Cholesterol-reducing Gut Bacteria Might Lower Heart Disease Risk
Key findings
- To investigate links between the gut microbiome and cardiovascular health, this study combined metagenomic sequencing with metabolomics to examine stool samples from 1,345 participants in the Framingham Heart Study
- Analysis uncovered >16,000 associations between gut microbes and metabolic features; one of the strongest was a negative association between species of Oscillibacter bacteria and cholesterol in the stool
- Oscillibacter species abundance was also associated with high overall microbiome diversity and low abundances of proinflammatory lipids and plasma triglycerides
- Experiments with three gut Oscillibacter isolates demonstrated cholesterol uptake and production of cholestenone, cholesterol glucoside, and hydroxycholesterol in vitro, suggesting multiple cholesterol metabolism pathways in Oscillibacter
- These findings pave the way for the discovery of other metabolic pathways affected by gut microbes that could be targeted therapeutically
The gut microbiome has been linked to atherosclerotic cardiovascular disease, acute coronary syndrome, ischemic heart disease, and CVD-related risk factors such as elevated blood lipids.
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Now, researchers at Massachusetts General Hospital have made substantial progress in understanding how gut microbial metabolic activity influences those conditions in humans, which could lead to targeted therapies. Most compellingly, the team found that certain gut bacteria species are associated with reduced blood cholesterol levels.
Ramnik J. Xavier, MD, PhD, director of the Center for the Study of IBD at Mass General and Kurt J. Isselbacher, professor of Medicine in the Field of Gastroenterology at Harvard Medical School, Chenhao Li, PhD, and Martin Stražar, PhD, computational scientists at the Broad Institute, and colleagues published the findings in Cell.
Initial Methods
The researchers comprehensively profiled the gut environment related to cardiovascular health by examining 1,345 stool samples from participants in the Framingham Heart Study. They combined shotgun metagenomic sequencing, which profiles all the microbial DNA in a sample, with metabolomics, which measured the levels of hundreds of known and thousands of unknown metabolites.
Links Between Microbes and Metabolites
The analysis uncovered >16,000 associations between gut microbes and metabolic features. One of the strongest was a negative association between species of Oscillibacter and cholesterol in the stool. These species were abundant, representing an average of 1% of all bacteria.
Furthermore, the abundance of Oscillibacter species was associated with high overall microbiome diversity and low abundances of proinflammatory lipids and plasma triglycerides, indicating potential benefits in cardiovascular health.
A decrease in blood cholesterol was observed in samples containing both Oscillibacter and Eubacterium species containing a gene called ismA. The Mass General team previously discovered, as reported in Cell Host & Microbe, that this gene is involved in cholesterol metabolism. Eubacterium may have a synergistic or additive effect with Oscillibacter in further lowering cholesterol levels.
Experimental Validation
In vitro experiments with three gut Oscillibacter isolates demonstrated cholesterol uptake and production of cholestenone, cholesterol glucoside, and hydroxycholesterol. These intermediate products can be broken down by other bacteria and excreted from the body.
Looking Ahead
Continued work to untangle complex microbial metabolic pathways should lead to the discovery of small molecules that could be developed as drugs to affect microbiome function. In particular, interventions targeting gut microbial cholesterol metabolism have the potential to mitigate hypercholesterolemia.
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