Universitat Rovira i Virgili, Departament de Bioquimica i Biotecnologia, Nutrigenomics Research Group, 43007, Tarragona, Spain.
Clin Nutr. 2021 Apr;40(4):1475-1486. doi: 10.1016/j.clnu.2021.02.035. Epub 2021 Feb 26.
BACKGROUND & AIMS: Oxylipins (OXLs) are bioactive lipid metabolites derived from polyunsaturated fatty acids (PUFAs) which act as signaling molecules and are involved in inflammatory processes such as those that occur in obesity. On the other hand, gut microbiota plays an essential role in regulating inflammatory responses. However, little is known about the potential impact of gut bacteria on OXLs metabolism. Thus, the objective of this study was to investigate the effect of gut microbiota dysbiosis on plasma oxylipins profile in healthy and diet-induced obese animals.
Eight-week-old male Wistar rats were fed with either a standard or cafeteria diet (CAF) for 5 weeks and administered an antibiotic cocktail (ABX) in the drinking water (Ampicillin: 1 g/ml, Vancomycin: 0.5 g/ml, Imipenem: 0.25 g/ml) for the last 2 weeks in order to induce gut microbiota dysbiosis. Metabolomics analysis of OXLs in plasma was performed by HPLC-MS analysis. No antibiotic treated animals were included as controls.
Plasma OXLs profile was significantly altered due to both CAF feeding and ABX administration. ABX effect was more pronounced under obesogenic conditions. Several significant correlations between different bacteria taxa and these lipid mediators were observed. Among these, the positive correlation of Proteobacteria with LTB4, a proinflammatory OXL involved in obesity-related disorders, was especially remarkable.
Gut microbiota plays a key role in regulating these lipid metabolites and, therefore, affecting oxylipins-mediated inflammatory processes. These results are the first evidence to our knowledge of gut microbiota impact on OXLs metabolism. Moreover, this can set the basis for developing new obesity markers based on OXLs and gut microbiota profiles.
氧化脂类（OXLs）是源自多不饱和脂肪酸（PUFAs）的生物活性脂质代谢物，作为信号分子，参与肥胖等炎症过程。另一方面，肠道微生物群在调节炎症反应中起着至关重要的作用。然而，人们对肠道细菌对 OXLs 代谢的潜在影响知之甚少。因此，本研究的目的是研究肠道微生物失调对健康和饮食诱导肥胖动物血浆氧化脂类谱的影响。
8 周龄雄性 Wistar 大鼠分别用标准或自助餐厅饮食（CAF）喂养 5 周，并在饮用水中给予抗生素混合物（ABX）（氨苄西林：1 g/ml，万古霉素：0.5 g/ml，亚胺培南：0.25 g/ml），以在最后 2 周诱导肠道微生物失调。通过 HPLC-MS 分析对血浆中 OXLs 的代谢组学分析。未用抗生素处理的动物作为对照。
由于 CAF 喂养和 ABX 给药，血浆 OXLs 谱发生了显著改变。ABX 效应在肥胖条件下更为明显。观察到不同细菌分类群与这些脂质介质之间存在许多显著相关性。其中，变形菌与 LTB4 的正相关尤其显著，LTB4 是一种参与肥胖相关疾病的促炎 OXL。
肠道微生物群在调节这些脂质代谢物方面起着关键作用，从而影响氧化脂类介导的炎症过程。这些结果是我们首次证明肠道微生物群对 OXLs 代谢的影响。此外，这可以为基于 OXLs 和肠道微生物群谱开发新的肥胖标志物奠定基础。
