Immunoprotective and neuroprotective properties of gut microbiome in psoriasis

Psoriasis impacts nearly 100 million people globally and is associated with neuropsychiatric comorbidities such as depression and anxiety. With gut microbiome dysbiosis serving as a primary pathophysiological factor, the gut-brain-skin axis provides a crucial framework for understanding this relationship. This review evaluates the mechanisms of the gut-brain-skin axis in psoriasis pathophysiology and assesses the therapeutic potential of microbiome-based treatments, combining preclinical, clinical, and multi-omics data. Patients with psoriasis show specific gut dysbiosis patterns, including reduced microbial diversity, lower SCFA-producing bacteria (especially Faecalibacterium and Akkermansia), and increased pro-inflammatory bacteria. This microbial imbalance damages intestinal barrier integrity, triggers systemic inflammation, activates cutaneous Th17 pathways, and induces neuroinflammation through blood-brain barrier disruption. Axis communication occurs through immune-inflammatory mechanisms mediated by SCFAs and neuroendocrine pathways involving microbially-derived neurotransmitters (GABA, serotonin, dopamine). Metagenomic research indicates functional deficiencies in neurotransmitter and SCFA synthesis pathways are more significant than taxonomic alterations. Machine learning models can utilize these functional features to identify patients at risk for neuropsychiatric comorbidities and predict treatment response. Recent randomized controlled trials demonstrate that targeted interventions (probiotics, prebiotics, postbiotics, fecal microbiota transplantation) significantly improve Psoriasis Area and Severity Index scores, inflammatory markers, and microbiota composition. The evidence supports a shift toward integrated microbiome strategies, emphasizing functional approaches including mitochondrial therapies, psychobiotics, precision nutrition, and multi-omics-guided therapies.