Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2025 Jun 5;45(1):230.
doi: 10.1007/s10792-025-03607-1.

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

Tianxiao Fu  1 , Wenwen Lu  1 , Danbin Wu  1 , Li Xu  1 , Guolin Wu  2
Affiliations

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

Tianxiao Fu et al. Int Ophthalmol. .

Abstract

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.

Keywords: Gut microbiota; Gut-eye axis; Immunomodulation; Sjögren’s syndrome-related dry eye; Total glucosides of paeony.

PubMed Disclaimer

Conflict of interest statement

Declarations. Conflict of interest: The authors declared that they have no conflicts of interest regarding this work. Ethics approval and consent to participate: The animal experiments strictly adhered to national guidelines on laboratory animal welfare and ethics and were approved by the Institutional Animal Ethics Committee (Approval No.: SYYXY2024091101). Consent for publication: Not Applicable.

Similar articles

See all similar articles

References

    1. Vivino F, Bunya VY, Massaro-Giordano G et al (2019) Sjogren’s syndrome: an update on disease pathogenesis, clinical manifestations and treatment. Clin Immunol 203:81–121 - DOI - PubMed
    1. Beydon M, McCoy S, Nguyen Y et al (2024) Epidemiology of Sjögren syndrome. Nat Rev Rheumatol 20(3):158–169 - DOI - PubMed
    1. Shen Y, Yu X, Wang Q et al (2024) Association between primary Sjögren’s syndrome and gut microbiota disruption: a systematic review and meta-analysis. Clin Rheumatol 43(2):603–619 - DOI - PubMed
    1. Wang F, Zhufeng Y, Chen Z et al (2023) The composition and function profile of the gut microbiota of patients with primary Sjögren’s syndrome. Clin Rheumatol 42(5):1315–1326 - DOI - PubMed
    1. Wang J, Zhu N, Su X et al (2023) Gut-microbiota-derived metabolites maintain gut and systemic immune homeostasis. Cells 12(5):793 - DOI - PubMed - PMC

LinkOut - more resources