Gut microbiota-derived lipid metabolites facilitate regulatory T cell differentiation
Abstract Commensal bacteria-derived metabolites are critical in regulating the host immune system. Although the impact of gut microbiota-derived hydrophilic metabolites, such as short-chain fatty acids, on immune cell functions and development has been well documented, the immunomodulatory effects o...
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2023-06-01
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| Series: | Scientific Reports |
| Online Access: | https://doi.org/10.1038/s41598-023-35097-5 |
| _version_ | 1797811554068987904 |
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| author | Hiroaki Shiratori Hiroyuki Oguchi Yosuke Isobe Kyu-Ho Han Akira Sen Kyosuke Yakebe Daisuke Takahashi Michihiro Fukushima Makoto Arita Koji Hase |
| author_facet | Hiroaki Shiratori Hiroyuki Oguchi Yosuke Isobe Kyu-Ho Han Akira Sen Kyosuke Yakebe Daisuke Takahashi Michihiro Fukushima Makoto Arita Koji Hase |
| author_sort | Hiroaki Shiratori |
| collection | DOAJ |
| description | Abstract Commensal bacteria-derived metabolites are critical in regulating the host immune system. Although the impact of gut microbiota-derived hydrophilic metabolites, such as short-chain fatty acids, on immune cell functions and development has been well documented, the immunomodulatory effects of gut microbiota-derived lipids are still of interest. Here, we report that lipid extracts from the feces of specific-pathogen-free (SPF), but not germ-free (GF), mice showed regulatory T (Treg)-cell-inducing activity. We conducted RP-HPLC-based fractionation and liquid chromatography–tandem mass spectrometry (LC–MS/MS)-based lipidome profiling and identified two bioactive lipids, 9,10-dihydroxy-12Z-octadecenoic acid (9,10-DiHOME) and all-trans retinoic acid (atRA), with Treg-inducing activity in vitro. The luminal abundance of 9,10-DiHOME in the large intestine was significantly decreased by dextran sulfate sodium (DSS)-induced colitis, indicating that 9,10-DiHOME may be a potential biomarker of colitis. These observations implied that commensal bacteria-derived lipophilic metabolites might contribute to Treg development in the large intestine. |
| first_indexed | 2024-03-13T07:25:27Z |
| format | Article |
| id | doaj.art-85741347bd59403a969ba6cc230932e8 |
| institution | Directory Open Access Journal |
| issn | 2045-2322 |
| language | English |
| last_indexed | 2024-03-13T07:25:27Z |
| publishDate | 2023-06-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj.art-85741347bd59403a969ba6cc230932e82023-06-04T11:26:12ZengNature PortfolioScientific Reports2045-23222023-06-0113111210.1038/s41598-023-35097-5Gut microbiota-derived lipid metabolites facilitate regulatory T cell differentiationHiroaki Shiratori0Hiroyuki Oguchi1Yosuke Isobe2Kyu-Ho Han3Akira Sen4Kyosuke Yakebe5Daisuke Takahashi6Michihiro Fukushima7Makoto Arita8Koji Hase9Division of Biochemistry, Department of Pharmaceutical Sciences, Faculty of Pharmacy, and Graduate School of Pharmaceutical Sciences, Keio UniversityDivision of Biochemistry, Department of Pharmaceutical Sciences, Faculty of Pharmacy, and Graduate School of Pharmaceutical Sciences, Keio UniversityLaboratory for Metabolomics, RIKEN Center for Integrative Medical Sciences (IMS)Department of Life and Food Sciences, Obihiro University of Agriculture and Veterinary MedicineDivision of Biochemistry, Department of Pharmaceutical Sciences, Faculty of Pharmacy, and Graduate School of Pharmaceutical Sciences, Keio UniversityDivision of Biochemistry, Department of Pharmaceutical Sciences, Faculty of Pharmacy, and Graduate School of Pharmaceutical Sciences, Keio UniversityDivision of Biochemistry, Department of Pharmaceutical Sciences, Faculty of Pharmacy, and Graduate School of Pharmaceutical Sciences, Keio UniversityDepartment of Life and Food Sciences, Obihiro University of Agriculture and Veterinary MedicineLaboratory for Metabolomics, RIKEN Center for Integrative Medical Sciences (IMS)Division of Biochemistry, Department of Pharmaceutical Sciences, Faculty of Pharmacy, and Graduate School of Pharmaceutical Sciences, Keio UniversityAbstract Commensal bacteria-derived metabolites are critical in regulating the host immune system. Although the impact of gut microbiota-derived hydrophilic metabolites, such as short-chain fatty acids, on immune cell functions and development has been well documented, the immunomodulatory effects of gut microbiota-derived lipids are still of interest. Here, we report that lipid extracts from the feces of specific-pathogen-free (SPF), but not germ-free (GF), mice showed regulatory T (Treg)-cell-inducing activity. We conducted RP-HPLC-based fractionation and liquid chromatography–tandem mass spectrometry (LC–MS/MS)-based lipidome profiling and identified two bioactive lipids, 9,10-dihydroxy-12Z-octadecenoic acid (9,10-DiHOME) and all-trans retinoic acid (atRA), with Treg-inducing activity in vitro. The luminal abundance of 9,10-DiHOME in the large intestine was significantly decreased by dextran sulfate sodium (DSS)-induced colitis, indicating that 9,10-DiHOME may be a potential biomarker of colitis. These observations implied that commensal bacteria-derived lipophilic metabolites might contribute to Treg development in the large intestine.https://doi.org/10.1038/s41598-023-35097-5 |
| spellingShingle | Hiroaki Shiratori Hiroyuki Oguchi Yosuke Isobe Kyu-Ho Han Akira Sen Kyosuke Yakebe Daisuke Takahashi Michihiro Fukushima Makoto Arita Koji Hase Gut microbiota-derived lipid metabolites facilitate regulatory T cell differentiation Scientific Reports |
| title | Gut microbiota-derived lipid metabolites facilitate regulatory T cell differentiation |
| title_full | Gut microbiota-derived lipid metabolites facilitate regulatory T cell differentiation |
| title_fullStr | Gut microbiota-derived lipid metabolites facilitate regulatory T cell differentiation |
| title_full_unstemmed | Gut microbiota-derived lipid metabolites facilitate regulatory T cell differentiation |
| title_short | Gut microbiota-derived lipid metabolites facilitate regulatory T cell differentiation |
| title_sort | gut microbiota derived lipid metabolites facilitate regulatory t cell differentiation |
| url | https://doi.org/10.1038/s41598-023-35097-5 |
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