Introduction: Depression is a complex neuropsychiatric disorder associated with behavioral abnormalities, neurotransmitter imbalance, oxidative stress, and neuroinflammation. Chronic alcohol exposure and withdrawal contribute to depressive-like behavior through disruption of neuronal function. The gut-brain axis has gained attention as a potential therapeutic target, with probiotics showing promising neuroprotective effects.
Aims: This study evaluated the antidepressant-like effects of Lactobacillus casei strain Shirota LcS () in an ethanol-induced depression mouse model by assessing behavioral, biochemical, inflammatory, and histopathological changes.
Materials and Methods: Male Swiss albino mice were divided into five groups (n = 5). Depression like behavior was induced by gradual ethanol exposure for 14 days, followed by withdrawal. LcS (0.5 × 109 and 1 × 109 colony forming unit [CFU]) was administered orally for 14 days. Behavioral assessments included the open field test, elevated plus maze, sucrose preference test, tail suspension test, and light/dark box test. Brain tissues were analyzed for γ-aminobutyric acid (GABA), malondialdehyde, tumor necrosis factor-alpha (TNF-α), interleukin (IL)-1β, and IL-6 levels, along with hippocampal histopathological evaluation.
Results: Ethanol exposure significantly induced depressive-like behavior, decreased GABA levels, increased lipid peroxidation, elevated pro-inflammatory cytokines (TNF-α, IL-1β, and IL-6), and caused hippocampal neuronal damage (P < 0.001). LcS treatment, particularly at 1 × 109 CFU, significantly improved behavioral abnormalities, partially restored GABA levels, reduced oxidative stress and proinflammatory cytokines without completely normalizing them, and preserved hippocampal neuronal architecture. The observed findings are consistent with modulation of the microbiota-gut-brain axis, although this mechanism was not directly investigated.
Conclusion: LcS demonstrated antidepressant-like activity in this preclinical model by improving behavioral outcomes, partially restoring neurotransmitter balance, reducing oxidative stress and neuroinflammation, and preserving hippocampal integrity. These findings are consistent with a potential role of the microbiotagut-brain axis, although this mechanism remains to be confirmed. LcS warrants further mechanistic studies and clinical evaluation as a potential psychobiotic intervention for alcohol-associated depression.
Keywords: Depression, ethanol withdrawal, gut-brain axis, Lactobacillus casei strain Shirota, probiotic