School of Civil and Environmental Engineering, Nanyang Technological University, 50 Nanyang Avenue, Singapore 639798; Nanyang Environment and Water Research Institute, Nanyang Technological University, Singapore 637141.
School of Civil and Environmental Engineering, Nanyang Technological University, 50 Nanyang Avenue, Singapore 639798; Nanyang Environment and Water Research Institute, Nanyang Technological University, Singapore 637141; Singapore Phenome Center, Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore 636921.
J Hazard Mater. 2021 Jul 5;413:125441. doi: 10.1016/j.jhazmat.2021.125441. Epub 2021 Feb 16.
The human gut microbiome is crucial in modulating host health mostly through bacterial metabolites. Chemical exposure is typical external stress which alters its composition and functionality. To date, very few studies have investigated the effect of feeding state on chemical-induced gut microbial metabolic dysregulations. Here, we set up an in vitro human gut microbiome and incorporated a metabolomics approach to investigate the effect of tetracycline (TET) at multiple doses (i.e., 10, 1, and 0.01 mg/L) on gut microbiome under the fed and fasted states. Overall, the metabolome was highly responsive at the fed state with 62 metabolites dysregulated while only 14 were altered at the fasted state under 10 mg/L (clinical TET dose). As expected, nutrient consumption was significantly inhibited under clinical TET dose at the fed state accumulating nutrients such as glutamate and leucine. Interestingly, at the fed state, TET could increase the synthesis of indole and phenyl derivatives including indole-3-aldehyde and hydrocinnamate, while inhibiting indoxyl, tryptamine, and vitamin B production, all of which have host health implications. Furthermore, metabolites like indoxyl and xanthurenic acid were still responsive at 0.01 mg/L (dietary TET dose). Collectively, results demonstrated that the feeding state greatly modulates the chemical-induced gut microbial metabolic alterations.
人类肠道微生物组在调节宿主健康方面起着至关重要的作用，主要通过细菌代谢物来实现。化学物质暴露是改变其组成和功能的典型外部应激源。迄今为止，很少有研究调查喂养状态对化学诱导的肠道微生物代谢失调的影响。在这里，我们建立了一个体外人类肠道微生物组，并采用代谢组学方法来研究在进食和禁食状态下，多种剂量（即 10、1 和 0.01mg/L）的四环素（TET）对肠道微生物组的影响。总的来说，在进食状态下，代谢组对 TET 的反应非常敏感，有 62 种代谢物失调，而在 10mg/L（临床 TET 剂量）下禁食状态下只有 14 种代谢物发生变化。正如预期的那样，在进食状态下，TET 会显著抑制营养物质的消耗，如谷氨酸和亮氨酸。有趣的是，在进食状态下，TET 可以增加吲哚和苯衍生物的合成，包括吲哚-3-醛和肉桂酸，同时抑制吲哚、色胺和维生素 B 的产生，所有这些都对宿主健康有影响。此外，在 0.01mg/L（饮食 TET 剂量）时，代谢物如吲哚和黄尿酸仍然有反应。总的来说，结果表明，喂养状态极大地调节了化学物质诱导的肠道微生物代谢变化。
