本研究的目的是在体外和体内抑制结肠癌细胞生长的过程中，证明小檗碱（BBR）对肠道菌群及相关表观遗传学的调节作用。我们使用HT29结肠癌细胞的裸鼠异种移植模型进行实验，并将其分为模型组和BBR组。小鼠接受为期四周的处理，BBR组的HT29细胞培养了48小时。将Cetuximab和DNA转甲基化酶（DNMT）抑制剂5-AZA-dC添加到HT29细胞中。通过苏木精-伊红（HE）染色进行组织病理学观察，测量肿瘤体积和重量。收集小鼠的粪便，并使用16S rDNA扩增子分析肠道菌群。通过ELISA测量HT29细胞上清液中细胞因子的水平。使用CCK-8试剂盒检测HT29细胞的增殖情况，并使用RT-PCR测量c-Myc、DNMT1、DNMT3A和DNMT3B的水平。我们发现，虽然与模型组相比差异没有统计学意义，但BBR在体外和体内对结肠癌细胞的生长有一定程度上的抑制作用。BBR显著调节了结肠癌小鼠肠道微生物群的丰度、组成和代谢功能。BBR对炎症细胞因子（包括IL-6、FGF和PDGF）的影响不明显，但BBR显著下调了IL-10水平（P < 0.05），并降低了c-Myc、DNMT1和DNMT3B的水平（P < 0.05）。使用5-AZA-dC抑制DNMTs显著抑制了HT29细胞的增殖，这与BBR的效果一致。小檗碱对结肠癌的抑制作用不仅与肠道菌群及其代谢功能有关，还与DNMTs的调节有关。© 2023. 作者，独家许可给Springer Science+Business Media，LLC的一部分，属于Springer Nature。

The purpose of this study was to demonstrate the regulatory effect of berberine (BBR) on the intestinal microbiota and related epigenetics during the inhibition of colon cancer cell growth in vitro and in vivo. We used a nude mouse xenograft model with HT29 colon cancer cells to establish and divide into a model group and BBR group. The mice were treated for four weeks, and HT29 cells in the BBR group were cultured for 48 h. Cetuximab and the DNA transmethylase (DNMT) inhibitor 5-AZA-dC were added to HT29 cells. Tumour volume and weight were measured by hematoxylin-eosin (HE) staining for histopathological observation. Mouse faeces were collected, and the gut microbiota was analysed with 16S rDNA amplicons. The levels of cytokines in the supernatant of HT29 cells were measured by ELISA. A CCK-8 kit was used to examine the proliferation of HT29 cells, and RT‒PCR was used to measure the levels of c-Myc, DNMT1, DNMT3A, and DNMT3B. We found that BBR reduced the growth of colon cancer cells to a certain extent in vitro and in vivo, although the difference was not statistically significant compared with that in the model group. BBR significantly mediated the abundance, composition and metabolic functions of the intestinal microbial flora in mice with colon cancer. The effect of BBR on inflammatory cytokines, including IL-6, FGF, and PDGF, was not obvious, but BBR significantly downregulated IL-10 levels (P < 0.05) and reduced c-Myc, DNMT1, and DNMT3B levels (P < 0.05). Inhibiting DNMTs with 5-AZA-dC significantly suppressed the proliferation of HT29 cells, which was consistent with the effect of BBR. The inhibitory effect of berberine on colon cancer is related not only to the intestinal microbiota and its metabolic functions but also to the regulation of DNMTs.© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.