Effect of a multi-strain probiotic mixture consumption on anxiety and depression symptoms induced in adult mice by postnatal maternal separation

Background: Intestinal microbial composition not only affects the health of the gut but also influences centrally mediated systems involved in mood, through the "gut-brain" axis, a bidirectional communication between gut microbiota and the brain. In this context, the modulation of intestinal microbiota and its metabolites through the administration of probiotics seems to represent a very promising approach in the treatment of the central nervous system alterations. Early postnatal life is a critical period during which the brain undergoes profound and essential modulations in terms of maturation and plasticity. Maternal separation (MS), i.e., the disruption of the mother-pup interaction, represents a pivotal paradigm in the study of stress-related mood disorders, by inducing persistent changes in the immune system, inflammatory processes, and emotional behavior in adult mammals. Results: We conducted experiments to investigate whether sustained consumption of a multi-strain probiotic formulation by adult male mice could mitigate the effects of maternal separation. Our data demonstrated that the treatment with probiotics was able to totally reverse the anxiety- and depressive-like behavior; normalize the neuro-inflammatory state, by restoring the resting state of microglia; and finally induce a proneurogenic effect. Mice subjected to maternal separation showed changes in microbiota composition compared to the control group that resulted in permissive colonization by the administered multi-strain probiotic product. As a consequence, the probiotic treatment also significantly affected the production of SCFA and in particular the level of butyrate. Conclusion: Gut microbiota and its metabolites mediate the therapeutic action of the probiotic mix on MS-induced brain dysfunctions. Our findings extend the knowledge on the use of probiotics as a therapeutic tool in the presence of alterations of the emotional sphere that significantly impact on gut microbiota composition. Video Abstract.