B0270 - Evaluation of Secondary Bile Acids in Stool as Predictors of Chronic Bile Acid (BA) Diarrhea

Saam Dilmaghani, MD, MPH, Wassel Sannaa, MBBS, Joelle BouSaba, MD, Ting Zheng, MD, Leslie Donato, PhD, Priya Vijayvargiya, MD, Michael Camilleri, MD
Mayo Clinic, Rochester, MN

Introduction: Bile acid diarrhea (BAD) accounts for ~25% of chronic “functional diarrhea” (FD). Diagnosis of BAD is currently based on serum 7αC4 >52ng/mL, total fecal BA (TBA) >2,337 µmol/48h, or fecal primary BAs [cholic acid (CA) and chenodeoxycholic acid (CDCA)] >10%. Secondary BAs [deoxycholic acid (DCA) and lithocholic acid (LCA)] are produced by 7α dehydroxylation of CA and CDCA, respectively. DCA promotes colonic secretion, serotonin release, and peristalsis. LCA is a potent stimulus of the Takeda G-protein coupled BA receptor (TGR5, or GPBAR1) which is a mechanism accelerating colonic transit. However, the utility of fecal secondary BAs (DCA and LCA) as markers of both diarrhea [increased fecal weight (FW)] and BAD is unclear.

Methods: We conducted a retrospective study of fecal BA 48h data of 913 patients with FD and no prior intestinal surgery or active inflammatory disease. Patients consumed a 100g fat diet for four days with stool collection in the final 48h. Objective diarrhea was defined as FW >400 g/48h. Associations between TBA, main BA components, observed FW, or objective diarrhea (FW >400g/48h) were assessed using linear or logistic regression as appropriate. Multivariate analyses, adjusting for age, sex, and other fecal BAs, were conducted to appraise the role of each BA component.

Results: Mean age was 51.5y (range: 11-90y), and 67.6% were female. Mean 48h FW was 546.1g (10-90%ile: 158-1056g). Mean TBA was 1921 µmol/48h (10-90%ile: 256-4328 µmol/48h). In the adjusted analyses, a 2-fold increase in CA and LCA was associated with 12.2% (95% CI: 7.4%-17.2%, p < 0.05) and 15.3% (7.9%-23.1%, p < 0.05) increases in FW, respectively. In contrast, a 2-fold increase in DCA was associated with a 6.8% (1.4%-11.9%, p < 0.05) decrease in FW. Table presents risk of FW >400g [OR (95% CI)] for a 2-fold increase in each BA (adjusted for age and sex) in all patients, and in 2 groups without or with BAD based on TBA >2,337 µmol/48h. The 48h total LCA conferred the greatest risk. In all patients, 48h fecal LCA of 360 µmol/48h had 46% sensitivity and 80% specificity for FW >400g (AUC=0.62, Figure). Adding total LCA to the prediction from total primary BAs increased the AUC from 0.75 to 0.78.

Discussion: Among patients presenting with FD, 48h fecal total LCA is associated with FW >400g with comparable risk estimates to total primary BAs and with CA alone. Therefore, fecal LCA also has potential utility in the diagnosis of BAD.




Disclosures:


Saam Dilmaghani, MD, MPH, Wassel Sannaa, MBBS, Joelle BouSaba, MD, Ting Zheng, MD, Leslie Donato, PhD, Priya Vijayvargiya, MD, Michael Camilleri, MD. B0270 - Evaluation of Secondary Bile Acids in Stool as Predictors of Chronic Bile Acid (BA) Diarrhea, ACG 2022 Annual Scientific Meeting Abstracts. Charlotte, NC: American College of Gastroenterology.