Raineri Silvia, Sherriff Julia A, Thompson Kevin S J, Jones Huw, Pfluger Paul T, Ilott Nicholas E, Mellor Jane
Department of Biochemistry, University of Oxford, Oxford, OX1 3QU, UK.
Chronos Therapeutics Ltd., Magdalen Centre, The Oxford Science Park, Oxford, OX4 4GA, UK.
BMC Microbiol. 2022 Apr 7;22(1):91. doi: 10.1186/s12866-022-02494-1.
Obesity, metabolic disease and some psychiatric conditions are associated with changes to relative abundance of bacterial species and specific genes in the faecal microbiome. Little is known about the impact of pharmacologically induced weight loss on distinct microbiome species and their respective gene programs in obese individuals.
Using shotgun metagenomics, the composition of the microbiome was obtained for two cohorts of obese female Wistar rats (n = 10-12, total of 82) maintained on a high fat diet before and after a 42-day treatment with a panel of four investigatory or approved anti-obesity drugs (tacrolimus/FK506, bupropion, naltrexone and sibutramine), alone or in combination.
Only sibutramine treatment induced consistent weight loss and improved glycaemic control in the obese rats. Weight loss was associated with reduced food intake and changes to the faecal microbiome in multiple microbial taxa, genes, and pathways. These include increased β-diversity, increased relative abundance of multiple Bacteroides species, increased Bacteroides/Firmicutes ratio and changes to abundance of genes and species associated with obesity-induced inflammation, particularly those encoding components of the flagellum and its assembly.
Sibutramine-induced weight loss in obese rats is associated with improved metabolic health, and changes to the faecal microbiome consistent with a reduction in obesity-induced bacterially-driven inflammation.
肥胖、代谢性疾病和一些精神疾病与粪便微生物群中细菌种类和特定基因的相对丰度变化有关。关于药物诱导的体重减轻对肥胖个体中不同微生物群种类及其各自基因程序的影响，人们知之甚少。
采用鸟枪法宏基因组学，对两组肥胖雌性Wistar大鼠（n = 10 - 12，共82只）进行研究，这些大鼠在接受一组四种研究性或已批准的抗肥胖药物（他克莫司/FK506、安非他酮、纳曲酮和西布曲明）单独或联合治疗42天前后，一直维持高脂饮食。
只有西布曲明治疗能使肥胖大鼠持续减重并改善血糖控制。体重减轻与食物摄入量减少以及多个微生物分类群、基因和途径中粪便微生物群的变化有关。这些变化包括β-多样性增加、多种拟杆菌属物种的相对丰度增加、拟杆菌/厚壁菌比例增加以及与肥胖诱导炎症相关的基因和物种丰度的变化，特别是那些编码鞭毛及其组装成分的基因。
西布曲明诱导肥胖大鼠体重减轻与代谢健康改善以及粪便微生物群的变化有关，这些变化与肥胖诱导的细菌驱动炎症的减少一致。
