EARLY-LIFE <EM DATA-START="471" DATA-END="494" >LACTOBACILLUS REUTERI</EM> SUPPLEMENTATION PREVENTS CHRONIC STRESS–INDUCED BEHAVIORAL DISINHIBITION IN ADOLESCENT OFFSPRING OF HIGH-FAT DIET–FED DAMS

Early developmental stages, both pre- and postnatal, critically shape stress-related behaviors during adolescence. Maternal exposure to high-fat diets (HFD) during pregnancy induces long-lasting alterations in neural circuits involved in emotional regulation; however, the contribution of early-life gut microbiota modulation to the maturation of stress-related pathways remains poorly characterized. This study evaluated whether maternal HFD alters behavioral and neuroendocrine responses to chronic stress in adolescent offspring, and whether Lactobacillus reuteri (LR) supplementation during lactation mitigates these effects.
Adolescent C57BL/6 mouse offspring from dams fed a control diet, an HFD, or an HFD supplemented with LR were subjected to a 21-day chronic unpredictable mild stress (UCMS) paradigm. Behavioral responses were assessed using the Open Field Test, Forced Swim Test, and Sucrose Preference Test. In parallel, plasma corticosterone levels and cortical BDNF expression were measured as indicators of stress responsivity and neuronal activity.
Maternal HFD did not alter total locomotor activity following UCMS exposure but significantly affected exploratory behavior, characterized by increased center exploration in the open field, consistent with stress-induced behavioral disinhibition. In contrast, offspring from LR-supplemented dams showed no changes in overall activity, but rather a redistribution of exploration toward peripheral zones, suggesting preservation of inhibitory control under chronic stress. These behavioral effects were accompanied by reduced plasma corticosterone levels and increased BDNF expression in the prefrontal cortex compared with non-supplemented groups. Hedonic-related behaviors were not affected across conditions.
Collectively, these findings suggest that probiotic supplementation during lactation modulates maternal HFD-induced programming of stress-dependent neurobiological pathways during adolescence.