Prosteatotic and Protective Components in a Unique Model of Fatty Liver: Gut Microbiota and Suppressed Complement System.
Prosteatotic and Protective Components in a Unique Model of Fatty Liver: Gut Microbiota and Suppressed Complement System.
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独特的脂肪肝模型中的前列腺癌和保护性成分：肠道微生物群和抑制补体系统
DOI：
10.1038/srep31763
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发表时间：
2016-08-23
影响因子：
4.6
通讯作者：
Gong D
中科院分区：
文献类型：
--
作者：
Liu L;Zhao X;Wang Q;Sun X;Xia L;Wang Q;Yang B;Zhang Y;Montgomery S;Meng H;Geng T;Gong D
鹅可以在没有明显损伤的情况下发生严重的肝脏脂肪变性，因此它可能成为揭示脂肪变性相关损伤如何预防的独特模型。为了确定显著的前骨化和保护机制，我们对肝脏转录本和肠道微生物元基因组进行了整合分析，使用在不同时间点从过度饲养和正常饲养的鹅身上收集的样本。结果表明，脂肪肝转录组最初的特点是“新陈代谢”途径，后来又加入了“细胞生长和死亡”途径和“免疫疾病”途径。肠道微生物区系在肝脏反应中发挥了协同作用，因为受过量喂养影响的微生物和肝脏基因共享多条途径。值得注意的是，作为炎症成分的补体系统在脂肪肝中被全面抑制，这部分是由于富含乳杆菌的血液乳酸增加所致。体外实验数据表明，乳酸通过HNF1α/C5途径抑制肿瘤坏死因子α。总之，肠道微生物及其宿主作为一个有机整体对过量能量内流做出反应，鹅肝的严重脂肪变性和相关耐受可能部分归因于肠道微生物产物和补体系统的抑制，肠道微生物区系中的乳酸通过HNF1α/C5途径参与了肝脏肿瘤坏死因子α/炎症的抑制。
Goose can develop severe hepatic steatosis without overt injury, thus it may serve as a unique model for uncovering how steatosis-related injury is prevented. To identify the markedly prosteatotic and protective mechanisms, we performed an integrated analysis of liver transcriptomes and gut microbial metagenomes using samples collected from overfed and normally-fed geese at different time points. The results indicated that the fatty liver transcriptome, initially featuring a ‘metabolism’ pathway, was later joined by ‘cell growth and death’ and ‘immune diseases’ pathways. Gut microbiota played a synergistic role in the liver response as microbial and hepatic genes affected by overfeeding shared multiple pathways. Remarkably, the complement system, an inflammatory component, was comprehensively suppressed in fatty liver, which was partially due to increased blood lactic acid from enrichedLactobacillus. Data fromin vitrostudies suggested that lactic acid suppressed TNFα via the HNF1α/C5 pathway. In conclusion, gut microbes and their hosts respond to excess energy influx as an organic whole, severe steatosis and related tolerance of goose liver may be partially attributable to gut microbiotic products and suppressed complement system, and lactic acid from gut microbiota participates in the suppression of hepatic TNFα/inflammation through the HNF1α/C5 pathway.