Maternal exposure to a human relevant mixture of persistent organic pollutants reduces colorectal carcinogenesis in A/J Min/+ mice
Maternal exposure to a human relevant mixture of persistent organic pollutants reduces colorectal carcinogenesis in A/J Min/+ mice
An increased risk of developing colorectal cancer has been associated with exposure to persistent organic pollutants (POPs) and alteration in the gut bacterial community. However, there is limited understanding about the impact of maternal exposure to POPs on colorectal cancer and gut microbiota. This study characterized the influence of exposure to a human relevant mixture of POPs during gestation and lactation on colorectal cancer, intestinal metabolite composition and microbiota in the A/J Min/+ mouse model. Surprisingly, the maternal POP exposure decreased colonic tumor burden, as shown by light microscopy and histopathological evaluation, indicating a restriction of colorectal carcinogenesis. 1H nuclear magnetic resonance spectroscopy-based metabolomic analysis identified alterations in the metabolism of amino acids, lipids, glycerophospholipids and energy in intestinal tissue. In addition, 16S rRNA sequencing of gut microbiota indicated that maternal exposure modified fecal bacterial composition. In conclusion, the results showed that early-life exposure to a mixture of POPs reduced colorectal cancer initiation and promotion, possibly through modulation of the microbial and biochemical environment. Further studies should focus on the development of colorectal cancer after combined maternal and dietary exposures to environmentally relevant low-dose POP mixtures.
Colorectal cancer, Gut microbiota, Metabolomics, Persistent organic pollutants
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Johanson, Silje M.
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Swann, Jonathan R.
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Umu, Özgün C O
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Aleksandersen, Mona
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Müller, Mette H.B.
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Berntsen, Hanne F.
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Zimmer, Karin E.
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Østby, Gunn C.
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Paulsen, Jan E.
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Ropstad, Erik
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August 2020
Johanson, Silje M.
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Swann, Jonathan R.
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Umu, Özgün C O
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Aleksandersen, Mona
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Müller, Mette H.B.
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Berntsen, Hanne F.
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Zimmer, Karin E.
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Østby, Gunn C.
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Paulsen, Jan E.
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Ropstad, Erik
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Johanson, Silje M., Swann, Jonathan R., Umu, Özgün C O, Aleksandersen, Mona, Müller, Mette H.B., Berntsen, Hanne F., Zimmer, Karin E., Østby, Gunn C., Paulsen, Jan E. and Ropstad, Erik
(2020)
Maternal exposure to a human relevant mixture of persistent organic pollutants reduces colorectal carcinogenesis in A/J Min/+ mice.
Chemosphere, 252, , [126484].
(doi:10.1016/j.chemosphere.2020.126484).
Abstract
An increased risk of developing colorectal cancer has been associated with exposure to persistent organic pollutants (POPs) and alteration in the gut bacterial community. However, there is limited understanding about the impact of maternal exposure to POPs on colorectal cancer and gut microbiota. This study characterized the influence of exposure to a human relevant mixture of POPs during gestation and lactation on colorectal cancer, intestinal metabolite composition and microbiota in the A/J Min/+ mouse model. Surprisingly, the maternal POP exposure decreased colonic tumor burden, as shown by light microscopy and histopathological evaluation, indicating a restriction of colorectal carcinogenesis. 1H nuclear magnetic resonance spectroscopy-based metabolomic analysis identified alterations in the metabolism of amino acids, lipids, glycerophospholipids and energy in intestinal tissue. In addition, 16S rRNA sequencing of gut microbiota indicated that maternal exposure modified fecal bacterial composition. In conclusion, the results showed that early-life exposure to a mixture of POPs reduced colorectal cancer initiation and promotion, possibly through modulation of the microbial and biochemical environment. Further studies should focus on the development of colorectal cancer after combined maternal and dietary exposures to environmentally relevant low-dose POP mixtures.
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More information
Accepted/In Press date: 12 March 2020
e-pub ahead of print date: 13 March 2020
Published date: August 2020
Keywords:
Colorectal cancer, Gut microbiota, Metabolomics, Persistent organic pollutants
Identifiers
Local EPrints ID: 439794
URI: http://eprints.soton.ac.uk/id/eprint/439794
ISSN: 0045-6535
PURE UUID: 6071c9ff-719e-4191-af4b-aeb6e5b27cf7
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Date deposited: 04 May 2020 16:34
Last modified: 06 Jun 2024 02:07
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Contributors
Author:
Silje M. Johanson
Author:
Özgün C O Umu
Author:
Mona Aleksandersen
Author:
Mette H.B. Müller
Author:
Hanne F. Berntsen
Author:
Karin E. Zimmer
Author:
Gunn C. Østby
Author:
Jan E. Paulsen
Author:
Erik Ropstad
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