Key Unit of Modulating Liver to Treat Hyperlipemia SATCM (State Administration of Traditional Chinese Medicine), Guangdong Pharmaceutical University, Guangzhou, China; Guangdong Metabolic Disease Research Center of Integrated Chinese and Western Medicine, Guangzhou, China.
Key Unit of Modulating Liver to Treat Hyperlipemia SATCM (State Administration of Traditional Chinese Medicine), Guangdong Pharmaceutical University, Guangzhou, China; Guangdong Metabolic Disease Research Center of Integrated Chinese and Western Medicine, Guangzhou, China.
Biomed Pharmacother. 2020 Jan;121:109550. doi: 10.1016/j.biopha.2019.109550. Epub 2019 Nov 5.
UNLABELLED: The aging process is accompanied by changes in the gut microbiota and metabolites. This study aimed to reveal the relationship between gut microbiota and the metabolome at different ages, as well as the anti-aging effect of FTZ, which is an effective clinical prescription for the treatment of hyperlipidemia and diabetes. METHODS: In the present study, mice were randomly divided into different age and FTZ treatment groups. The aging-relevant behavioral phenotype the levels of blood glucose, cholesterol, triglycerides, low density lipoprotein cholesterol, free fatty acids, high density lipoprotein-cholesterol and cytokine TNF-α,IL-6, IL-8 in the serum were measured. Changes of serum metabolties were analyzed by ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-Q-TOF/MS). Gut microbiota were identified using 16S rDNA sequencing. RESULTS: Our results indicated that with age, the aging-relevant behavioral phenotype appeared, glucose and lipid metabolism disordered, secretion levels of cytokine TNF-α, IL-6 and IL-8 increased.The Firmicutes/Bacteroidetes ratio changed with age, first increasing and then decreasing, and the microbial diversity and the community richness of the aging mice were improved by FTZ. The abundance of opportunistic bacteria decreased (Lactobacillus murinus, Erysipelatoclostridium), while the levels of protective bacteria such as Butyricimonas, Clostridium and Akkermansia increased. Metabolic analysis identified 24 potential biomarkers and 10 key pathways involving arachidonic acid metabolism, phospholipid metabolism, fatty acid metabolism, taurine and hypotaurine metabolism. Correlation analysis between the gut microbiota and biomarkers suggested that the relative abundance of protective bacteria was negatively correlated with the levels of leukotriene E4, 20-HETE and arachidonic acid, which was different from protective bacteria. CONCLUSION: Shifts of gut microbiota and metabolomic profiles were observed in the mice during the normal aging process, and treatment with FTZ moderately corrected the aging, which may be mediated via interference with arachidonic acid metabolism, sphingolipid metabolism, glycerophospholipid metabolism, taurine and hypotaurine metabolism and gut microbiota in mice.
未加标签：衰老过程伴随着肠道微生物群和代谢物的变化。本研究旨在揭示不同年龄肠道微生物群与代谢组之间的关系，以及 FTZ 的抗衰老作用，FTZ 是治疗高血脂和糖尿病的有效临床处方。
方法：本研究中，将小鼠随机分为不同年龄和 FTZ 处理组。测量衰老相关行为表型、血糖、胆固醇、甘油三酯、低密度脂蛋白胆固醇、游离脂肪酸、高密度脂蛋白胆固醇和血清细胞因子 TNF-α、IL-6、IL-8 的水平。采用超高效液相色谱-串联质谱（UPLC-Q-TOF/MS）分析血清代谢物的变化。采用 16S rDNA 测序鉴定肠道微生物群。
结果：结果表明，随着年龄的增长，出现了衰老相关行为表型，葡萄糖和脂质代谢紊乱，细胞因子 TNF-α、IL-6 和 IL-8 的分泌水平增加。厚壁菌门/拟杆菌门比值随年龄变化，先增加后减少，FTZ 改善了衰老小鼠的微生物多样性和群落丰富度。机会菌的丰度下降（乳酸乳球菌、产肠毒素梭菌），而保护性细菌如丁酸杆菌、梭菌和阿克曼氏菌的水平增加。代谢分析鉴定出 24 个潜在生物标志物和 10 个涉及花生四烯酸代谢、磷脂代谢、脂肪酸代谢、牛磺酸和次牛磺酸代谢的关键途径。肠道微生物群与生物标志物的相关性分析表明，保护性细菌的相对丰度与白三烯 E4、20-HETE 和花生四烯酸的水平呈负相关，这与保护性细菌不同。
结论：在正常衰老过程中，小鼠的肠道微生物群和代谢组图谱发生了变化，FTZ 的治疗适度纠正了衰老，这可能是通过干扰花生四烯酸代谢、鞘脂代谢、甘油磷脂代谢、牛磺酸和次牛磺酸代谢以及小鼠的肠道微生物群来实现的。
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