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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Bibliographic Details
Published in:Scientific reports 2021-11, Vol.11 (1), p.22462-22462, Article 22462
Main Authors: Martinez, Enid E., Lan, Jinggang, Konno, Takumi, Miranda-Ribera, Alba, Fiorentino, Maria, Mehta, Nilesh M., Fasano, Alessio
Format: Article
Language:English
Subjects:
631/1647/767/2199
692/308/3187
692/308/575
692/4020/2199
Adolescent
Animals
Child
Cohort Studies
Cytokines - blood
Disease Models, Animal
Duodenum
Female
Fluorescein
Gastric Emptying - genetics
Gastric motility
Gastric Mucosa - metabolism
Gastrointestinal Transit - genetics
Gene expression
Haptoglobin
Haptoglobins - genetics
Haptoglobins - metabolism
Humanities and Social Sciences
Humans
Inflammation
Injection
Interleukin 6
Intestinal Mucosa - metabolism
Isothiocyanate
Lipopolysaccharides
Lipopolysaccharides - administration & dosage
Lipopolysaccharides - adverse effects
Male
Mice
Mice, Inbred C57BL
Mice, Transgenic
Motility
multidisciplinary
Patients
Protein Precursors - blood
Protein Precursors - genetics
Proteins
Rodents
Science
Science (multidisciplinary)
Sepsis - blood
Sepsis - chemically induced
Transgenic mice
Translation
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Summary: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 
ISSN:2045-2322
2045-2322
DOI:10.1038/s41598-021-01879-y