β-glucan attenuates cognitive impairment via the gut-brain axis in diet-induced obese mice

Abstract Background: “Western” style dietary patterns are characterised by a high proportion of highly processed foods rich in fat and low in fibre. This diet-pattern is associated with myriad metabolic dysfunctions including neuroinflammation and cognitive impairment. β-glucan, the major soluble fibre in oat and barley grains, are fermented in the lower gastrointestinal tract, potentially impacting the microbial ecosystem and thus may improve elements of the gut-brain axis. The present study aimed to evaluate the effect of β-glucan on the microbiota-gut-brain axis and cognitive function in an obese mouse model induced by a high-fat and fibre deficient diet (HFFD). Results: After chronic supplementation for 15 weeks, β-glucan prevented HFFD diet-induced cognitive impairment assessed behaviourally by object location and nesting building tests. In the hippocampus, β-glucan countered the HFFD-induced microglia activation and its engulfment of synaptic puncta, and up-regulation of proinflammatory cytokine (TNF-α, IL-1β and IL-6) mRNA expression. Also in the hippocampus, β-glucan significantly promoted PTP1B-IRS-pAKT-pGSK3β-pTau signalling for synaptogenesis; improved the synaptic ultrastructure examined by transmission electron microscopy and increased both pre- and post-synaptic protein levels compared to the HFFD-treated group. In the colon, β-glucan reversed HFFD-induced gut barrier dysfunction: increased the thickness of colonic mucus (Alcian blue and mucin-2 glycoprotein immunofluorescence staining); increased the levels of tight junction proteins occludin and zonula occludens-1; and attenuated bacterial endotoxin translocation. The HFFD diet resulted in widespread microbiota dysbiosis, effects abrogated by chronic β-glucan supplementation, with the β-glucan effects on bacteroidetes and its lower taxa particularly striking. Importantly, acute study of β-glucan supplementation for 7 days demonstrated pronounced, rapid differentiating microbiota changes before the cognitive improvement, suggesting the possible causality of gut microbiota profile on cognition. In support, broad-spectrum antibiotic intervention to severely deplete gut microbiota colonisation, eliminated β-glucan’s effects on improving cognition, highlighting the role of gut microbiota to mediate cognitive behavior. Conclusion: This study provides the first evidence that β-glucan improves indices of cognition and brain function with major beneficial effects all along the gut microbiota-brain axis. Our data suggest that elevating consumption of β-glucan-rich foods is an easily implementable nutritional strategy to alleviate detrimental features of gut-brain dysregulation and prevent neurodegenerative diseases associated with Westernized dietary patterns.