Huang Chengyan, He Yuanhui, Chai Ping, Liu Zongxin, Su Sirui, Zhang Yanhui, Luo Yuelan, Fu Shuiping
Department of Medical Imaging, Fenyang College, Shanxi Medical University, Fengyang, China.
Department of Obstetrics and Gynecology, Beijing Tongren Hospital Affiliated to Capital Medical University, Beijing, China.
Front Microbiol. 2025 Feb 6;16:1480500. doi: 10.3389/fmicb.2025.1480500. eCollection 2025.
Orlistat reduces obesity by inhibiting gastrointestinal lipases, thereby blocking the absorption and accumulation of triglycerides in the intestine. It has been shown to improve lipid metabolism and alter intestinal microbial communities in animals and humans. However, the impact of Orlistat-induced changes in gut microbiota on obesity requires further investigation. In this study, we found that Orlistat significantly improved metabolic disorders, inhibited fat accumulation, and reshaped the structure of intestinal microbiota. Specifically, it reduced α diversity and increased the relative abundance of Verrucomicrobia and Akkermansia. Notably, antibiotic-induced gut microbiota depletion significantly weakened Orlistat's effect on improving metabolic disorders. Furthermore, microbiota transplanted from Orlistat-treated mice effectively alleviated lipid metabolic disorders caused by a high-fat diet. We also observed that Orlistat increased food intake in mice and inhibited the synthesis of appetite-regulating hormones glucose-dependent insulinotropic polypeptide (GIP) and glucagon (Gcg). However, antibiotic-depleted microbiota mitigated this inhibitory effect. Interestingly, although Orlistat altered the gut microbiota of mice, transplanting these microbiota did not inhibit the synthesis of appetite-regulating hormones. In summary, our results suggest that Orlistat can reshape the gut microbiota, and the altered gut microbiota works synergistically with Orlistat to improve metabolic disorders. This improvement is related to the increased abundance of Verrucomicrobia and Akkermansia.
奥利司他通过抑制胃肠道脂肪酶来减轻肥胖，从而阻止甘油三酯在肠道中的吸收和积累。在动物和人类中，奥利司他已被证明可改善脂质代谢并改变肠道微生物群落。然而，奥利司他引起的肠道微生物群变化对肥胖的影响仍需进一步研究。在本研究中，我们发现奥利司他显著改善了代谢紊乱，抑制了脂肪积累，并重塑了肠道微生物群的结构。具体而言，它降低了α多样性，并增加了疣微菌门和阿克曼氏菌的相对丰度。值得注意的是，抗生素诱导的肠道微生物群耗竭显著削弱了奥利司他改善代谢紊乱的作用。此外，从接受奥利司他治疗的小鼠移植的微生物群有效缓解了高脂饮食引起的脂质代谢紊乱。我们还观察到，奥利司他增加了小鼠的食物摄入量，并抑制了食欲调节激素葡萄糖依赖性促胰岛素多肽（GIP）和胰高血糖素（Gcg）的合成。然而，抗生素耗竭的微生物群减轻了这种抑制作用。有趣的是，尽管奥利司他改变了小鼠的肠道微生物群，但移植这些微生物群并未抑制食欲调节激素的合成。总之，我们的结果表明，奥利司他可以重塑肠道微生物群，改变后的肠道微生物群与奥利司他协同作用以改善代谢紊乱。这种改善与疣微菌门和阿克曼氏菌丰度的增加有关。
