Sex differences in the associations between lifestyle, intestinal permeability and brain health in middle-aged adults
Year: 2026
Type: article
Abstract: Background: Evidence suggests that brain health is related to intestinal health. Increased intestinal permeability (IP) biomarkers as risk factors for reduced brain health, considering sex differences in the gut-brain axis, in middle-aged adults has not been studied. Aim: To evaluate the associations between IP biomarkers and brain health in a middle-aged cohort of healthy women and men. Methods: 827 participants from the Barcelona Brain Health Initiative (BBHI) study with a complete neuropsychological evaluation, neurofilament light-chain (NfL), and brain-MRI data were studied (median age: 52y, 427 males). Analyses were adjusted for clinical variables, physical exercise, sleep, nutrition, social interactions, and vital plan. IP was evaluated by levels of lipopolysaccharide-binding protein (LBP), zonulin and soluble-CD14. Integrative analyses included multiple factor analysis. Diagnoses of neurological, psychiatric and a 19-diseases composite-endpoint score during a 4-year period were also analyzed. Results: Associations between individual IP biomarkers and brain health were minor in fully adjusted models in both women and men. In women, IP biomarkers were integrated with age, hypertension and hypercholesterolemia in dimension 2, which was inversely associated with cortical and white-matter volumes and positively associated with plasma NfL (all p < 0.05). In men, IP biomakers were combined with high alcohol consumption in dimension 3, which was associated with reduced hippocampal and cortical volumes, as well as higher plasma NfL (all p < 0.05). Only in women, dimensions including IP biomakers were associated with the diagnosis of neurological (OR, 95%CI: 2.3, 1.5-3.6) and other (OR, 95%CI: 1.3, 1.1-1.6) diseases. Conclusion: The association of IP biomarkers with brain health may vary according to sex, and clinical and lifestyle factors. In women, more so than men, IP biomarkers were associated with brain health in mid-life.
Institutions: Instituto de Salud Carlos III, Centro de Investigación Biomédica en Red, Centro de Investigación Biomédica en Red de Fragilidad y Envejecimiento Saludable, Universitat de Barcelona, Universitat Autònoma de Barcelona, Institut Guttmann, Institut d'Investigació en Ciències de la Salut Germans Trias i Pujol, Consorci Institut D'Investigacions Biomediques August Pi I Sunyer, Harvard University, Hebrew SeniorLife
Language: English
Topic: Gut microbiota and health
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $2,890
Funders: BrightFocus Foundation, Centro de Investigación Biomédica en Red Fragilidad y Envejecimiento Saludable, Ministerio de Ciencia, Innovación y Universidades, Generalitat de Catalunya, Institució Catalana de Recerca i Estudis Avançats, National Institutes of Health, LIFE programme, Agència de Gestió d'Ajuts Universitaris i de Recerca, Instituto de Salud Carlos III, European Regional Development Fund, Agencia Estatal de Investigación, National Institute on Aging, European Social Fund
Awards: Personalized brain activity modulation to improve balance and cognition in elderly fallers, G3016928132, G3029908536, G3185858455, Multifocal transcranial current stimulation for cognitive and motor dysfunction in dementia, G4022077041, G470133098, G5680818147, G602225582, G7215952827, G787121397, G8635956847
OpenAlex ID: W7163447191