Department of Clinical Pharmacology, Xiangya Hospital, Central South University, Changsha, 410008, People's Republic of China.
Institute of Clinical Pharmacology, Hunan Key Laboratory of Pharmacogenetics, Central South University, Changsha, 410078, People's Republic of China.
Psychopharmacology (Berl). 2021 Jan;238(1):239-248. doi: 10.1007/s00213-020-05677-8. Epub 2020 Oct 23.
Olanzapine is widely prescribed for patients with mental disorders; however, it may induce metabolic dysfunction. Metformin is an efficient adjuvant for preventing olanzapine-induced metabolic dysfunction in clinical practice. Although the mechanism of how metformin prevents this metabolic dysfunction remains unknown, changes in the gut-liver axis are considered a potential explanation.
Forty-eight male rats were gavaged with olanzapine and/or metformin for 35 consecutive days. Body weight, food intake, and water intake were measured daily. Histopathological and biochemical tests were performed to evaluate the metabolic dysfunction. The 16S rRNA obtained from fecal bacterial DNA was assessed.
Olanzapine treatment increased the body weight, blood glucose and triglyceride levels, and the number of adipocytes in the liver. While coadministration of metformin, there was a dose-dependent reverse of the abnormal changes induced by olanzapine treatment. Both olanzapine and metformin treatments altered the composition of the gut microbiota. Bacteroides acidifaciens and Lactobacillus gasseri were possibly played a positive role in metformin-mediated olanzapine-induced metabolic dysfunction prevention.
Metformin prevented olanzapine-induced metabolic dysfunction and regulated the gut microbiota in a dose-dependent manner.
奥氮平被广泛用于治疗精神障碍患者，但可能会引起代谢功能紊乱。在临床实践中，二甲双胍是一种预防奥氮平引起代谢功能紊乱的有效辅助药物。虽然二甲双胍预防这种代谢功能紊乱的机制尚不清楚，但人们认为肠道-肝脏轴的变化是一个潜在的解释。
48 只雄性大鼠连续 35 天灌胃奥氮平和/或二甲双胍。每天测量体重、食物摄入量和水摄入量。进行组织病理学和生化测试以评估代谢功能紊乱。评估来自粪便细菌 DNA 的 16S rRNA。
奥氮平治疗增加了体重、血糖和甘油三酯水平，以及肝脏中的脂肪细胞数量。而二甲双胍的共同给药，奥氮平治疗引起的异常变化呈剂量依赖性逆转。奥氮平和二甲双胍治疗均改变了肠道微生物群的组成。拟杆菌和戊糖乳杆菌可能在二甲双胍介导的奥氮平诱导的代谢功能紊乱预防中发挥积极作用。
二甲双胍以剂量依赖的方式预防奥氮平引起的代谢功能紊乱并调节肠道微生物群。
