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青春双歧杆菌 CGMCC 15058 可减轻 D-半乳糖胺处理大鼠的肝损伤,增强肠道屏障功能,并改变肠道微生物群。

Bifidobacterium adolescentis CGMCC 15058 alleviates liver injury, enhances the intestinal barrier and modifies the gut microbiota in D-galactosamine-treated rats.

机构信息

State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, Zhejiang University, Qingchun Road 79, Hangzhou, 31003, People's Republic of China.

Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Hangzhou, China.

出版信息

Appl Microbiol Biotechnol. 2019 Jan;103(1):375-393. doi: 10.1007/s00253-018-9454-y. Epub 2018 Oct 22.

Abstract

Acute liver failure is a drastic, unpredictable clinical syndrome with high mortality. Various preventive and adjuvant therapies based on modulating the gut flora have been proposed for hepatic injury. We aimed to explore the preventive and therapeutic effects of Bifidobacterium adolescentis CGMCC15058 on rat liver failure, as well as the potential microecological and immunological mechanisms of those effects. B. adolescentis CGMCC15058 (3 × 10 CFU), isolated from healthy human stool, was gavaged to Sprague-Dawley rats for 14 days. Acute liver injury was induced on the 15th day by intraperitoneal injection of D-galactosamine. After 24 h, liver and terminal ileum histology, liver function, plasma cytokines, bacterial translocation and gut microbiota composition were assessed. We found that pretreatment with B. adolescentis significantly relieved elevated serum levels of alanine aminotransferase (ALT), total bile acid and lipopolysaccharide-binding protein and enhanced the expression of mucin 4 and the tight junction protein zonula occludens-1. B. adolescentis exhibited anti-inflammatory properties as indicated by decreased levels of mTOR and the inflammatory cytokines TNF-α and IL-6, as well as elevated levels of the anti-inflammatory cytokine interleukins-10 in the liver. Similar anti-inflammatory signs were also found in plasma. B. adolescentis significantly altered the microbial community, depleting the common pathogenic taxon Proteus and markedly enriching the taxa Coriobacteriaceae, Bacteroidales and Allobaculum, which are involved in regulating the metabolism of lipids and aromatic amino acids. Our findings not only suggest B. adolescentis acts as a prospective probiotic against liver failure but also provide new insights into the prevention and treatment of liver disease.

摘要

急性肝衰竭是一种严重且不可预测的临床综合征,死亡率较高。各种基于调节肠道菌群的预防和辅助治疗方法已被提出用于肝损伤。我们旨在探索青春双歧杆菌 CGMCC15058 对大鼠肝衰竭的预防和治疗作用,以及这些作用的潜在微生态和免疫学机制。从健康人粪便中分离出青春双歧杆菌 CGMCC15058(3×10 CFU),连续灌胃 14 天。第 15 天通过腹腔注射 D-半乳糖胺诱导急性肝损伤。24 小时后,评估肝脏和末端回肠组织学、肝功能、血浆细胞因子、细菌易位和肠道微生物群组成。我们发现,青春双歧杆菌预处理显著缓解了血清丙氨酸氨基转移酶(ALT)、总胆汁酸和脂多糖结合蛋白的升高,并增强了粘蛋白 4 和紧密连接蛋白 zonula occludens-1 的表达。青春双歧杆菌表现出抗炎特性,表现为 mTOR 水平降低和炎症细胞因子 TNF-α和 IL-6 降低,以及抗炎细胞因子白细胞介素-10 水平升高。在血浆中也发现了类似的抗炎迹象。青春双歧杆菌显著改变了微生物群落,消耗了常见的致病性分类群变形杆菌,显著富集了科里氏菌科、拟杆菌目和 Allobaculum,这些分类群参与调节脂质和芳香族氨基酸的代谢。我们的研究结果不仅表明青春双歧杆菌可作为一种有前途的预防肝衰竭的益生菌,还为预防和治疗肝病提供了新的见解。

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