B. thetaiotaomicron-derived acetic acid modulate immune microenvironment and tumor growth in hepatocellular carcinoma.

IF 12.2 1区 医学 Q1 GASTROENTEROLOGY & HEPATOLOGY Gut Microbes Pub Date : 2024-01-01 Epub Date: 2024-01-25 DOI:10.1080/19490976.2023.2297846
Hongbin Ma, Liang Yang, Yingchao Liang, Fenghua Liu, Jinxiang Hu, Rui Zhang, Yong Li, Lei Yuan, Feiling Feng
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Abstract

Hepatocellular carcinoma (HCC) is a leading cause of cancer-related deaths worldwide, and emerging evidence suggests that the gut microbiota may play a role in its development and progression. In this study, the association between B. thetaiotaomicron, a gut microbiota species, and HCC recurrence, as well as patient clinical outcomes, was investigated. It was observed that B. thetaiotaomicron-derived acetic acid has the potential to modulate the polarization of pro-pro-inflammatory macrophagess, which promotes the function of cytotoxic CD8+ T cells. The increased biosynthesis of fatty acids was implicated in the modulation of pro-inflammatory macrophages polarization by B. thetaiotaomicron-derived acetic acid. Furthermore, B. thetaiotaomicron-derived acetic acid was found to facilitate the transcription of ACC1, a key enzyme involved in fatty acid biosynthesis, through histone acetylation modification in the ACC1 promoter region. Curcumin, an acetylation modification inhibitor, significantly blocked the inhibitory effects of B. thetaiotaomicron and acetic acid on HCC tumor growth. These findings highlight the potential role of gut microbiota-derived acetic acid in HCC recurrence and patient clinical outcomes, and suggest a complex interplay between gut microbiota, immune modulation, fatty acid metabolism, and epigenetic regulation in the context of HCC development. Further research in this area may provide insights into novel strategies for HCC prevention and treatment by targeting the gut microbiota and its metabolites.

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B. Thetaiotaomicron衍生的乙酸调节肝细胞癌的免疫微环境和肿瘤生长。
肝细胞癌(HCC)是全球癌症相关死亡的主要原因之一,而新出现的证据表明,肠道微生物群可能在其发展和恶化过程中起着一定的作用。本研究调查了肠道微生物群物种 B. thetaiotaomicron 与 HCC 复发以及患者临床预后之间的关系。研究发现,B. thetaiotaomicron 衍生的乙酸有可能调节促炎症巨噬细胞的极化,从而促进细胞毒性 CD8+ T 细胞的功能。脂肪酸生物合成的增加与泰妙菌素衍生乙酸对促炎巨噬细胞极化的调节有关。此外,研究还发现源于B. Thetaiotaomicron的乙酸可通过ACC1启动子区域的组蛋白乙酰化修饰促进参与脂肪酸生物合成的关键酶ACC1的转录。姜黄素是一种乙酰化修饰抑制剂,它能明显阻断B. thetaiotaomicron和乙酸对HCC肿瘤生长的抑制作用。这些发现凸显了肠道微生物群衍生的乙酸在 HCC 复发和患者临床预后中的潜在作用,并表明在 HCC 的发展过程中,肠道微生物群、免疫调节、脂肪酸代谢和表观遗传调控之间存在着复杂的相互作用。该领域的进一步研究可能会为针对肠道微生物群及其代谢产物的新型 HCC 预防和治疗策略提供新的见解。
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来源期刊
Gut Microbes
Gut Microbes Medicine-Microbiology (medical)
CiteScore
18.20
自引率
3.30%
发文量
196
审稿时长
10 weeks
期刊介绍: The intestinal microbiota plays a crucial role in human physiology, influencing various aspects of health and disease such as nutrition, obesity, brain function, allergic responses, immunity, inflammatory bowel disease, irritable bowel syndrome, cancer development, cardiac disease, liver disease, and more. Gut Microbes serves as a platform for showcasing and discussing state-of-the-art research related to the microorganisms present in the intestine. The journal emphasizes mechanistic and cause-and-effect studies. Additionally, it has a counterpart, Gut Microbes Reports, which places a greater focus on emerging topics and comparative and incremental studies.
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