# Behavioral, antioxidant, and kynurenine pathway modulation of a specific strain of Ligilactobacillus salivarius in a preclinical model of depression

## TL;DR

A specific strain of Ligilactobacillus salivarius may help reduce depression symptoms by improving antioxidant defenses and balancing harmful brain chemicals.

## Contribution

This study is the first to show that L. salivarius CECT 30632 modulates the kynurenine pathway and antioxidant systems in a rat model of depression.

## Key findings

- L. salivarius CECT 30632 reduced grooming latency in the splash test, suggesting improved anhedonia.
- The strain restored antioxidant markers like p-Nrf2 and GPx1 in stressed rats.
- It lowered the QUINA/KYNA ratio in plasma and frontal cortex, indicating reduced excitotoxic risk.

## Abstract

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.

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.

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.

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.

The online version contains supplementary material available at 10.1007/s00394-026-03941-9.