Interdisciplinary Graduate School, Institute for Health Technologies, Nanyang Technological University, Singapore.
Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore.
FASEB J. 2019 Sep;33(9):9706-9730. doi: 10.1096/fj.201802681RR. Epub 2019 Jun 25.
The human gut is colonized by commensal microorganisms, predominately bacteria that have coevolved in symbiosis with their host. The gut microbiota has been extensively studied in recent years, and many important findings on how it can regulate host metabolism have been unraveled. In healthy individuals, feeding timing and type of food can influence not only the composition but also the circadian oscillation of the gut microbiota. Host feeding habits thus influence the type of microbe-derived metabolites produced and their concentrations throughout the day. These microbe-derived metabolites influence many aspects of host physiology, including energy metabolism and circadian rhythm. Peroxisome proliferator-activated receptors (PPARs) are a group of ligand-activated transcription factors that regulate various metabolic processes such as fatty acid metabolism. Similar to the gut microbiota, PPAR expression in various organs oscillates diurnally, and studies have shown that the gut microbiota can influence PPAR activities in various metabolic organs. For example, short-chain fatty acids, the most abundant type of metabolites produced by anaerobic fermentation of dietary fibers by the gut microbiota, are PPAR agonists. In this review, we highlight how the gut microbiota can regulate PPARs in key metabolic organs, namely, in the intestines, liver, and muscle. Knowing that the gut microbiota impacts metabolism and is altered in individuals with metabolic diseases might allow treatment of these patients using noninvasive procedures such as gut microbiota manipulation.-Oh, H. Y. P., Visvalingam, V., Wahli, W. The PPAR-microbiota-metabolic organ trilogy to fine-tune physiology.
人体肠道定植着共生微生物，主要是细菌，它们与宿主共同进化并处于共生关系中。近年来，肠道微生物群已经得到了广泛的研究，许多关于其如何调节宿主代谢的重要发现已经被揭示出来。在健康个体中，喂养时间和食物类型不仅可以影响肠道微生物群的组成，还可以影响其昼夜节律振荡。因此，宿主的喂养习惯会影响微生物衍生代谢物的产生类型及其在一天中的浓度。这些微生物衍生代谢物会影响宿主生理学的许多方面，包括能量代谢和昼夜节律。过氧化物酶体增殖物激活受体（PPARs）是一组配体激活的转录因子，可调节脂肪酸代谢等各种代谢过程。与肠道微生物群类似，各种器官中的 PPAR 表达呈昼夜节律性波动，研究表明，肠道微生物群可以影响各种代谢器官中的 PPAR 活性。例如，短链脂肪酸是肠道微生物群对膳食纤维进行厌氧发酵产生的最丰富的代谢物类型，是 PPAR 激动剂。在这篇综述中，我们强调了肠道微生物群如何调节关键代谢器官（即肠道、肝脏和肌肉）中的 PPAR。了解肠道微生物群会影响代谢并在代谢疾病患者中发生改变，这可能允许使用非侵入性程序（如肠道微生物群操作）来治疗这些患者。
