PDF(Pubmed)
Abstract：
(1) Background: Dyslipidemia represents a major risk factor for atherosclerosis-driven cardiovascular disease. Emerging evidence suggests a close relationship between cholesterol metabolism and gut microbiota. Recently, we demonstrated that the short-chain fatty acid (SCFA) propionate (PA) reduces serum cholesterol levels through an immunomodulatory mechanism. Here, we investigated the effects of oral PA supplementation on the human serum metabolome and analyzed changes in the serum metabolome in relation to the cholesterol-lowering properties of PA. (2) Methods: The serum metabolome of patients supplemented with either placebo or propionate orally for 8 weeks was assessed using a combination of flow injection analysis-tandem (FIA-MS/MS) as well as liquid chromatography (LC-MS/MS) and mass spectrometry using a targeted metabolomics kit (MxP®Quant 500 kit: BIOCRATES Life Sciences AG, Innsbruck, Austria). A total of 431 metabolites were employed for further investigation in this study. (3) Results: We observed a significant increase in distinct bile acids (GCDCA: fold change = 1.41, DCA: fold change = 1.39, GUDCA: fold change = 1.51) following PA supplementation over the study period, with the secondary bile acid DCA displaying a significant negative correlation with the serum cholesterol levels. (4) Conclusions: Oral supplementation with PA modulates the serum metabolome with a particular impact on the circulatory bile acid profile. Since cholesterol and bile acid metabolism are interconnected, the elevation of the secondary bile acid DCA may contribute to the cholesterol-lowering effect of PA.
摘要：
（1）背景：血脂异常是动脉粥样硬化导致的心血管疾病的主要危险因素。新出现的证据表明，胆固醇代谢与肠道微生物群之间存在密切关系。最近,我们证明短链脂肪酸(SCFA)丙酸(PA)通过免疫调节机制降低血清胆固醇水平.这里,我们研究了口服补充PA对人血清代谢组的影响,并分析了与PA降胆固醇特性相关的血清代谢组变化.（2）方法：使用流动注射串联分析（FIA-MS/MS）以及液相色谱（LC-MS/MS）的组合评估口服安慰剂或丙酸盐口服8周的患者的血清代谢组使用靶向代谢组学试剂盒（MxP®Quant500试剂盒：BIOCRATESLifeSciencesAG，因斯布鲁克,奥地利)。在本研究中使用总共431种代谢物进行进一步研究。（3）结果：在研究期间补充PA后，我们观察到不同胆汁酸的显着增加（GCDCA：倍数变化=1.41，DCA：倍数变化=1.39，GUDCA：倍数变化=1.51）。次级胆汁酸DCA与血清胆固醇水平呈显著负相关。(4)结论:口服补充PA调节血清代谢组,对循环胆汁酸谱具有特别的影响。因为胆固醇和胆汁酸代谢是相互关联的，次级胆汁酸DCA的升高可能有助于PA的降胆固醇作用。
