Food and Microbiota Metabolites Associate with Cognitive Decline in Older Subjects: A 12‐Year Prospective Study

Scope Diet is considered an important modulator of cognitive decline and dementia, but the available evidence is, however, still fragmented and often inconsistent. Methods and Results The article studies the long‐term prospective Three‐City Cohort, which consists of two separate nested case‐control sample sets from different geographic regions (Bordeaux, n = 418; Dijon, n = 424). Cognitive decline is evaluated through five neuropsychological tests (Mini‐Mental State Examination, Benton Visual Retention Test, Isaac's Set Test, Trail‐Making Test part A, and Trail‐Making Test part B). The food‐related and microbiota‐derived circulating metabolome is studied in participants free of dementia at baseline, by subjecting serum samples to large‐scale quantitative metabolomics analysis. A protective association is found between metabolites derived from cocoa, coffee, mushrooms, red wine, the microbial metabolism of polyphenol‐rich foods, and cognitive decline, as well as a negative association with metabolites related to unhealthy dietary components, such as artificial sweeteners and alcohol. Conclusion These results provide insight into the early metabolic events that are associated with the later risk to develop cognitive decline within the crosstalk between diet, gut microbiota and the endogenous metabolism, which can help identify potential targets for preventive and therapeutic strategies to preserve cognitive health. A large‐scale quantitative metabolomics platform is employed to obtain a deeper insight into the role of diet in the early onset of cognitive decline. Strong evidence supports a protective association between metabolites derived from cocoa, coffee, mushrooms, red wine, the microbial metabolism of polyphenol‐rich foods and cognitive decline. The article also finds a negative association with metabolites related to unhealthy dietary components, such as artificial sweeteners and alcohol.