人类肠道微生物组对主要通过细菌代谢物调节宿主健康至关重要。化学暴露是典型的外部应力,会改变其组成和功能。迄今为止,很少有研究研究摄食状态对化学诱导的肠道微生物代谢失调的影响。这里,我们建立了一个体外人类肠道微生物组,并结合了代谢组学方法来研究多剂量四环素(TET)的作用(即,10、1和0.01mg/L)在进食和禁食状态下的肠道微生物组。总的来说,代谢组在进食状态下具有高度响应性,有62种代谢产物失调,而在10mg/L(临床TET剂量)下,只有14种代谢产物在禁食状态下发生改变.不出所料,在进食状态下积累诸如谷氨酸和亮氨酸的营养素的临床TET剂量下,营养素消耗被显着抑制。有趣的是,在美联储,TET可以增加吲哚和苯基衍生物的合成,包括吲哚-3-醛和氢化肉桂酸酯,同时抑制吲哚酚,色胺,和维生素B的生产,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,吲哚酚和黄苏烯酸等代谢物仍有反应.总的来说,结果表明,摄食状态极大地调节了化学诱导的肠道微生物代谢变化。
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.