较高的吲哚代谢物以及与吲哚丙酸产生相关的肠道菌群可能有助于改善心血管健康

Indole derivatives and their associated microbial genera are associated with the 1-year changes in cardiometabolic risk markers in Chinese adults

吲哚衍生物及其相关的微生物属与中国成年人1年心脏代谢风险指标的变化相关

Authors: Yutong Pan, Yamin Li, Zhaohong Peng, Xiaoyu Zhang, Shu Ye, Na Chen, Zhuang Zhang, Wanshui Yang

Source: Nutrition Journal

DOI: 10.1186/s12937-024-01067-4

Abstract

Background: Although emerging evidence suggests that indole derivatives, microbial metabolites of tryptophan, may improve cardiometabolic health, the effective metabolites remain unclear. Also, the gut microbiota that involved in producing indole derivatives are less studied. We identified microbial taxa that can predict serum concentrations of the key indole metabolite indole-3-propionic acid (IPA) at population level and investigated the associations of indole derivatives and IPA-predicting microbial genera with cardiometabolic risk markers.

Methods: In a cohort of 318 community-dwelling adults, serum indole metabolites and fecal microbiota (16S ribosomal RNA) were measured at baseline. Total cholesterol (TC), triglyceride (TG), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), and fasting blood glucose were repeatedly measured at baseline and again after 1 year. Brachial-ankle pulse wave velocity (baPWV) and ankle-brachial index (ABI) were measured after 1 year. The association between indole derivatives and the 1-year changes in blood lipids and glucose, and association of indole derivatives with baPWV and ABI were investigated using linear regression models.

Results: Each 1 μmol/L increase in indole-3-acetic acid (IAA) levels was associated with 5.08% (P = 0.046) decrease in LDL-C. IPA levels were inversely associated with baPWV (percentage difference = -1.32%, P = 0.036). Per 1 μmol/L increase in Indole-3-aldehyde (IAld) levels was associated with 1.91% (P = 0.004) decrease in TC and 0.58% (P = 0.019) increase in ABI, but 1.79% decrease in HDL-C with borderline significance (P = 0.050). We identified 18 bacterial genera whose relative abundance was positively associated with serum IPA concentrations (P_FDR < 0.05) and constructed a microbial score to reflect the overall IPA-producing potential. This score was inversely associated with baPWV (percentage difference = -0.48%, P = 0.007).

Conclusions: Our results suggest that IAA, IPA, IAld, and IPA-predicting microbial score are favorably associated with several cardiometabolic risk markers, although IAld may decrease HDL-C levels.

摘要

背景：尽管新兴证据表明，吲哚衍生物（色氨酸的微生物代谢产物）可能改善心脏代谢健康，但其具体的有效代谢物尚不确定。此外，与吲哚衍生物产生相关的肠道菌群研究较少。本研究旨在确定预测关键吲哚衍生物吲哚-3-丙酸（indole-3-propionic acid，IPA）的微生物种类，并评估吲哚衍生物及预测IPA微生物属与心脏代谢风险指标之间的关联。

方法：本研究纳入318名社区成年人，基线时测量了血清吲哚代谢物和粪便微生物（16S rRNA测序）。基线及1年后分别重复测量了总胆固醇（Total cholesterol，TC）、甘油三酯（triglyceride，TG）、高密度脂蛋白胆固醇（high-density lipoprotein cholesterol，HDL-C）、低密度脂蛋白胆固醇（low-density lipoprotein cholesterol，LDL-C）和空腹血糖；在1年后随访测量了肱踝脉搏波速度（Brachial-ankle pulse wave velocity，baPWV）和踝臂指数（ankle-brachial index，ABI）。通过线性回归模型，分析吲哚衍生物与血脂和血糖1年变化的关联，以及吲哚衍生物与baPWV和ABI的关联。

结果：每增加1 μmol/L的吲哚-3-乙酸（IAA），LDL-C下降5.08%（P = 0.046）。IPA水平与baPWV呈负相关（变化百分比 = -1.32%，P = 0.036）。每增加1 μmol/L的吲哚-3-醛（IAld），TC下降1.91%（P = 0.004），ABI增加0.58%（P = 0.019），但HDL-C下降1.79%（P = 0.050）。我们确定了18个相对丰度与IPA呈正相关的菌属（P_FDR < 0.05），并构建了一个微生物菌属评分以反映个体IPA产生能力。该评分与baPWV呈负相关（变化百分比 = -0.48%，P = 0.007）。

结论：研究结果表明，IAA、IPA、IAld及预测IPA微生物得分与多种心脏代谢风险指标呈现出有益关联，但IAld可能导致HDL-C水平下降。