High-cholesterol diet does not alter gut microbiota composition in mice.

Area of Science:

• Cardiovascular Health
• Microbiome Research
• Metabolic Disease

Background:

• Western diets, high in saturated fat and cholesterol, negatively impact cardio-metabolic health.
• Dietary fat influences gut microbiota, but the specific effects of high cholesterol diets remain unclear.
• Investigating the impact of isolated high cholesterol on host and microbiota is crucial for understanding diet-related diseases.

Purpose of the Study:

• To determine how a high cholesterol (HC) diet affects host cholesterol metabolism.
• To analyze the impact of an HC diet on the intestinal microbiota composition in susceptible mice.
• To differentiate the effects of dietary cholesterol versus dietary fat on the gut microbiome.

Main Methods:

• Utilized LDLR knockout mice, a model for cholesterol metabolism studies.
• Administered a 1.25% HC diet or a cholesterol-free control (NC) diet for 12 weeks.
• Assessed host cholesterol levels, sterol excretion, and performed next-generation sequencing for microbiota analysis.

Main Results:

• HC diet significantly increased plasma and liver cholesterol, biliary cholesterol secretion, and fecal neutral sterol excretion (p < 0.001).
• No significant alterations in gut microbial composition were observed between HC and NC groups.
• Dominant bacterial phyla in both groups included Bacteroidetes, Firmicutes, and Verrucomicrobia.

Conclusions:

• A high cholesterol diet alone does not alter gut microbiota composition in mice.
• Significant adaptive changes in whole-body cholesterol homeostasis occurred independently of microbial changes.
• The detrimental effects of Western diets on the gut microbiota are likely driven by high fat content, not cholesterol alone.