Fu Zidong Donna, Cui Julia Yue
Department of Environmental and Occupational Health Sciences, University of Washington, Seattle WA 98105.
Curr Pharmacol Rep. 2017 Jun;3(3):101-113. doi: 10.1007/s40495-017-0087-0. Epub 2017 Mar 3.
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.
包括宏基因组测序和代谢组学在内的近期技术进步，已使人们发现肠道微生物群在肥胖、营养不良、神经疾病、哮喘和外源性物质代谢中的关键作用。有人提出将人类肠道微生物群分类为不同的“肠型”，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例，因为在疾病发病过程中，许多器官会受到肠道微生物群改变的影响。肠道微生物群通过各种被吸收进入体循环的微生物代谢产物，与宿主的肝脏和其他代谢器官进行远程相互作用。
本综述总结了近期有关肠道微生物群在调节宿主各器官生理和病理反应中的重要性的文献，并描述了参与这一遥感过程的已知微生物代谢产物的功能，主要关注肠道微生物群-肝脏轴。
在生理条件下，肠道微生物群可调节肝脏转录组、蛋白质组和代谢组，最显著的是下调细胞色素P450 3a介导的外源性物质代谢。肠道微生物群还可能通过微生物代谢产物（如作为表观遗传修饰剂的丁酸和丙酸）调节肝脏基因表达的节律性。此外，肠道微生物群会改变宿主激素（如初级胆汁酸和胰高血糖素样肽1）的产生，从而改变宿主的中间代谢。
肠道微生物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治疗肝脏及其他类型人类疾病的新型治疗手段。
