Bile Acids in Health and Disease: Why Testing Matters

Our understanding of the gastrointestinal system continues to evolve, and the gut is now recognised as a central hub where the nervous system, the immune system, our metabolism, and microbiome converge. At the heart of this dynamic network lies a fascinating group of molecules, namely bile acids. Long considered merely facilitators of fat absorption, bile acids are now emerging as central signalling agents that orchestrate a wide array of physiological processes, from microbial balance and intestinal motility to metabolic regulation and immune modulation. 

In this blog, we explore the expanding role of bile acids in health and disease and examine how we can use functional testing to gain more insight and help us transform our approach to complex gastrointestinal and metabolic conditions.

What Are Bile Acids?

Bile acids are cholesterol derived molecules synthesised in the liver and conjugated with glycine or taurine before being stored in the gallbladder. They are released into the small intestine after food intake to aid in the emulsification of dietary fats in readiness for their absorption. 

Bile acids are categorised into two major types: primary and secondary. Primary bile acids, including cholic acid and chenodeoxycholic acid, are synthesised in the liver and released into the gut. Most bile acids (95%) are reabsorbed in the ileum of the small intestine and recycled through the enterohepatic circulation. However, a small fraction (5%) escapes reabsorption and reaches the colon, where it is metabolised by our gut microbiota into secondary bile acids such as deoxycholic acid, lithocholic acid and isolithocholic acid. This microbial transformation plays a crucial role in regulating the composition and balance of the gut ecosystem.

Physiological Roles of Bile Acids

Aside from the critical role bile acids play in the digestion and absorption of dietary fats making them vital for the bioavailability of essential fatty acids and fat-soluble vitamins such as A, D, E, and K, one of the most significant non-digestive functions of bile acids is their ability to shape the gut microbiome. Bile acids exhibit antimicrobial properties, disrupting bacterial cell membranes and altering the metabolic environment of the gut. This selective pressure influences microbial diversity and composition, helping to maintain a balanced and resilient microbial ecosystem. In particular, the transformation of primary bile acids into secondary bile acids by gut microbes adds another layer of complexity to this regulatory network. Secondary bile acids are not merely metabolic by-products; they possess distinct biological activities that can influence both microbial dynamics and host physiology. For example, secondary bile acids, such as iso-lithocholic acid and ursodeoxycholic acid, have been found to play key roles in modulating the host immune system. These molecules can promote the differentiation and function of regulatory T cells (Tregs), which are essential for maintaining immune tolerance and preventing excessive inflammation. Additionally, bile acids influence the production of cytokines and the activation of other immune cell types, underscoring their importance in immune homeostasis. 

Beyond the gut and immune system, bile acids also act as versatile signalling molecules. They activate a range of receptors, including the nuclear farnesoid X receptor (FXR) and the membrane-bound G protein-coupled bile acid receptor 1 (TGR5). Activation of FXR influences bile acid synthesis, lipid and glucose metabolism, and liver regeneration, while TGR5 signalling affects energy expenditure, insulin sensitivity, and anti-inflammatory responses. These pathways are integral to systemic metabolic regulation. 

Bile acids also contribute to gut health by maintaining the integrity of the intestinal barrier, promoting epithelial cell renewal, and regulating gut motility through effects on smooth muscle contraction and peristalsis. Finally, bile acids help trap fat-soluble toxins in the gut so they can be excreted instead of being reabsorbed. Together, these diverse actions position bile acids as key molecular integrators of digestion, microbial ecology, immunity, detoxification and metabolism thus highlighting their central role in maintaining physiological balance across multiple organ systems.

Clinical Relevance of Bile Acid imbalances

An imbalance in bile acid metabolism can be indicative of various gastrointestinal and systemic disorders. In conditions like irritable bowel syndrome with diarrhoea (IBS-D), excessive bile acids may reach the colon due to malabsorption, stimulating fluid secretion and accelerating transit, thus contributing to symptoms. Bile acid diarrhoea, a condition overlapping with IBS-D, is recognised as a common but underdiagnosed issue. 

On the other end of the spectrum, low bile acid levels in stool are often found in individuals with constipation or slow colonic transit. In these cases, efficient reabsorption may reflect limited excretion, but it could also signal insufficient bile production or release. 

Inflammatory bowel diseases, such as Crohn’s disease and ulcerative colitis, have also been linked to altered bile acid profiles. Disruption in the conversion of primary to secondary bile acids, often due to dysbiosis or inflammation, can exacerbate mucosal damage and perpetuate immune dysfunction. The relative deficiency of beneficial secondary bile acids may compromise gut barrier integrity and promote pro- inflammatory signalling. 

Metabolic syndrome and non-alcoholic fatty liver disease (NAFLD) are also increasingly recognised as being closely linked to disruptions in bile acid signalling pathways. These metabolic disorders are characterised by a constellation of abnormalities including insulin resistance, central obesity, dyslipidaemia, and hepatic steatosis which are now understood to be influenced, in part, by bile acid receptor activity. In particular, altered activation of key bile acid receptors such as the farnesoid X receptor (FXR) and TGR5 has been implicated in the pathophysiology of these conditions. With up to 1/3 of thepopulation of Western nations now experiencing NAFLD it is even more important that we are able to utilise an array of clinical tools to identify and support resolution of this condition. 

In addition, individuals who have undergone cholecystectomy, the surgical removal of the gallbladder, often exhibit altered bile acid physiology. Without the gallbladder's reservoir function, bile is continuously secreted into the intestine rather than being released in a regulated manner in response to meals. This can lead to changes in bile acid composition and flow, which may favour the accumulation of certain secondary bile acids, such as lithocholic acid (LCA) and its derivatives. Elevated levels of LCA have been linked to increased oxidative stress, mucosal damage, and even carcinogenic potential in the colon. These shifts in bile acid profiles following cholecystectomy may have broader implications for gut microbial balance, metabolic regulation, and susceptibility to inflammation-related conditions. 

Together, these findings highlight the emerging role of bile acid signalling as a critical modulator of metabolic and hepatic health. Disruptions in bile acid homeostasis can have far-reaching effects on both local gut function and systemic metabolic outcomes.

Testing bile acids: StoolOMX™

As the science evolves, so too must our clinical approach. The StoolOMX™ test, a cutting-edge add-on to the GI-MAP® by Diagnostic Solutions Laboratory, brings bile acids into clinical focus. By measuring bile acid metabolites and short chain fatty acids (SCFAs) directly from stool, this test provides a window into the biochemical dialogue between host and microbiota, offering insights that can help clarify symptoms, refine the evaluation, and guide more personalised intervention strategies. 

The StoolOMX™ panel provides a comprehensive overview of bile acid metabolism by analysing 25 distinct bile acid metabolites. These include both primary and secondary bile acids, measured in total concentrations, percentage distribution, and specific ratios. This detailed profile allows clinicians to assess bile acid production, transformation capacity and bile acid clearance and infer microbial activity and diversity. 

A particularly valuable aspect of the panel is its assessment of key ratios, such as the lithocholic acid to deoxycholic acid (LCA/DCA) ratio. A high LCA/DCA ratio has been associated with gallstone formation, cholecystectomy, and an increased risk of colorectal cancer, while a balanced ratio may indicate a more favourable physiological state. 

The panel also evaluates the relative abundance of primary and secondary bile acids. A high percentage of primary bile acids may indicate excessive delivery to the colon or impaired microbial conversion, both of which can suggest dysbiosis or inflammation. Conversely, a high percentage of secondary bile acids generally reflects a healthy, metabolically active microbiota capable of complex transformations.

Total bile acid concentration is another critical marker. Elevated levels can suggest bile acid malabsorption or overproduction, while low levels may point to hypochlorhydria, reduced gallbladder function, or slow gastrointestinal transit. These markers, interpreted within the clinical context, offer meaningful insights into the root causes of gastrointestinal symptoms.

Alongside bile acids, StoolOMX™ also provides information on 9 different short chain fatty acids (SCFAs), which are not the topic of this blog, but which can help to complete the gastrointestinal health picture and the combination offers valuable insights into motility, metabolism, microbial activity, immune function and intestinal barrier integrity.

Integrative Interpretation and GI-MAP Correlation

The most informative use of the StoolOMX™ data arises when integrated with microbial data from the GI-MAP® test which is why it is offered as an add-on test only. Together, they provide a multi-dimensional view of gut health. For instance, a client with high levels of primary bile acids, low levels of secondary bile acids, and a GI-MAP profile indicating dysbiosis and low abundance of bile acid-transforming microbes would be understood to have impaired bile acid conversion. This could contribute to ongoing gut inflammation, compromised barrier function, and motility issues. 

In another example, elevated bile acid levels coinciding with a high steatocrit may suggest fat malabsorption, potentially due to pancreatic insufficiency or small intestinal bacterial overgrowth (SIBO). Elevated calprotectin levels, when viewed alongside altered bile acid ratios, could highlight ongoing inflammation exacerbated by bile acid-induced mucosal irritation. 

Such integrated analysis enables a deeper understanding of gastrointestinal dysfunctions and facilitates the development of more precise, individualised interventions.

Who can benefit from the add-on StoolOMX™?

Clients who experience: 

• chronic diarrhoea or constipation 
• unexplained bloating 
• abdominal pain 
• fatty stools or signs of malabsorption 
• unresolved IBS or IBD symptoms 
• persistent gut inflammation 
• dysbiosis 
• leaky gut 
• food sensitivities 
• metabolic concerns
  

To learn more about the StoolOMX™ panel please visit: https://www.colabeu.com/our-tests-non-members/#tests-Gastrointestinal. If you sign up with us, you will be able to access more in-depth information and place your orders. You can contact us via email on [email protected] or by calling us on +44 (0)1522 846 902. 

Author's Note: This blog is intended for healthcare professionals. It is not a substitute for clinical training or individual client assessment. Always interpret test results within the broader clinical context.