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Microbial Metabolites of Flavanols in Urine are Associated with Enhanced Anti-Proliferative Activity in Bladder
Laura E Griffin1, Sarah E Kohrt2,3, Atul Rathore1
1Plants for Human Health Institute, Department of Food, Bioprocessing and Nutrition Sciences, North Carolina State University, Kannapolis, North Carolina, USA.
Abstract:
Flavanols are metabolized by the gut microbiota to bioavailable metabolites, and the absorbed fraction is excreted primarily via urine. Uroepithelial cells are thus a potential site of activity due to exposure to high concentrations of these compounds. Chemoprevention by flavanols may be partly due to these metabolites. In Vitro work in this area relies on a limited pool of commercially available microbial metabolites, and little has been done in bladder cancer. The impact of physiologically relevant mixtures of flavanols and their metabolites remains unknown. Rats were fed various flavanols and urine samples, approximating the bioavailable metabolome, were collected. Urines were profiled by UPLC-MS/MS, and their anti-proliferative activities were assayed In Vitro in four bladder cancer models. Significant interindividual variability was observed for composition and proliferation. Microbial metabolite concentrations (valerolactones, phenylalkyl acids and hippuric acids) were positively associated with reduced bladder cancer proliferation In Vitro, while native flavanols were poorly correlated with activity. These results suggest that microbial metabolites may be responsible for chemoprevention in uroepithelial cells following flavanol consumption. This highlights the potential to use individual genetics and microbial metabotyping to design personalized dietary interventions for cancer prevention and/or adjuvant therapy to reduce bladder cancer incidence and improve outcomes.
Insights
Gut microbes transform flavanols into metabolites that may prevent bladder cancer. Urine analysis revealed microbial metabolites, not flavanols, correlated with reduced cancer cell proliferation, suggesting personalized nutrition for cancer prevention.
Area of Science:
- Nutritional biochemistry
- Cancer chemoprevention
- Microbiome research
Background:
- Flavanols are plant compounds metabolized by gut microbes into bioavailable substances.
- Uroepithelial cells are exposed to high concentrations of these metabolites via urine.
- The role of flavanol metabolites in bladder cancer chemoprevention is largely unexplored.
Purpose of the Study:
- To investigate the anti-proliferative effects of flavanol metabolites on bladder cancer cells.
- To determine whether microbial metabolites or native flavanols are responsible for chemoprevention.
- To explore the potential for personalized dietary interventions based on metabotype.
Main Methods:
- Rats were administered various flavanols.
- Urine samples were collected to represent the bioavailable metabolome.
- UPLC-MS/MS was used for urine profiling, and anti-proliferative assays were performed on bladder cancer cell lines.
Main Results:
- Significant interindividual variability was observed in urine metabolite composition and anti-proliferative activity.
- Concentrations of microbial metabolites (valerolactones, phenylalkyl acids, hippuric acids) were positively associated with reduced bladder cancer cell proliferation.
- Native flavanols showed poor correlation with anti-proliferative activity.
Conclusions:
- Flavanol microbial metabolites, not native flavanols, may be responsible for chemopreventive effects in uroepithelial cells.
- Individual gut microbiome composition influences the anti-cancer potential of flavanols.
- Personalized dietary strategies targeting the gut microbiome could aid in bladder cancer prevention and treatment.
