Study of Environmental Enteropathy and Malnutrition (SEEM) in Pakistan: protocols for biopsy based biomarker discovery and validation
Abstract Background Environmental Enteropathy (EE), characterized by alterations in intestinal structure, function, and immune activation, is believed to be an important contributor to childhood undernutrition and its associated morbidities, including stunting. Half of all global deaths in children...
Main Authors: | , , , , , , , , , , , , , , , , , , , , , , , , |
---|---|
Format: | Article |
Language: | English |
Published: |
BMC
2019-07-01
|
Series: | BMC Pediatrics |
Subjects: | |
Online Access: | http://link.springer.com/article/10.1186/s12887-019-1564-x |
id |
doaj-0414bfb214f044bf863c410800397858 |
---|---|
record_format |
Article |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Najeeha T. Iqbal Sana Syed Kamran Sadiq Marium N. Khan Junaid Iqbal Jennie Z. Ma Fayaz Umrani Sheraz Ahmed Elizabeth A. Maier Lee A. Denson Yael Haberman Monica M. McNeal Kenneth D. R. Setchell Xueheng Zhao Shahida Qureshi Lanlan Shen Christopher A. Moskaluk Ta-Chiang Liu Omer Yilmaz Donald E. Brown Michael J. Barratt Vanderlene L. Kung Jeffrey I. Gordon Sean R. Moore S. Asad Ali |
spellingShingle |
Najeeha T. Iqbal Sana Syed Kamran Sadiq Marium N. Khan Junaid Iqbal Jennie Z. Ma Fayaz Umrani Sheraz Ahmed Elizabeth A. Maier Lee A. Denson Yael Haberman Monica M. McNeal Kenneth D. R. Setchell Xueheng Zhao Shahida Qureshi Lanlan Shen Christopher A. Moskaluk Ta-Chiang Liu Omer Yilmaz Donald E. Brown Michael J. Barratt Vanderlene L. Kung Jeffrey I. Gordon Sean R. Moore S. Asad Ali Study of Environmental Enteropathy and Malnutrition (SEEM) in Pakistan: protocols for biopsy based biomarker discovery and validation BMC Pediatrics Childhood undernutrition Low- middle income countries Environmental enteropathy Gut barrier function Endoscopy Duodenal biopsies |
author_facet |
Najeeha T. Iqbal Sana Syed Kamran Sadiq Marium N. Khan Junaid Iqbal Jennie Z. Ma Fayaz Umrani Sheraz Ahmed Elizabeth A. Maier Lee A. Denson Yael Haberman Monica M. McNeal Kenneth D. R. Setchell Xueheng Zhao Shahida Qureshi Lanlan Shen Christopher A. Moskaluk Ta-Chiang Liu Omer Yilmaz Donald E. Brown Michael J. Barratt Vanderlene L. Kung Jeffrey I. Gordon Sean R. Moore S. Asad Ali |
author_sort |
Najeeha T. Iqbal |
title |
Study of Environmental Enteropathy and Malnutrition (SEEM) in Pakistan: protocols for biopsy based biomarker discovery and validation |
title_short |
Study of Environmental Enteropathy and Malnutrition (SEEM) in Pakistan: protocols for biopsy based biomarker discovery and validation |
title_full |
Study of Environmental Enteropathy and Malnutrition (SEEM) in Pakistan: protocols for biopsy based biomarker discovery and validation |
title_fullStr |
Study of Environmental Enteropathy and Malnutrition (SEEM) in Pakistan: protocols for biopsy based biomarker discovery and validation |
title_full_unstemmed |
Study of Environmental Enteropathy and Malnutrition (SEEM) in Pakistan: protocols for biopsy based biomarker discovery and validation |
title_sort |
study of environmental enteropathy and malnutrition (seem) in pakistan: protocols for biopsy based biomarker discovery and validation |
publisher |
BMC |
series |
BMC Pediatrics |
issn |
1471-2431 |
publishDate |
2019-07-01 |
description |
Abstract Background Environmental Enteropathy (EE), characterized by alterations in intestinal structure, function, and immune activation, is believed to be an important contributor to childhood undernutrition and its associated morbidities, including stunting. Half of all global deaths in children < 5 years are attributable to under-nutrition, making the study of EE an area of critical priority. Methods Community based intervention study, divided into two sub-studies, 1) Longitudinal analyses and 2) Biopsy studies for identification of EE features via omics analyses. Birth cohorts in Matiari, Pakistan established: moderately or severely malnourished (weight for height Z score (WHZ) < − 2) children, and well-nourished (WHZ > 0) children. Blood, urine, and fecal samples, for evaluation of potential biomarkers, will be collected at various time points from all participants (longitudinal analyses). Participants will receive appropriate educational and nutritional interventions; non-responders will undergo further evaluation to determine eligibility for further workup, including upper gastrointestinal endoscopy. Histopathological changes in duodenal biopsies will be compared with duodenal biopsies obtained from USA controls who have celiac disease, Crohn’s disease, or who were found to have normal histopathology. RNA-Seq will be employed to characterize mucosal gene expression across groups. Duodenal biopsies, luminal aspirates from the duodenum, and fecal samples will be analyzed to define microbial community composition (omic analyses). The relationship between histopathology, mucosal gene expression, and community configuration will be assessed using a variety of bioinformatic tools to gain better understanding of disease pathogenesis and to identify mechanism-based biomarkers. Ethical review committees at all collaborating institutions have approved this study. All results will be made available to the scientific community. Discussion Operational and ethical constraints for safely obtaining intestinal biopsies from children in resource-poor settings have led to a paucity of human tissue-based investigations to understand and reverse EE in vulnerable populations. Furthermore, EE biomarkers have rarely been correlated with gold standard histopathological confirmation. The Study of Environmental Enteropathy and Malnutrition (SEEM) is designed to better understand the pathophysiology, predictors, biomarkers, and potential management strategies of EE to inform strategies to eradicate this debilitating pathology and accelerate progress towards the 2030 Sustainable Development Goals. Trial registration Retrospectively registered; clinicaltrials.gov ID NCT03588013. |
topic |
Childhood undernutrition Low- middle income countries Environmental enteropathy Gut barrier function Endoscopy Duodenal biopsies |
url |
http://link.springer.com/article/10.1186/s12887-019-1564-x |
work_keys_str_mv |
AT najeehatiqbal studyofenvironmentalenteropathyandmalnutritionseeminpakistanprotocolsforbiopsybasedbiomarkerdiscoveryandvalidation AT sanasyed studyofenvironmentalenteropathyandmalnutritionseeminpakistanprotocolsforbiopsybasedbiomarkerdiscoveryandvalidation AT kamransadiq studyofenvironmentalenteropathyandmalnutritionseeminpakistanprotocolsforbiopsybasedbiomarkerdiscoveryandvalidation AT mariumnkhan studyofenvironmentalenteropathyandmalnutritionseeminpakistanprotocolsforbiopsybasedbiomarkerdiscoveryandvalidation AT junaidiqbal studyofenvironmentalenteropathyandmalnutritionseeminpakistanprotocolsforbiopsybasedbiomarkerdiscoveryandvalidation AT jenniezma studyofenvironmentalenteropathyandmalnutritionseeminpakistanprotocolsforbiopsybasedbiomarkerdiscoveryandvalidation AT fayazumrani studyofenvironmentalenteropathyandmalnutritionseeminpakistanprotocolsforbiopsybasedbiomarkerdiscoveryandvalidation AT sherazahmed studyofenvironmentalenteropathyandmalnutritionseeminpakistanprotocolsforbiopsybasedbiomarkerdiscoveryandvalidation AT elizabethamaier studyofenvironmentalenteropathyandmalnutritionseeminpakistanprotocolsforbiopsybasedbiomarkerdiscoveryandvalidation AT leeadenson studyofenvironmentalenteropathyandmalnutritionseeminpakistanprotocolsforbiopsybasedbiomarkerdiscoveryandvalidation AT yaelhaberman studyofenvironmentalenteropathyandmalnutritionseeminpakistanprotocolsforbiopsybasedbiomarkerdiscoveryandvalidation AT monicammcneal studyofenvironmentalenteropathyandmalnutritionseeminpakistanprotocolsforbiopsybasedbiomarkerdiscoveryandvalidation AT kennethdrsetchell studyofenvironmentalenteropathyandmalnutritionseeminpakistanprotocolsforbiopsybasedbiomarkerdiscoveryandvalidation AT xuehengzhao studyofenvironmentalenteropathyandmalnutritionseeminpakistanprotocolsforbiopsybasedbiomarkerdiscoveryandvalidation AT shahidaqureshi studyofenvironmentalenteropathyandmalnutritionseeminpakistanprotocolsforbiopsybasedbiomarkerdiscoveryandvalidation AT lanlanshen studyofenvironmentalenteropathyandmalnutritionseeminpakistanprotocolsforbiopsybasedbiomarkerdiscoveryandvalidation AT christopheramoskaluk studyofenvironmentalenteropathyandmalnutritionseeminpakistanprotocolsforbiopsybasedbiomarkerdiscoveryandvalidation AT tachiangliu studyofenvironmentalenteropathyandmalnutritionseeminpakistanprotocolsforbiopsybasedbiomarkerdiscoveryandvalidation AT omeryilmaz studyofenvironmentalenteropathyandmalnutritionseeminpakistanprotocolsforbiopsybasedbiomarkerdiscoveryandvalidation AT donaldebrown studyofenvironmentalenteropathyandmalnutritionseeminpakistanprotocolsforbiopsybasedbiomarkerdiscoveryandvalidation AT michaeljbarratt studyofenvironmentalenteropathyandmalnutritionseeminpakistanprotocolsforbiopsybasedbiomarkerdiscoveryandvalidation AT vanderlenelkung studyofenvironmentalenteropathyandmalnutritionseeminpakistanprotocolsforbiopsybasedbiomarkerdiscoveryandvalidation AT jeffreyigordon studyofenvironmentalenteropathyandmalnutritionseeminpakistanprotocolsforbiopsybasedbiomarkerdiscoveryandvalidation AT seanrmoore studyofenvironmentalenteropathyandmalnutritionseeminpakistanprotocolsforbiopsybasedbiomarkerdiscoveryandvalidation AT sasadali studyofenvironmentalenteropathyandmalnutritionseeminpakistanprotocolsforbiopsybasedbiomarkerdiscoveryandvalidation |
_version_ |
1724596338408030208 |
spelling |
doaj-0414bfb214f044bf863c4108003978582020-11-25T03:25:33ZengBMCBMC Pediatrics1471-24312019-07-0119111710.1186/s12887-019-1564-xStudy of Environmental Enteropathy and Malnutrition (SEEM) in Pakistan: protocols for biopsy based biomarker discovery and validationNajeeha T. Iqbal0Sana Syed1Kamran Sadiq2Marium N. Khan3Junaid Iqbal4Jennie Z. Ma5Fayaz Umrani6Sheraz Ahmed7Elizabeth A. Maier8Lee A. Denson9Yael Haberman10Monica M. McNeal11Kenneth D. R. Setchell12Xueheng Zhao13Shahida Qureshi14Lanlan Shen15Christopher A. Moskaluk16Ta-Chiang Liu17Omer Yilmaz18Donald E. Brown19Michael J. Barratt20Vanderlene L. Kung21Jeffrey I. Gordon22Sean R. Moore23S. Asad Ali24Department of Paediatrics and Child Health, Aga Khan UniversityDepartment of Paediatrics and Child Health, Aga Khan UniversityDepartment of Paediatrics and Child Health, Aga Khan UniversityDepartment of Pediatrics, University of VirginiaDepartment of Paediatrics and Child Health, Aga Khan UniversityDepartment of Public Health Sciences, University of VirginiaDepartment of Paediatrics and Child Health, Aga Khan UniversityDepartment of Paediatrics and Child Health, Aga Khan UniversityDivision of Pediatric Gastroenterology, Hepatology, and Nutrition, Cincinnati Children’s Hospital Medical CenterDivision of Pediatric Gastroenterology, Hepatology, and Nutrition, Cincinnati Children’s Hospital Medical CenterDivision of Pediatric Gastroenterology, Hepatology, and Nutrition, Cincinnati Children’s Hospital Medical CenterDivision of Infectious Diseases, Cincinnati Children’s Hospital Medical CenterClinical Mass Spectrometry, Division of Pathology and Laboratory Medicine, Cincinnati Children’s Hospital Medical CenterClinical Mass Spectrometry, Division of Pathology and Laboratory Medicine, Cincinnati Children’s Hospital Medical CenterDepartment of Paediatrics and Child Health, Aga Khan UniversityDepartment of Pediatrics, Baylor College of Medicine, USDA/ARS Children’s Nutrition Research CenterDepartment of Pathology, University of VirginiaDepartment of Pathology and Immunology, Washington University School of MedicineDepartment of Pathology, Massachusetts General Hospital and Harvard Medical SchoolData Science Institute, University of VirginiaCenter for Genome Sciences and Systems Biology, Washington University School of MedicineCenter for Genome Sciences and Systems Biology, Washington University School of MedicineCenter for Genome Sciences and Systems Biology, Washington University School of MedicineDepartment of Pediatrics, University of VirginiaDepartment of Paediatrics and Child Health, Aga Khan UniversityAbstract Background Environmental Enteropathy (EE), characterized by alterations in intestinal structure, function, and immune activation, is believed to be an important contributor to childhood undernutrition and its associated morbidities, including stunting. Half of all global deaths in children < 5 years are attributable to under-nutrition, making the study of EE an area of critical priority. Methods Community based intervention study, divided into two sub-studies, 1) Longitudinal analyses and 2) Biopsy studies for identification of EE features via omics analyses. Birth cohorts in Matiari, Pakistan established: moderately or severely malnourished (weight for height Z score (WHZ) < − 2) children, and well-nourished (WHZ > 0) children. Blood, urine, and fecal samples, for evaluation of potential biomarkers, will be collected at various time points from all participants (longitudinal analyses). Participants will receive appropriate educational and nutritional interventions; non-responders will undergo further evaluation to determine eligibility for further workup, including upper gastrointestinal endoscopy. Histopathological changes in duodenal biopsies will be compared with duodenal biopsies obtained from USA controls who have celiac disease, Crohn’s disease, or who were found to have normal histopathology. RNA-Seq will be employed to characterize mucosal gene expression across groups. Duodenal biopsies, luminal aspirates from the duodenum, and fecal samples will be analyzed to define microbial community composition (omic analyses). The relationship between histopathology, mucosal gene expression, and community configuration will be assessed using a variety of bioinformatic tools to gain better understanding of disease pathogenesis and to identify mechanism-based biomarkers. Ethical review committees at all collaborating institutions have approved this study. All results will be made available to the scientific community. Discussion Operational and ethical constraints for safely obtaining intestinal biopsies from children in resource-poor settings have led to a paucity of human tissue-based investigations to understand and reverse EE in vulnerable populations. Furthermore, EE biomarkers have rarely been correlated with gold standard histopathological confirmation. The Study of Environmental Enteropathy and Malnutrition (SEEM) is designed to better understand the pathophysiology, predictors, biomarkers, and potential management strategies of EE to inform strategies to eradicate this debilitating pathology and accelerate progress towards the 2030 Sustainable Development Goals. Trial registration Retrospectively registered; clinicaltrials.gov ID NCT03588013.http://link.springer.com/article/10.1186/s12887-019-1564-xChildhood undernutritionLow- middle income countriesEnvironmental enteropathyGut barrier functionEndoscopyDuodenal biopsies |