Ophiopogonin D Mediates Therapeutic Effects on Primary Sjögren's Syndrome by Modulating Gut Microbiota and Metabolite Profiles

This study aimed to investigate the mechanism of ophiopogonin D (OD) in treating primary Sjögren's syndrome (pSS) through integrated analysis of gut microbiota and metabolomics. Non-obese diabetic/LtJ mice, a well-established pSS model, were used as the model group and treated with OD or hydroxychloroquine. Fecal and tissue samples were collected starting 4 weeks after administration. Basic pathological examination, 16S rRNA sequencing, and ultra-high-performance liquid chromatography-mass spectrometry were employed to assess changes in tissue function, inflammation levels, gut microbiota, and metabolite profiles across all groups. The results showed that OD reduced the expression levels of inflammatory factors, regulated immune balance, and ameliorated functional damage of the submandibular gland. It also modulated the abundance of Rikenella, Mycoplasmataceae, Mycoplasmatales, and Erysipelotrichales, thereby affecting glycerophospholipid metabolism and improving the disease phenotype in pSS mice. In conclusion, OD may treat pSS by lowering inflammation, restoring salivary gland function, and correcting gut microbiota and metabolic imbalances.