Cross-Disease Microbiome Signatures Associated with Autoimmune Disorders: A Comparative Meta-Analysis of Public Sequencing Datasets

<title>Abstract</title> <p>Background The gut microbiome may play a role in immune system regulation, and alterations in its composition have been associated with multiple autoimmune disorders. However, the extent to which microbial signatures are shared across different autoimmune diseases remains incompletely understood. Methods We conducted a systematic review and meta-analysis of publicly available 16S rRNA gene sequencing and metagenomic datasets from patients with rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), multiple sclerosis (MS), type 1 diabetes (T1D), inflammatory bowel disease (IBD), and ankylosing spondylitis (AS). Data were sourced from published studies and public repositories. Alpha and beta diversity analyses, differential abundance testing, and functional pathway predictions were performed. This meta-analysis was conducted according to the PRISMA 2020 reporting guidelines. Results Analysis of 47 studies comprising 3,847 autoimmune disease patients and 2,956 healthy controls revealed consistent patterns of reduced alpha diversity across all autoimmune conditions (p &lt; 0.001). Common microbial signatures included depletion of Faecalibacterium prausnitzii (present in 89% of studies), Roseburia spp. (76%), and Akkermansia muciniphila (71%), alongside enrichment of Prevotella copri in RA (67% of studies), Ruminococcus gnavus in SLE (82%), and Klebsiella pneumoniae in AS (45%). Statistical heterogeneity was moderate to high across studies (I² = 52–78%). The Firmicutes/Bacteroidetes ratio was significantly reduced in SLE (p &lt; 0.001) and T1D (p &lt; 0.01) but not consistently altered in RA. Functional analysis revealed decreased butyrate production pathways across all autoimmune diseases. Publication bias was assessed using funnel plots and Egger's test. Conclusions Our findings suggest that both shared and disease-specific microbiome signatures may exist across autoimmune disorders, with depletion of butyrate-producing bacteria representing a potentially common feature. These results are consistent with the hypothesis that gut dysbiosis may be associated with autoimmune pathogenesis through mechanisms potentially involving short-chain fatty acid alterations and intestinal barrier dysfunction, providing potential targets for future microbiome-based therapeutic research.</p>