TY - JOUR

T1 - Direct implementation of intestinal permeability test in nmr metabolomics for simultaneous biomarker discovery

T2 - a feasibility study in a preterm piglet model

AU - Alinaghi, Masoumeh

AU - Nguyen, Duc Ninh

AU - Bertram, Hanne Christine

AU - Sangild, Per Torp

PY - 2020

Y1 - 2020

N2 - 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 by1H NMR-based metabolomics. Urine L/M ratio measured by1H 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.

AB - 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 by1H NMR-based metabolomics. Urine L/M ratio measured by1H 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.

KW - Intestinal barrier dysfunction

KW - Lactulose

KW - Leaky gut

KW - Lipopolysaccharide (LPS)

KW - NMR metabolomics

KW - Prenatal inflammation

KW - Preterm infants

U2 - 10.3390/metabo10010022

DO - 10.3390/metabo10010022

M3 - Journal article

C2 - 31906404

AN - SCOPUS:85077847029

VL - 10

JO - Metabolites

JF - Metabolites

SN - 2218-1989

IS - 1

M1 - 22

ER -