Age-dependent gut barrier failure amplifies stroke injury via a microbiota-lipid axis
Abstract: ** Lecture will be given in English**
Aging is the strongest predictor of poor recovery after ischemic stroke, yet the mechanisms underlying this vulnerability remain incompletely understood and are often considered primarily within the brain. Here, we investigated whether age-related changes in the intestinal barrier contribute to worse stroke outcomes. Analysis of human colon tissue revealed substantial age-associated remodeling of the intestinal environment, including impaired barrier-supporting structures and increased inflammation. We then examined the response to experimental stroke in young and aged mice. Compared with young animals, aged mice developed more persistent intestinal damage, greater barrier leakage, and increased spread of microbial products and bacteria beyond the gut. These changes were accompanied by widespread and prolonged inflammatory responses across the intestine, circulation, and brain. We further identified age-dependent alterations in the gut microbiome and its metabolites, suggesting that aging disrupts protective communication between the gut and peripheral organs after stroke. Restoring a selected microbiome-derived metabolite improved intestinal barrier integrity and reduced brain injury in aged mice. Together, our findings identify the aging gut as an important regulator of systemic inflammation and neurological damage after stroke and highlight the gut-brain axis as a potential therapeutic target for improving recovery in older individuals.
