# Gut microbiota–cholesterol crosstalk in cardiovascular diseases: mechanisms, metabolites, and therapeutic modulation

**Authors:** Mohammad Abavisani, Seyed Mohammad Sajjadi, Negar Ebadpour, Sercan Karav, Amirhossein Sahebkar

PMC · DOI: 10.1186/s12986-025-01051-7 · Nutrition & Metabolism · 2025-12-04

## TL;DR

This paper explores how gut bacteria influence cholesterol levels and heart disease, and how targeting these bacteria could help treat cardiovascular issues.

## Contribution

The study provides an in-depth analysis of how gut microbiota regulate cholesterol metabolism and contribute to cardiovascular disease progression.

## Key findings

- Gut microbiota influence cholesterol levels through metabolites like bile acids and TMAO.
- Microbiota modulation strategies like probiotics and FMT show potential in treating CVD.
- Regulation of lipid metabolism and inflammatory responses by gut bacteria is critical in CVD.

## Abstract

Cardiovascular diseases (CVD) are one of the leading causes of death worldwide. Genetic factors, and various environmental factors, including nutrition and the composition of the gut microbiota, have been identified as important factors in the initiation of CVD. Among them, the pivotal role of the gut microbiota in modulating cholesterol metabolism and influencing cardiovascular outcomes has recently been highlighted. Extensive research has confirmed that the gut microbiota has direct and indirect regulatory effects on host cholesterol homeostasis. Recent studies have shown that the microbiota can influence blood cholesterol levels and thus the risk of CVD through various pathways, such as the production of certain metabolites such as bile acids (BAs), SCFAs, and TMAO, the activation of nuclear and membrane-bound receptors such as farnesoid X receptor (FXR), the regulation of gene expression involved in lipid metabolism and inflammatory responses, as well as microbial enzymatic pathways. These complex regulatory mechanisms make the gut microbiota a potential therapeutic target in cholesterol-related diseases and CVD. Microbiota-modulating strategies, including the use of probiotics, prebiotics, fecal microbiota transplantation (FMT), and selective antibiotics, have shown beneficial effects in previous studies. In this regard, in this study, we conducted an in-depth investigation of the regulatory effect of intestinal microbiota on cholesterol metabolism and their impact on the development and progression of atherosclerosis and CVD, and described potential therapeutic pathways based on the regulation of intestinal microbiota in CVD.

## Linked entities

- **Genes:** NR1H4 (nuclear receptor subfamily 1 group H member 4) [NCBI Gene 9971]
- **Chemicals:** TMAO (PubChem CID 1145)
- **Diseases:** atherosclerosis (MONDO:0005311)

## Full-text entities

- **Genes:** NR1H4 (nuclear receptor subfamily 1 group H member 4) [NCBI Gene 9971] {aka BAR, FXR, HRR-1, HRR1, PFIC5, RIP14}
- **Diseases:** death (MESH:D003643), CVD (MESH:D002318), inflammatory (MESH:D007249), atherosclerosis (MESH:D050197)
- **Chemicals:** SCFAs (MESH:D005232), cholesterol (MESH:D002784), TMAO (MESH:C005855), lipid (MESH:D008055), BAs (MESH:D001647)

## Full text

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## Figures

3 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12781766/full.md

## References

31 references — full list in the complete paper: https://tomesphere.com/paper/PMC12781766/full.md

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Source: https://tomesphere.com/paper/PMC12781766