The Association Between Blood Bacterial Endotoxin Level And Intestinal Barrier Function In Children With Lead Exposure

Background:Lead（Pb）exposure leads to dysfunction of gastrointestinal mucosa.Studies have shown that Pb entering the digestive tract through the food chain can not only change the composition and diversity of intestinal flora,but also directly damage the tissue structure of intestinal epithelial cells,leading to changes in the permeability of intestinal barrier,making intestinal antigens,microorganisms,and bacterial products（such as endotoxins）enter the tissues or blood.Endotoxin can bind to toll like receptor 4 expressed on the surface of immune cells,activate MyD88 dependent and MyD88 independent signaling pathways,and induce immune cells to express pro-inflammatory cytokines,which causes intestinal inflammation and leads to abdominal pain,diarrhea,dyspepsia,and other clinical symptoms.Children are in the important period of digestive system development and have higher absorption and lower excretion rate of Pb,which makes them more vulnerable to Pb toxicity and results in digestive system dysfunction.Therefore,the research on the effects of environmental Pb exposure on intestinal mucosal barrier function in children has become a hot topic in the field of environmental science and epidemiology.Objectives:This study aimed to investigate the effects of environmental Pb exposure on the intestinal barrier function of children by detecting the levels of plasma endotoxin,peripheral blood inflammatory cells,and blood Pb in children in an electronic-waste（e-waste）area.Methods:From November to December 2018,187 children aged 3-7（4.90±0.87 years old）were recruited,including 82 children in the exposure group（44 boys and 38 girls）and 105 children in the control group（64 boys and 41 girls）.An epidemiological questionnaire was conducted by children’s parents.Physical examination was also conducted for children.Fasting blood was collected from children,and the levels of bacterial endotoxin in plasma were detected by enzyme-linked immunosorbent assay（ELISA）;the counts of leukocyte,neutrophil,and monocyte in peripheral blood were measured by automatic hematology analyzer;the levels of blood Pb were determined by graphite furnace atomic absorption spectrometry.SPSS 22.0 software was used for statistical analysis.The data of normal distribution and skew distribution were expressed by mean±SD and median(P₂₅,P₇₅)respectively and compared by independent sample t-test and Mann Whitney U test between two groups,respectively.Multiple linear regression analyses were used to explore the influencing factors of blood Pb level and evaluate the relationships among plasma endotoxin,inflammatory cells,and blood Pb in children.The figures were drawn with Graph Pad Prism 8.0.Results:The levels of plasma endotoxin in the exposed group were higher than that in the reference group（median:2.24 EU/mL vs.1.85 EU/mL,P<0.05）;the peripheral blood monocyte counts in exposed children were higher than reference children（median:0.43×10⁹/L vs.0.37×10⁹/L,P<0.05）;the blood Pb levels in the exposed group were higher than reference group（median:4.49μg/d L vs.4.11μg/d L,P<0.05）.Multiple linear regression analyses showed that children’s local birth,eating tin cans,father’s work related to e-waste dismantling,and family income were related to children’s blood Pb level.Multivariable adjusted linear regression models showed that after adjustment for confounding factors,the natural logarithm conversion value of neutrophils and monocytes were positively correlated with plasma bacterial endotoxin[B（95%CI）:0.052（0.014,0.090）and 0.043（0.014,0.072）,respectively,P<0.05],and the increased natural logarithm conversion value of plasma endotoxin was correlated with the increased blood Pb level[B（95%CI）=0.069（0.006,0.132）].The height,weight,and body mass index of the exposure group were lower than those of the reference group（P<0.05）.The frequency of diarrhea at least once a month in the exposed group（33.8%）was higher compared with the reference group（16.8%）.Conclusion:Pb exposure in e-waste area interferes with the intestinal mucosal barrier function of children,inducing the increases of plasma bacterial endotoxin and peripheral inflammatory cells,which may affect the normal development of digestive system and body.This is the first study to explore the associations between environmental Pb exposure and intestinal barrier function in children,providing theoretical basis for further exploring the mechanism of Pb exposure on intestinal barrier function in children.