Biomarkers of Environmental Enteropathy, Inflammation, Stunting, and Impaired Growth in Children in Northeast Brazil.

Autor: Guerrant RL; University of Virginia School of Medicine (Division of Infectious Diseases and International Health, Department of Medicine, Department of Pediatrics and Center for Global Health), Charlottesville, VA, United States of America., Leite AM; Clinical Research Unit, Federal University of Ceara, Fortaleza, Brazil., Pinkerton R; University of Virginia School of Medicine (Division of Infectious Diseases and International Health, Department of Medicine, Department of Pediatrics and Center for Global Health), Charlottesville, VA, United States of America., Medeiros PH; Clinical Research Unit, Federal University of Ceara, Fortaleza, Brazil., Cavalcante PA; Clinical Research Unit, Federal University of Ceara, Fortaleza, Brazil., DeBoer M; University of Virginia School of Medicine (Division of Infectious Diseases and International Health, Department of Medicine, Department of Pediatrics and Center for Global Health), Charlottesville, VA, United States of America., Kosek M; Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, United States of America., Duggan C; Division of Gastroenterology at Boston Children's Hospital, Harvard University, Boston, MA, United States of America., Gewirtz A; Institute for Biomedical Sciences in the Center for Inflammation, Immunity and Infection at Georgia State University, Atlanta, GA, United States of America., Kagan JC; Division of Gastroenterology at Boston Children's Hospital, Harvard University, Boston, MA, United States of America., Gauthier AE; Division of Gastroenterology at Boston Children's Hospital, Harvard University, Boston, MA, United States of America., Swann J; Imperial College, London, United Kingdom., Mayneris-Perxachs J; Imperial College, London, United Kingdom., Bolick DT; University of Virginia School of Medicine (Division of Infectious Diseases and International Health, Department of Medicine, Department of Pediatrics and Center for Global Health), Charlottesville, VA, United States of America., Maier EA; Cincinnati Children's Hospital, Cincinnati, OH, United States of America., Guedes MM; Cincinnati Children's Hospital, Cincinnati, OH, United States of America., Moore SR; Cincinnati Children's Hospital, Cincinnati, OH, United States of America., Petri WA; University of Virginia School of Medicine (Division of Infectious Diseases and International Health, Department of Medicine, Department of Pediatrics and Center for Global Health), Charlottesville, VA, United States of America., Havt A; Clinical Research Unit, Federal University of Ceara, Fortaleza, Brazil., Lima IF; Clinical Research Unit, Federal University of Ceara, Fortaleza, Brazil., Prata MM; Clinical Research Unit, Federal University of Ceara, Fortaleza, Brazil., Michaleckyj JC; University of Virginia School of Medicine (Division of Infectious Diseases and International Health, Department of Medicine, Department of Pediatrics and Center for Global Health), Charlottesville, VA, United States of America., Scharf RJ; University of Virginia School of Medicine (Division of Infectious Diseases and International Health, Department of Medicine, Department of Pediatrics and Center for Global Health), Charlottesville, VA, United States of America., Sturgeon C; Mucosal Immunology and Biology Research Center and Division of Pediatric Gastroenterology and Nutrition at Massachusetts General Hospital for Children, Harvard University, Boston, MA, United States of America., Fasano A; Mucosal Immunology and Biology Research Center and Division of Pediatric Gastroenterology and Nutrition at Massachusetts General Hospital for Children, Harvard University, Boston, MA, United States of America., Lima AA; Clinical Research Unit, Federal University of Ceara, Fortaleza, Brazil.
Jazyk: angličtina
Zdroj: PloS one [PLoS One] 2016 Sep 30; Vol. 11 (9), pp. e0158772. Date of Electronic Publication: 2016 Sep 30 (Print Publication: 2016).
DOI: 10.1371/journal.pone.0158772
Abstrakt: Critical to the design and assessment of interventions for enteropathy and its developmental consequences in children living in impoverished conditions are non-invasive biomarkers that can detect intestinal damage and predict its effects on growth and development. We therefore assessed fecal, urinary and systemic biomarkers of enteropathy and growth predictors in 375 6-26 month-old children with varying degrees of malnutrition (stunting or wasting) in Northeast Brazil. 301 of these children returned for followup anthropometry after 2-6m. Biomarkers that correlated with stunting included plasma IgA anti-LPS and anti-FliC, zonulin (if >12m old), and intestinal FABP (I-FABP, suggesting prior barrier disruption); and with citrulline, tryptophan and with lower serum amyloid A (SAA) (suggesting impaired defenses). In contrast, subsequent growth was predicted in those with higher fecal MPO or A1AT and also by higher L/M, plasma LPS, I-FABP and SAA (showing intestinal barrier disruption and inflammation). Better growth was predicted in girls with higher plasma citrulline and in boys with higher plasma tryptophan. Interactions were also seen with fecal MPO and neopterin in predicting subsequent growth impairment. Biomarkers clustered into markers of 1) functional intestinal barrier disruption and translocation, 2) structural intestinal barrier disruption and inflammation and 3) systemic inflammation. Principle components pathway analyses also showed that L/M with %L, I-FABP and MPO associate with impaired growth, while also (like MPO) associating with a systemic inflammation cluster of kynurenine, LBP, sCD14, SAA and K/T. Systemic evidence of LPS translocation associated with stunting, while markers of barrier disruption or repair (A1AT and Reg1 with low zonulin) associated with fecal MPO and neopterin. We conclude that key noninvasive biomarkers of intestinal barrier disruption, LPS translocation and of intestinal and systemic inflammation can help elucidate how we recognize, understand, and assess effective interventions for enteropathy and its growth and developmental consequences in children in impoverished settings.
Competing Interests: The authors have declared that no competing interests exist.
Databáze: MEDLINE
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