Early Brain Ageing Linked to the Gut–Brain Axis

Higher functional-connectivity-derived brain age deviation was consistently associated with poorer cognitive performance—particularly working memory and executive function—and greater depressive symptoms in young and mid-life adults, while also showing links to gut microbial and metabolic signatures. In a discovery cohort of 674 participants, with replication in a cohort of 444 and an independent cohort of 344 participants, researchers used resting-state fMRI and whole-brain functional connectivity to derive a brain ageing index (BAI), defined as the difference between predicted and chronological age after correcting for age-related bias. Predicted brain age correlated moderately with chronological age across cohorts (r=0.50–0.59), and higher BAI was reproducibly associated with altered connectivity involving the posterior cingulate/precuneus and medial frontal regions, as well as poorer cognition and more depressive symptoms. In the independent cohort, integrated stool metagenomic and metabolomic analyses identified microbial taxa and metabolites—including ceramides, 24-hydroxycholesterol, dicarboxylic acids, and estetrol—associated with BAI. Pathway analyses suggested potential involvement of neuroimmune, vascular, synaptic, and mitochondrial processes. These findings suggest that functional brain connectivity can capture individual differences in early brain ageing and may provide a window into biological pathways linking the brain and gut to brain health. Source: https://www.thelancet.com/