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Certain gut bacteria lower cholesterol and the risk of heart disease

Alterations in the gut microbiota have been linked to various health issues, including type 2 diabetes, obesity, and inflammatory bowel disease. Recent findings by researchers from the Broad Institute of MIT and Harvard, in collaboration with Massachusetts General Hospital, have shed light on the gut microbiome’s influence on cardiovascular disease.

The study reveals that certain gut bacteria metabolize cholesterol, potentially reducing cholesterol levels and the risk of heart disease.

Bacteria that absorb cholesterol 

The experts analyzed the metabolites and microbial genomes of over 1,400 participants from the Framingham Heart Study – which has been examining cardiovascular disease risk factors for decades. 

The researchers discovered that the Oscillibacter bacteria absorb and metabolize cholesterol from their environment, leading to lower cholesterol levels in individuals with higher concentrations of these bacteria in their gut. 

Potential for microbiome-targeted interventions

Additionally, the experts uncovered the specific mechanism such bacteria likely utilize to decompose cholesterol. The findings suggest the potential for microbiome-targeted interventions to reduce cholesterol levels in the future and pave the way for more focused research on microbiome alterations and health.

Ramnik Xavier is a core institute member at the Broad Institute, director of the Immunology Program, co-director of the Infectious Disease and Microbiome Program, and a professor at Harvard Medical School and Massachusetts General Hospital.

“Our research integrates findings from human subjects with experimental validation to ensure we achieve actionable mechanistic insight that will serve as starting points to improve cardiovascular health,” said Xavier.

Gut microbiome and heart disease 

The investigation aimed to build on previous studies that linked gut microbiome composition with aspects of cardiovascular disease, such as triglycerides and blood sugar levels post-meal, which have yet to be addressed therapeutically due to incomplete metabolic pathway knowledge in the gut.

Beneficial gut bacteria found to be surprisingly common 

Utilizing shotgun metagenomic sequencing to profile microbial DNA in stool samples from the Framingham Heart Study, combined with metabolomics to measure various metabolites, the team identified over 16,000 microbe-metabolite associations. 

A notable finding was that individuals with several Oscillibacter species had lower cholesterol levels. These bacteria were found to be surprisingly common, averaging one in every 100 gut bacteria.

Finding the gut bacteria’s cholesterol-lowering pathways

The challenge then was to identify how these microbes metabolize cholesterol. Thanks to a unique library of bacteria collected from stool samples, including Oscillibacter, the team was able to cultivate these organisms and use mass spectrometry to pinpoint cholesterol metabolism byproducts, revealing the bacteria’s cholesterol-lowering pathways. 

They also explored another bacterial species, Eubacterium coprostanoligenes, known for its cholesterol metabolism contributions, uncovering its potential synergistic effects with Oscillibacter on cholesterol levels.

Targeted therapeutic strategies may be possible 

The research underscores the untapped potential of the gut microbiome, with many genes yet to be characterized. By focusing on specific bacteria and genes, the team hopes to achieve a systematic understanding of gut ecology and develop targeted therapeutic strategies. 

The work not only contributes to the understanding of microbial influence on cholesterol metabolism but also opens the door to discovering new metabolic pathways influenced by the gut microbiome, moving closer to a mechanistic understanding of microbe-host interactions.

Potentially many new discoveries to be made

“There are many clinical studies trying to do fecal microbiome transfer studies without much understanding of how the microbes interact with each other and the gut,” said study co-first author Chenhao Li, a postdoctoral fellow at the Broad Institute. 

“Hopefully stepping back by focusing on one particular bug or gene first, we’ll get a systematic understanding of gut ecology and come up with better therapeutic strategies like targeting one or a few bugs.”

“Because of the large number of genes of unknown function in the gut microbiome, there are gaps in our ability to predict metabolic functions. Our work highlights the possibility that additional sterol metabolism pathways may be modified by gut microbes. There are potentially a lot of new discoveries to be made that will bring us closer to a mechanistic understanding of how microbes interact with the host,” he concluded.

The study is published in the journal Cell.


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