scholarly journals Modulating gut microbiota in a mouse model of Graves’ orbitopathy and its impact on induced disease

Microbiome ◽  
2021 ◽  
Vol 9 (1) ◽  
Author(s):  
Sajad Moshkelgosha ◽  
◽  
Hedda Luise Verhasselt ◽  
Giulia Masetti ◽  
Danila Covelli ◽  
...  
Keyword(s):  
Gut Microbiota ◽  
Thyroid Autoimmunity ◽  
Treg Cells ◽  
Material Transfer ◽  
Disease Heterogeneity ◽  
Brown Adipose ◽  
Probiotic Treatment ◽  
Autoimmune Condition ◽  
Graves Orbitopathy ◽  
The Impact

Abstract Background Graves’ disease (GD) is an autoimmune condition in which autoantibodies to the thyrotropin receptor (TSHR) cause hyperthyroidism. About 50% of GD patients also have Graves’ orbitopathy (GO), an intractable disease in which expansion of the orbital contents causes diplopia, proptosis and even blindness. Murine models of GD/GO, developed in different centres, demonstrated significant variation in gut microbiota composition which correlated with TSHR-induced disease heterogeneity. To investigate whether correlation indicates causation, we modified the gut microbiota to determine whether it has a role in thyroid autoimmunity. Female BALB/c mice were treated with either vancomycin, probiotic bacteria, human fecal material transfer (hFMT) from patients with severe GO or ddH2O from birth to immunization with TSHR-A subunit or beta-galactosidase (βgal; age ~ 6 weeks). Incidence and severity of GD (TSHR autoantibodies, thyroid histology, thyroxine level) and GO (orbital fat and muscle histology), lymphocyte phenotype, cytokine profile and gut microbiota were analysed at sacrifice (~ 22 weeks). Results In ddH2O-TSHR mice, 84% had pathological autoantibodies, 67% elevated thyroxine, 77% hyperplastic thyroids and 70% orbital pathology. Firmicutes were increased, and Bacteroidetes reduced relative to ddH2O-βgal; CCL5 was increased. The random forest algorithm at the genus level predicted vancomycin treatment with 100% accuracy but 74% and 70% for hFMT and probiotic, respectively. Vancomycin significantly reduced gut microbiota richness and diversity compared with all other groups; the incidence and severity of both GD and GO also decreased; reduced orbital pathology correlated positively with Akkermansia spp. whilst IL-4 levels increased. Mice receiving hFMT initially inherited their GO donors’ microbiota, and the severity of induced GD increased, as did the orbital brown adipose tissue volume in TSHR mice. Furthermore, genus Bacteroides, which is reduced in GD patients, was significantly increased by vancomycin but reduced in hFMT-treated mice. Probiotic treatment significantly increased CD25+ Treg cells in orbital draining lymph nodes but exacerbated induced autoimmune hyperthyroidism and GO. Conclusions These results strongly support a role for the gut microbiota in TSHR-induced disease. Whilst changes to the gut microbiota have a profound effect on quantifiable GD endocrine and immune factors, the impact on GO cellular changes is more nuanced. The findings have translational potential for novel, improved treatments.

scholarly journals Immunological Mechanisms of Autoimmune Thyroid Diseases: A Shift in The Traditional TH1/TH2 Paradigm

2019 ◽  
Vol 73 (2) ◽  
pp. 67-77
Author(s):  
Tatjana Zaķe ◽  
Sandra Skuja ◽  
Aivars Lejnieks ◽  
Valērija Groma ◽  
Ilze Konrāde
Keyword(s):  
Thyroid Autoimmunity ◽  
Treg Cells ◽  
Thyroid Diseases ◽  
Autoimmune Response ◽  
Autoimmune Thyroid Diseases ◽  
Autoimmune Thyroid ◽  
Th17 Lymphocytes ◽  
Immunological Mechanisms ◽  
Thyroid Autoantigens ◽  
The Impact

Abstract Autoimmune thyroid diseases (AITD) mainly include Hashimoto’s thyroiditis (HT) and Graves’ disease (GD), which are characterised by the presence of circulating antibodies against various thyroid autoantigens and infiltration of the thyroid gland by autoreactive lymphocytes. Despite the significant advancement in the knowledge of AITD pathogenesis in the last decade, the specific immunological mechanisms responsible for development of the disease are not thoroughly understood. Classically, HT has long been considered as a T helper (Th)1-mediated disease, while a Th2-driven autoimmune response is dominant for GD development. However, this classification has changed due to the description of Th17 lymphocytes, which suggested participation of these cells in AITD, particularly HT pathogenesis. Moreover, a shift in the balance between Th17 and T regulatory (Treg) cells has been observed in thyroid autoimmunity. We have observed overexpression of IL-17, the prominent effector cytokine of Th17, within thyroid tissues from HT and GD patients in our studies. The present review will focus on recent data regarding the role of Treg and Th17 lymphocytes in AITD pathogenesis. In addition, the impact and proposed mechanisms of the predominant environmental factors triggering the autoimmune response to the thyroid will be discussed.

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

2021 ◽  
Vol 11 ◽  
Author(s):  
Jueyu Hou ◽  
Yunjing Tang ◽  
Yongjiang Chen ◽  
Danian Chen
Keyword(s):  
Gut Microbiota ◽  
Negative Impact ◽  
Bifidobacterium Longum ◽  
Autoimmune Disorder ◽  
Thyroid Stimulating Hormone ◽  
Clinical Syndrome ◽  
Graves Disease ◽  
Material Transfer ◽  
T Helper 17 ◽  
Graves Orbitopathy

Graves‘ disease (GD) is a clinical syndrome with an enlarged and overactive thyroid gland, an accelerated heart rate, Graves’ orbitopathy (GO), and pretibial myxedema (PTM). GO is the most common extrathyroidal complication of GD. GD/GO has a significant negative impact on the quality of life. GD is the most common systemic autoimmune disorder, mediated by autoantibodies to the thyroid-stimulating hormone receptor (TSHR). It is generally accepted that GD/GO results from complex interactions between genetic and environmental factors that lead to the loss of immune tolerance to thyroid antigens. However, the exact mechanism is still elusive. Systematic investigations into GD/GO animal models and clinical patients have provided important new insight into these disorders during the past 4 years. These studies suggested that gut microbiota may play an essential role in the pathogenesis of GD/GO. Antibiotic vancomycin can reduce disease severity, but fecal material transfer (FMT) from GD/GO patients exaggerates the disease in GD/GO mouse models. There are significant differences in microbiota composition between GD/GO patients and healthy controls. Lactobacillus, Prevotella, and Veillonella often increase in GD patients. The commonly used therapeutic agents for GD/GO can also affect the gut microbiota. Antigenic mimicry and the imbalance of T helper 17 cells (Th17)/regulatory T cells (Tregs) are the primary mechanisms proposed for dysbiosis in GD/GO. Interventions including antibiotics, probiotics, and diet modification that modulate the gut microbiota have been actively investigated in preclinical models and, to some extent, in clinical settings, such as probiotics (Bifidobacterium longum) and selenium supplements. Future studies will reveal molecular pathways linking gut and thyroid functions and how they impact orbital autoimmunity. Microbiota-targeting therapeutics will likely be an essential strategy in managing GD/GO in the coming years.

scholarly journals THU0340 DURATION AND SYSTEMIC SCLEROSIS SUBTYPE ARE ASSOCIATED WITH DIFFERENT GUT MICROBIOME PROFILES

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 401.2-401
Author(s):  
Y. Braun-Moscovici ◽  
S. Ben Simon ◽  
K. Dolnikov ◽  
S. Giryes ◽  
D. Markovits ◽  
...  
Keyword(s):  
Species Richness ◽  
Systemic Sclerosis ◽  
Gut Microbiota ◽  
Disease Duration ◽  
Alpha Diversity ◽  
Rrna Gene ◽  
Digital Ulcers ◽  
Diffuse Disease ◽  
Probiotic Treatment ◽  
The Impact

Background:A growing body of evidence suggests that the gut microbiota plays a significant role in the development of autoimmune diseases. Altered microbiota composition was associated with gastrointestinal and extraintestinal features in systemic sclerosis (SSc) patients.Objectives:To look for differences in gut microbiota between SSc patients regarding disease duration, disease subset and occurrence of digital ulcers (DU).Methods:SSc patients seen at our center were recruited in a prospective study. The exclusion criteria included antibiotic or probiotic treatment during the month prior to recruitment, recent hospitalization, BMI>30, diabetes mellitus or concomitant inflammatory bowel disease. Fecal samples were processed and 16S rRNA gene sequences were analyzed using the QIIME2 packageWeighted (quantitative) and unweighted (qualitative) UniFrac distances, alpha diversity for richness and homogeneity, taxa plots for species and phyla and ANCOM analyses were performed.Results:During July 2018-May 2019, 26 SSc patients (mean age [SD] 53[12.7] years) and disease duration 8.8 [7.1] years) fulfilled the criteria and were willing to participate in the study. Thirteen patients had diffuse SSc, 16 patients had active DU, 8 patients had Raynaud’s phenomenon only without DU, 2 patients had past DU. The microbiota was significantly more similar between patients without active DU compared to those with active DU (P=0.024), but species richness did not differ. Patients with SSc duration less than 6 years had significantly different microbiota compared to long-lasting SSc (unweighted PCoA – q=0.031). Significant variations concerning quantitative and qualitative UniFrac distances (q=0.063, q=0.005) and species richness (q=0.009) were found among patients with diffuse compared to limited SSc. Limited SSc was associated with greater species richness. Taxa plot analysis revealed higher relative abundance of Firmicutes in diffuse disease and of Actinobacteria and Bacteroidetes in limited SSc.Conclusion:Disease duration, disease subset and active DU were associated with shifts in the microbiome of SSc patients. The impact of these changes on disease progression needs further elucidation.Figure:Disclosure of Interests:Yolanda Braun-Moscovici: None declared, Shira Ben Simon: None declared, Katya Dolnikov: None declared, Sami Giryes: None declared, Doron Markovits: None declared, Yonit Tavor: None declared, Kohava Toledano: None declared, Alexandra Balbir-Gurman Consultant of: Novartis, Omry Koren: None declared

scholarly journals Salmon Gut Microbiota Correlates With Disease Infection Status: Potential for Monitoring Health in Farmed Animals  

2020 ◽  
Author(s):  
Davide Bozzi ◽  
Jacob A. Rasmussen ◽  
Christian Carøe ◽  
Harald Sveier ◽  
Kristian Nordøy ◽  
...  
Keyword(s):  
Health Status ◽  
Infectious Diseases ◽  
Gut Microbiota ◽  
Relative Abundance ◽  
Rrna Gene ◽  
Host Immune System ◽  
Positive Correlation ◽  
Growth Performances ◽  
Probiotic Treatment ◽  
The Impact

Abstract Background: Infectious diseases cause significant production losses in aquaculture every year. Given the pivotal role played by the gut microbiota in regulating the host immune system, health and physiology, interest has risen in the possibility of controlling the fish health status by modulating the gut microbiota. An altered gut microbiota is often associated with a disease status. However, few studies have examined the association between disease severity and degree of gut dysbiosis, especially when the gut is not the site of the primary infection. Moreover, there is a lack of knowledge on the impact of formalin, a commonly used disinfectant in aquaculture, on the gut microbiome. Here we investigate, through 16S rRNA gene metabarcoding, changes in the distal gut microbiota composition of a captive-reared cohort of Atlantic salmon (Salmo salar L.), in consequence of an external bacterial skin infection and the subsequent formalin treatment.Results: We show that the distal gut of diseased salmon presented a different composition from that of healthy individuals, with an increased relative abundance of strains regarded as opportunistic in sick fish. Conversely, healthy salmon were dominated by a new, yet undescribed, Mycoplasma genus. We also observed a positive correlation between fish weight and Mycoplasma sp. relative abundance, potentially indicating a beneficial effect for its host. Moreover, we observed that the treatment with formalin, while suited to resolve the external infection, was unable to recover the gut microbiota characteristic of healthy fish prior to treatment, potentially compromising the subsequent health status and growth performances of all treated fish.Conclusions: We conclude that infectious diseases have the potential of affecting the host gut microbiota at different body sites and that treatment optimization procedures should account for that. The formalin treatment is not an optimal solution from a holistic perspective, we suggest its coupling with a probiotic treatment aimed at re-establishing the original community. Lastly, we have observed a positive correlation of Mycoplasma sp. with salmon health and growth performances and, while inviting further research on this microorganism, we also encourage further investigations towards its potential utilization as a biomarker for monitoring health in salmon and potentially other farmed fish species.

scholarly journals Functional Dynamics of the Gut Microbiome in Elderly People during Probiotic Consumption

mBio ◽  
2015 ◽  
Vol 6 (2) ◽  
Author(s):  
Emiley A. Eloe-Fadrosh ◽  
Arthur Brady ◽  
Jonathan Crabtree ◽  
Elliott F. Drabek ◽  
Bing Ma ◽  
...  
Keyword(s):  
Gut Microbiota ◽  
Lactobacillus Rhamnosus ◽  
Probiotic Bacteria ◽  
Healthy Human ◽  
Content Type ◽  
Treatment Comparison ◽  
Functional Dynamics ◽  
Single Organism ◽  
Probiotic Treatment ◽  
The Impact

ABSTRACT A mechanistic understanding of the purported health benefits conferred by consumption of probiotic bacteria has been limited by our knowledge of the resident gut microbiota and its interaction with the host. Here, we detail the impact of a single-organism probiotic, Lactobacillus rhamnosus GG ATCC 53103 (LGG), on the structure and functional dynamics (gene expression) of the gut microbiota in a study of 12 healthy individuals, 65 to 80 years old. The analysis revealed that while the overall community composition was stable as assessed by 16S rRNA profiling, the transcriptional response of the gut microbiota was modulated by probiotic treatment. Comparison of transcriptional profiles based on taxonomic composition yielded three distinct transcriptome groups that displayed considerable differences in functional dynamics. The transcriptional profile of LGG in vivo was remarkably concordant across study subjects despite the considerable interindividual nature of the gut microbiota. However, we identified genes involved in flagellar motility, chemotaxis, and adhesion from Bifidobacterium and the dominant butyrate producers Roseburia and Eubacterium whose expression was increased during probiotic consumption, suggesting that LGG may promote interactions between key constituents of the microbiota and the host epithelium. These results provide evidence for the discrete functional effects imparted by a specific single-organism probiotic and challenge the prevailing notion that probiotics substantially modify the resident microbiota within nondiseased individuals in an appreciable fashion. IMPORTANCE Probiotic bacteria have been used for over a century to promote digestive health. Many individuals report that probiotics alleviate a number of digestive issues, yet little evidence links how probiotic microbes influence human health. Here, we show how the resident microbes that inhabit the healthy human gut respond to a probiotic. The well-studied probiotic Lactobacillus rhamnosus GG ATCC 53103 (LGG) was administered in a clinical trial, and a suite of measurements of the resident microbes were taken to evaluate potential changes over the course of probiotic consumption. We found that LGG transiently enriches for functions to potentially promote anti-inflammatory pathways in the resident microbes.

scholarly journals BOARD INVITED REVIEW: The pig microbiota and the potential for harnessing the power of the microbiome to improve growth and health1

2019 ◽  
Vol 97 (9) ◽  
pp. 3741-3757 ◽  
Author(s):  
Nirosh D Aluthge ◽  
Dana M Van Sambeek ◽  
Erin E Carney-Hinkle ◽  
Yanshuo S Li ◽  
Samodha C Fernando ◽  
...  
Keyword(s):  
Gastrointestinal Tract ◽  
Gut Microbiota ◽  
Therapeutic Potential ◽  
Animal Health ◽  
Microbial Colonization ◽  
Critical Importance ◽  
Specific Host ◽  
Microbiome Research ◽  
Health And Disease ◽  
The Impact

Abstract A variety of microorganisms inhabit the gastrointestinal tract of animals including bacteria, archaea, fungi, protozoa, and viruses. Pioneers in gut microbiology have stressed the critical importance of diet:microbe interactions and how these interactions may contribute to health status. As scientists have overcome the limitations of culture-based microbiology, the importance of these interactions has become more clear even to the extent that the gut microbiota has emerged as an important immunologic and metabolic organ. Recent advances in metagenomics and metabolomics have helped scientists to demonstrate that interactions among the diet, the gut microbiota, and the host to have profound effects on animal health and disease. However, although scientists have now accumulated a great deal of data with respect to what organisms comprise the gastrointestinal landscape, there is a need to look more closely at causative effects of the microbiome. The objective of this review is intended to provide: 1) a review of what is currently known with respect to the dynamics of microbial colonization of the porcine gastrointestinal tract; 2) a review of the impact of nutrient:microbe effects on growth and health; 3) examples of the therapeutic potential of prebiotics, probiotics, and synbiotics; and 4) a discussion about what the future holds with respect to microbiome research opportunities and challenges. Taken together, by considering what is currently known in the four aforementioned areas, our overarching goal is to set the stage for narrowing the path towards discovering how the porcine gut microbiota (individually and collectively) may affect specific host phenotypes.

scholarly journals Modulation of Gut Microbiota and Oxidative Status by β-Carotene in Late Pregnant Sows

2020 ◽  
Vol 7 ◽  
Author(s):  
Xupeng Yuan ◽  
Jiahao Yan ◽  
Ruizhi Hu ◽  
Yanli Li ◽  
Ying Wang ◽  
...  
Keyword(s):  
Gut Microbiota ◽  
Dietary Supplementation ◽  
Basal Diet ◽  
Fecal Microbiota ◽  
Control Group ◽  
Metabolic Activities ◽  
The Impact ◽  
Positive Effect ◽  
Β Carotene

Recent evidences suggest that gut microbiota plays an important role in regulating physiological and metabolic activities of pregnant sows, and β-carotene has a potentially positive effect on reproduction, but the impact of β-carotene on gut microbiota in pregnant sows remains unknown. This study aimed to explore the effect and mechanisms of β-carotene on the reproductive performance of sows from the aspect of gut microbiota. A total of 48 hybrid pregnant sows (Landrace × Yorkshire) with similar parity were randomly allocated into three groups (n = 16) and fed with a basal diet or a diet containing 30 or 90 mg/kg of β-carotene from day 90 of gestation until parturition. Dietary supplementation of 30 or 90 mg/kg β-carotene increased the number of live birth to 11.82 ± 1.54 and 12.29 ± 2.09, respectively, while the control group was 11.00 ± 1.41 (P = 0.201). Moreover, β-carotene increased significantly the serum nitric oxide (NO) level and glutathione peroxidase (GSH-Px) activity (P < 0.05). Characterization of fecal microbiota revealed that 90 mg/kg β-carotene increased the diversity of the gut flora (P < 0.05). In particular, β-carotene decreased the relative abundance of Firmicutes including Lachnospiraceae AC2044 group, Lachnospiraceae NK4B4 group and Ruminococcaceae UCG-008, but enriched Proteobacteria including Bilophila and Sutterella, and Actinobacteria including Corynebacterium and Corynebacterium 1 which are related to NO synthesis. These data demonstrated that dietary supplementation of β-carotene may increase antioxidant enzyme activity and NO, an important vasodilator to promote the neonatal blood circulation, through regulating gut microbiota in sows.

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