Curdlan Prevents the Cognitive Deficits Induced by a High-Fat Diet in Mice via the Gut-Brain Axis.

Xiaoying Yang,Xi Chen,Peng Zhang,Yinghua Yu,Danhong Lin,Hongli Shi,Alec Becvarovski,Minmin Hu,Kuiyang Zheng,Shanshan Hao,Mingxuan Zheng,Xu-Feng Huang,Wei Pan

doi:10.3389/fnins.2020.00384

Abstract

A high-fat (HF) diet is a major predisposing factor of neuroinflammation and cognitive deficits. Recently, changes in the gut microbiota have been associated with neuroinflammation and cognitive impairment, through the gut-brain axis. Curdlan, a bacterial polysaccharide widely used as food additive, has the potential to alter the composition of the microbiota and improve the gut-brain axis. However, the effects of curdlan against HF diet-induced neuroinflammation and cognitive decline have not been investigated. We aimed to evaluate the neuroprotective effect and mechanism of dietary curdlan supplementation against the obesity-associated cognitive decline observed in mice fed a HF diet. C57Bl/6J male mice were fed with either a control, HF, or HF with curdlan supplementation diets for 7 days (acute) or 15 weeks (chronic). We found that acute curdlan supplementation prevented the gut microbial composition shift induced by HF diet. Chronic curdlan supplementation prevented cognitive declines induced by HF diet. In addition, curdlan protected against the HF diet-induced abnormities in colonic permeability, hyperendotoxemia, and colonic inflammation. Furthermore, in the prefrontal cortex (PFC) and hippocampus, curdlan mitigated microgliosis, neuroinflammation, and synaptic impairments induced by a HF diet. Thus, curdlan—as a food additive and prebiotic—can prevent cognitive deficits induced by HF diet via the colon-brain axis.

Highlights

Obesity, a major global health concern, is closely associated with type 2 diabetes mellitus, cardiovascular disease, cancer, depression, and other chronic diseases but is a risk factor for neurodegenerative diseases, such as Alzheimer’s disease (AD) and vascular dementia (Fruh, 2017; O’Brien et al, 2017)
In the Y-maze test, the proportion of spontaneous alteration in HF mice was markedly lower than that of the LF and HFCurd mice [F(2,27) = 11.89, p = 0.0002, Figure 2C], suggestive of the deficits in spatial working memory caused by a HF diet, and these could be ameliorated by curdlan. These results indicate that cognitive deficits caused by a HF diet are preventable by chronic curdlan supplementation
An insoluble β-(1, 3)-glucan has been widely used as food additive, its potential effects on the gut-brain axis and cognition represent a gap in the current literature

Summary

Introduction

A major global health concern, is closely associated with type 2 diabetes mellitus, cardiovascular disease, cancer, depression, and other chronic diseases but is a risk factor for neurodegenerative diseases, such as Alzheimer’s disease (AD) and vascular dementia (Fruh, 2017; O’Brien et al, 2017). Brain development is abnormal when the gut microbiota is Dietary Curdlan Improves Cognition absent in germ-free animals (Gareau et al, 2011; Clarke et al, 2013). Previous research in germ-free and antibiotictreated, pathogen-free rodents has shown that gut microbiota dysbiosis negatively influences hippocampal neurogenesis and brain development through the activation of microglia (Erny et al, 2015; Sharon et al, 2016). A dysbiosis of the gut microbiota is a key initiating factor of neuroinflammation and subsequent neuronal dysfunction (Frohlich et al, 2016; Rogers et al, 2016; Sharon et al, 2016)

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