Exploring the immunomodulatory mechanism of total glucosides of paeony on Sjögren's syndrome dry eye disease based on the "gut-eye axis" pathway.

PURPOSE

Sjögren's syndrome-related dry eye disease (SS-DED) is an autoimmune disorder characterized by ocular surface inflammation and lacrimal gland dysfunction, with limited clinical treatment options currently available.

METHODS

Based on the traditional Chinese medicine theory of "the liver opens into the eyes" and the modern "gut-eye axis" hypothesis. This study investigated the therapeutic effects and immunomodulatory mechanisms of total glucosides of paeony (TGP) using a NOD mouse model.

RESULTS

The results showed that TGP significantly increased tear secretion in SS mice, alleviated corneal and conjunctival damage, improved pathological changes in the Harderian gland, reduced inflammatory infiltration, and restored glandular secretory function. At the molecular level, TGP markedly downregulated pro-inflammatory cytokines such as IL-6 and IL-17 while upregulating anti-inflammatory factors like IL-10 and TGF-β, effectively modulating the Th17/Treg immune balance. Additionally, TGP enhanced the expression of tight junction proteins (ZO-1, Occludin, and Claudin-3) in SS mice, repairing intestinal barrier function. 16S rRNA sequencing analysis revealed that TGP intervention regulated gut microbiota composition in SS mice, reducing the Firmicutes/Bacteroidetes ratio and increasing the abundance of beneficial bacteria such as Lactobacillus. Functional prediction analysis indicated that TGP-modulated gut microbiota primarily participated in key metabolic pathways, including carbohydrate and amino acid metabolism.

CONCLUSION

In conclusion, TGP can ameliorate ocular surface damage in SS mice by regulating gut microecology and immune homeostasis via the "gut-eye axis" pathway. Our study not only provides a novel therapeutic strategy for SS-DED but also offers scientific evidence for the modernization of traditional Chinese medicine theories.