ArticleMolecular medicine (Cambridge, Mass.)2025
High-salt diet decreases FOLFOX efficacy via gut bacterial tryptophan metabolism in colorectal cancer.
Article in Molecular medicine (Cambridge, Mass.), 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed.
- Exploring the gut microbiome and metabolomic interactions of antimetabolite drugs to optimize therapy.Gut microbes · 2026Review
- Spatiotemporal dynamics of the host-tumor metabolic interface: Implications for precision nutritional oncology.Genes & diseases · 2026Review
- High-salt diet in macrophage-associated metabolic disorders: Mechanisms and therapeutic implications.Chinese medical journal · 2026Review
- Therapeutic Potential of Polysaccharide-Modulated Gut Microbiota-Immune Axis in Gastrointestinal Cancers: Modern Insights From Traditional Pharmacy.Molecular nutrition & food research · 2026Review
- Gut microbiota drives cancer evolution and therapy resistance.Molecular cancer · 2026Review
- Investigating tryptophan metabolism in colorectal cancer using Single-cell RNA sequencing based on machine learning techniques.PloS one · 2026Article
- From high-salt diet to cancer immunity: gut microbiota and immune system interactions and their mechanisms.Frontiers in immunology · 2026Review
- Gut microbiome-shaped chemotherapy responses across cancer types: mechanisms of resistance, biomarkers, and targeted interventions.Frontiers in immunology · 2026Review
- Crosstalk between mFrontiers in immunology · 2026Review
- Global burden of gastric cancer attributed to high-salt diets: spatiotemporal trends and socio-demographic inequalities from 1990 to 2021.Journal of gastrointestinal oncology · 2025Article
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- Gut microbiota-derived metabolites in immunomodulation and gastrointestinal cancer immunotherapy.Frontiers in immunology · 2025Review
- The burden of gastric cancer attributed to high salt intake and predictions through the year 2042: a cross-national comparative analysis of China, Japan, and South Korea.Frontiers in nutrition · 2025Article
- Global, regional, and national burden of gastric cancer attributable to diet high in sodium from 1990 to 2021.Frontiers in nutrition · 2025Article
- Microbial metabolites and their influence on the tumor microenvironment.Frontiers in immunology · 2025Review
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Authors and funding
14 authors.
Funding
Abstract
backgroundFOLFOX is the recommended chemotherapy regimen for colorectal cancer (CRC), but its response rate remains low. Our previous studies have established a close relationship between gut microbiota and the anti-CRC effect of FOLFOX, though the underlying mechanisms remain unclear. Diet has been confirmed as a key factor influencing gut microbiota, and high-salt diets, representative of western dietary habits, has been shown to affect gut microbiota, immune function, and the risk of developing CRC. However, the impact of high-salt diets on the anti-CRC efficacy of FOLFOX remains unstudied. Therefore, we aimed to investigate the effect and mechanism of high-salt diets on the anti-CRC effect of FOLFOX.
methodsWe performed 16 S rRNA sequencing and T500 targeted metabolomics analysis on fecal samples from CRC patients and healthy adults. A CRC orthotopic xenograft mouse model was used to study the effect of a high-salt diet on FOLFOX's anti-CRC efficacy. 16 S rRNA sequencing and non-targeted metabolomics were conducted on mouse fecal samples. Flow cytometry was used to assess immune cell infiltration in tumor and paracancerous tissues. A mouse macrophage conditioned medium system, with tryptophan metabolites, was employed to annotate the functional metabolites, followed by in vivo verification using the orthotopic xenograft mouse model.
resultsThe structure and metabolic profiles of gut microbiota are significantly different between 9 healthy adults and 6 CRC patients. A high-salt diet significantly reduced the efficacy of FOLFOX in mice, with notable changes in gut microbiota and related metabolites. Correlation analysis revealed a significant relationship between gut microbiota, tryptophan metabolites and FOLFOX efficacy. Flow cytometry indicated that a high-salt diet altered macrophage infiltration (CD45
conclusionA high-salt diet reduces the anti-CRC efficacy of FOLFOX through gut bacterial tryptophan metabolism mediated macrophage immunomodulation.
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