Antibiotic-induced gut microbiota depletion exacerbates host hypercholesterolemia

Area of Science:

• Microbiology
• Metabolic Diseases
• Cardiovascular Research

Background:

• Hypercholesterolemia significantly drives atherosclerosis, leading to global morbidity and mortality.
• Gut microbiota are recognized as key modulators of host lipid metabolism, including cholesterol levels.
• Existing research on gut bacteria and host cholesterol presents conflicting findings, necessitating further investigation.

Purpose of the Study:

• To investigate the intricate relationship between intestinal bacteria and host cholesterol metabolism.
• To identify specific alterations in gut microbiota composition associated with hypercholesterolemia in humans.
• To determine the impact of pharmacological disruption of gut microbiota on serum cholesterol levels in a mouse model.

Main Methods:

• Fecal 16S rRNA targeted metagenomic sequencing was performed on a human cohort (n=24) not using cholesterol-lowering drugs.
• Hypercholesterolemic Apolipoprotein E knockout mice were treated with oral, non-absorbable antibiotics.
• Gene expression analysis and non-targeted serum metabolomics were employed to elucidate mechanisms.

Main Results:

• Hypercholesterolemic patients exhibited altered gut microbiota with depleted Bifidobacteria, expanded Clostridia, and an increased Firmicutes/Bacteroidetes ratio.
• Antibiotic treatment in mice elevated serum cholesterol, particularly in the fed state on a normal chow diet.
• These cholesterol elevations were reversible upon antibiotic cessation and linked to increased intestinal cholesterol uptake, diminished plant sterols, and reduced bile acid cycling.

Conclusions:

• The study elucidates the complex interplay between gut microbiota and host cholesterol metabolism.
• Pharmacological disruption of gut flora via antibiotics can exacerbate serum cholesterol levels.
• These findings suggest potential implications for cardiovascular disease risk and management strategies targeting the gut microbiome.