Is Bile Stealing the Spotlight in Gut-Heart Cross-Talks—Bile Acids and Cardiovascular Disease Revisited

Bile Acids and Cardiovascular Disease

Gut health conversations are everywhere — podcasts, panels, publications, and more. Perceived to be the second brain, the gut and the gut microbiome impact brain health, cardiovascular diseases (CVDs), lung health, reproductive functions, oral health, and everything in between. 

With CVDs contributing 30% of global deaths, the gut-heart axis has fueled extensive studies in the last decade. Among which, microbiota-derived bile acids have emerged as a key player in heart health and heart conditions. Or is it? We’ll find out as we learn more about the intricate relationship between bile acids and cardiovascular disease.

Bile Acids—Where Does It Stand in Cardiology?

From a cardiology standpoint, bile acids and their related mechanisms are intricately related to cardiovascular functions. 

Bile acid receptors, like the muscarinic receptor and Farnesoid X-activated receptor, are expressed in different cells of the cardiovascular system—namely the cardiomyocytes and the endothelial and smooth muscle cells of the blood vessels—understanding that bile acids and cardiovascular diseases are linked in more than one way. 

According to the study in Nature Cardiovascular Research (2025), TMAO (trimethylamine N-oxide), a compound produced by gut bacteria from dietary choline and known to offer active proatherogenic effects, ‘disrupts reverse cholesterol transport,’ a key protective mechanism against cardiovascular disease. It is also linked to the changes in the quantity and production of bile acids. When bile acid pools are altered or metabolized incorrectly due to disrupted TMAO production in gut dysbiosis, it can accelerate atherosclerosis, leading to heart attacks and strokes.

In a recent article, Dr. Cristina Menni goes into more detail, stating that "the gut microbiome's production of TMAO and its interaction with bile acids can significantly alter lipid profiles, leading to proatherogenic effects." 

Interestingly, bile acids are gut metabolites themselves and can independently impact cardiovascular health. 

As emerging cardiac influencers, albeit through different intricate mechanisms, they are being extensively studied in cardiac diseases, rewiring of critical cardiac signaling pathways, and driving CVD progression.

Bile Acids and Cardiovascular Diseases—What Do the Science Honchos Say?

Dr. Joshua S. Fleishman and Dr. Sunil Kumar in Signal Transduction and Targeted Therapy (2024) emphasizes the impact of bile acids in cardiovascular diseases (CVD), noting that they are ‘critical regulators of various cardiovascular functions, including platelet activation, vascular tone, and cholesterol metabolism.’ These metabolic pathways, they argue, ‘interact directly with the gut microbiota, making them a crucial part of the microbiota–gut–heart axis (MGHA).’

The study highlights that disruptions in bile acid metabolism due to intestinal dysbiosis lead to the accumulation of toxic metabolites, further increasing the risk of heart disease. 

On the flip side, a balanced microbiome helps produce short-chain fatty acids (SCFAs) and healthy bile acids, contributing to cardiac homeostasis.

Dr. Pierre Dupont further categorizes bile acids into hydrophobic and hydrophilic types, which impact vascular health. Hydrophobic bile acids are found to induce vasodilation by inhibiting calcium entry through membrane channels. This mechanism could explain the observed low blood pressure and increased vasodilation seen in patients with cholestatic liver diseases. However, long-term disruptions in bile acid homeostasis may lead to endothelial dysfunction and contribute to the progression of hypertension and heart failure.

The growing understanding of bile acids as mediators of cardiovascular risk opens up new possibilities. 

Though there is no curative treatment for any bile acid-related condition, the FDA just rejected the most promising and well-developed bile acid medication. Thus, a bottom-up approach to bile acids, mechanistically understanding their biochemistry, physiology, and pharmacology, can go a long way in unifying the pathogenic and non-pathogenic aspects of the compounds and their role in cardiovascular health. 

Dr Pushpass further adds the effects of prebiotics, probiotics, and polyphenol-rich foods on the circulating bile acids as a link between gut microbiota and cardiovascular health. She introduces the concept of primary and secondary bile acids. 

Primary bile acids produced by the liver are released into the intestine to help digest fats, but the plot thickens when the gut microbiota transforms these primary bile acids into secondary bile acids. 

Some of these secondary forms are not easily reabsorbed and instead exit the body in the stool. This loss of bile acids doesn’t go unnoticed—the liver compensates by making more bile acids from circulating cholesterol, particularly low-density lipoprotein (LDL). In essence, this creates a built-in cholesterol clearance mechanism, potentially lowering a major cardiovascular risk factor.

Consequently, probiotics, prebiotics, and polyphenol-rich foods (like berries, green tea, and dark chocolate) aren’t just good for digestion—they quietly reprogram the gut microbiota—to impact the levels of bile acids in the body. 

What do they do?

• Sequester bile in the gut, leading to its excretion.

• Possesses bile salt hydrolase activity, which modifies bile composition.

• And ferment dietary fiber to generate short-chain fatty acids (SCFAs), known to support bile acid metabolism and systemic anti-inflammatory effects.

Takeaway

As the bottom line, bile acids and cardiovascular diseases have a bittersweet journey that opens doors to potential molecular targets for drug development in the years to come. As key metabolic intermediaries, bile acid metabolism and related signaling pathways driven by the gut microbiota have been implicated in atherosclerosis, arrhythmias, endothelial dysfunction, and systemic inflammation. 

Diet, particularly prebiotics, probiotics, and polyphenol-rich foods, modulates this interplay by shifting microbiota composition and bile acid pools. As research advances, circulating bile acids may emerge as novel biomarkers and therapeutic levers in cardiovascular disease (CVD) management.