水平呈负相关。与酒精依赖相关的机会主义病原体包括促炎肠杆菌科，而肝硬化的特征包括肠道中口腔微生物的增加和异常群落结构的更频繁发生。有趣的是，这两个因素中的每一个都与许多双歧杆菌和乳酸杆菌的表达富集有关，但在酒精依赖和肝硬化之间，物种的确切集合是不同的。在功能电位水平上，患者表现出与酒精代谢和毒力因子相关的功能以及与炎症相关的途径的不同模式的增加。群落结构和代谢潜力的多重变化表明，酒精依赖和相关的肝功能障碍对肠道微生物群有强烈的负面影响。确定这两个因素之间影响模式的差异对于规划个性化治疗和通过微生物群调节预防这些病理是重要的。特别是，双歧杆菌和乳酸杆菌的扩张表明，使用同一分类群的代表对酒精相关疾病患者的益生菌干预应谨慎考虑。分类学和功能分析显示，肠道微生物群合成有毒乙醛的倾向增加，这表明酗酒者患结直肠癌和其他疾病的风险更高。本文的在线版本（10.1186/s40168-017-0359-2）包含补充材料，可供授权用户使用。
Alcohol abuse has deleterious effects on human health by disrupting the functions of many organs and systems. Gut microbiota has been implicated in the pathogenesis of alcohol-related liver diseases, with its composition manifesting expressed dysbiosis in patients suffering from alcoholic dependence. Due to its inherent plasticity, gut microbiota is an important target for prevention and treatment of these diseases. Identification of the impact of alcohol abuse with associated psychiatric symptoms on the gut community structure is confounded by the liver dysfunction. In order to differentiate the effects of these two factors, we conducted a comparative “shotgun” metagenomic survey of 99 patients with the alcohol dependence syndrome represented by two cohorts—with and without liver cirrhosis. The taxonomic and functional composition of the gut microbiota was subjected to a multifactor analysis including comparison with the external control group. Alcoholic dependence and liver cirrhosis were associated with profound shifts in gut community structures and metabolic potential across the patients. The specific effects on species-level community composition were remarkably different between cohorts with and without liver cirrhosis. In both cases, the commensal microbiota was found to be depleted. Alcoholic dependence was inversely associated with the levels of butyrate-producing species from the Clostridiales order, while the cirrhosis—with multiple members of the Bacteroidales order. The opportunist pathogens linked to alcoholic dependence included pro-inflammatory Enterobacteriaceae, while the hallmarks of cirrhosis included an increase of oral microbes in the gut and more frequent occurrence of abnormal community structures. Interestingly, each of the two factors was associated with the expressed enrichment in many Bifidobacterium and Lactobacillus—but the exact set of the species was different between alcoholic dependence and liver cirrhosis. At the level of functional potential, the patients showed different patterns of increase in functions related to alcohol metabolism and virulence factors, as well as pathways related to inflammation. Multiple shifts in the community structure and metabolic potential suggest strong negative influence of alcohol dependence and associated liver dysfunction on gut microbiota. The identified differences in patterns of impact between these two factors are important for planning of personalized treatment and prevention of these pathologies via microbiota modulation. Particularly, the expansion of Bifidobacterium and Lactobacillus suggests that probiotic interventions for patients with alcohol-related disorders using representatives of the same taxa should be considered with caution. Taxonomic and functional analysis shows an increased propensity of the gut microbiota to synthesis of the toxic acetaldehyde, suggesting higher risk of colorectal cancer and other pathologies in alcoholics. The online version of this article (10.1186/s40168-017-0359-2) contains supplementary material, which is available to authorized users.
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DOI：
10.1016/j.pnpbp.2015.06.013
发表时间：
2016-02-04
影响因子：
5.6
作者：
Gorky J;Schwaber J
通讯作者：
Schwaber J
影响因子：
30.3
作者：
Lewis JD;Chen EZ;Baldassano RN;Otley AR;Griffiths AM;Lee D;Bittinger K;Bailey A;Friedman ES;Hoffmann C;Albenberg L;Sinha R;Compher C;Gilroy E;Nessel L;Grant A;Chehoud C;Li H;Wu GD;Bushman FD
通讯作者：
Bushman FD
影响因子：
24.5
作者：
Llopis, M.;Cassard, A. M.;Perlemuter, G.
通讯作者：
Perlemuter, G.
影响因子：
12.3
作者：
Langmead B;Trapnell C;Pop M;Salzberg SL
通讯作者：
Salzberg SL
影响因子：
3.7
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
通讯作者：
Barve S