Effect of folpet on hypoglycaemia, intestinal microbiota, and drug resistance genes in mice

Abstract

Background: Folpet is a nonspecific sulfonamide fungicide widely used to protect crops from mildew. However, the in vivo effects of folpet on glucose metabolism homeostasis, gut microbiota, and abundance of drug resistance genes remain unknown. The purpose of this study was to assess the effects of the pesticide, folpet, on glucose metabolism homeostasis, and folpet-induced changes in the intestinal microbiota and resistance genes in mice.

Methods: Mice were orally administered folpet at 0, 1, 10, and 100 mg/kg body weight/day for 5 weeks. Blood sugar levels in mice were measured after 5 weeks of folpet administration. Metagenomic sequencing and drug resistance gene analyses were performed to explore changes in the abundance of gut microbiota members and drug resistance genes in mice after folpet administration. Correlation analysis was performed using metabolomics to explore the relationship between intestinal microbiota, drug resistance genes, and glucose metabolism.

Results: Mice in the folpet group had significantly lower blood glucose levels than those in the control group. The abundance of Atopobium, Libanicoccus, Collinsella, and Parabacteroides in the intestinal microbiota of folpet-treated mice was significantly higher than that in the control group. However, the abundance of Mailhella, Bilophila, Roseburia, and Bacteroides were reduced in folpet-treated mice. Compared with the control group, the abundance of APH6-Ic and AAC6-Ie-APH2-Ia resistance genes in mice treated with folpet significantly increased. The abundance of tetQ, ermE, and BahA resistance genes was significantly reduced after folpet treatment.

Conclusions: Folpet is associated with changes in the abundance of gut microbiota in mice and may also affect the abundance of drug-resistance genes and the regulation of blood glucose levels.

Keywords: Folpet; Intestinal microbiota; Metabolome; Resistance genes.

Fig. 1

Experimental technology roadmap for this study

Fig. 2

Effect of folpet on blood glucose levels and intestinal microbiota in mice. a: Effect of folpet on blood glucose levels in mice after 35 days of exposure. b: Principal coordinates analysis (PCOA) plots of significantly different species. c: Relative abundance cluster heat map of genus. Horizontal is sample information; vertical is species information. The cluster tree on the left is the species cluster tree, and the corresponding value of the heat map in the middle is the Z value of the relative abundance of species in each row after standardized processing. The Z value of a sample in a classification is the value obtained by dividing the difference between the relative abundance of the sample in the classification and the average relative abundance of all samples in the classification by the standard deviation of all samples in the classification. d: Distribution of resistance genes in different dose groups of folpet. e: Comparison of catS gene abundance in four groups of mice. f: Comparison of ermE gene abundance in four groups of mice. g: Comparison of vanRL gene abundance in four groups of mice. * p < 0.05 and ** p < 0.01 calculated using one-way ANOVA followed by the Student-Newman-Keuls test

Fig. 3

Heat map of correlation analysis between different differential resistance genes and differential metabolites. The X-axis shows differential metabolites and the Y-axis shows differential drug resistance genes. The legend on the right shows the correlation coefficient. The redder the color, the stronger the positive correlation. The bluer the color, the stronger the negative correlation. The flatter the ellipse, the higher the absolute value of the correlation coefficient. The Pearson correlation coefficient (r) was used to calculate the correlation coefficient r and p value between the relative abundance of each different bacterial genus and the quantitative value of different metabolites at the genus level. * p < 0.05