Naturalizing laboratory mice by housing in a farmyard-type habitat confers protection against colorectal carcinogenesis

Living in a farm environment in proximity to animals is associated with reduced risk of developing allergies and asthma, and has been suggested to protect against other diseases, such as inflammatory bowel disease and cancer. Despite epidemiological evidence, experimental disease models that recapit...

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Autores principales: Henriette Arnesen, Thomas C. A. Hitch, Christina Steppeler, Mette Helen Bjørge Müller, Linn Emilie Knutsen, Gjermund Gunnes, Inga Leena Angell, Ida Ormaasen, Knut Rudi, Jan Erik Paulsen, Thomas Clavel, Harald Carlsen, Preben Boysen
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Publicado: Taylor & Francis Group 2021
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spelling oai:doaj.org-article:73929f4613834897a636e69c6c0191172021-11-11T14:23:42ZNaturalizing laboratory mice by housing in a farmyard-type habitat confers protection against colorectal carcinogenesis1949-09761949-098410.1080/19490976.2021.1993581https://doaj.org/article/73929f4613834897a636e69c6c0191172021-01-01T00:00:00Zhttp://dx.doi.org/10.1080/19490976.2021.1993581https://doaj.org/toc/1949-0976https://doaj.org/toc/1949-0984Living in a farm environment in proximity to animals is associated with reduced risk of developing allergies and asthma, and has been suggested to protect against other diseases, such as inflammatory bowel disease and cancer. Despite epidemiological evidence, experimental disease models that recapitulate such environments are needed to understand the underlying mechanisms. In this study, we show that feralizing conventional inbred mice by continuous exposure to a livestock farmyard-type environment conferred protection toward colorectal carcinogenesis. Two independent experimental approaches for colorectal cancer induction were used; spontaneous (Apc Min/+ mice on an A/J background) or chemical (AOM/DSS). In contrast to conventionally reared laboratory mice, the feralized mouse gut microbiota structure remained stable and resistant to mutagen- and colitis-induced neoplasia. Moreover, the feralized mice exhibited signs of a more mature immunophenotype, indicated by increased expression of NK and T-cell maturation markers, and a more potent IFN-γ response to stimuli. In our study, hygienically born and raised mice subsequently feralized post-weaning were protected to a similar level as life-long exposed mice, although the greatest effect was seen upon neonatal exposure. Collectively, we show protective implications of a farmyard-type environment on colorectal cancer development and demonstrate the utility of a novel animal modeling approach that recapitulates realistic disease responses in a naturalized mammal.Henriette ArnesenThomas C. A. HitchChristina SteppelerMette Helen Bjørge MüllerLinn Emilie KnutsenGjermund GunnesInga Leena AngellIda OrmaasenKnut RudiJan Erik PaulsenThomas ClavelHarald CarlsenPreben BoysenTaylor & Francis Grouparticlegut microbiotaferalized micecolorectal cancerfarmyard-like habitatanimal modelnaturalized miceshort-chain fatty acidsimmunityDiseases of the digestive system. GastroenterologyRC799-869ENGut Microbes, Vol 13, Iss 1 (2021)
institution DOAJ
collection DOAJ
language EN
topic gut microbiota
feralized mice
colorectal cancer
farmyard-like habitat
animal model
naturalized mice
short-chain fatty acids
immunity
Diseases of the digestive system. Gastroenterology
RC799-869
spellingShingle gut microbiota
feralized mice
colorectal cancer
farmyard-like habitat
animal model
naturalized mice
short-chain fatty acids
immunity
Diseases of the digestive system. Gastroenterology
RC799-869
Henriette Arnesen
Thomas C. A. Hitch
Christina Steppeler
Mette Helen Bjørge Müller
Linn Emilie Knutsen
Gjermund Gunnes
Inga Leena Angell
Ida Ormaasen
Knut Rudi
Jan Erik Paulsen
Thomas Clavel
Harald Carlsen
Preben Boysen
Naturalizing laboratory mice by housing in a farmyard-type habitat confers protection against colorectal carcinogenesis
description Living in a farm environment in proximity to animals is associated with reduced risk of developing allergies and asthma, and has been suggested to protect against other diseases, such as inflammatory bowel disease and cancer. Despite epidemiological evidence, experimental disease models that recapitulate such environments are needed to understand the underlying mechanisms. In this study, we show that feralizing conventional inbred mice by continuous exposure to a livestock farmyard-type environment conferred protection toward colorectal carcinogenesis. Two independent experimental approaches for colorectal cancer induction were used; spontaneous (Apc Min/+ mice on an A/J background) or chemical (AOM/DSS). In contrast to conventionally reared laboratory mice, the feralized mouse gut microbiota structure remained stable and resistant to mutagen- and colitis-induced neoplasia. Moreover, the feralized mice exhibited signs of a more mature immunophenotype, indicated by increased expression of NK and T-cell maturation markers, and a more potent IFN-γ response to stimuli. In our study, hygienically born and raised mice subsequently feralized post-weaning were protected to a similar level as life-long exposed mice, although the greatest effect was seen upon neonatal exposure. Collectively, we show protective implications of a farmyard-type environment on colorectal cancer development and demonstrate the utility of a novel animal modeling approach that recapitulates realistic disease responses in a naturalized mammal.
format article
author Henriette Arnesen
Thomas C. A. Hitch
Christina Steppeler
Mette Helen Bjørge Müller
Linn Emilie Knutsen
Gjermund Gunnes
Inga Leena Angell
Ida Ormaasen
Knut Rudi
Jan Erik Paulsen
Thomas Clavel
Harald Carlsen
Preben Boysen
author_facet Henriette Arnesen
Thomas C. A. Hitch
Christina Steppeler
Mette Helen Bjørge Müller
Linn Emilie Knutsen
Gjermund Gunnes
Inga Leena Angell
Ida Ormaasen
Knut Rudi
Jan Erik Paulsen
Thomas Clavel
Harald Carlsen
Preben Boysen
author_sort Henriette Arnesen
title Naturalizing laboratory mice by housing in a farmyard-type habitat confers protection against colorectal carcinogenesis
title_short Naturalizing laboratory mice by housing in a farmyard-type habitat confers protection against colorectal carcinogenesis
title_full Naturalizing laboratory mice by housing in a farmyard-type habitat confers protection against colorectal carcinogenesis
title_fullStr Naturalizing laboratory mice by housing in a farmyard-type habitat confers protection against colorectal carcinogenesis
title_full_unstemmed Naturalizing laboratory mice by housing in a farmyard-type habitat confers protection against colorectal carcinogenesis
title_sort naturalizing laboratory mice by housing in a farmyard-type habitat confers protection against colorectal carcinogenesis
publisher Taylor & Francis Group
publishDate 2021
url https://doaj.org/article/73929f4613834897a636e69c6c019117
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