Pentachlorophenol (PCP) was used widely as preservative and biocide and has been banned due to with various harmful effects, such as carcinogenicity and teratogenicity. However, the effects of PCP on colitis induced by dextrose sodium sulfate (DSS) remain largely unknown. Serum metabolomics and gut microbiota were investigated to elucidate the underlying mechanisms. Exposure to 20 μg/L PCP aggravated DSS‐induced body weight loss, colon shortening, severe histological injuries, and upregulation of TNFα, iNOS, IL‐1β, and IL‐6. Serum metabolomics showed that both DSS and PCP could significantly disrupted tryptophan metabolism in normal mice. Interestingly, PCP exposure intensified the disturbance in purine metabolism but not tryptophan metabolism caused by DSS. Quantitative analysis of tryptophan and metabolites further confirmed that PCP exposure significantly increased the serum contents of serotonin, adenine, guanine, guanosine, inosine monophosphate (IMP), inosine, and hypoxanthine in DSS‐treated mice. The overall gut microbial community was significantly modified by PCP and DSS treatment alone. Rikenellaceae_RC9_Gut_group, Colidextribacter, and Desulfovibrio were more abundant in colitis mice following PCP exposure. Further integrative analysis of differential bacteria and purine metabolites highlighted a significant correlation between Desulfovibrio and several purine metabolites, including guanine, guanosine, hypoxanthine, IMP, and inosine. Adenosine ribonucleotides de novo biosynthesis, inosine‐5′‐phosphate biosynthesis I, and urate biosynthesis/inosine 5′‐phosphate degradation pathways were depleted in colitis mice upon PCP treatment. Taken together, PCP exposure delayed the recovery of colitis induced by DSS in association with altered gut microbiota and serum metabolites, which were enriched in tryptophan and purine metabolism.

中文翻译：

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五氯酚暴露会延迟结肠炎的恢复，与肠道微生物群和嘌呤代谢的改变有关


五氯苯酚（PCP）作为防腐剂和杀菌剂被广泛使用，但因其具有致癌、致畸等多种有害作用而被禁用。然而，PCP 对葡萄糖硫酸钠 (DSS) 诱导的结肠炎的影响仍不清楚。研究血清代谢组学和肠道微生物群以阐明潜在机制。暴露于 20 μg/L PCP 会加剧 DSS 引起的体重减轻、结肠缩短、严重组织学损伤以及 TNFα、iNOS、IL-1β 和 IL-6 的上调。血清代谢组学显示 DSS 和 PCP 均能显着扰乱正常小鼠的色氨酸代谢。有趣的是，五氯苯酚暴露加剧了DSS引起的嘌呤代谢紊乱，但没有加剧色氨酸代谢紊乱。色氨酸和代谢物的定量分析进一步证实，五氯苯酚暴露显着增加了 DSS 治疗小鼠血清中血清素、腺嘌呤、鸟嘌呤、鸟苷、肌苷一磷酸 (IMP)、肌苷和次黄嘌呤的含量。单独使用 PCP 和 DSS 治疗即可显着改变整个肠道微生物群落。暴露于五氯苯酚后的结肠炎小鼠中，Rikenellaceae_RC9_Gut_group、Colidextribacter 和 Desulfovibrio 的含量更高。对差异细菌和嘌呤代谢物的进一步综合分析强调了脱硫弧菌和几种嘌呤代谢物（包括鸟嘌呤、鸟苷、次黄嘌呤、IMP 和肌苷）之间的显着相关性。 PCP 治疗后，结肠炎小鼠的腺苷核糖核苷酸从头生物合成、肌苷-5'-磷酸生物合成 I 和尿酸生物合成/肌苷 5'-磷酸降解途径均被耗尽。 总而言之，五氯苯酚暴露延迟了 DSS 诱导的结肠炎的恢复，这与肠道微生物群和血清代谢物的改变有关，这些代谢物富含色氨酸和嘌呤代谢。