Key Laboratory of Integrative Chinese and Western Medicine for the Diagnosis and Treatment of Circulatory Diseases of Zhejiang Province, The First Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou, 310006 Zhejiang, China.
Department of Gastroenterology, Tongde Hospital of Zhejiang Province, Hangzhou, 310012 Zhejiang, China.
J Immunol Res. 2021 Aug 17;2021:2264737. doi: 10.1155/2021/2264737. eCollection 2021.
Gut microbiota (GM) dysbiosis and bile acid (BA) metabolism disorder play an important role in the pathogenesis of nonalcoholic fatty liver disease (NAFLD). Probiotics had a beneficial effect on NAFLD, but further study is needed to explore probiotics as a potential therapeutic agent to NAFLD. The aim of this study was to investigate the regulatory effect of probiotics on gut microbiota in NAFLD rats and to explore the possible mechanism of probiotics regulating the bile acid receptor farnesoid X receptor/growth factor 15 (FXR/FGF15) signaling pathway in rats. We established a rat model of NAFLD fed with a high-fat diet (HFD) for 14 weeks, which was given different interventions (312 mg/kg/day probiotics or 10 mg/kg/day atorvastatin) from the 7 week. Serum lipids and total bile acids (TBA) were biochemically determined; hepatic steatosis and lipid accumulation were evaluated with HE staining. The expression levels of FXR, FGF15 mRNA, and protein in rat liver were detected. 16S rDNA was used to detect the changes of gut microbiota in rats. Compared with the HFD group, probiotics and atorvastatin significantly reduced serum lipids and TBA levels. And probiotics increased dramatically the expression of FXR, FGF15 mRNA, and protein in the liver. But there were no significant changes in the atorvastatin group. Probiotics and atorvastatin can upregulate the diversity of gut microbiota and downregulate the abundance of pathogenic bacteria in NAFLD model rats. In summary, probiotics alleviated NAFLD in HFD rats via the gut microbiota/FXR/FGF15 signaling pathway.
肠道微生物群（GM）失调和胆汁酸（BA）代谢紊乱在非酒精性脂肪性肝病（NAFLD）的发病机制中起重要作用。益生菌对 NAFLD 有有益的作用，但需要进一步研究来探索益生菌作为治疗 NAFLD 的潜在治疗剂。本研究旨在研究益生菌对 NAFLD 大鼠肠道微生物群的调节作用，并探讨益生菌调节大鼠胆汁酸受体法尼醇 X 受体/生长因子 15（FXR/FGF15）信号通路的可能机制。我们建立了高脂肪饮食（HFD）喂养 14 周的 NAFLD 大鼠模型，从第 7 周开始给予不同干预（312mg/kg/天益生菌或 10mg/kg/天阿托伐他汀）。生化测定血清脂质和总胆汁酸（TBA）；用 HE 染色评估肝脂肪变性和脂质积聚。检测大鼠肝 FXR、FGF15mRNA 和蛋白的表达水平。用 16S rDNA 检测大鼠肠道微生物群的变化。与 HFD 组相比，益生菌和阿托伐他汀显著降低了血清脂质和 TBA 水平。益生菌显著增加了肝中 FXR、FGF15mRNA 和蛋白的表达。但阿托伐他汀组无明显变化。益生菌和阿托伐他汀可上调 NAFLD 模型大鼠肠道微生物群的多样性，并下调其致病菌的丰度。综上所述，益生菌通过肠道微生物群/FXR/FGF15 信号通路缓解 HFD 大鼠的 NAFLD。
