Remote Sensing between Liver and Intestine: Importance of Microbial Metabolites.
Remote Sensing between Liver and Intestine: Importance of Microbial Metabolites.
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DOI：
10.1007/s40495-017-0087-0
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发表时间：
2017-06
影响因子：
--
通讯作者：
Cui JY
中科院分区：
文献类型：
--
作者：
Fu ZD;Cui JY
最近的技术进步，包括宏基因组测序和代谢组学，使人们能够发现肠道微生物群在肥胖、营养不良、神经系统疾病、哮喘和外源代谢中的关键功能。人们提出将人类肠道微生物组分类为不同的“肠型”，以作为理解微生物变异与人类疾病表型之间相互作用的新范式，因为许多器官在疾病发病过程中受到肠道微生物组改变的影响。肠道微生物群通过被吸收到体循环中的各种微生物代谢物与宿主的肝脏和其他代谢器官远程相互作用。本综述总结了有关肠道微生物群在调节各种宿主器官的生理和病理反应中的重要性的最新文献，并描述了参与该遥感过程的已知微生物代谢物的功能，主要关注肠道微生物群-肝脏轴。在生理条件下，肠道微生物群调节肝脏转录组、蛋白质组和代谢组，最显着的是下调细胞色素 P450 3a 介导的异生物质代谢。肠道微生物组还可能通过微生物代谢物（例如充当表观遗传修饰剂的丁酸盐和丙酸盐）来调节肝脏基因表达的节律性。此外，宿主激素（例如初级胆汁酸和胰高血糖素样肽 1）的产生会被肠道微生物群改变，从而改变宿主的中间代谢。肠道菌群失调与多种肝脏疾病有关，如酒精性肝病、非酒精性脂肪性肝炎、肝硬化、胆管炎和肝癌。益生菌和益生元等肠道微生物群调节剂越来越被认为是肝脏和其他类型人类疾病的新型治疗方式。
Recent technological advancements including metagenomics sequencing and metabolomics have allowed the discovery of critical functions of gut microbiota in obesity, malnutrition, neurological disorders, asthma, and xenobiotic metabolism. Classification of the human gut microbiome into distinct “enterotypes” has been proposed to serve as a new paradigm for understanding the interplay between microbial variation and human disease phenotypes, as many organs are affected by gut microbiota modifications during the pathogenesis of diseases. Gut microbiota remotely interacts with liver and other metabolic organs of the host through various microbial metabolites that are absorbed into the systemic circulation. The present review summarizes recent literature regarding the importance of gut microbiota in modulating the physiological and pathological responses of various host organs, and describes the functions of the known microbial metabolites that are involved in this remote sensing process, with a primary focus on the gut microbiota-liver axis. Under physiological conditions, gut microbiota modulates the hepatic transcriptome, proteome, and metabolome, most notably down-regulating cytochrome P450 3a mediated xenobiotic metabolism. Gut microbiome also modulates the rhythmicity in liver gene expression, likely through microbial metabolites, such as butyrate and propionate that serve as epigenetic modifiers. Additionally, the production of host hormones such as primary bile acids and glucagon like peptide 1 is altered by gut microbiota to modify intermediary metabolism of the host. Dysregulation of gut microbiota is implicated in various liver diseases such as alcoholic liver disease, non-alcoholic steatohepatitis, liver cirrhosis, cholangitis, and liver cancer. Gut microbiota modifiers such as probiotics and prebiotics are increasingly recognized as novel therapeutic modalities for liver and other types of human diseases.