Comprehensive Analysis of the Relationships Between the Gut Microbiota and Fecal Metabolome in Individuals With Primary Sjogren’s Syndrome by 16S rRNA Sequencing and LC–MS-Based Metabolomics

Abstract

The gut microbiota has been associated with primary Sjogren’s syndrome (pSS), yet the biological implications of these associations are often elusive. We analyzed the fecal microbiota through 16S rRNA gene amplification and sequencing in 30 patients with pSS and 20 healthy controls (HCs); At the same time, the fecal metabolome was characterized by ultrahigh-performance liquid chromatography–mass spectrometry. In addition, correlation analyses of microbiota and metabolome data were performed to identify meaningful associations. We found that the microbiota composition of pSS patients was significantly different from that of HCs. The pSS gut microbiota is characterized by increased abundances of proinflammatory microbes, especially Escherichia-Shigella, and decreased abundances of anti-inflammatory microbes. Concerning the metabolome, a multivariate model with 33 metabolites efficiently distinguished cases from controls. Through KEGG enrichment analysis, we found that these metabolites were mainly involved in amino acid metabolism and lipid metabolism. The correlation analysis indicated that there were certain correlations between the microbiota and metabolism in pSS patients. In addition, an abundance of Escherichia-Shigella was found to be correlated with high levels of four metabolites (aflatoxin M1, glycocholic acid, L-histidine and phenylglyoxylic acid). Our research suggests that in pSS patients, the gut microbiota is characterized by a specific combination of proinflammatory changes and metabolic states. Escherichia-Shigella is a factor related to gut dysbiosis, which may promote intestinal damage and affect amino acid metabolism.