Urinary 1H-NMR-based metabolic profiling of children with NAFLD undergoing VSL#3 treatment
Background: Nowadays, non-alcoholic fatty liver disease (NAFLD) is one of the most common chronic liver diseases in children. Our recent clinical trial demonstrated that dietary and VSL#3-based interventions may improve fatty liver by ultrasound and body mass index (BMI) after 4 months. Objectives:...
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Veröffentlicht in: | International Journal of Obesity 2015-07, Vol.39 (7), p.1118-1125 |
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Format: | Artikel |
Sprache: | eng |
Schlagworte: | |
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Zusammenfassung: | Background:
Nowadays, non-alcoholic fatty liver disease (NAFLD) is one of the most common chronic liver diseases in children. Our recent clinical trial demonstrated that dietary and VSL#3-based interventions may improve fatty liver by ultrasound and body mass index (BMI) after 4 months.
Objectives:
As in this short-term trial, as in others, it is impracticable to monitor response to therapy or treatment by liver biopsy, we aimed to identify a panel of potential non-invasive metabolic biomarkers by a urinary metabolic profiling.
Methods:
Urine samples from a group of 31 pediatric NAFLD patients, enrolled in a VSL#3 clinical trial, were analyzed by high-resolution proton nuclear magnetic resonance spectroscopy in combination with analysis of variance-Simultaneous Component Analysis model and multivariate data analyses. Urinary metabolic profiles were interpreted in terms of clinical patient feature, treatment and chronology pattern correlations.
Results:
VSL#3 treatment induced changes in NAFLD urinary metabolic phenotype mainly at level of host amino-acid metabolism (that is, valine, tyrosine, 3-amino-isobutyrate or β-aminoisobutyric acid (BAIBA)), nucleic acid degradation (pseudouridine), creatinine metabolism (methylguanidine) and secondarily at the level of gut microbial amino-acid metabolism (that is, 2-hydroxyisobutyrate from valine degradation). Furthermore, some of these metabolites correlated with clinical primary and secondary trial end points after VSL#3 treatment: tyrosine and the organic acid U4 positively with alanine aminotransferase (
R
=0.399,
P
=0.026) and BMI (R=0.36,
P
=0.045); BAIBA and tyrosine negatively with active glucagon-like-peptide 1 (
R
=−0.51,
P
=0.003; R=-0.41,
P
=0.021, respectively).
Conclusions:
VSL#3 treatment-dependent urinary metabotypes of NAFLD children may be considered as non-invasive effective biomarkers to evaluate the response to treatment. |
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ISSN: | 0307-0565 1476-5497 |
DOI: | 10.1038/ijo.2015.40 |