Division of Metabolism and Biosystemic Science, Gastroenterology, and Hematology/Oncology, Department of Medicine, Asahikawa Medical University, Asahikawa, Hokkaido, Japan.
Division of Tumor Pathology, Department of Pathology, Asahikawa Medical University, Asahikawa, Hokkaido, Japan.
J Gastroenterol Hepatol. 2023 Oct;38(10):1847-1854. doi: 10.1111/jgh.16337. Epub 2023 Aug 30.
There have been several reports that some probiotics improve non-alcoholic fatty liver disease (NAFLD); however, many studies have involved cocktail therapies. We evaluated whether heat-killed Lactobacillus brevis SBL88 (L. brevis SBL88) monotherapy improves the clinical features of NAFLD.
The NAFLD model was induced in mice fed a high-fat diet (HFD) (HFD mice) or HFD + 1% heat-killed L. brevis SBL88 (SBL mice) for 16 weeks. Histopathological liver findings were analyzed. To evaluate the gut microbiota, a modified terminal restriction fragment length polymorphism analysis of the feces was performed. RNA sequencing in the liver was performed with Ion Proton™. To investigate the direct effects of heat-killed L. brevis SBL88, an in vitro study was performed.
Histopathological findings revealed that fat droplets in the liver were significantly reduced in SBL mice; however, terminal restriction fragment length polymorphism did not show alterations in the gut microbiota between HFD mice and SBL mice. RNA sequencing and pathway analysis revealed that the regulation of lipid and insulin metabolism was affected. The mRNA expression of insulin receptor substrate 2 (IRS-2) was significantly higher in SBL mice, whereas the expression of IRS-1 was not significantly different. Phospho-IRS-2 expression was also significantly increased in SBL mice. In addition, an in vitro study revealed significant alterations in IRS-2 and forkhead box protein O1 expression levels.
SBL mice exhibited partially improved selective hepatic insulin resistance. Our data suggest that heat-killed L. brevis SBL88 could attenuate the clinical features of NAFLD that are not mediated by alterations in the gut microbiota.
有几项报告表明，某些益生菌可改善非酒精性脂肪性肝病（NAFLD）；然而，许多研究都涉及鸡尾酒疗法。我们评估了热灭活短双歧杆菌 SBL88（L. brevis SBL88）单药治疗是否可改善 NAFLD 的临床特征。
用高脂肪饮食（HFD）喂养 NAFLD 模型（HFD 小鼠）或 HFD+1%热灭活 L. brevis SBL88（SBL 小鼠）16 周，分析肝组织病理学发现。为了评估肠道微生物群，对粪便进行改良末端限制性片段长度多态性分析。采用 Ion Proton™进行肝 RNA 测序。为了研究热灭活短双歧杆菌 SBL88 的直接作用，进行了体外研究。
组织病理学结果显示，SBL 小鼠肝内脂肪滴明显减少；然而，末端限制性片段长度多态性分析并未显示 HFD 小鼠和 SBL 小鼠之间肠道微生物群发生变化。RNA 测序和途径分析显示，脂质和胰岛素代谢受到调节。SBL 小鼠胰岛素受体底物 2（IRS-2）的 mRNA 表达显著升高，而 IRS-1 的表达无显著差异。SBL 小鼠磷酸化 IRS-2 表达也显著增加。此外，体外研究显示 IRS-2 和叉头框蛋白 O1 表达水平发生显著变化。
SBL 小鼠表现出部分改善的选择性肝胰岛素抵抗。我们的数据表明，热灭活短双歧杆菌 SBL88 可减轻非酒精性脂肪性肝病的临床特征，而不是通过改变肠道微生物群来介导。
