Alcohol decreases intestinal ratio of Lactobacillus to Enterobacteriaceae and induces hepatic immune tolerance in a murine model of DSS-colitis.
Alcohol decreases intestinal ratio of Lactobacillus to Enterobacteriaceae and induces hepatic immune tolerance in a murine model of DSS-colitis.
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DOI：
10.1080/19490976.2020.1838236
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发表时间：
2020-11-09
期刊：
影响因子：
12.2
通讯作者：
Choudhry MA
中科院分区：
文献类型：
--
作者：
Kuprys PV;Cannon AR;Shieh J;Iftekhar N;Park SK;Eberhardt JM;Ding X;Choudhry MA
酒精可以加重葡聚糖硫酸钠(DSS)结肠炎小鼠模型的疾病；然而，其潜在机制仍有待确定。在这项研究中，我们评估了这种加重的疾病是否与肠杆菌科和乳杆菌有关，因为它们的相对丰度的变化会影响肠道健康。我们还评估了酒精和DSS后肠道屏障是否受到损害，因为它可能会增加细菌易位和肝脏炎症。给小鼠灌胃DSS+酒精或水，产生4个实验组：(对照组+溶剂、对照组+乙醇、DSS+溶剂、DSS+乙醇)。从结肠和盲肠内容物中提取DNA，然后进行qPCR检测肠杆菌科和乳杆菌的水平。取结肠和肝脏切片进行组织学检查。从结肠分离肠上皮细胞，进行RNA表达。与DSS+赋形剂相比，DSS+乙醇的盲肠内容物在肠杆菌科中增加了1个对数(p<；2.05)，乳杆菌减少了0.5个对数，乳杆菌：肠杆菌科的比例减少了1.5个对数(p<；2.05)，结肠内容物也有类似的趋势。这些变化与结肠变短和体重减轻有关。不考虑乙醇给药，DSS损害了粘膜屏障的完整性，然而只有DSS+乙醇表现出循环内毒素的显著增加。此外，与接受DSS+Vehicle的小鼠相比，DSS+乙醇组小鼠的肝脏甘油三酯和单个核细胞水平显著增加，但肝脏炎症途径的表达显著降低，提示有耐受诱导作用。我们的结果表明，DSS结肠炎后乙醇增加了肠杆菌科细菌的肠道负担，这可能有助于肠道和肝脏的损伤，并诱导免疫耐受。
Alcohol can potentiate disease in a mouse model of dextran sodium sulfate (DSS) colitis; however, the underlying mechanism remains to be established. In this study, we assessed whether the potentiated disease could be related to Enterobacteriaceae and Lactobacillus, as changes in their relative abundance can impact intestinal health. We also assessed whether the intestinal barrier is compromised after alcohol and DSS as it may increase bacterial translocation and liver inflammation. Mice were administered DSS followed by binge ethanol or water vehicle, generating four experimental groups: (Control+Vehicle, Control+Ethanol, DSS+Vehicle, DSS+Ethanol). DNA was isolated from colon and cecal contents followed by qPCR for levels of Enterobacteriaceae and Lactobacillus. Colon and liver sections were taken for histology. Intestinal epithelial cells were isolated from the colon for RNA expression. DSS+Ethanol cecal contents exhibited a 1 log increase in Enterobacteriaceae (p < .05), a 0.5 log decrease in Lactobacillus, and a 1.5 log decrease (p < .05) in the Lactobacillus:Enterobacteriaceae ratio compared to DSS+Vehicle, with similar trends in colon contents. These changes correlated with shorter colons and more weight loss. Irrespective of ethanol administration, DSS compromised the mucosal barrier integrity, however only DSS+Ethanol exhibited significant increases in circulating endotoxin. Furthermore, the livers of DSS+Ethanol mice had significantly increased levels of triglycerides, mononuclear cells, yet exhibited significantly depressed expression of liver inflammatory pathways, suggestive of tolerance induction, compared to mice receiving DSS+Vehicle. Our results suggest that ethanol after DSS colitis increases the intestinal burden of Enterobacteriaceae which may contribute to intestinal and liver damage, and the induction of immune tolerance.
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影响因子：
3.1
作者：
Cohen, Aaron B.;Lee, Dale;Long, Millie D.;Kappelman, Michael D.;Martin, Christopher F.;Sandler, Robert S.;Lewis, James D.
通讯作者：
Lewis, James D.
DOI：
10.1152/ajpgi.2001.280.6.g1280
发表时间：
2001-06-01
影响因子：
4.5
作者：
Atkinson, KJ;Rao, RK
通讯作者：
Rao, RK
DOI：
10.1111/j.1365-2672.1991.tb04442.x
发表时间：
1991-02-01
期刊：
JOURNAL OF APPLIED BACTERIOLOGY
影响因子：
--
作者：
CHERRINGTON, CA;HINTON, M;CHOPRA, I
通讯作者：
CHOPRA, I
DOI：
10.1111/acer.12900
发表时间：
2015-12
期刊：
Alcoholism, clinical and experimental research
影响因子：
--
作者：
Chen P;Miyamoto Y;Mazagova M;Lee KC;Eckmann L;Schnabl B
通讯作者：
Schnabl B
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