Improvements of Age-Related Cognitive Decline in Mice by Lactobacillus helveticus WHH1889, a Novel Strain with Psychobiotic Properties.

A gradual decline in cognitive function occurs with age. Accumulating evidence suggests that certain probiotic strains exert beneficial effects on age-related cognitive decline. Our previous study revealed that WHH1889 attenuated symptoms of anxiety and depression in depressed mice via shaping the 5-hydroxytryptamine (5-HT) and 5-hydroxytryptophan (5-HTP) metabolism and gut microbial community, indicating the psychobiotic potential of WHH1889. In the present study, the effects of WHH1889 on age-related cognitive decline were investigated. WHH1889 was orally administrated (1 × 10 CFU/day) for twelve weeks in aged mice, and their cognitive behaviors, neurochemical factors, cognitive-related gene expressions, neuroinflammation, and serum tryptophan pathway-targeted metabolic profiling, as well as gut microbiome composition were assessed. WHH1889 demonstrated improvement of the cognitive behaviors via the novel object recognition test (NORT), the active shuttle avoidance test (ASAT), the Y-maze test, and the passive avoidance test (PAT). The hippocampal neuronal loss; the declined concentrations of BDNF, 5-HT, and 5-HTP; the decreased gene expressions of neurodegeneration biomarkers; and the increased production of hippocampal inflammatory cytokines in aged mice were restored by WHH1889. In addition, WHH1889 increased the 5-HT/5HTP levels and decreased the serum levels of tryptophan-derived metabolites (e.g., kynurenine, xanthurenic acid, 3-hydroxykynurenine, and 3-hydroxyanthranilic acid). Furthermore, WHH1889 was revealed to shape the gut microbiota community by reversing the relative abundances of Bacteroidota and Firmicutes. The present findings suggest that WHH1889 exerted cognitive improving effects on aged mice, which was associated with the modulation of 5-HT and 5-HTP metabolism and gut microbial composition. The supplementation of WHH1889 may therefore be a promising therapeutic agent for age-related cognitive deficits.