A new study reveals how gut microbes help regulate cholesterol via bile acid metabolism, highlighting the microbiome’s role in metabolic health.
Content Outline
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Scientists Find A New Way Gut Bacteria Help Control Cholesterol
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A Newly Discovered Microbial-Host Pathway That Prevents Fat Accumulation
Scientists Find A New Way Gut Bacteria Help Control Cholesterol
For decades, scientists believed that cholesterol metabolism was mostly controlled by organs, such as the liver and impacted by genetics and lifestyle choices, like diet. For the most part, this is true, but a growing body of evidence suggests that the gut microbiome may be another powerful regulator in cholesterol metabolism.
The gut microbiome is a complex ecosystem consisting of trillions of microbes residing in the human digestive tract, primarily the large intestine (colon) [1]. It plays a crucial role in several biological processes, including digestion, immunity, and metabolism [2]. Studies are also revealing that these microbes may also help regulate how the body processes fats and cholesterol [3].
New research published in Nature by Won and colleagues has uncovered a previously unknown pathway that sheds light on how gut microbes influence cholesterol metabolism. Here, we explore the latest research and its potential impact on our understanding of the interplay between the gut microbiota and lipids, and what this could mean for the future.
Cholesterol, Bile Acids, and Metabolism
Cholesterol gets a bad rap, but it’s actually a crucial molecule for forming cell membranes, supporting hormone production, and serving as the raw material used by the liver to make bile acids [4]. It’s a waxy, fatty substance that’s crucial for several important functions. About 80% of the cholesterol your body needs comes from your liver, while the rest, around 20%, comes from the animal-based foods you eat, such as meat, eggs, and dairy.
To travel around the body, cholesterol attaches to proteins called lipoproteins. There are two main types:
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Low-density lipoprotein (LDL) – also known as “bad” cholesterol. This is the type that transports cholesterol from your liver around your body, and in high amounts can lead to a buildup of plaque in your arteries, part of a condition called atherosclerosis, which increases the risk of heart disease and stroke.
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High-density lipoprotein (HDL) – often referred to as “good” cholesterol, HDL carries excess cholesterol away from your cells and back to the liver, where it can be removed from the body. High levels of HDL are healthy.
Primary bile acids are steroid acids produced by the liver and stored in the gall bladder. They are derived from cholesterol and are needed to help the body digest and absorb dietary fats and fat-soluble vitamins, such as vitamins A, D, E, and K. Secondary bile acids are made by gut bacteria [5].
Once they have performed their role, most bile acids are reabsorbed in the intestine and recycled back to the liver in a process known as enterohepatic circulation [6]. While some are converted into secondary bile acids by the gut microbiota and absorbed in the colon.
Bile acids used to be thought of as digestive detergents, but as research has progressed, scientists have found that they also act as signalling molecules, influencing metabolic pathways throughout the body.
Research has demonstrated that gut bacteria can modify the structure of bile acids, modifying their bioavailability, while bile acids themselves can promote microbial growth. By interacting with receptors such as the farnesoid X receptor (FXR), bile acids can regulate lipid metabolism [7].
The Role of The Gut Microbiome in Cholesterol Regulation
The human gut is home to trillions of microbes that help transform bile acids, which account for 50% of the daily turnover of cholesterol in the body [7]. They are the primary metabolic byproduct and excretion route for cholesterol.
After bile acids are released into the intestine, your gut microbes can modify them through several reactions to produce secondary bile acids, which differ in their biological activity and influence metabolic signalling pathways. For example, certain Lactobacillus strains can deconjugate primary bile acids, while Clostridioides can produce a pool of secondary bile acids through oxidation and dihydroxylation processes. This can produce deoxycholic acid (DCA) and lithocholic acid (LCA).
The interaction between bacteria and bile acids is an important component of the gut-liver axis, a communication network linking the gut microbiome to metabolic processes in the liver. For example, DCA activates the FXR receptor in the liver, which reduces bile acid synthesis [8], ultimately playing an important role in regulating lipid and glucose metabolism.
A Newly Discovered Microbial-Host Pathway That Prevents Fat Accumulation
Won and Co recently discovered bile acids-methylcysteamine (BA-MYC). A novel molecule that’s found abundantly in the intestine and inhibits the FXR receptor in the liver. This action promotes bile acid production and boosts fat metabolism.
Although BA-MYC is synthesised by host cells, its production requires gut microbes, which generate the bile acid precursors needed to facilitate the reaction. So, when gut microbes produce high levels of bile acids, the FXR receptor is strongly activated, and the body makes more BA-MCYS, which helps keep the bile acid system balanced.
In mice, the researchers found that increasing BA-MCYs reduced liver fat accumulation, suggesting this could be a potential treatment pathway for conditions such as fatty liver disease and cholesterol [9]. They also found that inulin fiber, a type of prebiotic fiber known to nourish gut bacteria, increased bile acids and BA-MCYs levels, indicating that the production of BA-MCY is regulated by the levels of free bile acids produced by gut bacteria.
Why This Research Matters
The results of this study help to confirm how the gut microbiome contributes to cholesterol and fat metabolism at a molecular level. In mice, manipulating this pathway influenced fat accumulation and metabolic balance. For example, mice receiving BA-MYC-related compounds showed reduced liver fat accumulation when fed a high-cholesterol diet. Although these findings need to be confirmed in humans, they highlight the potential importance of the gut microbiome in cholesterol metabolism.
The research also helps us to gain a greater understanding of human metabolic health, and that it is not controlled solely by the body. Instead, an intricate partnership between human cells and the microbial communities inhabiting the gut appears to play a substantial part.
Understanding how these microbial pathways work in greater depth may, one day, lead to new approaches for managing metabolic conditions, including:
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high cholesterol
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fatty liver disease
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type 2 diabetes
How To Support A Healthy Gut Microbiome Now
Although research is emerging into microbiome-based therapies, it is clear that diet and lifestyle are 2 major factors in shaping the composition of your gut microbiome. From choosing prebiotic fibers to regular exercise, there are several simple things you can do to support the precious ecosystem to thrive in your gut.
Prebiotics
One of the most important nutrients for supporting beneficial gut bacteria is fiber. Fiber acts as a prebiotic, providing nourishment and fuel to the bacteria that produce short-chain fatty acids (SCFAs) and other important metabolites, like vitamins, that influence many aspects of your health, including metabolism.
Fiber rich foods include:
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whole grains (oats, barley, bulgar wheat, quinoa)
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legumes (beans and lentils)
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fruits (apples, berries, citrus)
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vegetables (asparagus, broccoli, cabbage, sweet potatoes)
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nuts and seeds
Prebiotic compounds, such as human milk oligosaccharides (HMOs), also selectively nourish beneficial gut bacteria. These complex carbohydrates are the third most abundant component in human breast milk [10]. HMOs, such as 2’FL, LNnT, LNT, 3’SL, and 6’SL, have been shown to support the growth of beneficial bacteria, such as Bifidobacteria [11], which, in turn, can positively impact immunity, digestion, and metabolism.
Probiotics
Probiotic supplements are live microorganisms that, when consumed in high enough amounts, can provide health benefits [12]. Certain probiotic strains have been shown to influence bile acid metabolism and cholesterol levels. For example, some Lactobacillus and Bifidobacterium species possess bile salt hydrolase (BSH) enzymes that help break down bile acids in the intestine. This process can alter the bile acid pool and may encourage the body to use circulating cholesterol to produce new bile acids, potentially contributing to improved cholesterol balance [13].
Emerging research also suggests that probiotics may help support metabolic health by strengthening the gut barrier, modulating inflammation, and interacting with microbial metabolic pathways linked to lipid metabolism. While the effects can vary depending on the specific strain and individual microbiome, maintaining a diverse microbial ecosystem—through a combination of fibre-rich foods, prebiotics, probiotics, and other microbiome-supportive nutrients—may help create the conditions that support healthy metabolic signalling between gut microbes and the host.
In addition to supplements, another way to deliver live beneficial microbes to the gut is to eat fermented foods, such as kefir, kimchi, and sauerkraut.
Summary
The discovery of BA-MYC highlights how much remains to be learned about the complex chemistry occurring in the gut microbiome.
Scientists are now uncovering a growing catalogue of microbial metabolites that influence human physiology—from immune responses to brain signalling and metabolism.
Bile acids are emerging as particularly important messengers in this microbial-host communication network. Through interactions with receptors such as FXR, these molecules help coordinate the balance between cholesterol metabolism, fat digestion, and energy regulation.
The work by Won and colleagues reveals just one piece of this intricate puzzle. As microbiome research advances, scientists are likely to uncover additional microbial pathways that influence metabolic health.
Ultimately, these discoveries may lead to new strategies for supporting cardiovascular and metabolic health—by targeting not only human biology, but also the trillions of microbial partners that live within us.
Author Details
Written by: Leanne Edermaniger, M.Sc. Leanne is a professional science writer who specializes in human health and enjoys writing about all things related to the gut microbiome. She has written extensively on inflammatory bowel disease, prebiotics, and microbiome research.
Her work focuses on translating complex medical science into evidence-based, practical health guidance.
