• The Effect of Probiotics on the Gut Microbiome and Depression
  • Setayesh Nouri,1 Atena Tahmasebi,2 Yasna Azizpour,3,*
    1. Department of Biology, SR.C., Islamic Azad University, Tehran, Iran.
    2. Department of Biology, SR.C., Islamic Azad University, Tehran, Iran.
    3. Department of Biology, SR.C., Islamic Azad University, Tehran, Iran.


  • Introduction: Depression is among the most frequent mental disorders, ranking second according to the World Health Organization's statistics. At the beginning of the twentieth century, a new scientific hypothesis emerged: physicians noticed the concomitant onset of the symptoms of depression with bowel illnesses and concluded that bowel health may influence mental disorders like depression. However, that relation remained just a hypothesis until the early 2010s. During the last two decades, many studies have investigated the gut-brain axis and its reciprocal communications. Such relation was confirmed through neural, endocrine, and immune routes. The first experiments were conducted on germ-free mice, which demonstrated that the absence of gut microbiota led to depression-related outcomes, such as disordered stress responses and altered neurotransmitter levels. By the early 2010s, the evidence confirmed that probiotics are capable of decreasing the signs of depression; they are called psychobiotics and are helpful bacteria in the therapy of mental disorders. To synthesize preclinical and clinical evidence on how gut microbiota composition and microbiota-targeted therapies influence emotional regulation and depression.
  • Methods: This study reviews and synthesizes findings from 16 seminal papers (2010–2024) on probiotics, prebiotics, synbiotics, metabolite pathways, and microbiome composition.
  • Results: Evidence from animal models and human clinical trials indicates that the gut–brain axis plays a key role in the pathogenesis of depression. A specific strain of probiotic bacteria is CCFM1025, classified within the species Bifidobacterium breve. This organism plays a role in the regulation of the gut-brain axis, and research has shown its potential antidepressant properties. Findings from studies indicated that this bacterium is safe and does not produce adverse effects. Notably, this probiotic has a distinct impact on tryptophan pathways, and in human trials, it has resulted in a considerable decrease in depression scores over a short duration. Future Research Directions: Conducting studies with bigger sample sizes and longer duration; assessment of immune mediators and inflammatory markers; exploration of effect longevity following drug withdrawal; exploring special clinical subgroups (e.g., subjects with endogenous major depressive disorders or comorbid gastrointestinal disorders).
  • Conclusion: Psychobiotics are promising but require longer, large RCTs, mechanistic biomarker studies, and convergence with measures of diet and neuroimaging. Clinical utility is greatest in patients with gastrointestinal symptoms or serotonergic-related side effects, in whom probiotics may be employed as an add-on or alternative therapy.
  • Keywords: tryptophan metabolism • psychobiotics • probiotics • prebiotics • gut microbiota • depression