Lacticaseibacillus casei IDCC 3451 alleviates cognitive and behavioral functions by reshaping the gut microbiome and regulating intestinal barrier integrity in chronic stress animal models.

Lacticaseibacillus casei IDCC 3451 (3451) was evaluated for its effects on the gut-brain axis using Caenorhabditis elegans (C. elegans) and mouse models of stress and inflammation. In C. elegans, 3451 extended lifespans by 25 %, improved motility, and chemotaxis, enhanced survival under pathogen challenge, and reduced amyloid beta accumulation by 42 %. Transcriptomic profiling revealed upregulation of genes involved in neurotransmitter signaling and serine/threonine pathways. In the unpredictable chronic mild stress (UCMS) mouse model, 3451 administration increased the time spent in the center of the open field by 65 % and reduced immobility in the forced swim test by 32 %, indicating anxiolytic and antidepressant effects. Serum levels of aspartate aminotransferase (AST) and gamma-glutamyl transferase (GGT) were decreased by 18 % and 24 %, respectively. Additionally, 3451 restored the expressions of 5HT1AR, GABAR, and tight junction proteins, including ZO-1 and Claudin1. Metabolomic analysis showed increased glycine and decreased palmitic acid levels, associated with an increased abundance of Ruminococcus and Akkermansia. In the dextran sulfate sodium (DSS)-induced colitis model, 3451 reduced the disease activity index by 36 %, improved colon histology, increased goblet cell preservation, and upregulated ZO-1 and IL-10 expression. Threonine levels were also increased and correlated with a higher abundance of Coprococcus. These findings demonstrate that 3451 improved behavioral and intestinal outcomes through coordinated modulation of host signaling, metabolite production, and gut microbial composition, highlighting its therapeutic potential for managing IBD and neurobehavioral disorders.