The Gut–Brain Axis in Psychiatric Disorders: Emerging Evidence and Therapeutic Perspectives

Abstract Context. The microbiota-gut-brain axis is now extensively used in biological psychiatry, but there is still a big gap between the ability of rodents studies showing some plausible mechanisms to impact humans. There is a statement that the review focuses on what mechanisms, observational and interventional evidence show the connection between gastrointestinal microbiome and psychiatric disorders and which microbial therapies are clinically applicable. Methods. We conducted searches in PubMed/MEDLINE, Embase, PsycINFO, Scopus and the Cochrane Library for mechanistic studies, microbiota case–control studies, data from prospective cohorts, Mendelian randomisation studies, randomized controlled trials (RCTs) and meta-analyses investigating gut–brain signaling in psychiatric disorders from inception to May 2026. Evidence is synthesized in narrative form and graded in terms of study design, replicability and risk of bias. The outcome. There are a few communication routes that are backed strongly such as vagal afferent signaling, immune and inflammatory mediation, HPA axis programming and microbial metabolites which include short-chain fatty acids, bile acids and tryptophan catabolites. Case-control studies also state the changing microbial composition in major depressive disorder, schizophrenia, bipolarity disorder and autism but the results from various research lacking in taxon-level findings and the studies are conducted on a small-scale thus, they could be confounded by such things as diet, tobacco consumption and psychoactive drugs. In research work using the technique of fecal transfer from patients the behavior of animals that had been previously considered to be germ-free or treated with antibiotics were influenced thus proving that it works. Interventions in diet are the most effective ways of depression treatment, whereas, while probiotics are less effective in such situation than diet, pre-, pro- and post-biotics have not shown their effectiveness at all. Final thoughts. Rather than a common source of psychiatric disorders, the gut-brain axis is a valid contributing pathway in certain groups of individuals. For progress to be made, it will be necessary to implement longitudinal, multi-omic, sufficiently powered studies with pre-registered microbiota endpoints, strain-level resolution, and inclusion of participants with different levels of inflammation and metabolic phenotypes. Keywords: microbiota–gut–brain axis; gut microbiome; major depressive disorder; schizophrenia; probiotics; faecal microbiota transplantation; short-chain fatty acids; psychobiotics