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A Holistic View of Berberine Inhibiting Intestinal Carcinogenesis in Conventional Mice Based on Microbiome-Metabolomics Analysis.

ABSTRACT: Berberine (BBR) has been reported that it has effects on inhibiting colorectal cancer (CRC). However, the mechanism of BBR on CRC also remains largely unknown. Herein, we investigated the therapeutic effects of BBR on CRC from the perspective of gut microbiota and metabolic alterations, which can provide a holistic view to understand the effects of BBR on CRC. First, azoxymethane (AOM)/dextran sodium sulfate (DSS) mouse was used as CRC animal model, then the degree of colorectal carcinogenesis in AOM/DSS mice with or without BBR administration was measured. The composition and abundance of gut microbiota was investigated by using 16S rRNA. Meanwhile, feces samples were analyzed with 1H NMR spectroscopy to investigate the metabolic alterations. As a result, BBR significantly reduced intestinal tumor development with lower macroscopic polyps and ki-67 expression of intestinal tissue, and better colonic morphology in mice. Moreover, BBR altered the composition of gut microbiota in AOM/DSS mice obviously, which were characterized by a decrease of Actinobacteria and Verrucomicrobia significantly at the phylum level. At the genus level, it was able to suppress pathogenic species, such as f_Erysipelotrichaceae, Alistipes, and elevate some short-chain fatty acids (SCFA)-producing bacteria, including Alloprevotella, Flavonifractor, and Oscillibacter. Metabolic data further revealed that BBR induced metabolic changes in feces focus on regulating glycometabolism, SCFA metabolism and amino acid metabolism, which also provides evidence for alteration of the microbiota because these feces metabolites are the products of interactions between the host and the microbial community. This study showed that BBR induced alterations in microbiota and metabolic in AOM/DSS mice, which might providing new insight into the inhibition effects of BBR on CRC.

SUBMITTER: Chen H

PROVIDER: S-EPMC7541814 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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A Holistic View of Berberine Inhibiting Intestinal Carcinogenesis in Conventional Mice Based on Microbiome-Metabolomics Analysis.

Chen Haitao H Zhang Fan F Zhang Jin J Zhang Xinjie X Guo Yong Y Yao Qinghua Q

Frontiers in immunology 20200924

Berberine (BBR) has been reported that it has effects on inhibiting colorectal cancer (CRC). However, the mechanism of BBR on CRC also remains largely unknown. Herein, we investigated the therapeutic effects of BBR on CRC from the perspective of gut microbiota and metabolic alterations, which can provide a holistic view to understand the effects of BBR on CRC. First, azoxymethane (AOM)/dextran sodium sulfate (DSS) mouse was used as CRC animal model, then the degree of colorectal carcinogenesis i ...[more]

PMID: 33072135

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Project description:BackgroundThe role of Berberine (BBR) in colorectal cancer (CRC) and gut microbiota has begun to appreciate. However, there was no direct evidence confirm that the gut microbiota regulated by BBR could inhibit CRC. This report investigated the effect of stool from BBR treated subjects and its effect on CRC.MethodsA mouse model for CRC was developed using azoxymethane (AOM) and dextran sulfate sodium (DSS). Intestinal tissue from affected mice were used to determine the efficacy of BBR against CRC. Stool samples were collected for the 16s rRNA gene sequencing and fecal microbiota transplantation (FMT). Finally, the mechanism of gut microbiota from BBR treated mice on CRC was explored using immunohistochemistry, RNA-Sequencing, quantitative RT-PCR, and western blot analyses.ResultsBBR significantly reduced intestinal tumor development. The richness of gut microbiota were notably decreased by BBR. Specifically, the relative abundance of beneficial bacteria (Roseburia, Eubacterium, Ruminococcaceae, and Firmicutes_unclassified) was increased while the level of bacteria (Odoribacter, Muribaculum, Mucispirillum, and Parasutterella) was decreased by BBR treatment. FMT experiment determined that the mice fed with stool from BBR treated AOM/DSS mice demonstrated a relatively lower abundance of macroscopic polyps and a significantly lower expression of β-catenin, and PCNA in intestinal tissue than mice fed with stool from AOM/DSS mice. Mechanistically, intestinal tissue obtained from mice fed with stool from BBR treated AOM/DSS mice demonstrated a decreased expression of inflammatory cytokines including interleukin 1β (IL-1β), tumor necrosis factor-α (TNF-α), C-C motif chemokine 1 (Ccl1), Ccl6, and C-X-C motif ligand (Cxcl9). In addition, the NF-κB expression was greatly suppressed in mice fed with stool from BBR treated AOM/DSS mice. Real-time PCR arrays revealed a down-regulation of genes involved in cell proliferation, angiogenesis, invasiveness, and metastasis in mice fed with stool from BBR treated AOM/DSS mice.ConclusionsStool obtained from BBR treated AOM/DSS mice was able to increase colon length while simultaneously decreasing the density of macroscopic polyps, cell proliferation, inflammatory modulators and the expression of NF-κB. Therefore, it was concluded that suppression of pro-inflammatory genes and carcinogens factors by modulating gut microbiota was an important pathway for BBR to inhibit tumor growth in conventional mice.

Project description:This study aimed to investigate the microbial structure and function in the rectum of weaned piglets with berberine supplementation. Twelve healthy 21-day-old Duorc × (Landrace × Large White) weaned piglets (similar body weight) were evenly divided into control and berberine groups and were fed a basal diet supplemented with 0 and 0.1% berberine, respectively. After 21 days, metagenomic sequencing analysis was performed to detect microbial composition and function in the rectum of weaned piglets. Results showed that there were 10,597,721,931-14,059,392,900 base pairs (bp) and 10,186,558,171-15,859,563,342 bp of clean data in the control and berberine groups, respectively. The Q20s of the control and berberine groups were 97.15 to 97.7% and 96.26 to 97.68%, respectively. The microorganisms in the berberine group had lower (p < 0.05) Chao1, alternating conditional expectation, Shannon, and Simpson indices at the species levels than those in the control group. Analysis of similarity showed that there were significant differences (p < 0.01) between the control and berberine groups at the genus and species levels of the gut microorganisms. Dietary berberine significantly increased (p < 0.05) the abundance of Subdoligranulum variabile, but decreased (p < 0.05) the abundance of Prevotella copri compared with the control group. Carbohydrate-active enzymes analysis revealed that the levels of polysaccharide lyases and carbohydrate esterases were lower (p < 0.05) in the berberine group than that in the control group. Linear discriminant analysis effect size analysis showed that berberine supplementation could induce various significant Kyoto Encyclopedia of Genes and Genomes pathways, including carbohydrate metabolism, environmental information processing, and microbial metabolism in diverse environments. In conclusion, our findings suggest that berberine could improve the composition, abundance, structure, and function of gut microbiome in the weaned piglets, potentially providing a suitable approach for the application of berberine in human and animal health.

Dataset Information

A Holistic View of Berberine Inhibiting Intestinal Carcinogenesis in Conventional Mice Based on Microbiome-Metabolomics Analysis.

Publications

A Holistic View of Berberine Inhibiting Intestinal Carcinogenesis in Conventional Mice Based on Microbiome-Metabolomics Analysis.

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