Objective  To investigate the effect of the Yangyin Yiqi Huoxue formula on the oral microecology in a mouse model of Sjögren's syndrome (SS), and to explore the underlying mechanisms.

Methods  A total of 12 8-week-old non-obese diabetic (NOD) mice were randomly assigned to a model group, a traditional Chinese medicine (TCM) group, and a hydroxychloroquine (HCQ) group, with 4 mice in each group. In addition, 4 BALB/c mice were used as the normal control group. The TCM group was administered Yangyin Yiqi Huoxue formula (15 g/kg·d) via gavage and the HCQ group received HCQ (0.08 g/kg·d) via gavage. The normal control and model groups were maintained under standard feeding conditions without intervention. After 8 weeks of treatment, saliva samples were collected for 16S rRNA gene sequencing to analyze the oral microbiota. Alpha diversity, beta diversity, and functional prediction analyses were performed.

Results  Alpha diversity analysis showed that the Yangyin Yiqi Huoxue formula significantly increased oral microbiome diversity in NOD mice (P < 0.05). Species composition analysis indicated that the formula increased the abundance of the phylum Proteobacteria and decreased the abundance of the phylum Firmicutes (P < 0.01), while HCQ led to an abnormal decrease in the abundance of the phylum Firmicutes. Beta diversity analysis revealed distinct microbial clustering in the treatment groups and the model group, with the TCM group showing clustering in the phylum Proteobacteria and exhibiting lower intragroup dispersion than the HCQ group did. According to the functional prediction analysis, both the TCM and HCQ groups demonstrated regulatory potential in terms of amino acid transport and metabolism, transcription, and other related functions. KEGG analysis found greater microbial enrichment in cellular processes, environmental information processing, and disease-related pathways in the TCM group compared to the HCQ group (P < 0.05).

Conclusion  The Yangyin Yiqi Huoxue formula can restore oral microbiome diversity and improve the colony structure in in a mouse model of SS, providing experimental evidence for the advantages of TCM in regulating oral microecological functions.