Laboratory for Intestinal Ecosystem, RIKEN Center for Integrative Medical Sciences, Suehiro-cho, Tsurumi-ku, Yokohama, Kanagawa, Japan.
Intestinal Microbiota Project, Kanagawa Institute of Industrial Science and Technology, Sakado, Takatsu-ku, Kawasaki, Kanagawa 213-0012, Japan.
Int Immunol. 2020 Sep 30;32(10):629-636. doi: 10.1093/intimm/dxaa041.
The gut microbiota strongly impacts the physiology and pathology in the host. To understand the complex interactions between host and gut microbiota, an 'integrated omics' approach has been employed, where exhaustive analyses for the different layers of cellular functions, such as epigenomics, transcriptomics and metabolomics, in addition to metagenomics, are combined. With this approach, the mechanisms whereby short-chain fatty acids (SCFAs) regulate host defense and the immune system have been elucidated. In a gnotobiotic mouse model of enterohemorrhagic Escherichia coli infection, Bifidobacterium-derived acetate can protect from infection-mediated death by changing the gene expression profile of colonic epithelial cells. It has also been shown that gut microbiota-derived butyrate enhances colonic regulatory T-cell differentiation through its epigenetic modulatory ability via histone deacetylase inhibition. SCFAs are involved in many other immunomodulatory effects as well as host pathophysiological conditions. Dysbiosis in the gut has been implicated in the pathogenesis of many diseases. Although the causal relationship of gut microbial dysbiosis and/or metabolites with pathogenesis is mostly unknown, mechanistic insights have been elucidated in some cases. Metabolism in the gut microbiota and host liver produces trimethylamine N-oxide, which is known to aggravate atherosclerosis, and a secondary bile acid deoxycholate, which reportedly induces non-alcoholic steatohepatitis-related hepatocellular carcinoma. It has been reported that secondary bile acids could also induce the differentiation of peripherally derived regulatory T cells in the gut. Further studies on the interactions between the host and gut microbiota could lead to the development of new therapeutic strategies as well as in preventive medicine.
肠道微生物群强烈影响宿主的生理学和病理学。为了了解宿主和肠道微生物群之间的复杂相互作用，采用了一种“综合组学”方法，其中结合了对不同细胞功能层（如表观基因组学、转录组学和代谢组学）的详尽分析，除了宏基因组学之外。通过这种方法，阐明了短链脂肪酸（SCFA）调节宿主防御和免疫系统的机制。在肠出血性大肠杆菌感染的无菌小鼠模型中，双歧杆菌衍生的醋酸盐可以通过改变结肠上皮细胞的基因表达谱来保护免受感染介导的死亡。还表明，肠道微生物群衍生的丁酸盐通过抑制组蛋白去乙酰化酶的表观遗传调节能力增强结肠调节性 T 细胞分化。SCFAs 还参与许多其他免疫调节作用以及宿主病理生理状况。肠道微生物群失调与许多疾病的发病机制有关。尽管肠道微生物群失调和/或代谢物与发病机制的因果关系大多未知，但在某些情况下已阐明了机制见解。肠道微生物群和宿主肝脏的代谢产生三甲胺 N-氧化物，已知其可加重动脉粥样硬化，以及次级胆汁酸脱氧胆酸，据报道可诱导非酒精性脂肪性肝炎相关的肝细胞癌。据报道，次级胆汁酸也可诱导肠道中外周来源的调节性 T 细胞的分化。进一步研究宿主与肠道微生物群之间的相互作用可能会导致开发新的治疗策略以及预防医学。
