Bile and fat excretion are biomarkers of clinically significant diarrhoea and constipation in irritable bowel syndrome

Background: Biomarkers in irritable bowel syndrome (IBS) may guide targeted therapy in this multifactorial disease. It has been suggested that 75% accuracy and cost <$500 categorise biomarkers as cost-effective. Aim: To identify differences in faecal bile acids, faecal fat and fasting serum C4 (7a-hydroxy-4-cholesten-3-one) and fibroblast growth factor 19 (FGF19) among patients with IBS-D, IBS-C and healthy controls and to determine accurate, cost-effective biomarkers for clinically relevant diarrhoea and constipation. Methods: We assessed daily stool frequency and consistency (Bristol Stool Form Scale) from validated bowel diaries, 48 hours total and individual faecal bile acids, 48 hours faecal fat and weight, fasting serum C4 and FGF19, and colonic transit by scintigraphy from healthy volunteers (HV) and patients with IBS-D and IBS-C (Rome III criteria). We utilised multivariate logistic regression to determine biomarkers of clinically significant diarrhoea or constipation based on stool frequency, consistency and weight. Results: Among the 126 HV (44M/82F, 37.5 ± 10.9 years [SD]), 64 IBS-D (5M/59F, 41.9 ± 12.2 years), and 30 IBS-C (0M/30F, 44.6 ± 10 years) patients, there were significant differences between all groups in stool weight, frequency, and consistency; in addition, there were differences in colonic transit at 48 hours, faecal fat, and total and individual faecal bile acids between IBS-D and IBS-C. Reduced total and primary faecal bile acids and increased faecal lithocholic acid were significant predictors of decreased faecal weight, frequency and consistency with AUC > 0.82 (sensitivity >76%, specificity >72%). Total and primary faecal bile acids and faecal fat were significant predictors of increased stool weight, frequency and consistency with AUC > 0.71 (sensitivity >55%, specificity >74%).The faecal parameters had a 11.5 positive likelihood ratio in predicting elevated faecal weight. Conclusions: Faecal bile acids and faecal fat are cost-effective and accurate biomarkers associated with significant bowel dysfunction among IBS-D and IBS-C patients.