Introduction: Psychobiotics represent an emerging class of probiotics with distinct neuroactive and immunomodulatory capabilities that influence the microbiota–gut–brain (MGB) axis. Unlike conventional probiotics, psychobiotics produce or stimulate the synthesis of neurochemicals—such as gamma-aminobutyric acid (GABA), serotonin, dopamine, and short-chain fatty acids (SCFAs)—which exert modulatory effects on central nervous system (CNS) function, neuroinflammation, and hypothalamic-pituitary-adrenal (HPA) axis regulation. These properties have positioned psychobiotics as promising adjunctive interventions for neurodevelopmental, neurodegenerative, and mood disorders.
Methods: This review systematically analyzed cohort, case-control, and interventional studies published from 2019 to 2025, sourced via comprehensive keyword searches in PubMed, Scopus, Medline, and ScienceDirect. Emphasis was placed on clinical trials investigating psychobiotic efficacy, strain specificity, mechanistic pathways, and safety profiles across diverse neuropsychiatric populations.
Results: Accumulating evidence underscores the therapeutic potential of psychobiotics in restoring gut microbial homeostasis and alleviating symptomatology in disorders such as autism spectrum disorder (ASD), attention-deficit/hyperactivity disorder (ADHD), Alzheimer’s disease (AD), Parkinson’s disease (PD), depression, and anxiety. In ASD and ADHD cohorts, administration of Lactobacillus and Bifidobacterium strains normalized dysbiotic microbiota compositions, mitigated gastrointestinal dysfunction, and elicited measurable improvements in behavioral and cognitive parameters. Furthermore, adjunctive use of neuropeptides like oxytocin with psychobiotics demonstrated synergistic benefits in reducing core ASD symptoms. In neurodegenerative contexts, psychobiotic-mediated modulation of gut microbiota reduced peripheral and central neuroinflammation, potentially decelerating disease progression. Notably, Lactobacillus rhamnosus and Bifidobacterium longum exert anxiolytic and antidepressant-like effects via attenuation of systemic inflammation, modulation of neurotransmitter synthesis, and stabilization of HPA axis hyperactivity.
Conclusion: Psychobiotics constitute a novel, mechanistically informed therapeutic modality targeting the MGB axis to modulate neuropsychiatric pathology. While preclinical and emerging clinical data are promising, critical gaps remain in delineating optimal strain combinations, dosing regimens, treatment durations, and patient-specific factors influencing responsiveness. Rigorous, large-scale randomized controlled trials are imperative to validate efficacy, assess long-term safety, and enable integration into precision psychiatry frameworks. Ultimately, harnessing psychobiotics may revolutionize treatment paradigms by offering targeted, gut-centric approaches to improve mental health and neurological outcomes.