Depression and anxiety are common mental health disorders that can significantly impair quality of life. In recent years, functional foods, particularly fermented milk products, have gained attention as potential complementary therapies. Rich in probiotics and bioactive compounds, these products may help modulate the gut-brain axis, thereby improving mood and alleviating symptoms, supporting mental well-being. Hence, the potential antidepressant and anxiolytic effects of milk fermented (FM) with Lactiplantibacillus plantarum Lp39 were evaluated in a murine model. The antidepressant-like effect was assessed using unconditional behavioral tests, including the tail suspension test (TST), forced swimming test (FST), and sucrose preference test (SP). The anxiolytic-like effect was evaluated using the elevated plus maze (EPM), the light-dark box (LD), and the open field test (OFT). Additionally, oxidative stress and inflammation biomarkers were determined in the liver, plasma and hippocampus. Gut microbiota composition was also analyzed. The anxiolytic-like effect was evidenced by the OFT and LD tests. The antidepressant-like effect was demonstrated by TST and FST, along with an increased sucrose preference. FM administration significantly reduced the oxidative stress index and lipidic peroxidation and enhanced antioxidant activity in the hippocampus. Elevated IL-10 levels and lipoxygenase inhibition were observed in FM-treated animals. BNDF levels in the hippocampus were also significantly increased, and correlations were found between BNDF, oxidative stress index, IL-10, and TNF-α with SP outcomes, as well as between MDA and TNF with TST. The gut microbiota remained stable following FM consumption, while reduced Helicobacter and increased Lactobacillus populations. Weak correlations were observed between the presence of Mycoplasmataceae, Propionibacteriaceae, and Deferribacteriaceae and unconditional behavioral tests, oxidative and inflammation biomarkers. Our findings suggest that FM with Lpb. plantarum Lp39 may exert beneficial antidepressant and anxiolytic effects through neurotrophic support, anti-inflammatory and antioxidant mechanisms, without adversely affecting the gut microbiota and possibly contribute to a neuroprotective effect within the gut-brain axis.
