Tabriz University of Medical Sciences Health Promotion Perspectives 2228-6497 16 1 2026 06 06 Psychobiotic Effects of Postbiotics in Depression, Psychosis and Mania 27 47 10.34172/hpp.44340 EN Aziz Homayouni-Rad https://orcid.org/0000-0001-6766-0108 Jalil Houshyar Hossein Alikhah https://orcid.org/0000-0002-2224-4319 Saba Kamalledin Moghadam https://orcid.org/0000-0003-4858-5469 Zohreh Osouli Ali Asgharzadeh Vahideh Sarabi-Aghdam Alireza Asghari REVIEW 10.34172/hpp.44340 2025 02 09 2025 03 10 Background: The gut microbiota significantly influences mental health through the gut-brain axis, modulating mood, cognition, and emotional regulation. While probiotics and prebiotics have been widely studied for their psychobiotic effects, postbiotics—metabolic byproducts of probiotics—represent an underexplored area with potential therapeutic applications. Understanding the role of postbiotics in mental health disorders, such as depression, psychosis, and mania, could lead to novel treatment strategies. This review examines the psychobiotic potential of postbiotics and their mechanisms of action. Methods: A systematic literature review was conducted to evaluate the effects of postbiotics on mental health conditions. We searched PubMed, Medline, EMBASE, and the Cochrane Library for English-language articles published between January 1, 2015, and January 1, 2025, using keywords such as "postbiotic," "paraprobiotic," "depression," "anxiety," and "psychosis." A manual search supplemented the electronic search to ensure comprehensive coverage. Studies focusing on postbiotic effects on mood regulation, neuroinflammation, and neurotransmitter modulation were included. Results: Postbiotics demonstrate promising psychobiotic effects in depression, psychosis, and mania. They modulate neurotransmitter levels, including serotonin and gamma-aminobutyric acid (GABA), and reduce neuroinflammation, contributing to improved mood and cognitive function. Additionally, postbiotics influence the hypothalamic-pituitary-adrenal (HPA) axis, enhancing stress response and emotional regulation. These findings suggest that postbiotics may serve as effective therapeutic agents for mental health disorders. Conclusion: Postbiotics offer significant potential as novel interventions for mental health conditions, with mechanisms involving neurotransmitter modulation and neuroinflammation reduction. Further empirical research is needed to elucidate their clinical applications and optimize therapeutic protocols. This review highlights the importance of postbiotics in advancing innovative strategies to improve mental health outcomes and well-being.