2,6-dichloro-1,4-benzoquinone (DCBQ), as an emerging water disinfection byproducts (DBPs), has posed potential risks via the digestion system. However, little is known about the toxicity of DCBQ on the gut microbiome, which plays a critical role on human health. This study has comprehensively investigated the impact of DCBQ on the intestinal microbiome, metabolic functions, and immunity after the mice orally exposure to DCBQ at the concentration of 31.25, 62.5 and 125 mg/kg body weight for 28 days. Our results indicated that DCBQ exposure has perturbed the balance between T helper (Th) 1 mediated pro-inflammatory response and Th2 mediated anti-inflammatory response in mice, especially inducing the activation of immune system toward a Th2 response. DCBQ group has induced gut microbiota dysbiosis, and at phylum level, Proteobacteria was relatively less abundant compared with that in the control group. Furthermore, DCBQ exposure has dramatically perturbed metabolites profiles which were involved in 28 metabolic pathways, such as amino acids biosynthesis and metabolism, lipid metabolism. In particular, the altered gut microbiota showed strong correlations with both the altered metabolites and the altered immunological variables after DCBQ exposure. This study provides evidence on the adverse effects and mechanisms of water disinfection byproduct DCBQ through the interaction of immune-microbiome-metabolome, highlighting the importance to assess DBPs-associated risks.

2,6-二氯-1,4-苯醌（DCBQ）作为一种新兴的水消毒副产物（DBPs），通过消化系统存在潜在风险。然而，关于 DCBQ 对肠道微生物组的毒性知之甚少，这对人类健康起着至关重要的作用。本研究全面调查了小鼠口服31.25、62.5和125 mg/kg体重DCBQ 28天后，DCBQ对肠道菌群、代谢功能和免疫力的影响。我们的研究结果表明，DCBQ 暴露扰乱了小鼠 T 辅助 (Th) 1 介导的促炎反应和 Th2 介导的抗炎反应之间的平衡，特别是诱导免疫系统向 Th2 反应激活。DCBQ 组已诱导肠道菌群失调，在门水平，与对照组相比，变形菌的数量相对较少。此外，DCBQ 暴露极大地扰乱了代谢物谱，这些代谢物谱涉及 28 种代谢途径，例如氨基酸生物合成和代谢、脂质代谢。特别是，改变的肠道微生物群与 DCBQ 暴露后改变的代谢物和改变的免疫学变量都显示出强烈的相关性。该研究通过免疫-微生物组-代谢组的相互作用提供了水消毒副产物 DCBQ 的不利影响和机制的证据，强调了评估 DBP 相关风险的重要性。