Chronic exposure to low doses of Pb induces hepatotoxicity at the physiological, biochemical, and transcriptomic levels of mice.

Lead (Pb), a non-essential heavy metal, is a major global environmental contaminant with serious toxicological consequences. In the present study, the effects on hepatotoxicity of mice with chronic exposure to low doses of Pb were evaluated. While oral exposure to 0.03 or 0.1 mg/L Pb for 15 weeks in male adult mice had no significant effect on body weights, Pb exposure resulted in liver histopathological effects and increase of hepatic activities of aspartate aminotransferase (AST), alanine aminotransferase (ALT), and alkaline phosphatase (ALP). In addition, hepatic reactive oxygen species (ROS) and malondialdehyde (MDA) significantly accumulated after treatment. Conversely, glutathione (GSH) decreased significantly in both 0.03 and 0.1 mg/L Pb-treated groups. Moreover, the hepatic activities of superoxide dismutase 1 (SOD) and catalase (CAT) increased significantly following treatment with 0.1 mg/L Pb for 15 weeks, concomitant with increases in transcriptions of hepatic Sod, Cat, and Gpx. Furthermore, transcriptions of hepatic metallothionein (MT), zinc transporter 5 (Znt5) and copper transporter 1 (Ctr1), and subsequent protein levels were also increased in liver of mice when exposed to 0.1 mg/L Pb for 15 weeks. In addition, the transcriptome data showed that Pb has substantial influence on several pathways, including PPAR signaling pathways, AMPK signaling pathways, fatty acid metabolism, and drug metabolism. Our data suggested that chronic Pb exposure could induce hepatotoxicity at the physiological, biochemical, and transcriptomic levels in mice.

Effects of short term lead exposure on gut microbiota and hepatic metabolism in adult zebrafish.

Lead (Pb) is one of the most prevalent toxic, nonessential heavy metals that has been associated with a wide range of toxic effects in humans and environmental animals. Here, effects of short time exposure to 10 and 30 µg/L Pb on gut microbiota and hepatic metabolism were analyzed in adult male zebrafish. We observed that both 10 and 30 µg/L Pb increased the volume of mucus in the gut. At phylum level, the abundance of α-Proteobacteria decreased significantly and the abundance of Firmicutes increased significantly in the gut when treated with 30 µg/L Pb for 7 days. In addition, the 16S rRNA gene sequencing for V3-V4 region revealed a significant change in the richness and diversity of gut microbiota in 30 µg/L Pb exposed group. A more depth analysis, at the genus level, discovered that 52 gut microbes identified by operational taxonomic unit analysis were changed significantly in 30 µg/L Pb treated group. Based on GC/MS metabolomics analysis, a total of 41 metabolites were significantly altered in 30 µg/L Pb treatment group. These changed metabolites were mainly associated with the pathways of glucose and lipid metabolism, amino acid metabolism, nucleotide metabolism. In addition, we also confirmed that the transcription of some genes related to glycolysis and lipid metabolism, including Gk, Aco, Acc1, Fas, Apo and Dgat, decreased significantly in the liver of zebrafish when exposed to 30 µg/L Pb for 7 days. Our results observed that Pb could cause gut microbiota dysbiosis and hepatic metabolic disorder in zebrafish.

Chronic exposure to low concentrations of lead induces metabolic disorder and dysbiosis of the gut microbiota in mice.

Lead (Pb) is one of the most prevalent toxic, nonessential heavy metals that can contaminate food and water. In this study, effects of chronic exposure to low concentrations of Pb on metabolism and gut microbiota were evaluated in mice. It was observed that exposure of mice to 0.1mg/L Pb, supplied via drinking water, for 15weeks increased hepatic TG and TCH levels. The levels of some key genes related to lipid metabolism in the liver increased significantly in Pb-treated mice. For the gut microbiota, at the phylum level, the relative abundance of Firmicutes and Bacteroidetes changed obviously in the feces and the cecal contents of mice exposed to 0.1mg/L Pb for 15weeks. In addition, 16s rRNA gene sequencing further discovered that Pb exposure affected the structure and richness of the gut microbiota. Moreover, a 1H NMR metabolic analysis unambiguously identified 31 metabolites, and 15 metabolites were noticeably altered in 0.1mg/L Pb-treated mice. Taken together, the data indicate that chronic Pb exposure induces dysbiosis of the gut microbiota and metabolic disorder in mice. CAPSULE: Chronic Pb exposure induces metabolic disorder, dysbiosis of the gut microbiota and hepatic lipid metabolism disorder in mice.

Polystyrene microplastics induce microbiota dysbiosis and inflammation in the gut of adult zebrafish.

Microplastic (MP) are environmental pollutants and have the potential to cause varying degrees of aquatic toxicity. In this study, the effects on gut microbiota of adult male zebrafish exposed for 14 days to 100 and 1000 µg/L of two sizes of polystyrene MP were evaluated. Both 0.5 and 50 µm-diameter spherical polystyrene MP increased the volume of mucus in the gut at a concentration of 1000 µg/L (about 1.456 × 1010 particles/L for 0.5 µm and 1.456 × 104 particles/L for 50 µm). At the phylum level, the abundance of Bacteroidetes and Proteobacteria decreased significantly and the abundance of Firmicutes increased significantly in the gut after 14-day exposure to 1000 µg/L of both sizes of polystyrene MP. In addition, high throughput sequencing of the 16S rRNA gene V3-V4 region revealed a significant change in the richness and diversity of microbiota in the gut of polystyrene MP-exposed zebrafish. A more in depth analysis, at the genus level, revealed that a total of 29 gut microbes identified by operational taxonomic unit (OTU) analysis were significantly changed in both 0.5 and 50 µm-diameter polystyrene MP-treated groups. Moreover, it was observed that 0.5 µm polystyrene MP not only increased mRNA levels of IL1α, IL1ß and IFN but also their protein levels in the gut, indicating that inflammation occurred after polystyrene MP exposure. Our findings suggest that polystyrene MP could induce microbiota dysbiosis and inflammation in the gut of adult zebrafish.

Insights Into a Possible Influence on Gut Microbiota and Intestinal Barrier Function During Chronic Exposure of Mice to Imazalil.

The fungicide imazalil (IMZ) is widely used to prevent and treat fungal diseases in plants and animals. Here, male adult C57BL/6 mice were exposed to 0.1, 0.5, and 2.5 mg/kg body weight IMZ for 2, 5, or 15 weeks. The microbiota in cecal contents and feces changed during chronic IMZ exposure at phylum and genus levels. Sequencing of the V3-V4 region of the bacterial 16S rRNA gene revealed a significant change in the richness of microbiota in cecal contents and feces after exposure to 2.5 mg/kg IMZ for 15 weeks. Operational taxonomic unit (OTU) analysis indicated that 31.1% of cecal OTUs and 14.0% of fecal OTUs changed after IMZ exposure. In addition, chronic IMZ exposure also disturbed the intestinal barrier function of the mice, reducing mucus secretion, decreasing the expression of cystic fibrosis transmembrane conductance regulator (CFTR)-related genes in both the ileum and colon. Molecular docking analysis revealed that key hydrogen bonds were formed by nitrogen atoms of the imidazole bond with Val440 of CFTR and Ala697 of the SLC26 family. Our data suggested that gut microbiota and intestinal barrier were potential toxicological targets of IMZ.