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
Hauptverfasser: Miccheli, A, Capuani, G, Marini, F, Tomassini, A, Praticò, G, Ceccarelli, S, Gnani, D, Baviera, G, Alisi, A, Putignani, L, Nobili, V
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Sprache:eng
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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.
ISSN:0307-0565
1476-5497
DOI:10.1038/ijo.2015.40