{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T07:08:04Z","timestamp":1791529684763,"version":"4.3.4"},"reference-count":39,"publisher":"American Society of Tropical Medicine and Hygiene","issue":"2","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2017,2,8]]},"abstract":"<jats:p>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 \u03b1-1-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\u201324 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.<\/jats:p>","DOI":"10.4269\/ajtmh.16-0496","type":"journal-article","created":{"date-parts":[[2016,12,19]],"date-time":"2016-12-19T21:45:46Z","timestamp":1482183946000},"page":"465-472","source":"Crossref","is-referenced-by-count":85,"title":["Dynamics and Trends in Fecal Biomarkers of Gut Function in Children from 1\u201324 Months in the MAL-ED Study"],"prefix":"10.4269","volume":"96","author":[{"given":"Benjamin J. J.","family":"McCormick","sequence":"first","affiliation":[{"name":"Fogarty International Center\/National Institutes of Health, Bethesda, Maryland."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gwenyth O.","family":"Lee","sequence":"additional","affiliation":[{"name":"Fogarty International Center\/National Institutes of Health, Bethesda, Maryland."},{"name":"Tulane University, New Orleans, Louisiana."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jessica C.","family":"Seidman","sequence":"additional","affiliation":[{"name":"Fogarty International Center\/National Institutes of Health, Bethesda, Maryland."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rashidul","family":"Haque","sequence":"additional","affiliation":[{"name":"International Centre for Diarrhoeal Disease Research, Bangladesh (icddr,b), Dhaka, Bangladesh."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dinesh","family":"Mondal","sequence":"additional","affiliation":[{"name":"International Centre for Diarrhoeal Disease Research, Bangladesh (icddr,b), Dhaka, Bangladesh."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Josiane","family":"Quetz","sequence":"additional","affiliation":[{"name":"Universidade Federal do Ceara, Fortaleza, Brazil."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aldo A. M.","family":"Lima","sequence":"additional","affiliation":[{"name":"Universidade Federal do Ceara, Fortaleza, Brazil."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sudhir","family":"Babji","sequence":"additional","affiliation":[{"name":"Christian Medical College, Vellore, India."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gagandeep","family":"Kang","sequence":"additional","affiliation":[{"name":"Christian Medical College, Vellore, India."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sanjaya K.","family":"Shrestha","sequence":"additional","affiliation":[{"name":"Walter Reed\/Armed Forces Research Institute of Medical Science (AFRIMS) Research Unit, Kathmandu, Nepal."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carl J.","family":"Mason","sequence":"additional","affiliation":[{"name":"Walter Reed\/Armed Forces Research Institute of Medical Science (AFRIMS) Research Unit, Kathmandu, Nepal."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shahida","family":"Qureshi","sequence":"additional","affiliation":[{"name":"Aga Khan University, Karachi, Pakistan."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zulfiqar A.","family":"Bhutta","sequence":"additional","affiliation":[{"name":"Aga Khan University, Karachi, Pakistan."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maribel Paredes","family":"Olortegui","sequence":"additional","affiliation":[{"name":"Asociacion Ben\u00e9fica Proyectos en Informatica, Salud, Medicina, y Agricultura (A. B. PRISMA), Iquitos, Peru."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pablo Pe\u00f1ataro","family":"Yori","sequence":"additional","affiliation":[{"name":"Asociacion Ben\u00e9fica Proyectos en Informatica, Salud, Medicina, y Agricultura (A. B. PRISMA), Iquitos, Peru."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amidou","family":"Samie","sequence":"additional","affiliation":[{"name":"University of Venda, Thohoyandou, South Africa."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pascal","family":"Bessong","sequence":"additional","affiliation":[{"name":"University of Venda, Thohoyandou, South Africa."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Caroline","family":"Amour","sequence":"additional","affiliation":[{"name":"Haydom Lutheran Hospital, Haydom, Tanzania."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Estomih","family":"Mduma","sequence":"additional","affiliation":[{"name":"Haydom Lutheran Hospital, Haydom, Tanzania."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Crystal L.","family":"Patil","sequence":"additional","affiliation":[{"name":"University of Illinois at Chicago, Chicago, Illinois."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard L.","family":"Guerrant","sequence":"additional","affiliation":[{"name":"University of Virginia, Charlottesville, Virginia."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dennis R.","family":"Lang","sequence":"additional","affiliation":[{"name":"Fogarty International Center\/National Institutes of Health, Bethesda, Maryland."},{"name":"Foundation for the National Institutes of Health, Bethesda, Maryland."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Gottlieb","sequence":"additional","affiliation":[{"name":"Foundation for the National Institutes of Health, Bethesda, Maryland."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura E.","family":"Caulfield","sequence":"additional","affiliation":[{"name":"Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Margaret N.","family":"Kosek","sequence":"additional","affiliation":[{"name":"Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"2795","reference":[{"key":"ref1","series-title":"Trends Mol Med","first-page":"328","article-title":"Environmental enteropathy: critical implications of a poorly understood condition","volume":"18","author":"Korpe","year":"2012"},{"key":"ref2","series-title":"Am J Trop Med Hyg","first-page":"756","article-title":"Enteropathies in the developing world: neglected effects on global health","volume":"86","author":"Prendergast","year":"2012"},{"issue":"(Suppl 4)","key":"ref3","series-title":"Clin Infect Dis","first-page":"S207","article-title":"Environmental enteric dysfunction: pathogenesis, diagnosis, and clinical consequences","volume":"59","author":"Keusch","year":"2014"},{"issue":"(Suppl 4)","key":"ref4","series-title":"Clin Infect Dis","first-page":"S239","article-title":"Assessment of environmental enteropathy in the MAL-ED cohort study: theoretical and analytic framework","volume":"59","author":"Kosek","year":"2014"},{"key":"ref5","series-title":"Dis Colon Rectum","first-page":"1283","article-title":"Review of fecal biomarkers in inflammatory bowel disease","volume":"51","author":"Sutherland","year":"2008"},{"key":"ref6","series-title":"Lancet","article-title":"Causal pathways of environmental enteropathy: the MAL-ED multicenter birth cohort study","author":"MAL-ED Network Investigators"},{"key":"ref7","series-title":"Am J Trop Med Hyg","first-page":"269","article-title":"Fecal markers of environmental enteropathy are associated with animal exposure and caregiver hygiene in Bangladesh","volume":"93","author":"George","year":"2015"},{"key":"ref8","series-title":"Am J Trop Med Hyg","first-page":"412","article-title":"Responses of small intestinal architecture and function over time to environmental factors in a tropical population","volume":"70","author":"Kelly","year":"2004"},{"key":"ref9","series-title":"Am J Trop Med Hyg","first-page":"390","article-title":"Fecal markers of intestinal inflammation and permeability associated with the subsequent acquisition of linear growth deficits in infants","volume":"88","author":"Kosek","year":"2013"},{"key":"ref10","series-title":"EBioMedicine","first-page":"1759","article-title":"Environmental enteropathy, oral vaccine failure and growth faltering in infants in Bangladesh","volume":"2","author":"Naylor","year":"2015"},{"key":"ref11","series-title":"J Nutr","first-page":"1","article-title":"The immunological components of human milk and their effect on immune development in infants","volume":"135","author":"Field","year":"2005"},{"issue":"(Suppl 2)","key":"ref12","series-title":"J Pediatr","first-page":"S26","article-title":"Bioactive proteins in human milk: mechanisms of action","volume":"156","author":"L\u00f6nnerdal","year":"2010"},{"issue":"(Suppl 4)","key":"ref13","series-title":"Clin Infect Dis","first-page":"S193","article-title":"The MAL-ED study: a multinational and multidisciplinary approach to understand the relationship between enteric pathogens, malnutrition, gut physiology, physical growth, cognitive development, and immune responses in infants and children up to 2 years of age in resource-poor environments","volume":"59","author":"MAL-ED Network Investigators","year":"2014"},{"issue":"(Suppl 4)","key":"ref14","series-title":"Clin Infect Dis","first-page":"S248","article-title":"Infant feeding practices, dietary adequacy, and micronutrient status measures in the MAL-ED study","volume":"59","author":"Caulfield","year":"2014"},{"issue":"(Suppl 4)","key":"ref15","series-title":"Clin Infect Dis","first-page":"S220","article-title":"Disease surveillance methods used in the 8-site MAL-ED cohort study","volume":"59","author":"Richard","year":"2014"},{"issue":"(Suppl 4)","key":"ref16","series-title":"Clin Infect Dis","first-page":"S225","article-title":"Microbiologic methods utilized in the MAL-ED cohort study","volume":"59","author":"Houpt","year":"2014"},{"issue":"(Suppl 4)","key":"ref17","series-title":"Clin Infect Dis","first-page":"S255","article-title":"Modeling environmental influences on child growth in the MAL-ED cohort study: opportunities and challenges","volume":"59","author":"Richard","year":"2014"},{"key":"ref18","series-title":"Popul Health Metr","first-page":"8","article-title":"Measuring socioeconomic status in multicountry studies: results from the eight-country MAL-ED study","volume":"12","author":"Psaki","year":"2014"},{"key":"ref19","series-title":"Methods Ecol Evol","first-page":"133","article-title":"A general and simple method for obtaining R2 from generalized linear mixed-effects models","volume":"4","author":"Nakagawa","year":"2013"},{"key":"ref20","series-title":"Kurume Med J","first-page":"69","article-title":"Myeloperoxidase concentrations in the stool as a new parameter of inflammatory bowel disease","volume":"45","author":"Saiki","year":"1998"},{"key":"ref21","series-title":"Pteridines","first-page":"155","article-title":"Neopterin concentrations in colon dialysate","volume":"12","author":"Ledjeff","year":"2013"},{"key":"ref22","series-title":"Mikro\u00f6kologie des Darms: Grundlagen\u2013Diagnostik\u2013Therapie","author":"Beckmann","year":"2000"},{"key":"ref23","series-title":"Core Questions on Drinking Water and Sanitation for Household Surveys","author":"United Nations International Children's Emergency Fund, World Health Organization","year":"2006"},{"key":"ref24","series-title":"Arch Dis Child Fetal Neonatal Ed","first-page":"F52","article-title":"Intestinal permeability in relation to birth weight and gestational and postnatal age","volume":"88","author":"van Elburg","year":"2003"},{"key":"ref25","series-title":"Pediatr Res","first-page":"519","article-title":"Early feeding, antenatal glucocorticoids, and human milk decrease intestinal permeability in preterm infants","volume":"44","author":"Shulman","year":"1998"},{"key":"ref26","series-title":"Pediatr Allergy Immunol","first-page":"414","article-title":"The gut mucosal immune system in the neonatal period","volume":"24","author":"Battersby","year":"2013"},{"key":"ref27","series-title":"Microbiome","first-page":"38","article-title":"Development of the preterm infant gut microbiome: a research priority","volume":"2","author":"Groer","year":"2014"},{"key":"ref28","series-title":"Trends Microbiol","first-page":"298","article-title":"Nursing our microbiota: molecular linkages between bifidobacteria and milk oligosaccharides","volume":"18","author":"Sela","year":"2010"},{"key":"ref29","series-title":"Am J Clin Nutr","first-page":"828","article-title":"Alpha(1)-antitrypsin and antichymotrypsin in human milk: origin, concentrations, and stability","volume":"76","author":"Chowanadisai","year":"2002"},{"key":"ref30","series-title":"Am J Clin Nutr","first-page":"110","article-title":"Biopterin and neopterin in various milks and infant formulas","volume":"41","author":"Matsubara","year":"1985"},{"key":"ref31","series-title":"Complementary Feeding of Young Children in Developing Countries: A Review of Current Scientific Knowledge","author":"World Health Organization","year":"1998"},{"key":"ref32","series-title":"Pediatr Res","first-page":"614","article-title":"Tryptophan released from mother's milk has antioxidant properties","volume":"66","author":"Tsopmo","year":"2009"},{"key":"ref33","series-title":"J Nutr","first-page":"1417","article-title":"Tryptophan from human milk induces oxidative stress and upregulates the Nrf-2-mediated stress response in human intestinal cell lines","volume":"141","author":"Elisia","year":"2011"},{"key":"ref34","series-title":"Acta Paediatr Scand","first-page":"137","article-title":"Fecal alpha 1-antitrypsin in breast-fed infants is derived from human milk and is not indicative of enteric protein loss","volume":"79","author":"Davidson","year":"1990"},{"key":"ref35","series-title":"J Nutr","first-page":"965","article-title":"Catch-up growth occurs after diarrhea in early childhood","volume":"144","author":"Richard","year":"2014"},{"key":"ref36","series-title":"Lancet","article-title":"Enteric pathogens and dietary intakes, but not diarrhoea, affect growth velocity and attained size at 24 months: the MAL-ED multicenter birth cohort study","author":"MAL-ED Network Investigators"},{"key":"ref37","series-title":"Pediatr J Gastroenterol Nutr","article-title":"Factors associated with gut permeability over time as assessed by the lactulose: mannitol test in the eight-site MAL-ED birth cohort study","author":"Lee"},{"key":"ref38","series-title":"Gut","first-page":"483","article-title":"Geography of intestinal permeability and absorption","volume":"44","author":"Menzies","year":"1999"},{"key":"ref39","series-title":"J Transl Sci","first-page":"134","article-title":"Comparisons between myeloperoxidase, lactoferrin, calprotectin and lipocalin-2, as fecal biomarkers of intestinal inflammation in malnourished children","volume":"2","author":"Prata","year":"2016"}],"container-title":["The American Society of Tropical Medicine and Hygiene"],"original-title":[],"link":[{"URL":"https:\/\/www.ajtmh.org\/view\/journals\/tpmd\/96\/2\/article-p465.xml","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.ajtmh.org\/downloadpdf\/journals\/tpmd\/96\/2\/article-p465.xml","content-type":"text\/html","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/www.ajtmh.org\/downloadpdf\/journals\/tpmd\/96\/2\/article-p465.xml","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,8,7]],"date-time":"2024-08-07T18:41:26Z","timestamp":1723056086000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.ajtmh.org\/view\/journals\/tpmd\/96\/2\/article-p465.xml"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2017,2,8]]},"references-count":39,"journal-issue":{"issue":"2"},"URL":"https:\/\/doi.org\/10.4269\/ajtmh.16-0496","relation":{},"ISSN":["0002-9637","1476-1645"],"issn-type":[{"value":"0002-9637","type":"print"},{"value":"1476-1645","type":"electronic"}],"subject":[],"published":{"date-parts":[[2017,2,8]]}}}