长双歧杆菌CCFM1077缓解小鼠肝内胆汁淤积症的作用机制
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R 151.3

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国家“十四五”重点研发计划项目(2022YFD2100704)


Mechanism of Action of Bifidobacterium longum CCFM1077 in Alleviating Intrahepatic Cholestasis in Mice
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    摘要:

    肝内胆汁淤积症是一种胆汁分泌及排泄异常引起的病理状态,对人体健康有不利影响。使用α-萘异硫氰酸酯(ANIT)构建肝内胆汁淤积小鼠模型,探究长双歧杆菌CCFM1077(Bifidobacterium longum CCFM1077)对该症状的缓解作用。结果表明,B. longum CCFM1077可显著改善ANIT诱导的小鼠肝脏组织损伤,降低血清中谷草转氨酶(AST)、谷丙转氨酶(ALT)、碱性磷酸酶(ALP)等主要肝功能相关酶水平以及胆汁酸(BAs)浓度。此外,B. longum CCFM1077可能通过激活肠-肝轴FXR-FGF-15信号通路来上调fxr基因的表达,进而抑制BAs合成基因cyp7a1的表达。该菌株可显著提高具有高胆盐水解酶活性的乳杆菌属、双歧杆菌属等肠道共生菌的相对丰度,降低小鼠肝脏中结合态BAs(T-β-MCA、TCDCA、TUDCA)水平,升高游离态BAs(CDCA、CA、DCA、UDCA)水平,进而促进BAs排出体外。B. longum CCFM1077可降低小鼠肠道中志贺氏埃希氏菌属的相对丰度,升高Ruminococcaceae_UCG_014菌属的相对丰度。这些结果表明B. longum CCFM1077能够通过抑制BAs的合成代谢来缓解肝内胆汁淤积,这与菌株调控小鼠肠道菌群结构有关。

    Abstract:

    Intrahepatic cholestasis is a pathological condition caused by abnormal bile secretion and excretion, which has a adverse impact on human health. A typical model of intrahepatic cholestasis induced by α-naphthylisothiocyanate (ANIT) was constructed to investigate the alleviating effect of Bifidobacterium longum CCFM1077 on intrahepatic cholestasis in mice. The results showed that B. longum CCFM1077 could ameliorate liver histological damage induced by ANIT, reducing the levels of major liver function-related enzymes in serum such as aspartate aminotransferase (AST), alanine transaminase (ALT), and alkaline phosphatase (ALP), as well as the levels of bile acids (BAs). Furthermore, B. longum CCFM1077 could significantly upregulate the expression of fxr gene by activating the enterohepatic axis FXR-FGF-15 signaling, thereby inhibiting the expression of cyp7a1, a gene involved in the synthesis of BAs. This strain significantly increased the abundance of gut commensals, such as Lactobacillus and Bifidobacterium, with high bile salt hydrolase activity, decreased the levels of bound BAs (T-β-MCA, TCDCA, and TUDCA) in the liver of mice, and increased the levels of free BAs (CDCA, CA, DCA, and UDCA), thus promoting BAs excretion. B. longum CCFM1077 also reduced the relative abundance of Escherichia_Shigella and upregulated the relative abundance of Ruminococcaceae_UCG_014 in the intestine of mice. These results indicate that intervention with B. longum CCFM1077 can inhibit the anabolism of BAs to alleviate intrahepatic cholestasis, which may be related to the regulation of the strain on the gut microbiota structure of mice.

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柳雅茹,于雷雷,张程程,张青松,田丰伟,翟齐啸.长双歧杆菌CCFM1077缓解小鼠肝内胆汁淤积症的作用机制[J].食品与生物技术学报,2024,43(4):62-71.

LIU Ya-ru, YU Lei-lei, ZHANG Cheng-cheng, ZHANG Qing-song, TIAN Feng-wei, ZHAI Qi-xiao. Mechanism of Action of Bifidobacterium longum CCFM1077 in Alleviating Intrahepatic Cholestasis in Mice[J]. Journal of Food Science and Biotechnology,2024,43(4):62-71.

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  • 在线发布日期: 2024-05-27
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