Department of Pathology, Division of Microbiology and Immunology, University of Utah School of Medicine, Salt Lake City, UT 84112, USA.
Department of Nutrition and Integrative Physiology, College of Health, University of Utah, Salt Lake City, UT 84112, USA.
Science. 2019 Jul 26;365(6451). doi: 10.1126/science.aat9351.
The microbiota influences obesity, yet organisms that protect from disease remain unknown. During studies interrogating host-microbiota interactions, we observed the development of age-associated metabolic syndrome (MetS). Expansion of and loss of Clostridia were key features associated with obesity in this model and are present in humans with MetS. T cell-dependent events were required to prevent disease, and replacement of Clostridia rescued obesity. Inappropriate immunoglobulin A targeting of Clostridia and increased antagonized the colonization of beneficial Clostridia. Transcriptional and metabolic analysis revealed enhanced lipid absorption in the obese host. Colonization of germ-free mice with Clostridia, but not , down-regulated genes that control lipid absorption and reduced adiposity. Thus, immune control of the microbiota maintains beneficial microbial populations that constrain lipid metabolism to prevent MetS.
微生物群影响肥胖，但保护机体免受疾病影响的微生物仍未知。在研究宿主-微生物群相互作用的过程中，我们观察到与年龄相关的代谢综合征（MetS）的发展。在该模型中， 和梭状芽胞杆菌的扩张和损失是与肥胖相关的关键特征，并且存在于患有 MetS 的人类中。需要 T 细胞依赖性事件来预防疾病，而梭状芽胞杆菌的替代可以挽救肥胖。针对梭状芽胞杆菌的不适当免疫球蛋白 A 和增加的 拮抗了有益的梭状芽胞杆菌的定植。转录和代谢分析显示肥胖宿主的脂质吸收增强。用梭状芽胞杆菌而非 定植无菌小鼠可下调控制脂质吸收并减少肥胖的基因。因此，微生物群的免疫控制维持有益的微生物群，限制脂质代谢以预防 MetS。
