Progression of Colorectal cancer (CRC) is influenced by single or compounded environmental factors. Accumulating evidence shows that microbiota can influence the outcome of cancer immunotherapy. T cell, one of the main populations of effector immune cells in antitumor immunity, has been considered as a double-edged sword during the progression of CRC. Our previous studies indicate that traditional Chinese herbs (TCM) have potential anticancer effects in improving quality of life and therapeutic effect. However, little is known about the mechanism of TCM formula in cancer prevention. Here, we used C57BL/6 J ApcMin/+ mice, an animal model of human intestinal tumorigenesis, to investigate the gut bacterial diversity and their mechanisms of action in gastrointestinal adenomas, and to evaluate the effects of Yi-Yi-Fu-Zi-Bai-Jiang-San (YYFZBJS) on of colon carcinogenesis in vivo and in vitro. Through human-into-mice fecal microbiota transplantation (FMT) experiments from YYFZBJS volunteers or control donors, we were able to differentially modulate the tumor microbiome and affect tumor growth as well as tumor immune infiltration. We report herein, YYFZBJS treatment blocked tumor initiation and progression in ApcMin/+ mice with less change of body weight and increased immune function. Moreover, diversity analysis of fecal samples demonstrated that YYFZBJS regulated animal’s natural gut flora, including Bacteroides fragilis, Lachnospiraceae and so on. Intestinal tumors from conventional and germ-free mice fed with stool from YYFZBJS volunteers had been decreased. Some inflammation’ expression also have been regulated by the gut microbiota mediated immune cells. Intestinal lymphatic, and mesenteric lymph nodes (MLN), accumulated CD4+ CD25+ Foxp3 positive Treg cells were reduced by YYFZBJS treatment in ApcMin/+ mice. Although YYFZBJS had no inhibition on CRC cell proliferation by itself, the altered Tregs mediated by YYFZBJS repressed CRC cancer cell growth, along with reduction of the phosphorylation of β-catenin. In conclusion, we demonstrated that gut microbiota and Treg were involved in CRC development and progression, and we propose YYFZBJS as a new potential drug option for the treatment of CRC.

中文翻译：

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YYFZBJS 通过重塑肠道微生物群和抑制调节性 T 细胞生成来改善 ApcMin/+ 小鼠的结直肠癌进展。

结直肠癌 (CRC) 的进展受单一或复合环境因素的影响。越来越多的证据表明，微生物群可以影响癌症免疫治疗的结果。T细胞是抗肿瘤免疫中效应免疫细胞的主要群体之一，被认为是CRC进展过程中的一把双刃剑。我们之前的研究表明，传统中草药 (TCM) 在改善生活质量和治疗效果方面具有潜在的抗癌作用。然而，人们对中医方剂在癌症预防中的作用机制知之甚少。在这里，我们使用 C57BL/6 J ApcMin/+ 小鼠（一种人类肠道肿瘤发生的动物模型）来研究肠道细菌多样性及其在胃肠道腺瘤中的作用机制，并评价益益附子-白-姜-散 (YYFZBJS) 在体内和体外对结肠癌发生的影响。通过来自 YYFZBJS 志愿者或对照供体的人-小鼠粪便微生物群移植 (FMT) 实验，我们能够差异调节肿瘤微生物组并影响肿瘤生长以及肿瘤免疫浸润。我们在此报告，YYFZBJS 治疗阻止了 ApcMin/+ 小鼠的肿瘤发生和进展，体重变化较小，免疫功能增强。此外，粪便样本的多样性分析表明，YYFZBJS 调节动物的天然肠道菌群，包括脆弱拟杆菌、毛螺菌科等。喂食 YYFZBJS 志愿者粪便的常规和无菌小鼠的肠道肿瘤已经减少。一些炎症的表达也受到肠道微生物群介导的免疫细胞的调节。在 ApcMin/+ 小鼠中，YYFZBJS 治疗减少了肠道淋巴和肠系膜淋巴结 (MLN) 积累的 CD4+ CD25+ Foxp3 阳性 Treg 细胞。尽管 YYFZBJS 本身对 CRC 细胞增殖没有抑制作用，但由 YYFZBJS 介导的改变的 Treg 抑制了 CRC 癌细胞的生长，同时降低了 β-连环蛋白的磷酸化。总之，我们证明肠道微生物群和 Treg 参与了 CRC 的发生和进展，我们建议 YYFZBJS 作为治疗 CRC 的新潜在药物选择。尽管 YYFZBJS 本身对 CRC 细胞增殖没有抑制作用，但由 YYFZBJS 介导的改变的 Treg 抑制了 CRC 癌细胞的生长，同时降低了 β-连环蛋白的磷酸化。总之，我们证明肠道微生物群和 Treg 参与了 CRC 的发生和进展，我们建议 YYFZBJS 作为治疗 CRC 的新潜在药物选择。尽管 YYFZBJS 本身对 CRC 细胞增殖没有抑制作用，但由 YYFZBJS 介导的改变的 Treg 抑制了 CRC 癌细胞的生长，同时降低了 β-连环蛋白的磷酸化。总之，我们证明肠道微生物群和 Treg 参与了 CRC 的发生和进展，我们建议 YYFZBJS 作为治疗 CRC 的新潜在药物选择。