Effects of Lacticaseibacillus rhamnosus L156.4 and Lactococcus lactis NCDO 2118 strains on reducing alcohol intake and preference in an animal model of high alcohol consumption and preference.

Alcohol use disorder (AUD) involves a progressive series of neuroadaptations influenced by interactions along the gut-brain axis. Disruption of the intestinal barrier enables bacterial-derived metabolites and inflammatory mediators to translocate into the systemic circulation, amplifying neuroimmune activation within mesocorticolimbic reward circuits. Probiotic strains have emerged as promising adjuvant therapies for AUD due to their ability to regulate the gut microbiota and thereby influence neurotransmission. In this study, we investigated the potential of a probiotic blend containing the strains Lacticaseibacillus rhamnosus L156.4 and Lactococcus lactis NCDO 2118 to reduce alcohol intake and preference behaviors in a free-access drinking paradigm (H₂O vs. 10% v/v ethanol). The blend significantly decreased ethanol intake and preference and was accompanied by striatum upregulation of genes related to dopaminergic inhibitory control and downregulation of inflammation-related genes. Serum biochemical parameters remained unchanged and comparable between vehicle- and probiotic-treated groups, supporting the safety of the intervention. Additionally, we observed improved tissue integrity and structural restoration in both the colon and liver. Behavioral assessments using the open field test and marble-burying tests revealed reduced anxiety- and compulsive-like behaviors in the treated groups. These results suggest that this probiotic blend modulates distinct pathways, thereby attenuating alcohol`s rewarding effects and associated compulsive behaviors.