背景:先前的研究强调了循环超长链饱和脂肪酸(VLCSFA)水平与冠心病(CHD)之间的负相关。然而,涉及VLCSFA的复杂链接,肠道菌群,和胆汁酸仍未充分开发。
目的:本研究检查了红细胞VLCSFAs与冠心病发病率的关系,重点研究肠道菌群和粪便胆汁酸的中介作用。
方法:这项为期10年的前瞻性研究包括2383名基线无冠心病的参与者。红细胞VLCSFAs(花生酸[C20:0],二十二烷酸[C22:0],和二十四酸[C24:0])在基线时使用气相色谱法进行测量,并且在三年一次的随访中记录了274起CHD事件。在中期使用16SrRNA测序和UPLC-MS/MS分析了1744名参与者的肠道微生物群和945名参与者的粪便胆汁酸代谢物。
结果:冠心病发病率的多变量校正HR(95CI)C20:0的最低四分位数为0.87(0.61,1.25),C22:0的最低四分位数为0.63(0.42,0.96),C24:0的最低四分位数为0.59(0.41,0.85),总VLCSFA为0.57(0.39,0.83)。具有较高总VLCSFA水平的参与者表现出增加的Holdemanella丰度,科氏杆菌。,RuminoccycaceaeUCG-005和UCG-010,以及LachnospirosaceaeND3007组。这五个属产生的微生物评分(ODMS)占总VLCSFAs-CHD关联的11.52%(Pmediation=0.018)。胆汁酸tauro_α_和tauro_β_胞嘧啶酸(T_α_和T_β_MCA)与ODMS呈负相关,与冠心病呈正相关。发现了糖硫胆酸(GLCA)的相反关联,乙丙胆酸(GDCA)。中介分析表明,GLCA,GDCA,T_α_和T_β_MCA解释56.40%,35.19%,和26.17%的ODMS-CHD关联,分别(Pmediation=0.002、0.008和0.020)。
结论:中国人群中红细胞VLCSFAs升高与冠心病风险呈负相关,肠道菌群和粪便胆汁酸谱可能介导这种关联。确定的微生物群和胆汁酸代谢产物可作为未来研究的潜在干预目标。
背景:NCT03179657。
BACKGROUND: Prior researches have highlighted inverse associations between levels of circulating very-long chain saturated fatty acids (VLCSFAs) and coronary heart disease (CHD). However, the intricate links involving VLCSFAs, gut microbiota, and bile acids remain underexplored.
OBJECTIVE: This study examined the association of erythrocyte VLCSFAs with CHD incidence, focusing on the mediating role of gut microbiota and fecal bile acids.
METHODS: This 10-year prospective study included 2383 participants without CHD at baseline. Erythrocyte VLCSFAs (arachidic acid [C20:0], behenic acid [C22:0], and lignoceric acid [C24:0]) were measured using gas chromatography at baseline and 274 CHD incidents were documented in triennial follow-ups. Gut microbiota in 1744 participants and fecal bile acid metabolites in 945 participants were analyzed using 16S rRNA sequencing and UPLC-MS/MS at middle-term.
RESULTS: The multivariable-adjusted HRs (95%CI) for CHD incidence in highest vs. lowest quartiles were 0.87 (0.61, 1.25) for C20:0, 0.63 (0.42,0.96) for C22:0, 0.59 (0.41,0.85) for C24:0, and 0.57 (0.39, 0.83) for total VLCSFAs. Participants with higher total VLCSFA levels exhibited increased abundances of Holdemanella, Coriobacteriales Incertae Sedis spp., Ruminococcaceae UCG-005 and UCG-010, and Lachnospiraceae ND3007 group. These five genera generated microbial score (ODMS) that accounted for 11.52% of the total VLCSFAs-CHD association (Pmediation =0.018). Bile acids tauro_α_ and tauro_β_muricholic acid (T_α_ and T_β_MCA) were inversely associated with ODMS and positively associated with incident CHD. Opposite associations were found for glycolithocholic acid (GLCA), glycodeoxycholic acid (GDCA). Mediation analyses indicated that GLCA, GDCA, and T_α_ and T_β_MCA explained 56.40%, 35.19%, and 26.17% of the ODMS-CHD association, respectively (Pmediation =0.002, 0.008, and 0.020).
CONCLUSIONS: Elevated erythrocyte VLCSFAs are inversely associated with CHD risk in the Chinese population, with gut microbiota and fecal bile acid profiles potentially mediating this association. The identified microbiota and bile acid metabolites may serve as potential intervention targets in future studies.
BACKGROUND: NCT03179657.