TY  - JOUR
AU  - Zhang, He
AU  - Chen, Keyu
AU  - Yun, Zihan
AU  - Shao, Yating
AU  - Yang, Shuai
AU  - Liu, Siqiang
AU  - Zhang, Xiaohan
AU  - Cang, Suhua
AU  - Chen, Yang
AU  - Chen, Renjin
AU  - Jia, Erteng
PY  - 2025
TI  - Dietary Timing Modulates Bile Acid Metabolism and TGR5 Activation to Influence Atherosclerotic Progression
JO  - Food Science and Human Wellness
SN  - 2097-0765
AB  - Feeding patterns are emerging as critical regulators of cardiometabolic health; however, their impact on atherosclerotic cardiovascular disease (ASCVD) remains incompletely understood. Here, we demonstrate that feeding during the active phase (i.e., the dark/nighttime phase, when mice are active), either ad libitum (unrestricted access) or restricted to the nighttime (limited to the dark phase), confers significant protection against atherosclerosis in Apoe⁻/⁻ mice, compared to misaligned feeding during the inactive phase (restricted to the light phase). Multi–omics integration revealed that this atheroprotective effect is mediated by gut microbiota–driven modulation of bile acid (BA) metabolism, particularly involving taurolithocholic acid (TLCA), a potent agonist of the G protein–coupled bile acid receptor TGR5. Daytime feeding disrupted the relative abundance of BA–transforming taxa (e.g., Dubosiella, Clostridium) and downregulated key microbial genes (baiA, baiB, cbh, hdhA, and AMACR), leading to reduced TLCA biosynthesis. Despite unaltered hepatic expression of BAAT, FXR, and CYP7A1, compensatory upregulation of CYP7B1 was insufficient to restore TLCA levels. Consequently, impaired vascular TGR5 signaling promoted endothelial inflammation and reduced cholesterol efflux by downregulating ABCA1 expression, thereby facilitating plaque formation. These findings identify the microbiota–BA–TGR5 axis as a critical mediator of feeding rhythm–linked atheroprotection and underscore the therapeutic potential of chrono–nutrition in ASCVD prevention.
UR  - https://doi.org/10.26599/FSHW.2025.9250799
DO  - 10.26599/FSHW.2025.9250799