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

doi:10.1016/j.chom.2016.03.007

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

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275 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 language	English
Pages (from-to)	455-469
Number of pages	15
Journal	Cell Host and Microbe
Volume	19
Issue number	4
DOIs	https://doi.org/10.1016/j.chom.2016.03.007
State	Published - 13 Apr 2016
Externally published	Yes

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Moschen, A. R., Gerner, R. R., Wang, J., Klepsch, V., Adolph, T. E., Reider, S. J., Hackl, H., Pfister, A., Schilling, J., Moser, P. L., Kempster, S. L., Swidsinski, A., Orth-Höller, D., Weiss, G., Baines, J. F., Kaser, A., & Tilg, H. (2016). Lipocalin 2 Protects from Inflammation and Tumorigenesis Associated with Gut Microbiota Alterations. Cell Host and Microbe, 19(4), 455-469. https://doi.org/10.1016/j.chom.2016.03.007

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title = "Lipocalin 2 Protects from Inflammation and Tumorigenesis Associated with Gut Microbiota Alterations",

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.",

author = "Moschen, {Alexander R.} and Gerner, {Romana R.} and Jun Wang and Victoria Klepsch and Adolph, {Timon E.} and Reider, {Simon J.} and Hubert Hackl and Alexandra Pfister and Johannes Schilling and Moser, {Patrizia L.} and Kempster, {Sarah L.} and Alexander Swidsinski and Dorothea Orth-H{\"o}ller and G{\"u}nter Weiss and Baines, {John F.} and Arthur Kaser and Herbert Tilg",

note = "Publisher Copyright: {\textcopyright} 2016 Elsevier Inc.",

year = "2016",

month = apr,

day = "13",

doi = "10.1016/j.chom.2016.03.007",

language = "English",

volume = "19",

pages = "455--469",

journal = "Cell Host and Microbe",

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Moschen, AR, Gerner, RR, Wang, J, Klepsch, V, Adolph, TE, Reider, SJ, Hackl, H, Pfister, A, Schilling, J, Moser, PL, Kempster, SL, Swidsinski, A, Orth-Höller, D, Weiss, G, Baines, JF, Kaser, A & Tilg, H 2016, 'Lipocalin 2 Protects from Inflammation and Tumorigenesis Associated with Gut Microbiota Alterations', Cell Host and Microbe, vol. 19, no. 4, pp. 455-469. https://doi.org/10.1016/j.chom.2016.03.007

TY - JOUR

T1 - Lipocalin 2 Protects from Inflammation and Tumorigenesis Associated with Gut Microbiota Alterations

AU - Moschen, Alexander R.

AU - Gerner, Romana R.

AU - Wang, Jun

AU - Klepsch, Victoria

AU - Adolph, Timon E.

AU - Reider, Simon J.

AU - Hackl, Hubert

AU - Pfister, Alexandra

AU - Schilling, Johannes

AU - Moser, Patrizia L.

AU - Kempster, Sarah L.

AU - Swidsinski, Alexander

AU - Orth-Höller, Dorothea

AU - Weiss, Günter

AU - Baines, John F.

AU - Kaser, Arthur

AU - Tilg, Herbert

PY - 2016/4/13

Y1 - 2016/4/13

N2 - 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.

AB - 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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AN - SCOPUS:84963594969

SN - 1931-3128

VL - 19

SP - 455

EP - 469

JO - Cell Host and Microbe

JF - Cell Host and Microbe

IS - 4

ER -

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

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