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Pediatrics

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

International Journal of Obesity volume 39, pages 1118–1125 (2015)Cite this article

Subjects

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.

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Acknowledgements

We are indebted to Professor Claudio De Simone who provided VSL#3 with verified composition and indistinguishable placebo and intellectual contribution to the study. This study was funded by the Italian Ministry of Health (Fondi di Ricerca Corrente and 5X1000) to Professor Valerio Nobili.

Author information

Authors and Affiliations

  1. Department of Chemistry, Sapienza University of Rome, Rome, Italy

    A Miccheli, G Capuani, F Marini, A Tomassini & G Praticò

  2. Liver Research Unit, 'Bambino Gesù' Children's Hospital, IRCCS, Rome, Italy

    S Ceccarelli, D Gnani, A Alisi & V Nobili

  3. Family Pediatrician, Rome, Italy

    G Baviera

  4. Hepato-Metabolic Disease Unit, 'Bambino Gesù' Children's Hospital, IRCCS, Rome, Italy

    A Alisi & V Nobili

  5. Parasitology Unit, 'Bambino Gesù' Children's Hospital, IRCCS, Rome, Italy

    L Putignani

  6. Metagenomics Unit, ‘Bambino Gesù’ Children’s Hospital, IRCCS, Rome, Italy

    L Putignani

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  1. A Miccheli
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Correspondence to V Nobili.

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Miccheli, A., Capuani, G., Marini, F. et al. Urinary 1H-NMR-based metabolic profiling of children with NAFLD undergoing VSL#3 treatment. Int J Obes 39, 1118–1125 (2015). https://doi.org/10.1038/ijo.2015.40

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