Summary:
Diet and lifestyle play an important role in maintaining health and preventing chronic disease, including cognitive decline. Emerging evidence suggests that these effects may be partly explained by interactions between diet, the gut microbiota, and the brain. This ‘diet-gut-brain axis’ highlights how dietary patterns can influence brain structure and function through changes in metabolism, inflammation, and microbial composition. This study is a cross-sectional study which examined the relationship between an antioxidant-rich diet, gut microbiota, brain structure, and cognitive function. The analysis included 246 dementia-free individuals aged 65 years and older. Dietary intake was assessed using a three-day food diary to estimate antioxidant capacity, while cognitive function, gut microbiota diversity, and brain volumes were measured using validated tools and imaging techniques. The study also accounted for lifestyle factors by combining diet, physical activity, and smoking into a healthy lifestyle score. The findings showed that higher adherence to an antioxidant-rich diet was associated with greater gut microbiota diversity and increased abundance of beneficial bacterial groups. Participants with higher antioxidant intake also demonstrated larger total brain, grey matter, and white matter volumes, along with better cognitive performance. These associations were stronger among individuals with healthier lifestyles, particularly those who were physically active and non-smokers. Overall, this study suggests that an antioxidant-rich diet, particularly when combined with other healthy lifestyle behaviours, is associated with improved gut microbiota composition, better brain structure, and enhanced cognitive function. These findings support the role of diet and lifestyle as modifiable factors that may help maintain brain health and reduce cognitive decline.
Abstract:
Background and aims: Healthy diet and lifestyle have been linked to improved gut microbiota diversity and neurocognitive outcomes. However, few human studies have simultaneously examined an antioxidant-rich diet (ARD) in combination with other lifestyle factors and their effects on gut microbiota diversity, brain morphometry, and cognitive function. Our aim was to investigate how the dietary antioxidant capacity and a healthy lifestyle profile influence gut microbiota diversity and composition, brain morphometry, and global cognitive function in older adults. Methods: In a cross-sectional analysis of the NutBrain study (2019–2023), a cohort of 246 dementia-free individuals aged ≥65 years, completed a 3-day food diary to estimate the total dietary antioxidant capacity (Oxygen Radical Absorbance Capacity – ORAC). Global cognitive function was assessed using the Mini-Mental State Examination (MMSE). Gut microbiota α- and β-diversities and taxa abundances were derived by 16S rRNA amplicon-based sequencing of stool samples. Brain morphometry – including total brain, white matter, grey matter, and ventricular cerebrospinal fluid volumes – was assessed using magnetic resonance imaging. Multiple linear regression models, accounting for many potential confounders (i.e.: socio-demographics, use of drugs, energy intake, inflammatory and anthropometric markers, and APOE genotyping) examined how ORAC, both alone and combined with smoking and physical activity (devising a healthy lifestyle score, Hscore), affected microbiota diversity, MMSE scores, and brain volumes. Results: Higher ORAC adherence was associated with greater gut microbiota diversity (p ≤ 0.05). Several taxa, such as Barnesiella, Coprococcus, Ruminococcus, Parabacteroides, Lachnospiraceae NK4A136 group, and Clostridia UCG-014 group exhibited increased abundances within the highest ORAC and Hscore tertiles, as compared to the lowest ones. The highest tertile of total ORAC was also positively and significantly associated with greater total brain, white matter, and grey matter volumes (p ≤ 0.05). These associations were stronger in participants classified as having a favourable lifestyle profile (regular physical activity, non-smokers), with notable correlations observed for total brain volume, gut α-diversity, white matter volume and MMSE (p ≤ 0.05). Conclusions: ARD is associated with increased gut microbiota diversity and enrichment of specific taxa, better cognitive function and brain morphometry outcomes. These associations were stronger in individuals with a healthy lifestyle profile.
Article Publication Date: 02/02/2026
DOI: 10.1016/j.clnu.2026.106585
