Down-regulation of serum SIRT6 levels is associated with an increased risk of chronic intestinal inflammation in children exposed to airborne particulate matter and polycyclic aromatic hydrocarbons from e-waste

Informal e-waste recycling releases airborne particulate matter (PM) and polycyclic aromatic hydrocarbons (PAHs), which are linked to intestinal barrier dysfunction and chronic inflammation. SIRT6, a histone deacetylase, modulates inflammation by suppressing NF-κB signaling, but its role in mitigating e-waste pollutant-induced childhood enteritis remains unclear. This cross-sectional study evaluated associations between e-waste exposure, intestinal inflammation, and SIRT6 levels in 217 preschool children from Guiyu (e-waste-exposed, n = 109) and Haojiang (non-exposed control, n = 108), China. Airborne pollutant exposure was quantified via the Air Quality Composite Index (AQCI) and average daily dose (ADD) for PM_2.5, PM₁₀, NO₂, and SO₂. Urinary PAH metabolites, serum SIRT6, inflammatory markers (GM-CSF, IL-10), and intestinal barrier biomarkers (IFABP, endotoxins) were measured using GC/MS, ELISA, and automated hematology analyzers. Dietary patterns, residential proximity to e-waste sites, and gastrointestinal symptoms were assessed via questionnaires. Statistical analyses included Spearman correlations, multivariate regression, and Bayesian kernel machine regression (BKMR) to evaluate pollutant effects on SIRT6 and inflammation. Children residing in Guiyu demonstrated significantly elevated urinary PAH metabolites and higher ADD of PM_2.5, PM₁₀, NO₂, and SO₂ compared to reference populations. Concurrently, this cohort exhibited biomarker patterns indicative of intestinal barrier compromise, including elevated IFABP and systemic endotoxin levels. Serum analyses revealed quantifiable reductions in SIRT6 and GM-CSF concentrations, accompanied by increased circulating monocytes and lymphocytes. Notably, BKMR modeling identified non-linear U-shaped associations between mixed PM/PAH exposures and progressive SIRT6 suppression. Proximity to e-waste sites, lower parental education, and poor household ventilation correlated with heightened pollutant exposure and gastrointestinal morbidity. Chronic e-waste exposure was associated with decreased serum SIRT6 levels and concurrent elevation of intestinal inflammatory biomarkers in children. Our cross-sectional analysis revealed significant correlations between SIRT6 downregulation, altered GM-CSF/IL-10 signaling profiles, and disrupted macrophage-Treg homeostasis. These observational findings suggest SIRT6 may serve as a potential protective mediator in environmental enteritis.