Nur M Shahir1,2,3, Jeremy R Wang2, E Ashley Wolber4, Matthew S Schaner4, Daniel N Frank5, Diana Ir5, Charles E Robertson5, Nicole Chaumont6, Timothy S Sadiq6, Mark J Koruda6, Reza Rahbar7, B Darren Nix8, Rodney D Newberry8, R Balfour Sartor3,4, Shehzad Z Sheikh2,3,4, Terrence S Furey2,3,9,10. 1. Curriculum in Bioinformatics and Computational Biology, University of North Carolina (UNC) at Chapel Hill, Chapel Hill, North Carolina, USA. 2. Department of Genetics, UNC at Chapel Hill, Chapel Hill, North Carolina, USA. 3. Center for Gastrointestinal Biology and Disease, UNC at Chapel Hill, Chapel Hill, North Carolina, USA. 4. Department of Medicine, UNC at Chapel Hill, Chapel Hill, North Carolina, USA. 5. Department of Medicine, University of Colorado Anschutz Medical Campus, Aurora, Colorado, USA. 6. Department of Surgery, UNC at Chapel Hill, Chapel Hill, North Carolina, USA. 7. Department of Surgery, REX Healthcare of Wakefield, Wakefield, North Carolina, USA. 8. Division of Gastroenterology, John T. Milliken Department of Medicine, Washington University in St. Louis, School of Medicine, St. Louis, Missouri, USA. 9. Lineberger Comprehensive Cancer Center, UNC at Chapel Hill, Chapel Hill, North Carolina, USA. 10. Department of Biology, UNC at Chapel Hill, Chapel Hill, North Carolina, USA.
Abstract
BACKGROUND: The intestinal microbiota play a key role in the onset, progression, and recurrence of Crohn disease (CD). Most microbiome studies assay fecal material, which does not provide region-specific information on mucosally adherent bacteria that directly interact with host systems. Changes in luminal oxygen have been proposed as a contributor to CD dybiosis. METHODS: The authors generated 16S rRNA data using colonic and ileal mucosal bacteria from patients with CD and without inflammatory bowel disease. We developed profiles reflecting bacterial abundance within defined aerotolerance categories. Bacterial diversity, composition, and aerotolerance profiles were compared across intestinal regions and disease phenotypes. RESULTS: Bacterial diversity decreased in CD in both the ileum and the colon. Aerotolerance profiles significantly differed between intestinal segments in patients without inflammatory bowel disease, although both were dominated by obligate anaerobes, as expected. In CD, high relative levels of obligate anaerobes were maintained in the colon and increased in the ileum. Relative abundances of similar and distinct taxa were altered in colon and ileum. Notably, several obligate anaerobes, such as Bacteroides fragilis, dramatically increased in CD in one or both intestinal segments, although specific increasing taxa varied across patients. Increased abundance of taxa from the Proteobacteria phylum was found only in the ileum. Bacterial diversity was significantly reduced in resected tissues of patients who developed postoperative disease recurrence across 2 independent cohorts, with common lower abundance of bacteria from the Bacteroides, Streptococcus, and Blautia genera. CONCLUSIONS: Mucosally adherent bacteria in the colon and ileum show distinct alterations in CD that provide additional insights not revealed in fecal material.
BACKGROUND: The intestinal microbiota play a key role in the onset, progression, and recurrence of Crohn disease (CD). Most microbiome studies assay fecal material, which does not provide region-specific information on mucosally adherent bacteria that directly interact with host systems. Changes in luminal oxygen have been proposed as a contributor to CD dybiosis. METHODS: The authors generated 16S rRNA data using colonic and ileal mucosal bacteria from patients with CD and without inflammatory bowel disease. We developed profiles reflecting bacterial abundance within defined aerotolerance categories. Bacterial diversity, composition, and aerotolerance profiles were compared across intestinal regions and disease phenotypes. RESULTS: Bacterial diversity decreased in CD in both the ileum and the colon. Aerotolerance profiles significantly differed between intestinal segments in patients without inflammatory bowel disease, although both were dominated by obligate anaerobes, as expected. In CD, high relative levels of obligate anaerobes were maintained in the colon and increased in the ileum. Relative abundances of similar and distinct taxa were altered in colon and ileum. Notably, several obligate anaerobes, such as Bacteroides fragilis, dramatically increased in CD in one or both intestinal segments, although specific increasing taxa varied across patients. Increased abundance of taxa from the Proteobacteria phylum was found only in the ileum. Bacterial diversity was significantly reduced in resected tissues of patients who developed postoperative disease recurrence across 2 independent cohorts, with common lower abundance of bacteria from the Bacteroides, Streptococcus, and Blautia genera. CONCLUSIONS: Mucosally adherent bacteria in the colon and ileum show distinct alterations in CD that provide additional insights not revealed in fecal material.
Authors: Janet G M Markle; Daniel N Frank; Steven Mortin-Toth; Charles E Robertson; Leah M Feazel; Ulrike Rolle-Kampczyk; Martin von Bergen; Kathy D McCoy; Andrew J Macpherson; Jayne S Danska Journal: Science Date: 2013-01-17 Impact factor: 47.728
Authors: Yael Haberman; Timothy L Tickle; Phillip J Dexheimer; Mi-Ok Kim; Dora Tang; Rebekah Karns; Robert N Baldassano; Joshua D Noe; Joel Rosh; James Markowitz; Melvin B Heyman; Anne M Griffiths; Wallace V Crandall; David R Mack; Susan S Baker; Curtis Huttenhower; David J Keljo; Jeffrey S Hyams; Subra Kugathasan; Thomas D Walters; Bruce Aronow; Ramnik J Xavier; Dirk Gevers; Lee A Denson Journal: J Clin Invest Date: 2014-07-08 Impact factor: 14.808
Authors: Benjamin J Callahan; Paul J McMurdie; Michael J Rosen; Andrew W Han; Amy Jo A Johnson; Susan P Holmes Journal: Nat Methods Date: 2016-05-23 Impact factor: 28.547
Authors: Dermot P B McGovern; Jonathan Braun; Jonathan P Jacobs; Maryam Goudarzi; Venu Lagishetty; Dalin Li; Tytus Mak; Maomeng Tong; Paul Ruegger; Talin Haritunians; Carol Landers; Philip Fleshner; Eric Vasiliauskas; Andrew Ippoliti; Gil Melmed; David Shih; Stephan Targan; James Borneman; Albert J Fornace Journal: Genome Med Date: 2022-08-15 Impact factor: 15.266