Fecal metabolomic analysis of the role of gut microbiota and short-chain fatty acids in the therapeutic mechanism of Timosaponin AIII in Sjögren's syndrome.

INTRODUCTION/OBJECTIVES: Sjogren's syndrome (SS) is a chronic inflammatory and difficult-to-treat autoimmune disease. Timosaponin AIII (TAIII), a plant-derived steroidal saponin, effectively inhibits cell proliferation, induces apoptosis, and exhibits anti-inflammatory properties. This study explored the mechanisms of action of TAIII in SS treatment by studying gut microbiota and short-chain fatty acids (SCFAs) using fecal metabolomics.

METHODS

The model group used non-obese diabetic (NOD) mice. The treatment group was classified into TAIII and hydroxychloroquine groups. The gut microbiota, SCFAs, and metabolites were analyzed using 16S rRNA sequencing, gas chromatography-mass spectrometry analysis, and liquid chromatography-mass spectrometry, respectively.

RESULTS

TAIII effectively alleviated dry mouth in NOD mice, slowed the progression of salivary gland tissue injury, reduced inflammatory factor expression, and increased the levels of aquaporins 1 and 5. TAIII regulated SCFA content and tryptophan metabolism by altering the abundance of the Rikenellaceae_RC9_gut_group, thereby reducing the inflammatory response. TAIII can improve imbalances in the gut microbiota and the metabolic levels of related SCFAs and tryptophan, thereby reducing the level of inflammation.

CONCLUSION

The significant differences observed in the abundance of the Rikenellaceae_RC9_gut_group between the treatment and control groups indicated the potential relationship between bacteria and metabolites in SS. Key Points • The safe and effective treatment of SS with traditional Chinese medicine • Multi-means study on intestinal flora, short-chain fatty acids, and metabonomics.