Probiotic Mixture Attenuates Colorectal Tumorigenesis in Murine AOM/DSS Model by Suppressing STAT3, Inducing Apoptotic p53 and Modulating Gut Microbiota.
- 2024-12-06
- Probiotics and antimicrobial proteins 17(4)
- Hoi Kit Matthew Leung
- Emily Kwun Kwan Lo
- Congjia Chen
- Fangfei Zhang
- Felicianna
- Marsena Jasiel Ismaiah
- Hani El-Nezami
- PubMed: 39641861
- DOI: 10.1007/s12602-024-10405-1
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.
Research Insights
| Supplement | Health Outcome | Effect Type | Effect Size |
|---|---|---|---|
| Lactococcus lactis SD-5584 | Improved Gut Microbiota Composition | Beneficial | Moderate |
| Lactococcus lactis SD-5584 | Reduced Colorectal Tumorigenesis | Beneficial | Large |
| Lactococcus lactis SD-5584 | Reduced Proinflammatory Signaling | Beneficial | Moderate |