Bile Acid Composition Changes over 6 Months Following Fecal Microbiota Transplantation in Children with Recurrent C. difficile Infections: 2016 ACG Presidential Poster Award

Abstract

Introduction: The mechanism by which Fecal Microbiota Transplant (FMT) cures C. difficile infection (CDI) is incompletely understood. Some studies have suggested that bile acid composition may contribute to FMT effects independent of restored bacterial diversity. We aimed to determine bile acid profiles of pediatric CDI patients before and after FMT as well as from FMT donors. We further compared these results to our previously published 16S rRNA sequencing data from these samples. Methods: Children with a history of recurrent CDI underwent FMT by colonoscopy. Stool was collected from donors, as well as recipients prior to FMT and after FMT at 2-10 weeks, 10-20 weeks and 6 months. After acetonitrile extraction, fecal bile acids were assessed as their methyl ester derivatives by LC-MS using a Simultaneous Ion Monitoring program. The proportions of primary (1°: cholic and chenodeoxycholic) and secondary (2°: deoxycholic and lithocholic) bile acids were determined for each sample, and results were compared using independent t-tests.Figure 1Figure 2Results: All 8 children had resolution of CDI symptoms and eradication of C. difficile 10-20 weeks after FMT, as well as at 6 months for those tested. Before FMT, patients had lower proportions of 2° bile acids compared to donors (31.5% vs 95.0%, p < 0.001), but were restored to donor levels by 6 months (p=0.16). Of the patients, 5 had IBD. Bile acid proportions did not differ by IBD status at baseline. However after 6 months, differences between non-IBD patients and donors persisted for both 1° (23.5% vs 4.7%, p < 0.05) and 2° (74.3% vs 95.0%, p < 0.05) bile acids whereas IBD patients normalized. In comparison to bacterial diversity, bile acid profiles took longer to normalize. Furthermore, whereas bacterial diversity remained restored in non-IBD patients but returned to low baseline values among IBD patients at 6 months, 2° bile acids levels remained normal in IBD patients. Conclusion: Increased 1° bile acids were found in pre-FMT samples, regardless of IBD status. Interestingly, IBD patients exhibited a stronger reversion towards donor bile acid compositions following FMT even though they did not differ from non-IBD patients at baseline. Furthermore, IBD patients had normalized bile acid profiles, even though their gut bacterial diversity returned to pre-FMT values by 6 months. Our results demonstrate that bile acid profiles may change independently of gut bacterial diversity following FMT and may differ by IBD status.