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

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.

Keywords: Uganda; anemia; environmental enteric dysfunction; growth; iron; systemic inflammation.