Jill Gaidos, MD, FACG
Associate Professor of Internal Medicine; Director, Inflammatory Bowel Disease
Virginia Commonwealth University; Hunter Holmes McGuire VA Medical Center
Richmond, VA
Jill Gaidos, MD, FACG1, Jason D. Kang, BS1, Genta Kakiyama, PhD1, William M. Pandak, Jr., MD2, Phillip B. Hylemon, PhD1
1Virginia Commonwealth University, Richmond, VA; 2McGuire Veterans Affairs Medical Center, Richmond, VA
Introduction: Ulcerative colitis (UC) is a chronic relapsing inflammatory disease of the colon associated with an increased risk for Clostridioides difficile infection (CDI). C. difficile is a spore-forming organism that colonizes the GI tract and is potentially pathogenic. Under healthy conditions, homeostasis of the gut microbiome plays a role in preventing germination of C. difficile spores while bile acids are vital to the germination process. Primary bile acids can stimulate germination of C. difficile spores while secondary bile acids inhibit growth of the vegetative form. The aim of this study is to assess for changes in the gut microbiome and bile acid profile with active UC as compared to remission that may explain the increased CDI risk.
Methods: After obtaining IRB approval, we performed a single center, prospective, cohort study of Veteran’s with active UC at the McGuire VA Medical Center. After obtaining consent, subjects with active UC, based on markers of inflammation and elevated Simple Clinical Colitis Activity Index score (≥ 5), provided a stool sample for analysis of the gut microbiome (using fingerprinting of the 16S rRNA), bile acid profile (using high performance liquid chromatography) and for the presence of Clostridioides species (using 7α-dehydroxylating bacteria analysis). Subjects were treated for their active UC and a second stool sample was collected in the setting of clinical remission for repeat analyses.
Results: Four males with active UC enrolled, median age 61 yrs, however subject 2 was excluded due to suboptimal sample size. The total bile acids were relatively unchanged in both samples however there were less secondary bile acids (deoxycholic acid and lithocholic acid) in the remission samples in 2 of 3 subjects (Table 1). With active UC, study subjects had a higher concentration of C. scindens (Figure 1). Inversely, subjects had higher concentrations of the C. difficile toxin B gene during clinical remission (Figure 2). The results of the microbiome analysis are pending.
Discussion: In this limited pilot study, we found that patients with UC have a decreased luminal concentration of both total and secondary bile acids compared to healthy controls. Active UC seems to lead to a decrease in secondary bile acids, including C. scindens, with a subsequent increase in the presence of C. difficile toxin. This change in bile acid profile could be contributing to the increased prevalence of CDI in IBD patients.
Citation: Jill Gaidos, MD, FACG; Jason D. Kang, BS; Genta Kakiyama, PhD; William M. Pandak, Jr., MD; Phillip B. Hylemon, PhD. P1392 - PILOT STUDY OF GUT DYSBIOSIS AND BILE ACID DYSMETABOLISM IN ACTIVE ULCERATIVE COLITIS. Program No. P1392. ACG 2019 Annual Scientific Meeting Abstracts. San Antonio, Texas: American College of Gastroenterology.