Objective To explore the mechanism underlying the antiatherosclerotic effect of Huayu Qutan Formula（HQF

化瘀祛痰方）. Methods Twenty-four ApoE

-/-

mice were randomly divided into model group

simvastatin group and HQF group with eight mice in each group

fed with high fat diet to prepare AS models. Eight C57 BL/6 J mice as the blank group were fed with normal diet. After modelling

2.275 mg/（kg·d） simvastatin and 20 g/（kg·d） HQF were administered by gavage in simvastatin group and HQF group

respectively; equal volume normal saline（0.5 ml） was given by gavage in blank group and model group

once daily for four weeks. The hepatic pathological histology

gut microbiota of cecal contents

plasma trimethylamine（TMA） and trimethylamine oxide（TMAO） contents

and liver flavin monooxygenase 3（FMO3） mRNA and protein expression were assessed. Results Compared to those in the model group

the swelling of cells

the fat vacuole and lipid droplet deposition were significantly reduced in HQF group. Compared to blank group

the model group had significantly higher plasma TMA and TMAO contents

as well as higher FMO3 mRNA and protein expression（P

<

0.05）. Compared to those in the model group

TMA and TMAO contents and FMO3 mRNA and protein expression decreased in simvastatin group and HQF group（P

<

0.05）. There were no significantly statistical differences between simvastatin group and HQF group in all outcomes（P

>

0.05）. Beta-diversity analysis of the intestinal flora indicated that different group samples can be significantly distinguished. In terms of the genus level

model group had decreased relative abundance of Prevotella

Bacteroides

Shigella of Escherichia and Parabacteroides

as well as increased g

L

achnospiraceae

U

GG-006 and Rosella compared to the blank group（P

<

0.05）; relative abundance of anaerobic bacillus

g

E

ubacterium

x

ylanophilum

g

roup

g

L

achnospiraceae

U

CG-006

g

R

ikenellaceae

R

C9

g

ut

g

roup

and Rosella decreased

while Bacteroides

Citrobacter

Shigella of Escherichia

Parabacteroides

and Staphylococcus increased in HQF group

compared to those in model group（P

<

0.05）; Bacteroides and Parabacteroides were negatively correlated with TMA

while Prevotella

Bacteroides and Parabacteroides were negatively correlated with TMAO（P

<

0.05）. Conclusion HQF can change gut microbiota structure

decrease TMA

reduce FMO3 expression

and limit TMAO synthesis

thereby inhibit the development of atherosclerosis.