Fecal Non-targeted Metabolomics Study Of Primary Sj?gren’s Syndrome Based On Positive Anti-SSA Antibody

Objective:pSS is an autoimmune disease caused by exocrine adenitis.Gut microbes play an important role in human autoimmune diseases.Several recent studies have demonstrated the role of gut microbes in p SS.Fecal metabolites are key messengers in gut microbe-host interactions.For example,butyrate,one of the metabolites of gut microbes,can participate in the pathogenesis of p SS by regulating T cells and B cells.Although a large number of metabolomics and microbiome studies have been carried out in recent years,the link between gut microbes and the pathogenesis of p SS has not been clearly elucidated,so further research is needed.Based on this,we performed fecal metabolomics of serum anti-SSA antibody-positive p SS,and screened differential metabolites to find potential biomarkers and differential metabolite-related metabolic pathways.Methods:A liquid chromatography mass spectrometry(LC-MS)metabolomic analysis platform combined with univariate and multivariate analysis techniques was used to conduct untargeted metabolomic analysis of feces from 11 p SS patients with positive serum anti-SSA antibody and 18 HC.Multivariate statistical analysis included unsupervised principal component analysis(PCA)with supervised partial least squares discriminant analysis(PLS-DA)and orthogonal partial least squares discriminant analysis(OPLS-DA).Differential metabolites and related metabolic pathways associated with anti-SSA antibody-positive p SS disease were analyzed.Results:1.In this study,a total of 149 endogenous differential metabolites were screened,including 115 up-regulated metabolites and 34 down-regulated metabolites.2.Differential metabolic pathways mainly involve linoleic acid metabolism,ABC transporters,arginine biosynthesis,and tyrosine metabolism pathways.3.Four differential metabolites of undecanoic acid,9,10:12,13-diepoxyoctadecanoate,2-ketobutyric acid,and hydroxyjunine have good diagnostic properties as potential biomarkers associated with anti-SSA antibody-positive p SS disease.Conclusion:The fecal metabolism of p SS patients with positive serum anti-SSA antibody has unsaturated fatty acid and amino acid metabolism disorder.Therefore,gut microbes may be involved in p SS pathogenesis.Fecal metabolomics is an effective tool to study p SS,and provides an innovative and feasible research method for studying the involvement of gut microbes and their metabolites in the pathogenesis of p SS.