Zonulin as a biomarker and potential therapeutic target in multisystem inflammatory syndrome in children

Hensley-McBain, Tiffany; Manuzak, Jennifer A.

doi:10.1172/jci151467

Cited by 10 publications

(5 citation statements)

References 23 publications

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“…Zonulin, already known to be an important modulator of TJs and intestinal barrier functions, is secreted by intestinal epithelial cells when stimulated by dietary or local infectious factors. Infectious aggression can lead to the destruction of the intestinal barrier by apoptosis of intestinal epithelial cells, which will generate a strong proinflammatory environment with the differentiation of autoreactive Th17 and other T-helper cells [ 136 , 158 , 159 ].…”

Section: Discussionmentioning

confidence: 99%

Celiac Disease and Targeting the Molecular Mechanisms of Autoimmunity in COVID Pandemic

Ailioaie

Litscher

et al. 2022

IJMS

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Celiac disease (CD) comprises over 1% of the world’s population and is a chronic multisystem immune-mediated condition manifested by digestive and/or extradigestive symptoms caused by food intake of gluten. This review looked at the risk of children diagnosed with CD developing SARS-CoV-2 infection and possible severe forms of COVID-19. A better understanding of the interaction and effects of SARS-CoV-2 infection in CD is very important, as is the role of environmental and genetic factors, but especially the molecular mechanisms involved in modulating intestinal permeability with impact on autoimmunity. CD inspired the testing of a zonulin antagonist for the fulminant form of multisystem inflammatory syndrome in children (MIS-C) and paved the way for the discovery of new molecules to regulate the small intestine barrier function and immune responses. Original published works on COVID-19 and CD, new data and points of view have been analyzed because this dangerous virus SARS-CoV-2 is still here and yet influencing our lives. Medical science continues to focus on all uncertainties triggered by SARS-CoV-2 infection and its consequences, including in CD. Although the COVID-19 pandemic seems to be gradually extinguishing, there is a wealth of information and knowledge gained over the last two years and important life lessons to analyze, as well as relevant conclusions to be drawn to deal with future pandemics. Zonulin is being studied extensively in immunoengineering as an adjuvant to improving the absorption of new drugs and oral vaccines.

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Section: Discussionmentioning

confidence: 99%

Celiac Disease and Targeting the Molecular Mechanisms of Autoimmunity in COVID Pandemic

Ailioaie

Litscher

et al. 2022

IJMS

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“…Zonulin is also a potential inflammatory marker and contributes to intestinal innate immunity. Increased IP coinciding with inflammation has been described in mental disorders in children [ 15 ]. Zonulin has been associated with low-grade inflammation and autoimmune diseases, as well as ASD, which might have an autoimmune component [ 16 ].…”

Section: Introductionmentioning

confidence: 99%

Leaky gut biomarkers in casein- and gluten-rich diet fed rat model of autism

Dera

Alrafaei

tamimi

et al. 2021

Translational Neuroscience

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It is proposed that gluten- and casein-rich diets (GRD and CRD) can synergistically exacerbate dysbiosis as comorbidity in autism by worsening leaky gut that affects the brain through the gut–brain axis. In this study, 35 young male rats were divided into 7 groups, Group 1 serves as control; Group 2, clindamycin (CL)-treated; and Group 3, propionic acid (PPA)-induced rodent model of autism. These three groups were fed standard diet until the end of the experiment. Groups 4–7 are rats treated similarly with CL and PPA, then fed on CRD or GRD until the end of the experiment. Serum zonulin, glutathione (GSH), lipid peroxides, and gut microbial composition were measured in the seven studied groups. Data demonstrate the significant increase in serum zonulin as marker of leaky gut in the CL-treated groups fed on CRD or GRD. Lipid peroxides were significantly higher in the serum of GRD-fed rats compared to CRD-fed or normal diet-fed rats. GSH was much lower in CL-treated groups fed on CRD or GRD compared to PPA-treated rats fed on both diets. Both diets differentially affected the diversity of the gut microbiota. This study demonstrates that CRD and GRD exacerbates leaky gut, according to serum zonulin, which was used as marker for increased gut permeability.

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“…In children with multisystemic inflammatory syndrome (MIS-C), elevated plasma zonulin levels were associated with gastrointestinal permeability after SARS-CoV-2 infection and therefore, suggested to serve as a biomarker [51]. In line, the zonulin antagonist Larazotide (AT1001) might offer potential benefit in treatment of MIS-C patients, by preventing a break-down of tight junctions and subsequent protection of gastrointestinal barrier integrity [52]. Altogether, these findings highlight the importance of well stratified ME/CFS patients in research and medical care.…”

Section: Discussionmentioning

confidence: 99%

Immunological Patient Stratification in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome

Rohrhofer,

Hauser,

Lettenmaier

et al. 2023

Preprint

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Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) is a complex disease characterized by profound fatigue, post-exertional malaise (PEM), and neurocognitive dysfunction. Immune dysregulation and gastrointestinal symptoms are commonly observed in ME/CFS patients. Despite affecting approximately 0.89% of the general population, the underlying pathophysiological mechanisms remain poorly understood. This study aimed to elucidate the relationship between immunological characteristics and intestinal barrier function in ME/CFS patients. ME/CFS patients were stratified into two groups based on their immune competence. After documentation of detailed medical records, serum and plasma samples were collected for assessment of inflammatory immune mediators and biomarkers for intestinal barrier integrity by ELISA. We found reduced complement protein C4a levels in immunodeficient ME/CFS patients suggesting a sub-group specific innate immune dysregulation. ME/CFS patients without immunodeficiencies exhibit a mucosal barrier leakage, as indicated by elevated levels of Lipopolysaccharide-binding protein (LBP). Stratifying ME/CFS patients based on immune competence enabled the distinction of two subgroups with different pathophysiological patterns. The study highlights the importance of emphasizing precise patient stratification in ME/CFS, particularly in the context of defining suitable treatment strategies. Given the substantial health and socioeconomic burden associated with ME/CFS, urgent attention and research efforts are needed to define causative treatment approaches.

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Zonulin as a biomarker and potential therapeutic target in multisystem inflammatory syndrome in children

Cited by 10 publications

References 23 publications

Celiac Disease and Targeting the Molecular Mechanisms of Autoimmunity in COVID Pandemic

Celiac Disease and Targeting the Molecular Mechanisms of Autoimmunity in COVID Pandemic

Leaky gut biomarkers in casein- and gluten-rich diet fed rat model of autism

Immunological Patient Stratification in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome

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