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

Alexander R. Moschen, Romana R. Gerner, Jun Wang, Victoria Klepsch, Timon E. Adolph, Simon J. Reider, Hubert Hackl, Alexandra Pfister, Johannes Schilling, Patrizia L. Moser, Sarah L. Kempster, Alexander Swidsinski, Dorothea Orth-Höller, Günter Weiss, John F. Baines, Arthur Kaser, Herbert Tilg

Research output: Contribution to journalArticlepeer-review

235 Scopus citations

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.

Original languageEnglish
Pages (from-to)455-469
Number of pages15
JournalCell Host and Microbe
Volume19
Issue number4
DOIs
StatePublished - 13 Apr 2016
Externally publishedYes

Fingerprint

Dive into the research topics of 'Lipocalin 2 Protects from Inflammation and Tumorigenesis Associated with Gut Microbiota Alterations'. Together they form a unique fingerprint.

Cite this