Microbiome-immune-cutaneous and neuro-metabolic axis in complex chronic inflammatory diseases: transcontinental cohort and therapeutic prediction algorithm

Abstract

Introduction: Complex chronic inflammatory diseases (CCIDs), including psoriasis, inflammatory bowel disease (IBD), atopic dermatitis, and neuropsychiatric disorders, exhibit high comorbidity and share pathophysiological mechanisms mediated by the gut-brain-skin axis (Hawkins et al., 2025; Pearson et al., 2025). Gut microbial dysbiosis, characterized by depletion of short-chain fatty acid (SCFA)-producing taxa and enrichment of pro-inflammatory taxa, emerges as a unifying factor in these conditions (Hawkins et al., 2025). Objective: To synthesize the available evidence on the microbiome-immune-cutaneous and neuro-metabolic axis in CCIDs, and to evaluate the potential of therapeutic prediction algorithms based on multimodal phenotyping to guide personalized interventions. Methodology: Systematic review following PRISMA 2020 guidelines (Page et al., 2021). A systematic search was conducted in PubMed, LILACS, SciELO and Cochrane for studies published between 2020 and 2026 on the gut-brain-skin axis, multimodal phenotyping and predictive algorithms in CCIDs. Observational studies, technological developments and clinical trials were included. Quality was assessed using the adapted Newcastle-Ottawa scale (Wells et al., 2000). Results: Eight relevant studies were identified. Evidence confirms that gut dysbiosis, characterized by reduction of Faecalibacterium, Roseburia and Eubacterium, and increase of pro-inflammatory taxa, is consistently associated with CCIDs and their neuropsychiatric comorbidities (Hawkins et al., 2025; Vestergaard et al., 2026). Multi-omics studies have demonstrated significant genetic correlations between IBD and psoriasis (ρ = 0.23-0.25) (Vestergaard et al., 2026). Microbiome-directed interventions, including probiotics, prebiotics and dietary modifications, have shown promising effects in reducing systemic inflammation and improving cutaneous and neuropsychiatric symptoms (Biazzo et al., 2026; Hawkins et al., 2025). Conclusion: The microbiome-immune-cutaneous and neuro-metabolic axis represents an integrative paradigm for understanding the pathogenesis of CCIDs and their comorbidities. Therapeutic prediction algorithms based on multimodal phenotyping offer a promising pathway for precision medicine, enabling personalized selection of microbiome-directed interventions in the context of transcontinental cohorts.