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Background: The oral microbiome has been increasingly associated with systemic lupus erythematosus (SLE). While research suggests a correlation between the oral microbiome and SLE, the definitive causal relationship remains unclear and warrants further investigation.
Objectives: To investigate the causal relationship between the oral microbiome and SLE using Mendelian randomization (MR) analysis in East Asians.
Methods: We conducted a bidirectional two-sample MR analysis to explore the causal link between the oral microbiome and SLE. Oral microbiome data were obtained from a genome-wide association study (GWAS) involving 2017 tongue dorsum samples and 1915 salivary samples. SLE summary statistics were derived from a GWAS meta-analysis of 4222 cases and 8431 controls of East Asian ancestry. Multiple testing correction was performed using the Benjamini-Hochberg method ( P FDR <0.05).
Results: Significant associations were identified between 47 salivary microbiome taxa (20 positive and 27 negative) and 39 tongue microbiome taxa (26 positive and 13 negative) with SLE (Figure 1). Among saliva microbiome, the top two microbes identified as increasing the risk of SLE were TM7x unclassified species-level clusters ( uSGB) 1848 (β = 0.551, P FDR = 5.67 × 10 −5 ), and Pseudoramibacter (β = 0.590, P FDR = 2.42 × 10 −5 ). Conversely, Solobacterium uSGB 2890 (β = −0.562, P FDR = 0.001), and Lancefieldella uSGB 3453 (β = −0.701, P FDR = 3.34 × 10 −5 ) were associated with a reduced risk. Within the tongue microbiome, f_Saccharimonadaceae uSGB 2936 (β = 0.420, P = 0.0229) and Lachnoanaerobaculum uSGB 645 (β = 0.469, P = 0.0003) were linked to an increased risk of SLE, while Streptococcus uSGB 2551 (β = -0.515, P = 0.0191) and Streptococcus uSGB 1472 (β = -0.466, P = 0.0066) conferred a protective effect. The protective effect of Streptococcus uSGB 1472 was linked to the rs71423231 variant, associated with the KYNU gene, which plays a role in tryptophan metabolism. Additionally, metabolites in the kynurenine pathway were implicated in SLE [1]. Negative correlations were observed between SLE and Porphyromonas in both saliva and tongue, while positive correlations were noted with Prevotella in saliva and Veillonella in the tongue ( P uncorrected < 0.05). These findings align with previous studies reporting significant abundance differences in these taxa between SLE patients and healthy controls [2, 3].
Conclusion: To our knowledge, our study represents the first effort to investigate the causal relationship between the oral microbiome and SLE. The results support a causal link, offering novel insights into potential therapeutic targets for SLE.
REFERENCES: [1] Åkesson K, et al. Lupus Sci Med 2018.
[2] Liu F, et al. Front Immunol 2021.
[3] Guo J et al. J Transl Med 2023.
Forward MR analysis revealed causal relationships between the salivary and tongue microbiomes and SLE. (a) The bar plot represents the causal effects of 47 significant salivary microbiome taxa on SLE, as estimated by MR analysis ( P FDR < 0.05). The MR effect size estimates (Beta) are displayed. (b) The bar plot shows the causal effects of 39 significant tongue microbiome taxa on SLE, as estimated by MR analysi ( P FDR < 0.05). Known species-level clusters are denoted as kSGB(“g__” represents genus levels, while “p__” represents Phylum levels).
Reverse MR analysis identified causal relationships between SLE and the salivary and tongue microbiomes. (a) Bar plot shows the causal effects of SLE on 44 significant salivary microbiome taxa, as estimated by MR analysis ( P uncorrected < 0.05). The MR effect size estimates (Beta) are displayed. (b) Bar plot illustrates the causal effects of SLE on 64 significant tongue microbiome taxa, as estimated by MR analysis ( P uncorrected < 0.05).
Acknowledgements: NIL.
Disclosure of Interests: None declared.
© The Authors 2025. This abstract is an open access article published in Annals of Rheumatic Diseases under the CC BY-NC-ND license (