Sharma Nisha, Navik Umashanker, Tikoo Kulbhushan
Laboratory of Epigenetics and Diseases, Department of Pharmacology and Toxicology, National Institute of Pharmaceutical Education and Research, S.A.S. Nagar, Punjab-160062, India.
Laboratory of Epigenetics and Diseases, Department of Pharmacology and Toxicology, National Institute of Pharmaceutical Education and Research, S.A.S. Nagar, Punjab-160062, India.
J Nutr Biochem. 2020 Oct;84:108442. doi: 10.1016/j.jnutbio.2020.108442. Epub 2020 Jun 2.
Gut dysbiosis, particularly bacteria from Firmicutes and Bacteroidetes phyla, plays a fundamental role in the progression of metabolic disorders. Probiotics have shown to restore the gut microbiota composition in metabolic disorders with subsequent beneficial effects. Recent studies have reported that several species of Lactobacillus as probiotic supplementation improve insulin sensitivity and glucose metabolism. Nonetheless, whether Lactobacillus could influence the epigenetic modifications that underlie insulin-resistant conditions is still unexplored. Therefore, the current study examined the therapeutic effects and underlying epigenetic mechanisms of three different species of Lactobacillus in the high-fat diet (HFD)-induced insulin-resistant rats. Three different species of Lactobacillus; Lactobacillus casei, Lactobacillus gasseri, and Lactobacillus rhamnosus were individually supplemented orally (10 CFU/mL) to insulin-resistant SD rats for 12 weeks. Lactobacillus supplementation led to a significant reduction in the hyperglycemia, hyperinsulinemia, and hyperlipidemia associated with HFD-induced insulin resistance. Histopathological examination also indicated the protective effects of Lactobacillus supplementation against the hepatic and intestinal damage caused by the high-fat diet. Lactobacillus supplementation also down-regulated the expression of FOXO1, a major transcription factor of insulin signaling. In addition, at the epigenetic level, Lactobacillus supplementation predominantly prevented methylation and demethylation of H3K79me2 and H3K27me3, respectively. Chromatin Immunoprecipitation (ChIP) coupled with quantitative PCR (ChIP-qPCR) assay revealed the presence of cross-talk between these two histone modifications at the promoter region of FOXO1. Taken together, this is the first report to observe that the effects of Lactobacillus supplementation involve alteration in FOXO1 expression via cross-talking between H3K79me2 and H3K27me3 histone modifications.
肠道微生物群失调，尤其是厚壁菌门和拟杆菌门的细菌，在代谢紊乱的进展中起重要作用。益生菌已被证明可恢复代谢紊乱中的肠道微生物群组成，随后产生有益效果。最近的研究报道，几种作为益生菌补充剂的乳酸杆菌物种可改善胰岛素敏感性和葡萄糖代谢。然而，乳酸杆菌是否会影响胰岛素抵抗状态下的表观遗传修饰仍未得到探索。因此，本研究考察了三种不同的乳酸杆菌物种对高脂饮食（HFD）诱导的胰岛素抵抗大鼠的治疗作用及其潜在的表观遗传机制。将三种不同的乳酸杆菌物种；干酪乳杆菌、加氏乳杆菌和鼠李糖乳杆菌分别以口服方式（10 CFU/mL）补充给胰岛素抵抗的SD大鼠，持续12周。补充乳酸杆菌导致与HFD诱导的胰岛素抵抗相关的高血糖、高胰岛素血症和高脂血症显著降低。组织病理学检查还表明，补充乳酸杆菌对高脂饮食引起的肝脏和肠道损伤具有保护作用。补充乳酸杆菌还下调了胰岛素信号的主要转录因子FOXO1的表达。此外，在表观遗传水平上，补充乳酸杆菌主要分别预防了H3K79me2和H3K27me3的甲基化和去甲基化。染色质免疫沉淀（ChIP）与定量PCR（ChIP-qPCR）分析相结合，揭示了在FOXO1启动子区域这两种组蛋白修饰之间存在相互作用。综上所述，这是第一份观察到补充乳酸杆菌的作用涉及通过H3K79me2和H3K27me3组蛋白修饰之间的相互作用改变FOXO1表达的报告。
