Screening and combining serum biomarkers to improve their diagnostic performance in the detection of intestinal barrier dysfunction in patients after major abdominal surgery

Kong, Can; Li, Shumin; Yang, Hua; Xiao, Weidong; Cen, Yunyun; Wu, Yi; Li, Weiming; Sun, Dingyong; Xu, Pan

doi:10.21037/atm.2019.07.102

Cited by 14 publications

(12 citation statements)

References 39 publications

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“…Several circulating biomarkers have been tested and validated for the assessment of intestinal barrier integrity and bacterial translocation. Intestinal fatty acid-binding protein (I-FABP) and diamine oxidase (DAO) are cytosolic proteins in intestinal epithelial cells and are immediately released into the circulation when the intestinal epithelium is disrupted ( 14 , 15 ). Zonulin, the only known physiological regulator of intestinal permeability, reversibly opens tight junctions between intestinal epithelial cells ( 16 ).…”

Section: Introductionmentioning

confidence: 99%

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

et al. 2021

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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.

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Section: Introductionmentioning

confidence: 99%

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

et al. 2021

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“…Generally, D-lactic acid is seldom present in the intestinal lumen, and its concentration could signal initial damage to the intestinal barrier. In our study, we found that GA could significantly reduce the levels of D-lactose, a reliable biomarker of intestinal permeability (26). Similarly, since only a small proportion of lactulose could permeate through the intestinal mucosa, while mannitol could always pass through, intestinal permeability can be measured by detecting the LMR in the urine (27).…”

Section: Discussionmentioning

confidence: 57%

D-galacturonic acid ameliorates the intestinal mucosal permeability and inflammation of functional dyspepsia in rats

Wu¹,

Zhong²,

Ye³

et al. 2021

Ann Palliat Med

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Background: Functional dyspepsia (FD) is a gastrointestinal disease caused by imbalanced gastrointestinal function. Traditional treatments are deemed to be limited, and new therapeutic drugs are required. New study suggested that duodenal low-grade inflammation and increased intestinal permeability play an important role in the pathogenesis of FD. Previous studies have shown that polysaccharides containing D-galacturonic acid (GA) could modulate intestinal immune activity in vitro and in animal models. However, the ability of GA monomer to improve intestinal mucosal permeability and inflammation in FD has not been clearly elucidated.Methods: A FD rat model was established using iodoacetamide (IA). FD Rats were administrated different doses of GA. Subsequently, the body weight and behavioral sensitivity of the rats were measured and evaluated; the permeability of the intestinal barrier was measured by determining D-lactose, lactulose/ mannitol ratio (LMR), and permeability-related genes [desmocollin-2 (DSC2), TJP1, and OCLN] in FD rats. Also, inflammatory cells [cluster of differentiation (CD)3+ cells and mast cells] were assessed by immunohistochemistry, and the levels of immune-related factors, such as the Toll-like receptor-nuclear factor kappa B (TLR/NF-κB) pathway, were monitored by reverse transcription quantitative polymerase chain reaction (RT-qPCR) or western blot assays.Results: Our results suggested that GA could markedly increase the body weight and attenuate the behavioral sensitivity of FD rats. Moreover, GA also has an obvious ameliorating effect on the intestinal mucosal permeability and inflammatory response of FD rats. Furthermore, we found that GA could markedly downregulate TLR2, TLR4, and NF-κB in FD rats.Conclusions: These findings indicate that GA could significantly attenuate the intestinal mucosal permeability and inflammation FD rats. The effect of GA was partially mediated by the TLR/NF-κB signaling pathway.

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“…Serum biomarkers that reflect damage of the intestinal mucosal barrier have been identified in several clinical and animal studies [4]. Peters et al 1989 [8] and Khurana et al 2002 [9] examined the activity of GST enzymes in the small and large intestines and proved that intestinal epithelial cells have a high content and activity of cytosolic GST and when the cell membrane of intestinal epithelial cells is damaged, these enzymes are released and their serum levels correlate with the degree of intestinal epithelial damage.…”

Section: Discussionmentioning

confidence: 99%

“…Intestinal epithelial barrier dysfunction increases intestinal mucosal permeability. As a result, intestinal bacteria, endotoxins, and other harmful substances pass through the intestinal tissue and initiate a series of pathophysiological changes and even a systemic inflammatory response and multiorgan dysfunction syndrome [4]. Although there has been progress in tests that assess the function of the intestinal epithelial barrier, the evaluation of the integrity and function of the intestinal epithelium for clinicians remains challenging [3].…”

Section: Introductionmentioning

confidence: 99%

Alpha Glutathione S-transferase – A Potential Biomarker for Intestinal Epithelial Damage in Infants with Acute Gastroenteritis

Dimitrovska-Ivanova

Zisovska

2020

Open Access Maced J Med Sci

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BACKGROUND: Acute gastroenteritis is a leading cause of morbidity and mortality in children under 3 years of age worldwide and mostly can be dangerous in the first 12 months of life especially in infants who are not exclusively breastfed. Intestinal pathogens cause enterocyte infection which leads to cell death, lumen extrusion, and intestinal villous atrophy. AIM: The aim of this study was to assess whether alpha glutathione S-transferase (α-GST) can be a biomarker for early intestinal epithelial damage in infants with acute gastroenteritis and the degree of correlation of its serum values with the degree of intestinal epithelial damage associated with infant nutrition. MATERIALS AND METHODS: A total of 23 infants with acute gastroenteritis divided into two groups based on the feeding patterns (type of milk) were included in the study. The values of α-GST in serum between exclusively breastfed and non-exclusively breastfed infants were examined. RESULTS: It was found a statistically significant association between group affiliation and the α-GST levels in serum between the first and the second group (p = 0.002260). It was revealed that Rotavirus can cause erosion of the intestinal epithelium through the positive values of α-GST in Rotavirus positive cases. CONCLUSION: In this study, it was found that α-GST is a biomarker for early intestinal epithelial damage in infants primarily with Rotavirus acute gastroenteritis. α-GST serum values were significantly lower in infants who were exclusively breastfed compared with infants who were not exclusively breastfed.

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Screening and combining serum biomarkers to improve their diagnostic performance in the detection of intestinal barrier dysfunction in patients after major abdominal surgery

Cited by 14 publications

References 39 publications

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

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

D-galacturonic acid ameliorates the intestinal mucosal permeability and inflammation of functional dyspepsia in rats

Alpha Glutathione S-transferase – A Potential Biomarker for Intestinal Epithelial Damage in Infants with Acute Gastroenteritis

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