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肠道菌群代谢物丁酸盐通过组蛋白去乙酰化酶抑制调控结肠癌免疫微环境的机制与研究进展综述
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Abstract:
结肠癌作为全球高发恶性肿瘤，其发生发展与肠道菌群失调密切相关。丁酸盐作为肠道菌群发酵膳食纤维产生的主要短链脂肪酸，在维持肠道稳态和抑制结肠癌进展中发挥关键作用。近年来研究揭示，丁酸盐通过抑制组蛋白去乙酰化酶活性，调控免疫细胞功能及肿瘤微环境，从而影响结肠癌的免疫逃逸与抗肿瘤免疫应答。然而，现有研究多聚焦于单一细胞类型或信号通路，缺乏对丁酸盐调控结肠癌免疫微环境整体机制的整合性分析。基于此，文章系统综述了丁酸盐的代谢来源、组蛋白去乙酰化酶抑制机制及其对结肠癌免疫微环境中T细胞、巨噬细胞、树突状细胞等多种免疫细胞的调控作用，并探讨了基于丁酸盐的免疫治疗策略及未来研究方向，旨在为结肠癌的精准治疗提供理论依据。
Colorectal cancer is a highly prevalent malignant tumor worldwide, and its occurrence and progression are closely associated with gut microbiota dysbiosis. Butyrate, a major short-chain fatty acid produced by gut microbiota fermenting dietary fiber, plays a vital role in maintaining intestinal homeostasis and restraining colorectal cancer development. Recent studies have demonstrated that butyrate modulates immune cell functions and tumor microenvironment by inhibiting histone deacetylase activity, thereby regulating tumor immune escape and anti-tumor immune responses in colorectal cancer. Nevertheless, most current research focuses on individual cell types or signaling pathways, lacking a comprehensive analysis of the overall mechanism underlying butyrate-mediated regulation of the colorectal cancer immune microenvironment. This paper systematically reviews the metabolic origin of butyrate, its histone deacetylase inhibitory effect, as well as its regulatory impacts on multiple immune cells, including T cells, macrophages, and dendritic cells within the colorectal cancer immune microenvironment. It also discusses butyrate-based immunotherapeutic strategies and future research prospects, aiming to provide theoretical references for the precise treatment of colorectal cancer.
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