Modulation of the Nuclear factor erythroid 2-related factor 2 (Nrf2) pathway by the probiotic Limosilactobacillus reuteri DSM 17938 prevents diet-induced rat brain dysfunction

Changes in fructose gut absorption and consequent major frontal cortex alterations induced by the western diet (left) and the western diet plus L.reuteri supplementation (right). Up arrows indicate increased parameters and down arrows indicate reduced parameters. NMDA receptor, the N-methyl-D-aspartate receptor; pCREB, pospho-cAMP-response element binding protein; BDNF, brain derived neurotrophic factor; NOR Test, novel object recognition test; Glycogen synthase kinase 3 beta, GSK; MAO, monoamine oxidase; Nrf2, nuclear factor erythroid 2-related factor 2 ; SOD, superoxide dismutase; GR, glutathione reductase; N-Tyr, Nitro-tyrosine; TBARS, thiobarbituric acid reactive substances. [Display omitted] •Western diet, rich in sugar and fat, induces memory dysfunction and redox unbalance.•The Nrf2 pathway is implicated in the Western diet-linked frontal cortex alterations.•The Limosilactobacillus reuteri prevents diet-linked brain dysfunction through Nrf2.•The probiotic reduces gut absorption of fructose and its delivery to brain. Dietary patterns high in fat and sugar promote brain dysfunction, but the preventive efficacy of probiotics has been little explored. This study investigated whether the administration of Limosilactobacillus reuteri DSM 17938 (L.reuteri; 108 CFU/day) counteracts cognitive dysfunction and brain redox unbalance induced in male Wistar rats fed a western diet (WD) for 8 weeks. The results showed that L. reuteri prevented the WD-associated impairment in brain memory function, as evaluated by NOR test, and consistently increased specific molecular markers of synaptic plasticity. The condition of oxidative stress induced by WD, namely enhanced oxidation to proteins and lipids, increased oxidants-producing enzymes as well as reduced nuclear Nrf2 and Nrf2-dependent antioxidant enzymes, was ameliorated by the probiotic. Unexpectedly, mitochondria displayed a diet-induced increase in oxidative capacity, not modified by the probiotic. A protective effect of the probiotic on gut absorption of fructose and its further delivery to brain was evidenced as mechanism involved in cortex redox homeostasis. These findings evidence the potential utility of L. reuteri against WD-induced brain dysfunction and implicate the Nrf2 pathway as a potential mechanism for this effect.