Postbiotic Lactobacillus reuteri LRE02 Enriched with Sodium Selenite Demonstrates Antidepressant- and Anxiolytic-Like Effects in Mice.
Gonçalves Aline Silveira, Paim Mariana Parron, Zuge Narryman Pinto, da Rocha Marcia Juciele, Presa Marcelo Heinemann, Besckow Evelyn Mianes, Leite Fábio Pereira Leivas, Savegnago Lucielli, Sousa Fernanda Severo Sabedra, Seixas Fabiana Kommling, Collares Tiago Veiras, Gohlke Gustavo, Flores Erico Marlon de Moraes, Mesko Marcia Foster, Bortolatto Cristiani Folharini, Birmann Paloma Taborda, Brüning César Augusto
Abstract
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.
Key Findings
- All Lactobacillus reuteri-based treatments showed antidepressant-like effects and reduced corticosterone levels, indicating modulation of the HPA axis.
- Postbiotic formulations improved oxidative stress parameters, reduced pro-inflammatory cytokines TNF-α and IL-6 in the prefrontal cortex, hippocampus, and small intestine, and restored IDO expression.
- The selenium-enriched postbiotic (ILr/Se) exhibited anxiolytic-like effects and upregulated PI3K/Akt/mTOR signaling and NRF2 expression in the intestine, suggesting enhanced redox balance and neuroplasticity support.
Clinical Significance
This study suggests that selenium-enriched Lactobacillus reuteri postbiotics may offer a safe and stable microbiota-based therapeutic approach to alleviate depression and anxiety by modulating oxidative stress and inflammation along the microbiota-gut-brain axis.
Citation
Gonçalves Aline Silveira, Paim Mariana Parron, Zuge Narryman Pintoet al.. Postbiotic Lactobacillus reuteri LRE02 Enriched with Sodium Selenite Demonstrates Antidepressant- and Anxiolytic-Like Effects in Mice. Molecular neurobiology. 2026-Jun-19.