The Hidden Ecosystem Behind Immune-Mediated Disorders: A Systematic Review and Meta-Analysis of Microbiome Dysbiosis and Disease Activity

Abstract

Background: It is becoming more well acknowledged that systemic immune dysfunction is modulated by the gut microbiome. No comprehensive synthesis has examined gut dysbiosis patterns and their association with disease activity measures throughout the whole spectrum of rheumatic disorders, despite isolated studies linking certain microbial taxa to various rheumatic diseases.

Objectives: To conduct a systematic review and meta-analysis of gut microbiome modifications in rheumatoid arthritis (RA), psoriatic arthritis (PsA), ankylosing spondylitis (AS), systemic lupus erythematosus (SLE), and systemic sclerosis (SSc); to quantify correlations between microbial taxa and established disease activity indices; and to assess the therapeutic potential of microbiome-targeted interventions.

Methods: We conducted a search of PubMed/MEDLINE, EMBASE, Cochrane Library, and Web of Science for studies published from 2015 to 2025, adhering to PRISMA 2020 recommendations. Studies that presented gut microbiome data in conjunction with validated disease activity scores in adult patients with rheumatic illnesses were included. A random-effects meta-analysis utilizing the Der Simonian-Laird technique was conducted, with heterogeneity evaluated through I² statistics. The quality of the study was assessed utilizing the modified Newcastle-Ottawa Scale.

Results: A total of sixty-five studies (42 incorporated in the meta-analysis; 23,847 individuals) were synthesized. A distinct pan-rheumatic dysbiosis profile was identified, characterized by a reduction in anti-inflammatory taxa and an increase in pro-inflammatory species Probiotics, dietary changes, and biological therapy (TNF/IL-17 inhibitors) have been shown to partially restore the microbiota and simultaneously increase disease activity.

In conclusion: different microbial fingerprints linked to disease activity indicate that gut dysbiosis is a constant and quantifiable feature of rheumatic disorders. Microbiome-focused interventions offer a promising additional treatment approach, but they necessitate large-scale randomized controlled studies