Alleviation of Anxiety/Depressive-Like Behaviors and Improvement of Cognitive Functions by Lactobacillus plantarum WLPL04 in Chronically Stressed Mice

BACKGROUND: Intestinal microorganisms play an important role in regulating the neurodevelopment and the brain functions of the host through the gut-brain axis. Lactobacillus, one of the most representative intestinal probiotics, produces important effects on human physiological functions. Our previous studies reveal that the Lactobacillus plantarum WLPL04 has a series of beneficial actions, such as antiadhesion of pathogens, protection from the harmful effect of sodium dodecyl sulfate, and anti-inflammatory stress on Caco2 cells. However, its effects on brain functions remain unknown. The present study aims to evaluate the potential effect of L. plantarum WLPL04 on anxiety/depressive-like behaviors in chronically restrained mice. METHODS: Newly weaned mice were exposed to chronic restraint stress for four weeks and raised daily with or without L. plantarum WLPL04 water supplement. Animals were behaviorally assessed for anxiety/depression and cognitive functions. The 16S rRNA sequencing was performed to analyze the intestinal microbiota structure. The levels of the medial prefrontal cortical (mPFC) brain-derived neurotrophic factor (BDNF)/tropomyosin-related kinase B (TrkB) and serum 5-hydroxytryptamine (5-HT) were examined using Western blot and enzyme-linked immunosorbent assay. RESULTS: The chronic stress-induced anxiety/depressive-like behaviors and cognitive deficits were significantly alleviated by the L. plantarum WLPL04 treatment. The 16S rRNA sequencing analysis showed that the chronic stress reduced the diversity and the richness of intestinal microbiota, which were rescued by the L. plantarum WLPL04 treatment. The levels of BDNF and TrkB in the mPFC and the concentration of 5-HT in the serum remained unchanged in chronically restrained mice treated with the L. plantarum WLPL04. CONCLUSIONS: The L. plantarum WLPL04 can rescue anxiety/depressive-like behaviors and cognitive dysfunctions, reverse the abnormal change in intestinal microbiota, and alleviate the reduced levels of 5-HT, BDNF, and TrkB induced by chronic stress in mice, providing an experimental basis for the therapeutic application of L. plantarum on anxiety/depression.