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Open AccessArticle

Direct Implementation of Intestinal Permeability Test in NMR Metabolomics for Simultaneous Biomarker Discovery—A Feasibility Study in a Preterm Piglet Model

1
Department of Food Science, Aarhus University, Kirstinebjergvej 10, 5792 Aarslev, Denmark
2
Section for Comparative Pediatrics and Nutrition, Department of Veterinary and Animal Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Dyrlaegevej 68, 1860 Frederiksberg C, Denmark
*
Author to whom correspondence should be addressed.
Metabolites 2020, 10(1), 22; https://doi.org/10.3390/metabo10010022
Received: 24 October 2019 / Revised: 22 December 2019 / Accepted: 29 December 2019 / Published: 1 January 2020
(This article belongs to the Special Issue Metabolomics Methodologies and Applications)
Measurement of intestinal permeability (IP) is often used in the examination of inflammatory gastrointestinal disorders. IP can be assessed by measurement of urinary recovery of ingested non-metabolizable lactulose (L) and mannitol (M). The present study aimed to examine how measurements of IP can be integrated in a NMR-based metabolomics approach for a simultaneous quantification of L/M ratio and biomarker exploration. For this purpose, plasma and urine samples were collected from five-day-old preterm piglets (n = 20) with gastrointestinal disorders (subjected to intra-amniotic lipopolysaccharide (LPS, 1 mg/fetus)) after they had been administrated a 5% lactulose and 5% mannitol solution (15 mL/kg). The collected plasma and urine samples were analyzed by 1H NMR-based metabolomics. Urine L/M ratio measured by 1H NMR spectroscopy showed high correlation with the standard measurement of the urinary recoveries by enzymatic assays (r = 0.93, p < 0.05). Partial least squares (PLS) regressions and correlation analyses between L/M ratio and NMR metabolomics data revealed that L/M ratio was positively correlated with plasma lactate, acetate and succinate levels and negatively correlated with urinary hippuric acid and glycine. In conclusion, the present study demonstrated that NMR metabolomics enables simultaneous IP testing and discovery of biomarkers associated with an impaired intestinal permeability. View Full-Text
Keywords: intestinal barrier dysfunction; leaky gut; preterm infants; lipopolysaccharide (LPS); prenatal inflammation; NMR metabolomics; lactulose intestinal barrier dysfunction; leaky gut; preterm infants; lipopolysaccharide (LPS); prenatal inflammation; NMR metabolomics; lactulose
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Alinaghi, M.; Nguyen, D.N.; Sangild, P.T.; Bertram, H.C. Direct Implementation of Intestinal Permeability Test in NMR Metabolomics for Simultaneous Biomarker Discovery—A Feasibility Study in a Preterm Piglet Model. Metabolites 2020, 10, 22.

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