Regulatory Effects of Probiotics on Anxiety and Depression-Like Behaviors in H. pylori-Infected Rats

Helicobacter pylori (H. pylori) is a highly prevalent gastrointestinal infection associated with peptic ulcers, gastritis, and psychological disorders like anxiety and depression. This study explored whether probiotic supplementation with Lactobacillus rhamnosus (L. rhamnosus) and/or Lactobacillus plantarum (L. plantarum) could mitigate anxiety- and depressive-like behaviors in H. pylori-infected rats. In addition, specific biochemical mechanisms underlying H. pylori and probiotic effects were investigated. Rats were infected with H. pylori and treated with L. rhamnosus, L. plantarum, or both probiotics via oral gavage. Anxiety- and depression-like behaviors were assessed using open field, elevated plus maze, forced swimming, and marble burying tests. Oxidative stress markers, inflammatory cytokines, brain-derived neurotrophic factor (BDNF), serotonergic function, and corticosterone level were quantified in cortical tissues. Both L. rhamnosus and L. plantarum, particularly when co-administered, potently reversed the anxiogenic and depressogenic effects of H. pylori infection. These behavioral rescues were paralleled by normalization of dysregulated cortical oxidative and inflammatory parameters including suppressed anti-inflammatory cytokine IL-10 and reduced antioxidant defenses. Similarly, H. pylori-induced attenuation of neurotrophic capacity and serotonin availability alongside heightened corticosterone level were all opposed by L. rhamnosus and L. plantarum supplementation. Our integrative methodology provided pivotal evidence that multispecies probiotic intervention with L. plantarum and L. rhamnosus alleviates anxiety/depressive-like symptoms in a preclinical model of gastrointestinal inflammation. We propose that adjunctive probiotic therapy could promote the behavioral resilience by optimizing the redox regulation, suppression of inflammatory response, enhancement of neurotrophic support, and maintenance of serotonergic transmission in brain cortex. These data signify probiotic supplementation warrants further evaluation in infected patients with psychiatric comorbidities.