title: Urinary (1)H-NMR-based metabolic profiling of children with NAFLD undergoing VSL#3 treatment.
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.
  
  
  OBJECTIVE
  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.
authors: Department of Chemistry, Sapienza University of Rome, Rome, Italy.
authors: A
authors: A
authors: Miccheli
authors: Department of Chemistry, Sapienza University of Rome, Rome, Italy.
authors: G
authors: G
authors: Capuani
authors: Department of Chemistry, Sapienza University of Rome, Rome, Italy.
authors: F
authors: F
authors: Marini
authors: Department of Chemistry, Sapienza University of Rome, Rome, Italy.
authors: A
authors: A
authors: Tomassini
authors: Department of Chemistry, Sapienza University of Rome, Rome, Italy.
authors: G
authors: G
authors: Praticò
authors: Liver Research Unit, 'Bambino Gesù' Children's Hospital, IRCCS, Rome, Italy.
authors: S
authors: S
authors: Ceccarelli
authors: Liver Research Unit, 'Bambino Gesù' Children's Hospital, IRCCS, Rome, Italy.
authors: D
authors: D
authors: Gnani
authors: Family Pediatrician, Rome, Italy.
authors: G
authors: G
authors: Baviera
authors: 1] Liver Research Unit, 'Bambino Gesù' Children's Hospital, IRCCS, Rome, Italy [2] Hepato-Metabolic Disease Unit, 'Bambino Gesù' Children's Hospital, IRCCS, Rome, Italy.
authors: A
authors: A
authors: Alisi
authors: 1] Parasitology Unit, 'Bambino Gesù' Children's Hospital, IRCCS, Rome, Italy [2] Metagenomics Unit, 'Bambino Gesù' Children's Hospital, IRCCS, Rome, Italy.
authors: L
authors: L
authors: Putignani
authors: 1] Liver Research Unit, 'Bambino Gesù' Children's Hospital, IRCCS, Rome, Italy [2] Hepato-Metabolic Disease Unit, 'Bambino Gesù' Children's Hospital, IRCCS, Rome, Italy.
authors: V
authors: V
authors: Nobili
mesh_terms: D000410:Alanine Transaminase / Q000652:urine; D000621:Aminoisobutyric Acids / Q000652:urine; D015415:Biomarkers / Q000652:urine; D015992:Body Mass Index; D002648:Child; D019587:Dietary Supplements; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D006885:Hydroxybutyrates / Q000652:urine; D008099:Liver / Q000378:metabolism*; D009682:Magnetic Resonance Spectroscopy / Q000379:methods*; D008297:Male; D055432:Metabolomics; D065626:Non-alcoholic Fatty Liver Disease / Q000178:diet therapy* / Q000652:urine; D063766:Pediatric Obesity / Q000150:complications / Q000178:diet therapy* / Q000652:urine; D019936:Probiotics / Q000627:therapeutic use*; D040242:Risk Reduction Behavior; D016896:Treatment Outcome
chemical_list: D000621:Aminoisobutyric Acids; D015415:Biomarkers; D006885:Hydroxybutyrates; C008039:2-hydroxyisobutyric acid; D000410:Alanine Transaminase; C033435:3-aminoisobutyric acid