Fecal Primary Bile Acids: An Alternative in Chronic Diarrhea Diagnosis?

Primary bile acids (BAs) in fecal samples have a similar association as total fecal BAs when measuring fecal weight and colonic transit in the diagnosis of irritable bowel syndrome with diarrhea (IBS-D). This finding from a retrospective study suggests primary BAs can be an alternative to total fecal BAs in diagnostic testing.


Bile acid diarrhea (BAD) accounts for 1 in 4 cases of functional diarrhea or IBS-D. BAD cases are typically identified based on increased levels of BAs in fecal samples collected over a 48-hour period while on a 100-g fat diet. Other diagnostic approaches are retention of 75Se-labeled homocholic acid taurine (a test not available in the United States), serum levels of 7α-hydroxy-4-cholesten-3-one (C4) (available through referral to diagnostic laboratories), or serum levels of fibroblast growth factor 19 (a research test). 


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Until recently, the diagnosis of BAD in the United States had been based on total fecal BA excretion over 48 hours or fasting serum C4.


“Recent studies show that even when the total fecal bile acid secretion is not more than 2337 micromoles per 48 hours, the increase in primary fecal bile acids alone can provide similar diagnostic value in terms of association with increased fecal weight and accelerated colonic transit,” Michael Camilleri, MD, professor of medicine at the Mayo Clinic in Rochester, Minnesota, and coauthor of the study, told Gastroenterology Consultant.


For this study, the researchers measured fecal weight over 48 hours, colonic transit over 24 hours, and percentages of different BAs in stool samples of 64 patients with IBS-D, 30 patients with constipation-dominant IBS (IBS-C), and 30 healthy control patients.


Area under the curve analyses were performed to determine association between results of serum and stool tests and high fecal weight or rapid colonic transit.


To assess the utility of the cutoff values, the prevalence of abnormal total and percentage primary BAs during 48-hour fecal collection was also measured in a validation cohort of 938 patients with chronic diarrhea.


Outcomes >>

Overall, primary BAs of more than 10% of the total fecal bile acids identified patients with increased fecal weight with a sensitivity of 49% and specificity of 91%, and rapid colonic transit with a sensitivity of 48% and specificity of 87%.


Fecal samples collected over a 48-hour period alone, or in combination with percentage of primary fecal BAs, identified patients with increased fecal weight with an area under the receiver operating characteristics (AUROC) of 0.86.

The percentage of primary fecal BA alone measured in the 48-hour fecal collection identified patients with increased fecal weight with an AUROC of 0.73, irrespective of total fecal BA excretion.


Among the validation cohort, 45.6% of participants had fecal primary BAs of more than 10%, and 27% had increased total fecal BAs.


“More validation studies are needed to ensure diagnostic accuracy based on a random stool sample,” Camilleri said. “Until then, the bottom line is that if a patient is suspected to have bile acid malabsorption [BAM], the best test at present is the 48-hour stool test. If you only want to screen for BAM, serum 7α-hydroxy-4-cholesten-3-one is a reasonable first test, although its sensitivity is relatively lower than bile acids measured in a 48-hour fecal collection.”


—Melinda Stevens



Vijayvargiya P, Camilleri M, Chedid V, et al. Analysis of fecal primary bile acids detects increased stool weight and colonic transit in patients with chronic functional diarrhea. Clin Gastroenterol Hepatol. 2019;17(5):922-929.e2.