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Recent Research Reveals the Mechanism of Gut Bacteria in Cholesterol Breakdown


Ongoing research continues to uncover the synergistic effects of gut bacteria in clearing cholesterol, with higher levels of bacteria linked to lower cholesterol.

New research emphasizes the importance of certain species of healthy gut bacteria in regulating cholesterol levels.

Published on April 2 in Cell, the study found that bacteria in the genus Oscillibacter consume cholesterol, and individuals with higher levels of Oscillibacter in their gut tend to have lower levels of cholesterol. This discovery was part of the extensive Framingham Heart study involving over 1,400 samples aimed at reducing cardiovascular disease damage.

Stool samples are commonly used to analyze the microbial composition of the gut microbiome, consisting of bacteria, viruses, fungi, and other microorganisms.

Researchers aimed to understand the gut’s role in reducing the risk of heart disease, the leading cause of death in the United States. Cardiovascular disease was responsible for about 695,000 deaths in 2021, according to the CDC.

Unveiling Microscopic Discoveries

The study involved the collection of a vast library of stool samples over many years and examined over 16,000 relationships between microbes and their metabolic traits. The study highlighted that higher levels of Oscillibacter appeared to protect against cholesterol levels.

Cholesterol can lead to plaque buildup, called atherosclerosis, which can obstruct arteries and lead to heart disease, stroke, heart attack, and blood clots.

Further investigations, including growing bacteria to study metabolic pathways, revealed that bacteria convert cholesterol into other products before breakdown and excretion by other bacteria. Machine learning assisted in identifying Oscillibacter’s role in this biochemical conversion.

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Another bacterial species, Eubacterium coprostanoligenes, previously found to aid in lowering cholesterol, may work synergistically with Oscillibacter in cholesterol metabolism.

Dr. Ramnik Xavier, co-director of the infectious disease and microbiome program at Broad, Harvard Medical School professor, and chief of gastroenterology at Massachusetts General Hospital, stated in a news release, “Our research integrates human subjects’ findings with experimental validation to provide actionable mechanistic insights to enhance cardiovascular health.”

Expanding Knowledge

According to a Harvard Medical School article, for a century, scientists have known that gut bacteria break down cholesterol into coprostanol but were unaware of the mechanism or species involved.

A previous study from the team, published in 2020 in Cell Host and Microbe, examined 3,097 stool samples and found that individuals with a specific gene in their microbiome, called IsmA, had reduced cholesterol in their stool and lower blood cholesterol levels. The gene encodes an enzyme that metabolizes cholesterol, explaining why some individuals can consume cholesterol-rich diets without affecting their blood cholesterol levels.

“The findings further support the idea that altering the microbiome could have a therapeutic impact,” said study co-author Dr. Stanley Shaw in the article. Dr. Shaw, a cardiologist at Brigham and Women’s Hospital and associate dean for executive education at Harvard Medical School, emphasized that microbiome-based therapy for heart disease will require years of development.

Potential Future Microbiome Interventions

Potential therapies could involve enzyme therapy, probiotics, dietary adjustments, or other approaches. Probiotics are present in foods like yogurt, fermented vegetables, or supplements.

The recent study suggests that research could pave the way for manipulating the microbiome to reduce cholesterol levels in the future.

Postdoctoral researcher Chenhao Li, a co-first author of the study, added, “Our work indicates the possibility of modifying additional sterol metabolism pathways by gut microbes. This could lead to many new discoveries enhancing our understanding of how microbes interact with the host.”

Overreliance on Medical Solutions?

Dr. Craig Backs cautioned that focusing solely on bacteria oversimplifies the complexities surrounding cholesterol regulation, ignores underlying issues, and promotes a medication-centric approach to healthcare.

He emphasized that managing cholesterol involves addressing multiple risk factors, including smoking, obesity, diet, diabetes, and high blood pressure, not just the microbiome.

Dr. Backs, an internist and founder of the Cure Center for Chronic Disease, educates patients on healthier dietary habits, advocating against excess sugar consumption, which can also increase cholesterol levels and impact cardiometabolism adversely.

Understanding the root cause of elevated cholesterol levels and reducing the reliance on medication is crucial. The Mayo Clinic notes that inactivity, poor dietary choices, and certain medications can contribute to high cholesterol levels, with genetics playing a smaller role than commonly believed.

“If your cholesterol is high, it likely results from a poor diet, lack of exercise, and aging,” said interventional cardiologist Dr. Leslie Cho in a Cleveland Clinic article.

Returning to the Microbiome Connection

Lifestyle factors are also linked to dysbiosis, an imbalance in gut microbes that reduces beneficial bacteria. Lower levels of Oscillibacter have been associated with obesity.
Oscillibacter metabolizes to form the short-chain fatty acid butyrate. Butyrate plays various roles in the body, including improving oxidative status. Uncontrolled oxidation can trigger inflammation contributing to plaque formation.
With trillions of bacteria residing in the human gut, including unidentified species, understanding the intricate associations between functional foods and cholesterol-lowering mechanisms in the gut microbiota remains a significant area of study, as noted in a 2023 study in Foods.

The study concludes, “Dysbiosis of gut microbiota poses a risk factor in pathophysiological processes related to cholesterol-related diseases, representing a subtle yet potent mechanism of disease initiation. The interaction between natural functional [food] ingredients and the cholesterol-lowering actions of the gut microbiota holds promise for novel therapeutic strategies.”



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