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Alterations of the Gut Microbiota in Hashimoto's Thyroiditis Patients

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Alterations of the Gut Microbiota in Hashimoto's Thyroiditis Patients

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Background: Hashimoto's thyroiditis (HT) is an organ-specific autoimmune disease in which both genetic predisposition and environmental factors serve as disease triggers. Many studies have indicated that alterations in the gut microbiota are important environmental factors in the development of inflammatory and autoimmune diseases. We systematically performed a comparative analysis of the gut microbiota in HT patients and healthy controls. Methods: We first conducted a cross-sectional study of 28 HT patients and 16 matched healthy controls. Faecal samples were collected, and microbiota were analysed using 16S ribosomal RNA gene sequencing. Second, an independent cohort of 22 HT patients and 11 healthy controls was used to evaluate the diagnostic potential of the selected biomarkers. Results: Similar levels of bacterial richness and diversity were found in the gut microbiota of HT patients and healthy controls (p = 0.11). A detailed faecal microbiota Mann-Whitney U-test (Q value < 0.05) revealed that the abundance levels of Blautia, Roseburia, Ruminococcus_torques_group, Romboutsia, Dorea, Fusicatenibacter and Eubacterium_hallii_group genera were increased in HT patients, whereas the abundance levels of Faecalibacterium, Bacteroides, Prevotella_9 and Lachnoclostridium genera were decreased. A correlation matrix based on the Spearman correlation distance confirmed correlations among 7 clinical parameters. Additionally, the LEfSe method showed significant differences in 27 genera between the two groups that were strongly correlated with clinical parameters. We used the linear discriminant analysis (LDA) value to select the first 10 species from the 27 different genera as biomarkers, achieving area under the curve (AUC) values of 0.91 and 0.88 for exploration and validation data, respectively. Conclusions: Characterization of the gut microbiota in HT patients confirmed that HT patients have altered gut microbiota and that gut microbiota are correlated with clinical parameters, suggesting that microbiome composition data could be used for disease diagnosis. Further investigation is required to better understand the role of the gut microbiota in the aetiopathogenesis of HT.

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... The literature sheds light on the differences in the composition of intestinal microbiota in patients suffering from thyroid diseases compared to healthy individuals. For instance, a study by Zhao et al. [13] demonstrated that the microbiome of patients with HT was of higher richness and diversity compared to healthy controls. The Firmicutes/Bacteroidetes ratio, used as an indicator of intestinal eubiosis, was elevated in HT patients. ...
... Most importantly, however, the results of the study by Zhao et al. [13] showed that there are associations between the abundance of selected types of bacteria and the diagnostic parameters associated with autoimmune thyroiditis, such as antibodies against thyroid peroxidase (anti-TPO) and thyroglobulin (anti-TG). The abundance of 18 types of bacteria was demonstrated to be positively correlated with anti-TPO and anti-TG, while for six types of bacteria, the correlation was negative. ...
... A positive correlation for Alloprevotella and a negative correlation for Fusicatenibacter with FT4 were also demonstrated. Based on linear discriminant analysis, it was concluded that Bacteroides, Streptococcus, Faecalibacterium, Fusicatenibacter, Prevotella, Blautia, Eubacterium, Ruminococcus, Alloprevotella, and Roseburia can serve as biomarkers in the non-invasive monitoring of thyroid health [13]. ...
Article
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Thyroid diseases are common conditions that have a negative impact on the health of all populations. The literature sheds light on the differences in the composition of the intestinal microbiota in patients suffering from thyroid diseases compared to healthy individuals. The microbiome affects the proper functioning of the thyroid gland, and the existence of the gut–thyroid axis is discussed in the context of both thyroid diseases and intestinal dysbiosis. The purpose of this review is to describe associations between the microbiome and its metabolites and thyroid dysfunction. We try to explain the role of the microbiome in the metabolism of thyroid hormones and the impact of thyroid autoimmune diseases. In addition, we raise issues related to the influence of bacterial metabolites, such as short-chain fatty acids or secondary bile acids, in the functioning of the thyroid gland. Last but not least, we explored the interactions between the gut microbiota and therapeutics and supplements typically administered to patients with thyroid diseases.
... It is generally believed that genetic susceptibility, environmental and survival factors (gender difference), stress, and other factors have important roles (Ajjan and Weetman 2015;Yoo and Chung 2016;Banga and Schott 2018). Moreover, recent evidence has suggested that the gut microbiota is closely associated with some immune-related diseases, including type 1 diabetes mellitus (T1DM) (Kugelberg 2017), rheumatoid arthritis (RA) (Lynch and Pedersen 2016;Horta-Baas et al. 2017), multiple sclerosis, Graves' ophthalmopathy (Covelli and Ludgate 2017;Shi et al. 2019), HT, and inflammatory bowel disease (Masetti et al. 2018;Zhao et al. 2018;Kozhieva et al. 2019). The gut microbiota has a crucial role in the metabolism, absorption, immune function, and defense mechanism against pathogens 2 174 (Pickard et al. 2017;Azad et al. 2018;Reddel et al. 2019). ...
... A previous retro spective study showed the highest alteration in the abundance of Bacteroidetes, Proteobacteria, and Firmicutes between the systemic inflammatory disease group and the healthy group (Nam et al. 2013;Clemente et al. 2018;Faucher et al. 2020). Zhao et al. (2018) found a higher gut microbiota richness and diversity in HT patients with normal thyroid function. Firmicutes were the most abundant, while Bacteroides were less common in HT patients, consistent with our findings. ...
... Firmicutes were the most abundant, while Bacteroides were less common in HT patients, consistent with our findings. Nevertheless, in this study, HT patients were all hypothyroidism patients, that are different from the study reported by Zhao et al. (2018). Furthermore, Zhou et al. (2014) showed the gut microbiota diversity in the GD patients; Bifidobacteria and Lacto bacillus were significantly reduced, but Clostridium and Enterococcus were increased compared to the healthy groups. ...
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To explore the role of gut microbiota in Graves' disease (GD) and Hashimoto's thyroiditis (HT). Seventy fecal samples were collected, including 27 patients with GD, 27 with HT, and 16 samples from healthy volunteers. Chemiluminescence was used to detect thyroid function and autoantibodies (FT3, FT4, TSH, TRAb, TGAb, and TPOAb); thyroid ultrasound and 16S sequencing were used to analyze the bacteria in fecal samples; KEGG (Kyoto Encyclopedia of Genes and Genomes) and COG (Clusters of Orthologous Groups) were used to analyze the functional prediction and pathogenesis. The overall structure of gut microbiota in the GD and HT groups was significantly different from the healthy control group. Proteobacteria and Actinobacteria contents were the highest in the HT group. Compared to the control group, the GD and HT groups had a higher abundance of Erysipelotrichia, Cyanobacteria, and Ruminococcus_2 and lower levels of Bacillaceae and Megamonas. Further analysis of KEGG found that the "ABC transporter" metabolic pathway was highly correlated with the occurrence of GD and HT. COG analysis showed that the GD and HT groups were enriched in carbohydrate transport and metabolism compared to the healthy control group but not in amino acid transport and metabolism. Our data suggested that Bacillus, Blautia, and Ornithinimicrobium could be used as potential markers to distinguish GD and HT from the healthy population and that "ABC transporter" metabolic pathway may be involved in the pathogenesis of GD and HT.
... Previous studies have observed bacterial diversity in hyperthyroid and hypothyroid patients, which may be associated with bacterial overgrowth in the intestinal tract (Lauritano et al., 2007;Zhou et al., 2014). Recently, increased microbial diversity has also been reported in patients with Hashimoto's thyroiditis and thyroid carcinoma (Zhao et al., 2018;Feng et al., 2019). ...
... These findings are consistent with those of previous studies in patients with GD and Graves' orbitopathy (Shi et al., 2019;Jiang et al., 2021). However, in other studies of patients with Hashimoto's thyroiditis or thyroid cancer, Firmicutes was found to be more abundant and Bacteroidetes less abundant (Zhao et al., 2018;Feng et al., 2019). The ratio of Firmicutes to Bacteroidetes has been considered as an index of the health of the gut microbiota and has been correlated with obesity (Mariat et al., 2009;Tilg and Kaser, 2011). ...
... It may also influence the efficacy of drug therapy for GD (Yan et al., 2020). Our study found significantly high levels of Prevotella_9 in GD patients, which is consistent with previous reports in GD patients (Ishaq et al., 2018), while decreased levels of Prevotella_9 have been found in HT patients (Zhao et al., 2018). Besides, our study showed that the abundance of the family Veillonellaceae in patients with GD was increased, which is consistent with the previous studies (Yan et al., 2020;Chen et al., 2021). ...
Article
Graves’ disease (GD) is a systemic autoimmune disease characterized by hyperthyroidism. Evidence suggests that alterations to the gut microbiota may be involved in the development of autoimmune disorders. The aim of this study was to characterize the composition of gut microbiota in GD patients. Fecal samples were collected from 55 GD patients and 48 healthy controls. Using 16S rRNA gene amplification and sequencing, the overall bacterial richness and diversity were found to be similar between GD patients and healthy controls. However, principal coordinate analysis and partial least squares-discriminant analysis showed that the overall gut microbiota composition was significantly different (ANOSIM; p < 0.001). The linear discriminant analysis effect size revealed that Firmicutes phylum decreased in GD patients, with a corresponding increase in Bacteroidetes phylum compared to healthy controls. In addition, the families Prevotellaceae, and Veillonellaceae and the genus Prevotella_9 were closely associated with GD patients, while the families Lachnospiraceae and Ruminococcaceae and the genera Faecalibacterium, Lachnospira, and Lachnospiraceae NK4A136 were associated with healthy controls. Metagenomic profiles analysis yielded 22 statistically significant bacterial taxa: 18 taxa were increased and 4 taxa were decreased. Key bacterial taxa with different abundances between the two groups were strongly correlated with GD-associated clinical parameters using Spearman’s correlation analysis. Importantly, the discriminant model based on predominant microbiota could effectively distinguish GD patients from healthy controls (AUC = 0.825). Thus, the gut microbiota composition between GD patients and healthy controls is significantly difference, indicating that gut microbiota may play a role in the pathogenesis of GD. Further studies are needed to fully elucidate the role of gut microbiota in the development of GD.
... The participation of the intestinal microbiota in autoimmune thyroiditis has been determined since 1988 (72). Some studies highlight the presence of an alteration in the intestinal microbiota in HT patients regardless of thyroid functional status (73,74). In addition, some authors point out that the charge alterations of specific microorganisms decrease the anti-inflammatory activities by reducing the polarization of TH17 lymphocytes and promoting the differentiation of anti-inflammatory Treg lymphocytes at the intestinal level (74,75). ...
... Some studies highlight the presence of an alteration in the intestinal microbiota in HT patients regardless of thyroid functional status (73,74). In addition, some authors point out that the charge alterations of specific microorganisms decrease the anti-inflammatory activities by reducing the polarization of TH17 lymphocytes and promoting the differentiation of anti-inflammatory Treg lymphocytes at the intestinal level (74,75). Furthermore, the simulation presented in Fig. 3 demonstrates a successful compensation of resistance to autoimmunity and the failure to trigger HT disease, which shows the conditions for interventions that reverse the established HT. ...
... The proinflammatory change in the intestinal mucosa called intestinal dysbiosis could lead to an overgrowth of TH17 lymphocytes and thus contribute to autoimmunity and the development of HT (Fig. 4 A). Our simulation found similar results reported by Ishaq et al (73) and Zhao et al (74). In these studies, HT patients were shown to have an altered gut microbiota profile compared to the healthy population (normal plasma levels of free 3,5,3′-triiodothyronine [T 3 ], free thyroxine [T 4 ], and thyrotropin [TSH] without hormonal therapy). ...
Article
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Hashimoto's Thyroiditis (HT) is a pathology which often causes a gradual thyroid insufficiency in affected patients due to the autoimmune destruction of this gland. The cellular immune response mediated by T helper lymphocytes TH1 and TH17 can induce the HT disease. In this pathologic condition, there is an imbalance between the TH17 and Treg lymphocytes as well as a gut microbiota dysfunction. The objective of this work was to describe the interactions of the cell subpopulations that participate in HT. To achieve this goal, we generated a mathematical model that allowed the simulation of different scenarios for the dynamic interaction between thyroid cells, the immune system, and the gut microbiota. We used a hypothetical-deductive design of mathematical modeling based on a system of ordinary differential equations, where the state variables are the TH1, TH17 and Treg lymphocytes, the thyrocytes and the bacteria from gut microbiota. This work generated a compartmental model of the cellular immune response occurring in the thyroid gland. It was observed that TH1 and TH17 lymphocytes could increase the immune cells activity, as well as activate effector cells directly and trigger the apoptosis and inflammation processes of healthy thyrocytes indirectly. Likewise, the model showed that a reduction in Treg lymphocytes could increase the activity of TH17 lymphocytes when an imbalance of the gut microbiota composition occurred. The numerical results highlight the TH1, TH17 and bacterial balance of the gut microbiota activities as important factors for the development of Hashimoto’s Autoimmune Thyroiditis disease.
... The etiology of HD remains unclear at the moment. Similarly, as in the diseases debated above, the interplay of genetic predisposition and epigenetic factors could have an impact on the onset and progression of HD [127]. A detailed interconnection of HD, immunity and gut microbiota is described in the review article by Virili and colleagues [128]. ...
... Interestingly, there were no significant gut microbiota differences between the HD group and Graves's disease patients [129]. A cross-sectional study of 28 HD patients and 16 matching controls described comparable bacterial richness and diversity indices [127]. αdiversity estimators, ACE, Chao1 and observed species, were significantly increased in HD, but surprisingly, no aberrations in the Simpson and Shannon diversity index were presented between groups in the study of 29 HD patients and 12 healthy volunteers [130]. ...
... A sequencing analysis proposed group variances at several taxonomic levels [127]. Bacterial phyla Firmicutes and Actinobacteria were increased in the fecal matter of HD individuals, whereas phyla Bacteroidetes and Proteobacteria were decreased [127]. ...
Article
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Gut microbiota dysbiosis has recently been reported in a number of clinical states, including neurological, psychiatric, cardiovascular, metabolic and autoimmune disorders. Yet, it is not completely understood how colonizing microorganisms are implicated in their pathophysiology and molecular pathways. There are a number of suggested mechanisms of how gut microbiota dysbiosis triggers or sustains extraintestinal diseases; however, none of these have been widely accepted as part of the disease pathogenesis. Recent studies have proposed that gut microbiota and its metabolites could play a pivotal role in the modulation of immune system responses and the development of autoimmunity in diseases such as rheumatoid arthritis, multiple sclerosis or type 1 diabetes. Fecal microbiota transplantation (FMT) is a valuable tool for uncovering the role of gut microbiota in the pathological processes. This review aims to summarize the current knowledge about gut microbiota dysbiosis and the potential of FMT in studying the pathogeneses and therapies of autoimmune diseases. Herein, we discuss the extraintestinal autoimmune pathologies with at least one published or ongoing FMT study in human or animal models.
... Parabacteroides may reduce gut inflammation by influencing the anti-inflammatory cytokine IL-10 and inhibiting the secretion of inflammatory cytokines such as IL-17, IL-6, and IFN-γ. 46 The positive immune system influence and the inflammatory regulation of an impaired microbiota may relieve autoimmune diseases such as autoimmune thyroid diseases. 43 Lactobacilli and Bifidobacteria are considered typical probiotic microorganisms that are advantageous for human health and can regulate the immune system 47 and improve intestinal functions. ...
... 49 Prevotella can produce anti-inflammatory metabolites, which subsequently induce Th17 polarization and stimulate the differentiation of antiinflammatory cells in the digestive tract. 46 In summary, this study supports previous opinions that the more frequent occurrence of thyroid disease in women than in men is related to gut microbiota. 1,12 In the future, several indepth studies should be conducted to confirm the role and mechanism of gut microbiota in regulating thyroid homeostasis. ...
Article
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Iodine plays a key role in maintaining thyroid homeostasis, which is influenced by hormones through almost all nucleated cells and is essential for growth and metabolism. The most common kinds of thyroid dysfunction, hypothyroidism and hyperthyroidism, are markedly related to iodine intake. In addition, the prevalence and incidence of hypothyroidism and hyperthyroidism are much higher in women than in men. However, the association between thyroid homeostasis and the gut microbiota is not yet completely clear, especially when comparing women and men. In this study, differences in the gut microbiota compositions, metabolic syndromes, and molecular mechanisms of female and male mice were investigated after iodine supplementation. The gut microbiota in male mice was changed more than that of female mice. The abundances of Muribacium intestinale, Barnesiella, Alloprevotella, Enterococcus, Desulfovibrionaceae, and Clostridium were significantly increased in female mice. This finding indicates that the high risk of thyroid disease in women could be related to the gut microbiota composition.
... Hashimoto thyroiditis (HT) is the most common autoimmune disorder characterized by the distortion of thyroid gland regular function through its chronic inflammation and hormonal disbalance (McLeod and Cooper, 2012). Several studies pointed out the relationship between gut dysbiosis, linked with immunological and lymphoid disbalance, and the features of HT (Zhao et al., 2018a). A comparative study demonstrated that although without differences in richness and diversity, subjects with HT had elevated and decreased levels of Blautia, Roseburia, Ruminococcus torques, Romboutsia, Dorea, Fusicatenibacter, and Fecalibacterium, Bacteroides, Prevotella_9, and Lachnoclostridium, respectively. ...
... A comparative study demonstrated that although without differences in richness and diversity, subjects with HT had elevated and decreased levels of Blautia, Roseburia, Ruminococcus torques, Romboutsia, Dorea, Fusicatenibacter, and Fecalibacterium, Bacteroides, Prevotella_9, and Lachnoclostridium, respectively. This study also demonstrated correlations between clinical parameters, including anti-thyroperoxidase antibody, anti-thyroglobulin antibody, free thyroxine and thyroid-stimulating hormone, with levels of microbial genera (Zhao et al., 2018a), finally indicating functional differences in microbiota profiles in HT subjects in comparison with controls. Furthermore, a review paper summarized the interaction between immunological and microbiota dysregulation in HT (Virili et al., 2018), and in a comparative approach summarized the results from two studies examining fecal microbiota features (Ishaq et al., 2017;Virili et al., 2018). ...
Chapter
Human gut microbiota varies in richness and functional capacity. Microbiota profiles are promising biomarkers in health and disease risk management, and prognostic biomarkers in chronic and communicable disease onset and progression. Gut microflora is modulated through tailored, personalized dietary and nutritional regimes, based on an individual's characteristics. Interventional strategies inducing changes in gut microflora, could cluster subjects to either responder or non-responder group. Further studies should elucidate the role of microbiota in disease etiology, especially diseases associated with inflammation burden such as non-alcoholic fatty liver disease, or immunological disorders such as Hashimoto thyroiditis.
... In HT patients, an increase in Prevotellaceae and Pasteurellaceae has been recorded and in particular, at the genus level, an increase in Blautia, Roseburia, Ruminococcus, Romboutsia, Dorea, Fusicatenibacter and Eubacterium. On the contrary, a decrease in Enterobacteriaceae, Veillonellaceae and the genera Rikenella, Faecalibacterium, Bacteroides, Prevotella and Lachnoclostridium has been highlighted (Ishaq et al., 2018;Zhao et al., 2018). It is more than plausible that a microbial pattern like this may affect Treg modulation and functions (Köhling et al., 2017). ...
... GM can modulate the synthesis of neurotransmitters, such as dopamine, which can inhibit TSH and modulate the hypothalamus-pituitary axis. So, an imbalance in GM could contribute to thyroid disorder development and maintenance with mechanisms involving microbial metabolic pathways (Zhao et al., 2018;Fröhlich and Wahl, 2019). Coeliac disease (CD) is an autoimmune disorder triggered by the interaction between GALT and undigested gluten peptides that translocate across the epithelial barrier into the lamina propria. ...
Article
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Pharmaceutical interest in the human intestinal microbiota has increased considerably, because of the increasing number of studies linking the human intestinal microbial ecology to an increasing number of non-communicable diseases. Many efforts at modulating the gut microbiota have been made using probiotics, prebiotics and recently postbiotics. However, there are other, still little-explored opportunities from a pharmaceutical point of view, which appear promising to obtain modifications of the microbiota structure and functions. This review summarizes all in vitro, in vivo and clinical studies demonstrating the possibility to positively modulate the intestinal microbiota by using probiotics, prebiotics, postbiotics, essential oils, fungus and officinal plants. For the future, clinical studies investigating the ability to impact the intestinal microbiota especially by using fungus, officinal and aromatic plants or their extracts are required. This knowledge could lead to effective microbiome modulations that might support the pharmacological therapy of most non-communicable diseases in a near future.
... This bacterial unbalance is able to trigger low-grade chronic inflammation that impacts gut integrity and disease development [1]. Different human diseases have been associated with intestinal dysbiosis, including autoimmune disorders, such as thyroiditis [2,3], metabolic disorders, such as obesity and type II diabetes [4,5], and neurological disorders, such as Parkinson [6] and Alzheimer's disease [7]. In this context, an increasing number of probiotics and prebiotics have been developed in order to modulate the intestinal microbiota, often with the main purpose of relieving GI symptoms such as diarrhea, constipation, and bloating [8] as side effects of the aforementioned diseases. ...
Article
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The search for new fiber supplements that can claim to be “prebiotic” is expanding fast, as the role of prebiotics and intestinal microbiota in well-being has been well established. This work explored the prebiotic potential of a novel fiber plus D-Limonene supplement (FLS) in comparison to fructooligosaccharides (FOS) over distal colonic fermentation with the in vitro model MICODE (multi-unit in vitro colon gut model). During fermentation, volatilome characterization and core microbiota quantifications were performed, then correlations among volatiles and microbes were interpreted. The results indicated that FLS generated positive effects on the host gut model, determining: (i) eubiosis; (ii) increased abundance of beneficial bacteria, as Bifidobacteriaceae; (iii) production of beneficial compounds, as n-Decanoic acid; (iv) reduction in detrimental bacteria, as Enterobaceteriaceae; (v) reduction in detrimental compounds, as skatole. The approach that we followed permitted us to describe the prebiotic potential of FLS and its ability to steadily maintain the metabolism of colon microbiota over time. This aspect is two-faced and should be investigated further because if a fast microbial turnover and production of beneficial compounds is a hallmark of a prebiotic, the ability to reduce microbiota changes and to reduce imbalances in the productions of microbial metabolites could be an added value to FLS. In fact, it has been recently demonstrated that these aspects could serve as an adjuvant in metabolic disorders and cognitive decline.
... At the genus level, the abundance of Lactobacillus, Blautia, Turicibacter and Dorea changed signi cantly. In patients with depression, multiple sclerosis (MS) and Hashimoto's thyroiditis, the abundance of Blautia and Dorea was increased [33][34][35][36]. Lactobacillus regulated emotional behavior and the expression of central gamma-aminobutyric acid (GABA) receptor through the vagus nerve [37]. ...
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Background: Perioperative neurocognitive disorders (PND) occur frequently in elderly patients after surgery, but the mechanism of PND is not very clear at present. It is reported that anesthesia/surgery could cause intestinal flora imbalance and induce neurocognitive impairment. However, the effect of intestinal flora on PND is poorly understood. We previously found that peripheral interleukin-17A (IL17A) destroyed the blood-brain barrier (BBB), leading to central inflammation and neurocognitive impairment. The small intestine is the main place where Th17 cells are produced. Therefore, we hypothesized that Th17 cells and IL-17 may be an important bridge for intestinal microbes to cause neuroinflammation. Methods: Exploratory laparotomy was performed to establish PND model under sevoflurane anesthesia. 16S rRNA high-throughput sequencing was used to detect the changes of intestinal flora. To explore the relationship between intestinal flora and PND, compound antibiotics were used to eliminate intestinal flora before anesthesia/surgery, and behavior tests, such as open field, Y maze, and fear conditioning tests were applied to detect the changes of memory ability and which was compared with the rats that did not receive compound antibiotics. The number of Th17 cells and Foxp3 cells was detected by flow cytometry in the Peyer's patches (PP), mesenteric lymph nodes (MLN), blood and brain. Hippocampus IL17, IL17RA, IL6 and IL10 were detected by Western blot. Hippocampus IL17, IL17R and IBA1 (ionized calcium binding adaptor molecule1) were detected by immunofluorescence. Results: Anesthesia/surgery caused intestinal flora imbalance and induced neurocognitive impairment, increased the number of Th17 cells in the PP, MLN, blood and brain, up-regulated the lever of IL17, IL17R and inflammatory factor production in the hippocampus. The administration of compound antibiotics before anesthesia/surgery evidently inhibited this effect, including decreased the number of Th17 cells, down-regulated the lever of IL17, IL17R and inflammatory factor production, and improved the memory function. In addition, we found that IL17R was co-labeled with IBA1 in a large amount in the hippocampus through immunofluorescence double-staining. Conclusion: Our study suggested that intestinal dysbacteriosis-propelled T helper 17 cells activation might play an important role in the pathogenesis of PND.
... Differences in the gut microbiome have been shown in patients with Hashimoto"s thyroiditis compared with control patients and compared with patients with Graves disease (258)(259)(260)(261). Patients with celiac disease with and without Hashimoto"s disease also appear to have distinct gut microbiomes (262). ...
Article
Hypothyroidism is a common endocrinopathy and levothyroxine is frequently prescribed. Despite the basic tenets of initiating and adjusting levothyroxine being agreed upon, there are many nuances and complexities to consistently maintaining euthyroidism. Understanding the impact of patient weight and residual thyroid function on initial levothyroxine dosage and consideration of age, co-morbidities, TSH goal, life stage, and quality of life as levothyroxine is adjusted can be challenging and continually evolving. As levothyroxine is a life-long medication it is important to avoid risks from periods of overtreatment or undertreatment. For the subset of patients not restored to baseline health with levothyroxine, causes arising from all aspects of the patient’s life (co-existent medical conditions, stressors, lifestyle, psychosocial factors) should be broadly considered. If such factors do not appear to be contributing, and biochemical euthyroidism has been successfully maintained, there may be benefit to a trial of combination therapy with levothyroxine and liothyronine. This is not supported by the majority of randomized clinical trials, but may be supported by other studies providing lower quality evidence and by animal studies. Given this discrepancy, it is important that any trial of combination therapy only be continued as long as a patient benefit is being enjoyed. Monitoring for adverse effects, particularly in older or frail individuals, is necessary and combination therapy should not be utilized during pregnancy. A sustained release liothyronine preparation has completed phase 1 testing and may soon be available for better designed and powered studies assessing whether combination therapy provides superior therapy for hypothyroidism.
... Also, the gut microbiota has been discussed as a further possible cause of influencing thyroid immunity and the development of HT [7]. Different studies have shown a changed intestinal microbiota composition in patients with HT as compared to healthy controls, thus possibly having an influence on the reactivity of the immune system and the development of HT [8][9][10][11]. However, further studies on this topic have to be awaited to determine whether gut dysbiosis may have an impact on the development of HT [7,8,12]. ...
Article
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Hashimoto’s thyroiditis (HT), also known as chronic lymphocytic thyroiditis, is a frequent disorder of the thyroid gland caused by autoimmune-trigged lymphocytic infiltration and destruction of the thyroid gland. With the progressive destruction of the organ, the thyroid gland shrinks in size, thus commonly leading to hypothyroidism. Therapy of HT is mainly focused on managing the thyroid dysfunction by oral substitution of L‑thyroxine. However, patients with HT often complain about a broad spectrum of symptoms, with some of them hardly explained by HT itself. Several other disorders are known to be associated with HT. The etiology of HT seems to be multifactorial, including environmental influences such as iodine supply, infections, and stress as triggers of immune modulation. In addition, also a genetic background based on changes of the human leukocyte antigen (HLA) status seems to be evident. The paper will provide an overview of diseases related to HT, including their correlation to certain HLA patterns. This presentation should give a broader view on HT-related disorders and facilitate detailed examination and management of patients with HT.
... Finally, as already seen, there are indications that intestinal dysbiosis and development of HT, as well as other autoimmune pathologies, may be associated [48]. Some studies focused on the search for dysbiosis in HT patients through the analysis of fecal samples and the researchers concluded that there was an alteration in the intestinal microbiota, that is, dysbiosis was confirmed [157,158]. Recent evidence from experimental research studies proved that the intestinal microbiota generates physiological levels of oxidative stress that interfere in intestine permeability, increasing the chances of xenomolecules entrance [159] and, in turn, could lead to molecular mimicry. ...
Article
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A number of studies have shown that oxidative stress is related to the pathogenesis of several immunological diseases, such as Hashimoto’s thyroiditis (HT), although there is no plausible mechanism to explain it. Thus, we aimed at hypothesizing and providing some possible mechanisms linking oxidative stress to autoimmunity aspects and its implications for HT, as well as adjuvant therapeutic proposals to mitigate the deleterious effects. Our hypothesis is that deficient eating habits, autoimmune regulator gene predisposing gene, dysbiosis and molecular mimicry, unfolded proteins and stress in the endoplasmic reticulum, and thymus involution appear to be the main potential factors leading to HT oxidative stress. Likewise, we show that the use of minerals selenium and zinc, vitamins D and C, as well as probiotics, can be interesting adjuvant therapies for the control of oxidative damage and poor prognosis of HT. Further clinical trials are needed to understand the real beneficial and side effects of these supplements. Graphical abstract
... Se-enriched L. acidophilus can reduce the relative abundance of Romboutsia. It has been reported that the relative abundance of Romboutsia in the intestinal microbiota of patients with the autoimmune disease Hashimoto's thyroiditis is increased (39). Our study also found that the relative abundance of Romboutsia in DSS-induced colitis was increased, suggesting that Romboutsia may play a role in promoting autoimmune diseases, which needs further research. ...
Article
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Aim: To evaluate the effect of Selenium-enriched Lactobacillus acidophilus (Se-enriched L. acidophilus ) on dextran sulfate sodium (DSS)-induced colitis in mice. Methods: Mice were randomly divided into four groups: a control group, a control + Se-enriched L. acidophilus group, a chronic colitis group, and a chronic colitis + Se-enriched L. acidophilus group ( n = 10 each group). The mice were sacrificed on the 26th day. The disease activity index, survival rates, and histological injury score were determined. Cytokines produced by lamina propria lymphocytes (LPLs), the selenium (Se) concentrations in serum and colon tissue and the mouse intestinal microbiota were evaluated. Results: Se-enriched L. acidophilus can improve histological injury and the disease activity index in mice with chronic colitis and reduce IL-1β, IL-6, IL-12p70, TNF-α, IL-23, IFN-γ, IL-17A, and IL-21 ( P < 0.05) and increase IL-10 ( P < 0.05) expression levels. Moreover, Se-enriched L. acidophilus can increase the β diversity of intestinal microbiota in mice with chronic colitis, significantly reduce the relative abundance of Lactobacillus and Romboutsia ( P < 0.05), and significantly increase the relative abundance of Parasutterella ( P < 0.05). Conclusions: Se-enriched L. acidophilus can improve DSS-induced chronic colitis by regulating inflammatory cytokines and intestinal microbiota.
... Lauritano E.C. et al. have found that about 54% of patients with HT suffered from SIBO [14]. Zhao F. et al. have found bacterial overgrowth and differences in the GM composition of patients suffering from HT and healthy individuals in the form of increased genera Blautia, Romboutsia, EubacteriumRoseburia, Ruminococcus, Fusicatenibacter, Dorea and Eubacterium and decreased levels of Fecalibacterium, Bacteroides, Prevotella [15]. The change in GM correlated with clinical parameters, which could be actively used for the diagnosis of diseases. ...
Article
Gut microbiota is considered as a pathogenetic factor of various diseases nowadays. The patients with autoimmune diseases are known to suffer from dysbiosis. There are studies in the modern literature that demonstrate changes in the composition of the gut microbiota in case of thyroid dysfunction. This review examines a contemporary view of the gut microbiota, its role in the development of autoimmune diseases. We investigated the interaction between the thyroid gland and the gut microbiota, its species composition in hypo- and hyperthyroidism. Possible methods of correction, including the use of pre- and probiotics and transplantation of fecal microbiota have been demonstrated.
... High microbial diversity, even if often proposed as beneficial for human health, can entail increased protein catabolism, as well as decreased polyphenol conversion, epithelial turnover and mucus secretion [10,73]. HT patients not only show alterations in their gut microbiota but their microbiota composition is also correlated with clinical parameters, indicating that data about individual microbial composition could help with diagnosis and therapy [74]. In GD, the constitution of the gut microbiota, especially the presence of certain strains like Paludibacter and Allobaculum, Limibacter, Anaerophaga and Ureaplasma seems to increase susceptibility to disease [75]. ...
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Celiac disease (CD) and autoimmune thyroid diseases (AITD) like Hashimoto’s thyroiditis (HT) and Graves’ disease (GD) frequently coexist, entailing numerous potential impacts on diagnostic and therapeutic approaches. Possible correlations might exist through gut microbiota, regulating the immune system and inflammatory responses, promoting autoimmune diseases, as well as shared cytokines in pathogenesis pathways, cross-reacting antibodies or malabsorption of micronutrients that are essential for the thyroid like iron or vitamin D. Vitamin D deficiency is a common finding in patients with AITD, but might protect from autoimmunity by wielding immunoregulatory and tolerogenic impacts. Additionally, vitamin D is assumed to be involved in the onset and progression of CD, presumably plays a substantial protective role for intestinal mucosa and affects the thyroid via its immunomodulatory effects. Iron is an essential micronutrient for the thyroid gland needed for effective iodine utilization by the iron-dependent enzyme thyroid iodine peroxidase (TPO). Despite being crucial for thyroid hormone synthesis, iron deficiency (ID) is a common finding in patients with hypothyroidism like HT and is frequently found in patients with CD. A literature research was conducted to examine the interplay between CD, AITD, vitamin D and iron deficiency. This narrative review highlights the relevant correlation of the two disease entities CD and AITD, their reciprocal impact and possible therapeutic options that should be further explored by future studies.
... Based on the MDA values, the top 10 genera were further selected as potential bacterial signatures. According to the descending order of MDA values, these 10 potential bacterial signatures were iteratively eliminated to identify a set of features to train the RF model with the highest overall accuracy for sample classification [39]. The performance of the model was assessed with a tenfold cross-validation approach. ...
... The role of Blautia in health and disease is controversially discussed as some species appear to be healthy while others are harmful. A higher abundance of Blautia is reported to be associated with Type 2 Diabetes and Hashimoto's Thyroiditis, but one species, Blautia obeum, previously known as Ruminococcus obeum, appeared to be a sign of gut microbiota recovery after Vibrio cholerae infection in children [10,51,52]. Other species of Blautia are reported to be associated with obesity and metabolic inflammation [53]. ...
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An essential role of the gut microbiota in health and disease is strongly suggested by recent research. The composition of the gut microbiota is modified by multiple internal and external factors, such as diet. A vegan diet is known to show beneficial health effects, yet the role of the gut microbiota is unclear. Within a 4-week, monocentric, randomized, controlled trial with a parallel group design (vegan (VD) vs. meat-rich (MD)) with 53 healthy, omnivore, normal-weight participants (62% female, mean 31 years of age), fecal samples were collected at the beginning and at the end of the trial and were analyzed using 16S rRNA gene amplicon sequencing (Clinical Trial register: DRKS00011963). Alpha diversity as well as beta diversity did not differ significantly between MD and VD. Plotting of baseline and end samples emphasized a highly intra-individual microbial composition. Overall, the gut microbiota was not remarkably altered between VD and MD after the trial. Coprococcus was found to be increased in VD while being decreased in MD. Roseburia and Faecalibacterium were increased in MD while being decreased in VD. Importantly, changes in genera Coprococcus, Roseburia and Faecalibacterium should be subjected to intense investigation as markers for physical and mental health.
... According to this proposal, the intestinal microbiota affects mechanisms related to the absorption of iodide, conversion of T4 to T3, and also participates in the modulation of the immune system (11,101). This is corroborated by studies where gut microbiota dysbiosis was correlated to Hashimoto's thyroiditis (102)(103)(104), Graves' disease (104), thyroid cancer and thyroid nodules (105). In parallel in the field of toxicology, recent studies indicate that GBH is able to affect the intestinal microbiome of mice (106), rats (107)(108)(109)(110)(111)(112), honeybees (113,114), Japanese quails (115) and Daphnia magna (116). ...
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The increased incidence of thyroid diseases raises a series of questions about what the main predisposing factors are nowadays. If dietary restriction of iodine was once a major global health concern, today, the processes of industrialization of food and high exposure to a wide variety of environmental chemicals may be affecting, directly or indirectly, thyroid function. The homeostasis of hypothalamus–pituitary–thyroid (HPT) axis is finely regulated through the negative feedback mechanism exerted by thyroid hormones. Allostatic mechanisms are triggered to adjust the physiology of HPT axis in chronic conditions. Glyphosate and glyphosate-based herbicides are pesticides with controversial endocrine disrupting activities and only few studies have approached their effects on HPT axis and thyroid function. However, glyphosate has an electrophilic and nucleophilic zwitterion chemical structure that may affect the mechanisms involved in iodide oxidation and organification, as well as the oxidative phosphorylation in the ATP synthesis. Thus, in this review, we aimed to: (1) discuss the critical points in the regulation of HPT axis and thyroid hormones levels balance, which may be susceptible to the toxic action of glyphosate and glyphosate-based herbicides, correlating the molecular mechanisms involved in glyphosate toxicity described in the literature that may, directly or indirectly, be associated to the higher incidence of thyroid diseases; and (2) present the literature regarding glyphosate toxicity in HPT axis.
... Besides genetics, the diets as well as host hormones or neurotransmitters, can affect gut microbial diversity of the hosts (Koren et al., 2012). Studies in humans showed that hyperthyroid patients had significant enrichments in pathogenic bacteria such as Enterobacteriaceae and Clostridium in the gut in comparison with a healthy group (Zhou et al., 2014), while hypothyroidism was accompanied by a modest intestinal bacterial overgrowth (Lauritano et al., 2007;Zhao et al., 2018). Both rat (Shin et al., 2020) and gerbil models (in the present study) of thyroid dysfunction revealed that profile of gut microbiota varied with different thyroid functional status. ...
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Endothermic mammals have a high energy cost to maintain a stable and high body temperature (Tb , around 37°C). Thyroid hormones are a major regulator for energy metabolism and Tb . The gut microbiota is involved in modulating host energy metabolism. However, whether the interaction between the gut microbiota and thyroid hormones is involved in metabolic and thermal regulations is unclear. We hypothesized that thyroid hormones via an interaction with gut microbiota orchestrate host thermogenesis and Tb . l-thyroxine-induced hyperthyroid Mongolian gerbils (Meriones unguiculatus) increased resting metabolic rate (RMR) and Tb , whereas Methimazole-induced hypothyroid animals decreased RMR. Both hypothyroid and hyperthyroid animals differed significantly in faecal bacterial community. Hyperthyroidism increased the relative abundance of pathogenic bacteria, such as Helicobacter and Rikenella, and decreased abundance of beneficial bacteria Butyricimonas and Parabacteroides, accompanied by reduced total bile acids and short-chain fatty acids. Furthermore, the hyperthyroid gerbils transplanted with the microbiota from control donors increased type 2 deiodinase (DIO2) expression in the liver and showed a greater rate of decline of both serum T3 and T4 levels and, consequently, a more rapid recovery of normal RMR and Tb . These findings indicate that thyroid hormones regulate thermogenesis depending on gut microbiota and colonization with normal microbiota by caecal microbial transplantation attenuates hyperthyroid-induced thermogenesis. This work reveals the functional consequences of the gut microbiota-thyroid axis in controlling host metabolic physiology and Tb in endotherms.
... 37 In patients with HT, some genera of bacteria, such as Blautia, Roseburia, Ruminococcus_toques_group, Romboustsia, Dorea, Fusicatenibacter, and Eubacterium_hallii_group, are increased and correlated with clinical parameters. 38 In the Graves' orbitopathy or ophthalmopathy (GO) murine model, the abundance of Firmicutes in the intestine is higher and positively correlated with orbital adipogenesis. 39 The microbiota can also affect the uptake of iodine, selenium, iron, and zinc. ...
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As the gut microbiota exerts various effects on the intestinal milieu which influences distant organs and pathways, it is considered to be a full-fledged endocrine organ. The microbiota plays a major role in the reproductive endocrine system throughout a woman’s lifetime by interacting with estrogen, androgens, insulin, and other hormones. Imbalance of the gut microbiota composition can lead to several diseases and conditions, such as pregnancy complications, adverse pregnancy outcomes, polycystic ovary syndrome (PCOS), endometriosis, and cancer; however, research on the mechanisms is limited. More effort should be concentrated on exploring the potential causes and underlying the mechanisms of microbiota-hormone-mediated disease, and providing novel therapeutic and preventive strategies.As the gut microbiota exerts various effects on the intestinal milieu which influences distant organs and pathways, it is considered to be a full-fledged endocrine organ. The microbiota plays a major role in the reproductive endocrine system throughout a woman’s lifetime by interacting with estrogen, androgens, insulin, and other hormones. Imbalance of the gut microbiota composition can lead to several diseases and conditions, such as pregnancy complications, adverse pregnancy outcomes, polycystic ovary syndrome (PCOS), endometriosis, and cancer; however, research on the mechanisms is limited. More effort should be concentrated on exploring the potential causes and underlying the mechanisms of microbiota-hormone-mediated disease, and providing novel therapeutic and preventive strategies.
... AIT має багатофакторну етіологію, на яку впливають генетичні фактори, такі як поліморфізм рТТГ, Tg, антигенів лейкоцитів людини та інших генів, пов'язаних з імунною відповіддю [25], фактори зовнішнього середовища -радіація, йод, куріння, інфекції, селен, наркотики, стрес і дієтичні звички [23,25], ендогенні фактори -індекс маси тіла, адипокіни, естрогени, селективна інактивація Х-хромосом, мікрохімеризм, глюкокортикоїди [23] і потенційно -шлунково-кишковий мікробіом [26]. ...
Article
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Background. Vitamin D (VD) is a versatile steroid hormone that regulates the activity of several thousand genes. Over the past decades, numerous diseases associated with VD deficiency have been reported, including cancer and autoimmune thyroid disorders. Researches revealed that VD can influence the development and course of these diseases. The VD participation in modulation of the hypothalamus-pituitary-thyroid gland axis, both at the level of the pituitary gland and at that of the thyroid, has been shown. The effect of VD on autoimmune diseases, including thyroid autoimmune diseases, is widely studied. Most of the existing data support the relationship between VD deficiency and a greater tendency to develop and higher antibody titers associated with Hashimoto’s thyroiditis, Graves’ disease (GD) and postpartum thyroiditis. An important fact is that epidemiological studies have demonstrated a high prevalence of VD deficiency or insufficiency throughout the world. VD insufficiency is a potent dietary trigger that results in severe, chronic diseases. The question arises how reliable is the relationship between VD and autoimmune thyroid diseases (AITD). Although the results of the studies performed are somewhat contradictory, the vast majority of data indicates a link between VD deficiency and an increased risk of developing the disease, high antibody titers, and difficulties in treatment. Genetic polymorphisms associated with VD function and metabolism also have some influence on the risk of ATD. With regard to the precise nature of the relationship between VD and AITD, it is believed that VD plays a small but significant role in the AITD pathogenesis. After the AITD development, its consequence may be an increase in VD deficiency. It is the need to determine the effect of VD supplementation in the prevention and treatment of AITD and its optimal level directly for clinical practice. It is necessary for clinical practice to determine the effect of VD supplements in the prevention and treatment of AITD and its optimal level. A study, the purpose of which was to study the content of VD, namely 25(OH)D in 176 patients with GD complicated by autoimmune ophthalmopathy (AO) and to identify a correlation relationship with antithyroid antibodies (TPO, TSHR-Ab) was carried out at the State Institution “V.P. Komissarenko Institute of Endocrinology and Metabolism of the National Academy of Medical Sciences of Ukraine”. Materials and methods. The levels of 25(OH)D, TSH, TSHR-Ab, TPO were determined by enzyme immunoassay using standard kits from Siemens firm. During the study, 176 patients were divided into two groups, depending on the presence of AO: the first group consisted of patients with GD without AO (62 people), the second group included patients with GD and AO (114 people). Results. In GD, 91.78 % of patients (161 people) have an insufficient level of 25(OH)D content: a suboptimal level was recorded in 42 patients (23.86 %), and a deficit — in 119 patients (67.61 %). A significant negative correlation relationship was revealed between TSHR-Ab and 25(OH)D in the group of patients with GD and AO — with a lower level of 25(OH)D, the higher values of TSHR-Ab correlate. Compensation of the 25(OH)D deficiency leads to a significant (P < 0.05) decrease in the levels of TSHR-Ab and TPO in patients with GD. Besides, there is a large body of literature available lin-king vitamin D to thyroid autoimmunity as a result of cross-sectional studies and observations. Conclusions. Thus, there is still an urgent need for large multicenter studies to evaluate the effect of vitamin D supplementation on meaningful long-term clinical endpoints in AITD.
... AIT має багатофакторну етіологію, на яку впливають генетичні фактори, такі як поліморфізм рТТГ, Tg, антигенів лейкоцитів людини та інших генів, пов'язаних з імунною відповіддю [25], фактори зовнішнього середовища -радіація, йод, куріння, інфекції, селен, наркотики, стрес і дієтичні звички [23,25], ендогенні фактори -індекс маси тіла, адипокіни, естрогени, селективна інактивація Х-хромосом, мікрохімеризм, глюкокортикоїди [23] і потенційно -шлунково-кишковий мікробіом [26]. ...
Article
Full-text available
Effects of vitamin D in thyroid autoimmune pathologies: literature review and own data. Abstract. Background. Vitamin D (VD) is a versatile steroid hormone that regulates the activity of several thousand genes. Over the past decades, numerous diseases associated with VD deficiency have been reported, including cancer and autoimmune thyroid disorders. Researches revealed that VD can influence the development and course of these diseases. The VD participation in modulation of the hypothalamus-pituitary-thyroid gland axis, both at the level of the pituitary gland and at that of the thyroid, has been shown. The effect of VD on autoimmune diseases, including thyroid autoimmune diseases, is widely studied. Most of the existing data support the relationship between VD deficiency and a greater tendency to develop and higher antibody titers associated with Hashimoto’s thyroiditis, Graves’ disease (GD) and postpartum thyroiditis. An important fact is that epidemiological studies have demonstrated a high prevalence of VD deficiency or insufficiency throughout the world. VD insufficiency is a potent dietary trigger that results in severe, chronic diseases. The question arises how reliable is the relationship between VD and autoimmune thyroid diseases (AITD). Although the results of the studies performed are somewhat contradictory, the vast majority of data indicates a link between VD deficiency and an increased risk of developing the disease, high antibody titers, and difficulties in treatment. Genetic polymorphisms associated with VD function and metabolism also have some influence on the risk of ATD. With regard to the precise nature of the relationship between VD and AITD, it is believed that VD plays a small but significant role in the AITD pathogenesis. After the AITD development, its consequence may be an increase in VD deficiency. It is the need to determine the effect of VD supplementation in the prevention and treatment of AITD and its optimal level directly for clinical practice. It is necessary for clinical practice to determine the effect of VD supplements in the prevention and treatment of AITD and its optimal level. A study, the purpose of which was to study the content of VD, namely 25(OH)D in 176 patients with GD complicated by autoimmune ophthalmopathy (AO) and to identify a correlation relationship with antithyroid antibodies (TPO, TSHR-Ab) was carried out at the State Institution “V.P. Komissarenko Institute of Endocrinology and Metabolism of the National Academy of Medical Sciences of Ukraine”. Materials and methods. The levels of 25(OH)D, TSH, TSHR-Ab, TPO were determined by enzyme immunoassay using standard kits from Siemens firm. During the study, 176 patients were divided into two groups, depending on the presence of AO: the first group consisted of patients with GD without AO (62 people), the second group included patients with GD and AO (114 people). Results. In GD, 91.78 % of patients (161 people) have an insufficient level of 25(OH)D content: a suboptimal level was recorded in 42 patients (23.86 %), and a deficit — in 119 patients (67.61 %). A significant negative correlation relationship was revealed between TSHR-Ab and 25(OH)D in the group of patients with GD and AO — with a lower level of 25(OH)D, the higher values of TSHR-Ab correlate. Compensation of the 25(OH)D deficiency leads to a significant (P < 0.05) decrease in the levels of TSHR-Ab and TPO in patients with GD. Besides, there is a large body of literature available linking vitamin D to thyroid autoimmunity as a result of cross-sectional studies and observations. Conclusions. Thus, there is still an urgent need for large multicenter studies to evaluate the effect of vitamin D supplementation on meaningful long-term clinical endpoints in AITD. Keywords: vitamin D; thyroid gland; autoimmune diseases; immune system
... Recently, many researchers have found that AITD patients have reduced a diversity and abundances of certain microbiota compared with healthy controls (21)(22)(23). The a diversity mainly contains community diversity (Simpson and Shannon) and community richness indices (ACE and Chao1) (24). ...
Article
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Background Autoimmune thyroid disease (AITD) is characterized by thyroid dysfunction and deficits in the autoimmune system. Growing attention has been paid toward the field of gut microbiota over the last few decades. Several recent studies have found that gut microbiota composition in patients with AITD has altered, but no studies have conducted systematic reviews on the association between gut microbiota and ATID.Methods We searched PubMed, Web of Science, Embase, and Cochrane databases without language restrictions and conducted a systematic review and meta-analysis of eight studies, including 196 patients with AITD.ResultsThe meta-analysis showed that the alpha diversity and abundance of certain gut microbiota were changed in patients with AITD compared to the controls. Chao1,the index of the microflora richness, was increased in the Hashimoto’s thyroiditis group compared to controls (SMD, 0.68, 95%CI: 0.16 to 1.20), while it was decreased in the Graves’ disease group (SMD, -0.87, 95%CI: -1.46 to -0.28). In addition, we found that some beneficial bacteria like Bifidobacterium and Lactobacillus were decreased in the AITD group, and harmful microbiota like Bacteroides fragilis was significantly increased compared with the controls. Furthermore, the percentage of relevant abundance of other commensal bacteria such as Bacteroidetes, Bacteroides, and Lachnospiraceae was increased compared with the controls.Conclusions This meta-analysis indicates an association between AITD and alteration of microbiota composition at the family, genus, and species levels.Systematic Review RegistrationPROSPERO, identifier CRD42021251557.
... Many studies showed that GD is related to yersinia enterocolitica, e.g., mice fed only with yersinia enterocolitica did not develop GD (Weiss et al., 1983;Wang et al., 2010). There were also significant differences in the microbiota profile between HT patients and healthy controls (Zhao et al., 2018). Zhou hyperthyroid patients (Zhou et al., 2014). ...
Article
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Graves’ disease (GD) is an autoimmune thyroid disease (AITD), which is one of the most common organ-specific autoimmune disorders with an increasing prevalence worldwide. But the etiology of GD is still unclear. A growing number of studies show correlations between gut microbiota and GD. The dysbiosis of gut microbiota may be the reason for the development of GD by modulating the immune system. Metabolites act as mediators or modulators between gut microbiota and thyroid. The purpose of this review is to summarize the correlations between gut microbiota, microbial metabolites and GD. Challenges in the future study are also discussed. The combination of microbiome and metabolome may provide new insight for the study and put forward the diagnosis, treatment, prevention of GD in the future.
... In systemic sclerosis (SSc) it has been reported that commensal genera deemed to protect against inflammation, such as Clostridium, Faecalibacterium, and Bacteroides, were less frequent compared to healthy controls. Given the emerging evidence that suggests alterations in gut microbiota exist in SSc 29 and Hashimoto's thyroiditis, 30 we highlight our results with these important studies. Similar to the Volkmann study, we observed a contraction of taxa within Clostridium. ...
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Anti-SSA/Ro antibodies, while strongly linked to fetal cardiac injury and neonatal rash, can associate with a spectrum of disease in the mother, ranging from completely asymptomatic to overt Systemic Lupus Erythematosus (SLE) or Sjögren's Syndrome (SS). This study was initiated to test the hypothesis that the microbiome, influenced in part by genetics, contributes to disease state. The stool microbiome of healthy controls (HC) was compared to that of anti-SSA/Ro positive women whose children had neonatal lupus. At the time of sampling, these women were either asymptomatic (Asym), had minor rheumatic symptoms or signs considered as an undifferentiated autoimmune syndrome (UAS), or were diagnosed with SLE or SS. Differences in microbial relative abundances among these three groups were tested assuming an ordering in clinical severity (HC<Asym/UAS<SS/SLE) and then again without the ordinal assumption. Those taxa that showed differential relative abundances were then tested for whether the effect size differed depending on the women's HLA SLE-risk allele genotype (DRB1*03:01, DRB1*15:01, DQB1*02:01 and DQB1*06:02) or anti-SSA/Ro autoantibody levels. Multiple genera within the families Ruminococcaceae and Lachnospiraceae showed evidence of an HLA-by-genus interaction (P < .05). Four genera exhibited evidence of an interaction with anti-Ro52 IgA: Lachnoclostridium, Romboutsia, Bacteroides and Actinomyces (P < .01). In addition to documenting differences in microbial relative abundances across clinical severity of disease, these data provide a first-time demonstration that microbial differences are correlated with HLA SLE-risk alleles. Taken together, these data suggest that the clinical spectrum from benign to overt clinical autoimmunity may partially result from or trigger a complex interplay among specific microbial profiles, anti-Ro autoantibodies, and genetics.
... In a cross-sectional study with 45 HT patients with euthyroidism, 18 HT patients with hypothyroidism, and 34 healthy controls, the microbial richness and diversity of gut microbiota was significantly lower in patients with HT, especially in hypothyroidism, compared with the controls [162]. Another cross-sectional study of 28 HT patients and 16 matched healthy controls confirmed that HT patients have altered gut microbiota [163]. Therefore, further research should be carried out to show the role of the microbiota in the pathogenesis and progression of HT. ...
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Hashimoto’s thyroiditis (HT) is the most common autoimmune disease and the leading cause of hypothyroidism, in which damage to the thyroid gland occurs due to the infiltration of lymphocytes. It is characterized by increased levels of antibodies against thyroid peroxidase and thyroglobulin. In this review, we present the metabolic profile, the effectiveness of micronutrient supplementation and the impact of dietary management in patients with HT. For this current literature review, the databases PubMed, Cochrane, Medline and Embase were reviewed from the last ten years until March 2022. This article provides a comprehensive overview of recent randomized controlled trials, meta-analyses, and clinical trials. Many patients with HT, even in the euthyroid state, have excess body weight, metabolic disorders, and reduced quality of life. Due to frequent concomitant nutritional deficiencies, the role of vitamin D, iodine, selenium, magnesium, iron and vitamin B12 is currently debated. Several studies have underlined the benefits of vitamin D and selenium supplementation. There is still no specific diet recommended for patients with HT, but a protective effect of an anti-inflammatory diet rich in vitamins and minerals and low in animal foods has been suggested. There is insufficient evidence to support a gluten-free diet for all HT patients. Pharmacotherapy, along with appropriate nutrition and supplementation, are important elements of medical care for patients with HT. The abovementioned factors may decrease autoantibody levels, improve thyroid function, slow down the inflammatory process, maintain proper body weight, relieve symptoms, and prevent nutritional deficiencies and the development of metabolic disorders in patients with HT.
... Ishaq et al. demonstrated the correlation between the altered composition and increased diversity of the microbiota in HT patients relative to healthy individuals, where the microbiota of HT patients was found impaired (60). Similar results were reported by Zhao et al. stating that the changes in the gut microbes are correlated with the thyroid function (61). It is important to note that both of the above studies found a declined abundance of Prevotella in HT patients, which is consistent with that found in MS and hepatocellular carcinoma (16,17). ...
Article
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Emerging studies have provided a preliminary understanding of the thyroid-gut axis, indicating that intestinal microbiota and its metabolites may act directly or indirectly on the thyroid by influencing intestinal microelements uptake, iodothyronine conversion and storage, and immune regulation, providing new insights into the pathogenesis of thyroid disorders and clinical management strategies. However, the research on gut microbiota and thyroid has only presented the tip of the iceberg. More robust clinical data and basic experiments are still required to elucidate the specific relationships and mechanisms in the future. Here we will characterize the associations between the microbiota and thyroid diseases to evaluate their potential implications in the pathophysiology and open up scientific avenues for future precision studies of the thyroid-gut axis.
... Microbes affect thyroid hormone levels by regulating iodine intake, degradation and enterohepatic circulation [3]. The development of autoimmune diseases of the thyroid gland is most often explained by the mechanisms of molecular mimicry, i.e., the appearance of autoreactive clones of T and B lymphocytes as a result of an immune cross-response to homologous bacterial or viral antigens [4]. Another explanation is that tissue transglutaminase serum immunoglobulin G (IgG) and gliadin immunoglobulin A (IgA) antibodies are significant predictors of anti-thyroid antibodies in patients with Hashimoto's thyroiditis. ...
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The popularization of the gluten-free diet brings with it a fashion for its use, which can harm the treatment of Hashimoto’s disease. The few studies in this regard do not confirm positive changes resulting from a gluten-free diet. At the same time, the presence of other comorbid autoimmune diseases in this group of patients is increasing. This may have important implications for the interpretation of test results and the need for a gluten-free diet in some patients. In this review, the PubMed database was searched for links between a gluten-free diet, Hashimoto’s disease, and autoimmune diseases. When analyzing the available literature, we found no basis for introducing a gluten-free diet for the standard management of Hashimoto patients. The recommended diet is instead an anti-inflammatory diet that levels the supply (to compensate for deficiencies) of vitamin D, iodine, and selenium, which are found in plant products rich in polyphenols, antioxidants, and omega-3 fatty acids, as illustrated in this article.
... Nevertheless, some data from animal model-based studies allow us to suggest various potential roles, among them the action of the microbiota on the metabolism of iodothyronines [84] and the absorption of micronutrients, which are essential for normal thyroid function (iodine, iron, copper, zinc, and, above all, selenium) [86] . Furthermore, several studies in humans have shown, albeit unevenly, the presence of dysbiosis in Helicobacter pylori (HP)and Hashimoto's thyroiditis (HT) patients [87] . In the latter case, a correlation between the abundance of selected types of bacteria and diagnostics parameters has been observed, connected with autoimmune thyroiditis, such as antibodies to the thyroid gland peroxidase (anti-TPO) and thyroglobulin (anti-TG) [88] . ...
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The infant gut microbiota is the set of microorganisms colonizing the baby’s intestine. This complex ecosystem appears to be related to various physiological conditions of the host and it has also been shown to act as one of the most crucial determinants of infant’s health. Furthermore, the mother’s endocrine system, through its hormones, can have an effect on the composition of the newborn’s gut microbiota. In this perspective, we summarize the recent state of the art on the intricate relationships involving the intestinal microbiota and the endocrine system of mother/baby to underline the need to study the molecular mechanisms that appear to be involved.
... In addition, pregnancy as a special period of life, the composition of intestinal microflora of them may be different from that of normal people due to significant changes in maternal hormone levels. Prevotella and Haemophilus are floras belonging to Gram-negative bacteria and settle normally in the human gastrointestinal tract; its disorder can cause Hashimoto's Thyroiditis, inflammatory bowel disease and other diseases (25,26). The increased abundance of Prevotella and Haemophilus in hypothyroidism during pregnancy may be related to its characteristics in autoimmune process. ...
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Objective: To investigate the lipid profiles and intestinal microflora in pregnant patients with hypothyroidism and their correlation with pregnancy outcomes. Methods: In total, 27 pregnant women with hypothyroidism (study case) and 28 normal pregnant women (control group) were enrolled in this study. The lipid profiles and intestinal microflora in the two groups were compared using untargeted liquid chromatography-mass spectrometry (LC-MS) and 16S rRNA amplicon sequencing, respectively. The association among the differential metabolites, intestinal microflora, serological indicators and pregnancy outcomes was further analyzed. Results: Patients in study case had higher C-reactive protein (CRP) levels (P = 0.025) and lower birth weight (P=0.005) than the control group. A total of 42 differential lipid metabolites and 7 enrichment KEGG pathways were obtained between the two groups (VIP ≥ 1, P < 0.05). Ten lipid metabolites can be used as characteristic metabolites of study case, including phosphatidylcholine (PC), phosphatidylethanolamine (PE) and sphingomyelin (SM). The richness and diversity of intestinal microflora in study case were lower than those in the control group (P>0.05). LEfSe analysis revealed that patients in study case had higher abundance of Prevotella and Haemophilus and lower abundance of Blautia than the control group (P < 0.05). Blautia was positively correlated with SM and negatively correlated with PC and PE; the CRP level and Prevotella were positively correlated; the neonatal weight and PC level were negatively correlated (P < 0.05). Conclusion: The lipid profile and intestinal microflora of pregnant women with hypothyroidism significantly differed from those of normal pregnant women and were associated with adverse pregnancy outcomes. The interaction between lipid metabolism and intestinal microflora may be a potential target for further studies investigating the pathogenesis of hypothyroidism during pregnancy.
... A decrease in the levels of Bifidobacteria and Lactobacillaceae has also been reported in patients with hyperthyroidism 35 . In patients with HT, a significant increase in the abundance of Bacteroides species and a decrease in that of Bifidobacterium in stool samples have been observed 36 ; however, a decreased abundance of Bacteroides members has also been observed 37 . Prevotellaceae, Bacteroides, and Bifidobacteria also showed a negative relationship with anti-TPO levels in this study, further indicating their immunoregulatory effect. ...
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Papillary thyroid carcinoma (PTC) has a high incidence, and its proper treatment remains challenging. Therefore, identifying PTC progression markers is essential. Here, using 16S RNA sequences, we analyzed the PTC intratumor microbiome and its role in tumor progression. Substantial microbial abundance was detected in PTC from all patients. The tumor bacterial diversity in patients with advanced lesions (T3/T4) was significantly higher than that in patients with relatively mild lesions (T1/T2). Importantly, we identified signatures of eight tumor bacterial taxa highly predictive of PTC invasion status. Hence, microbial host factors—independent of the genomic composition of the tumor—may determine tumor behaviors and patient outcomes. Furthermore, the correlation between specific bacterial genus and thyroid hormones or autoimmune thyroid disease-related antibodies may indicate the potential contribution of the microbiome in the relationship between autoimmune thyroid disease or irregular thyroid function and PTC progression, intervention of which might therefore be worth exploring for advancing oncology care.
... Escherichia coli is facultative anaerobic bacteria, which grows well under either oxic or anoxic conditions. Studies have reported that the abundance of Ruminococcus torques in the gut of patients with autoimmune diseases, such as IBD, Hashimoto's thyroiditis and amyotrophic lateral sclerosis, was significantly increased [24][25][26], whereas the abundance of Bacteroides was decreased in Hashimoto's thyroiditis patients [23]. Studies have also reported the abundance of Ruminococcus guavus enriched in the gut of patients with IBD [27], and intestinal dysbiosis with increased Ruminococcus gnavus abundance associated with allergic diseases in infants [28]. ...
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Background: Many studies have reported minor complications and disturbance of the gut microbiota after colonoscopy. Compared with air, carbon dioxide (CO2) insufflation could decrease minor complications, but its impact on gut microbiota remains unknown. Methods: Thirty-eight healthy subjects were assessed and twenty were randomized to receive either CO2 or air insufflation during colonoscopy. Neither the participants nor the staff involved in the follow-up knew which gas was used. Minor complications were assessed using symptom scores. Fecal samples were collected at eight time-points for microbiome analysis by full-length 16S rRNA gene amplicon analysis. Results: Baseline characteristics were similar in both groups. The recovery of minor complications after colonoscopy was faster in the CO2 group (the day of the colonoscopy) than in the air group (the day after the colonoscopy). There was no significant reduction in alpha diversity (species richness) of the first stool after colonoscopy in the CO2 group (115.0 ± 32.81 vs. 97.4 ± 42.31, p = 0.28) compared with the air group (123.8 ± 37.25 vs. 84.8 ± 31.67, p = 0.04). However, there were no differences in beta diversity between the groups. Linear discriminant analysis effect size (LEfSe) analysis indicated that anaerobic probiotics such as Bacteroides caccae, Bacteroides finegoldii and Bacteroides thetaiotaomicron were more abundant in the CO2 group than in the air group within 14 days after colonoscopy. On the contrary, the content of Escherichiacoli, Ruminococcus torques and Ruminococcus guavus was higher in the air group. Conclusions: CO2 is beneficial to gut microbiota homeostasis during colonoscopy in healthy subjects. The effects in patients with different diseases need to be further studied.
... Όμως, απαιτούνται περισσότερα δεδομένα, καθ' όσον σε προηγούμενη μελέτη είχαν δημοσιευτεί διαφορετικά αποτελέσματα. 38 Συγκεκριμένα, σε ασθενείς με HT σημειώθηκε αύξηση των βακτηρίων που ανήκουν στα γένη Blautia, Roseburia, Ruminococcus, Rombutsia, Dorea, Fusicatenibacter, Eubacterium με σύγχρονη ελάττωση των βακτηρίων τα οποία ανήκουν στα γένη Bacteroides, Faecalibacterium και Prevotella. Σε μια ενδιαφέρουσα έρευνα 39 μελετήθηκε η σχέση μεταξύ του Helicobacter pylori και της HT. ...
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The human microbiome constitutes an integral part of health. In particular, it is quite necessary for the develop- ment, differentiation and maturation of the immune system, 70% of which resides in the intestinal mucosa. Microbi- ome studies until now revealed an association between disturbance of microbiota (dysbiosis) and various patholog- ical disorders including changes in host immune status. Autoimmune thyroid diseases are one of the most common organ-specific autoimmune disorders with a worldwide prevalence higher than 5%. Among the latters, those that predominate are Hashimoto’s thyroiditis and Graves’ disease. Several factors have been studied such as genetic and environmental ones. According to recent studies, it is assumed that gut microbiome might play a significant role in triggering autoimmune diseases of the thyroid gland. However, the exact etiology has not been elucidated yet. The present review aims to describe the work done so far regarding the role of gut microflora in the pathogenesis of au- toimmune thyroid diseases and its involvement in the appearance of benign nodules and papillary thyroid cancer. It appears that future work is needed to elucidate more precisely the mechanism of involvement of gut microbiota to the development of autoimmune thyroid diseases.
... With the development of medicine, the probability of disease being discovered also increases, which makes the treatment method more reasonable and efficient. Thyroid is more likely to be the target organ for autoimmune diseases (18). If the autoimmune system is disordered, attacking the thyroid can easily induce various thyroid diseases, such as Hashimoto's thyroiditis. ...
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Background: This study was to analyze the correlation between abnormal thyroid function detection and thyroid autoimmune disease, so as to provide theoretical guidance for clinical diagnosis of thyroid autoimmune disease. Methods: The Chinese databases were searched with a combination of words "thyroid", "thyroid autoimmune disease", "thyroid function testing", "meta-analysis". The entire database was searched in English language databases with the search terms "thyroid", "thyroid autoimmune disease", "thyroid function test ", "meta-analysis". Review manager software was applied for meta-analysis. Results: A total of 8 articles were finally included. 4 articles reported the T3 level, showing P=0.95, I2=0%, odds ratio (OR) =2.39, 95% confidence interval (CI): 0.79-7.25; 3 articles reported the T4 levels, showing P=0.81, I2=0%, OR =2.16, 95% CI: 0.43-10.71; and 4 articles reported the thyroid stimulating hormone (TSH) level, showing P=0.48, I2=0%, OR =3.20, 95% CI: 1.45-7.07. Discussion: After a systematic review of the literature, a significant difference was found in T3 and TSH levels between patients with autoimmune thyroid disease and those with a healthy thyroid, but the difference in T4 level was not significant.
... A-E ROC curves for the 5 differential genera and F the combination of Comamonas and Sphingomonas were plotted based on microbial relative abundance tissues was also observed in patients with lung cancer and gastric cancer [22,23]. Nevertheless, an increase in gut microbiota diversity is observed in patients with TC, Hashimoto's thyroiditis, and hyperthyroidism [14,16,24]. At the genus level, the core microbiota of thyroid tissues included Comamonas, Acinetobacter, Pseudomonas, Microvirgula, Soonwooa, and Sphingomonas, while the core gut microbiota of TC encompassed Faecalibacterium, Bacteroides, Blautia, Rosebulia, Dialister, and Lachnoclostridium. ...
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Background In recent years, the incidence rate of Thyroid carcinoma (TC) has been increasing worldwide. Thus, research on factors of TC carcinogenesis may promote TC prevention and decrease the incidence rate. There are several studies targeting the correlation between gut microbiota and thyroid disease. Carcinogenesis of several malignancies is influenced by microbiota. However, thyroid microbiome of TC has not been revealed. This study investigated thyroid microbiota in different TC microhabitats. Methods We performed 16s rRNA gene sequencing using tumor tissues and matched peritumor tissues from 30 patients with TC to characterize thyroid microbiota. Results The richness and diversity of thyroid microbiota were lower in TC tumor samples than in matched peritumor tissues. At the genus level, the core microbiota of thyroid included Sphingomonas , Comamonas , Acinetobacter , Pseudomonas , Microvirgula , and Soonwooa . The abundance of Sphingomonas and Aeromonas was significantly increased in tumor tissues, while the abundance of Comamonas , Acinetobacter , and Peptostreptococcus was significantly enhanced in peritumor tissues. The combination of Comamonas and Sphingomonas could discriminate tumor samples from peritumor samples with an area under the curve (AUC) of 0.981 (95% confidence interval [CI] 0.949–1.000). The abundance of Sphingomonas was significantly higher in N1 stage than in N0 stage. Sphingomonas could distinguish between N0 and N1 stage with an AUC of 0.964 (95% CI 0.907–1.000). Conclusions The microbial diversity and composition were significantly different between peritumor and tumor microhabitats from patients with TC, which may eventually affect TC carcinogenesis and progression. The combination of Comamonas and Sphingomonas could serve as a powerful biomarker for discrimination between tumor and peritumor tissues. Furthermore, the higher abundance of Sphingomonas was correlated with lymph node metastasis, indicating that the abundance of Sphingomonas may indicate a poor prognosis for TC patients, and Sphingomonas may play a role in promoting TC progression.
... Some studies have confirmed that 17 cells are involved in the occurrence and development of Hashimoto's thyroiditis, and the elevated level of 17 cells is positively correlated with thyroid autoimmune injury [26,27]. However, Zhao et al. [28] conducted a study in which prevotella was reduced in patients with normal thyroid function and elevated TGAb and TPOAb. As there are several types of Hashimoto's disease with normal, overactive, and decreased thyroid function, the relationship between the difference in results and thyroid function needs to be further verified. ...
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The intestinal microbiota is essential for the host to ensure digestive and immunologic homeostasis. When microbiota homeostasis is impaired and dysbiosis occurs, the malfunction of epithelial barrier leads to intestinal and systemic disorders, chiefly immunologic and metabolic. The role of the intestinal tract is crucial in the metabolism of nutrients, drugs, and hormones, including exogenous and endogenous iodothyronines as well as micronutrients involved in thyroid homeostasis. In the studies, intestinal dysbiosis was detected mostly in autoimmune thyroid diseases and thyroid carcinoma. In addition, a correlation was observed between bacterial diversity and plasma thyroid parameters and bacterial diversity in thyroid diseases. However, the link between thyroid homeostasis and microbiota composition has not yet been clarified. When treating patients suffering from thyroid diseases, it is seen that there is a need for relevant clinical studies on making the probiotic supplement to be recommended in accordance with the intestinal composition.
Chapter
Evidence from animal models and humans suggests the role of intestinal dysbiosis in autoimmune disease development. Dysbiosis is associated with decreased microbiota function and diversity, increased intestinal permeability and pathobionts, and deregulated immune response. The proposed mechanisms to connect dysbiosis with autoimmunity include molecular mimicry, bystander T-cell activation, epitope spreading, post-translational modification of luminal proteins, and amplification by inflammatory cytokines. Probiotic bacteria favor the balance and maintenance of a healthy microbiota and epithelial barrier and directly impact systemic immunity, supporting their use in immune-mediated diseases. This article describes studies concerning dysbiosis and probiotics in autoimmune diseases.
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The gut microbiota plays a crucial role in healthy individuals as well as in patients with thyroid diseases, including thyroid cancer. Although the prognosis of differentiated thyroid cancer is predictable, that of some poorly differentiated, medullary, and anaplastic thyroid cancers remains unpromising. As the interaction between the gut microbiota and thyroid cancer has been gradually revealed in recent years, the thyroid gland, a crucial endocrine organ, is shown to have a complex connection with the body's metabolism and is involved in inflammation, autoimmunity, or cancer progression. Dysbiosis of the gut microbiota and its metabolites can influence changes in hormone levels and susceptibility to thyroid cancer through multiple pathways. In this review, we focus on the interactions of the gut microbiota with thyroid function diseases and thyroid cancer. In addition, we also discuss some potential new strategies for the prevention and treatment of thyroid disease and thyroid cancer. Our aim is to provide some possible clinical applications of gut microbiota markers for early diagnosis, treatment, and postoperative management of thyroid cancer. These findings were used to establish a better multi-disciplinary treatment and prevention management strategy and to individualize the treatment of patients in relation to their gut microbiota composition and pathological characteristics.
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Chapter
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Chapter
The gut has long been considered to be a “neglected” organ. However, in the past 10–15 years, many studies highlighted the potential of the microbial community residing in the gut—the gut microbiota—to interact with the host immune system and to produce active compounds, including hormone-like molecules. The increased or decreased abundances of certain bacterial species and their bio-products were associated with health and disease conditions. While the role of the gut microbiota can be more easily understood in gut-related diseases (e.g., IBD, Crohn's disease, colon cancer…), such relationships have also been described in non-gut-related diseases, including autoimmune and endocrine diseases. The present work aims to describe the role of the gut microbiota from its establishment to the “state-of-the-art” methodologies used for its investigation. More in detail, the relationship between the gut microbiota and endocrine diseases, such as thyroid diseases and diabetes, will be described, including the translational promise of potential therapeutic applications.
Chapter
Several evidence in animal models and humans pointed to the involvement of oral and intestinal dysbiosis in the development of autoimmune diseases. Dysbiosis is associated with decreased bacterial function and diversity, as well as decreased beneficial microbes, increased pathobionts, impaired barrier function, bacterial translocation, systemic inflammation, and decreased immune regulatory mechanisms in the gut mucosa. The mechanisms proposed to link dysbiosis with autoimmune diseases include molecular mimicry, bystander T-cell activation, T helper cell skewing, epitope spreading, dual T-cell receptors, posttranslational modification of luminal proteins by dysbiotic microbiota, and amplification by inflammatory cytokines. Studies suggest that probiotics influence systemic immune responses, ensure the homeostasis of the healthy microbiota in the intestinal mucosa, and therefore, could be used as adjuvant therapy to treat immune-mediated diseases. The mechanisms to achieve these effects include mucus secretion, antimicrobial peptide production, cross-feeding other resident microbes, production of organic acids and enzymes, gastrointestinal epithelial barrier maintenance, decreasing oxidative stress, competition with pathogens, and finally, modulation of the host immunity. Here, we described several reports concerning dysbiosis and probiotic applications in animal models of autoimmune diseases, human studies, and clinical trials concerning the applicability of probiotics in autoimmune diabetes, autoimmune thyroid diseases, rheumatoid arthritis, systemic lupus erythematosus, and Sjögren syndrome.
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Bifidobacterium bifidum 791 (commercially available as B. bifidum BIM B-733D) cell-surface biopolymers (BPs) interact selectively with human serum thyroid peroxidase (TPO) and thyroglobulin (Tg) autoantibodies (anti TPO and anti Tg, respectively). BPanti-TPO and BPanti-Tg were isolated from the soluble fraction of B. bifidum BIM B-733D by affinity chromatography with anti-TPO or anti-Tg, respectively. Homogeneity of affinity eluates (AEanti-TPO and AEanti-Tg) was tested by size exclusion chromatography. For each AE, the elution profiles generated on the basis of absorbance at 280 nm do not conform to ELISA data for functional activity characteristic of BPs. Moreover, high functional activity was detected in chromatographic fractions that had significantly different molecular weights and no absorbance at 280 nm, which suggests a non-protein (carbohydrate) nature of BPanti-TPO and BPanti-Tg. The semi-preparative size exclusion chromatography of AEanti-TPO and AEanti-Tg with detection by refractometer gave 5,000-7,000 Da fractions containing substances that interact selectively with either anti TPO (BPanti-TPO) or anti-Tg (BPanti-Tg) according to ELISA data. Analysis by two-dimensional NMR spectroscopy including a 1H, 13C-heteronuclear single-quantum coherence experiment indicated that both substances are linear α-1,6-glucans. For the first time, an immunological similarity (molecular mimicry) of glycopolymers of B. bifidum BIM B-733D and human thyroid proteins, TPO and Tg, was shown. On the whole, our data point to a possible role of bifidobacteria in the pathogenesis of autoimmune thyroid diseases (ATD). The main requirements for triggering/acceleration or prevention/abrogation of ATD by bifidobacteria through molecular mimicry mechanism are hypothesised to be (1) genetic predisposition to ATD and (2) intestinal epithelium penetration by α-1,6-glucan.
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High proportions of autistic children suffer from gastrointestinal (GI) disorders, implying a link between autism and abnormalities in gut microbial functions. Increasing evidence from recent high-throughput sequencing analyses indicates that disturbances in composition and diversity of gut microbiome are associated with various disease conditions. However, microbiome-level studies on autism are limited and mostly focused on pathogenic bacteria. Therefore, here we aimed to define systemic changes in gut microbiome associated with autism and autism-related GI problems. We recruited 20 neurotypical and 20 autistic children accompanied by a survey of both autistic severity and GI symptoms. By pyrosequencing the V2/V3 regions in bacterial 16S rDNA from fecal DNA samples, we compared gut microbiomes of GI symptom-free neurotypical children with those of autistic children mostly presenting GI symptoms. Unexpectedly, the presence of autistic symptoms, rather than the severity of GI symptoms, was associated with less diverse gut microbiomes. Further, rigorous statistical tests with multiple testing corrections showed significantly lower abundances of the genera Prevotella, Coprococcus, and unclassified Veillonellaceae in autistic samples. These are intriguingly versatile carbohydrate-degrading and/or fermenting bacteria, suggesting a potential influence of unusual diet patterns observed in autistic children. However, multivariate analyses showed that autism-related changes in both overall diversity and individual genus abundances were correlated with the presence of autistic symptoms but not with their diet patterns. Taken together, autism and accompanying GI symptoms were characterized by distinct and less diverse gut microbial compositions with lower levels of Prevotella, Coprococcus, and unclassified Veillonellaceae.
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Irritable bowel syndrome (IBS) is a functional gastrointestinal disorder that has been associated with aberrant microbiota. This review focuses on the recent molecular insights generated by analysing the intestinal microbiota in subjects suffering from IBS. Special emphasis is given to studies that compare and contrast the microbiota of healthy subjects with that of IBS patients classified into different subgroups based on their predominant bowel pattern as defined by the Rome criteria. The current data available from a limited number of patients do not reveal pronounced and reproducible IBS-related deviations of entire phylogenetic or functional microbial groups, but rather support the concept that IBS patients have alterations in the proportions of commensals with interrelated changes in the metabolic output and overall microbial ecology. The lack of apparent similarities in the taxonomy of microbiota in IBS patients may partially arise from the fact that the applied molecular methods, the nature and location of IBS subjects, and the statistical power of the studies have varied considerably. Most recent advances, especially the finding that several uncharacterized phylotypes show non-random segregation between healthy and IBS subjects, indicate the possibility of discovering bacteria specific for IBS. Moreover, tools are being developed for the functional analysis of the relationship between the intestinal microbiota and IBS. These approaches may be instrumental in the evaluation of the ecological dysbiosis hypothesis in the gut ecosystem. Finally, we discuss the future outlook for research avenues and candidate microbial biomarkers that may eventually be used in IBS diagnosis.
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