Decreased microglial activation through gut-brain axis by prebiotics, probiotics, or synbiotics effectively restored cognitive function in obese-insulin resistant rats

Abstract

BACKGROUND: Chronic high-fat diet (HFD) consumption caused not only obese-insulin resistance, but also cognitive decline and microglial hyperactivity. Modified gut microbiota by prebiotics and probiotics improved obese-insulin resistance. However, the effects of prebiotics, probiotics, and synbiotics on cognition and microglial activity in an obese-insulin resistant condition have not yet been investigated. We aimed to evaluate the effect of prebiotic (Xyloolidosaccharide), probiotic (Lactobacillus paracasei HII01), or synbiotics in male obese-insulin resistant rats induced by a HFD. METHODS: Male Wistar rats were fed with either a normal diet or a HFD for 12 weeks. At week 13, the rats in each dietary group were randomly divided into four subgroups including vehicle group, prebiotics group, probiotics group, and synbiotics group. Rats received their assigned intervention for an additional 12 weeks. At the end of experimental protocol, the cognitive functioning of each rat was investigated; blood and brain samples were collected to determine metabolic parameters and investigate brain pathology. RESULTS: We found that chronic HFD consumption leads to gut and systemic inflammation and impaired peripheral insulin sensitivity, which were improved by all treatments. Prebiotics, probiotics, or synbiotics also improved hippocampal plasticity and attenuated brain mitochondrial dysfunction in HFD-fed rats. Interestingly, hippocampal oxidative stress and apoptosis were significantly decreased in HFD-fed rats with all therapies, which also decreased microglial activation, leading to restored cognitive function. CONCLUSIONS: These findings suggest that consumption of prebiotics, probiotics, and synbiotics restored cognition in obese-insulin resistant subjects through gut-brain axis, leading to improved hippocampal plasticity, brain mitochondrial function, and decreased microglial activation.