High-fat and high-carbohydrate diets worsen the mouse brain susceptibility to damage produced by enterohemorrhagic Escherichia coli Shiga toxin 2

Abstract

Background: Nutrition quality could be one of the reasons why, in the face of a Shiga toxinproducing enterohemorrhagic Escherichia coli outbreak, some patients experience more profound deleterious effects than others, including unfortunate deaths. Thus, the aim of this studywas to determine whether high-fat and/or high-carbohydrate diets could negatively modulate thedeleterious action of Shiga toxin 2 on ventral anterior and ventral lateral thalamic nuclei and theinternal capsule, the neurological centers responsible for motor activity.Methods: Mice were fed a regular, high-fat, high-carbohydrate diet or a combination of bothprevious to the intravenous administration of Shiga toxin 2 or vehicle. Four days after intravenousadministration, mice were subjected to behavioral tests and then sacrificed for histological andimmunofluorescence assays to determine alterations in the neurovascular unit at the cellular andfunctional levels. Statistical analysis was performed using one-way analysis of variance followedby Bonferroni post hoc test. The criterion for significance was p = 0.0001 for all experiments.Results: The high-fat and the high-carbohydrate diets significantly heightened the deleteriouseffect of Stx2, while the combination of both diets yielded the worst results, including endothelialglycocalyx and oligodendrocyte alterations, astrocyte and microglial reactivity, neurodegeneration, and motor and sensitivity impairment.