解淀粉芽孢杆菌缓解非酒精性脂肪肝病的作用机制

Mechanisms of Bacillus amyloliquefaciens in alleviating non-alcoholic fatty liver disease

为探讨解淀粉芽孢杆菌缓解非酒精性脂肪肝病(non-alcoholic fatty liver disease,NAFLD)的作用机制,构建高脂饮食诱导的NAFLD小鼠模型,饲喂低、高剂量(10^(6)、10^(8) CFU)解淀粉芽孢杆菌BLCC1-0238予以干预,通过检测血清生理生化指标和肝脏病理变化评估其益生作用,然后利用基因组学和转录组学分别分析其对肠道微生物菌群结构和肝脏脂质代谢的影响,并采用定量逆转录PCR(qRT-PCR)检测小鼠肝脏转录组结果的可靠性。血清指标检测结果显示,解淀粉芽孢杆菌BLCC1-0238干预显著降低了血清中ALT、AST、TC和TG水平;肝组织病理学染色发现,解淀粉芽孢杆菌BLCC1-0238明显减少了肝细胞的脂质沉积。基因组学分析发现,解淀粉芽孢杆菌BLCC1-0238改变了肠道微生物菌群结构,在属水平显著增加了产短链脂肪酸的双歧杆菌相对丰度;肝脏转录组学结果显示,解淀粉芽孢杆菌BLCC1-0238主要抑制了脂肪酸和胆固醇合成等脂质代谢过程。qRT-PCR检测结果验证了转录组学结果的可靠性。综上所述,解淀粉芽孢杆菌BLCC1-0238能通过改变肠道微生物菌群结构,增加双歧杆菌相对丰度,调控肝脏脂质代谢来缓解NAFLD,可以作为预防和治疗NAFLD的候选益生菌加以开发和利用。

To investigate the mechanism of Bacillus amyloliquefaciens BLCC1-0238 in alleviating non-alcoholic fatty liver disease(NAFLD),a mice NAFLD model induced by a high-fat diet was established,and then low and high dose(10^(6) or 10^(8) CFU)B.amyloliquefaciens BLCC1-0238 was used to intervene.The protective effects of B.amyloliquefaciens BLCC1-0238 on the NAFLD mice were evaluated by examining physiochemical indexes in the serum and histopathological changes in the liver.The effects of B.amyloliquefaciens BLCC1-0238 on gut microbiota and hepatic lipid metabolism in the NAFLD mice were analyzed by genomics and transcriptomics,respectively.Quantitative reverse transcription PCR(qRT-PCR)was applied to verify the reliability of transcriptomics results.The results of physiochemical indexes showed that the levels of TC,TG,ALT,and AST were significantly reduced by B.amyloliquefaciens BLCC1-0238 intervention and the liver histopathological changes demonstrated that B.amyloliquefaciens BLCC1-0238 significantly reduced lipid deposition in hepatocytes.The results of genomic analysis showed that B.amyloliquefaciens BLCC1-0238 altered the microbial community structure in the gut,and significantly increased the relative abundance of Bifidobacteria,which produce short chain fatty acids.The liver transcriptomic analysis showed that B.amyloliquefaciens BLCC1-0238 was mainly involved in negative regulation of lipid metabolism pathways,such as fatty acid and cholesterol syntheses.Additionally,qRT-PCR confirmed the reliability of transcriptomic results.Collectively,B.amyloliquefaciens BLCC1-0238 can alleviate mice NAFLD by changing the microbial community structure in the gut and regulating hepatic lipid metabolism.