Effects of improved water, sanitation, and hygiene and improved complementary feeding on environmental enteric dysfunction in children in rural Zimbabwe: A cluster-randomized controlled trial

Author summary Child stunting remains a global health challenge rooted in an intergenerational cycle of poor health, reduced neurodevelopment and poverty. Environmental enteric dysfunction (EED) is an acquired condition of the small intestine likely resulting from frequent faecal-oral microbial exposure, which is hypothesized to underlie stunting. We found dynamic changes in EED biomarkers between 1 and 18 months of age in a cohort of rural Zimbabwean infants, suggesting a complex developmental period of intestinal maturation, adaptation and response to environmental insults. Randomized improved infant and young child feeding, and improved water, sanitation and hygiene (WASH) interventions had no meaningful impact on EED. Greater investment in transformative WASH is needed to prevent EED in low-income countries. Background Environmental enteric dysfunction (EED) may be an important modifiable cause of child stunting. We described the evolution of EED biomarkers from birth to 18 months in rural Zimbabwe and tested the independent and combined effects of improved water, sanitation, and hygiene (WASH), and improved infant and young child feeding (IYCF), on EED. Methodology and findings The Sanitation Hygiene Infant Nutrition Efficacy (SHINE) trial was a 2x2 factorial cluster-randomised trial of improved IYCF and improved WASH on child stunting and anaemia at 18 months of age. 1169 infants born to HIV-negative mothers provided plasma and faecal specimens at 1, 3, 6, 12, and 18 months of age. We measured EED biomarkers that reflect all domains of the hypothesized pathological pathway. Markers of intestinal permeability and intestinal inflammation declined over time, while markers of microbial translocation and systemic inflammation increased between 1-18 months. Markers of intestinal damage (I-FABP) and repair (REG-1 beta) mirrored each other, and citrulline (a marker of intestinal epithelial mass) increased from 6 months of age, suggesting dynamic epithelial turnover and regeneration in response to enteric insults. We observed few effects of IYCF and WASH on EED after adjustment for multiple comparisons. The WASH intervention decreased plasma IGF-1 at 3 months (beta:0.89, 95%CI:0.81,0.98) and plasma kynurenine at 12 months (beta: 0.92, 95%CI:0.87,0.97), and increased plasma IGF-1 at 18 months (beta:1.15, 95%CI:1.05,1.25), but these small WASH effects did not translate into improved growth. Conclusions Overall, we observed dynamic trends in EED but few effects of IYCF or WASH on biomarkers during the first 18 months after birth, suggesting that these interventions did not impact EED. Transformative WASH interventions are required to prevent or ameliorate EED in low-income settings.