Zhang Boya, Fan Xingpei, Du Haining, Zhao Meimei, Zhang Ziyi, Zhu Ruijiao, He Bo, Zhang Yuxia, Li Xiaoyan, Li Jiaxin, Gu Ning
School of Life Science and Technology, Harbin Institute of Technology, Harbin 150001, China.
State Key Laboratory of Urban Water Resource and Environment, Harbin Institute of Technology, Harbin 150006, China.
ACS Nano. 2023 Mar 28;17(6):6081-6094. doi: 10.1021/acsnano.3c01005. Epub 2023 Mar 10.
Foodborne carbon dots (CDs), an emerging food nanocontaminant, are an increasing risk factor for metabolic toxicity in mammals. Here, we report that chronic CD exposure induced glucose metabolism disorders via disruption of the gut-liver axis in mice. 16s rRNA analysis demonstrated that CD exposure decreased the abundance of beneficial bacteria (Bacteroides, Coprococcus, and S24-7) and increased the abundance of harmful bacteria (Proteobacteria, Oscillospira, Desulfovibrionaceae, and Ruminococcaceae), as well as increased the Firmicutes/Bacteroidetes ratio. Mechanistically, the increased pro-inflammatory bacteria release the endotoxin lipopolysaccharide, which induces an intestinal inflammation and disruption of the intestinal mucus layer, activating systemic inflammation and inducing hepatic insulin resistance in mice via the TLR4/NFκB/MAPK signaling pathway. Furthermore, these changes were almost completely reversed by probiotics. Fecal microbiota transplantation from CD-exposed mice induced glucose intolerance, damaged liver function, intestinal mucus layer injury, hepatic inflammation, and insulin resistance in the recipient mice. However, microbiota-depleted mice exposed to CDs had normal levels of these biomarkers consistent with microbiota-depleted control mice, which revealed that gut microbiota dysbiosis contributes to CD-induced inflammation-mediated insulin resistance. Together, our findings revealed that gut microbiota dysbiosis contributes to CD-induced inflammation-mediated insulin resistance and attempted to elucidate the specific underlying mechanism. Furthermore, we emphasized the importance of assessing the hazards associated with foodborne CDs.
食源性病原体碳点（CDs）作为一种新兴的食品纳米污染物，正成为哺乳动物代谢毒性的一个日益严重的风险因素。在此，我们报告慢性CD暴露通过破坏小鼠的肠-肝轴诱导葡萄糖代谢紊乱。16s rRNA分析表明，CD暴露降低了有益菌（拟杆菌属、粪球菌属和S24-7）的丰度，增加了有害菌（变形菌门、颤螺菌属、脱硫弧菌科和瘤胃球菌科）的丰度，同时也增加了厚壁菌门与拟杆菌门的比例。从机制上来说，促炎细菌增加会释放内毒素脂多糖，从而引发肠道炎症并破坏肠道黏液层，通过TLR4/NFκB/MAPK信号通路激活全身炎症并诱导小鼠肝脏产生胰岛素抵抗。此外，这些变化几乎被益生菌完全逆转。将暴露于CD的小鼠的粪便微生物群移植到受体小鼠中会导致葡萄糖不耐受、肝功能受损、肠道黏液层损伤、肝脏炎症和胰岛素抵抗。然而，暴露于CD的微生物群耗竭小鼠这些生物标志物的水平与微生物群耗竭的对照小鼠一致，均处于正常水平，这表明肠道微生物群失调会导致CD诱导的炎症介导的胰岛素抵抗。总之，我们的研究结果表明肠道微生物群失调会导致CD诱导的炎症介导的胰岛素抵抗，并试图阐明其具体的潜在机制。此外，我们强调了评估与食源性CD相关危害的重要性。
