Butyrate, a bacterial derived short chain fatty acid is implicated in gastrointestinal, immunological and host cell metabolic functions. The present study was undertaken to evaluate the role butyrate on the gut microbiome, proteinopathies, cognitive performance, and blood brain barrier integrity in rats subjected to chronic cerebral hypoperfusion (permanent bilateral common carotid arteries occlusion). Administration of butyrate (300 mg/kg, p.o) for 120 days in the post-surgical state improved the spatial memory (Morris water maze test) and which correlates to the decreased hippocampal expression of amyloid-, p-tau and TDP-43. Interestingly, butyrate improved the gut microbial composition and abundance when compared to the vehicle treated ischemic rats. For the first time, we found a positive correlation between the improved gut microbiome and autophagy process (improved protein expression of AMPK, PIK3, LC3A) in ischemic brains. This improved autophagy may be reason for the decreased expression of amyloid-, p-tau and TDP-43. Similarly, butyrate improved blood brain barrier integrity by improving tight junction protein expression (Claudin, Occludin, Laminin, Catenin). Thus, we conclude that butyrate improves memory in ischemic rats via improving gut dysbiosis and autophagy.
December 28, 2025