Dataset Information

Non-invasive urinary metabolomic profiles discriminate biliary atresia from infantile hepatitis syndrome

ABSTRACT:

INTRODUCTION: Neonatal cholestatic disorders are a group of hepatobiliary diseases occurring in the first 3 months of life. The most common causes of neonatal cholestasis are infantile hepatitis syndrome (IHS) and biliary atresia (BA). The clinical manifestations of the two diseases are too similar to distinguish them. However, early detection is very important in improving the clinical outcome of BA. Currently, a liver biopsy is the only proven and effective method used to differentially diagnose these two similar diseases in the clinic. However, this method is invasive. Therefore, sensitive and non-invasive biomarkers are needed to effectively differentiate between BA and IHS. We hypothesized that urinary metabolomics can produce unique metabolite profiles for BA and IHS.

OBJECTIVES: The aim of this study was to characterize urinary metabolomic profiles in infants with BA and IHS, and to identify differences among infants with BA, IHS, and normal controls (NC).

METHODS: Urine samples along with patient characteristics were obtained from 25 BA, 38 IHS, and 38 NC infants. A non-targeted gas chromatography-mass spectrometry (GC-MS) metabolomics method was used in conjunction with orthogonal partial least squares discriminant analysis (OPLS-DA) to explore the metabolomic profiles of BA, IHS, and NC infants.

RESULTS: In total, 41 differentially expressed metabolites between BA vs. NC, IHS vs. NC, and BA vs. IHS were identified. N-acetyl-D-mannosamine and alpha-aminoadipic acid were found to be highly accurate at distinguishing between BA and IHS.

CONCLUSIONS: BA and IHS infants have specific urinary metabolomic profiles. The results of our study underscore the clinical potential of metabolomic profiling to uncover metabolic changes that could be used to discriminate BA from IHS.

INSTRUMENT(S): Gas Chromatography MS - Positive (GC-MS (Positive))

SUBMITTER: weiwei li

PROVIDER: MTBLS689 | MetaboLights | 2019-06-25

REPOSITORIES: MetaboLights

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Non-invasive urinary metabolomic profiles discriminate biliary atresia from infantile hepatitis syndrome.

Li Wei-Wei WW Yang Yan Y Dai Qi-Gang QG Lin Li-Li LL Xie Tong T He Li-Li LL Tao Jia-Lei JL Shan Jin-Jun JJ Wang Shou-Chuan SC

Metabolomics : Official journal of the Metabolomic Society 20180621 7

<h4>Introduction</h4>Neonatal cholestatic disorders are a group of hepatobiliary diseases occurring in the first 3 months of life. The most common causes of neonatal cholestasis are infantile hepatitis syndrome (IHS) and biliary atresia (BA). The clinical manifestations of the two diseases are too similar to distinguish them. However, early detection is very important in improving the clinical outcome of BA. Currently, a liver biopsy is the only proven and effective method used to differentially ...[more]

PMID: 30830373

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Project description:The prevalence of immune-mediated diseases such as allergies and autoimmune diseases is on the rise in the developed world. Microbial exposure is known to modulate the risk for these diseases. In order to explore differences in the gene expression patterns induced in utero in infants born in contrasting standards of living and hygiene, we collected umbilical cord blood RNA samples from full-term newborn infants born with normal vaginal delivery in Finland (modern society), Estonia (rapidly developing society) and the Republic of Karelia, Russia (poor economical conditions). Transcriptomic profiles were analyzed using whole genome microarrays including gender, gestational age, birth month and HLA allele genotype as confounding variables in the analysis. The data revealed that the whole blood transcriptome of Finnish and Estonian neonates differ from their Karelian counterparts. Samples from Karelian infants had an increase in transcripts associated with LPS induction and bacterial sepsis observed in 1-year-old infants in earlier studies. The results suggest exposure to toll like receptor (TLR) ligands and a more matured immune response in infants born in Petrozavodsk compared to the Finnish and Estonian infants. These results further support the concept of a conspicuous plasticity in the developing immune system: the environmental factors that play a role in the susceptibility/protection towards immune-mediated diseases begin to shape the neonatal immunity already in utero and direct the maturation of both the adaptive and the innate immune responses in accordance with the surrounding microbial milieu. These 15 rehybridized samples were only utilized in the batch correction and excluded from any further analysis steps. Umbilical cord blood was drawn into Tempus Blood RNA tubes (Applied Biosystems) from children born at the maternity unit of Jorvi hospital (Espoo, Finland; n=4), maternity units of Tartu and PM-CM-5lva (Estonia; n=4), or two maternity departments in Petrozavodsk (capital of the Republic of Karelia, Russian Federation; n=7) according to the manufacturerM-BM-4s protocol and then stored in -70 M-BM-0C until analyzed.

Project description:The prevalence of immune-mediated diseases such as allergies and autoimmune diseases is on the rise in the developed world. Microbial exposure is known to modulate the risk for these diseases. In order to explore differences in the gene expression patterns induced in utero in infants born in contrasting standards of living and hygiene, we collected umbilical cord blood RNA samples from full-term newborn infants born with normal vaginal delivery in Finland (modern society), Estonia (rapidly developing society) and the Republic of Karelia, Russia (poor economical conditions). Transcriptomic profiles were analyzed using whole genome microarrays including gender, gestational age, birth month and HLA allele genotype as confounding variables in the analysis. The data revealed that the whole blood transcriptome of Finnish and Estonian neonates differ from their Karelian counterparts. Samples from Karelian infants had an increase in transcripts associated with LPS induction and bacterial sepsis observed in 1-year-old infants in earlier studies. The results suggest exposure to toll like receptor (TLR) ligands and a more matured immune response in infants born in Petrozavodsk compared to the Finnish and Estonian infants. These results further support the concept of a conspicuous plasticity in the developing immune system: the environmental factors that play a role in the susceptibility/protection towards immune-mediated diseases begin to shape the neonatal immunity already in utero and direct the maturation of both the adaptive and the innate immune responses in accordance with the surrounding microbial milieu. Umbilical cord blood was drawn into Tempus Blood RNA tubes (Applied Biosystems) from children born between January and May 2010 at the maternity unit of Jorvi hospital (Espoo, Finland; n=48), maternity units of Tartu and PM-CM-5lva (Estonia; n=25), or two maternity departments in Petrozavodsk (capital of the Republic of Karelia, Russian Federation; n=40) according to the manufacturerM-BM-4s protocol and then stored in M-bM-^HM-^R70 M-BM-0C until analyzed. All newborn infants were full-term (>36 gestational weeks) and born vaginally. 113 cord blood RNA samples were analyzed with Affymetrix U219 gene array. Gender, pregnancy week, month of birth and HLA risk class were included as confounding factors in the analysis model.

Dataset Information

Non-invasive urinary metabolomic profiles discriminate biliary atresia from infantile hepatitis syndrome

Publications

Non-invasive urinary metabolomic profiles discriminate biliary atresia from infantile hepatitis syndrome.

Similar Datasets

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