Psoriasis: microbiome dysbiosis and pathogenic mechanisms

TL;DR

This paper reviews how gut and skin microbiome imbalances contribute to psoriasis by influencing immune responses and disease progression.

Contribution

The paper introduces a novel mechanistic framework showing that microbiome dysbiosis is a central regulatory factor in psoriasis pathogenesis.

Findings

Gut dysbiosis reduces SCFA production and weakens the intestinal barrier, promoting systemic inflammation.

Cutaneous dysbiosis, especially Staphylococcus aureus dominance, amplifies IL-17-driven inflammation in the skin.

Specific infections like HCV and H. pylori trigger psoriasis by activating shared inflammatory pathways.

Abstract

Psoriasis is a chronic immune-mediated inflammatory disease whose pathogenesis is a triad of genetic predisposition, immune dysregulation, and environmental triggers. This review provides a novel, in-depth synthesis arguing that microbial dysbiosis is not merely an associative phenomenon but a central regulatory node within this triad, actively shaping immune responses and clinical phenotypes. We move beyond cataloging microbial shifts to construct a detailed mechanistic framework of the gut-skin axis. Gut dysbiosis; characterized by reduced diversity, a diminished Bacteroidetes/Firmicutes ratio, and depleted SCFA producers, compromises intestinal barrier integrity, reduces systemic immunoregulatory tone via diminished SCFA signaling, and promotes Th17 polarization. This systemic inflammation is directly communicated to the skin. Concurrently, cutaneous dysbiosis, featuring Staphylococcus aureus dominance and fungal alterations, disrupts the local barrier, provides chronic antigenic stimulation, and amplifies IL-17-driven inflammation, creating a self-sustaining loop. Crucially, we analyze how specific infections (HCV, H. pylori, Streptococcus) act as environmental triggers by sharing or activating these very pathways. The bidirectional relationship with therapy is dissected: while biologics induce drug-specific microbiome shifts that often correlate with clinical normalization, they also carry infection risks that must be strategically managed. Emerging microbiome-targeted interventions like specific probiotics show promise but are hampered by methodological inconsistencies. This review uniquely highlights the causality gap and proposes that future breakthroughs require a shift from correlation to mechanism. We conclude that the microbiome is a dynamic interface between genes and environment in psoriasis; its successful integration into diagnostic and therapeutic paradigms demands standardized multi-omics approaches, functional validation, and personalized medicine strategies that target this critical axis.

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