Lipocalin 2 Protects from Inflammation and Tumorigenesis Associated with Gut Microbiota Alterations.

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Abstract

High mucosal and fecal concentrations of the antimicrobial siderophore-binding peptide Lipocalin-2 (Lcn2) are observed in inflammatory bowel disease. However, Lcn2 function in chronic intestinal inflammation remains unclear. Here, we demonstrate that Lcn2 protects from early-onset colitis and spontaneous emergence of right-sided colonic tumors resulting from IL-10 deficiency. Exacerbated inflammation in Lcn2(-/-)/Il10(-/-) mice is driven by IL-6, which also controls tumorigenesis. Lcn2(-/-)/Il10(-/-) mice exhibit profound alterations in gut microbial composition, which contributes to inflammation and tumorigenesis, as demonstrated by the transmissibility of the phenotype and protection conferred by antibiotics. Specifically, facultative pathogenic Alistipes spp. utilize enterobactin as iron source, bloom in Lcn2(-/-)/Il10(-/-) mice, and are sufficient to induce colitis and right-sided tumors when transferred into Il10(-/-) mice. Our results demonstrate that Lcn2 protects against intestinal inflammation and tumorigenesis associated with alterations in the microbiota.

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Journal

Journal ID (iso-abbrev): Cell Host Microbe

Title: Cell host & microbe

Publisher: Elsevier BV

ISSN (Electronic): 1934-6069

ISSN (Print): 1931-3128

Publication date (Electronic): Apr 13 2016

Volume: 19

Issue: 4

Affiliations

[1 ] Division of Internal Medicine I (Gastroenterology, Endocrinology and Metabolism), Department of Medicine, Medical University Innsbruck, Innsbruck 6020, Austria. Electronic address: alexander.moschen@i-med.ac.at.

[2 ] Division of Internal Medicine I (Gastroenterology, Endocrinology and Metabolism), Department of Medicine, Medical University Innsbruck, Innsbruck 6020, Austria.

[3 ] Max Planck Institute for Evolutionary Biology, Plön 24308, Germany; Institute for Experimental Medicine, Christian-Albrechts-University of Kiel, Kiel 24118, Germany.

[4 ] Department of Medical Genetics, Molecular and Clinical Pharmacology, Division of Translational Cell Genetics, Medical University Innsbruck, Innsbruck 6020, Austria.

[5 ] Division of Bioinformatics, Biocenter Innsbruck, Medical University Innsbruck, Innsbruck 6020, Austria.

[6 ] Charité Hospital, CCM, Laboratory for Molecular Genetics, Polymicrobial Infections and Bacterial Biofilms and Department of Medicine, Gastroenterology, Universitätsmedizin Berlin, Berlin 10117, Germany.

[7 ] Department of Pathology, Medical University Innsbruck, Innsbruck 6020, Austria.

[8 ] Division of Gastroenterology and Hepatology, Department of Medicine, University of Cambridge, Addenbrooke's Hospital, Cambridge CB2 0QQ, UK.

[9 ] Division of Hygiene and Medical Microbiology, Department of Hygiene, Microbiology and Social Medicine, Medical University Innsbruck, Innsbruck 6020, Austria.

[10 ] Division of Internal Medicine VI (Infectious Diseases, Immunology, Rheumatology and Pneumology), Department of Medicine, Medical University Innsbruck, Innsbruck 6020, Austria.

[11 ] Division of Internal Medicine I (Gastroenterology, Endocrinology and Metabolism), Department of Medicine, Medical University Innsbruck, Innsbruck 6020, Austria. Electronic address: herbert.tilg@i-med.ac.at.

Article

Publisher Item ID: S1931-3128(16)30099-3

DOI: 10.1016/j.chom.2016.03.007

PubMed ID: 27078067

SO-VID: eed0f8f4-c00a-47cb-820b-236c095b980f

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