From gut microbial ecology to lipid homeostasis: Decoding the role of gut microbiota in dyslipidemia pathogenesis and intervention

🎖️ Top 10% JournalSep 4, 2025World journal of gastroenterology

How Gut Bacteria Affect Fat Levels in the Blood and Their Role in Treating Cholesterol Problems

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Abstract

Dyslipidemia affects more than half of adults globally and is a major modifiable risk factor for cardiovascular disease.

The gut microbiota is correlated with atherogenic lipid profiles through various metabolic processes.
Host-microbe interactions influencing dyslipidemia involve complex gene-environment interactions, including epigenetic factors.
Disruptions in gut microbiota can lead to lipid imbalances and increased production of harmful lipoproteins in the liver.
Short-chain fatty acids from gut bacteria may impact fat breakdown in adipose tissue.
Microbial activity can alter cholesterol metabolism through specific receptor pathways.
Current research identifies critical gaps in understanding the causal relationships between microbial taxa and lipid pathways.

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Dyslipidemia, a complex disorder characterized by systemic lipid profile abnormalities, affects more than half of adults globally and constitutes a major modifiable risk factor for atherosclerotic cardiovascular disease. Mounting evidence has established the gut microbiota (GM) as a pivotal metabolic modulator that is correlated with atherogenic lipid profiles through dietary biotransformation, immunometabolic regulation, and bioactive metabolite signaling. However, the host-microbe interactions that drive dyslipidemia pathogenesis involve complex gene-environment crosstalk spanning epigenetic modifications to circadian entrainment. Mechanistically, GM perturbations disrupt lipid homeostasislipopolysaccharide-triggered hepatic very low-density lipoprotein overproduction, short-chain fatty acid-G protein-coupled receptor 43/41-mediated adipocyte lipolysis, bile acid-farnesoid X receptor/Takeda G protein-coupled receptor 5 axis dysfunction altering cholesterol flux, microbial β-oxidation intermediates impairing mitochondrial energetics, and host-microbiota non-coding RNA crosstalk regulating lipogenic genes. This comprehensive review systematically examines three critical dimensions, including bidirectional GM-lipid axis interactions, molecular cascades bridging microbial ecology to metabolic dysfunction, and translational applications of GM modulation through precision probiotics, structure-specific prebiotics, and a metabolically optimized fecal microbiota transplantation protocol. Notwithstanding these advances, critical gaps persist in establishing causal microbial taxa-pathway relationships and optimal intervention timing. Future directions require longitudinal multi-omic studies, gnotobiotic models for mechanistic validation, and machine learning-driven personalized microbiota profiling. This synthesis provides a framework for developing microbiota-centric strategies targeting dyslipidemia pathophysiology, with implications for precision dyslipidemia management and next-generation cardiovascular disease prevention. via

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