Martín Hernández, DavidCaso Fernández, Javier RubénDíaz García, CésarRegidor, Pedro-AntonioRizo, José MiguelRomán, MartaGutiérrez, RocíoLeza Cerro, Juan Carlos2026-03-102026-03-102026-03-09Martín-Hernández D, Caso JR, Díaz-García C, Regidor P-A, Rizo JM, Román M, et al. Behavioral, antioxidant, and kynurenine pathway modulation of a specific strain of Ligilactobacillus salivarius in a preclinical model of depression. Eur J Nutr 2026;65:86. https://doi.org/10.1007/s00394-026-03941-910.1007/s00394-026-03941-9https://hdl.handle.net/20.500.14352/133901The data that support the findings of this study are openly available in Docta Complutense at https://hdl.handle.net/20.500.14352/118406.Purpose Current antidepressants targeting neurotransmitters often fail to alleviate symptoms. Alternative hypotheses suggest inflammation may trigger an alternative route that converts tryptophan into kynurenine, reducing the bioavailability of tryptophan to synthesize serotonin while producing neuroactive metabolites such as quinolinic acid (QUINA, excitotoxic) and kynurenic acid (KYNA, neuroprotective). This study evaluates the effects on these systems of a specific strain of Ligilactobacillus salivarius (L. salivarius), identified in the Spanish Type Culture Collection as CECT 30632, in a preclinical model depression. Methods Male Wistar rats (n = 32) were divided into control (CT) and chronic mild stress (CMS) groups, treated with either vehicle or L. salivarius CECT 30632 for four weeks, starting one week before CMS exposure. Behavioral assessments, including the splash test (ST) and open field test (OF), were conducted. Biochemical analyses of peripheral blood mononuclear cells (PBMCs), plasma, and frontal cortex (FC) samples assessed antioxidant markers phospho-nuclear factor (erythroid-derived 2)-like 2 (p-Nrf2) and glutathione peroxidase 1 (GPx1), as well as tryptophan metabolites. Results In the ST, L. salivarius CECT 30,632 reduced latency to groom, indicating improved anhedonia and self-care, while no changes were observed in the OF test. CMS reduced p-Nrf2 and GPx1 expression in PBMCs, which was restored by L. salivarius CECT 30,632. This bacterium also reduced the QUINA/KYNA ratio in plasma and FC, suggesting a lower excitotoxicity risk. Conclusion Ligilactobacillus salivarius CECT 30632 improved behavioral outcomes, enhanced antioxidant defenses, and modulated tryptophan metabolism in a rat model of CMS. These findings support its potential as a probiotic intervention for depression.engAttribution 4.0 Internationalhttp://creativecommons.org/licenses/by/4.0/journal articlehttps://doi.org/10.1007/s00394-026-03941-9https://link.springer.com/article/10.1007/s00394-026-03941-9open accessLigilactobacillus salivariusAntidepressantChronic mild stressAntioxidantKynurenine metabolitesBioquímica (Medicina)Farmacología (Medicina)Neurociencias (Medicina)PsiquiatríaBiología molecular (Biología)2403 Bioquímica2490 Neurociencias3211 Psiquiatría