中药健脾解毒汤（JPJDF）用于结直肠癌（CRC）治疗已有四十多年的历史。 JPJDF 通过调节肠道菌群及其代谢物抑制 CRC 的潜力仍不确定。本研究旨在进一步研究 JPJDF 在 CRC 中的治疗机制。使用氧化偶氮甲烷 (AOM) 和葡聚糖硫酸钠 (DSS) 建立 CAC 小鼠模型。对肠道组织和内容物进行 16S rRNA 基因测序和非靶向代谢组学分析。使用 ELISA 测量 IL-1β 和 TNF-α 的血清水平。利用免疫组织化学评估 Ki67、ZO-1、Occludin、CD68 和 CD206 的表达。此外，进行蛋白质印迹法评估AhR和NF-κB的蛋白表达。JPJDF抑制AOM/DSS处理小鼠的结直肠肿瘤发生，同时还抑制肿瘤细胞增殖并上调紧密连接蛋白的表达。 16S rRNA 基因测序分析结果显示，JPJDF 通过增加有益细菌的丰度来改变肠道微生物群组成。此外，JPJDF 减少了色氨酸代谢，有效减轻了 CAC 小鼠的炎症并显着恢复了肠道屏障功能。分子生物学实验证实JPJDF抑制AhR和M2型肿瘤相关巨噬细胞的表达水平，从而促进抗肿瘤免疫并对CAC生长产生抑制作用。JPJDF可以通过调节肠道菌群来调节色氨酸代谢-AhR途径，减少肠道炎症，改善肠道屏障功能，增强抗肿瘤免疫力，有效抑制CAC生长。Copyright © 2024 The Author(s).由 Elsevier B.V. 出版。保留所有权利。

Traditional Chinese medicine, JianpiJiedu decoction (JPJDF), has been utilized in colorectal cancer (CRC) treatment for over forty years. The potential of JPJDF to inhibit CRC through modulation of intestinal microbiota and their metabolites remains uncertain.This study aims to further investigate the therapeutic mechanisms of JPJDF in CRC.CAC mouse models were developed using azoxymethane (AOM) and dextran sulfate sodium (DSS). Intestinal tissues and contents underwent 16S rRNA gene sequencing and untargeted metabolomics analysis. Serum levels of IL-1β and TNF-α were measured using ELISA. Immunohistochemistry was utilized to assess the expression of Ki67, ZO-1, Occludin, CD68, and CD206. Furthermore, western blotting was performed to evaluate the protein expression of AhR and NF-κB.JPJDF inhibited colorectal tumourigenesis in AOM/DSS treated mice, while also suppressing tumor cell proliferation and upregulating the expression of tight junction proteins. The results of 16S rRNA gene sequencing analysis revealed that JPJDF altered intestinal microbiota composition by increasing the abundance of beneficial bacteria. Additionally, JPJDF reduced tryptophan metabolites, effectively alleviating inflammation and significantly restoring intestinal barrier function in CAC mice. Molecular biology experiments confirmed that JPJDF suppressed the expression levels of AhR and M2-type tumor-associated macrophages, thereby promoting anti-tumor immunity and exerting inhibitory effects on CAC growth.JPJDF can regulate the tryptophan metabolism-AhR pathway by modulating the gut microbiota, reducing intestinal inflammation, improving intestinal barrier function, enhancing anti-tumor immunity, and effectively inhibiting CAC growth.Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.