Effects of Diethyl Phosphate, a Non-Specific Metabolite of Organophosphorus Pesticides, on Serum Lipid, Hormones, Inflammation, and Gut Microbiota

Abstract

Organophosphorus pesticides (OPs) can be metabolized to diethyl phosphate (DEP) in the gut environment, which may affect the immune and endocrine systems and the microbiota. Correlations between OPs and diseases have been established by epidemiological studies, mainly based on the contents of their metabolites, including DEP, in the serum or urine. However, the effects of DEP require further study. Therefore, in this study, adult male rats were exposed to 0.08 or 0.13 mg/kg DEP for 20 weeks. Serum levels of hormones, lipids, and inflammatory cytokines as well as gut microbiota were measured. DEP significantly enriched opportunistic pathogens, including Paraprevotella, Parabacteroides, Alloprevotella, and Helicobacter, leading to a decrease in interleukin-6 (IL-6). Exposure to the high dose of DEP enriched the butyrate-producing genera, Alloprevotella and Intestinimonas, leading to an increase in estradiol and a resulting decrease in total triglycerides (TGs) and low-density lipoprotein cholesterol (LDL-C); meanwhile, DEP-induced increases in peptide tyrosine‒tyrosine (PYY) and ghrelin were attributed to the enrichment of short-chain fatty acid-producing Clostridium sensu stricto 1 and Lactobacillus. These findings indicate that measuring the effects of DEP is not a proxy for measuring the effects of its parent compounds.

Keywords: DNA sequencing; endocrine system; hormones; inflammation; microbiome.

Figure 1

Body weight (A) and food consumption (B) of rats during the experimental period. Data are expressed as mean ± standard deviation. Control, vehicle treatment; a low dose of diethyl phosphate (DEP-L), 0.08 mg/kg body weight; a high dose of diethyl phosphate (DEP-H), 0.13 mg/kg body weight. The symbol * indicates significant differences from the corresponding control group at the confidence interval of 95%.

Figure 2

Inhibition in the activity of acetylcholin esterase (AChE) in the serum of rats exposed to DEP compared with the control group. The inhibition rate was calculated as the percentage of the activity value in DEP groups divided by the value in the control group.

Figure 3

Serum levels of sex hormones (A) and adrenal hormones (B) and blood lipid profiles (C) in rats. The symbol * indicates significant differences from the corresponding control group at the confidence interval of 95%. LH, luteinizing hormone; FSH, follicle-stimulating hormone; ACTH, adrenocorticotropic hormone; TC, total cholesterol; HDL-C, high density lipoprotein cholesterol.

Figure 4

Serum levels of gut hormones (A) and inflammatory cytokines (B) in rats. The symbol * indicates significant differences from the corresponding control group at the confidence interval of 95%. PP, pancreatic polypeptide; GLP-1, glucagon-like peptide 1; GIP, gastric inhibitory polypeptide; PYY, peptide tyrosine tyrosine; IL-6, interleukin 6; MCP-1, monocyte chemoattractant protein 1; TNF-α, tumor necrosis factor alpha.

Figure 5

Altered gut microbiome community structure induced by DEP. (A) Principal coordinate analysis (PCoA) plots of gut microbiome patterns (circles, control; triangles, DEP-L; diamonds, DEP-H). The percentage of variation explained by the plotted principal coordinates is indicated on the axes. (B, C) Significantly altered genera analyzed by the Student’s t-test in the DEP-L and DEP-H groups, respectively, compared with the control.