Microbiome and Graves’ Orbitopathy

Masetti, Giulia; Ludgate, Marian

doi:10.1159/000512255

Cited by 17 publications

(18 citation statements)

References 49 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…As multiple pathogenic pathways are implicated in GO, several targeted therapies are worth exploring in clinical trials, e.g., monoclonal antibodies and/or small molecules targeting the TSHR (187,188) or the CD40 molecule expressed in both thyrocytes and orbital fibroblasts (189), or anti-IL-23/anti-IL-17 for the IL-23/IL-17 axis and sirolimus for the mTOR pathway (190). Worthwhile is also a modulating impact on the microbiome in patients with GO (191). Overall, any novel therapeutic strategy in GO must be examined in RCTs, hopefully adopting the same assessment of treatment primary outcomes, before any conclusion regarding efficacy (i.e., proptosis and diplopia) and safety can be drawn.…”

Section: Discussionmentioning

confidence: 99%

The 2021 European Group on Graves’ orbitopathy (EUGOGO) clinical practice guidelines for the medical management of Graves’ orbitopathy

Bartalena

Kahaly

Baldeschi

et al. 2021

European Journal of Endocrinology

472

497

View full text Add to dashboard Cite

Graves’ orbitopathy (GO) is the main extrathyroidal manifestation of Graves’ disease (GD). Choice of treatment should be based on assessment of clinical activity and severity of GO. Early referral to specialized centers is fundamental for most patients with GO. Risk factors include smoking, thyroid dysfunction, high serum level of thyrotropin receptor antibodies, radioactive iodine (RAI) treatment, and hypercholesterolemia. In mild and active GO, control of risk factors, local treatments and selenium (selenium-deficient areas) are usually sufficient; if RAI treatment is selected to manage GD, low-dose oral prednisone prophylaxis is needed, especially if risk factors coexist. For both active moderate-to-severe and sight threatening GO, antithyroid drugs are preferred when managing Graves’ hyperthyroidism. In moderate-to-severe and active GO, intravenous (iv) glucocorticoids are more effective and better tolerated than oral glucocorticoids. Based on current evidence and efficacy/safety profile, costs and reimbursement, drug availability, long-term effectiveness and patient choice after extensive counselling, a combination of iv methylprednisolone and mycophenolate sodium is recommended as first-line treatment. A cumulative dose of 4.5 grams (g) of iv methylprednisolone in 12 weekly infusions is the optimal regimen. Alternatively, higher cumulative doses not exceeding 8 g can be used as monotherapy in most severe cases and constant/inconstant diplopia. Second-line treatments for moderate-to-severe and active GO include: a) a second course of iv methylprednisolone (7.5 g) subsequent to careful ophthalmic and biochemical evaluation, b) oral prednisone/prednisolone combined with either cyclosporine or azathioprine; c) orbital radiotherapy combined with oral or iv glucocorticoids, d) teprotumumab; e) rituximab and f) tocilizumab. Sight threatening GO is treated with several high single doses of iv methylprednisolone per week and, if unresponsive, with urgent orbital decompression. Rehabilitative surgery (orbital decompression, squint and eyelid surgery) is indicated for inactive residual GO manifestations.

show abstract

Section: Discussionmentioning

confidence: 99%

The 2021 European Group on Graves’ orbitopathy (EUGOGO) clinical practice guidelines for the medical management of Graves’ orbitopathy

Bartalena

Kahaly

Baldeschi

et al. 2021

European Journal of Endocrinology

472

497

View full text Add to dashboard Cite

show abstract

“…Modulating gut microbiota can change the incidence and severity of GD/GO ( Su et al., 2020 ; Moshkelgosha et al., 2021 ). These results uncovered a crucial role of gut microbiota in initiating and developing GD/GO mouse models ( Masetti and Ludgate, 2020 ).…”

Section: Changes Of the Gut Microbiome In Gd/gomentioning

confidence: 94%

“…Because both animal facilities in Brussels and Cardiff are not pathogen-free, environmental microbial factors are possible reasons that TSHRinduced GO could not be generated in Cardiff. This result was the first scientific evidence suggesting that gut microbiota may be related to GD/GO pathogenesis (Baker et al, 2005;Masetti and Ludgate, 2020). The commonly used GD/GO mouse models are generally BALB/c female mice, induced by electroporation of DNA plasmids expressing human TSHR A-subunit (Moshkelgosha et al, 2013) or injection of adenovirus expressing human TSHR Asubunit (Ad-TSHR289) (Chen et al, 2006).…”

Section: Animal Models Of Gd/gomentioning

confidence: 94%

“…However, the exact mechanism is still elusive. Some studies support the causative roles of microbiota in the pathogenesis of GD/GO ( Kohling et al., 2017 ; Masetti and Ludgate, 2020 ).…”

Section: Introductionmentioning

confidence: 90%

“…Dendritic cells also produce retinoic acid, which can promote Treg development but suppress Th17 cells. Gut macrophages can inhibit Th17 development by producing IL-2 and IL-10 ( Masetti and Ludgate, 2020 ). Thus, dysbiosis may increase Th17 cells and suppress Treg production, which can cause many intestine inflammatory conditions and some extraintestinal diseases such as autoimmune uveitis ( Zhuang et al., 2017 ).…”

Section: How Gut Microbiota Affect Gd/go Developmentmentioning

confidence: 99%

See 2 more Smart Citations

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

Hou

Tang²,

Chen³

et al. 2021

Front. Cell. Infect. Microbiol.

View full text Add to dashboard Cite

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.

show abstract

The relationship between thyroid and human-associated microbiota: A systematic review of reviews

Virili,

Stramazzo,

Bagaglini

et al. 2023

Rev Endocr Metab Disord

View full text Add to dashboard Cite

In recent years, a growing number of studies have examined the relationship between thyroid pathophysiology and intestinal microbiota composition. The reciprocal influence between these two entities has been proven so extensive that some authors coined the term "gut-thyroid axis". However, since some papers reported conflicting results, several aspects of this correlation need to be clarified. This systematic review was conceived to achieve more robust information about: 1)the characteristics of gut microbiota composition in patients with the more common morphological, functional and autoimmune disorders of the thyroid; 2)the influence of gut microbial composition on micronutrients that are essential for the maintenance of thyroid homeostasis; 3)the effect of probiotics, prebiotics and synbiotics, some of the most popular over-the-counter products, on thyroid balance; 4)the opportunity to use specific dietary advice. The literature evaluation was made by three authors independently. A five steps strategy was a priori adopted. After duplicates removal, 1106 records were initially found and 38 reviews were finally included in the analysis. The systematic reviews of reviews found that: 1) some significant variations characterize the gut microbiota composition in patients with thyroid disorders. However, geographical clustering of most of the studies prevents drawing definitive conclusions on this topic; 2) the available knowledge about the effect of probiotics and synbiotics are not strong enough to suggest the routine use of these compounds in patients with thyroid disorders; 3) specific elimination nutrition should not be routine suggested to patients, which, instead have to be checked for possible micronutrients and vitamins deficiency, often owed to gastrointestinal autoimmune comorbidities.

show abstract

Microbiome and Graves’ Orbitopathy

Cited by 17 publications

References 49 publications

The 2021 European Group on Graves’ orbitopathy (EUGOGO) clinical practice guidelines for the medical management of Graves’ orbitopathy

The 2021 European Group on Graves’ orbitopathy (EUGOGO) clinical practice guidelines for the medical management of Graves’ orbitopathy

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

The relationship between thyroid and human-associated microbiota: A systematic review of reviews

Contact Info

Product

Resources

About