Efeitos atenuantes de um blend probiótico no comportamento de preferência pelo etanol em modelo animal

Abstract

Compulsive alcohol consumption induces profound neuroadaptations in the mesocorticolimbic dopaminergic circuit of the striatum. These adaptations result from the ethanol absorption process itself, leading to structural and functional impairments in the gut-brain axis, which contribute to the maintenance of alcohol-related addictive behaviors. The use of specific bacterial strains has emerged as a promising adjuvant therapeutic approach for alcohol use disorder, owing to their ability to interact with the host and positively influence physiology and behavior through the gut-brain axis, particularly under conditions of intestinal dysbiosis. Based on this, we hypothesized that administering these bacteria could potentially modify the intestinal ecosystem and influence brain reward circuits associated with alcohol consumption. The strains Lacticaseibacillus rhamnosus L156.4 and Lactococcus lactis NCDO 2118 were selected for their ability to modulate intestinal barrier integrity and regulate ethanol preference behavior by displacing bacterial substrates that function as neuromodulators. In this study, we employed a validated animal model to investigate the brain systems involved in ethanol-seeking and preference. Conventional C57BL/6 mice were subjected to a high sugar and butter diet (HSB) for eight weeks (T1), followed by its withdrawal and the introduction of ethanol in a free-choice paradigm for two weeks (T2). Subsequently, the animals received a blend of probiotic bacteria for an additional two weeks (T3). Our results demonstrated that administration of the probiotic blend led to reduced ethanol consumption and preference in the animals, accompanied by decreased compulsivity, improved episodic memory retention, and restored exploratory activity. These outcomes correlated with the upregulation of a gene associated with dopaminergic inhibitory control in the striatum and long-term potentiation consolidation in the hippocampus, facilitating the reestablishment of motivational control. Furthermore, structural restitution was observed in both the intestine and liver. These findings suggest that the probiotic blend modulates various neuroimmune pathways, reducing the rewarding effects of alcohol and mitigating consumption and associated behaviors.