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The Gut Microbiota Is Involved in the Regulation of Cognitive Flexibility in Adolescent BALB/c Mice Exposed to Chronic Physical Stress and a High-Fat Diet

Abstract

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 ( < 0.0001). Significant changes occurred in spp. (MM vs. MS:MD; < 0.0001), spp. (FC vs. FS; = 0.0002; FC vs. FD, = 0.0033); spp. (MC vs. MD, = 0.0008; MM vs. MD, < 0.0001) and spp. (MC vs. MD and FM vs. FS, < 0.0001; FM vs. MD, = 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 ( < 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.

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