摘要The growing aging population along with the shifting dietary paradigm to Western-type diet worldwide has been implicated in the increasing prevalence of cognitive impairment.Emerging evidence suggests that a high-fiber diet may help improve cognitive function through the gut-brain axis.Euglena gracilis,a unicellular microalga rich in β-1,3-glucans,has gained attention due to its modulatory effect on gut dysbiosis and inflammatory response.This study aimed to explore the efficacy and mechanism of β-1,3-glucans-rich E.gracilis powder(EG)against high-fat-high-fructose(HFHF)diet-induced cognitive disorders in mice.A middle-aged(52-week-old C57BL/6J)mouse model with the following groups was adopted:HFHF,HFHF+EG,and control.At the end of the dietary intervention(8 weeks),cognitive behaviors,metabolic parameters,endotoxin levels,gut microbiota composition,and colon and brain pathology were examined.The results showed that EG supplementation attenuated HFHF-induced cognitive impairment,promoted synaptogenesis in the hippocampus,and improved synaptic ultrastructure.These beneficial effects were partly mediated through the upregulation of protein tyrosine phosphatase 1B(PTP1B)-recombinant insulin receptor substrate(IRS)-phosphorylated protein kinase B(p-AKT)-phosphorylated recombinant glycogen synthase kinase 3β(p-GSK3β)-microtubule associated protein tau(p-Tau)signaling.Furthermore,it prevented gut dysbiosis as evidenced by an increase in β-diversity and enrichment of Akkermansia relative to the control group.EG supplementation was also able to partly reverse the HFHF-induced disruption of intestinal barrier,which was accompanied by reduced systemic and neuronal inflammation,normalized short-chain fatty acid production,and decreased serum lipopolysaccharide concentration.The findings from the present study support that β-1,3-glucans-rich EG is a promising natural agent for the prevention of HFHF diet-induced deterioration in cognitive function that merits further investigation.