Markers of Environmental Enteric Dysfunction Are Associated with Poor Growth and Iron Status in Rural Ugandan infants

Abstract

Abstract Objectives Environmental enteric dysfunction (EED), characterized by altered intestinal permeability/inflammation, microbial translocation, and systemic inflammation (SI), may be a significant contributor to poor growth and micronutrient deficiencies in infants from low-resource setting. The objective of this study was to examine relationships among EED, SI, growth, and iron status in a sample of 6-months old infants from rural Uganda. Methods We performed a cross-sectional analysis using a subset of infants (n = 548) enrolled in a birth cohort study conducted in 16 sub-counties across northern and southwestern Uganda. EED was assessed via serum levels of antibodies to the bacterial components flagellin and lipopolysaccharide (LPS); SI was assessed via serum levels of alpha(1)-acid glycoprotein (AGP) and C-reactive protein (CRP); iron status was assessed via serum levels of hemoglobin (Hb), soluble transferrin receptor (sTfR), and ferritin. Associations were assessed using adjusted linear regression analysis. Results At 6 months, ∼35% of infants were stunted (LAZ < −2), and ∼53% were anemic (Hb < 11.0 g/dL). Nearly half (∼46%) had elevated AGP (>1 g/L) and ∼30% had elevated CRP (>5 mg/L). EED biomarkers were significantly correlated with SI biomarkers (r = 0.142–0.193, P < 0.001 for all). In adjusted linear regression models, which included adjustments for SI, higher anti-flagellin IgA, anti-LPS IgA, and anti-LPS IgG levels were significantly associated with lower LAZ [β: −0.21 (95% CI: −0.41, 0.00), β: −0.23 (95% CI: −0.44, −0.03), and β: −0.33 (95% CI: −0.58, −0.09)]. Furthermore, higher anti-flagellin IgA, anti-flagellin IgG, and anti-LPS IgA levels were significantly associated with lower Hb levels [β: −0.24 (95% CI: −0.45, −0.02), β: −0.58 (95% CI: −1.13, 0.00), and β: −0.26 (95% CI: −0.51, 0.00)]; higher anti-flagellin IgG and anti-LPS IgG levels were significantly associated with higher sTfR levels [β: 2.31 (95% CI: 0.34, 4.28) and β: 3.13 (95% CI: 0.75, 5.51)]. Conclusions Independent of SI, EED is associated with both low LAZ and iron status in 6-months old infants. Further research on the mechanisms by which EED affects growth and micronutrient status is warranted. Funding Sources USAID, award AID-OAA-L-10–00006 to the Friedman School of Nutrition Science and Policy at Tufts University. CD was supported in part by NIH grants K24DK104676 and 2P30 DK040561.