Probiotic Mixture Attenuates Colorectal Tumorigenesis in Murine AOM/DSS Model by Suppressing STAT3, Inducing Apoptotic p53 and Modulating Gut Microbiota.

IF 4.4 2区 生物学 Q1 BIOTECHNOLOGY & APPLIED MICROBIOLOGY
Hoi Kit Matthew Leung, Emily Kwun Kwan Lo, Congjia Chen, Fangfei Zhang, Felicianna, Marsena Jasiel Ismaiah, Hani El-Nezami
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引用次数: 0

Abstract

Colorectal cancer (CRC) is one of the most common cancers worldwide. The standard CRC chemo drug, 5-Fluorouracil (5-FU), has a poor response rate and chemoresistance, prompting the need for a more effective and affordable treatment. In this study, we aimed to evaluate whether Prohep, a novel probiotic mixture, would alleviate azoxymethane/dextran sodium sulfate (AOM/DSS)-induced colorectal tumorigenesis and enhance 5-FU efficacy and its mechanism. Our results suggested that Prohep showed stronger anti-tumorigenesis effects than 5-FU alone or when combined in the AOM/DSS model. Prohep significantly reduced the total tumor count, total tumor size, caecum weight, colonic crypt depth, colonic inflammation, and collagen fibrosis. Prohep downregulated pro-inflammatory TNF-α and proliferative p-STAT3 and upregulated apoptotic p53. Metagenomics analysis indicated that Prohep-enriched Helicobacter ganmani, Desulfovibrio porci, Helicobacter hepaticus, and Candidatus Borkfalkia ceftriaxoniphila were inversely correlated to the total tumor count. In addition, Prohep-enriched Prevotella sp. PTAC and Desulfovibrio porci were negatively correlated to AOM/DSS enriched bacteria, while forming a co-existing community with other beneficial bacteria. From KEGG analysis, Prohep downregulated CRC-related pathways and enhanced pathways related to metabolites suppressing CRC like menaquinone, tetrapyrrole, aminolevulinic acid, and tetrahydrofolate. From Metacyc analysis, Prohep downregulated CRC-related peptidoglycan, LPS, and uric acid biosynthesis, and conversion. Prohep elevated the biosynthesis of the beneficial L-lysine, lipoic acid, pyrimidine, and palmitate. Prohep also elevated metabolic pathways related to energy utilization of lactic acid-producing bacteria (LAB) and acetate producers. Similarly, fecal acetate concentration was upregulated by Prohep. To sum up, Prohep demonstrated exceptional anti-tumorigenesis effects in the AOM/DSS model, which revealed its potential to develop into a novel CRC therapeutic in the future.

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来源期刊
Probiotics and Antimicrobial Proteins
Probiotics and Antimicrobial Proteins BIOTECHNOLOGY & APPLIED MICROBIOLOGYMICROB-MICROBIOLOGY
CiteScore
11.30
自引率
6.10%
发文量
140
期刊介绍: Probiotics and Antimicrobial Proteins publishes reviews, original articles, letters and short notes and technical/methodological communications aimed at advancing fundamental knowledge and exploration of the applications of probiotics, natural antimicrobial proteins and their derivatives in biomedical, agricultural, veterinary, food, and cosmetic products. The Journal welcomes fundamental research articles and reports on applications of these microorganisms and substances, and encourages structural studies and studies that correlate the structure and functional properties of antimicrobial proteins.
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