Gut and Orbital Dysbiosis Associated with Graves' Disease and Graves' Orbitopathy: A Systematic Review

Background/Objectives: Graves' disease (GD) is a prevalent autoimmune thyroid disorder marked by thyrotoxicosis, goiter, and Graves' orbitopathy (GO). Recent studies highlighted its association with dysbiosis. This systematic review aims to update the current literature and clarify the distinctive microbial signatures and dysbiosis associated with GD/GO. Methods: A systematic search for relevant studies was conducted across multiple databases (2000-2023), employing appropriate keywords. Relevant data were extracted from 25 eligible studies. Results: Microbiota analysis from 19 GD studies (713 patients, 546 controls) and eight GO studies (356 patients, 187 controls), primarily conducted in China (21/25), were examined. The gut microbiota richness and evenness were reduced in GD patients compared to controls in 62.5% of fecal samples. No consistent pattern in alpha diversity was observed in GO. Significant taxonomic divergence was observed between GD/GO and controls. At the phylum level, the Firmicutes to Bacteroidetes ratio was consistently decreased in GD patients (66.7%). Most GO patients also exhibited a similar disequilibrium in their gut and orbital adipose microflora. At the genus level, Prevotella (11 studies), genera within the Lactobacillaceae family (three studies), and Streptococcus (three studies) consistently showed an increase. Genera from the families Lachnospiraceae (nine studies), Ruminococcaceae (six studies), and Veillonellaceae (five studies), as well as the genus Bacteroides (three studies), were decreased. Conclusions: GD/GO-associated dysbiosis is characterized by reduced microbial richness and evenness and alterations in gut phyla balance (↓ Firmicutes, ↑ Bacteroidetes, ↑ Proteobacteria). Specific genera-including Lactobacillus, Prevotella, Bacteroides, and members of the Lachnospiraceae family-may plausibly act as contributors to the onset or progression of GD/GO by influencing the Th17/Treg balance, although their exact roles remain uncertain and largely hypothetical. Systematic review registration: PROSPERO identifier CRD42024512007.