👤 Alessandra Prinelli

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. 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. 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). 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. NCT04461951, https://clinicaltrials.gov/. Show less

Dendritic cells (DCs) shape immune responses by influencing T-cell activation. Thus, they are considered both an interesting model for studying nano-immune interactions and a promising target for nano-based biomedical applications. However, the accentuated ability of nanoparticles (NPs) to interact with biomolecules may have an impact on DC function that poses an unexpected risk of unbalanced immune reactions. Here, we investigated the potential effects of gold nanoparticles (AuNPs) on DC function and the consequences for effector and memory T-cell responses in the presence of the microbial inflammatory stimulus lipopolysaccharide (LPS). Overall, we found that, in the absence of LPS, none of the tested NPs induced a DC response. However, whereas 4-, 8-, and 11 nm AuNPs did not modulate LPS-dependent immune responses, 26 nm AuNPs shifted the phenotype of LPS-activated DCs toward a tolerogenic state, characterized by downregulation of CD86, IL-12 and IL-27, upregulation of ILT3, and induction of class E compartments. Moreover, this DC phenotype was less proficient in promoting Th1 activation and central memory T-cell proliferation. Taken together, these findings support the perception that AuNPs are safe under homeostatic conditions; however, particular care should be taken in patients experiencing a current infection or disorders of the immune system. Show less