Abstract
Background: Berberine (BBR) has been extensively reported to inhibit colorectal cancer (CRC) development, though its bioavailability is poor. Nowadays, an increasing number of studies have shown that BBR significantly accumulates in the intestines and could regulate gut microbiota in obesity. The purpose of this study was to further explore the effects of BBR on gut microbiota in Apc min/+ mice receiving a high fat diet (HFD). Methods: Apc min/+ mice received either HFD alone or HFD and BBR for 12 weeks. The intestinal tissues were collected to evaluate the efficiency of BBR on neoplasm development by hematoxylin and eosin staining. Meanwhile, immunohistochemistry was conducted to investigate the effects of BBR on cyclin D1 and β-catenin in colon tissues. Fecal samples were subjected to 16S rRNA sequencing. Results: BBR significantly reduced intestinal tumor development and altered the structure of gut microbiota in Apc min/+ mice fed with an HFD. At the phylum level, it was able to significantly inhibit the increase in Verrucomicrobia. At the genus level, it was able to suppress Akkermansia and elevate some short chain fat acid (SCFA)-producing bacteria. Conclusions: BBR significantly alleviated the development of CRC in Apc min/+ mice fed with HFD and restored the enteric microbiome community.
Highlights
Colorectal cancer (CRC), which progresses from adenomas to adenocarcinomas, is a leading cause of cancer death worldwide [1]
A histological analysis of the tissues from the Apc min/+ mice fed with an high fat diet (HFD) showed that compared with normal crypts, their crypts were dysplasic, and their adenomas appeared with nuclear hyperchromasia and increased nucleus-to-cytoplasmic ratios (Figure 1B)
Immunohistochemistry and Western blot analysis showed that the expressions of cyclin D1 and β-catenin were upregulated in the Apc min/+ mice fed with an HFD, while their expressions in BBR-treated mice were significantly reduced (Figure 2A–C)
Summary
Colorectal cancer (CRC), which progresses from adenomas to adenocarcinomas, is a leading cause of cancer death worldwide [1]. With increasing insight, people have realized that intestinal dysbiosis might be associated with CRC [3]. Berberine (BBR) has been extensively reported to inhibit colorectal cancer (CRC) development, though its bioavailability is poor. An increasing number of studies have shown that BBR significantly accumulates in the intestines and could regulate gut microbiota in obesity. The purpose of this study was to further explore the effects of BBR on gut microbiota in. Apc min/+ mice receiving a high fat diet (HFD). Methods: Apc min/+ mice received either HFD alone or HFD and BBR for 12 weeks. Results: BBR significantly reduced intestinal tumor development and altered the structure of gut microbiota in Apc min/+ mice fed with an HFD. It was able to significantly inhibit the increase in Verrucomicrobia. It was able to suppress Akkermansia and elevate some short chain fat acid (SCFA)-producing bacteria
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