Department of Anesthesiology, Peking University Shenzhen Hospital, Shenzhen, 518036, China; Department of Respiratory and Critical Care Medicine, The Second Clinical Medical College (Shenzhen People's Hospital) of Jinan University, Shenzhen Institute of Respiratory Diseases, Shenzhen, China.
Department of Infectious Disease, The Second Clinical Medical College (Shenzhen People's Hospital), Jinan University, No. 1017 Dongmen North Road, Shenzhen, China.
Environ Pollut. 2021 Jan 1;268(Pt B):115738. doi: 10.1016/j.envpol.2020.115738. Epub 2020 Sep 28.
Phenanthrene (Phe), among the most ubiquitous polycyclic aromatic hydrocarbons (PAHs) existing in nature and foodstuffs, has severe effects on hepatic lipids metabolism. However, the detailed mechanism involved is still unknown. For environmental chemicals can disturb intestinal microbiota, which plays a vital role in lipids metabolism, we hypothesized that oral exposure to Phe may disrupt the intestinal microbiota, leading to the induction of an abnormal inflammatory response and lipid metabolism dysfunction. Herein, male mice were orally exposed to Phe (0.05, 0.5 and 5 mg/kg/2d) for ten weeks and the results showed that long term exposure to Phe induced significant alteration in relative Bacteroidetes, Firmicutes and Proteobacteria abundance in male mice. Histopathological anomalies, and significantly increased hepatic levels of free fatty acid, cholesterol and triglyceride were observed as well. The expression of hepatic proteins linked to lipid metabolism including peroxisome proliferator-activated receptors (PPARs), liver X receptor β (LXRβ) and retinoid X receptors (RXRs) were upregulated. The importance of the gut microbiota in Phe-altered lipid metabolism disorder was further confirmed by fecal microbiota transplantation (FMT). FMT intervention boosted microbial diversity and attenuated Phe-induced elevation in liver somatic index and hepatic total lipids levels. These results demonstrated that environmental-level Phe altered the composition of gastrointestinal bacteria and subsequently induced hepatic lipid metabolism disorder. These results would be helpful for understanding the health risk posed by Phe.
菲（Phe）是自然界和食物中最普遍存在的多环芳烃（PAHs）之一，对肝脏脂质代谢有严重影响。然而，其涉及的详细机制尚不清楚。由于环境化学物质会干扰在脂质代谢中起重要作用的肠道微生物群，我们假设口服暴露于 Phe 可能会破坏肠道微生物群，导致异常炎症反应和脂质代谢功能障碍的诱导。在此，雄性小鼠经口暴露于 Phe（0.05、0.5 和 5mg/kg/2d）十周，结果表明，长期暴露于 Phe 可诱导雄性小鼠肠道拟杆菌门、厚壁菌门和变形菌门的相对丰度发生显著变化。还观察到组织病理学异常以及肝游离脂肪酸、胆固醇和甘油三酯水平显著升高。与脂质代谢相关的肝蛋白的表达，包括过氧化物酶体增殖物激活受体（PPARs）、肝 X 受体β（LXRβ）和视黄醇 X 受体（RXRs），上调。粪便微生物群移植（FMT）进一步证实了肠道微生物群在 Phe 改变的脂质代谢紊乱中的重要性。FMT 干预可提高微生物多样性，并减弱 Phe 诱导的肝体指数和肝总脂质水平升高。这些结果表明，环境水平的 Phe 改变了胃肠道细菌的组成，随后诱导了肝脂质代谢紊乱。这些结果有助于了解 Phe 带来的健康风险。
