Effects of Oat Fiber Intervention on Cognitive Behavior in LDLR–/– Mice Modeling Atherosclerosis by Targeting the Microbiome–Gut–Brain Axis

It is known that cardiovascular disease can result in cognitive impairment. However, whether oat fiber improves cognitive behavior through a cardiovascular-related mechanism remains unclear. The present work was aimed to elucidate the potential of oat fiber on cognitive behavior by targeting the neuroinflammation signal and microbiome-gut-brain axis in a mouse model of atherosclerosis. Male low-density lipoprotein receptor knock-out (LDLR-/-) mice were treated with a high fat/cholesterol diet without or with 0.8% oat fiber for 14 weeks. Behavioral tests indicated that LDLR-/- mice exhibited a significant cognitive impairment; however, oat fiber can improve cognitive behavior by reducing latency to the platform and increasing the number of crossing and swimming distance in the target quadrant. Oat fiber can inhibit Aβ plaque processing in both the cortex and hippocampus via decreasing the relative protein expression of GFAP and IBα1. Notably, oat fiber inhibited the nod-like receptor family pyrin domain-containing 3 inflammasome activation and blocked the toll-like receptor 4 signal pathway in both the cortex and hippocampus, accompanied by a reduction of circulating serum lipopolysaccharide. In addition, oat fiber raised the expressions of short-chain fatty acid (SCFA) receptors and tight junction proteins (zonula occludens-1 and occludin) and improved intestinal microbiota diversity via increasing the contents of gut metabolites SCFAs. In summary, the present study provided experimental evidence that dietary oat fiber retarded the progression of cognitive impairment in a mouse model of atherosclerosis. Mechanistically, the neuroprotective potential was related to oat fiber and its metabolites SCFAs on the diversity and abundance of gut microbiota that produced anti-inflammatory metabolites, leading to repressed neuroinflammation and reduced gut permeability through the microbiome-gut-brain axis.