β-1,3-Glucans-rich Euglena gracilis supplementation alleviates high-fat-high-fructose diet-induced cognitive impairment in middle-aged mice via the gut-brain axis

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.