Lactocaseibacillus rhamnosus zz-1 Supplementation Mitigates Depression-Like Symptoms in Chronic Stress-Induced Depressed Mice via the Microbiota–Gut–Brain Axis

Accumulating evidence has revealed an association between depression and disordered intestinal microecology. The discovery of psychobiotics has provided a promising perspective for studying the treatment of psychiatric disorders. Here, we aimed to investigate the antidepressant abilities of Lactocaseibacillus rhamnosus zz-1 (LRzz-1) and elucidate the underlying mechanisms. The viable bacteria (2 × 109 CFU/day) were orally supplemented to depressed C57BL/6 mice induced by chronic unpredictable mild stress (CUMS), and the behavioral, neurophysiological, and intestinal microbial effects were assessed, with fluoxetine used as a positive control. The treatment with LRzz-1 effectively mitigated the depression-like behavioral disorders of depressed mice and reduced the expression of inflammatory cytokine mRNA (IL-1β, IL-6, and TNF-α) in the hippocampus. In addition, LRzz-1 treatment also improved tryptophan metabolic disorder in the mouse hippocampus, as well as its peripheral circulation. These benefits are associated with the mediation of microbiome–gut–brain bidirectional communication. CUMS-induced depression impaired the intestinal barrier integrity and microbial homeostasis in mice, neither of which was restored by fluoxetine. LRzz-1 prevented intestinal leakage and significantly ameliorated epithelial barrier permeability by up-regulating tight-junction proteins (including ZO-1, occludin, and claudin-1). In particular, LRzz-1 improved the microecological balance by normalizing the threatened bacteria (e.g., Bacteroides and Desulfovibrio), exerting beneficial regulation (e.g., Ruminiclostridium 6 and Alispites), and modifying short-chain fatty acid metabolism. In summary, LRzz-1 showed considerable antidepressant-like effects and exhibited more comprehensive intestinal microecological regulation than other drugs, which offers novel insights that can facilitate the development of depression therapeutic strategies.