近日，美国犹他大学医学院教授June L. Round及其课题组的最新研究发现T细胞可通过调控微生物群防止肥胖。 这一研究成果于2019年7月26日发表在国际顶尖学术期刊《科学》上。

在对宿主与微生物群相互作用的研究中，课题组人员观察了年龄相关代谢综合征(MetS)的发展。在这个模型中，研究人员观察到了与肥胖相关的两个关键特征：脱硫弧菌的增加和梭状芽胞杆菌的丢失; 这些特征在年龄相关代谢综合征患者中也存在 。T细胞依赖的免疫事件在预防疾病的过程中是必须的，而梭状芽孢杆菌的替代则拯救了肥胖。免疫球蛋白A异常靶向梭状芽孢杆菌和增加的脱硫弧菌拮抗了有益梭状芽孢杆菌的定植。转录和代谢分析结果显示肥胖宿主的脂质吸收增强。在无菌小鼠体内定植梭状芽孢杆菌，而不定植脱硫弧菌，会下调控制脂肪吸收和减少肥胖的基因。因此，微生物群的免疫调节维持了有益的微生物种群，从而抑制脂质代谢来预防代谢综合征的发生。

据介绍，微生物群影响肥胖，然而机体防御肥胖的机制未知。


Title: T cell–mediated regulation of the microbiota protects against obesity

Author: Charisse Petersen, Rickesha Bell, Kendra A. Klag, Soh-Hyun Lee, Raymond Soto, Arevik Ghazaryan, Kaitlin Buhrke, H. Atakan Ekiz, Kyla S. Ost, Sihem Boudina, Ryan M. O’Connell, James E. Cox, Claudio J. Villanueva, W. Zac Stephens, June L. Round

Issue&Volume: Vol 365 Issue 6451

Abstract: 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 Desulfovibrio 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 Desulfovibrio 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 Desulfovibrio, 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.

DOI: 10.1126/science.aat9351

Source: https://science.sciencemag.org/content/365/6451/eaat9351