Abstract
Bifidobacterium animalis subsp. lactis is a well-known probiotic with potential benefits for alleviating sub-health symptoms, including immune dysfunction and anxiety. Given the strain-specific nature of its probiotic effects, identifying effective strains for sub-health alleviation is crucial. In this study, we characterized 16 B animalis subsp. lactis isolates from fecal samples and probiotic sources. We assessed the genotype-phenotype correlations related to growth, carbon source utilization, and stress tolerance in vitro. Subsequently, we profiled 107 metabolites (including 28 alcohols and 17 esters) and quantified the levels of short-chain fatty acids and three other organic acids. Three B. animalis strains, GOLDGUT-BB21, WLBA7, and WLBA6, were selected and evaluated in a sleep-deprived mouse model. In vivo, WLBA3 reduced inflammation and oxidative stress by inhibiting the NLRP3 inflammasome pathway and modulating gut microbiota (e.g., Lactobacillus and Alistipes), which in turn significantly improved weight gain and fatigue resistance, attenuated cognitive function, and anxiety-like behavior. These findings provide insights into the diversity of B. animalis subsp. lactis strain resources and highlight the potential of WLBA3 as a candidate for alleviating sub-health symptoms.