Childhood hunger and under nutrition are prevalent in low income countries, and are typically observed in populations facing states of chronic or seasonal food shortage, or food insecurity. Stunting, attained length or height-for-age beyond -2 Z- scores from the median of the international growth standard, remains an intractable consequence of chronic deprivation in many low and middle income countries. In adults, being stunted contributes to compromised reproductive outcomes in women, and lower educational achievement, poorer socioeconomic prospects, and an increased risk of non-communicable diseases in men and women. Globally, the greatest number of stunted individuals resides in South Asia, where over 35% of preschool age children are stunted. Height at 24 months predicts adult height, and the greatest decrements in linear growth occur between 6 and 24 months of age. Efforts have therefore focused on the first 1000 days, conception to 24 months, which is considered a critical window for improving growth. However, to date, efforts to improve linear growth through nutrition interventions alone have yielded modest, albeit positive, results, indicating unrealized potential for improving growth during this period of life. A new generation of lipid-based complementary food products, fortified with micronutrients, may offer the best hope of prospectively improving linear growth in settings where complementary (or weaning) foods are poor in nutrient diversity and density. However, children in such environments are also subject to environmental exposures that may limit their ability to utilize nutrients, with oneof the greatest concerns being environmental enteropathy (EE), or damage to the gut from repeated exposure to enteric pathogens, resulting in inflammation, compromised nutrient absorptive capacity, and excess gut permeability that may lead to the translocation of pathogens that trigger systemic immune responses. In rural northwestern Bangladesh, EE will be assessed in 18 month old children following 12 months of supplemental complementary foods, versus nutrition counseling alone, in the context of a cluster-randomized, controlled trial of four different food formulations on growth and development. While over 5,300 children were enrolled in that trial, a more intensive study of 500 children, a ~10% subsample, will be done to characterize EE using stool markers of gut inflammation, serum markers of bacterial translocation, and the relative absorption of mannitol and lactulose to evaluate gut absorptive capacity and gut permeability, respectively. We hypothesize that children who received supplemental foods for the past year will have less evidence of EE than those who received nutrition counseling alone. This study will take advantage of biospecimens and longitudinal data on diet, morbidity and anthropometry, as well as household characteristics and feeding and parenting practices, which have already been collected. [Results will demonstrate whether improving the diet with access to high quality complementary foods can ameliorate EE, and will examine relationships of EE to growth trajectories and biological mediators of growth, providing supportive data for future study of the gut microbiome in these children.]

Public Health Relevance

In a South Asian context, where 50% of children experience stunting by the age of 24 months and pathogenic exposures are high, we will characterize environmental enteropathy (EE), a condition that results in inflammation of the gut, reduced capacity to absorb nutrients, and excess gut permeability that may predispose to bacterial and viral translocation and systemic immune system stimulation. Using biospecimens collected in a community-based, randomized trial of supplementation with different types of specially formulated complementary foods from 6 to 18 months of age, [we will examine the potential for high quality food products to promote improved gut health, a potential pathway for improved linear growth in supplemented children.

Agency
National Institute of Health (NIH)
Institute
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Type
Exploratory/Developmental Grants (R21)
Project #
5R21HD081503-02
Application #
9042409
Study Section
Kidney, Nutrition, Obesity and Diabetes (KNOD)
Program Officer
Raiten, Daniel J
Project Start
2015-04-01
Project End
2017-03-31
Budget Start
2016-04-01
Budget End
2017-03-31
Support Year
2
Fiscal Year
2016
Total Cost
Indirect Cost
Name
Johns Hopkins University
Department
Public Health & Prev Medicine
Type
Schools of Public Health
DUNS #
001910777
City
Baltimore
State
MD
Country
United States
Zip Code
21205
Campbell, Rebecca K; Schulze, Kerry J; Shaikh, Saijuddin et al. (2017) Biomarkers of Environmental Enteric Dysfunction Among Children in Rural Bangladesh. J Pediatr Gastroenterol Nutr 65:40-46