Abstract
Dysfunction in the prefrontal cortex can lead to cognitive inflexibility due to multifactorial causes as included cardiometabolic disorders, stress, inadequate diets, as well as an imbalance of the gut-brain axis microbiota. However, these risk factors have not been evaluated jointly. The purpose of this study was to evaluate the effect of physical stress (MS: Male Stress and FS: Female Stress) and high-fat diet (MD: Male Diet and FD: Female Diet) supplementation on the gut microbiota and cognitive flexibility. METHODS: The study was performed on 47 mice, 30 male (M) and 17 female (F) BALBc, exposed to chronic stress physical (S) and high-fat diet (D). Cognitive flexibility was evaluated using the Attentional Set-Shifting Test (ASST) and the gut microbiota composition in terms of relative abundance (%) and alpha-beta diversity. RESULTS: Results showed that S and D reduced cognitive flexibility in male and female mice (p < 0.0001). Significant changes occurred in Alistipes spp. (MM vs. MS:MD; p < 0.0001), Barnesiella spp. (FC vs. FS; p = 0.0002; FC vs. FD, p = 0.0033); Dorea spp. (MC vs. MD, p = 0.0008; MM vs. MD, p < 0.0001) and Lactobacillus spp. (MC vs. MD and FM vs. FS, p < 0.0001; FM vs. MD, p = 0.0393) genera among groups. Predictive functional analysis (QIIME2 and PICRUSt2) showed a significant increase in the expression of histidine kinase, alanine dehydrogenase, glutamine synthase, glutamate synthase, arginine succinyl synthase, and tryptophan synthase genes (p < 0.05), the latter being a precursor of serotonin (5-HT). CONCLUSIONS: Chronic physical stress and a high-fat diet modify cognitive flexibility and the composition and predictive function of the gut microbiota.