Environmental enteric dysfunction influences linear growth of children through insulin-like growth factor-1: findings from the Indonesian Action Against Stunting Hub birth cohort

Abstract:
Poor gut health, characterized by persistent immune activation and increased intestinal permeability, is considered a significant underlying cause of impaired child growth. This study aimed to investigate effects of environmental enteric dysfunction (EED) and systemic inflammation on plasma insulin-like growth factor (IGF)-1 and linear growth among Indonesian infants. In this longitudinal cohort study (Action Against Stunting Hub), faecal and plasma samples were collected at six months of age, and anthropometry assessment was conducted at six and twelve months of age. EED markers included faecal myeloperoxidase, alpha-1 antitrypsin and plasma intestinal fatty acid binding protein (IFABP). Systemic inflammation markers included C-reactive protein, alpha-1 acid glycoprotein and cluster of differentiation-14 (CD14). IGF-1 was measured as a growth biomarker. Correlation and multivariable regression analyses assessed association with length-for-age z-score (LAZ). Structural equation
modelling explored potential pathways. Elevated EED markers were common among the infants (>80%). Maternal height, birth weight and IGF-1 were significant determinants of LAZ at 12 months. Pathway analysis showed IGF-1 was negatively associated with CD14, whereas CD14 was positively associated with IFABP. EED influences linear growth indirectly through systemic inflammation and altered growth signalling. Studies to urther address gut integrity and systemic inflammation to improve linear growth are recommended. This article is part of the theme issue ‘Biological, biomedical and environmental drivers of stunting’