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

Abstract 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 l...

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Autores principales:	Enid E. Martinez, Jinggang Lan, Takumi Konno, Alba Miranda-Ribera, Maria Fiorentino, Nilesh M. Mehta, Alessio Fasano
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/84dd7522ce2c43afb6bab28781611450
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spelling	oai:doaj.org-article:84dd7522ce2c43afb6bab287816114502021-11-21T12:24:23ZNovel role of zonulin in the pathophysiology of gastro-duodenal transit: a clinical and translational study10.1038/s41598-021-01879-y2045-2322https://doaj.org/article/84dd7522ce2c43afb6bab287816114502021-11-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-01879-yhttps://doaj.org/toc/2045-2322Abstract 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.Enid E. MartinezJinggang LanTakumi KonnoAlba Miranda-RiberaMaria FiorentinoNilesh M. MehtaAlessio FasanoNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-11 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Enid E. Martinez Jinggang Lan Takumi Konno Alba Miranda-Ribera Maria Fiorentino Nilesh M. Mehta Alessio Fasano Novel role of zonulin in the pathophysiology of gastro-duodenal transit: a clinical and translational study
description	Abstract 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.
format	article
author	Enid E. Martinez Jinggang Lan Takumi Konno Alba Miranda-Ribera Maria Fiorentino Nilesh M. Mehta Alessio Fasano
author_facet	Enid E. Martinez Jinggang Lan Takumi Konno Alba Miranda-Ribera Maria Fiorentino Nilesh M. Mehta Alessio Fasano
author_sort	Enid E. Martinez
title	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_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_sort	novel role of zonulin in the pathophysiology of gastro-duodenal transit: a clinical and translational study
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/84dd7522ce2c43afb6bab28781611450
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Novel role of zonulin in the pathophysiology of gastro-duodenal transit: a clinical and translational study

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