scholarly journals Elevated Levels of Circulating Biomarkers Related to Leaky Gut Syndrome and Bacterial Translocation Are Associated With Graves’ Disease

2021 ◽  
Vol 12 ◽  
Author(s):  
Dekai Zheng ◽  
Huimin Liao ◽  
Shuze Chen ◽  
Xiuying Liu ◽  
Chuyin Mao ◽  
...  

BackgroundA growing number of studies have found dysbiosis of the intestinal microbiota in patients with Graves’ disease (GD). The intestinal epithelial barrier serves as the first line of defense, protecting the immune system from excessive stimulation of microbiota and toxins. Most autoimmune diseases are associated with a gut barrier dysfunction (leaky gut) which allows bacterial translocation. However, to date, potential correlations between intestinal barrier dysfunction and GD have not been explored.MethodsSerum lipopolysaccharide (LPS), intestinal fatty acid-binding protein (I-FABP), zonulin, D-lactate, and diamine oxidase (DAO) were measured to assess barrier integrity in 91 patients with GD (61 initial GD and 30 euthyroid GD) and 44 healthy controls. The quality of life (QOL) of patients with GD was assessed using the thyroid-specific patient-reported outcome (ThyPRO-39) questionnaire.ResultsThe serum levels of LPS, I-FABP, zonulin, and D-lactate were significantly higher in patients with initial GD than in healthy controls. Logistic regression analysis revealed that zonulin and D-lactate were independently associated with risk for GD and circulating zonulin could effectively distinguish patients with initial GD from healthy controls. Correlation analyses showed that I-FABP, LPS, and D-lactate were positively associated with FT4 and negatively associated with TSH. In addition, circulating LPS, zonulin, and D-lactate levels were all independent predictors of TRAb levels. Moreover, higher circulating LPS levels in patients with GD were associated with more severe hyperthyroidism (higher concentrations of FT3, FT4, and TRAb and lower TSH concentrations) and worse scores of hyperthyroid and eye symptoms.ConclusionPatients with initial GD show a disrupted intestinal barrier, characterized by elevated levels of leaky gut biomarkers. Increased intestinal permeability and bacterial translocation were associated with TRAb levels and hyperthyroidism in GD. Further research is required to elucidate the underlying mechanisms.

2006 ◽  
Vol 51 (9) ◽  
pp. 1549-1556 ◽  
Author(s):  
Desheng Song ◽  
Bin Shi ◽  
Hua Xue ◽  
Yousheng Li ◽  
Xiaodong Yang ◽  
...  

2020 ◽  
pp. 219256822094774
Author(s):  
Jamal Bech Bouknaitir ◽  
Leah Y. Carreon ◽  
Stig Brorson ◽  
Mikkel Østerheden Andersen

Study Design: Validation study. Objectives: To translate and validate the Zurich Claudication Questionnaire (ZCQ) into a Danish version of the disease-specific patient-reported outcome measure (PROM) for patients with lumbar spinal stenosis (LSS), which assesses symptom severity, physical function, and satisfaction after surgery. Method: Translation into a Danish version of the original questionnaire by back- and forward-translating the questionnaire and finally transforming a prefinal test version into a final and cross-cultural adapted version. Validation was performed as a cohort study assessing floor-ceiling effects, internal consistency, test-retest reproducibility, criterion validity, discriminant validity, and responsiveness to change. Results: Fifty-three patients were consecutively included in the study, 53 healthy controls were matched. Floor effect was seen in the postoperative data. Internal consistency, Cronbach’s alpha was good to excellent. Substantial test-retest reproducibility was found using Cohen’s weighted kappa. The Danish ZCQ showed moderate to strong association with similar domains of Oswestry Disability Index, Short Form 36, Euro QoL 5D, visual analogue scale–leg and back. The questionnaire showed significant responsiveness to change and a significant discriminant validity between LSS patients and healthy controls. Conclusion: This study shows the Danish translation of the original ZCQ to be well understood by Danish patients. The Danish version is furthermore a reliable and valid questionnaire, which is responsive to change.


2009 ◽  
Vol 161 (5) ◽  
pp. 787-793 ◽  
Author(s):  
Jacek Daroszewski ◽  
Edyta Pawlak ◽  
Lidia Karabon ◽  
Irena Frydecka ◽  
Anna Jonkisz ◽  
...  

ObjectiveGraves' disease (GD) is an autoimmune disorder with genetic and environmental background. CTLA-4 is a candidate gene for thyroid autoimmunity. Increased serum levels of soluble CTLA-4 (sCTLA-4) were found in some autoimmune diseases.AimThe aim of the study was to evaluate the relation between sCTLA-4 level and clinical manifestation of Graves' ophthalmopathy (GO), thyroid status, and CTLA-4 gene polymorphisms.DesignSerum sCTLA-4 concentrations were determined in 93 GO patients and 93 healthy controls. In the GO group, CTLA-4 gene was genotyped in five polymorphic sites: g.319C>T, c.49A>G, CT60 by means of PRC-RFLP, Jo31, and g.*642AT(8_33) by means of minisequencing assay.ResultsSerum sCTLA-4 level was significantly higher in the GO group than in controls (median: 7.94 vs 0.00 ng/ml, P=0.000001). This level was higher in severe than in nonsevere GO (median: 10.3 vs 5.6 ng/ml, P=0.01). sCTLA-4 concentration was related neither to the activity of GO nor to thyroid function. Elevated sCTLA-4 levels were observed in carriers Jo31[G] allele (genotype GG+GT) as compared with subjects with an absence of the [G] allele (TT genotype; median: 9.18 vs 4.0 ng/ml, P=0.02). Also patients possessing CT60[G] allele (genotype GG+GA) had higher serum sCTLA-4 levels than subjects who lack the [G] allele (AA genotype; median: 8.73 vs 2.28 ng/ml, P=0.03).ConclusionsIt was shown for the first time that increased serum concentration of sCTLA-4 correlate with the severity of GO. Genetic variation in the CTLA-4 gene region in GD patients at least partially determines the level of sCTLA-4.


2021 ◽  
Author(s):  
Bercis Imge Ucar ◽  
Gulberk Ucar

Sepsis, as a complex entity, comprises multiple pathophysiological mechanisms which bring about high morbidity and mortality. The previous studies showed that the gastrointestinal tract is damaged during sepsis, and its main symptoms include increased permeability, bacterial translocation (BT), and malabsorption. BT is the invasion of indigenous intestinal bacteria via the gut mucosa to other tissues. It occurs in pathological conditions such as disruption of the intestine’s ecological balance and mucosal barrier permeability, immunosuppression, and oxidative stress through transcellular/paracellular pathways and initiate an excessive systemic inflammatory response. Thereby, recent clinical and preclinical studies focus on the association between sepsis and intestinal barrier dysfunction. This chapter overviews the current knowledge about the molecular basis of BT of the intestine, its role in the progress of sepsis, detection of BT, and actual therapeutic approaches.


2021 ◽  
Author(s):  
Jianli Lin ◽  
Desheng Chen ◽  
Kexin Chang ◽  
Dan Li ◽  
Lvxin Guan ◽  
...  

Abstract HDM (House dust mites) are important environmental trigger factors of airway allergic diseases, the allergens of HDM were detected in the human gut mucosa, which induces local inflammation and increases intestinal permeability. This study tests a hypothesis that house dust mites contribute to the development of OVA (ovalbumin)-induced food allergy. The serum levels of IgE against HDM in patients with food allergy were detected with UniCAP100 (Pharmacia, Uppsala, Sweden); the HDM-induced/the OVA-induced mouse model of food allergy was developed. Difference between 2 groups was determined by Student t test or ANOVA if more than two groups. Compared to the healthy controls, the patients with food allergy have higher levels of serum IgE against HDM. Compared to food allergy alone groups, the levels of IgE against HDM in food allergy with asthma or allergic rhinitis groups were increased significantly. In mouse models, we found that HDM/OVA induced allergy-like symptoms, lower body temperature, and lower body weight. The levels of IgE, IgG1, mMCP-1 (mouse mast cell protease-1), IL-4 and IL-5 in the HDM and HDM + CT (cholera toxin) groups were higher than the control groups, and the levels of IgE, IgG1, IL-4 and IL-5 in the HDM, OVA and HDM + OVA groups were higher than the control groups. The pathology of intestinal tract in the HDM and HDM + CT/the HDM, OVA and HDM + OVA groups were more severe and exhibited more eosinophils than the control groups. Moreover, the prior exposure to HDM induced intestinal barrier dysfunction, and facilitated the development of intestinal allergy in mice. Based on above data and previous researches, we put forward that HDM exposure enhances subsequent responses to OVA-induced food allergy.


Nutrients ◽  
2020 ◽  
Vol 12 (12) ◽  
pp. 3767
Author(s):  
Su Yadana ◽  
Sameera A. Talegawkar ◽  
Jyoti S. Mathad ◽  
Mallika Alexander ◽  
Kripa Rajagopalan ◽  
...  

In pregnant women, studies are lacking on the relationship of vegetable and animal flesh (poultry, red meat and seafood) intake with inflammation, especially in low- and middle-income countries. We conducted a cohort study of pregnant women receiving antenatal care at BJ Medical College in Pune, India. The dietary intake of pregnant women was queried in the third trimester using a validated food frequency questionnaire. Twelve inflammatory markers were measured in plasma samples using immunoassays. Only 12% of the study population were vegetarians, although animal flesh intake levels were lower compared to Western populations. In multivariable models, higher intakes of total vegetables were associated with lower levels of the T-helper (Th) 17 cytokine interleukin (IL)-17a (p = 0.03) and the monocyte/macrophage activation marker soluble CD163 (sCD163) (p = 0.02). Additionally, higher intakes of poultry were negatively associated with intestinal fatty-acid binding protein (I-FABP) levels (p = 0.01), a marker of intestinal barrier dysfunction and Th2 cytokine IL-13 (p = 0.03), and higher seafood was associated with lower IL-13 (p = 0.005). Our data from pregnant women in India suggest that a higher quality diet emphasizing vegetables and with some animal flesh is associated with lower inflammation. Future studies should confirm these findings and test if modulating vegetables and animal flesh intake could impact specific aspects of immunity and perinatal health.


2020 ◽  
Vol 17 (1) ◽  
Author(s):  
Beatriz Gutierrez ◽  
Isabel Gallardo ◽  
Lorena Ruiz ◽  
Yolanda Alvarez ◽  
Victoria Cachofeiro ◽  
...  

Abstract Background Multiple sclerosis (MS) is a chronic demyelinating autoimmune disease affecting the CNS. Recent studies have indicated that intestinal alterations play key pathogenic roles in the development of autoimmune diseases, including MS. The triterpene oleanolic acid (OA), due to its anti-inflammatory properties, has shown to beneficially influence the severity of the experimental autoimmune encephalomyelitis (EAE), a preclinical model of MS. We herein investigate EAE-associated gut intestinal dysfunction and the effect of OA treatment. Methods Mice with MOG35–55-induced EAE were treated with OA or vehicle from immunization day and were daily analyzed for clinical deficit. We performed molecular and histological analysis in serum and intestinal tissues to measure oxidative and inflammatory responses. We used Caco-2 and HT29-MTX-E12 cells to elucidate OA in vitro effects. Results We found that OA protected from EAE-induced changes in intestinal permeability and preserved the mucin-containing goblet cells along the intestinal tract. Serum levels of the markers for intestinal barrier damage iFABP and monocyte activation sCD14 were consistently and significantly reduced in OA-treated EAE mice. Beneficial OA effects also included a decrease of pro-inflammatory mediators both in serum and colonic tissue of treated-EAE mice. Moreover, the levels of some immunoregulatory cytokines, the neurotrophic factor GDNF, and the gastrointestinal hormone motilin were preserved in OA-treated EAE mice. Regarding oxidative stress, OA treatment prevented lipid peroxidation and superoxide anion accumulation in intestinal tissue, while inducing the expression of the ROS scavenger Sestrin-3. Furthermore, short-chain fatty acids (SCFA) quantification in the cecal content showed that OA reduced the high iso-valeric acid concentrations detected in EAE-mice. Lastly, using in vitro cell models which mimic the intestinal epithelium, we verified that OA protected against intestinal barrier dysfunction induced by injurious agents produced in both EAE and MS. Conclusion These findings reveal that OA ameliorates the gut dysfunction found in EAE mice. OA normalizes the levels of gut mucosal dysfunction markers, as well as the pro- and anti-inflammatory immune bias during EAE, thus reinforcing the idea that OA is a beneficial compound for treating EAE and suggesting that OA may be an interesting candidate to be explored for the treatment of human MS.


Shock ◽  
2018 ◽  
Vol 50 (6) ◽  
pp. 640-647 ◽  
Author(s):  
Mitsunori Ikeda ◽  
Kentaro Shimizu ◽  
Hiroshi Ogura ◽  
Takashi Kurakawa ◽  
Eiji Umemoto ◽  
...  

Antioxidants ◽  
2021 ◽  
Vol 10 (3) ◽  
pp. 384
Author(s):  
Jacob W. Ballway ◽  
Byoung-Joon Song

Emerging data demonstrate the important roles of altered gut microbiomes (dysbiosis) in many disease states in the peripheral tissues and the central nervous system. Gut dysbiosis with decreased ratios of Bacteroidetes/Firmicutes and other changes are reported to be caused by many disease states and various environmental factors, such as ethanol (e.g., alcohol drinking), Western-style high-fat diets, high fructose, etc. It is also caused by genetic factors, including genetic polymorphisms and epigenetic changes in different individuals. Gut dysbiosis, impaired intestinal barrier function, and elevated serum endotoxin levels can be observed in human patients and/or experimental rodent models exposed to these factors or with certain disease states. However, gut dysbiosis and leaky gut can be normalized through lifestyle alterations such as increased consumption of healthy diets with various fruits and vegetables containing many different kinds of antioxidant phytochemicals. In this review, we describe the mechanisms of gut dysbiosis, leaky gut, endotoxemia, and fatty liver disease with a specific focus on the alcohol-associated pathways. We also mention translational approaches by discussing the benefits of many antioxidant phytochemicals and/or their metabolites against alcohol-mediated oxidative stress, gut dysbiosis, intestinal barrier dysfunction, and fatty liver disease.


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