Detection of Alterations in the Gut Microbiota and Intestinal Permeability in Patients With Hashimoto Thyroiditis

Abstract

Hashimoto thyroiditis (HT) is the most common autoimmune disease worldwide, characterized by chronic inflammation and circulating autoantibodies against thyroid peroxidase and thyroglobulin. Patients require hormone replacement with oral levothyroxine, and if untreated, they can develop serious adverse health effects and ultimately death. There is a lot of evidence that the intestinal dysbiosis, bacterial overgrowth, and increased intestinal permeability favor the HT development, and a thyroid–gut axis has been proposed, which seems to impact our entire metabolism. Here, we evaluated alterations in the gut microbiota in Brazilian patients with HT and correlated this data with dietary habits, clinical data, and systemic cytokines and zonulin concentrations. Stool samples from 40 patients with HT and 53 controls were analyzed using real-time PCR, the serum cytokine levels were evaluated by flow cytometry, zonulin concentrations by ELISA, and the dietary habits were recorded by a food frequency questionnaire. We observed a significant increase (p < 0.05) in the Bacteroides species and a decrease in Bifidobacterium in samples of patients with HT. In addition, Lactobacillus species were higher in patients without thyroid hormone replacement, compared with those who use oral levothyroxine. Regarding dietary habits, we demonstrated that there are significant differences in the consumption of vegetables, fruits, animal-derived proteins, dairy products, saturated fats, and carbohydrates between patients and control group, and an inverse correlation between animal-derived protein and Bacteroides genus was detected. The microbiota modulation by diet directly influences the inflammatory profile due to the generated microbiota metabolites and their direct or indirect action on immune cells in the gut mucosa. Although there are no differences in systemic cytokines in our patients with HT, we detected increased zonulin concentrations, suggesting a leaky gut in patients with HT. These findings could help understand the development and progression of HT, while further investigations to clarify the underlying mechanisms of the diet–microbiota–immune system axis are still needed.

Association Between Gut Microbiota and Autoimmune Thyroid Disease: A Systematic Review and Meta-Analysis

“…The gut microbiota shapes the thyroid mainly through the following possible microbial-related mechanisms. First, dysbiosis leads to the damaged intestinal barrier and increased intestinal permeability, allowing the antigens to pass into the circulation and activate the immune system ( 12 ). Second, the antibodies in the circulation may react with the bacterial antigen and enhance the activation of the inflammasome in the thyroid gland ( 13 ).…”

Microbiome Metabolites and Thyroid Dysfunction

“…From the point of view of the thyroid, it is worth noting the SCFAs' control over intestinal barrier integrity and their regenerative effects on the intestinal epithelium [77]. SCFAs are a valuable source of nutrients for enterocytes, additionally stimulating their differentiation, together with thyroid hormones (chiefly triiodothyronine) [78,79]. Short-chain fatty acids strengthen intercellular integrity, minimising the risk of a 'leaky gut'.…”

“…Secondary bile acids appear to be a potentially powerful instrument modulating systemic homeostasis. This is because they are involved in processes regulating energy metabolism as well as exerting endocrine effects that impact TSH levels [79,89]. Their effects can mainly be attributed to the interaction with two valuable receptors, namely the farnesoid X receptor (FXR) and the G-coupled protein receptor that is specific for the bile acid (TGR5) receptor [90].…”

“…It is therefore a self-regulation mechanism, making sure the synthesis of these acids remains in balance. It needs to be emphasised, however, that bile acid homeostasis is mainly controlled by thyroid hormones, which also affect hepatic CYP7A1, regulate the rate of bile acid synthesis, and may additionally increase their outflow in the liver and gut [79,93]. Moreover, under clinically stable conditions, thyroid hormones may control the breakdown of cholesterol while modulating the primary and secondary bile acids.…”

Gut Microbiome and the Role of Metabolites in the Study of Graves’ Disease

“…SCFAs contribute to the maintenance of intestinal barrier integrity and its regeneration effect on the intestinal epithelium ( Memba et al, 2017 ). SCFAs are valuable sources of nutrients for enterocytes, together with thyroid hormones (chiefly triiodothyronine), stimulating enterocyte differentiation ( Cayres et al, 2021 ; Meng et al, 1999 ). It also increases intercellular integrity and reduces the risk of a “leaky gut” by improving the adhesion of intestinal cells and reducing the PH in the intestinal tract, thus avoiding the invasion of pathological organisms ( Memba et al, 2017 ; Bargiel et al, 2021 ).…”