Gut-brain axis dysfunction induced by fructose is prevented by Bacillus spores through neuroprotective secondary bile acids

By 2020, the intake of added sweeteners (including fructose) has increased by approximately 200% compared to the 1960s. Despite evidence that fructose rich diets modulate gut microbiota composition, its impact on specific bacteria-derived metabolites acting as a signaling molecules to the brain remains an understudied topic. This study aimed to highlight the consequences of a fructose-rich diet on the gut-brain axis and whether a strategy based on probiotic spore supplementation can ameliorate cognitive dysfunction and molecular alterations induced by the sugar. A metabolomic analysis prompted us to focus on secondary bile acids (sBA), which act as a bridge along the gut-brain axis. Interestingly, a significant reduction of the neuroprotective sBA deoxycholic acid (DCA) and of its specific receptor TGR5 was observed in brain of fructose fed rats compared to controls, while these changes were prevented in sugar fed rats concomitantly treated with probiotic spores. The results showed that spores-associated improvement in brain memory function and in markers of synaptic plasticity as well as reduced neuroinflammation were driven by the increase in DCA and activation of pathways downstream its specific receptor TGR5. The results are indicative of a role for BA signaling in regulating brain health and support the hypothesis that sBA form a key communication bridge along the microbiota gut- brain axis in the fructose-induced model of brain dysfunction.