Dietary fibre reverses adverse post-stroke outcomes in mice via short-chain fatty acids and its sensing receptors GPR41, GPR43 and GPR109A

Abstract Dietary fibre intake is associated with fewer cases of ischaemic stroke. This is likely via the microbiota-gut-brain axis, where fibre is fermented by the gut microbiota, releasing short-chain fatty acids (SCFAs). However, whether fibre or SCFAs can reverse adverse post-stroke outcomes remains unknown. Here, we demonstrated that a low fibre diet exacerbates post-stroke outcomes in mice. This was reversed by a high fibre diet or direct supplementation with SCFAs (delivered either in the water or a high SCFA-releasing diet) immediately after stroke. These modulated the gut microbiome and improved the gut epithelial barrier integrity, which was associated with fewer activated neutrophils and more neuroblast cells in the brain. We then investigated the SCFA-receptors GPR41/43/109A using a triple knockout mouse model, which exhibited poorer stroke outcomes and recovery. These results show that post-stroke interventions using dietary fibre and/or SCFA supplementation, acting via GPR41/43/109A signalling, may represent new therapeutic strategies for stroke-induced brain injury.