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Markers of Environmental Enteric Dysfunction Are Associated With Neurodevelopmental Outcomes in Tanzanian Children
Analee J Etheredge1, Karim Manji2, Mark Kellogg3
1Division of Gastroenterology, Hepatology and Nutrition, Boston Children's Hospital, Boston, MA.
Insights
Environmental enteric dysfunction (EED) biomarkers and vitamin A status are linked to improved neurodevelopment in Tanzanian children. These findings suggest immune response pathways may play a role in neuroprotection during early development.
Area of Science:
- Pediatric neurodevelopment
- Gastroenterology
- Nutritional science
Background:
- Environmental enteric dysfunction (EED) from chronic enteropathogen exposure is linked to poor child growth and neurodevelopment.
- Sensitive postnatal periods are critical for brain development, making early interventions crucial.
Purpose of the Study:
- To investigate the impact of novel EED biomarkers, systemic inflammation, and micronutrient status on neurodevelopment in Tanzanian children.
- To explore potential mechanistic pathways between gut health, inflammation, and cognitive and motor development.
Main Methods:
- Blood samples from 107 non-stunted children at 6 weeks and 6 months were analyzed for EED biomarkers (citrulline, anti-LPS IgG, anti-flagellin IgA/IgG), micronutrients (iron, RBP, vitamin D), and inflammation markers (CRP, AAG).
- Neurodevelopmental measures were assessed at 15 months.
- Statistical analyses correlated biomarker concentrations with cognitive, language, and motor scores.
Main Results:
- Higher concentrations of anti-lipopolysaccharide IgG and anti-flagellin IgA/IgG at 6 months were associated with better cognitive scores at 15 months.
- Increased citrulline levels at 6 months correlated with higher receptive language and gross motor scores.
- Retinol-binding protein (RBP) at 6 months was positively associated with gross motor scores.
- Systemic inflammation markers showed no significant association with neurodevelopmental outcomes.
Conclusions:
- Plasma citrulline, indicating gastrointestinal mucosal integrity, and vitamin A status are associated with enhanced gross motor development.
- Novel EED biomarkers, rather than systemic inflammation, showed positive associations with cognitive development, suggesting a role in immune-mediated neuroprotection.
Background:
Chronic exposure to enteropathogens may result in environmental enteric dysfunction (EED), a subclinical condition associated with poor child growth. Growth faltering is strongly associated with poor neurodevelopment, and occurs during sensitive periods of postnatal brain development. We investigated the role of novel EED biomarkers, systemic inflammation, and micronutrient status on neurodevelopment in Tanzanian children.
Methods:
Non-stunted subjects with 6-week and 6-month blood samples and neurodevelopmental measures (n = 107) were included in this study. Samples were tested for biomarkers of gastrointestinal function (citrulline, antibodies to lipopolysaccharide, and flagellin), micronutrient status (iron, retinol binding protein [RBP], and vitamin D), systemic inflammation (C-reactive protein [CRP] and alpha-1-acid glycoprotein), and growth (insulin-like growth factor and insulin-like growth factor binding protein 3).
Results:
Cognitive scores at 15 months were associated with higher concentrations of 6-month anti-lipopolysaccharide IgG (β = 1.95, P = 0.02), anti-flagellin IgA (β = 2.41, P = 0.04), and IgG (β = 2.99, P = 0.009). Higher receptive language scores were positively associated with anti-flagellin IgG (β = 0.95, P = 0.05), and receptive language and gross motor scores were positively associated with citrulline at 6 months (β = 0.09, P = 0.02; β = 0.10, P = 0.03, respectively). Gross motor scores were positively associated with RBP at 6 months (β = 1.70, P = 0.03). Markers of systemic inflammation were not significantly associated with neurodevelopment.
Conclusions:
Plasma citrulline, a marker of gastrointestinal mucosal surface area, and vitamin A status were associated with higher gross motor development scores. Novel markers for EED, but not inflammation, were positively associated with cognitive scores, suggesting a possible mechanistic pathway involving immune response and neuroprotection.
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