Yeast β-glucan alleviates alcohol-related brain injury by restoring gut-brain axis homeostasis

This study investigated the protective effects of yeast β-glucan (YBG) against alcohol-related brain injury (ARBI), with a focus on potential mechanisms mediated by the gut-brain axis. Our findings revealed that YBG supplementation significantly alleviated alcohol-induced anxiety-like behaviors and cognitive deficits in mice. In the brain, YBG mitigated oxidative stress, reduced neuroinflammation, and ameliorated neurotransmitter dysregulation. In the gut, YBG protected the alcohol-damaged intestinal barrier, upregulating the expression of tight junction proteins (Claudin-1, Occludin, and ZO-1) by 1.5- to 4.5-fold. Furthermore, YBG modulated the gut microbial community, markedly increasing the relative abundance of genera such as Akkermansia (from 0.13% to 4.3%) and Lactobacillus (from 0% to 0.89%), while suppressing alcohol-associated taxa including Alistipes (from 0.20% to 0.05%) and Colidextribacter (from 0.61% to 0.01%). These gut-level ecological changes were accompanied by significant shifts in the microbial metabolome, including elevated short-chain fatty acid levels and altered profiles of neuroactive amino acids, particularly L-tryptophan and L-tyrosine (which exhibited 2.9- and 2.7-fold increases, respectively). KEGG pathway analysis revealed that differential metabolites were primarily enriched in amino acid biosynthesis pathways. Correlation analysis showed strong positive associations among YBG-enriched bacteria, favorable metabolites, and markers of brain health. Together, these findings suggest that YBG's protective effects against ARBI are closely associated with the restoration of gut barrier integrity, restructuring the gut microbiota, and modulating microbial metabolism, which collectively correlate with the attenuation of neuroinflammation and oxidative stress.