Psychobiotics in mental health: insights from human clinical trials via the gut-brain axis

Recent research has highlighted the gut-brain axis as a critical modulator of mental health, positioning probiotics as promising psychobiotic interventions for anxiety, stress, depression, and cognitive function. Clinical trials investigating strains such as Lactobacillus rhamnosus, Bifidobacterium longum, Lactobacillus gasseri, and multi-strain formulations have demonstrated strain- and context-specific effects on psychological and physiological outcomes. While some studies reported improvements in mood, anxiety, sleep quality, and cognitive performance, others showed limited effects, particularly in healthy populations with low baseline stress levels, reflecting the challenges of translating preclinical findings into clinical applications in humans. Mechanistic evidence suggests that psychobiotics may influence neuroactive metabolites, short-chain fatty acids, γ-aminobutyric acid, serotonin, and anti-inflammatory pathways, thereby modulating cognitive and emotional processes. The effects happen dependent on factors such as dosage, strain specificity, delivery method, baseline stress or symptom levels, and co-administration with conventional treatments. Collectively, these findings underscore the potential of targeted psychobiotics to enhance mental well-being and support stress resilience, while highlighting the need for carefully designed clinical trials to clarify efficacy and mechanisms.