Oral microbiome dysbiosis in primary Sjögren’s syndrome: a systematic review and meta-analysis

OBJECTIVES: Dry mouth symptoms in patients with primary SS (pSS) may be associated with oral microbiome dysbiosis, which plays a critical role in the pathogenesis of pSS and potentially contributes to disease progression. This study systematically reviews and meta-analyses the latest research on the relationship between the oral microbiome and pSS to identify potential diagnostic biomarkers. METHODS: A systematic search was conducted across nine international databases (PubMed, Cochrane Library, Embase, Web of Science, Scopus, VIP, CNKI, Wanfang, and SinoMed) up to 1 October 2024, using a combination of Medical Subject Headings (MeSH) and free-text terms: 'oral microbiome' OR 'oral flora' AND 'Sjögren's Syndrome' OR 'pSS'. Only studies analysing the oral microbiota of pSS patients were included. A random-effects meta-analysis was performed for quantitative synthesis, and funnel chart was used to assess the publication bias of the included articles. The conclusions are tempered by the moderate risk of bias in some of the included studies, the substantial heterogeneity (partly attributed to methodological heterogeneity), and the limited number of studies for certain subgroup analyses, which may affect the precision of the pooled estimates. RESULTS: A total of 833 studies were identified, 21 of which were included, with 16S rRNA sequencing being the most commonly used technique. Quantitative Insights Into Microbial Ecology (QIIME) is a mainstream bioinformatics analysis tool. Of the 21 studies (1094 participants) included, 19 provided data on α diversity. Overall, declines in the α diversity index were common in pSS [Chao1: SMD = -0.79, (95% CI = -1.381, -0.21), P < 0.001; Shannon index: SMD = -0.16, (95% CI = -0.53, -0.21), P = 0.400; Simpson index: SMD = -0.14, (95% CI = -0.79, -1.06)], P = 0.770. Ten of these studies provided data on β diversity, suggesting a clear difference between the pSS group and the healthy control (HC) group. Firmicutes (mainly including Streptococcus spp., Velon spp., etc.) showed a significant enrichment trend in pSS patients, and the relative abundance of Proteobacteria (Haemophilus), Actinomycetes and Spiromycetes decreased in pSS patients. CONCLUSION: pSS patients demonstrate reduced oral microbiome diversity compared with HCs. Enrichment of Veillonella, Streptococcus and Prevotella may correlate with pSS pathogenesis, whereas Haemophilus parainfluenzae might serve as a protective taxon. Oral dysbiosis appears to be a distinctive feature of pSS compared with SLE. Further mechanistic studies are needed to explore causal relationships and therapeutic targets. TRIAL REGISTRATION: Trial registration: PROSPERO, https://www.crd.york.ac.uk/prospero/, CRD42024611041.