title: Urinary N-methylnicotinamide and β-aminoisobutyric acid predict catch-up growth in undernourished Brazilian children.
abstract: Enteric infections, enteropathy and undernutrition in early childhood are preventable risk factors for child deaths, impaired neurodevelopment, and later life metabolic diseases. However, the mechanisms linking these exposures and outcomes remain to be elucidated, as do biomarkers for identifying children at risk. By examining the urinary metabolic phenotypes of nourished and undernourished children participating in a case-control study in Semi-Arid Brazil, we identified key differences with potential relevance to mechanisms, biomarkers and outcomes. Undernutrition was found to perturb several biochemical pathways, including choline and tryptophan metabolism, while also increasing the proteolytic activity of the gut microbiome. Furthermore, a metabolic adaptation was observed in the undernourished children to reduce energy expenditure, reflected by increased N-methylnicotinamide and reduced β-aminoisobutyric acid excretion. Interestingly, accelerated catch-up growth was observed in those undernourished children displaying a more robust metabolic adaptation several months earlier. Hence, urinary N-methylnicotinamide and β-aminoisobutyric acid represent promising biomarkers for predicting short-term growth outcomes in undernourished children and for identifying children destined for further growth shortfalls. These findings have important implications for understanding contributors to long-term sequelae of early undernutrition, including cognitive, growth, and metabolic functions.
authors.affiliation: Division of Computational and Systems Medicine, Department of Surgery and Cancer, Imperial College London, UK.
authors.forename: Jordi
authors.initials: J
authors.lastname: Mayneris-Perxachs
authors.affiliation: Department of Physiology and Pharmacology &INCT-Biomedicine, Faculty of Medicine, Federal Unversity of Ceará, Fortaleza, Ceará, Brazil.
authors.forename: Aldo A M
authors.initials: AA
authors.lastname: Lima
authors.affiliation: Department of Physiology and Pharmacology &INCT-Biomedicine, Faculty of Medicine, Federal Unversity of Ceará, Fortaleza, Ceará, Brazil.|UVA Center for Global Health, Division of Infectious Diseases and International Health, University of Virginia, School of Medicine, Charlottesville VA, US.
authors.forename: Richard L
authors.initials: RL
authors.lastname: Guerrant
authors.affiliation: Department of Physiology and Pharmacology &INCT-Biomedicine, Faculty of Medicine, Federal Unversity of Ceará, Fortaleza, Ceará, Brazil.|Institute for the Promotion of Nutrition and Human Development &Department of Child and Maternal Health, Faculty of Medicine, Federal University of Ceará, Fortaleza, Ceará, Brazil.
authors.forename: Álvaro M
authors.initials: ÁM
authors.lastname: Leite
authors.affiliation: Department of Physiology and Pharmacology &INCT-Biomedicine, Faculty of Medicine, Federal Unversity of Ceará, Fortaleza, Ceará, Brazil.|Institute for the Promotion of Nutrition and Human Development &Department of Child and Maternal Health, Faculty of Medicine, Federal University of Ceará, Fortaleza, Ceará, Brazil.
authors.forename: Alessandra F
authors.initials: AF
authors.lastname: Moura
authors.affiliation: Department of Physiology and Pharmacology &INCT-Biomedicine, Faculty of Medicine, Federal Unversity of Ceará, Fortaleza, Ceará, Brazil.|Institute for the Promotion of Nutrition and Human Development &Department of Child and Maternal Health, Faculty of Medicine, Federal University of Ceará, Fortaleza, Ceará, Brazil.
authors.forename: Noélia L
authors.initials: NL
authors.lastname: Lima
authors.affiliation: Department of Physiology and Pharmacology &INCT-Biomedicine, Faculty of Medicine, Federal Unversity of Ceará, Fortaleza, Ceará, Brazil.
authors.forename: Alberto M
authors.initials: AM
authors.lastname: Soares
authors.affiliation: Department of Physiology and Pharmacology &INCT-Biomedicine, Faculty of Medicine, Federal Unversity of Ceará, Fortaleza, Ceará, Brazil.
authors.forename: Alexandre
authors.initials: A
authors.lastname: Havt
authors.affiliation: Division of Gastroenterology, Hepatology, &Nutrition, Center for Global Health, Department of Pediatrics, Cincinnati Children's Hospital Medical, University of Cincinnati, USA.
authors.forename: Sean R
authors.initials: SR
authors.lastname: Moore
authors.affiliation: UVA Center for Global Health, Division of Infectious Diseases and International Health, University of Virginia, School of Medicine, Charlottesville VA, US.
authors.forename: Relana
authors.initials: R
authors.lastname: Pinkerton
authors.affiliation: Division of Computational and Systems Medicine, Department of Surgery and Cancer, Imperial College London, UK.
authors.forename: Jonathan R
authors.initials: JR
authors.lastname: Swann
mesh_terms: D000621:Aminoisobutyric Acids / Q000652:urine*; D001938:Brazil; D002657:Child Development; D002675:Child, Preschool; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007223:Infant; D007228:Infant Nutrition Disorders / Q000503:physiopathology / Q000652:urine; D008297:Male; D044342:Malnutrition / Q000503:physiopathology / Q000652:urine; D009536:Niacinamide / Q000031:analogs & derivatives* / Q000652:urine; D012189:Retrospective Studies
chemical_list: D000621:Aminoisobutyric Acids; D009536:Niacinamide; C033435:3-aminoisobutyric acid; C008472:N-methylnicotinamide
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