The microbiota-gut-brain axis is a complex central nexus, intricately communicating with human health, affecting neurophysiological and cognitive processes. In this review article, the therapeutic potential of psychobiotics is comprehensively examined as a relatively new category of probiotics that have been shown to have beneficial effects on mental health, particularly in the context of the increasing prevalence of neurological and gastrointestinal pathologies in developing economies particularly Pakistan. This current discussion examines the pathways through which psychobiotics are postulated to influence their beneficial effect such as their role in biosynthesis of neuroactive substances, the regulation of the hypothalamic-pituitary-adrenal (HPA) axis, and inflammatory response. Some specific strains of bacteria including Lactobacillus plantarum PS128, Lactobacillus helveticus NS8, Bifidobacterium longum 1714, Lactobacillus rhamnosus (JB-1), and Bifidobacterium infantis (35624) play an important role in overcoming anxiety and mood disorders. The neuroactive chemicals (gamma-aminobutyric acid (GABA), dopamine, norepinephrine, acetylcholine, and serotonin) are extracted from gut microbes and have the ability to alter the brain activity. Other metabolites and intermediate substances, such as Brain-Derived Neurotrophic Factor (BDNF) and short-chain fatty acids (SCFAs), maintain the integrity of the intestinal barrier and control the immune system and inflammatory response. The psychobiotic food pyramid aims to protect gut and mental health while psychobiotic supplements are been known to alleviate chronic stress and anxiety. They are used to treat different types of mental conditions, such as neurodegenerative, neurodevelopmental, psychiatric, and GI disorders as well. Mental health disorders (with depression having the highest percentage) are increasing in various countries including Pakistan every day, with women being affected more than men. The review incorporates existing evidence based on both preclinical and clinical studies and clarifies the nexus of critical importance between the disorder of gut microbiota and the pathogenesis of mental health disorders that were aggravated in the course of the COVID-19 pandemic. Additional research is imperative in determining the long-term effectiveness and safety of psychobiotic interventions, particularly against a diverse population and different socioeconomic environments. This study therefore, contributes to highlighting the tremendous potential of psychobiotics as a cost-effective and innovative approach to supplementing traditional mental healthcare modalities.
