Gut-brain axis targeting postbiotics for treatment of psychological and neurodegenerative disorders

Current pharmacological treatments for psychological and neurodegenerative disorders largely ignore the vital role of the gut microbiome in cognition. Antipsychotics and antidepressants often disturb the gut environment, impacting mood stabilisation, neurotransmitter signalling, and cognitive functions mediated by the gut-brain axis. This ultimately undermines treatment efficacy while triggering cascading metabolic side effects, including weight gain and hyperglycaemia. Coupled with the rising global burden of these disorders, there is a need for innovative therapies that effectively target the gut microbiome to pharmacologically mediate the gut-brain axis. Postbiotics, comprising inert microorganisms or their components, are one such microbiome-targeted therapy that has recently shown the capacity to treat an array of psychological and neurodegenerative disorders, including depression, anxiety, Alzheimer's, and Parkinson's disease, while mitigating common manufacturing, storage, and efficacy limitations of conventional probiotics. However, clinical trials validating postbiotic treatment efficacy in neurological diseases are lacking, indicating the need for further investigation. This review therefore aims to examine the therapeutic potential of postbiotics and bridge the gap between preclinical research and clinical practice. • Postbiotics offer a therapeutic option as an adjuvant or alternative to standalone pharmacological therapy. • Stringent manufacturing, handling and storage requirements typically plaguing probiotics are circumvented by postbiotics whilst offering similar clinical efficacy. • Postbiotics present an opportunity to viably alter neurogenetics and trigger meaningful changes to psychological and neurodegenerative pathways. • Stress hormonal responses are notably altered by postbiotics, thereby mitigating pathogenesis pathways for anxiety and depression.