Bile acid diarrhoea (BAD) is a common yet under-diagnosed and under-recognised disease.
The primary symptoms are watery diarrhoea with high frequency of unpredictable bowel
movements,urgency and faecal incontinence making BAD a debilitating condition. The
pathophysiology of BAD involves spill-over of bile acids to the colon where bile acids
irritate the colonic mucosa and cause osmotic-induced fluid secretion. The aetiology of
BAD can be either idiopathic (termed primary BAD or type 2 BAD) or the disease can
develop secondary to ileal dysfunction (due to, e.g., intestinal surgery or Chron's
disease, termed type 1 BAD) or other conditions interfering with ileal absorption (due
to, e.g., cholecystectomy or radiation therapy, termed type 3 BAD).
Irritable bowel syndrome (IBS) with predominant diarrhoea is a common condition in the
general population (prevalence of around 4%) and emerging data suggest that around 1/3
suffering from this condition in fact have BAD. Many of these patients remains
undiagnosed and thus,inappropriately treated or even untreated. A major reason for this
is challenges associated with diagnosing BAD. Several diagnostic modalities have been
suggested including 14C-glycocholate breath test, stool test and assessment of 48-hour
faecal bile acid output. These tests are cumbersome, time-consuming, and not widely
available. The 75selenium homocholic acid taurine (SeHCAT) test is considered the gold
standard for the diagnosis of BAD. It measures, via a standard gamma camera, the 7-day
retention of a taurine-conjugated bile acid analogue labelled with the gamma-emitter
75selenium. This test provides a quantitative assessment to estimate the severity of BAD,
but there is no general agreement regarding its cut-off value and the test is not widely
available or even approved for clinical use in many countries outside Europe, including
the USA. Furthermore, the SeHCAT test is cumbersome due to its dependence on two visits
to the clinic exactly seven days apart, it is expensive, and involves radioactive
exposure to the patient. Given the limited availability and the challenges associated
with the abovementioned tests, excluding BAD is unfortunately not within current routine
investigational algorithms for diarrhoea-predominant IBS, Crohn's disease, or
gastrointestinal cancers. In many cases, BAD diagnosis is considered after therapeutic
trial using bile acid sequestrants. However, these agents are expensive, often
ineffective and/or associated with gastrointestinal side effects in patients with
established BAD why their potential as diagnostic tools is limited. Taken together,
diagnosing BAD is currently associated with challenges that may preclude relevant
treatment of this debilitating condition warranting development of easy and accessible
yet safe and effective BAD diagnostics. Recently, the investigators have developed a new
BAD diagnostic method based on a single blood sample from the patient. Our approach is
based on unbiased, metabolic profiling of serum from BAD patients and carefully matched
healthy individuals using comprehensive ultra-high-performance liquid chromatography
time-of-flight mass-spectrometry. These comprehensive datasets were subjected to
state-of-the-art machine learning and used to build a BAD diagnostic score (BDS) that can
distinguish a patient suffering BAD from healthy individuals with high precision
(sensitivity of 78% and specificity of 93%). In the present study, the investigators will
refine the BDS to distinguish between patients suffering from BAD and patients suffering
from other diarrhoeal diseases by using the same methods and data analyses as in the
previous project, but in this case applied to serum samples collected from patients
referred to diagnostic SeHCAT test, i.e., samples from both test-positive and
test-negative patients.