Microgeographic Proteomic Networks of the Human Colonic Mucosa and Their Association With Inflammatory Bowel DiseaseSummary

Xiaoxiao Li; James LeBlanc; David Elashoff; Ian McHardy; Maomeng Tong; Bennett Roth; Andrew Ippoliti; Gildardo Barron; Dermot McGovern; Keely McDonald; Rodney Newberry; Thomas Graeber; Steve Horvath; Lee Goodglick; Jonathan Braun

Cellular and Molecular Gastroenterology and Hepatology (Sep 2016)

Microgeographic Proteomic Networks of the Human Colonic Mucosa and Their Association With Inflammatory Bowel DiseaseSummary

Xiaoxiao Li,
James LeBlanc,
David Elashoff,
Ian McHardy,
Maomeng Tong,
Bennett Roth,
Andrew Ippoliti,
Gildardo Barron,
Dermot McGovern,
Keely McDonald,
Rodney Newberry,
Thomas Graeber,
Steve Horvath,
Lee Goodglick,
Jonathan Braun

Affiliations

Xiaoxiao Li: Department of Molecular and Medical Pharmacology, University of California Los Angeles David Geffen School of Medicine, Los Angeles, California; Department of Pathology and Laboratory Medicine, University of California Los Angeles David Geffen School of Medicine, Los Angeles, California; Inflammatory Bowel and Immunobiology Research Institute, Cedars-Sinai Medical Center, Los Angeles, California
James LeBlanc: Department of Pathology and Laboratory Medicine, University of California Los Angeles David Geffen School of Medicine, Los Angeles, California
David Elashoff: Department of Medicine, University of California Los Angeles David Geffen School of Medicine, Los Angeles, California
Ian McHardy: Department of Pathology and Laboratory Medicine, University of California Los Angeles David Geffen School of Medicine, Los Angeles, California
Maomeng Tong: Department of Molecular and Medical Pharmacology, University of California Los Angeles David Geffen School of Medicine, Los Angeles, California
Bennett Roth: Department of Medicine, University of California Los Angeles David Geffen School of Medicine, Los Angeles, California
Andrew Ippoliti: Inflammatory Bowel and Immunobiology Research Institute, Cedars-Sinai Medical Center, Los Angeles, California
Gildardo Barron: Inflammatory Bowel and Immunobiology Research Institute, Cedars-Sinai Medical Center, Los Angeles, California
Dermot McGovern: Inflammatory Bowel and Immunobiology Research Institute, Cedars-Sinai Medical Center, Los Angeles, California
Keely McDonald: Department of Internal Medicine, Washington University School of Medicine, St. Louis, Missouri
Rodney Newberry: Department of Internal Medicine, Washington University School of Medicine, St. Louis, Missouri
Thomas Graeber: Department of Molecular and Medical Pharmacology, University of California Los Angeles David Geffen School of Medicine, Los Angeles, California
Steve Horvath: Department of Human Genetics and Biostatistics, University of California Los Angeles David Geffen School of Medicine, Los Angeles, California
Lee Goodglick: Department of Pathology and Laboratory Medicine, University of California Los Angeles David Geffen School of Medicine, Los Angeles, California
Jonathan Braun: Department of Molecular and Medical Pharmacology, University of California Los Angeles David Geffen School of Medicine, Los Angeles, California; Department of Pathology and Laboratory Medicine, University of California Los Angeles David Geffen School of Medicine, Los Angeles, California; Correspondence Address correspondence to: Jonathan Braun, MD, PhD, Department of PathologyÂ and Laboratory Medicine, University of California Los Angeles David Geffen School of Medicine, Los Angeles, California 90095. fax: (310) 267-4486.

Journal volume & issue: Vol. 2, no. 5
pp. 567 – 583

Abstract

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Background & Aims: Interactions between mucosal cell types, environmental stressors, and intestinal microbiota contribute to pathogenesis in inflammatory bowel disease (IBD). Here, we applied metaproteomics of the mucosalâluminal interface to study the disease-related biology of the human colonic mucosa. Methods: We recruited a discovery cohort of 51 IBD and non-IBD subjects endoscopically sampled by mucosal lavage atÂ 6 colonic regions, and a validation cohort of 38 no-IBD subjects. Metaproteome data sets were produced for each sample and analyzed for association with colonic site and disease state using a suite of bioinformatic approaches. Localization of select proteins was determined by immunoblot analysis and immunohistochemistry of human endoscopic biopsy samples. Results: Co-occurrence analysis of the discovery cohort metaproteome showed that proteins at the mucosal surface clustered into modules with evidence of differential functional specialization (eg, iron regulation, microbial defense) and cellular origin (eg, epithelial or hemopoietic). These modules, validated in an independent cohort, were differentially associated spatially along the gastrointestinal tract, and 7 modules were associated selectively with non-IBD, ulcerative colitis, and/or Crohnâs disease states. In addition, the detailed composition of certain modules was altered in disease vs healthy states. We confirmed the predicted spatial and disease-associated localization of 28 proteins representing 4 different disease-related modules by immunoblot and immunohistochemistry visualization, with evidence for their distribution as millimeter-scale microgeographic mosaic. Conclusions: These findings suggest that the mucosal surface is a microgeographic mosaic of functional networks reflecting the local mucosal ecology, whose compositional differences in disease and healthy samples may provide a unique readout of physiologic and pathologic mucosal states. Keywords: Inflammatory Bowel Disease, Mucosal, Networks, Ecology, Metaproteomics

Published in Cellular and Molecular Gastroenterology and Hepatology

ISSN: 2352-345X (Online)
Publisher: Elsevier
Country of publisher: Netherlands
LCC subjects: Medicine: Internal medicine: Specialties of internal medicine: Diseases of the digestive system. Gastroenterology
Website: https://www.journals.elsevier.com/cellular-and-molecular-gastroenterology-and-hepatology/

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