State Key Laboratory of Freshwater Ecology and Biotechnology, Institute of Hydrobiology, Chinese Academy of Sciences, Wuhan 430072, China.
College of Life Sciences, Henan Normal University, Xinxiang, Henan 453007, China.
Environ Pollut. 2019 Dec;255(Pt 3):113357. doi: 10.1016/j.envpol.2019.113357. Epub 2019 Oct 7.
Gut microbiota is of critical importance to host health. Aryl hydrocarbon receptor (AhR) is found to be closely involved in the regulation of gut microbial dynamics. However, it is still not clear how AhR signaling shapes the gut microbiota. In the present study, adult zebrafish were acutely exposed to an AhR antagonist (CH223191), an AhR agonist (polychlorinated biphenyl 126; PCB126) or their combination for 7 d. Overall intestinal health and gut microbial community were temporally monitored (1 d, 3 d and 7 d) and inter-compared among different groups. The results showed that single exposure to PCB126 significantly disrupted the overall health of intestines (i.e., neural signaling, inflammation, epithelial barrier integrity, oxidative stress). However, CH223191 failed to inhibit but enhanced the physiological toxicities of PCB126, implying the involvement of extra mechanisms rather than AhR in the regulation of intestinal physiological activities. Dysbiosis of gut microbiota was also caused by PCB126 over time as a function of sex. It is intriguing that CH223191 successfully abolished the holistic effects of dioxin on gut microbiota, which inferred that growth of gut microbes was directly controlled by AhR activation without the involvement of host feedback modulation. When coming to detailed alterations at certain taxon, both antagonistic and synergistic interactions existed between CH223191 and dioxin, depending on fish sex, exposure duration and bacterial species. Correlation analysis found that gut inflammation was positively associated with pathogenic Legionella bacteria, but was negatively associated with epithelial barrier integrity, suggesting that integral intestinal epithelial barrier can prevent the influx of pathogenic bacteria to induce inflammatory response. Overall, this study has deciphered, for the first time, the direct regulative effects of AhR activity on gut microbiota. Future research is warranted to elucidate the specific mechanisms of AhR action on certain bacterial population.
肠道微生物群对宿主健康至关重要。芳基烃受体（AhR）被发现密切参与肠道微生物动态的调节。然而，AhR 信号如何塑造肠道微生物群仍不清楚。在本研究中，成年斑马鱼急性暴露于 AhR 拮抗剂（CH223191）、AhR 激动剂（多氯联苯 126；PCB126）或它们的组合中 7 天。总体肠道健康和肠道微生物群落被进行了时间监测（1 天、3 天和 7 天），并在不同组之间进行了比较。结果表明，单一暴露于 PCB126 显著破坏了肠道的整体健康（即神经信号、炎症、上皮屏障完整性、氧化应激）。然而，CH223191 未能抑制而是增强了 PCB126 的生理毒性，这意味着除了 AhR 之外，还有其他机制参与了肠道生理活动的调节。随着时间的推移，肠道微生物群的失调也因性别而异。有趣的是，CH223191 成功地消除了二恶英对肠道微生物群的整体影响，这表明肠道微生物的生长直接受到 AhR 激活的控制，而不涉及宿主的反馈调节。当涉及到特定分类群的详细变化时，CH223191 与二恶英之间存在拮抗和协同相互作用，这取决于鱼类的性别、暴露时间和细菌种类。相关性分析发现，肠道炎症与致病性军团菌呈正相关，但与上皮屏障完整性呈负相关，这表明完整的肠道上皮屏障可以防止致病菌的内流，从而引起炎症反应。总的来说，这项研究首次揭示了 AhR 活性对肠道微生物群的直接调节作用。未来的研究需要阐明 AhR 对某些细菌群体作用的具体机制。
