Fig. 4: Bacterial metabolites responsible for the mitigation of AgNP reproductive toxicity. | Nature Communications

Fig. 4: Bacterial metabolites responsible for the mitigation of AgNP reproductive toxicity.

From: Gut microbiota mitigate the reproductive toxicity of silver nanoparticles through thiamine-derived metabolites

Fig. 4

a Spearman correlation analysis revealed significant associations between the reproduction of C. elegans colonized with different bacteria and exposed to 17.6 μg/m2 of AgNPs in toxicity tests and the MS peak areas of six metabolites (MTE—4-methyl-5-thiazoleethanol, ThMP—thiamine monophosphate, 4-PA—4-pyridoxic acid, spermidine, thiamine, and Cys-Gly—cysteinylglycine) from four bacterial species. b Reproduction of GF nematodes exposed to 17.6 μg/m2 of AgNPs in the presence of the six metabolites in (a) at concentrations of 0, 0.176, 1.76, and 17.6 μg/m2. MTE: 1.76 vs 0: p = 1.99 × 10−4; ThMP: 17.6 vs 0: p = 3.54 × 10−3; Cys-Gly: 17.6 vs 0: p = 9.85 × 10−4. c Gene expression in GF nematodes exposed to 17.6 μg/m2 of AgNPs and supplemented or not with 1.76 μg/m2 of MTE, 17.6 μg/m2 of ThMP, or 17.6 μg/m2 of thiamine. A control group (Ctrl), untreated with AgNPs, MTE, ThMP, or thiamine was also included. The genes analyzed are pivotal to the adverse outcome pathways mediating AgNP reproductive toxicity. bli-3: Ctrl vs GF: p = 2.03 × 10−2; pmk-1: Ctrl vs GF: p = 1.08 × 10−6, MTE vs GF: p = 1.39 × 10−4, ThMP vs GF: p = 3.89 × 10−2; ndx-4: Ctrl vs GF: p = 5.83 × 10−6; nth-1: Ctrl vs GF: p = 3.82 ×  10−4, ThMP vs GF: p = 2.44 × 10−2; hif-1: ThMP vs GF: p = 1.91 × 10−10, Thiamine vs GF: p = 2.64 × 10−3; fmo-2: Ctrl vs GF: p = 2.0 × 10−5, ThMP vs GF: p = 3.59 × 10−3; Thiamine vs GF: p = 1.14 × 10−3; ced-13: Ctrl vs GF: p = 1.61 × 10−2, MTE vs GF: p = 2.47 × 10−2; sod-3: Thiamine vs GF: p = 5.05 × 10−3. d Metabolic pathway enrichment in GF nematodes exposed to 17.6 μg/m2 of AgNPs in the presence of 1.76 μg/m2 of MTE, 17.6 μg/m2 of ThMP, or 17.6 μg/m2 of thiamine. For comparison, the pathways enriched in AgNP-exposed nematodes colonized by P. mendocina (P.m.) are also presented. One-way ANOVA was performed in (b, c) with two-sided comparisons, and post hoc comparisons were corrected using Dunnett’s method. The hypergeometric test was used in (d), which defaults to one-sided testing and employs the Bonferroni correction for multiple comparisons. *p < 0.05, **p < 0.01. Data in (b, c) are presented as the mean ± standard deviation (n = 3 independent experiments).

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