AUTHOR=Liu Siyuan , Li Fan , Cai Yunjia , Ren Linan , Sun Lin , Gang Xiaokun , Wang Guixia 

TITLE=Bacteroidaceae, Bacteroides, and Veillonella: emerging protectors against Graves’ disease

JOURNAL=Frontiers in Cellular and Infection Microbiology

VOLUME=14

YEAR=2024

URL=https://www.frontiersin.org/journals/cellular-and-infection-microbiology/articles/10.3389/fcimb.2024.1288222

DOI=10.3389/fcimb.2024.1288222

ISSN=2235-2988

ABSTRACT=<sec><title>Background</title><p>Graves’ disease (GD) is the most common cause of hyperthyroidism, and its pathogenesis remains incompletely elucidated. Numerous studies have implicated the gut microbiota in the development of thyroid disorders. This study employs Mendelian randomization analysis to investigate the characteristics of gut microbiota in GD patients, aiming to offer novel insights into the etiology and treatment of Graves’ disease.</p></sec><sec><title>Methods</title><p>Two-sample Mendelian randomization (MR) analysis was employed to assess the causal relationship between Graves’ disease and the gut microbiota composition. Gut microbiota data were sourced from the international consortium MiBioGen, while Graves’ disease data were obtained from FINNGEN. Eligible single nucleotide polymorphisms (SNPs) were selected as instrumental variables. Multiple analysis methods, including inverse variance-weighted (IVW), MR-Egger regression, weighted median, weighted mode, and MR-RAPS, were utilized. Sensitivity analyses were conducted employing MR-Egger intercept test, Cochran’s Q test, and leave-one-out analysis as quality control measures.</p></sec><sec><title>Results</title><p>The Mendelian randomization study conducted in a European population revealed a decreased risk of Graves’ disease associated with <italic>Bacteroidaceae</italic> (Odds ratio (OR) [95% confidence interval (CI)]: 0.89 [0.89 ~ 0.90], adjusted <italic>P</italic> value: &lt;0.001), <italic>Bacteroides</italic> (OR: [95% CI]: 0.555 [0.437 ~ 0.706], adjusted <italic>P</italic> value: &lt;0.001), and <italic>Veillonella</italic> (OR [95% CI]: 0.632 [0.492 ~ 0.811], adjusted <italic>P</italic> value: 0.016). No significant evidence of heterogeneity, or horizontal pleiotropy was detected. Furthermore, the preliminary MR analysis identified 13 bacterial species including <italic>Eubacterium brachy</italic> group and <italic>Family XIII AD3011</italic> group, exhibiting significant associations with Graves’ disease onset, suggesting potential causal effects.</p></sec><sec><title>Conclusion</title><p>A causal relationship exists between gut microbiota and Graves’ disease. <italic>Bacteroidaceae</italic>, <italic>Bacteroides</italic>, and <italic>Veillonella</italic> emerge as protective factors against Graves’ disease development. Prospective probiotic supplementation may offer a novel avenue for adjunctive treatment in the management of Graves’ disease in the future.</p></sec>