An enteropathy score predicts subsequent length better than lactulose mannitol (L:M) ratio alone in children enrolled in a community‐based randomized trial of complementary food supplements in rural Bangladesh
Authors: Campbell Rebecca , Schulze Kerry , Shaikh Saijuddin , Ali Hasmot , Mehra Sucheta , Wu Lee , Christian Parul 
Published: June 2021

Childhood stunting rate in South Asia, including Bangladesh, continues to be high. Subclinical enteropathy may exacerbate stunting though nutrient malabsorption and sequestration, but the magnitude of its effect is unknown, in part due to limited methods for characterizing enteropathy in field‐based studies. Our objective was to derive a composite enteropathy score using a comprehensive set of biomarkers measuring aspects of gut integrity and systemic inflammation, and to determine the extent to which it, relative to the lactulose:mannitol (L:M) test alone, explained attained length. This was done in the context of a randomized controlled trial of complementary food supplements (CFS) for 6–18 mo old children in rural Bangladesh. In a 10% subsample (n=516), stool, serum and urine (2h post lactulose mannitol solution dosing) were collected at age 18 mo. The L:M recovery ratio, a measure of gut permeability and absorptive capacity, was assessed in urine. Stool markers of inflammation (myeloperoxidase and neopterin) and permeability (α−1 antitrypsin) and serum markers of pathogen translocation (endotoxin core antibody immunoglobulin G) and enterocyte repair (glucagon‐like peptide‐1) were measured. A composite enteropathy score (ES) was developed using partial least squares regression with insulin‐like growth factor‐1 (IGF‐1) as the dependent variable. The score was standardized and assessed as an independent variable in regression models with outcome attained length, alone and adjusted for potential confounders. Stunting prevalence among participants was 27.6%, 45.1% and 40.9% at ages 6, 18 and 24 mo, respectively. L:M was elevated (≥0.07) in 42.4% of participants, suggesting prevalent enteropathy, but was not associated with length at 18 or 24 mo. Enteropathy scores ranged from 2.9 to 5.5, with higher scores indicative of poorer intestinal health. In adjusted models, every SD increase in ES was associated with 0.32 (0.06, 0.59) cm lower length at 24 mo. ES trended toward a negative association with length at 18 mo, but confidence intervals included 0 in adjusted models. An enteropathy score inclusive of biomarkers of intestinal permeability, inflammation, absorptive capacity, and repair predicted subsequent length in a setting of prevalent stunting, but its contribution was small (univariate model R2=0.02). A comprehensive index of enteropathy, developed with an analytic approach that accounts for overlapping information from multiple interrelated biomarkers, may be more informative than the L:M test alone; however, our findings suggest compromised gut health has a smaller than expected role in explaining variability in early childhood growth in the rural Bangladesh context, consistent with findings that other growth‐inhibiting mechanisms need to be explored.Support or Funding InformationUSDA NIFA/FANEP [Award # 2010‐38418‐21732], National Institutes of Health [Award # R21HD081503], Bill and Melinda Gates Foundation (GH614) and the Johns Hopkins Sight and Life Global Nutrition Research Institute.