Multi‐Omics Evidence Linking Gualou Xiebai Banxia Decoction Intervention to Atherosclerosis Mitigation and Gut Microbiota–Bile Acid Signatures in ApoE −/− Mice

TL;DR

This study shows that a traditional Chinese herbal formula, GXBD, reduces atherosclerosis in mice by improving gut bacteria and bile acid levels, which in turn affects harmful genes and plaque stability.

Contribution

GXBD's novel mechanism of mitigating atherosclerosis via gut microbiota and bile acid modulation is revealed through multi-omics analysis.

Findings

GXBD reduced aortic plaque burden and hepatic steatosis in ApoE−/− mice.

GXBD increased protective bile acids like 11-LCA and 23-DCA while decreasing harmful metabolites.

GXBD modulated vascular genes, upregulating PPARG and SIRT1 while downregulating MMP9 and CASP3.

Abstract

Atherosclerosis presents a persistent health challenge, with limited therapies addressing residual cardiovascular risk. Gualou Xiebai Banxia Decoction (GXBD), a classical Chinese herbal formula traditionally used for chest obstruction syndromes, was evaluated as a dietary‐style intervention in ApoE−/− mice fed a high‐fat diet for 14 weeks. Using a multi‐omics strategy that combined UHPLC‐QE‐MS/MS chemical profiling, network pharmacology, 16S rRNA sequencing, targeted bile acid metabolomics, and biological validation, we assessed vascular and metabolic outcomes alongside gut ecology. Chemical profiling identified 348 constituents, including bioactive flavonoids and saponins. In vivo, GXBD intervention significantly improved lipid profiles by reducing serum TC, TG, and LDL‐C, and by raising HDL (p < 0.05). It markedly reduced aortic plaque burden and alleviated hepatic steatosis (p < 0.05). Mechanistically, GXBD reshaped the gut microbiota, characterized by the enrichment of beneficial Bacteroides and Alloprevotella and the depletion of pro‐inflammatory Blautia and Bilophila. This microbial shift coincided with significantly higher levels of protective secondary bile acids, such as 11‐LCA and 23‐DCA, and fewer cytotoxic chenodeoxycholic acid–derived metabolites (p < 0.05). Correlation and constrained ordination analyses linked these microbial‐bile acid signatures to the concordant modulation of vascular hub targets, including the downregulation of MMP9 and CASP3 and upregulation of PPARG and SIRT1. These findings suggest that GXBD mitigates atherosclerosis in this murine model through a coordinated remodeling of the gut microbiota–bile acid–host axis, supporting its potential as a microbiome‐informed, multi‐component adjunct for cardiometabolic health.

Gualou Xiebai Banxia Decoction (GXBD) promotes atherosclerotic plaque stabilization via the “gut microbiota—bile acid—host” axis. GXBD treatment remodels the gut microbiota, promoting the production of secondary bile acids (11‐LCA and 23‐DCA). These metabolites enter the systemic circulation and modulate vascular gene expression—specifically upregulating PPARG and SIRT1 while downregulating MMP9 and CASP3—thereby enhancing fibrous cap thickness and reducing plaque vulnerability.

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