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 2;14(6):34.
doi: 10.1167/tvst.14.6.34.

Inflammatory Proteins Mediate the Effect of Gut Microbiota on Graves' Ophthalmopathy: A Mendelian Randomization Study

Yipao Li  1   2 , Lu Chen  1   2 , Shaokai Lin  1   2 , Wei An  1   2 , Linfeng Miao  1   2 , Minghui Wan  1   2 , Binjun Zhang  1   2
Affiliations

Inflammatory Proteins Mediate the Effect of Gut Microbiota on Graves' Ophthalmopathy: A Mendelian Randomization Study

Yipao Li et al. Transl Vis Sci Technol. .

Abstract

Purpose: This study investigates the causal relationship between gut microbiota (GM) and Graves' ophthalmopathy (GO) and explores the mediating role of circulating inflammatory proteins (IPs) in this association.

Methods: A two-step, two-sample Mendelian randomization (MR) analysis was performed using GM data from MiBioGen (N = 18,340), GO data from the FinnGen Research Project (691 cases, 411,490 controls), and IP data from a genome-wide association study (N = 14,824). The primary MR analysis utilized the inverse variance-weighted approach, supplemented by MR Egger, weighted median, maximum likelihood, and MR robust adjusted profile score methods. Mediation MR was used to assess the mediating role of IPs.

Results: We identified 26 GM taxa causally associated with GO. Notably, the genus Parabacteroides exhibited a protective effect on GO (odds ratio = 0.29; 95% confidence interval, 0.16-0.51; P < 0.001). Additionally, five circulating IPs demonstrated protective effects, while three IPs (CXCL10, CXCL11, EN-RAGE) were associated with increased GO risk. Mediation MR showed that CXCL10 mediated the pathway from Parabacteroides to GO (mediation effect = -0.07), accounting for 5.27% of the total effect.

Conclusions: This study supports a causal link between GM and GO, mediated by circulating IPs. These findings offer new insights into GO pathogenesis and potential targets for clinical intervention.

Translational relevance: Our findings reveal how gut microbiota influences Graves' ophthalmopathy through inflammatory proteins, providing potential therapeutic targets for disease prevention and treatment.

PubMed Disclaimer

Conflict of interest statement

Disclosure: Y. Li, None; L. Chen, None; S. Lin, None; W. An, None; L. Miao, None; M. Wan, None; B. Zhang, None

Figures

Figure 1.
Figure 1.
A two-step Mendelian randomization study of GM on GO mediated by inflammatory proteins.
Figure 2.
Figure 2.
MR results of gut microbiota taxa on Graves’ ophthalmopathy. This circular diagram displays the MR analysis results examining the relationship between gut microbiota taxa and Graves’ ophthalmopathy. The visualization shows different bacterial taxa arranged in a circular pattern, with color intensity indicating their association with the disease. The inner rings represent results from different statistical methods, including inverse variance weighted, MR-Egger, penalized weighted median, maximum likelihood, and robust adjusted profile score approaches.
See this image and copyright information in PMC

References

    1. Bartalena L, Piantanida E, Gallo D, Lai A, Tanda ML. Epidemiology, natural history, risk factors, and prevention of Graves’ orbitopathy. Front Endocrinol (Lausanne). 2020; 11: 615993. - PMC - PubMed
    1. Ackuaku-Dogbe EM, Akpalu J, Abaidoo B. Epidemiology and clinical features of thyroid-associated orbitopathy in Accra. Middle East Afr J Ophthalmol. 2017; 24(4): 183–189. - PMC - PubMed
    1. Yu CY, Ford RL, Wester ST, Shriver EM. Update on thyroid eye disease: regional variations in prevalence, diagnosis, and management. Indian J Ophthalmol. 2022; 70(7): 2335–2345. - PMC - PubMed
    1. Hiromatsu Y, Eguchi H, Tani J, Kasaoka M, Teshima Y. Graves’ ophthalmopathy: epidemiology and natural history. Intern Med. 2014; 53(5): 353–360. - PubMed
    1. Ludgate M. Fibrosis in dysthyroid eye disease. Eye (Lond). 2020; 34(2): 279–284. - PMC - PubMed