title: Common beans and cowpeas as complementary foods to reduce environmental enteric dysfunction and stunting in Malawian children: study protocol for two randomized controlled trials.
abstract: BACKGROUND
  Interventions to decrease the burden of childhood malnutrition are urgently needed, as millions of children die annually owing to undernutrition and hundreds of millions more are left cognitively and physically stunted. Environmental enteric dysfunction (EED), a pervasive chronic subclinical inflammatory condition among children that develops when complementary foods are introduced, places them at high risk of stunting, malabsorption, and poor oral vaccine efficacy. Improved interventions to reduce the burden of EED and stunting are expected to markedly improve the nutritional status and survival of children throughout resource-limited settings.
  
  
  METHODS
  We will conduct, in parallel, two prospective randomized controlled clinical trials to determine whether common beans or cowpeas improve growth, ameliorate EED, and alter the intestinal microbiome during a high-risk period in the lives of rural Malawian children. Study 1 will enroll children at 6 months of age and randomize them to receive common beans, cowpeas, or a standard complementary food for 6 months. Anthropometry will be compared among the three groups; EED will be assessed using a dual-sugar absorption test and by quantifying human intestinal mRNA for inflammatory messages; and the intestinal microbiota will be characterized by deep sequencing of fecal DNA, to enumerate host microbial populations and their metabolic capacity. Study 2 will enroll children 12-23 months old and follow them for 12 months, with similar interventions and assessments as Study 1.
  
  
  CONCLUSIONS
  By amalgamating the power of rigorous clinical trials and advanced biological analysis, we aim to elucidate the potential of two grain legumes to reduce stunting and EED in a high-risk population. Legumes have potential as an affordable and effective complementary food intervention, given their cultural acceptability, nutritional content, and agricultural feasibility in sub-Saharan Africa.
  
  
  BACKGROUND
  Clinicaltrials.gov NCT02472262 and NCT02472301 .
authors.affiliation: Department of Pediatrics, Washington University in St. Louis, One Children's Place, Campus Box 8116, Saint Louis, MO, 63110, USA. indi@alum.berkeley.edu.|Department of Paediatrics and Child Health, University of Malawi, Blantyre, Malawi. indi@alum.berkeley.edu.
authors.forename: Indi
authors.initials: I
authors.lastname: Trehan
authors.affiliation: Department of Pediatrics, Washington University in St. Louis, One Children's Place, Campus Box 8116, Saint Louis, MO, 63110, USA. benzonin@wustl.edu.
authors.forename: Nicole S
authors.initials: NS
authors.lastname: Benzoni
authors.affiliation: University of Texas Southwestern Medical School, Dallas, TX, USA. alfred.wang@utsouthwestern.edu.
authors.forename: Alfred Z
authors.initials: AZ
authors.lastname: Wang
authors.affiliation: Department of Pediatrics, Washington University in St. Louis, One Children's Place, Campus Box 8116, Saint Louis, MO, 63110, USA. lbollin@wustl.edu.
authors.forename: Lucy B
authors.initials: LB
authors.lastname: Bollinger
authors.affiliation: Department of Food Science and Technology, Lilongwe University of Agriculture and Natural Resources, Lilongwe, Malawi. tnakoma@gmail.com.
authors.forename: Theresa N
authors.initials: TN
authors.lastname: Ngoma
authors.affiliation: Department of Food Science and Technology, Lilongwe University of Agriculture and Natural Resources, Lilongwe, Malawi. ulemukankwatira@gmail.com.
authors.forename: Ulemu K
authors.initials: UK
authors.lastname: Chimimba
authors.affiliation: Department of Pediatrics, Washington University in St. Louis, One Children's Place, Campus Box 8116, Saint Louis, MO, 63110, USA. kbstephe@gmail.com.|Columbia University College of Physicians and Surgeons, New York, NY, USA. kbstephe@gmail.com.
authors.forename: Kevin B
authors.initials: KB
authors.lastname: Stephenson
authors.affiliation: Columbia University College of Physicians and Surgeons, New York, NY, USA. shtepaz@gmail.com.
authors.forename: Sophia E
authors.initials: SE
authors.lastname: Agapova
authors.affiliation: Department of Community Health, University of Malawi, Blantyre, Malawi. kmaleta@medcol.mw.
authors.forename: Kenneth M
authors.initials: KM
authors.lastname: Maleta
authors.affiliation: Department of Pediatrics, Washington University in St. Louis, One Children's Place, Campus Box 8116, Saint Louis, MO, 63110, USA. manary@kids.wustl.edu.|Department of Community Health, University of Malawi, Blantyre, Malawi. manary@kids.wustl.edu.|Children's Nutrition Research Center, Baylor College of Medicine, Houston, TX, USA. manary@kids.wustl.edu.
authors.forename: Mark J
authors.initials: MJ
authors.lastname: Manary
mesh_terms: D002657:Child Development; D004032:Diet; D004777:Environment; D007887:Fabaceae; D000069196:Gastrointestinal Microbiome; D006130:Growth Disorders / Q000175:diagnosis / Q000382:microbiology / Q000503:physiopathology / Q000517:prevention & control*; D006801:Humans; D007223:Infant; D007227:Infant Nutritional Physiological Phenomena; D007410:Intestinal Diseases / Q000175:diagnosis / Q000382:microbiology / Q000503:physiopathology / Q000517:prevention & control*; D007422:Intestines / Q000382:microbiology / Q000503:physiopathology*; D008286:Malabsorption Syndromes / Q000175:diagnosis / Q000382:microbiology / Q000503:physiopathology / Q000517:prevention & control*; D008295:Malawi; D015596:Nutrition Assessment; D009752:Nutritional Status; D027805:Phaseolus; D011446:Prospective Studies; D012107:Research Design; D012307:Risk Factors; D013997:Time Factors; D016896:Treatment Outcome