Correlations between serum cytokines and gut microbiota in patients with Graves' disease: A case-control study

Abstract

Graves' disease (GD) is the most prevalent autoimmune thyroid disorder. Gut microbiome as a critical modulator of autoimmune pathogenesis through its bidirectional communication with host immunity. To elucidate the pathophysiological interplay between cellular immunity and gut microbiome composition in GD through systematic analysis of associations between peripheral blood cytokine profiles and microbial community dynamics. This case-control study enrolled 30 untreated GD patients consecutively admitted to the Department of Endocrinology at the Third Affiliated Hospital of Qiqihar Medical University between January and July 2023, along with 30 age/sex-matched healthy controls (HC). Comprehensive evaluations included: electrochemiluminescence immunoassay quantification of thyroid function parameters, high-resolution Illumina HiSeq 2000 platform-based 16S rRNA gene sequencing for fecal microbial community profiling, multiplex cytokine array analysis of peripheral blood immune markers. Spearman correlation analyses were conducted to delineate relationships among cytokines, thyroid function index and gut microbial taxa alterations in GD pathogenesis. Alpha diversity analysis revealed that the abundance and diversity of certain microbiota in the GD group decreased. Beta diversity analysis revealed that the intestinal microbiome composition of GD patients was significantly different from that of HC. The proportion of Firmicutes in patients with GD was lower than that in HC, while the proportion of Bacteroidetes in patients with GD was greater than that in HC. Immunoregulatory cytokine interleukin-10 exhibited positive correlations with commensal genera Bifidobacterium (R = 0.28) and Parasutterella (R = 0.30), while showing negative correlations with the pathobionts Prevotella_9 (r = -0.51) and Megamonas (r = -0.31). Transforming growth factor β demonstrated similar positive correlations with Bifidobacterium (R = 0.31) and negative correlations with Prevotella_9 (r = -0.45) and Megamonas (r = -0.38). Interleukin-17A displayed positive correlated with Prevotella_9 (R = 0.43) and Megamonas (R = 0.32), but negative correlations with Bifidobacterium (r = -0.27), Veillonella (r = -0.47), Prevotella_9 (r = -0.51) and Megamonas (r = -0.31). Clinically, key microbial taxa showed significant associations with thyroid dysfunction parameters. Our findings identify that GD gut ecosystem demonstrates profound microbial dysbiosis characterized by depleted commensal symbionts and expansion of immunomodulatory pathobionts. Specific bacterial taxa correlate with both cytokine and clinical thyroid dysfunction markers.

Keywords: 16S rRNA; Graves’ disease; correlation analysis; cytokines; gut microbiota.