LAUSR

Objectives We tested whether environmental enteric dysfunction (EED) is associated with risk of micronutrient deficiencies adjusting for diet and systemic inflammation, and whether it mediates the relation between intake and micronutrient status. Methods Data from 1283 children in the MAL-ED birth cohort were examined to evaluate risk of anemia, low plasma retinol, zinc, and ferritin, and high plasma transferrin receptor (TfR) at 15 months. We characterized gut inflammation and permeability by myeloperoxidase, neopterin, and alpha-1-antitrypsin concentrations from monthly asymptomatic fecal samples averaged from 9-15 months, and urinary recovery of lactulose (L) and mannitol (M) from LM tests at 9 and 15 months, converted to a ratio z score (LMZ) and averaged. Nutrient intakes from complementary foods were quantified monthly from 9-15 months and densities were averaged. Plasma alpha-1 acid glycoprotein at 15 months characterized systemic inflammation. Relationships among variables were modelled using a direct acyclic graph. Results Greater risk of anemia was associated with permeability [LMZ: 1.15 (95% confidence interval: 1.01-1.31)] and inflammation [myeloperoxidase: 1.16 (1.01-1.34)]. Greater risk of low ferritin was associated with alpha-1-antitrypsin [1.19 (1.03-1.37)] and neopterin [1.22 (1.04-1.43)]. Greater risk of low retinol was associated with LMZ [1.25 (1.07-1.45)]. However, myeloperoxidase was associated with lower risk of high TfR [0.86 (0.74-0.98)], neopterin with lower risk of low retinol [0.75 (0.62-0.89)], and alpha-1-antripysin with lower risk of low plasma zinc [0.83 (0.70-0.99)]. Greater nutrient densities of vitamin A, B6, calcium, protein and zinc were negatively associated with EED. Inverse associations between nutrient densities and micronutrient deficiency largely disappeared after adjustment for EED, suggesting that EED mediates associations between intake and status. Conclusions EED is independently associated with increased risk of low ferritin, low retinol and anemia. Greater nutrient density from complementary foods may reduce EED, and control of micronutrient deficiency may require control of EED. Funding Sources The MAL-ED study was supported by the Bill & Melinda Gates Foundation, through awards to the Foundation for the NIH and NIH/FIC.