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

Abstract

ABSTRACT Background Environmental enteric dysfunction (EED), characterized by altered intestinal permeability/inflammation, microbial translocation, and systemic inflammation (SI), may be a significant contributor to micronutrient deficiencies and poor growth in infants from low-resource settings. Objective We examined associations among EED, SI, growth, and iron status at 6 mo of age. Methods We performed a cross-sectional analysis of 6-mo-old infants (n = 548) enrolled in a Ugandan birth-cohort study (NCT04233944). EED was assessed via serum concentrations of anti-flagellin and anti- LPS immunoglobulins (Igs); SI was assessed via serum concentrations of ɑ1-acid glycoprotein (AGP) and C-reactive protein (CRP); iron status was assessed via serum concentrations of hemoglobin (Hb), soluble transferrin receptor (sTfR), and ferritin. Associations were assessed using adjusted linear regression analysis. Results At 6 mo, ∼35% of infants were stunted [length-for-age z score (LAZ) < −2] and ∼53% were anemic [hemoglobin (Hb) <11.0 g/dL]. Nearly half (∼46%) had elevated AGP (>1 g/L) and ∼30% had elevated CRP (>5 mg/L). EED and SI biomarkers were significantly correlated (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 concentrations were each significantly associated with lower LAZ [β (95% CI): −0.21 (−0.41, 0.00), −0.23 (−0.44, −0.03), and −0.33 (−0.58, −0.09)]. Furthermore, higher anti-flagellin IgA, anti-flagellin IgG, and anti-LPS IgA concentrations were significantly associated with lower Hb [β (95% CI): −0.24 (−0.45, −0.02), −0.58 (−1.13, 0.00), and −0.26 (−0.51, 0.00)] and higher anti-flagellin IgG and anti-LPS IgG concentrations were significantly associated with higher sTfR [β (95% CI): 2.31 (0.34, 4.28) and 3.13 (0.75, 5.51)]. Conclusions EED is associated with both low LAZ and iron status in 6-mo-old infants. Further research on the mechanisms by which EED affects growth and micronutrient status is warranted.