Oxidized polyunsaturated fatty acid promotes colitis and colitis-associated tumorigenesis in mice.

Autor:	Wang W; Department of Food Science, University of Massachusetts, Amherst, MA, USA.; Department of Food Science, Purdue University, West Lafayette, IN, USA., Wang Y; Department of Food Science, University of Massachusetts, Amherst, MA, USA.; Department of Food Science, Purdue University, West Lafayette, IN, USA., Sanidad KZ; Department of Food Science, University of Massachusetts, Amherst, MA, USA.; Molecular and Cellular Biology Graduate Program, University of Massachusetts, Amherst, MA, USA.; Gale and Ira Drukier Institute for Children's Health, Weill Cornell Medicine, New York, NY, USA.; Department of Pediatrics, Weill Cornell Medicine, New York, NY, USA., Wang Y; Department of Nutrition, University of California, Davis, CA, USA., Zhang J; Department of Food Science, University of Massachusetts, Amherst, MA, USA., Yang W; Department of Nutrition, University of California, Davis, CA, USA., Sun Q; Department of Health, Nutrition, and Food Sciences, Florida State University, Tallahassee, FL, USA., Bayram I; Department of Food Science, University of Massachusetts, Amherst, MA, USA., Song R; Epigenetics and RNA Biology Program Centenary Institute, The University of Sydney, Camperdown, New South Wales, Australia.; Faculty of Medicine and Health, The University of Sydney, Camperdown, New South Wales, Australia., Yang H; Department of Food Science, University of Massachusetts, Amherst, MA, USA., Johnson D; Department of Food Science, University of Massachusetts, Amherst, MA, USA., Sherman HL; Department of Veterinary and Animal Sciences, University of Massachusetts, Amherst, MA, USA., Kim D; Department of Mathematics & Statistics, University of Massachusetts, Amherst, MA, USA., Minter LM; Molecular and Cellular Biology Graduate Program, University of Massachusetts, Amherst, MA, USA.; Department of Veterinary and Animal Sciences, University of Massachusetts, Amherst, MA, USA., Wong JJ; Epigenetics and RNA Biology Program Centenary Institute, The University of Sydney, Camperdown, New South Wales, Australia.; Faculty of Medicine and Health, The University of Sydney, Camperdown, New South Wales, Australia., Zeng MY; Gale and Ira Drukier Institute for Children's Health, Weill Cornell Medicine, New York, NY, USA.; Department of Pediatrics, Weill Cornell Medicine, New York, NY, USA., Decker EA; Department of Food Science, University of Massachusetts, Amherst, MA, USA., Zhang G; Department of Food Science, University of Massachusetts, Amherst, MA, USA.; Department of Nutrition, University of California, Davis, CA, USA.
Jazyk:	angličtina
Zdroj:	Journal of Crohn's & colitis [J Crohns Colitis] 2024 Sep 16. Date of Electronic Publication: 2024 Sep 16.
DOI:	10.1093/ecco-jcc/jjae148
Abstrakt:	Background and Aims: Human studies suggest that a high intake of polyunsaturated fatty acid (PUFA) is associated with an increased risk of inflammatory bowel disease (IBD). PUFA is highly prone to oxidation. To date, it is unclear whether unoxidized or oxidized PUFA is involved in the development of IBD. Here, we aim to compare the effects of unoxidized PUFA vs. oxidized PUFA on the development of IBD and associated colorectal cancer. Methods: We evaluated the effects of unoxidized and oxidized PUFA on dextran sodium sulfate (DSS)- and IL-10 knockout-induced colitis, and azoxymethane (AOM)/DSS-induced colon tumorigenesis in mice. Additionally, we studied the roles of gut microbiota and Toll-like receptor 4 (TLR4) signaling involved. Results: Administration of a diet containing oxidized PUFA, at human consumption-relevant levels, increases the severity of colitis and exacerbates the development of colitis-associated colon tumorigenesis in mice. Conversely, a diet rich in unoxidized PUFA doesn't promote colitis. Furthermore, oxidized PUFA worsens colitis-associated intestinal barrier dysfunction and leads to increased bacterial translocation, and it fails to promote colitis in Toll-like receptor 4 (TLR4) knockout mice. Finally, oxidized PUFA alters the diversity and composition of gut microbiota, and it fails to promote colitis in mice lacking the microbiota. Conclusions: These results support that oxidized PUFA promotes the development of colitis and associated tumorigenesis in mouse models via TLR4- and gut microbiota-dependent mechanisms. Our findings highlight the potential need to update regulation policies and industrial standards for oxidized PUFA levels in food. (© The Author(s) 2024. Published by Oxford University Press on behalf of European Crohn’s and Colitis Organisation. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)
Databáze:	MEDLINE
Externí odkaz:	Zobrazit plný text záznamu