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.

Urinary 1H-NMR-based metabolic profiling of children with NAFLD undergoing VSL#3 treatment / Miccheli, Alfredo; Capuani, Giorgio; Marini, Federico; Tomassini, Alberta; Praticò, Giulia; Ceccarelli, Sara; Gnani, Daniela; Baviera, Giuseppe; Alisi, Anna; Putignani, Lorenza; Nobili, Valerio. - In: INTERNATIONAL JOURNAL OF OBESITY. - ISSN 0307-0565. - STAMPA. - 39:7(2015), pp. 1118-1125. [10.1038/ijo.2015.40]

Urinary 1H-NMR-based metabolic profiling of children with NAFLD undergoing VSL#3 treatment

Miccheli, Alfredo;Capuani, Giorgio;Marini, Federico;Tomassini, Alberta;Praticò, Giulia;Alisi, Anna;Putignani, Lorenza;Nobili, Valerio
2015

Abstract

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.
2015
NMR-based metabolomics; NAFLD; microbiota; probiotics
01 Pubblicazione su rivista::01a Articolo in rivista
Urinary 1H-NMR-based metabolic profiling of children with NAFLD undergoing VSL#3 treatment / Miccheli, Alfredo; Capuani, Giorgio; Marini, Federico; Tomassini, Alberta; Praticò, Giulia; Ceccarelli, Sara; Gnani, Daniela; Baviera, Giuseppe; Alisi, Anna; Putignani, Lorenza; Nobili, Valerio. - In: INTERNATIONAL JOURNAL OF OBESITY. - ISSN 0307-0565. - STAMPA. - 39:7(2015), pp. 1118-1125. [10.1038/ijo.2015.40]
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11573/783147
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