Urinary Metabolome Analysis Reveals Potential Microbiota Alteration and Electrophilic Burden Induced by High Red Meat Diet: Results from the French NutriNet‐Santé Cohort and an in vivo Intervention Study in Rats

International audience; Scope: High red and processed meat consumption is associated with several adverse outcomes such as colorectal cancer and overall global mortality. However, the underlying mechanisms remain debated and need to be elucidated.Methods and results: Urinary untargeted LC-MS metabolomics data from 240 subjects from the French cohort NutriNet-Santé were analysed. Individuals were matched and divided into 3 groups according to their consumption of red and processed meat: high red and processed meat consumers, non-red and processed meat consumers and an at random group. Results were supported by a preclinical experiment where rats were fed either a high red meat or a control diet. Microbiota derived metabolites, in particular indoxyl sulfate and cinnamoylglycine, were found impacted by the high red meat diet in both studies, suggesting a modification of microbiota by the high red/processed meat diet. Rat microbiota sequencing analysis strengthened this observation. Although not evidenced in the human study, rat mercapturic acid profile concomitantly revealed an increased lipid peroxidation induced by high red meat diet.Conclusion: Novel microbiota metabolites were identified as red meat consumption potential biomarkers, suggesting a deleterious effect, which could partly explain the adverse effects associated with high red and processed meat consumption.