**5.2 Autoimmune thyroid diseases**

Thyroid AIDS are conditioned as other auto-immunities by a genetic predisposition, but other factors play an important role in triggering and evolving the autoimmune pathological process [72]. They occur with a frequency of about 4% in the human population and express by either hyper- or hypothyroidism. In both cases, the thyroid may increase in volume (goiter), while ophthalmopathy may develop in

### *Dysbiosis, Tolerance, and Development of Autoimmune Diseases DOI: http://dx.doi.org/10.5772/intechopen.104221*

hyperthyroidism only [73]. Autoimmune thyroid disease affects especially women and from an immunological point of view, it is characterized by the presence of circulating autoantibodies, activated T cells against thyroid antigens, and by lymphocytic infiltration of the organ. Three specificities of anti-thyroid autoantibodies have been described—anti-thyroid peroxidase (microsomal antigen); anti-thyroglobulin; anti-TSH receptor of thyroid acinar cells [74, 75].

AIDS that cause thyroid failure, generically called thyroiditis, are characterized by lymphocytic infiltration. Depending on the clinical aspects there are two pathological conditions—Hashimoto's thyroiditis and atrophic thyroiditis (primary myxedema). In both cases, the thyroid tissue is lysed. Autoimmune thyroid disease is influenced by various factors, such as age, sex, race, and hormonal status [76, 77].

Autoimmune thyroid diseases (Graves and Hashimoto's thyroiditis) often coexist with intestinal diseases, especially celiac disease. The composition of the microbiota population is influenced by diet, affects the thyroid function, mostly by providing the micronutrients essential for the synthesis of thyroid hormones—iodine, iron, and copper. Selenium and zinc are essential for the conversion of T4 to T3, and vitamin D has an immune regulatory effect. Probiotic supplementation favorably influences the secretion of thyroid hormones [26].

Autoimmune thyroiditis is the most common thyroid disorder, with a prevalence of 10–12%. It is triggered by genetic and environmental factors (viral infections) and has an increased prevalence in patients with celiac disease. The commensal microbiota activates the proinflammatory response through innate immunity receptors from the toll-like receptor family and disrupts the intestinal permeability, which may be a triggering factor for Hashimoto's thyroiditis [78].

Hashimoto's thyroiditis is the most common endocrine AIDS (i.e., 10–12% of total autoimmune endocrinopathies), which is characterized by autoimmune destruction of thyroid follicles. The incidence increases with age and is 10 times higher in women. In the serum of patients with Hashimoto's thyroiditis are detected various specific autoantibodies, such as anti-thyroglobulin and/or anti-TPO (thyroid-peroxidase), anti-TSH receptor. Definitive for Hashimoto's disease is the replacement of thyroid tissue with lymphoid tissue. An impressive increase in thyroid volume may be observed, but no hormones are synthesized instead (dry goiter). The symptoms of Hashimoto's thyroiditis and celiac disease often overlap and share epidemiological, clinical, serological, pathological, hormonal, genetic, and immune similarities. Microbiome analysis performed on patients with this ailment revealed that abundance levels of *Blautia, Roseburia, Ruminococcus torques groups, Dorea, Fusicatenibacter, and Eubacterium hallii* group genera were significantly higher whereas *Faecalibacterium, Prevotella, and Bacteroides* genera were decreased [79–82].

Celiac disease (CD) is an autoimmune condition characterized by a specific serological and histological profile triggered by gluten ingestion in genetically predisposed individuals [83]. CD is the only AID known to be triggered by an exogenous antigen, that is, wheat gluten. Gluten is a mixture of proteins grouped in the fraction of gliadin and glutenin, which is the source of carbon and nitrogen for germinating seedlings. Gliadin triggers specific auto-antibody synthesis, the clinical feature being strictly dependent on dietary exposure to gluten and homologous proteins from other cereals. CD is one of the most common autoimmune disorders, with a reported prevalence of 0.5–1% of the general population, except in areas showing a low frequency of CD-predisposing genes and low gluten consumption [84]. Studies have shown that most CD cases remain undetected in the absence of serological screening due to heterogeneous symptoms and/or poor disease awareness. CD has a strong hereditary

component confirmed by its high familial recurrence (~10–15%) and the high concordance of the disease among monozygotic twins (75–80%) [85]. Also common to other AIDS, the HLA class II heterodimers, specifically DQ2 and DQ8, have a relevant role, in the heritability of CD. HLA-DQ2 homozygosis confers a much higher risk (25–30%) of developing early-onset CD in infants with a first-degree family member affected by the disease [86].

Dysbiosis is considered an important factor in the interaction of intestinal and thyroid AIDS. The mechanisms that mediate the interaction of microbiota imbalance and thyroid auto-immunities include: (i) intestinal dysbiosis, which interrupts self-tolerance and tolerance to non-pathogenic bacteria, by post-translational modification of proteins. The bacterial enzymatic apparatus can transform the self or nonself peptide into initiators of the autoimmune reaction, (ii) lipopolysaccharidesinduced TLR activation, which is associated with thyroiditis and synthesis of anti-thyroglobulin antibodies, (iii) induction of Th-2 lymphocyte differentiation, inhibition of Th-17 lymphocyte differentiation and induction of oral acid tolerance to retinoic acid, which can activate an immune response of tolerance at intestinal level, (iv) permeabilization of the intestinal barrier through injuries of the integrity of tight junctions, deficiency of butyric acid produced by the fermented components in the microbiota or excess of ingested proteins that are metabolized by the microbiota with an increase of putrefaction components; all these factors increase the permeability of the intestinal barrier, facilitating the passage of gliadin and activation of the immune response [26]; (v) changes in the transcriptome, proteome and metabolome of the microbiota [34].

Hashimoto's thyroiditis and CD share common antibodies, that is anti-tissular transglutaminase (anti-tTg). In patients with CD, tTg binds to the thyroid follicles and the extracellular matrix of the follicles, therefore amplifying the interactions of the microbiota with the thyroid tissue. There is a direct correlation between serum titers of anti-tTg anti-TPO antibodies. DR3-DQ2 and DR4-DQ8 alleles, involved in CD, are reported as common genes that predispose to endocrine AIDS [80].
