Gut Flora-Mediated Metabolic Health, the Risk Produced by Dietary Exposure to Acetamiprid and Tebuconazole

Abstract

The low-level and long-term exposure of pesticides was found to induce metabolic syndrome to mice. Metabolic pathways and mechanisms were investigated by detecting gut flora with metabolites, host circulation, and their interrelations. Results showed that the abundances of flora species and their metabolism were altered, consequently leading to metabolic disorders. A correlation analysis between gut flora and their metabolic profiling further explained these changes and associations. The metabolic profiling of host circulation was also performed to characterize metabolic disorders. The associations of host circulation with gut flora were established via their significantly different metabolites. Alterations to the liver metabolism clarified potential pathways and mechanisms for the disorders. Metabolic disorders were evidently released by dietary and micro-ecological intervention, directly proving that gut flora comprise a vital medium in metabolic health risk caused by pesticide exposure. This work supplied theoretical bases and intervention approaches to body metabolic problems caused by pesticide exposure mediated by gut flora.

Keywords: gut flora; health risk; metabolic syndrome; metabolite; pesticide residues exposure.

Figure 1

Effects of pesticide exposure on mice glucose tolerance (a) and IR (insulin resistance) degree (b); a high value of homeostasis model assessment–IR (HOMA–IR) means high degree of IR) (n = 4). Data are expressed as the mean ± SEM (* p < 0.05; ** p < 0.01). CK: control check group; D: acetamiprid treated group; W: tebuconazole treated group; DW: combination treatment group.

Figure 2

Concentrations of mice serum inflammation factors (n = 4). Data are expressed as the mean ± SEM (* p < 0.05; ** p < 0.01).

Figure 3

HE (hematoxylin eosin) staining of mice liver sections (a) and colon sections (b).

Figure 4

Evolutionary branches in LDA (Linear Discriminant Analysis) effect size (LEfSe) analysis to mice gut flora: (a) LDA score is 3 and (b) LDA score is 4, n = 4).

Figure 5

Associations of gut microbial species with their metabolites (a) and associations of gut microbial metabolites with host circulation metabolites (b). Yellow round nodes: different genera of the intestinal microbiota; blue square nodes: metabolites of the microbiota; red dashed lines: negative correlation; blue solid lines: positive correlation. The width of lines indicates the magnitude of correlations, from −0.7 to −1.0 or from 0.7 to 1.0 (Spearman). The size of nodes represents how many correspondences of this element were involved with another type of element.

Figure 6

Enriched metabolic pathways in mice liver according to the announced metabolites. orange: upregulation; blue: downregulation; ‘all’ represented as D, W, and DW.

Figure 7

Alterations to metabolites of gut flora and serum after intervention to mice circulation (n = 8).

Figure 8

Effects of the interventions on host physiology: (a) IR condition and (b) inflammation condition (n = 4). Data are expressed as the mean ± SEM (* p < 0.05; ** p < 0.01), and the basis of significance analysis was the DW group.