生物钟与肠道菌群调控哺乳动物能量代谢研究进展

Research progress on the regulation of mammalian energy metabolism by the circadian clock system and gut microbiota

生物钟作为哺乳动物进化过程中产生的一种适应机体内外环境昼夜变化的内在机制,控制着机体的睡眠-觉醒及进食等生理活动,使生物体在每个昼夜周期的能量需求和营养供给呈现出与环境相适应的节律性变化。哺乳动物的肝脏、骨骼肌、胰腺、心血管等组织的葡萄糖代谢、脂质代谢和激素分泌等都受到生物钟的调控。作为宿主特殊的“器官”,肠道菌群在共同进化过程中与宿主微环境(组织、细胞、代谢产物)构成了一个微生态系统,在宿主对营养物质的消化和吸收过程中发挥重要作用。近年来的一些研究证据表明,肠道菌群的构成、数量、定植以及功能活动均具有显著的昼夜节律性变化,而这与生物钟调控下的各种生理功能变化是密切相关的。此外,有研究发现肠道菌群可通过分解宿主无法消化的膳食纤维等营养物质产生短链脂肪酸等代谢产物,部分代谢产物具有调节宿主生物钟并影响代谢的功能。本文将重点阐述生物钟与肠道菌群的互作及其对哺乳动物能量代谢的影响,以期为代谢性疾病的预防和治疗提供新的线索和思路。

The mammalian internal circadian clock system has been evolved to adapt to the diurnal changes in the internal and external environment of the organism to regulate diverse physiological functions,such as the sleep-wake cycle and feeding rhythm,thereby coordinating the rhythmic changes of energy demand and nutrition supply in each diurnal cycle.The circadian clock regulates glucose metabolism,lipid metabolism,and hormones secretion in diverse tissues and organs,including the liver,skeletal muscle,pancreas,heart,and vessels.As a special“organ”of the host,the gut microbiota,together with the intestinal microenvironment(tissues,cells,and metabolites)in a co-evolutionary process,constitutes a micro-ecosystem and plays an important role in the process of nutrient digestion and absorption in the intestine of the host.In recent years,accumulating evidence indicates that the compositions,quantities,colonization,and functional activities of the gut microbiota exhibit significant circadian variations,which are closely related to the changes of various physiological functions under the regulation of host circadian clock system.In addition,several studies have shown that the gut microbiota can produce many important metabolites such as the short-chain fatty acids through the degradation of indigestive dietary fibers.A portion of gut microbiota-derived metabolites can regulate the circadian clock system and metabolism of the host.This article mainly discusses the interaction between the host circadian clock system and the gut microbiota,and highlights its influence on energy metabolism of the host,providing a novel clues and thought for the prevention and treatment of metabolic diseases.