Development and Evaluation of a Synbiotic Drink on Gut Microbiota, Stress Response, and Behavioral Outcomes in Mice model

Introduction: Dysregulation of the gut-brain axis under chronic stress contributes to the onset of anxiety and depressive disorders, with dysbiosis and HPA axis hyperactivity as key mechanisms. Emerging research highlights synbiotics the combinations of probiotics and prebiotics as promising interventions to restore microbial balance and alleviate neuropsychiatric symptoms.

Methods: This study evaluated the antidepressant, anxiolytic, microbiota-modulating, and stress biomarker effects of synbiotic drink (SKD) in a chronic unpredictable mild stress (CUMS) mice model. Thirty male Swiss Albino mice (5-8 weeks, 25-40 g) were randomized into five groups (n=6 each): non-stressed control, CUMS with distilled water, CUMS + imipramine (20 mg/kg/day), CUMS + kefir drink (5 mg/kg/day), and CUMS + SKD (5 mg/kg/day). CUMS was induced for 3 weeks, followed by 2 weeks of intervention.

Results: Behavioral tests showed SKD significantly increased active swimming time and decreased immobility in the forced swim test (comparable to imipramine and control), reduced passive hanging in the tail suspension test, and increased open arm time in the elevated plus maze, indicating robust antidepressant and anxiolytic effects. Stool analysis via 16S rRNA RT-PCR revealed SKD restored Gram-positive bacteria to 1.87 log10 copies/µL and normalized elevated Gram-negative bacteria to 1.08 log10 copies/µL compared to untreated mice, countering dysbiosis. Serum cortisol decreased significantly to 87.84 ng/mL with SKD compared with 114.6 ng/mL in untreated CUMS mice.

Conclusions: These multifaceted benefits highlight SKD's potential as a nutraceutical for stress-related disorders via gut microbiota restoration and HPA axis regulation.