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Environ Sci Ecotechnol
2024 Sep 21;21:100415. doi: 10.1016/j.ese.2024.100415.
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Gut pathobiome mediates behavioral and developmental disorders in biotoxin-exposed amphibians.
Pan Q
,
Lv T
,
Xu H
,
Fang H
,
Li M
,
Zhu J
,
Wang Y
,
Fan X
,
Xu P
,
Wang X
,
Wang Q
,
Matsumoto H
,
Wang M
.
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Emerging evidence suggests a link between alterations in the gut microbiome and adverse health outcomes in the hosts exposed to environmental pollutants. Yet, the causal relationships and underlying mechanisms remain largely undefined. Here we show that exposure to biotoxins can affect gut pathobiome assembly in amphibians, which in turn triggers the toxicity of exogenous pollutants. We used Xenopus laevis as a model in this study. Tadpoles exposed to tropolone demonstrated notable developmental impairments and increased locomotor activity, with a reduction in total length by 4.37%-22.48% and an increase in swimming speed by 49.96%-84.83%. Fusobacterium and Cetobacterium are predominant taxa in the gut pathobiome of tropolone-exposed tadpoles. The tropolone-induced developmental and behavioral disorders in the host were mediated by assembly of the gut pathobiome, leading to transcriptome reprogramming. This study not only advances our understanding of the intricate interactions between environmental pollutants, the gut pathobiome, and host health but also emphasizes the potential of the gut pathobiome in mediating the toxicological effects of environmental contaminants.
Fig. 1. Alterations in the density of frogs in paddy fields and development and locomotor activity of the tadpoles upon exposure to biotoxin. a, Regression analysis of the density of the frog population and the biotoxin tropolone (TR) levels in different region-specific rice paddies (Zhejiang, Jiangsu, and Fujian). b–e, Effects of biotoxin tropolone (TR) exposure (TR at 0, 1, 10, and 100 μg L−1) on the total length (b), hindlimb length (c), weight (d), and body length (e) of tadpoles (n = 6 replicates). f–g, Comparison of swimming speed (f) and average activity (g) of tadpoles in the control (CK: TR at 0 μg L−1) and TR-exposed groups (TR at 1, 10, and 100 μg L−1) (n = 18 replicates). h, Visualization of the swimming speed and average activity of tadpoles in the control (TR at 0 μg L−1) and TR-exposed groups (TR at 1, 10, and 100 μg L−1). The whole tracking of tadpoles recorded for 10 min is shown. Different letters with error bars indicate a significant difference based on a one-way analysis of variance (ANOVA) with least significant difference (LSD) test (p < 0.05).
Fig. 2. Characterization of the gut microbial community in the biotoxin-exposed tadpoles. a–b, Analysis of the gut microbial community structure based on alpha (a) and beta (b) diversities. Significant differences were observed between the control (TR at 0 μg L−1) and TR-exposed groups (10 μg L−1). n = 6 replicates. c–d, Comparison of the gut microbial community composition between the control (TR at 0 μg L−1) and TR-exposed group (10 μg L−1) at the phylum (c) and genus (d) levels. n = 6 replicates. c and f indicate unassigned taxa at the taxonomic levels of class and family, respectively. e, UpSet plot of the gut microbial community in the TR-exposed (10 μg L−1) tadpoles at the genus level. The length of the red bars (bottom left) indicates the total size sets of the genera. The blue symbols, connected with blue lines, represent the intersections between the sets and the number. The yellow columns indicate the frequency of these intersections.
Fig. 3. Identification of core taxa of the gut pathobiome in biotoxin-exposed tadpoles. a, Co-occurrence network of the microbial community of the gut pathobiome in the tadpoles upon exposure to 10 μg L−1 TR. Nodes indicate the top 20 most abundant taxa in each treatment, with node size indicating relative abundance. The pie graphs at nodes show the proportion of each treatment, and labels demonstrate taxa. c, o, and f indicate unassigned taxa at the taxonomic levels of class, order, and family, respectively. b, Analysis of the relative abundance of the core taxa of the gut pathobiome in the tadpoles. Student's t-test (two-tailed). ∗p < 0.05, ∗∗p < 0.01. The values are presented as the means ± s.d. (shown as error bars, n = 6).
Fig. 4. Core gut pathobiome taxa responsible for the altered development and locomotor activity of the biotoxin-exposed tadpoles. a, Whole tracking of tadpoles recorded for 10 min is shown for the control group and those transplanted with Fusobacterium or Cetobacterium groups. b–c, Quantitative analysis of the colonization of Fusobacterium (b) and Cetobacterium (c) in the gut of the tadpoles after microbial transplantation. n = 3 replicates. d–g, Effects of the transplantation of Fusobacterium and Cetobacterium on the total length (d), body length (e), hindlimb length (f), and weight (g) of the tadpoles. n = 12 replicates. h–i, Effects of the transplantation of Fusobacterium and Cetobacterium on the swimming speed (h) and average activity (i) of the tadpoles. n = 19 for each. Different letters with error bars indicate a significant difference based on ANOVA with LSD test (p < 0.05).
Fig. 5. Transcriptome reprogramming in the gut pathobiome-harboring tadpoles. a, KEGG pathways with enrichment of genes whose expression was significantly upregulated and downregulated genes in the TR-treated group (10 μg L−1), respectively. The number on the x-axis represents the p values of the enrichment of the KEGG pathway by log10-transformed. The quantity of DEGs in each enrichment pathway is exhibited by the numbers in the plot, and the proportion of all genes is also indicated in the pathway (in parentheses). b, Network analysis of the DEGs associated with the top ten KEGG enrichment pathways. The circle size denotes the relative fold change (log2-transformed) of gene expression. c–d, The colonization of Fusobacterium (c) and Cetobacterium (d) in the gut of the tadpoles upon exposure to 10 μg L−1 TR. n = 3 for replicates. e–f, The expressions of gene cldn2 (e) and fabp3 (f) in the TR-exposed tadpoles (10 μg L−1). n = 5 for replicates. g–h, The gene cldn2 (g) and fabp3 (h) expressions in the tadpoles fed with Fusobacterium and Cetobacterium, respectively. n = 5 for replicates. The values are presented as the means ± s.d. Student's t-test (two-tailed), p values were shown on the top of the paired columns.
Fig. 6. Proposed schematic illustration of developmental and behavioral disorders mediated by biotoxin exposure-driven assembly of the gut pathobiome. The left panel of the figure shows that the biotoxin TR exposure drives the shift of the normal gut microbiome to the pathobiome, which causes developmental and behavioral disorders in the tadpoles. The detailed mechanism underlying the gut pathobiome-mediated disorder is shown in the right panel of the figure. In the reprogrammed transcriptome, a series of genes in the gut–brain axis involving fabp3, cldn2, cldn15, and drd2, differentially express and trigger the excitability of locomotor activity and morphogenesis impairment in tadpoles. The upregulated genes are indicated with red ellipses, and the downregulated genes are denoted with green. The red arrow demonstrates an increased level of dopamine.
