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

Abstract

BackgroundChronic 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.MethodsMale 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.ResultsWe 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.ConclusionsThese 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.

Testosterone deprivation intensifies cognitive decline in obese male rats via glial hyperactivity, increased oxidative stress, and apoptosis in both hippocampus and cortex

“…5 To determine the cell apoptosis, fixed brains were also cut with the cryosection (Leica CM1950; Leica Biosystem Nussloch GmbH) at 10 µm. Then the brains were sliced by cryosection (Leica CM1950; Leica Biosystem Nussloch GmbH, Nussloch, Germany) with 20 μm of thickness.…”

“…Sections were treated with copper sulphate in ammonium acetate buffer to quench endogenous auto-fluorescence of the brain tissue. 5 To determine the cell apoptosis, fixed brains were also cut with the cryosection (Leica CM1950; Leica Biosystem Nussloch GmbH) at 10 µm. Sections were subjected to label immunofluorescence.…”

“…[3][4][5][6][7] It has been shown that microglia play important roles in normal and pathological brain, such as the excessive synaptic pruning in the brains of patients with Alzheimer's disease, and excessive brain inflammation in obesity. [3][4][5][6][7] It has been shown that microglia play important roles in normal and pathological brain, such as the excessive synaptic pruning in the brains of patients with Alzheimer's disease, and excessive brain inflammation in obesity.…”

“…developed peripheral insulin resistance and systemic inflammation, but also brain insulin resistance, increased brain oxidative stress, brain mitochondrial dysfunction, reduced long-term potentiation (LTP), dendritic spine loss, and increased microglial activity, leading to cognitive decline. [3][4][5][6][7] It has been shown that microglia play important roles in normal and pathological brain, such as the excessive synaptic pruning in the brains of patients with Alzheimer's disease, and excessive brain inflammation in obesity. [8][9][10] Growing evidence also showed that astrocytes also play an important role in cognitive function.…”

Ghrelin Levels in Elderly, Diabetic Patients with Mild Cognitive Impairment

“…This phenomenon is called "gut-brain axis" and it incorporates bidirectional communication between the central nervous system and the gastrointestinal system [9,10]. Strong objective evidence of a linkage between gut bacteria and brain function comes from several human and animal studies [11][12][13]. Both dysbacteriosis in the gut and higher systemic inflammation in diabetic population can lead to the intestinal barrier and blood brain barrier dysfunction.…”