T cell-mediated regulation of the microbiota protects against obesity
T cell-mediated regulation of the microbiota protects against obesity
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DOI：
10.1126/science.aat9351
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发表时间：
2019-07-26
期刊：
影响因子：
56.9
通讯作者：
Round, June L.
中科院分区：
文献类型：
--
作者：
Petersen, Charisse;Bell, Rickesha;Round, June L.
微生物群影响肥胖，但保护免受疾病的生物体仍然未知。在询问宿主-微生物群相互作用的研究中，我们观察到年龄相关代谢综合征（MetS）的发展。脱硫弧菌的扩增和梭菌的损失是该模型中与肥胖相关的关键特征，并且存在于患有MetS的人类中。T细胞依赖性事件是预防疾病所必需的，梭菌的替代拯救了肥胖。梭菌的不适当的免疫球蛋白A靶向和脱硫弧菌的增加拮抗有益梭菌的定殖。转录和代谢分析显示，肥胖宿主的脂质吸收增强。梭菌（而非脱硫弧菌）在无菌小鼠体内定植，下调了控制脂质吸收和减少肥胖的基因。因此，微生物群的免疫控制维持了限制脂质代谢以防止MetS的有益微生物群体。
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.