Abstract Objective The increased intake of added sweeteners, such as high-fructose corn syrup, has been associated with a rise in metabolic dysfunctions in gut and brain. While different evidence showed that dietary fructose induces gut microbiota reshaping, the sugar impact on specific bacteria-derived metabolites remains an understudied topic. In this study, we identified secondary bile acids (sBAs) as molecules differentially represented in plasma of rats fed a fructose-rich diet compared to control animals, and hypothesized that these metabolites might be a target for probiotic-based strategies to counteract sugar-induced metabolic disorders. To this aim, we investigated whether probiotic spores of Shouchella clausii SF174 ameliorate fructose-induced cognitive and metabolic dysfunctions and prevent molecular alterations in hippocampus and frontal cortex. Methods Wistar rats were fed a fructose-rich diet, alone or in combination with the daily administration of Shouchella clausii spores, for six weeks. At the end of treatment, behavioral, metabolomic and molecular analyses were performed. Results The probiotic spores exerted a protective effect on the memory function of fructose fed rats and prevented the decrease of markers of synaptic plasticity. This was associated with the maintenance of plasma and brain levels of the sBA deoxycholic acid and of its specific receptor Takeda G protein-coupled receptor 5. Further, spores beneficial modulation of fructose-induced peripheral and central inflammation was observed. Also, probiotic spores produced reshaping of the gut microbiota towards a composition exerting neuroprotective and anti-inflammatory effects. Conclusion These results suggest that sBAs might act as a communication bridge along the microbiota gut-brain axis and suggest that their modulation, through probiotic administration, represents an effective strategy to counteract fructose-induced neuroinflammation and gut-brain dysfunction. Graphical Abstract
Spagnuolo et al. (Sat,) studied this question.