FADS1-arachidonic acid axis enhances arachidonic acid metabolism by altering intestinal microecology in colorectal cancer
Abstract Colonocyte metabolism shapes the microbiome. Metabolites are the main mediators of information exchange between intestine and microbial communities. Arachidonic acid (AA) is an essential polyunsaturated fatty acid and its role in colorectal cancer (CRC) remains unexplored. In this study, we...
| Main Authors: | , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2023-04-01
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| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-023-37590-x |
| _version_ | 1827966208228458496 |
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| author | Chunjie Xu Lei Gu Lipeng Hu Chunhui Jiang Qing Li Longci Sun Hong Zhou Ye Liu Hanbing Xue Jun Li Zhigang Zhang Xueli Zhang Qing Xu |
| author_facet | Chunjie Xu Lei Gu Lipeng Hu Chunhui Jiang Qing Li Longci Sun Hong Zhou Ye Liu Hanbing Xue Jun Li Zhigang Zhang Xueli Zhang Qing Xu |
| author_sort | Chunjie Xu |
| collection | DOAJ |
| description | Abstract Colonocyte metabolism shapes the microbiome. Metabolites are the main mediators of information exchange between intestine and microbial communities. Arachidonic acid (AA) is an essential polyunsaturated fatty acid and its role in colorectal cancer (CRC) remains unexplored. In this study, we show that AA feeding promotes tumor growth in AOM/DSS and intestinal specific Apc −/− mice via modulating the intestinal microecology of increased gram-negative bacteria. Delta-5 desaturase (FADS1), a rate-limiting enzyme, is upregulated in CRC and effectively mediates AA synthesis. Functionally, FADS1 regulates CRC tumor growth via high AA microenvironment-induced enriched gram-negative microbes. Elimination of gram-negative microbe abolishes FADS1 effect. Mechanistically, gram-negative microbes activate TLR4/MYD88 pathway in CRC cells that contributes FADS1-AA axis to metabolize to prostaglandin E2 (PGE2). Cumulatively, we report a potential cancer-promoting mechanism of FADS1-AA axis in CRC that converts raising synthesized AA to PGE2 via modulating the intestinal microecology of gram-negative. |
| first_indexed | 2024-04-09T17:46:22Z |
| format | Article |
| id | doaj.art-b1939796f2504b4ab1a222c5648bd58f |
| institution | Directory Open Access Journal |
| issn | 2041-1723 |
| language | English |
| last_indexed | 2024-04-09T17:46:22Z |
| publishDate | 2023-04-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Nature Communications |
| spelling | doaj.art-b1939796f2504b4ab1a222c5648bd58f2023-04-16T11:19:20ZengNature PortfolioNature Communications2041-17232023-04-0114111510.1038/s41467-023-37590-xFADS1-arachidonic acid axis enhances arachidonic acid metabolism by altering intestinal microecology in colorectal cancerChunjie Xu0Lei Gu1Lipeng Hu2Chunhui Jiang3Qing Li4Longci Sun5Hong Zhou6Ye Liu7Hanbing Xue8Jun Li9Zhigang Zhang10Xueli Zhang11Qing Xu12Department of Gastrointestinal Surgery, Renji Hospital, School of Medicine, Shanghai Jiao Tong UniversityDepartment of Gastrointestinal Surgery, Renji Hospital, School of Medicine, Shanghai Jiao Tong UniversityState Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, Shanghai Jiao Tong UniversityDepartment of Gastrointestinal Surgery, Renji Hospital, School of Medicine, Shanghai Jiao Tong UniversityState Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, Shanghai Jiao Tong UniversityDepartment of Gastrointestinal Surgery, Renji Hospital, School of Medicine, Shanghai Jiao Tong UniversityDepartment of Gastrointestinal Surgery, Renji Hospital, School of Medicine, Shanghai Jiao Tong UniversityDepartment of Gastrointestinal Surgery, Renji Hospital, School of Medicine, Shanghai Jiao Tong UniversityDivision of Gastroenterology and Hepatology; Key Laboratory of Gastroenterology and Hepatology, Ministry of Health; Renji Hospital, School of Medicine, Shanghai Jiao Tong UniversityState Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, Shanghai Jiao Tong UniversityState Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, Shanghai Jiao Tong UniversityState Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, Shanghai Jiao Tong UniversityDepartment of Gastrointestinal Surgery, Renji Hospital, School of Medicine, Shanghai Jiao Tong UniversityAbstract Colonocyte metabolism shapes the microbiome. Metabolites are the main mediators of information exchange between intestine and microbial communities. Arachidonic acid (AA) is an essential polyunsaturated fatty acid and its role in colorectal cancer (CRC) remains unexplored. In this study, we show that AA feeding promotes tumor growth in AOM/DSS and intestinal specific Apc −/− mice via modulating the intestinal microecology of increased gram-negative bacteria. Delta-5 desaturase (FADS1), a rate-limiting enzyme, is upregulated in CRC and effectively mediates AA synthesis. Functionally, FADS1 regulates CRC tumor growth via high AA microenvironment-induced enriched gram-negative microbes. Elimination of gram-negative microbe abolishes FADS1 effect. Mechanistically, gram-negative microbes activate TLR4/MYD88 pathway in CRC cells that contributes FADS1-AA axis to metabolize to prostaglandin E2 (PGE2). Cumulatively, we report a potential cancer-promoting mechanism of FADS1-AA axis in CRC that converts raising synthesized AA to PGE2 via modulating the intestinal microecology of gram-negative.https://doi.org/10.1038/s41467-023-37590-x |
| spellingShingle | Chunjie Xu Lei Gu Lipeng Hu Chunhui Jiang Qing Li Longci Sun Hong Zhou Ye Liu Hanbing Xue Jun Li Zhigang Zhang Xueli Zhang Qing Xu FADS1-arachidonic acid axis enhances arachidonic acid metabolism by altering intestinal microecology in colorectal cancer Nature Communications |
| title | FADS1-arachidonic acid axis enhances arachidonic acid metabolism by altering intestinal microecology in colorectal cancer |
| title_full | FADS1-arachidonic acid axis enhances arachidonic acid metabolism by altering intestinal microecology in colorectal cancer |
| title_fullStr | FADS1-arachidonic acid axis enhances arachidonic acid metabolism by altering intestinal microecology in colorectal cancer |
| title_full_unstemmed | FADS1-arachidonic acid axis enhances arachidonic acid metabolism by altering intestinal microecology in colorectal cancer |
| title_short | FADS1-arachidonic acid axis enhances arachidonic acid metabolism by altering intestinal microecology in colorectal cancer |
| title_sort | fads1 arachidonic acid axis enhances arachidonic acid metabolism by altering intestinal microecology in colorectal cancer |
| url | https://doi.org/10.1038/s41467-023-37590-x |
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