P0124 - Bile Acid Profile Changes and Persistent Gastrointestinal Symptoms in Patients Following Clostridioides difficile Infection

Janice Cho, MD, William Harmsen, , Michael Camilleri, MD, Madhusudan Grover, MBBS, Darrell Pardi, MD, MS, Sahil Khanna, MBBS, MS
Mayo Clinic, Rochester, MN

Introduction: Patients commonly develop persistent gastrointestinal (GI) symptoms following C. difficile infection (CDI). There is sparse literature regarding fecal bile acid (BA) composition in patients with persistent GI symptoms post-CDI. Fecal BA excretion in a random stool sample is highly concordant to a 48-hour collection (correlation coefficient of 0.947); coefficients are moderate for the secondary BAs, lithocholic acid (LCA) and deoxycholic acid (DCA), and higher for primary BAs, chenodeoxycholic acid (CDCA), cholic acid (CA) in patients with intact colon, suggesting random stool samples may be used. We measured primary and secondary BAs at the time of diagnosis and after CDI treatment and compared the individual BAs and primary to secondary BA ratios in patients with and without persistent gastrointestinal (GI) symptoms after CDI.

Methods: Adult patients without chronic diarrhea who tested positive for C. difficile by toxin PCR for an index CDI episode were enrolled prospectively. Patients were contacted every 14 days to fill out GI symptom questionnaires for the first 8 weeks and then at 3 and 6 months. Single stool samples at CDI diagnosis and at the end of treatment were used for BA analysis. Fecal BA analysis (primary and secondary BAs) was performed by high performance liquid chromatography and tandem mass spectrometry.

Results: A total of 33 patients (63.6% female and 90.9% Caucasian, median age 64 years [range 19 - 86 years]) completed at least 8 weeks of follow-up. Most patients were treated with vancomycin (n=31, 93.9%). Overall, 8 patients (24.2%,) developed persistent gastrointestinal symptoms similar to irritable bowel syndrome (IBS) with 6 submitting end-of-treatment stool sample. The median length of time between CDI diagnosis and development of GI symptoms similar to of IBS was 40.5 days (IQR 23 to 78 days). Five of 6 patients (83.3%) who developed GI symptoms suggestive of IBS and 17 of 20 (85%) patients who did not develop these symptoms; had a higher post-treatment primary to secondary bile acid ratio. Table 1 outlines the bile acid composition comparisons amongst the 2 groups.

Discussion: Patients with and without GI symptoms similar to IBS post-CDI had higher post-treatment primary to secondary bile acid ratio. Bile acid profiles post-treatment may reflect gut microbial changes that may lead to reduction of secondary BA conversion.

Bile acid	No GI symptoms (N = 25)	GI symptoms (N = 10)	P-value
Total primary BA at diagnosis	1.1 (0.2, 8)	1.4 (0.2, 147.7)	0.92
CDCA at diagnosis	0.4 (0.1, 3.6)	0.2 (0.1, 3.4)	0.95
CA at diagnosis	0.5 (0.1, 3.8)	0.9 (0.1, 7.8)	0.77
Total secondary BA at diagnosis	3.2 (0.6, 14.3)	10.8 (1, 30.3)	0.25
LCA at diagnosis	0.4 (0.1, 5.0)	4.2 (0.4, 5.6)	0.20
DCA at diagnosis	0.5 (0.3, 5.5)	6.2 (0.4, 15.1)	0.18
UDCA at diagnosis	0.3 (0, 0.9)	0.2 (0.1, 0.3)	0.77
Primary to secondary BA ratio at diagnosis	0.4 (0.1, 1.7)	0.8 (0, 1.6)	0.75
	No GI symptoms (N = 20)	GI symptoms (N = 6)
Total primary BA at end-of-treatment	16.4 (9.3, 33.1)	11.8 (5.2, 15.6)	0.38
CDCA at end-of-treatment	4.4 (1.8, 7.6)	1.5 (1.2, 1.9)	0.06
CA at end-of-treatment	11 (6.1, 23.1)	11.1 (3.9, 13.7)	0.69
Total secondary BA at end-of-treatment	1 (0.3, 5.3)	2.1 (0.5, 2.7)	0.95
LCA at end-of-treatment	0.2 (0, 0.4)	0 (0, 0.4)	0.36
DCA at end-of-treatment	0.2 (0.2, 0.4)	0.3 (0.1, 0.7)	0.83
UDCA at end-of-treatment	0.3 (0, 4.3)	0.7 (0.2, 0.2)	0.88
Primary to secondary BA ratio at end-of-treatment	21.5 (2.6, 96.9)	12 (2.2, 32.6)	0.69
	End-of-treatment primary to secondary BA ratio >1	End-of-treatment primary to secondary BA ratio < 1
Patients with GI symptoms suggestive of IBS after CDI (total N = 6)	5 (83.3%)	1 (16.7%)
Patients who did not develop GI symptoms suggestive of IBS after CDI (total N = 20)	17 (85%)	3 (15%)

Table: Bile acid composition at CDI diagnosis and end-of-treatment (data in mcmol/L, median, IQR)


Disclosures:
Janice Cho indicated no relevant financial relationships.
William Harmsen indicated no relevant financial relationships.
Michael Camilleri indicated no relevant financial relationships.
Madhusudan Grover indicated no relevant financial relationships.
Darrell Pardi indicated no relevant financial relationships.
Sahil Khanna indicated no relevant financial relationships.


Janice Cho, MD, William Harmsen, , Michael Camilleri, MD, Madhusudan Grover, MBBS, Darrell Pardi, MD, MS, Sahil Khanna, MBBS, MS. P0124 - Bile Acid Profile Changes and Persistent Gastrointestinal Symptoms in Patients Following Clostridioides difficile Infection, ACG 2021 Annual Scientific Meeting Abstracts. Las Vegas, Nevada: American College of Gastroenterology.