Bile acids (BAs) undergo extensive microbial metabolism in the gut and exert hormone-like functions on physiological processes underlying metabolic risk. However, the extent to which gut BA profiles predict cardiometabolic risk and explain individual responses to dietary interventions in humans is still unclear. In the DIRECT-PLUS Trial, we conducted a multi-omics analysis of 284 participants randomized into three groups: healthy dietary guidelines and two Mediterranean diet (MedDiet) groups. We longitudinally measured 44 fecal BAs using liquid chromatography-mass spectrometry, the gut microbiome through shotgun metagenomic sequencing, and body adiposity and serum lipids at baseline, 6, and 18 months. Fecal levels of 14 BAs, such as lithocholic acid and ursodeoxycholic acid, were prospectively associated with body mass index (BMI) and serum lipid profiles (false discovery rate [q]<0.05). Baseline fecal BA levels significantly modified the beneficial effects of the MedDiet; for example, BMI reduction induced by MedDiet interventions was more pronounced in individuals with lower 12-dehydrocholic acid levels (q-interaction <0.001). We confirmed that the gut microbiome is a major modifier of the secondary BA pool in humans. Furthermore, the association of fecal BAs with body adiposity and serum lipids varied significantly in individuals with different abundances of gut microbes carrying BA metabolism enzymes, e.g. several Ruminococcus spp. In summary, our study identifies novel predictive biomarkers for cardiometabolic risk and offers new mechanistic insights to guide personalized dietary interventions.

中文翻译：

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在一项随机对照试验中，胆汁酸的肠道微生物代谢改变了地中海饮食干预对心脏代谢风险的影响。


胆汁酸 （BAs） 在肠道中经历广泛的微生物代谢，并对潜在代谢风险的生理过程发挥激素样功能。然而，肠道 BA 谱在多大程度上预测心脏代谢风险并解释个体对人类饮食干预的反应仍不清楚。在 DIRECT-PLUS 试验中，我们对 284 名参与者进行了多组学分析，随机分为三组：健康饮食指南和两个地中海饮食 （MedDiet） 组。我们使用液相色谱-质谱法纵向测量了 44 个粪便 BAs，通过鸟枪法宏基因组测序测量了肠道微生物组，以及基线、 6 和 18 个月时的体脂和血脂。14 种 BAs 的粪便水平，如石胆酸和熊去氧胆酸，与体重指数 （BMI） 和血脂谱前瞻性相关 （假检出率 [q]<0.05）。基线粪便 BA 水平显着改变了 MedDiet 的有益效果;例如，MedDiet 干预诱导的 BMI 降低在 12-脱氢胆酸水平较低的个体中更为明显 （q-相互作用 <0.001）。我们证实肠道微生物组是人类次级 BA 库的主要修饰因子。此外，粪便 BAs 与身体肥胖和血脂的关联在携带 BA 代谢酶的肠道微生物丰度不同的个体中显着变化，例如几种瘤胃球菌属。总之，我们的研究确定了心脏代谢风险的新型预测生物标志物，并提供了新的机制见解来指导个性化饮食干预。