Postbiotic Lactobacillus reuteri LRE02 Enriched with Sodium Selenite Demonstrates Antidepressant- and Anxiolytic-Like...

Postbiotics, including inactivated microorganisms and their bioactive components, have emerged as innovative candidates for microbiota-targeted therapies. Among them, Lactobacillus reuteri-derived postbiotics represent a promising and underexplored strategy for modulating host physiology without the risks associated with live bacteria. Selenium enrichment may further enhance these benefits by strengthening antioxidant defenses and regulating inflammation, two central mechanisms to microbiota-gut-brain axis communication. In this study, we investigated the antidepressant- and anxiolytic-like effects of L. reuteri LRE02 in three formulations: a live probiotic (Lr), an inactivated postbiotic (ILr), and a selenium-enriched postbiotic (ILr/Se) in male Swiss mice. Animals were assigned to five groups: vehicle, Lr, ILr, ILr/Se, and fluoxetine, and treated intragastrically for 14 days (300 μL, 10⁹ CFU/mL). Behavioral tests and biochemical analyses were subsequently performed. All L. reuteri-based treatments presented antidepressant-like effect and reduced corticosterone levels, indicating HPA axis modulation. The postbiotic formulations also improved oxidative stress parameters, reduced TNF-α and IL-6 across the prefrontal cortex, hippocampus, and small intestine, and restored IDO expression. Notably, ILr/Se exhibited anxiolytic-like effects and upregulated PI3K/Akt/mTOR signaling and NRF2 expression in the intestine, suggesting enhanced redox and neuroplasticity support. The key innovation of this work lies in demonstrating that inactivated and selenium-enriched L. reuteri postbiotics exert antidepressant-like and anxiolytic-like effects, offering advantages in stability, safety, and reproducibility. These findings highlight postbiotics, especially when combined with selenium, as promising candidates for future microbiota-based interventions targeting mental health.