Alteration of Intestinal Microbiota and Hydrogen Sulfide Metabolism in Patients with Hashimoto's Thyroiditis.

Objective: To analyze the intestinal microbiota and H2S levels in patients with HT. Methods: Twenty euthyroid HT patients and twenty healthy control individuals were recruited. Fecal samples were collected, and the microbiota was examined using 16S RNA gene sequencing. We also collected serum samples to examine the H2S levels. Results: Compared with patients with HT, the ACE and Chao indices were significantly lower in healthy controls (P=0.04, 0.03, respectively). The microbial composition of the HT group differed significantly from that of the healthy group. We observed a significant increase in the proportions of Bacteroides, Fusobacterium, Sutterella, and Veillonella in patients with HT (P < 0.05). Linear discriminant analysis and effect size analysis also revealed that Bacteroides and Ralstonia were enriched in patients with HT. Additionally, patients with HT had significantly lower H2S levels than healthy controls (P < 0.005). The enrichment of H2S anabolism was linked to the alteration of intestinal microbiota in patients with HT. Conclusion: We demonstrated that patients with HT have aberrant intestinal microbiome and that H2S anabolism may contribute to HT pathogenesis.

Analysis of gut microbiota diversity in Hashimoto's thyroiditis patients.

BACKGROUND: Hashimoto's thyroiditis (HT) is an autoimmune disease. Recent studies have found that the gut microbiota may play an important role in inducing HT, but there are no systematic studies on the changes in the gut microbiota during the development of HT. METHODS: In this study, 16S rDNA high-throughput sequencing technology in combination with the Kruskal-Wallis test, CCA/RDA analysis, Spearman correlation analysis, and other statistical methods were used to analyze the effects of age, gender, hormones, and other environmental factors on gut microbiota by comparing the differences in the microbiota at different stages of HT development. RESULTS: The results showed that there were differences in the gut microbiota composition between healthy people (HCA) and in patients with HT. Lachnoclostridium, Bilophila, and Klebsiella were enriched in the HCA group, while Akkermansia, Lachnospiraceae, Bifidobacterium, Shuttleia, and Clostriworthdia were enriched in the HT group. Environmental factors analysis revealed that the Bifidobacterium and Klebsiella were two groups of bacteria that have undergone dramatic changes in HCA and HT, and mainly affected by gender. Romboutsia and Haemophilus regulated by the hormone of free triiodothyronine (FT3) may promote the development of HT, while Faecalibacterium and Lachnospiraceae regulated by free thyroxine (FT4) may protect the host. CONCLUSIONS: Comprehensive studies have shown that gender is an important factor affecting gut microbial composition, but with the development of HT, hormones, age, and TSH begin to become dominant factors.

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

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. Results: The 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 Registration: PROSPERO, identifier CRD42021251557.

Simulation Model for Hashimoto Autoimmune Thyroiditis Disease.

Hashimoto thyroiditis (HT) is a pathology that 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 HT disease.

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

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

The Human Microbiota in Endocrinology: Implications for Pathophysiology, Treatment, and Prognosis in Thyroid Diseases.

The human microbiota is an integral component in the maintenance of health and of the immune system. Microbiome-wide association studies have found numerous diseases associated to dysbiosis. Studies are needed to move beyond correlations and begin to address causation. Autoimmune thyroid diseases (ATD) are one of the most common organ-specific autoimmune disorders with an increasing prevalence, higher than 5% worldwide. Most frequent manifestations of ATD are Hashimoto's thyroiditis and Graves' disease. The exact etiology of ATD remains unknown. Until now it is not clear whether bacterial infections can trigger ATD or modulate the efficacy of treatment and prognosis. The aim of our review is to characterize the microbiota and in ATD and to evaluate the impact of dysbiosis on treatment and prognosis. Moreover, variation of gut microbiome has been associated with thyroid cancer and benign nodules. Here we will characterize the microbioma in benign thyroid nodules, and papillary thyroid cancer to evaluate their implications in the pathophysiology and progression.

Microorganisms associated to thyroid autoimmunity.

Autoimmune thyroid diseases are a group of diseases characterized by a dysfunction of the immune system concerning the thyroid gland, associated with hypothyroidism or hyperthyroidism. The thyroid gland autoimmunity has been recognized as multifactorial. It has been reported that microorganisms may play a role on the pathogenesis of Hashimoto's thyroiditis and Graves´ disease. These could explain the high incidence of the autoimmune thyroid diseases. Helicobacter Pylori (H. pylori) and Hepatitis C virus (HCV) are the microorganisms in which the association with autoimmune thyroid diseases is clearer. The pathophysiologic mechanisms are still not well defined. For H. pylori, molecular mimicry has been the most accepted mechanism. It has been proposed Hepatitis C virus as the trigger of the thyroid autoimmunity by exacerbating the production of thyroid auto-antibodies, while some mention that the real factor that triggers the thyroid autoimmunity is the treatment with Interferon alpha (IFN-alpha) by upregulating MHC class I and inducing ligation of CD40+ cells to thyrocytes. Other microorganisms such as Toxoplasma gondii, Human Immunodeficiency virus, Herpes virus and others have reported information about their association with thyroid autoimmune diseases There are no proposals on how these last microorganisms induce thyroid autoimmunity. There is still a lack of evidence on this topic. Further research must be done to determine the interaction of these microorganisms and the best way to manage these patients.

Gut microbiota and metabolites in the pathogenesis of endocrine disease.

Type 1 diabetes (T1D) and Hashimoto's thyroiditis (HT) are the two most common autoimmune endocrine diseases that have rising global incidence. These diseases are caused by the immune-mediated destruction of hormone-producing endocrine cells, pancreatic beta cells and thyroid follicular cells, respectively. Both genetic predisposition and environmental factors govern the onset of T1D and HT. Recent evidence strongly suggests that the intestinal microbiota plays a role in accelerating or preventing disease progression depending on the compositional and functional profile of the gut bacterial communities. Accumulating evidence points towards the interplay between the disruption of gut microbial homeostasis (dysbiosis) and the breakdown of host immune tolerance at the onset of both diseases. In this review, we will summarize the major recent findings about the microbiome alterations associated with T1D and HT, and the connection of these changes to disease states. Furthermore, we will discuss the potential mechanisms by which gut microbial dysbiosis modulates the course of the disease, including disruption of intestinal barrier integrity and microbial production of immunomodulatory metabolites. The aim of this review is to provide broad insight into the role of gut microbiome in the pathophysiology of these diseases.

The role of infections in autoimmune encephalitides.

Autoimmune encephalitides are autoimmune neurological disorders characterized by rapidly progressive central nervous system symptoms associated with specific auto-antibodies targeting neuronal cell-surface proteins. The clinical features of encephalitis are frequently preceded by symptoms suggesting an infectious process, and specific pathogens have been detected at the early phase of the disease in some patients, suggesting that it can be triggered by infections. Moreover, recent data have shown an association with specific HLA haplotypes, suggesting a genetic susceptibility to develop at least some subtypes of autoimmune encephalitis. Nonetheless, the immunological mechanisms leading from an adequate response to infection to autoimmunity against neuronal self-antigens remain highly hypothetical. Molecular mimicry, inborn errors of the host immune system, as well as epitope spreading and chronic activation of innate immunity actors, may be involved. Importantly, the frequency of prodromal infectious symptoms and association with HLA haplotypes differ among autoimmune encephalitides, suggesting that depending on the subtype distinct immunopathogenic mechanisms are involved. A direct link between infection and autoimmune encephalitis was recently provided by the demonstration that most of the so-called relapsing neurological symptoms post-herpes simplex virus encephalitis corresponded to viral-induced autoimmune encephalitis with antibodies against NMDA receptors or other, yet unknown, neuronal surface antigens. Although this association has also been demonstrated experimentally in mice, the underlying immunological mechanisms remain unknown. Overall, a body of clinical, epidemiological and experimental data suggests infections are involved in the pathogenesis of autoimmune encephalitides. Further studies, focusing on the interplays between pathogens, genetic determinants of the host immune response, and brain inflammation, are needed to clarify the immunological mechanisms that lead to autoimmune encephalitis after infection.

Gut microbiota and Hashimoto's thyroiditis.

About two third of the human microbial commensal community, namely the gut microbiota, is hosted by the gastrointestinal tract which represents the largest interface of the organism to the external environment. This microbial community co-evolved in a symbiotic relationship with the human beings. Growing evidence support the notion that the microbiota plays a significant role in maintaining nutritional, metabolic and immunologic homeostasis in the host. Microbiota, beside the expected role in maintaining gastrointestinal homeostasis also exerts metabolic functions in nutrients digestion and absorption, detoxification and vitamins' synthesis. Intestinal microbiota is also key in the correct development of the lymphoid system, 70% of which resides at the intestinal level. Available studies, both in murine models and humans, have shown an altered ratio between the different phyla, which characterize a" normal" gut microbiota, in a number of different disorders including obesity, to which a significant part of the studies on intestinal microbiota has been addressed so far. These variations in gut microbiota composition, known as dysbiosis, has been also described in patients bearing intestinal autoimmune diseases as well as type 1 diabetes mellitus, systemic sclerosis and systemic lupus erythematosus. Being Hashimoto's thyroiditis the most frequent autoimmune disorder worldwide, the analysis of the reciprocal influence with intestinal microbiota gained interest. The whole thyroid peripheral homeostasis may be sensitive to microbiota changes but there is also evidence that the genesis and progression of autoimmune thyroid disorders may be significantly affected from a changing intestinal microbial composition or even from overt dysbiosis. In this brief review, we focused on the main features which characterize the reciprocal influence between microbiota and thyroid autoimmunity described in the most recent literature.

Alterations of the Gut Microbiota in Hashimoto's Thyroiditis Patients.

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. A comparative analysis was systematically performed of the gut microbiota in HT patients and healthy controls. METHODS: First, a cross-sectional study of 28 HT patients and 16 matched healthy controls was conducted. Fecal samples were collected, and microbiota were analyzed 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 fecal 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 Fecalibacterium, Bacteroides, Prevotella_9, and Lachnoclostridium genera were decreased. A correlation matrix based on the Spearman correlation distance confirmed correlations among seven clinical parameters. Additionally, the linear discriminant analysis effect size method showed significant differences in 27 genera between the two groups that were strongly correlated with clinical parameters. The linear discriminant analysis value was used to select the first 10 species from the 27 different genera as biomarkers, achieving area under the curve 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 understand better the role of the gut microbiota in the pathogenesis of HT.

Molecular estimation of alteration in intestinal microbial composition in Hashimoto's thyroiditis patients.

The gut microbiota has a crucial effect on human health and physiology. Hypothyroid Hashimoto's thyroiditis (HT) is an autoimmune disorder manifested with environmental and genetic factors. However, it is hypothesized that intestinal microbes might play a vital role in the pathogenesis of HT. The aim of current was to investigate and characterize the gut microbial composition of HT patients both quantitatively and qualitatively. The fecal samples from 29 HT patients and 12 healthy individuals were collected. The PCR-DGGE targeted V3 site of 16S rRNA gene and real time PCR for Bifidobacterium Lactobacillus, Bacteroides vulgatus and Clostridium leptum were performed. Pyrosequencing of 16S rRNA gene with V4 location was performed on 20 randomly selected samples. The comparative analysis of diversity and richness indices revealed diversification of gut microbiota in HT as compared to control. The statistical data elucidate the alterations in phyla of HT patients which was also affirmed at the family level. We observed the declined abundance of Prevotella_9 and Dialister, while elevated genera of the diseased group included Escherichia-Shigella and Parasutterella. The alteration in gut microbial configuration was also monitored at the species level, which showed an increased abundance of E. coli in HT. Therefore, the current study is in agreement with the hypothesis that HT patients have intestinal microbial dysbiosis. The taxa statistics at species-level along with each gut microbial community were modified in HT. Thus, the current study may offer the new insights into the treatment of HT patients, disease pathway, and mechanism.

The microbiota and autoimmunity: Their role in thyroid autoimmune diseases.

Since the 1970s, the role of infectious diseases in the pathogenesis of Graves' disease (GD) has been an object of intensive research. The last decade has witnessed many studies on Yersinia enterocolitica, Helicobacter pylori and other bacterial organisms and their potential impact on GD. Retrospective, prospective and molecular binding studies have been performed with contrary outcomes. Until now it is not clear whether bacterial infections can trigger autoimmune thyroid disease. Common risk factors for GD (gender, smoking, stress, and pregnancy) reveal profound changes in the bacterial communities of the gut compared to that of healthy controls but a pathogenetic link between GD and dysbiosis has not yet been fully elucidated. Conventional bacterial culture, in vitro models, next generation and high-throughput DNA sequencing are applicable methods to assess the impact of bacteria in disease onset and development. Further studies on the involvement of bacteria in GD are needed and may contribute to the understanding of pathogenetic processes. This review will examine available evidence on the subject.

Chronic inflammation and extra-nodal marginal-zone lymphomas of MALT-type.

Extranodal marginal zone lymphoma of mucosa associated lymphoid tissue (MALT) is an indolent B-cell non-Hodgkin lymphoma (NHL) arising in lymphoid populations that are induced by chronic inflammation in extra nodal sites. The stomach is the most commonly affected organ, and MALT lymphoma is clearly associated with a gastroduodenitis induced by a microbial pathogen, Helicobacter pylori, thus gastric MALT lymphoma represents a paradigm for evaluating inflammatory-associated lymphomagenesis. Variable levels of evidence have indicated a possible association between other microorganisms and non-gastric MALT lymphomas. In addition to infectious etiology, chronic inflammation arising as a result of autoimmune diseases such as Sjogren's syndrome or Hashimoto thyroiditis, poses a significant risk factor for developing NHL. Recently, genetic alterations affecting the NF-κB pathway, a major signaling pathway involved in many cancers, have been identified in MALT lymphoma. This review will present MALT lymphoma as an example of the close pathogenetic link between chronic microenvironmental inflammation and tumor development, showing how these observations can be integrated into daily clinical practice, also in terms of therapeutic implications, with particular focus on the NF-κB pathway.

Associations of Helicobacter pylori infection and cytotoxin-associated gene A status with autoimmune thyroid diseases: a meta-analysis.

BACKGROUND: Helicobacter pylori infection is reportedly associated with extradigestive diseases such as immune thrombocytopenic purpura and coronary heart disease. The risk factors for autoimmune thyroid diseases (ATDs) remain largely unknown, and whether H. pylori infection is associated with ATDs is still controversial. The aim of this meta-analysis was to determine the association between H. pylori infection and ATDs. METHODS: Studies comparing the prevalence rate of H. pylori infection in patients with ATDs and healthy controls, published in English, were identified through a systematic search in MEDLINE and EMBAS up to June 2012. Serological or nonserological tests were used to confirm H. pylori infection and the presence of cytotoxin-associated gene A (CagA) antigens. The odds ratios (OR) and associated 95% confidence intervals [CI] were obtained. RESULTS: Seven studies involving a total of 862 patients met the inclusion criteria and thus were included in our meta-analysis. Overall, H. pylori infection was associated with ATDs (OR 1.92 [CI 1.41-2.61]); the association was significant for Graves' disease (OR 4.35 [CI 2.48-7.64]) but not for Hashimoto's thyroiditis (OR 1.45 [CI 0.92-2.26], p=0.11). No association was observed in the subanalysis of studies using only enzyme-linked immunosorbent assay to detect H. pylori infection (OR 1.38 [CI 0.86-2.19], p=0.18). Five of the seven articles reported the association of CagA seroprevalence and ATDs. CagA seropositivity significantly increased the risk for ATDs by 2.24-fold [CI 1.06-4.75]. CONCLUSIONS: Both the prevalence of H. pylori infection and the seroprevalence of CagA-positive strains are associated with ATDs. These findings suggest that H. pylori infection potentially plays a part in the development of ATDs.

Does the gut microbiota trigger Hashimoto's thyroiditis?

Hashimoto's thyroiditis is an organ-specific autoimmune disease in which both genetic predisposition and environmental factors serve as the trigger of the disease. A growing body of evidence suggests involvement of viral infection in the development of Hashimoto's thyroiditis. However, not only pathogenic microorganisms but also non-pathogenic commensal microorganisms induce proinflammatory or regulatory immune responses within the host. In accordance, series of studies indicate a critical role of intestinal commensal microbiota in the development of autoimmune diseases including inflammatory bowel diseases, type 1 diabetes, rheumatoid arthritis, and multiple sclerosis. In contrast, the role of the gut and indigenous microorganisms in Hashimoto's thyroiditis has received little attention. Whereas activation of innate pattern recognition receptors such as Toll-like receptors and disturbed intestinal epithelial barrier may contribute to thyroiditis development, only a few studies have addressed a link between the gut and Hashimoto's thyroiditis and provided just indirect and weak evidence for such a link. Despite this unsatisfactory situation, we here focus on the possible interaction between the gut and thyroid autoimmunity. Further studies are clearly needed to test the hypothesis that the gut commensal microflora represents an important environmental factor triggering Hashimoto's thyroiditis.

Autoimmune thyroid diseases and Helicobacter pylori: the correlation is present only in Graves's disease.

AIM: To investigate the correlation between autoimmune thyroid diseases (ATDs) and the prevalence of Cag-A positive strains of Helicobacter pylori (H. pylori) in stool samples. METHODS: Authors investigated 112 consecutive Caucasian patients (48 females and 4 males with Graves' disease and 54 females and 6 males with Hashimoto's thyroiditis HT), at their first diagnosis of ATDs. Authors tested for H. pylori in stool samples using an amplified enzyme immunoassay and Cag-A in serum samples using an enzyme-linked immunoassay method (ELISA). The results were analyzed using the two-sided Fisher's exact test and the respective odds ratio (OR) was calculated. RESULTS: A marked correlation was found between the presence of H. pylori (P ≤ 0.0001, OR 6.3) and, in particular, Cag-A positive strains (P ≤ 0.005, OR 5.3) in Graves' disease, but not in Hashimoto's thyroiditis, where authors found only a correlation with Cag-A strains (P ≤ 0.005, OR 8.73) but not when H. pylori was present. CONCLUSION: The marked correlation between H. pylori and Cag-A, found in ATDs, could be dependent on the different expression of adhesion molecules in the gastric mucosa.

The lactic acid bacterium Pediococcus acidilactici suppresses autoimmune encephalomyelitis by inducing IL-10-producing regulatory T cells.

BACKGROUND: Certain intestinal microflora are thought to regulate the systemic immune response. Lactic acid bacteria are one of the most studied bacteria in terms of their beneficial effects on health and autoimmune diseases; one of which is Multiple sclerosis (MS) which affects the central nervous system. We investigated whether the lactic acid bacterium Pediococcus acidilactici, which comprises human commensal bacteria, has beneficial effects on experimental autoimmune encephalomyelitis (EAE), an animal model of MS. METHODOLOGY/PRINCIPAL FINDINGS: P. acidilactici R037 was orally administered to EAE mice to investigate the effects of R037. R037 treatment suppressed clinical EAE severity as prophylaxis and therapy. The antigen-specific production of inflammatory cytokines was inhibited in R037-treated mice. A significant increase in the number of CD4(+) Interleukin (IL)-10-producing cells was observed in the mesenteric lymph nodes (MLNs) and spleens isolated from R037-treated naive mice, while no increase was observed in the number of these cells in the lamina propria. Because only a slight increase in the CD4(+)Foxp3(+) cells was observed in MLNs, R037 may primarily induce Foxp3(-) IL10-producing T regulatory type 1 (Tr1) cells in MLNs, which contribute to the beneficial effect of R037 on EAE. CONCLUSIONS/SIGNIFICANCE: An orally administered single strain of P. acidilactici R037 ameliorates EAE by inducing IL10-producing Tr1 cells. Our findings indicate the therapeutic potential of the oral administration of R037 for treating multiple sclerosis.

Chlamydia psittaci Infection in nongastrointestinal extranodal MALT lymphomas and their precursor lesions.

Extranodal marginal zone lymphomas of mucosa-associated lymphoid tissue (MALT) are associated with various infectious pathogens. We analyzed the presence of Chlamydia psittaci, Chlamydia pneumoniae, and Chlamydia trachomatis DNA in 47 nongastrointestinal and 14 gastrointestinal MALT lymphomas, 37 nonmalignant control samples, and 27 autoimmune precursor lesions by polymerase chain reaction amplification and direct sequencing. In 47 nongastrointestinal MALT lymphomas, 13 (28%) were positive for C psittaci DNA compared with 4 (11%) of 37 nonmalignant control samples (P = .09). C psittaci was detected at variable frequencies in MALT lymphomas of different sites: lung, 100% (5/5; P < .01); thyroid gland, 30% (3/10; P > .05); salivary gland, 13% (2/15; P > .05); ocular adnexa, 15% (2/13); and skin, 25% (1/4). Of 27 autoimmune precursor lesions (11 Hashimoto thyroiditis and 16 Sjögren syndrome), 11 (41%) contained C psittaci DNA. Only 1 (7%) of 14 gastrointestinal MALT lymphomas was positive for C psittaci. All specimens were negative for C trachomatis and C pneumoniae. Besides ocular adnexal lymphomas, C psittaci infection is associated with nongastrointestinal MALT lymphomas and autoimmune precursor lesions, suggesting possible involvement of C psittaci-induced antigenic-driven MALT lymphomagenesis.

Proposing a relationship between Mycobacterium avium subspecies paratuberculosis infection and Hashimoto's thyroiditis.

Humans are widely exposed to Mycobacterium avium subspecies paratuberculosis (MAP), a proven multi-host chronic enteric pathogen that has recently been linked to autoimmune diabetes. In the present study we used a MAP species-specific polymerase chain reaction with the insertion element IS900-specific probe to detect MAP infection in members of the same family suffering from Hashimoto's thyroiditis.