Chronoregulatory and neuroprotective effects of yeast β-glucan against systemic inflammation

Circadian rhythms play a critical role in regulating immune function and behavior, and disruptions to these rhythms are increasingly linked to systemic inflammation and neuroinflammation. This study aimed to investigate the effects of prebiotic polysaccharides, yeast β-glucan and chicory inulin, on systemic inflammation-induced disruptions in circadian rhythms, gut microbiota composition and neuroinflammation, in comparison with melatonin and ibuprofen. Here, we induced systemic inflammation in C57BL/6J mice using intraperitoneal (i.p.) injections of lipopolysaccharide (LPS). The i.p. injection of LPS disrupted diurnal expressions of circadian clock genes and proinflammatory cytokines, inducing inflammatory responses in liver and brain tissues. Yeast β-glucan and chicory inulin modulated diurnal rhythmicity of circadian clock genes and proinflammatory cytokines, and reduced neuroinflammation. These modulatory effects were comparable to those observed following melatonin and ibuprofen treatment. Notably, yeast β-glucan reversed LPS-induced microglial activation in the hippocampus and memory deficits. Both prebiotics reversed LPS-induced gut microbial imbalance, showing similar modulatory effects to melatonin and ibuprofen treatment. Network analysis revealed strong correlations between bacterial taxa, short-chain fatty acids production, and expression of circadian clock genes and proinflammatory cytokines. These findings underscore the novel potential role of prebiotic polysaccharides (yeast β-glucan and chicory inulin) for ameliorating circadian disruption and neuroinflammation under challenge.