Surgery for Crohn’s Disease Is Associated With a Dysbiotic Microbiome and Metabolome: Results From Two Prospective Cohorts
James D. Lewis, Scott G. Daniel, Hongzhe Li, Fuhua Hao, Andrew D. Patterson, Aaron L. Hecht, Colleen Brensinger, Gary D. Wu, Kyle Bittinger, Douglas C. Wolf, Bridget M. Hron, John S. Hanson, Sanjib Mohanty, Sanjib P. Mohanty, L. Campbell Levy, Heba Iskandar, Monika Fischer, Benjamin L. Cohen, Arun Swaminath, Sunanda V. Kane, Robert P. McCabe, Eugene F. Yen, Stephen B. Hanauer, David Hudesman, Anita Afzali, Colleen Kelly, John R. Weber, Uma Mahadevan, Hans Herfarth, J.N. Katz, Sasha Taleban, David T. Rubin, Bruce Yachyshyn, Gorman Reynolds, Mark E. Gerich, Gerald W. Dryden, Sandra Quezada, Peter Higgins, Eugenia Shmidt, James D. Lewis, Marc Schwartz, Ann D. Flynn, Sumona Saha, Sara Horst, Michael Chiorean, Patrick D. Green, Ellen Scherl, Robert S. Sandler, Carol Brotherton, Lindsey Albenberg, John F. Valentine, David L. Suskind, Andrea H. Meyer, Charlene Compher, Meenakshi Bewtra, John S. Hanson, Manreet Kaur, Themistocles Dassopoulos, Scott B. Snapper, Joshua R. Korzenik, Matthew Bohm, Laura E. Raffals, Poonam Beniwal‐Patel, David Hudesman, Kirk Russ, Loren Brook, Joel Pekow, Raymond K. Cross, Uni Wong, Shrinivas Bishu, Meenakshi Bewtra, James D. Lewis, Richard H. Duerr, Sumona Saha, Freddy Caldera, Elizabeth Scoville, Parakkal Deepak, Matthew A. Ciorba, Elizabeth Scoville, Parakkal Deepak, Matthew A. Ciorba
Abstract
BACKGROUND & AIMS: Crohn's disease is associated with alterations in the gut microbiome and metabolome described as dysbiosis. We characterized the microbial and metabolic consequences of ileal resection, the most common Crohn's disease surgery. METHODS: H nuclear magnetic resonance spectroscopy. Fecal bile acids and plasma 7α-hydroxy-4-cholesten-3-one (C4) was measured with mass spectrometry. RESULTS: Intestinal resection was associated with reduced alpha diversity and altered beta diversity with increased Proteobacteria and reduced Bacteroidetes and Firmicutes. Surgery was associated with higher representation of genes in the KEGG pathway for ABC transporters and reduction in genes related to bacterial metabolism. Surgery was associated with reduced concentration of the But gene but this did not translate to reduced fecal butyrate concentration. Surgery was associated with decreased abundance of bai operon genes, with increased plasma C4 concentration, increased primary bile acids and reduced secondary bile acids, including isoLCA. Additionally, Egerthella lenta, Adlercreutzia equalofaciens, and Gordonibacter pamelaeae were lower in abundance among patients with prior surgery in both cohorts. CONCLUSIONS: In 2 different populations, prior surgery in Crohn's disease is associated with altered fecal microbiome. Patients who had undergone ileal resection had reduction in the potentially beneficial bacteria E lenta and related actinobacteria and secondary bile acids, including isoLCA, suggesting that these could be biomarkers of patients at higher risk for disease progression.