锅匠裁缝士兵间谍：科学家破解生物钟被打乱者代谢疾病风险增加的奥秘
既往研究已经明确，肠道菌群是显著影响哺乳动物能量储存和脂肪积累的环境因素。肠道菌群通过肠道代谢活动，从食物获取能量，并转移至脂肪进行储存，该过程与许多其他代谢通路相似，能够通过组成人体生物钟的分子而与昼夜光周期同步，可以解释为什么那些昼夜节律生物钟被打乱者（例如轮班工作或国际旅行）代谢疾病风险增加（包括肥胖、糖尿病、心血管疾病），但是该作用的确切机制尚不明确。
2017年9月1日，美国科学促进会《科学》发表德克萨斯大学西南医学中心、日本理化学研究所、东京理科大学的研究报告，发现肠道菌群可以通过NFIL3和昼夜节律生物钟调节人体脂肪代谢。
受到白细胞介素3（IL3）控制的上皮细胞昼夜节律核转录因子（NF）NFIL3是由Nfil3基因编码的蛋白质，为肠道关键代谢活动中枢。本研究发现，某些肠道菌群产生的鞭毛蛋白和脂多糖，通过固有淋巴细胞3（ILC3）、信号转导及转录激活蛋白3（STAT3）、上皮细胞时钟，调控NFIL3昼夜循环，继而控制脂肪代谢通路的昼夜波动，该通路能调控脂肪的吸收并将其输送到肠道上皮细胞。
因此，上述发现阐明了为什么扰乱生物钟与肠道菌群的相互作用可以导致代谢疾病（包括肥胖、糖尿病、心血管疾病）风险增加。
谨以此文向那些常年三班倒的临床一线工作者致敬！
Science. 2017 Sep 1;357(6354):912-916.
The intestinal microbiota regulates body composition through NFIL3 and the circadian clock.
Wang Y, Kuang Z, Yu X, Ruhn KA, Kubo M, Hooper LV.
The University of Texas Southwestern Medical Center, Dallas, TX, USA; RIKEN Yokohama Institute, Yokohama, Kanagawa, Japan; Tokyo University of Science, Noda-shi, Chiba, Japan.
Light, fat, and commensals
Two signals, light and gut bacteria, interact via immune signaling to regulate host metabolism and health.
The gut microbiota facilitates energy harvest from food and transfers it into fat storage. Working in mice, Wang et al. found that an epithelial cell circadian transcription factor, NFIL3, is involved in regulating body composition through lipid uptake. Flagellin and lipopolysaccharide produced by certain microbes tuned the amplitude of oscillation of NFIL3 through innate lymphoid cell (ILC3) signaling, STAT3, and the epithelial cell clock. Such interactions may help to explain why circadian clock disruptions in humans, arising from shift work or international travel, frequently track with metabolic diseases, including obesity, diabetes, and cardiovascular disease.
The intestinal microbiota has been identified as an environmental factor that markedly affects energy storage and body-fat accumulation in mammals, yet the underlying mechanisms remain unclear. Here we show that the microbiota regulates body composition through the circadian transcription factor NFIL3. Nfil3 transcription oscillates diurnally in intestinal epithelial cells, and the amplitude of the circadian oscillation is controlled by the microbiota through group 3 innate lymphoid cells, STAT3 (signal transducer and activator of transcription 3), and the epithelial cell circadian clock. NFIL3 controls expression of a circadian lipid metabolic program and regulates lipid absorption and export in intestinal epithelial cells. These findings provide mechanistic insight into how the intestinal microbiota regulates body composition and establish NFIL3 as an essential molecular link among the microbiota, the circadian clock, and host metabolism.
PMID: 28860383
DOI: 10.1126/science.aan0677