Inflammation during inflammatory bowel disease may alter nutrient availability to adherent mucosal bacteria and impact their metabolic function. Microbial metabolites may regulate intestinal CD4+ T-cell homeostasis. We investigated the relationship between inflammation and microbial function by inferred metagenomics of the mucosal microbiota from colonic pinch biopsies of patients with inflammatory bowel disease.
Paired pinch biopsy samples of known inflammation states were analyzed from ulcerative colitis (UC) (23), Crohn's disease (CD) (21), and control (24) subjects by 16S ribosomal sequencing, histopathologic assessment, and flow cytometry. PICRUSt was used to generate metagenomic data and derive relative Kyoto Encyclopedia of Genes and Genomes Pathway abundance information. Leukocytes were isolated from paired biopsy samples and analyzed by multicolor flow cytometry. Active inflammation was defined by neutrophil infiltration into the epithelium.
Carriage of metabolic pathways in the mucosal microbiota was relatively stable among patients with inflammatory bowel disease, despite large variations in individual bacterial community structures. However, microbial function was significantly altered in inflamed tissue of UC patients, with a reduction in carbohydrate and nucleotide metabolism in favor of increased lipid and amino acid metabolism. These differences were not observed in samples from CD patients. In CD, microbial lipid, carbohydrate, and amino acid metabolism tightly correlated with the frequency of CD4+Foxp3+ Tregs, whereas in UC, these pathways correlated with the frequency of CD4+IL-22+ (TH22) cells.
Metabolic pathways of the mucosal microbiota in CD do not vary as much as UC with inflammation state, indicating a more systemic perturbation of host–bacteria interactions in CD compared with more localized dysfunction in UC.
Supplemental Digital Content is Available in the Text.Article first Published online 27 February 2014
Departments of *Medicine, and
†Microbiology, New York University School of Medicine, New York, New York;
‡Department of Medicine, Division of Gastroenterology, Mount Sinai School of Medicine, New York, New York;
§Immunology Institute, Mount Sinai School of Medicine, New York, New York; and
‖VA New York Harbor Healthcare System, New York, New York.
Reprints: P'ng Loke, PhD, Department of Microbiology, New York University School of Medicine, 341 East 25th Street, New York, NY 10010 (e-mail: Png.firstname.lastname@example.org).
The authors have no conflicts of interest to disclose.
Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal's Web site (www.ibdjournal.org).
M. Davenport, J. Poles and J. M. Leung contributed equally to this study.
Supported by the National Institutes of Health (NIH) grants (5R01AI093811 and 3R21AI094166), the Broad Medical Research Program of The Broad Foundation, and the Kevin and Masha Keating Family Foundation (P.L.); L. Mayer is supported by NIH grant (P01 DK072201); I. Cho is supported in part by NIH grant (UL1 TR000038). J. Poles is a recipient of an AGA-Eli and Edythe Broad Student Research Fellowship.
Received November 25, 2013
Accepted January 24, 2014