The co-fermentation of whole-grain black barley and quinoa improves murine cognitive impairment induced by a high-fat diet altering gut microbial ecology and suppressing neuroinflammation.

A high-fat diet (HFD) is associated with various adverse health outcomes, including cognitive impairment and an elevated risk of neurodegenerative conditions. This relationship is partially attributed to the influence of an HFD on the gut microbiota. The objective of this research was to evaluate the neuroprotective benefits of co-fermented black barley and quinoa with (FG) against cognitive impairments triggered by an HFD and to investigate the microbiota-gut-brain axis mechanisms involved. C57BL/6J mice were randomized into four groups: the normal control group (NC, = 10), the high-fat diet group (HFD, = 10), the high-fat diet group supplemented with FG (HFG, 10 mL per kg BW, = 10), and the high-fat diet group supplemented with (HFL, 10 mL per kg BW, = 10). Our results showed that the FG intervention enhanced the behavioral and locomotor skills of the mice, elevated the levels of dopamine (DA) and norepinephrine (NPI) in brain tissues, and alleviated synaptic ultrastructural damage in the hippocampus. Furthermore, FG intervention was observed to exert a protective effect on both the blood-brain barrier and the colonic barrier, as evidenced by an increase in the mRNA levels of (), , and in the hippocampus and colon. These beneficial effects may be attributed to FG's regulation of gut microbiota dysbiosis, which involves the restoration of intestinal flora diversity, reduction of the / (F/B) ratio, and a decrease in the levels of pro-inflammatory bacteria such as and ; moreover, there was an increase in the abundances of anti-inflammatory bacteria, such as and . Metagenomic analysis revealed that the FG treatment downregulated the lipopolysaccharide (LPS) pathway and upregulated neurotransmitter biosynthetic pathways. These probiotic effects of FG resulted in reduced production and "leakage" of LPS and decreased mRNA expression of (), (), and () in hippocampal and colon tissues. Consequently, a reduction was observed in the levels of inflammatory cytokines in the serum, hippocampus, and colon, along with suppression of the immunoreactivity of microglia and astrocytes. Our results suggest that FG may serve as an intervention strategy for preventing cognitive impairments caused by an HFD.