title: Dynamics and Trends in Fecal Biomarkers of Gut Function in Children from 1-24 Months in the MAL-ED Study.
abstract: Growth and development shortfalls that are disproportionately prevalent in children living in poor environmental conditions are postulated to result, at least in part, from abnormal gut function. Using data from The Etiology, Risk Factors, and Interactions of Enteric Infections and Malnutrition and the Consequences for Child Health and Development (MAL-ED) longitudinal cohort study, we examine biomarkers of gut inflammation and permeability in relation to environmental exposures and feeding practices. Trends in the concentrations of three biomarkers, myeloperoxidase (MPO), neopterin (NEO), and α-1-antitrypsin (AAT), are described from fecal samples collected during the first 2 years of each child's life. A total of 22,846 stool samples were processed during the longitudinal sampling of 2,076 children 0-24 months of age. Linear mixed models were constructed to examine the relationship between biomarker concentrations and recent food intake, symptoms of illness, concurrent enteropathogen infection, and socioeconomic status. Average concentrations of MPO, NEO, and AAT were considerably higher than published references for healthy adults. The concentration of each biomarker tended to decrease over the first 2 years of life and was highly variable between samples from each individual child. Both MPO and AAT were significantly elevated by recent breast milk intake. All three biomarkers were associated with pathogen presence, although the strength and direction varied by pathogen. The interpretation of biomarker concentrations is subject to the context of their collection. Herein, we identify that common factors (age, breast milk, and enteric infection) influence the concentration of these biomarkers. Within the context of low- and middle-income communities, we observe concentrations that indicate gut abnormalities, but more appropriate reference standards are needed.
authors.affiliation: Fogarty International Center/National Institutes of Health, Bethesda, Maryland.
authors.forename: Benjamin J J
authors.initials: BJJ
authors.lastname: McCormick
authors.affiliation: Tulane University, New Orleans, Louisiana.|Fogarty International Center/National Institutes of Health, Bethesda, Maryland.
authors.forename: Gwenyth O
authors.initials: GO
authors.lastname: Lee
authors.affiliation: Fogarty International Center/National Institutes of Health, Bethesda, Maryland.
authors.forename: Jessica C
authors.initials: JC
authors.lastname: Seidman
authors.affiliation: International Centre for Diarrhoeal Disease Research, Bangladesh (icddr,b), Dhaka, Bangladesh.
authors.forename: Rashidul
authors.initials: R
authors.lastname: Haque
authors.affiliation: International Centre for Diarrhoeal Disease Research, Bangladesh (icddr,b), Dhaka, Bangladesh.
authors.forename: Dinesh
authors.initials: D
authors.lastname: Mondal
authors.affiliation: Universidade Federal do Ceara, Fortaleza, Brazil.
authors.forename: Josiane
authors.initials: J
authors.lastname: Quetz
authors.affiliation: Universidade Federal do Ceara, Fortaleza, Brazil.
authors.forename: Aldo A M
authors.initials: AAM
authors.lastname: Lima
authors.affiliation: Christian Medical College, Vellore, India.
authors.forename: Sudhir
authors.initials: S
authors.lastname: Babji
authors.affiliation: Christian Medical College, Vellore, India.
authors.forename: Gagandeep
authors.initials: G
authors.lastname: Kang
authors.affiliation: Walter Reed/Armed Forces Research Institute of Medical Science (AFRIMS) Research Unit, Kathmandu, Nepal.
authors.forename: Sanjaya K
authors.initials: SK
authors.lastname: Shrestha
authors.affiliation: Walter Reed/Armed Forces Research Institute of Medical Science (AFRIMS) Research Unit, Kathmandu, Nepal.
authors.forename: Carl J
authors.initials: CJ
authors.lastname: Mason
authors.affiliation: Aga Khan University, Karachi, Pakistan.
authors.forename: Shahida
authors.initials: S
authors.lastname: Qureshi
authors.affiliation: Aga Khan University, Karachi, Pakistan.
authors.forename: Zulfiqar A
authors.initials: ZA
authors.lastname: Bhutta
authors.affiliation: Asociacion Benéfica Proyectos en Informatica, Salud, Medicina, y Agricultura (A. B. PRISMA), Iquitos, Peru.
authors.forename: Maribel Paredes
authors.initials: MP
authors.lastname: Olortegui
authors.affiliation: Asociacion Benéfica Proyectos en Informatica, Salud, Medicina, y Agricultura (A. B. PRISMA), Iquitos, Peru.
authors.forename: Pablo Peñataro
authors.initials: PP
authors.lastname: Yori
authors.affiliation: University of Venda, Thohoyandou, South Africa.
authors.forename: Amidou
authors.initials: A
authors.lastname: Samie
authors.affiliation: University of Venda, Thohoyandou, South Africa.
authors.forename: Pascal
authors.initials: P
authors.lastname: Bessong
authors.affiliation: Haydom Lutheran Hospital, Haydom, Tanzania.
authors.forename: Caroline
authors.initials: C
authors.lastname: Amour
authors.affiliation: Haydom Lutheran Hospital, Haydom, Tanzania.
authors.forename: Estomih
authors.initials: E
authors.lastname: Mduma
authors.affiliation: University of Illinois at Chicago, Chicago, Illinois.
authors.forename: Crystal L
authors.initials: CL
authors.lastname: Patil
authors.affiliation: University of Virginia, Charlottesville, Virginia.
authors.forename: Richard L
authors.initials: RL
authors.lastname: Guerrant
authors.affiliation: Foundation for the National Institutes of Health, Bethesda, Maryland.|Fogarty International Center/National Institutes of Health, Bethesda, Maryland.
authors.forename: Dennis R
authors.initials: DR
authors.lastname: Lang
authors.affiliation: Foundation for the National Institutes of Health, Bethesda, Maryland.
authors.forename: Michael
authors.initials: M
authors.lastname: Gottlieb
authors.affiliation: Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland.
authors.forename: Laura E
authors.initials: LE
authors.lastname: Caulfield
authors.affiliation: Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland.
authors.forename: Margaret N
authors.initials: MN
authors.lastname: Kosek
mesh_terms: D001459:Bangladesh; D015415:Biomarkers; D001938:Brazil; D002463:Cell Membrane Permeability / Q000502:physiology*; D002675:Child, Preschool; D015331:Cohort Studies; D005243:Feces / Q000382:microbiology*; D005260:Female; D005500:Follow-Up Studies; D000069196:Gastrointestinal Microbiome / Q000502:physiology*; D006801:Humans; D007194:India; D007223:Infant; D007249:Inflammation / Q000503:physiopathology*; D016014:Linear Models; D008137:Longitudinal Studies; D008297:Male; D019798:Neopterin / Q000032:analysis*; D009390:Nepal; D010154:Pakistan; D009195:Peroxidase / Q000032:analysis*; D010568:Peru; D012959:Socioeconomic Factors; D013019:South Africa; D013636:Tanzania; D000515:alpha 1-Antitrypsin / Q000032:analysis*
chemical_list: D015415:Biomarkers; D000515:alpha 1-Antitrypsin; D019798:Neopterin; D009195:Peroxidase