Reinventing BAD diagnosis with fast, non-invasive testing

Reinventing BAD diagnosis with fast, non-invasive testing

Professor Julian Walters, Consultant Gastroenterologist, Imperial College Healthcare Trust

Bile acid diarrhoea (BAD) is a common but often overlooked condition that can have a significant impact on a patient’s quality of life, affecting their mental health and productivity.¹ The disorder can leave individuals housebound due to their unpredictable and uncomfortable symptoms, including persistent or intermittent diarrhoea, urgency, incontinence, flatulence and abdominal pain. This blog looks at challenges facing BAD detection, and the need for fast and accurate diagnostic testing to speed up triage and enable earlier treatment.

Prevalence and causes of BAD

BAD affects approximately 1-2 % of the UK population, a prevalence similar to that of coeliac disease,^2,3 and is present in up to a third of patients diagnosed with diarrhoea-predominant irritable bowel syndrome (D-IBS).⁴ The condition arises when bile acids are not adequately reabsorbed or when they are overproduced, for example due to an impaired fibroblast growth factor 19 (FGF19) signalling feedback mechanism. Secondary BAD frequently occurs in patients with Crohn’s disease – over 90 % of Crohn’s patients who have undergone terminal ileal resection may develop BAD⁵ – and following radiotherapy for gynaecological or prostate cancers, due to post-radiation enteropathy or small intestinal bacterial overgrowth, both of which can disrupt the enterohepatic recycling of bile acids. BAD is a recognised complication of gastrointestinal surgeries, including cholecystectomy, right-sided hemicolectomy, ileal resection and gastrectomy. On top of this, 25-50 % of people with functional diarrhoea exhibit signs of BAD in their blood tests, bile acid retention assessments or faecal measurements.²

Barriers to accurate diagnosis

Diagnosing BAD earlier benefits both healthcare providers and patients as it reduces the number of investigations required. It can also enable earlier treatment with bile acid sequestrants like colestyramine and colesevelam, which bind bile acids in the gut, preventing diarrhoea. Despite the condition being more prevalent than some better-known gastrointestinal conditions, delayed diagnosis is still a major problem; one study showed that 44 % of BAD patients can experience symptoms for more than five years before a diagnosis is confirmed. One reason for this is the current testing pathway.⁶ If a patient presents with chronic diarrhoea, British Society of Gastroenterology guidelines prioritise ruling out serious conditions like colorectal cancer and inflammatory bowel disease (IBD), followed by investigations for thyroid dysfunction, medication side effects, anaemia, coeliac disease  and gastrointestinal inflammation.⁷ The guidelines also recommend testing for BAD only in patients who experience persistent diarrhoea but show normal results in all other tests. However, by this time, patients have already gone through many tests and a lot of time has passed before clinicians can conclusively identify BAD as the root cause.⁷ BAD is also frequently misdiagnosed as functional diarrhoea or D-IBS because the symptoms overlap, and this effectively halts any further investigation. In the absence of a definitive diagnostics pathway for BAD, patients may instead be treated empirically to see if symptoms improve, particularly in younger patients with longstanding intermittent symptoms. Unfortunately, the success rate of trial treatment with bile acid sequestrants without a formal prior diagnosis of BAD is only around 25 %.⁸

Testing options for BAD

Once BAD is suspected, there are several testing options available, with the gold standard in many countries being to measure faecal bile acids during a 48-hour collection. Diagnosing BAD using this approach is based on three parameters: the total faecal bile acid excretion over 48 hours, the presence of more than 10 % primary bile acids in the stool, and the combination of total faecal bile acids in excess of 1,000 µmol/48 h plus more than 4 % primary bile acids. The test has a sensitivity of 57 % and a relative specificity of 77 % at a cut-off of 4.3 µmol/g, indicating that while it can be useful, it may not be definitive for all patients.⁵ It is also time consuming and cumbersome, presenting challenges with storage and homogenisation, and requiring specialised mass spectrophotometry for primary bile acid determination, making it impractical for routine use.⁹

Another option is the seven-day scintigraphy ⁷⁵selenium homotaurocholic acid (⁷⁵SeHCAT) test – a nuclear medicine scan – which measures bile acid retention using a radiolabelled bile acid compound. It is non-invasive, requiring only gamma scanning and two visits over seven days, making it more patient friendly than faecal bile acid collections. The test shows high specificity and sensitivity, providing a direct and reliable measure of bile acid retention. This makes it particularly helpful for differentiating BAD from D-IBS and other causes of chronic diarrhoea, guiding targeted treatment and reducing unnecessary procedures like colonoscopies and CT scans. The ⁷⁵SeHCAT test is also useful for identifying primary and secondary BAD in conditions like Crohn’s disease, post-cholecystectomy and radiation enteropathy, and can help in long-term disease management, predicting the severity of bile acid loss in chronic cases. However, even if BAD is suspected, patients in the UK are not immediately referred for ⁷⁵SeHCAT testing; it is an expensive hospital-based investigation and GPs usually cannot request it directly, limiting its application in routine healthcare.

Serum C4 (7α-hydroxy-4-cholesten-3-one) is a biomarker for hepatic bile acid synthesis that can indicate bile acid malabsorption. High C4 levels suggest increased bile acid production due to excessive loss, but the test lacks sensitivity, meaning that BAD cannot be ruled out with borderline or low results.⁵ Some patients with low ⁷⁵SeHCAT results do not show elevated C4 levels, though adjusting cut-off values can improve accuracy. A newer approach combines a single fasting serum C4 sample with primary bile acid measurement in the stool, improving sensitivity to around 60 % and specificity to 80 %.⁹ In the UK, research comparing total bile acid concentration from a single stool sample with ⁷⁵SeHCAT retention suggests this could be a viable screening method, achieving approximately 75 % sensitivity at 80 % specificity.¹⁰

The need for a new diagnostic pathway

There are a number of simple, non-invasive and cost-effective tests available that can simultaneously test for – and exclude – cancer, inflammation and other major treatable conditions as the cause of diarrhoea. However, these tests cannot definitively exclude BAD, and so there is a pressing need for non-invasive and reliable screening tests that can be used to quickly and confidently determine the likelihood of an individual having BAD. The IDK^® Faecal Bile Acids assay has the potential to provide a fast, affordable and non-invasive approach to distinguish between different causes of chronic diarrhoea. This photometric assay can be integrated into initial diagnostic steps; if a faecal calprotectin test comes back negative, the same stool sample can be used to check for bile acids as a follow-up test. This streamlined approach enables clinicians to gather additional diagnostic insights without requiring extra patient visits or sample collections. Making the IDK bile acids test more widely available – and requestable by GPs – could present a quick and efficient method to rule out BAD as a potential cause of chronic diarrhoea, reducing the need for more expensive or invasive procedures like the ⁷⁵SeHCAT scan or colonoscopy. With a price of approximately £15 per test – significantly lower than the £400 cost of a ⁷⁵SeHCAT scan or the £500+ expense of a colonoscopy – early faecal bile acid testing is a cost-effective tool for guiding further investigations, while keeping patients themselves out of secondary care. This approach may lead to quicker diagnosis, improving patient outcomes, cutting healthcare expenses and reducing clinician workload.

Next steps in BAD diagnosis and management

The future of BAD diagnosis and treatment is focused on developing and validating new tests, releasing more effective treatments and conducting ongoing research into how bile acid sequestrants affect gut health and metabolism. A single-sample test would be the most practical option in clinical practice – helping with patient compliance in stool collection – but it must be sensitive enough to avoid misdiagnosis. Currently, bile acid sequestrants help manage symptoms, but they don’t regulate bile acid production. However, emerging treatments – like the FXR agonists obeticholic acid and tropifexor,  and FGF19 analogues such as aldafermin  – could soon change that.^2,9,11 With better understanding of which bile acids cause symptoms, doctors will be able to refine diagnostics and treatment strategies, improving outcomes and supporting easier disease management.

You can find out more about BIOHIT HealthCare’s IDK Bile Acids assay here.

Read more about challenges in diagnosing BAD in this blog.

References

BouSaba J, Sannaa W, McKinzie S, et al. Impact of Bile Acid Diarrhea in Patients With Diarrhea-Predominant Irritable Bowel Syndrome on Symptoms and Quality of Life. Clinical Gastroenterology and Hepatology. 2022;20(9):2083-2090.e1. doi:10.1016/j.cgh.2021.11.035
British Society of Gastroenterology. BSG Global Grand Rounds Episode 1: Bile Salt Malabsorption with Professor Camilleri . https://www.bsg.org.uk/web-education/ggr-bile-salt-malabsorption. Published online May 21, 2023.
Valentin N, Camilleri M, Altayar O, et al. Biomarkers for bile acid diarrhoea in functional bowel disorder with diarrhoea: a systematic review and meta-analysis. Gut. 2016;65(12):1951-1959. doi:10.1136/gutjnl-2015-309889
Walters JRF, Pattni SS. Managing bile acid diarrhoea. Therap Adv Gastroenterol. 2010;3(6):349-357. doi:10.1177/1756283X10377126
Kumar A. The Effects of Bile Acid Sequestrants on the Microbiome in the Diagnosis and Management of Bile Acid Diarrhoea and Post-Operative Crohn’s Disease. PhD thesis . University of Wolverhampton ; 2023. Accessed March 18, 2025. https://wlv.openrepository.com/handle/2436/625267
Bannaga A, Kelman L, O’Connor M, Pitchford C, Walters JRF, Arasaradnam RP. How bad is bile acid diarrhoea: an online survey of patient-reported symptoms and outcomes. BMJ Open Gastroenterol. 2017;4(1):e000116. doi:10.1136/bmjgast-2016-000116
Arasaradnam RP, Brown S, Forbes A, et al. Guidelines for the investigation of chronic diarrhoea in adults: British Society of Gastroenterology, 3rd edition. Gut. 2018;67(8):1380-1399. doi:10.1136/gutjnl-2017-315909
Costa S, Gattoni S, Nicolardi ML, et al. Prevalence and clinical features of bile acid diarrhea in patients with chronic diarrhea. J Dig Dis. 2021;22(2):108-112. doi:10.1111/1751-2980.12969
Camilleri M, Nurko S. Bile Acid Diarrhea in Adults and Adolescents. Neurogastroenterology & Motility. 2022;34(4). doi:10.1111/nmo.14287
Kumar A, Al-Hassi HO, Jain M, et al. A single faecal bile acid stool test demonstrates potential efficacy in replacing SeHCAT testing for bile acid diarrhoea in selected patients. Sci Rep. 2022;12(1):8313. doi:10.1038/s41598-022-12003-z
Walters JRF, Sikafi R. Managing bile acid diarrhea: aspects of contention. Expert Rev Gastroenterol Hepatol. 2024;18(9):521-528. doi:10.1080/17474124.2024.2402353