Dept. of Life Sciences, Central University of Tamil Nadu, Thiruvarur, Tamil Nadu, India.
ER Stress and Mucosal Immunology Lab, School of Health Sciences, University of Tasmania, Launceston, Tasmania, Australia 7248.
Dis Markers. 2022 Feb 8;2022:2941248. doi: 10.1155/2022/2941248. eCollection 2022.
The gut bacterial community is involved in the metabolism of bile acids and short-chain fatty acids (SCFAs). Bile acids are involved in the absorption of fat and the regulation of lipid homeostasis through emulsification and are transformed into unconjugated bile acids by the gut microbiota. The gut microbiota is actively involved in the production of bile acid metabolites, such as deoxycholic acid, lithocholic acid, choline, and SCFAs such as acetate, butyrate, and propionate. Metabolites derived from the gut microbiota or modified gut microbiota metabolites contribute significantly to host pathophysiology. Gut bacterial metabolites, such as deoxycholic acid, contribute to the development of hepatocellular carcinoma and colon cancer by factors such as inflammation and oxidative DNA damage. Butyrate, which is derived from gut bacteria such as , , , and , is associated with the activation of Treg cell differentiation in the intestine through histone acetylation. Butyrate averts the action of class I histone deacetylases (HDAC), such as HDAC1 and HDAC3, which are responsible for the transcription of genes such as p21/Cip1, and cyclin D3 through hyperacetylation of histones, which orchestrates G1 cell cycle arrest. It is essential to identify the interaction between the gut microbiota and bile acid and SCFA metabolism to understand their role in gastrointestinal carcinogenesis including colon, gastric, and liver cancer. Metagenomic approaches with bioinformatic analyses are used to identify the bacterial species in the metabolism of bile acids and SCFAs. This review provides an overview of the current knowledge of gut microbiota-derived bile acid metabolism in tumor development and whether it can stand as a marker for carcinogenesis. Additionally, this review assesses the evidence of gut microbiota-derived short-chain fatty acids including butyric acid in antitumor activity. Future research is required to identify the beneficial commensal gut bacteria and their metabolites which will be considered to be therapeutic targets in inflammation-mediated gastrointestinal cancers.
肠道细菌群落参与胆汁酸和短链脂肪酸 (SCFA) 的代谢。胆汁酸通过乳化作用参与脂肪吸收和脂质动态平衡的调节，并被肠道微生物群转化为非共轭胆汁酸。肠道微生物群积极参与胆汁酸代谢物的产生，如脱氧胆酸、石胆酸、胆碱和 SCFA，如乙酸盐、丁酸盐和丙酸盐。源自肠道微生物群或修饰的肠道微生物群代谢物的代谢物对宿主病理生理学有重要贡献。肠道细菌代谢物，如脱氧胆酸，通过炎症和氧化 DNA 损伤等因素，有助于肝癌和结肠癌的发展。而来源于肠道细菌，如 、 、 、 等的丁酸盐，通过组蛋白乙酰化与肠道中 Treg 细胞分化的激活有关。丁酸盐通过组蛋白的过度乙酰化来避免 I 类组蛋白去乙酰化酶（HDAC）的作用，如 HDAC1 和 HDAC3，这些酶负责 p21/Cip1 等基因的转录，以及通过组蛋白乙酰化来协调 G1 细胞周期停滞。识别肠道微生物群与胆汁酸和 SCFA 代谢之间的相互作用对于理解它们在包括结肠癌、胃癌和肝癌在内的胃肠道致癌作用至关重要。采用生物信息学分析的宏基因组学方法来鉴定胆汁酸和 SCFA 代谢中的细菌种类。这篇综述概述了肠道微生物群衍生的胆汁酸代谢在肿瘤发展中的作用及其是否可以作为致癌作用的标志物。此外，这篇综述评估了肠道微生物群衍生的短链脂肪酸（包括丁酸）在抗肿瘤活性中的证据。需要进一步的研究来鉴定有益的共生肠道细菌及其代谢物，这些代谢物将被视为炎症介导的胃肠道癌症的治疗靶点。
