Ysopia Bioscience, 17 place de la Bourse, 33076 Bordeaux, France.
Micalis Institute, INRAE, AgroParisTech, University Paris-Saclay, 78350 Jouy-en-Josas, France.
Cells. 2021 Apr 6;10(4):823. doi: 10.3390/cells10040823.
Obesity is associated with gut microbiota dysbiosis, characterized by a high Firmicutes/Bacteroidetes ratio. Gut-dwelling bacteria of the Christensenellaceae family have been proposed to act as keystones of the human gut ecosystem and to prevent adipogenesis. The objectives of the present study were to demonstrate the antiobesity potential of a new strain of in preclinical models and explore related mechanisms of action. The antiobesity potential of DSM33407 was assessed in a diet-induced obesity mouse model. Changes in hepatic lipid metabolism were explored using targeted transcriptomics. Effects on gut microbiota were further assessed in a humanized Simulator of the Human Intestinal Microbial Ecosystem (SHIME) model inoculated with obese fecal samples. Shotgun metagenomics was applied to study microbial community structures in both models. DSM33407 protected from diet-induced obesity and regulated associated metabolic markers such as glycemia and leptin. It also regulated hepatic lipid metabolism through a strong inhibition of de novo lipogenesis and maintained gut epithelial integrity. In the humanized SHIME model, these effects were associated with modulations of the intestinal microbiota characterized by a decreased Firmicutes/Bacteroidetes ratio. These data indicate that DSM33407 is a convincing therapeutic candidate for the management of obesity and associated metabolic disorders.
肥胖与肠道微生物群落失调有关,其特征是厚壁菌门/拟杆菌门比值较高。Christensenellaceae 科的肠道细菌被认为是人类肠道生态系统的关键,并能防止脂肪生成。本研究的目的是在临床前模型中证明新型菌株 的减肥潜力,并探索相关的作用机制。在饮食诱导的肥胖小鼠模型中评估了 DSM33407 的减肥潜力。使用靶向转录组学探索肝脂质代谢的变化。进一步在接种肥胖粪便样本的人类肠道微生物生态系统模拟器(SHIME)模型中评估对肠道微生物群的影响。 shotgun 宏基因组学用于研究两种模型中的微生物群落结构。DSM33407 可预防饮食诱导的肥胖,并调节相关代谢标志物,如血糖和瘦素。它还通过强烈抑制从头脂肪生成来调节肝脂质代谢,并维持肠道上皮细胞的完整性。在人类 SHIME 模型中,这些作用与肠道微生物群的调节有关,其特征是厚壁菌门/拟杆菌门比值降低。这些数据表明,DSM33407 是治疗肥胖症和相关代谢紊乱的有前途的候选药物。