袁静团队:促脂肪肝的高产酒精肺炎克雷伯菌如何生成内源性酒精?
  • 表征并对比高产酒精(HiAlc)和中产酒精的肺炎克雷伯菌(Kpn)的基因组,建敲除乙醇脱氢酶必需基因的HiAlc Kpn W14菌株(W14Δadh)并建立小鼠模型;
  • HiAlc Kpn在肠道内生长期间,参与2,3-丁二醇发酵途径的10个蛋白质和6个主要代谢产物发生了明显变化;
  • 与野生型W14菌株相比,产酒精能力减弱的W14Δadh菌株诱导小鼠脂肪肝的时间更晚、程度更轻;
  • 因此,HiAlc Kpn通过2,3-丁二醇途径诱导产生内源性酒精,促进脂肪肝病。
主编推荐语
mildbreeze
肠道菌群中的高产酒精肺炎克雷伯菌(HiAlc Kpn)已被证实是脂肪肝病的致病因子。然而,该菌在体内产生酒精的分解代谢途径尚不清楚。首都儿科研究所袁静团队近期在Gut Microbes发表研究,对这一问题进行了回答。该研究表明,HiAlc Kpn通过2,3-丁二醇发酵途径将碳水化合物底物分解代谢产生乙醇和2,3-丁二醇,为脂肪肝病的诊断、预防和治疗提供了新见解。
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Gut Microbes [IF:10.245]

High alcohol-producing Klebsiella pneumoniae causes fatty liver disease through 2,3-butanediol fermentation pathway in vivo

高产酒精肺炎克雷伯菌在体内通过2,3-丁二醇发酵途径引起脂肪性肝病

10.1080/19490976.2021.1979883

2021-10-10, Article

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High alcohol-producing (HiAlc ) in the gut microbiota had been demonstrated to be the causative agent of fatty liver disease (FLD). However, the catabolic pathways for alcohol production remain unclear. Here, we characterized the genome of HiAlc and medium alcohol-producing (MedAlc) and constructed an (an essential gene encoding alcohol dehydrogenase) knock-out HiAlc W14 strain (W14) using CRISPR-Cas9 system. Subsequently, we established the mouse model gavage administration of HiAlc W14 and W14 strains, respectively. Proteome and metabolome analysis showed that 10 proteins and six major metabolites involved in the 2,3-butanediol fermentation pathway exhibited at least a three-fold change or greater during intestinal growth. Compared with HiAlc W14-fed mice, W14-fed mice with weak alcohol-producing ability did not show apparent pathological changes at 4 weeks, although some steatotic hepatocytes were observed at 12 weeks. Our data demonstrated that carbohydrate substances are catabolized to produce alcohol and 2,3-butanediol the 2,3-butanediol fermentation pathway in HiAlc , which could be a promising clinical diagnostic marker. The production of high amounts of endogenous alcohol is responsible for the observed steatosis effects in hepatocytes .

First Authors:
NanNan Li,Jun-Xia Feng

Correspondence Authors:
Jing Yuan

All Authors:
NanNan Li,Wei Li,Jun-Xia Feng,Weiwei Zhang,Rui Zhang,Shu-Heng Du,Shi-Yu Liu,Guanhua Xue,Chao Yan,Jinghua Cui,Han-Qing Zhao,Yan-Ling Feng,Lin Gan,Qun Zhang,Chen Chen,Di Liu,Jing Yuan

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