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Front Microbiol
2022 Apr 14;13:895383. doi: 10.3389/fmicb.2022.895383.
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Subchronic Toxicity of Microcystin-LR on Young Frogs (Xenopus laevis) and Their Gut Microbiota.
Li J
,
Sun H
,
Wang C
,
Li S
,
Cai Y
.
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Although toxic effects of microcystins (MCs) in mammals and fish have been extensively studied, the effects of MCs on the immune system and gut microbiota of amphibians have not received sufficient attention. As MCs cause general damage to the vertebrate liver and immune system and trigger an inflammatory response, and the gut microbiota is closely related to host metabolism and immunity, we speculated that MCs can cause changes in the immune system and gut microbiota of amphibians. To verify this, we examined the intestinal and liver injury of Xenopus laevis exposed to different microcystin-leucine-arginine (MC-LR) concentrations and the effects on the gut microbiota through high-throughput sequencing of 16S rDNA of the gut microbiota combined with histopathological analysis, enzyme activity determination, and qRT-PCR. Our results showed that MC-LR caused focal infiltration of inflammatory cells and increased the number of T cells and local congestion and vacuolization in X. laevis liver, but reduced the number, density, height, and regularity of villi. These liver and intestinal injuries became more obvious with an increase in MC-LR concentration. MC-LR significantly decreased the activities of malondialdehyde and alkaline phosphatase and the expression of TGF-β in the liver. Moreover, MC-LR significantly altered the gut microbiota of X. laevis. The relative abundance of Firmicutes and Bacteroidetes in high-concentration MC-LR groups was significantly reduced compared to that in low-concentration MC-LR groups, whereas Fusobacteria was significantly enriched. The metabolic gene composition of the gut microbiota in low-concentration MC-LR (≤5 μg/L) groups was significantly different from that in high-concentration MC-LR (≥20 μg/L) groups. These results deepen our understanding of the toxicity of MCs to aquatic organisms and assessment of the ecological risk of MCs in amphibians.
FIGURE 1. Framework shows the experimental design of the study.
FIGURE 2. Liver microstructural changes of Xenopus laevis exposed to different concentrations of MC-LR. (A–E) Indicate the liver micrographs of Xenopus laevis exposed to 0, 1, 5, 20, and 50 μg/L MC-LR, respectively. Red and blue arrows indicate focal infiltration of inflammatory cells and congestion, respectively.
FIGURE 3. Intestinal microstructural changes of Xenopus laevis exposed to different concentrations of MC-LR. (A–E) Indicate the intestinal micrographs of Xenopus laevis exposed to 0, 1, 5, 20, and 50 μg/L MC-LR, respectively. (F) Intestinal villus height. Green and black arrows indicate the gap between the base and villi and vesicular vacuolization, respectively. Numbers after the letter C in the group names indicate MC-LR concentrations. Different letters above boxes indicate significant differences between the groups (P < 0.05).
FIGURE 4. Changes in inflammatory factor gene expression in Xenopus laevis liver under different MC-LR concentration treatments. (A) TNF-α. (B) IL-8. (C) TGF-β. Numbers after the letter C in the group names indicate MC-LR concentrations. Different letters above the bars indicate significant differences between data.
FIGURE 5. Changes in the gut microbiota composition of Xenopus laevis exposed to different MC-LR concentrations. (A) Principal coordinates analysis profile of the gut microbiota composition. (B) Dominant phyla of the gut microbiota. (C) Significant differences of the dominant phyla of the gut microbiota. (D) Cladogram showed the significantly different taxa of the gut microbiota. Numbers after the letter C in the group names indicate MC-LR concentrations. Different letters above boxes indicate significant differences between the groups (P < 0.05).
FIGURE 6. Heatmap profile shows significantly different dominant genera between Xenopus laevis gut microbiota with different environmental MC-LR contents (A) and the correlation of these genera with TNF-α, IL-8, and TGF-β (B). *p < 0.05; **p < 0.01; ***p < 0.001.
FIGURE 7. PCA profile based on metabolic characteristics of Xenopus laevis gut microbiota treated with different MC-LR concentrations. Numbers after the letter C in the group names indicate MC-LR concentrations.
Supplementary Figure 1 | Number of T cells in the liver of Xenopus laevis exposed to different MC-LR concentrations. (A–E) Indicate the immunofluorescence liver micrographs of Xenopus laevis exposed to 0, 1, 5, 20, and 50 μg/L MC-LR, respectively. (F) Number of T cells in Xenopus laevis liver. Different letters above boxes indicate significant differences between the groups (P < 0.05).
Supplementary Figure 2 | Changes in the content of MAD (A), GSH (B), CAT (C), and AKP (D) in the liver of Xenopus laevis under different MC-LR treatments. Numbers after the letter C in the group names indicate MC-LR concentrations. Different letters above the bars indicate significant differences between data.
Supplementary Figure 3 | PCA (A) and heatmap (B) profiles showed changes of genes participating in the lipid metabolism. **p < 0.01; ***p < 0.001.
Supplementary Figure 4 | PCA (A) and heatmap (B) profiles showed changes of genes participating in the carbohydrate metabolism. ***p < 0.001.
Supplementary Figure 5 | PCA (A) and heatmap (B) profiles showed changes of genes participating in the energy metabolism. **p < 0.01; ***p < 0.001.
Supplementary Figure 6 | PCA (A) and heatmap (B) profiles showed changes of genes participating in the glycan metabolism. *p < 0.05; ***p < 0.001.
Supplementary Figure 7 | PCA (A) and heatmap (B) profiles showed changes of genes participating in the amino acid metabolism. ***p < 0.001.
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