Gut microbiome and thyroid autoimmunity

Virili, Camilla; Stramazzo, Ilaria; Centanni, Marco

doi:10.1016/j.beem.2021.101506

Cited by 47 publications

(40 citation statements)

References 68 publications

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“…TRAb is the main pathogenic autoantibody involved in the hyperthyroidism disorder associated with GD. As self-tolerance against the TSH receptor is lost, thyroid B cells differentiate into plasma cells and release TRAb ( 27 ). Our study shows that zonulin, LPS and D-lactate were independently associated with the level of TRAb in patients with GD.…”

Section: Discussionmentioning

confidence: 99%

Elevated Levels of Circulating Biomarkers Related to Leaky Gut Syndrome and Bacterial Translocation Are Associated With Graves’ Disease

et al. 2021

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BackgroundA growing number of studies have found dysbiosis of the intestinal microbiota in patients with Graves’ disease (GD). The intestinal epithelial barrier serves as the first line of defense, protecting the immune system from excessive stimulation of microbiota and toxins. Most autoimmune diseases are associated with a gut barrier dysfunction (leaky gut) which allows bacterial translocation. However, to date, potential correlations between intestinal barrier dysfunction and GD have not been explored.MethodsSerum lipopolysaccharide (LPS), intestinal fatty acid-binding protein (I-FABP), zonulin, D-lactate, and diamine oxidase (DAO) were measured to assess barrier integrity in 91 patients with GD (61 initial GD and 30 euthyroid GD) and 44 healthy controls. The quality of life (QOL) of patients with GD was assessed using the thyroid-specific patient-reported outcome (ThyPRO-39) questionnaire.ResultsThe serum levels of LPS, I-FABP, zonulin, and D-lactate were significantly higher in patients with initial GD than in healthy controls. Logistic regression analysis revealed that zonulin and D-lactate were independently associated with risk for GD and circulating zonulin could effectively distinguish patients with initial GD from healthy controls. Correlation analyses showed that I-FABP, LPS, and D-lactate were positively associated with FT4 and negatively associated with TSH. In addition, circulating LPS, zonulin, and D-lactate levels were all independent predictors of TRAb levels. Moreover, higher circulating LPS levels in patients with GD were associated with more severe hyperthyroidism (higher concentrations of FT3, FT4, and TRAb and lower TSH concentrations) and worse scores of hyperthyroid and eye symptoms.ConclusionPatients with initial GD show a disrupted intestinal barrier, characterized by elevated levels of leaky gut biomarkers. Increased intestinal permeability and bacterial translocation were associated with TRAb levels and hyperthyroidism in GD. Further research is required to elucidate the underlying mechanisms.

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Section: Discussionmentioning

confidence: 99%

Elevated Levels of Circulating Biomarkers Related to Leaky Gut Syndrome and Bacterial Translocation Are Associated With Graves’ Disease

et al. 2021

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“…During the past 20 years, animal model studies have indicated a critical role of the gut microbiota in regulating innate and adaptive immune responses ( Virili et al., 2021 ). Germ-free (GF) mouse models provide the most strong evidence to support that notion, including models of spontaneous ankylosing enteropathy ( Rehakova et al., 2000 ), autoimmune arthritis ( Wu et al., 2010 ), autoimmune encephalomyelitis ( Lee et al., 2011 ), and autoimmune uveitis ( Heissigerova et al., 2016 ; Fu et al., 2021 ).…”

Section: Changes Of the Gut Microbiome In Gd/gomentioning

confidence: 99%

The Role of the Microbiota in Graves’ Disease and Graves’ Orbitopathy

Hou

Tang²,

Chen³

et al. 2021

Front. Cell. Infect. Microbiol.

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Graves‘ disease (GD) is a clinical syndrome with an enlarged and overactive thyroid gland, an accelerated heart rate, Graves’ orbitopathy (GO), and pretibial myxedema (PTM). GO is the most common extrathyroidal complication of GD. GD/GO has a significant negative impact on the quality of life. GD is the most common systemic autoimmune disorder, mediated by autoantibodies to the thyroid-stimulating hormone receptor (TSHR). It is generally accepted that GD/GO results from complex interactions between genetic and environmental factors that lead to the loss of immune tolerance to thyroid antigens. However, the exact mechanism is still elusive. Systematic investigations into GD/GO animal models and clinical patients have provided important new insight into these disorders during the past 4 years. These studies suggested that gut microbiota may play an essential role in the pathogenesis of GD/GO. Antibiotic vancomycin can reduce disease severity, but fecal material transfer (FMT) from GD/GO patients exaggerates the disease in GD/GO mouse models. There are significant differences in microbiota composition between GD/GO patients and healthy controls. Lactobacillus, Prevotella, and Veillonella often increase in GD patients. The commonly used therapeutic agents for GD/GO can also affect the gut microbiota. Antigenic mimicry and the imbalance of T helper 17 cells (Th17)/regulatory T cells (Tregs) are the primary mechanisms proposed for dysbiosis in GD/GO. Interventions including antibiotics, probiotics, and diet modification that modulate the gut microbiota have been actively investigated in preclinical models and, to some extent, in clinical settings, such as probiotics (Bifidobacterium longum) and selenium supplements. Future studies will reveal molecular pathways linking gut and thyroid functions and how they impact orbital autoimmunity. Microbiota-targeting therapeutics will likely be an essential strategy in managing GD/GO in the coming years.

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“…Since SSc involves the upper digestive tract and at that level most of immune signaling takes place, it is obvious to look at an interaction between the behavior of Breg cells, the resident microbiota composition, and the autoimmune disorders. While the linkage between autoimmune thyroid disorders and gut microbiota (43,44) and Breg cells is well known (20)(21)(22), data on the SSc-gut microbiota interplay are scarce. Enteric bacteria activate IL-10 + intestinal B cells that are able to maintain mucosal homeostasis in an in vitro mouse model (45).…”

Section: Discussionmentioning

confidence: 99%

Regulatory B Cells in Systemic Sclerosis Isolated or Concomitant With Hashimoto Thyroiditis

et al. 2022

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Systemic sclerosis (SSc) is a systemic autoimmune disease in which gastrointestinal disorders represent a complication in up to 90% of patients. SSc may associate with thyroid autoimmune disorders, with Hashimoto’s thyroiditis (HT) being the more prevalent worldwide. Previous studies have examined the behavior of Th17 lymphocytes and Breg cells in patients with HT and concomitant autoimmune organ-specific disorders. These immune phenotypes seem to play a significant role in the pathogenesis of both these autoimmune processes, but their behavior when these two disorders coexist has not been described. We analyzed Th17 and Breg (CD24hiCD38hi) cell subsets in 50 subjects (45F/5M; median age = 49 years): 18 were healthy donors (HD), 20 had isolated HT, and 12 had SSc, seven of whom had both HT and SSc. Breg cells’ function was also evaluated by measuring their IL-10 production when stimulated by specific activators. An increased percentage of Th17 lymphocytes characterized HT patients as compared to both HD and the whole group of SSc patients (p = 0.0018). On the contrary, the percentage of unstimulated Breg cells in SSc patients was higher (p = 0.0260), either associated or not with HT, as compared to both HT patients and HD, which, instead, showed a similar percentage of Breg cells. Following a specific stimulation with CpG, the percentages of Breg cells were increased in the whole sample of SSc patients (p < 0.001) as well as in isolated SSc and in SSc+HT ones as compared to isolated HT. However, qualitative analysis, obtained through the detection of the IL-10-producing phenotype, revealed that the percentage of CpG-stimulated CD24hiCD38hi-IL10+cells was significantly decreased in SSc patients (p < 0.0001) with no difference between isolated SSc and SSc+HT patients. The IL-10-producing phenotype was instead slightly increased in HT patients as compared to HD (4.1% vs. 2.8%). The presence of SSc seems to be characterized by an enrichment of total Breg cells but by a reduced Breg IL-10-producing phenotype, representing functional Bregs. This last finding was entirely due to the presence of SSc independently from the association with HT. This behavior is different from the ones described about the association of HT with organ-specific autoimmune disorders.

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Gut microbiome and thyroid autoimmunity

Cited by 47 publications

References 68 publications

Elevated Levels of Circulating Biomarkers Related to Leaky Gut Syndrome and Bacterial Translocation Are Associated With Graves’ Disease

Elevated Levels of Circulating Biomarkers Related to Leaky Gut Syndrome and Bacterial Translocation Are Associated With Graves’ Disease

The Role of the Microbiota in Graves’ Disease and Graves’ Orbitopathy

Regulatory B Cells in Systemic Sclerosis Isolated or Concomitant With Hashimoto Thyroiditis

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