Zhu Airu, Chen Jingjing, Wu Pengfei, Luo Mei, Zeng Yilan, Liu Yong, Zheng Han, Zhang Li, Chen Zishou, Sun Qun, Li Wenwen, Duan Yixiang, Su Danmei, Xiao Zhixiong, Duan Zhongping, Zheng Sujun, Bai Li, Zhang Xiaohui, Ju Zhongyuan, Li Yan, Hu Richard, Pandol Stephen J, Han Yuan-Ping
Center for Growth, Metabolism and Aging, Analytical and Testing Center, Key Laboratory of Bio-resource and Eco-environment, College of Life Sciences, Sichuan University, Chengdu, China.
Public Health Clinical Center of Chengdu, Chengdu, China.
Diabetes. 2017 Aug;66(8):2137-2143. doi: 10.2337/db17-0070. Epub 2017 Apr 26.
A pandemic of metabolic diseases, consisting of type 2 diabetes, nonalcoholic fatty liver disease, and obesity, has imposed critical challenges for societies worldwide, prompting investigation of underlying mechanisms and exploration of low-cost and effective treatment. In this report, we demonstrate that metabolic disorders in mice generated by feeding with a high-fat diet without dietary vitamin D can be prevented by oral administration of polycationic amine resin. Oral administration of cholestyramine, but not the control uncharged polystyrene, was able to sequester negatively charged bacterial endotoxin in the gut, leading to ) reduced plasma endotoxin levels, ) resolved systemic inflammation and hepatic steatohepatitis, and ) improved insulin sensitivity. Gut dysbiosis, characterized as an increase of the phylum Firmicutes and a decrease of Bacteroidetes and was fully corrected by cholestyramine, indicating that the negatively charged components in the gut are critical for the dysbiosis. Furthermore, fecal bacteria transplant, derived from cholestyramine-treated animals, was sufficient to antagonize the metabolic disorders of the recipient mice. These results indicate that the negatively charged components produced by dysbiosis are critical for biogenesis of metabolic disorders and also show a potential application of cationic polystyrene to treat metabolic disorders through promoting gut eubiosis.
由2型糖尿病、非酒精性脂肪性肝病和肥胖组成的代谢性疾病大流行给全球社会带来了严峻挑战，促使人们对其潜在机制进行研究，并探索低成本且有效的治疗方法。在本报告中，我们证明，通过口服聚阳离子胺树脂，可以预防喂食不含膳食维生素D的高脂饮食所导致的小鼠代谢紊乱。口服消胆胺（而非对照性的不带电荷的聚苯乙烯）能够螯合肠道中带负电荷的细菌内毒素，从而导致：（1）血浆内毒素水平降低；（2）全身性炎症和肝脂肪性肝炎得到缓解；（3）胰岛素敏感性提高。以厚壁菌门增加、拟杆菌门减少为特征的肠道菌群失调通过消胆胺得到了完全纠正，这表明肠道中带负电荷的成分对于菌群失调至关重要。此外，源自经消胆胺处理动物的粪便细菌移植足以对抗受体小鼠的代谢紊乱。这些结果表明，菌群失调产生的带负电荷成分对于代谢紊乱的发生至关重要，同时也显示了阳离子聚苯乙烯通过促进肠道微生态平衡来治疗代谢紊乱的潜在应用价值。
