<i>Lactobacillus</i> yogurts alleviate anxious- and depressive-like effects in CUMS mice via multiple pathways and regulating gut-brain axis

<b>Background:</b> Current researches suggest that the microbiota-gut-brain axis plays a critical role in modulating human cognition and emotion, particularly in the context of psychiatric disorders. Probiotic fermented dairy products have been shown to regulate gut microbiota composition and alleviate depressive symptoms; however, the underlying mechanism and associated metabolic pathways remain unclear.<b>Methods:</b> In this study, we compared the effects of probiotics (Lactobacillus reuteri and Lactobacillus bulgaricus) fermented yogurt on chronic unpredictable mild stress (CUMS)-induced anxious and depressive-like symptoms in mice, as well as discussed potential mechanisms.<b>Results:</b> Behavioral tests revealed that both L. reuteri and L. bulgaricus fermented yogurt significantly alleviated these symptoms. We also observed that Lactobacillus fermented yogurt exerted an overall neuroprotective effect in the hippocampus and helped maintain normal cerebral activity. L. reuteri and L. bulgaricus fermented yogurts were also observed to ameliorate the levels of monoamine neurotransmitters and inflammatory cytokines via inhibiting the activation of the NF-κB pathway accompanied by elevating the CREB-BDNF pathway.<b>Conclusion:</b> Our findings suggest that L. reuteri and L. bulgaricus fermented yogurts may modulate gut microbiota composition and host metabolism, thereby performing neuroprotective effects and ameliorating depressive behaviors in mice by at least partially microbiota-gut-brain axis. These findings have important implications for understanding the antidepressant mechanisms of fermented dairy products that target the intestinal microbiota and provide a promising new way for the development of novel treatments for depression.