AimHere, we evaluated any beneficial effects of a potential probiotic bacterial strain (Lactobacillus plantarum MTCC 9510) in two different stress paradigms in mice. Methods and ResultsLactobacillus plantarum MTCC 9510 (2x10(10) CFU per mice) was supplemented to male Swiss albino mice either subjected to chronic unpredictable mild stress or sleep deprivation (SD) stress. Various behavioural and biochemical tests along with selected gut bacterial abundances were determined. Lactobacillus plantarum MTCC 9510 supplementation prevented stress-induced behavioural despair (depression, anxiety, learning and memory, stereotypic behaviour), oxidative stress markers and inflammatory cytokines in brain and serum. Its supplementation also improved gut and blood brain barrier integrity. It also affected caecal short-chain fatty acids along with the promotion of Lactobacillus sp. and reduction in Enterobacteriaceae abundances. We also observed that two different stresses variably affected various behavioural and biochemical changes but L. plantarum MTCC 9510 supplementation most effectively prevented all these changes. ConclusionWe provide evidence that positive modulation of the selected beneficial gut microbial population could serve as a viable strategy to neutralize day-to-day and SD stress-induced pathological alterations. Significance and Impact of the StudyTherapeutic potential of this/other probiotic strains in tackling the deleterious neurobiological effects on exposure to various stress-related conditions can be explored.