Unlocking the Power of Bile Acids: A New Frontier in Gut Health

 

By Abigail Basson, PhD

When most people think about gut health, the usual suspects come to mind: probiotics, fibre-rich foods, maybe even kombucha. But there is a lesser-known player quietly gaining attention- bile acids. Once thought simply as digestive aids or pharmaceuticals for liver diseases, bile acids are now being recognized for their powerful role in shaping our gut microbiome and, in turn, our overall health

So, what are bile acids, and how can they be used to improve our gut health? 

Bile acids are molecules made in the liver from cholesterol. They’re stored in the gallbladder until they are released into the small intestine after we eat, where they help break down dietary fats and carbohydrates, so that the body can better absorb them (1).

However, bile acids have been used in medicine, long before they were revealed to help digest your greasy pizza! While ancient Chinese practitioners didn’t describe "bile acids" in the modern scientific sense, they did recognize the therapeutic value of animal bile, using it to treat ailments from fevers to liver diseases to epilepsy (2).

 

 

In Alzheimer’s disease, several studies performed with different mice models showed that the development of AD pathologies, including Aβ plaque, hyperphosphorylated tau, synaptic dysfunction, and microglial activation appears to be influenced by the gut microbiome (5). Moreover, a recent report by Grabrucker, Marizzoni (2) evidenced how gut microbiota from AD patients harmed adult hippocampal neurogenesis in mice after fecal microbiota transplantation (FMT), with cognitive and behavioral consequences. In Parkinson’s disease (PD), the gut has emerged as a potential origin site for alpha-synuclein (α-syn) misfolding, a pathological process that leads to the loss of dopaminergic neurons. The “gut-first” hypothesis of PD suggests that certain gut microbes can induce misfolding of α-syn, which then spreads to the central nervous system (6). In Multiple Sclerosis (MS), an autoimmune neurodegenerative disease, gut microbiota is thought to play a role in modulating neuroinflammation and immune responses. In MS patients, the gut microbiota influences immune function via modulation of serotonin production in the gut and through complex interactions with components of the immune system, such as T cells and B cells (7).

Together, these findings suggest that targeting the gut microbiota through dietary interventions, pre-, pro-, postbiotics and FMT may offer promising new therapeutic strategies for neurodegenerative diseases. However, significant challenges remain, including understanding the precise microbial mechanisms involved and developing targeted interventions that can effectively modulate the microbiome without unintended side effects.

 

 

Where does gut health come in?

Your gut microbiome, the trillion-strong collection of bacteria, viruses, fungi, and other microbes living in your digestive system, plays a critical role in digestion, immunity, inflammation and mental health. Keeping this microbial community balanced is key to staying healthy (3).

Primary bile acids secreted by the liver, travel through your intestines and interact directly with the gut microbiome, transforming into secondary bile acids (Fig.1). 

In fact, by this transformation, bile acids act as chemical signals that can either promote or inhibit the growth of certain bacteria. Some bacteria thrive in the presence of bile acids, while others are held in check by them. This balance is one that researchers are starting to understand better in terms of health and disease, with altered ratios of primary to secondary bile acids found in individuals with irritable bowel syndrome (IBS), type 2 diabetes and obesity, and even neurological diseases, such as Parkinson’s and Alzheimer's disease (4–6).

Fig. 1: Diagram depicting the synthesis of primary bile acids from cholesterol in the liver, their release into the small intestine and conversion into secondary bile acids by the gut microbiota. 5% of bile acids are excreted in stool, whilst 95% enter the enterohepatic circulation, recycled back into the liver. Image made in BioRender.com.

 

From Digestion to Defence

Certain bile acids help defend the body against pathogenic invaders like Clostridium difficile (C. diff) from gaining a foothold, which can cause severe, even life-threatening diarrhoea. Yet, bile acids don’t just keep the bad guys out - they also play favourites with the good ones.7

Some probiotic bacteria, such as Lactobacillus and Bifidobacterium species, thrive in the presence of specific bile acids. These friendly microbes possess bile salt hydrolase (BSH) enzymes that allow them to modify bile acids into less toxic forms, helping them survive and flourish in the gut. In return, these beneficial bacteria support bile acid recycling and conversion into their more potent "secondary" forms — compounds known to reduce inflammation and inhibit harmful microbes (8–10).

Bile Acid Therapies for Better Health

It’s a two-way street: bile acids shape the microbiome and the microbiome reshapes bile acids. This dynamic interaction helps maintain a healthy balance, favouring beneficial probiotic bacteria while suppressing potential harmful pathogens. By restoring or enhancing this bile acid-microbiome partnership, scientists hope to tip the microbial scales in our favour. Scientists are now exploring bile acid-based therapies, either by modifying existing bile acids, creating synthetic versions, or even repurposing bile acids that are currently used in medicine (11–13).

Early clinical trials have shown promise in treating conditions like C. diff infections, non-alcoholic fatty liver disease, and even metabolic disorders like type 2 diabetes — all by adjusting bile acid levels and their interactions with the microbiome (see Fig.2) (14–18).

 

Fig. 2: Bile acid therapeutics offer clinical potential, to provide treatments for several disease states, from atherosclerotic cardiovascular disease (ASCVD), obesity, Type 2 diabetes mellitus, Non-alcoholic fatty liver disease (NAFLD), Non-alcoholic steatohepatitis (NASH), Inflammatory Bowel Disease (IBD) and C. difficile infections. Image made in BioRender.com.

 

A Targeted Tool, Not a Magic Pill

It’s important to note that while bile acid therapies are promising, they’re not a magic cure-all! The gut ecosystem is incredibly complex, and what works for one person might not work for another. 

You don’t need to start taking bile acid supplements just yet, many of these treatments are still being tested in labs or clinical studies. But what you can do is support your own bile acid production and microbiome health in everyday ways (Fig.3):

- Eat a balanced, fibre-rich diet: Fiber feeds beneficial gut bacteria, which in turn can help convert bile acids into their more beneficial forms.19,20

- Stay active: Exercise has been shown to influence bile acid levels and gut bacteria positively (21, 22).

- Better sleep: Bile acid production follows a circadian rhythm, meaning it's linked to your body’s internal clock. Disrupted sleep can interfere with this rhythm, potentially altering bile acid balance and negatively impacting the gut microbiome. Prioritising consistent, high-quality sleep may help maintain healthy bile acid cycles and support a more balanced gut (23).

 

Fig. 3: A high-fibre diet, better sleep and moderate physical activity can modify the gut microbiome, increasing beneficial bacteria species and supporting bile acid synthesis. Image made in BioRender.com

 

Looking Ahead

As researchers continue to unravel the complex relationship between bile acids and the gut microbiome, we may soon have personalized treatments that use our body’s own chemistry to fight disease and, maintain and improve health. It’s an exciting time in gut science and bile acids, once perhaps slightly overlooked, are stepping into the spotlight.

References

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