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基于16S rRNA测序与粪便代谢组学整合探究归芍异功汤对结直肠癌的改善作用

Amelioration of Guishao Yigong Decoction on Colorectal Cancer Through the Integration of 16S rRNA Sequencing and Fecal Metabolomics.

作者信息

Zhou Wenwen, Fan Yuwen, Zhang Xiaoxiao, Liu Meijuan, Jiang Shu, Shang Erxin, Duan Jinao

机构信息

Jiangsu Collaborative Innovation Center of Chinese Medicinal Resources Industrialization, Nanjing University of Chinese Medicine, Nanjing, China.

出版信息

Biomed Chromatogr. 2025 Oct;39(10):e70198. doi: 10.1002/bmc.70198.

Abstract

Guishao Yigong Decoction (GYD), a classical formula, has been used to treat colorectal cancer (CRC) in clinical practices. However, its mechanism is still unclear. Increasing evidence suggests that the gut microbiota may serve as a potential target for treating CRC. Therefore, this study aims to elucidate the amelioration and potential mechanism of GYD on CRC by comprehensively analyzing the metagenome of gut microbiota and fecal metabolome. The results indicated that GYD significantly reduced the number and size of adenomas in the mouse colon, decreased spleen index, alleviated mouse emaciation and rectal bleeding, and protected the colonic barrier. 16S rRNA gene sequencing analysis revealed that GYD could markedly improve the dysbiosis of gut microbiota in CRC mice, increasing the abundance of beneficial bacteria and decreasing the abundance of pathogenic bacteria. Furthermore, the disordered fecal metabolic profiling of CRC mice was notably reversed by GYD. Following GYD administration, metabolites such as thiamine pyrophosphate, 3-methylpentanoic acid, and propanoic acid significantly increased, whereas 2-hydroxy-2-methylpropanoic acid, levodopa, and stearic acid remarkably decreased. Correlation analysis further indicated a close relationship between differential gut microbiota and metabolites. In conclusion, the amelioration of GYD on CRC might involve the regulation of gut microbiota and its metabolism.

摘要

归芍异功汤(GYD)是一种经典方剂,已在临床实践中用于治疗结直肠癌(CRC)。然而,其作用机制仍不清楚。越来越多的证据表明,肠道微生物群可能是治疗CRC的潜在靶点。因此,本研究旨在通过综合分析肠道微生物群的宏基因组和粪便代谢组,阐明GYD对CRC的改善作用及其潜在机制。结果表明,GYD显著减少了小鼠结肠腺瘤的数量和大小,降低了脾脏指数,减轻了小鼠消瘦和直肠出血,并保护了结肠屏障。16S rRNA基因测序分析显示,GYD可显著改善CRC小鼠肠道微生物群的失调,增加有益菌的丰度,降低病原菌的丰度。此外,GYD显著逆转了CRC小鼠粪便代谢谱的紊乱。给予GYD后,焦磷酸硫胺素、3-甲基戊酸和丙酸等代谢物显著增加,而2-羟基-2-甲基丙酸、左旋多巴和硬脂酸显著减少。相关性分析进一步表明,差异肠道微生物群与代谢物之间存在密切关系。总之,GYD对CRC的改善作用可能涉及对肠道微生物群及其代谢的调节。

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