Coordinated oral-gut microbiota relocation in connective tissue diseases: a systematic review

Alterations of the gut microbiome are well documented in connective tissue diseases, whereas the oral microbiome has largely been studied in isolation. Emerging evidence suggests coordinated dysbiosis across mucosal sites with oral-gut relocation of pathobionts occurring in animal models; however, it remains unclear whether consistent oral and gut microbiome alterations occur in systemic lupus erythematosus (SLE) and primary Sjögren's syndrome (pSS). This review systematically synthesizes evidence on oral and gut microbiome alterations in SLE and pSS with a focus on recurrent opposing abundance patterns across anatomical sites compatible with oral-gut microbial relocation.

Observational studies comparing adult patients with SLE or pSS to healthy controls and reporting oral and/or gut microbiome data were included. Interventional studies, case reports, reviews, and non-human studies were excluded. PubMed was searched from inception to November 2024. Study quality was assessed using the Newcastle-Ottawa Scale. Microbial alterations were harmonized using current NCBI taxonomy and synthesized descriptively without meta-analysis.

Thirty-three studies comprising 1,385 patients and 2,131 healthy controls were included. Intestinal Shannon and Simpson α-diversity were frequently reduced, whereas oral diversity was preserved or increased. Recurrent opposing abundance patterns were observed for specific taxa, most consistently involving Streptococcus and Actinomycetota in SLE and Pseudomonadota in pSS, characterized by decreased oral and increased intestinal relative abundance. Several taxa, including Veillonella and Veillonellaceae, showed parallel enrichment across both sites.

SLE and pSS are characterized by coordinated dysregulation of the oral and gut microbiomes. Opposing abundance patterns across anatomical sites support the concept of disease-associated microbial redistribution although causal inference is limited given the data was derived primarily from cross-sectional studies with relative abundances. Overall, this study highlights the oral-gut axis as an underexplored dimension of mucosal immune dysregulation in connective tissue diseases.