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Novel role of zonulin in the pathophysiology of gastro-duodenal transit: a clinical and translational study

We examined the relationship between zonulin and gastric motility in critical care patients and a translational mouse model of systemic inflammation. Gastric motility and haptoglobin (HP) 2 isoform quantification, proxy for zonulin, were examined in patients. Inflammation was triggered by lipopolysa...

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Autores principales: Martinez, Enid E., Lan, Jinggang, Konno, Takumi, Miranda-Ribera, Alba, Fiorentino, Maria, Mehta, Nilesh M., Fasano, Alessio
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8599512/
https://www.ncbi.nlm.nih.gov/pubmed/34789790
http://dx.doi.org/10.1038/s41598-021-01879-y
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author Martinez, Enid E.
Lan, Jinggang
Konno, Takumi
Miranda-Ribera, Alba
Fiorentino, Maria
Mehta, Nilesh M.
Fasano, Alessio
author_facet Martinez, Enid E.
Lan, Jinggang
Konno, Takumi
Miranda-Ribera, Alba
Fiorentino, Maria
Mehta, Nilesh M.
Fasano, Alessio
author_sort Martinez, Enid E.
collection PubMed
description We examined the relationship between zonulin and gastric motility in critical care patients and a translational mouse model of systemic inflammation. Gastric motility and haptoglobin (HP) 2 isoform quantification, proxy for zonulin, were examined in patients. Inflammation was triggered by lipopolysaccharide (LPS) injection in C57Bl/6 zonulin transgenic mouse (Ztm) and wildtype (WT) mice as controls, and gastro-duodenal transit was examined by fluorescein-isothiocyanate, 6 and 12 h after LPS-injection. Serum cytokines and zonulin protein levels, and zonulin gastric-duodenal mRNA expression were examined. Eight of 20 patients [14 years, IQR (12.25, 18)] developed gastric dysmotility and were HP2 isoform-producing. HP2 correlated with gastric dysmotility (r = − 0.51, CI − 0.81 to 0.003, p = 0.048). LPS injection induced a time-dependent increase in IL-6 and KC-Gro levels in all mice (p < 0.0001). Gastric dysmotility was reduced similarly in Ztm and WT mice in a time-dependent manner. Ztm had 16% faster duodenal motility than WT mice 6H post-LPS, p = 0.01. Zonulin mRNA expression by delta cycle threshold (dCT) was higher in the stomach (9.7, SD 1.4) than the duodenum (13.9, SD 1.4) 6H post-LPS, p = 0.04. Serum zonulin protein levels were higher in LPS-injected mice compared to vehicle-injected animals in a time-dependent manner. Zonulin correlated with gastric dysmotility in patients. A mouse model had time-dependent gastro-duodenal dysmotility after LPS-injection that paralleled zonulin mRNA expression and protein levels.
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spelling pubmed-85995122021-11-19 Novel role of zonulin in the pathophysiology of gastro-duodenal transit: a clinical and translational study Martinez, Enid E. Lan, Jinggang Konno, Takumi Miranda-Ribera, Alba Fiorentino, Maria Mehta, Nilesh M. Fasano, Alessio Sci Rep Article We examined the relationship between zonulin and gastric motility in critical care patients and a translational mouse model of systemic inflammation. Gastric motility and haptoglobin (HP) 2 isoform quantification, proxy for zonulin, were examined in patients. Inflammation was triggered by lipopolysaccharide (LPS) injection in C57Bl/6 zonulin transgenic mouse (Ztm) and wildtype (WT) mice as controls, and gastro-duodenal transit was examined by fluorescein-isothiocyanate, 6 and 12 h after LPS-injection. Serum cytokines and zonulin protein levels, and zonulin gastric-duodenal mRNA expression were examined. Eight of 20 patients [14 years, IQR (12.25, 18)] developed gastric dysmotility and were HP2 isoform-producing. HP2 correlated with gastric dysmotility (r = − 0.51, CI − 0.81 to 0.003, p = 0.048). LPS injection induced a time-dependent increase in IL-6 and KC-Gro levels in all mice (p < 0.0001). Gastric dysmotility was reduced similarly in Ztm and WT mice in a time-dependent manner. Ztm had 16% faster duodenal motility than WT mice 6H post-LPS, p = 0.01. Zonulin mRNA expression by delta cycle threshold (dCT) was higher in the stomach (9.7, SD 1.4) than the duodenum (13.9, SD 1.4) 6H post-LPS, p = 0.04. Serum zonulin protein levels were higher in LPS-injected mice compared to vehicle-injected animals in a time-dependent manner. Zonulin correlated with gastric dysmotility in patients. A mouse model had time-dependent gastro-duodenal dysmotility after LPS-injection that paralleled zonulin mRNA expression and protein levels. Nature Publishing Group UK 2021-11-17 /pmc/articles/PMC8599512/ /pubmed/34789790 http://dx.doi.org/10.1038/s41598-021-01879-y Text en © The Author(s) 2021 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Article
Martinez, Enid E.
Lan, Jinggang
Konno, Takumi
Miranda-Ribera, Alba
Fiorentino, Maria
Mehta, Nilesh M.
Fasano, Alessio
Novel role of zonulin in the pathophysiology of gastro-duodenal transit: a clinical and translational study
title Novel role of zonulin in the pathophysiology of gastro-duodenal transit: a clinical and translational study
title_full Novel role of zonulin in the pathophysiology of gastro-duodenal transit: a clinical and translational study
title_fullStr Novel role of zonulin in the pathophysiology of gastro-duodenal transit: a clinical and translational study
title_full_unstemmed Novel role of zonulin in the pathophysiology of gastro-duodenal transit: a clinical and translational study
title_short Novel role of zonulin in the pathophysiology of gastro-duodenal transit: a clinical and translational study
title_sort novel role of zonulin in the pathophysiology of gastro-duodenal transit: a clinical and translational study
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8599512/
https://www.ncbi.nlm.nih.gov/pubmed/34789790
http://dx.doi.org/10.1038/s41598-021-01879-y
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