The microbiota metabolite, phloroglucinol, confers long-term protection against inflammation
Phloroglucinol is a key byproduct of gut microbial metabolism that has been widely used as a treatment for irritable bowel syndrome. Here, we demonstrate that phloroglucinol tempers macrophage responses to pro-inflammatory pathogens and stimuli. In vivo, phloroglucinol administration decreases gut a...
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Taylor & Francis Group
2024-12-01
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| Series: | Gut Microbes |
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| Online Access: | https://www.tandfonline.com/doi/10.1080/19490976.2024.2438829 |
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| author | Janire Castelo Sarai Araujo-Aris Diego Barriales Samuel Tanner Pasco Iratxe Seoane Ainize Peña-Cearra Ainhoa Palacios Carolina Simó Virginia Garcia-Cañas Muthita Khamwong Itziar Martín-Ruiz Monika Gonzalez-Lopez Laura Barcena José Ezequiel Martín Rodríguez José Luís Lavín Naiara Gutiez Raquel Marcos Estibaliz Atondo Arantza Cobela Laura Plaza-Vinuesa Adrián Plata Eneko Santos-Fernandez Alberto Fernandez-Tejada Mari Carmen Villarán José Miguel Mancheño Juana Maria Flores Ana María Aransay Aize Pellón Blanca de las Rivas Rosario Muñoz Abelardo Margolles Patricia Ruas-Madiedo Maria Victoria Selma Mercedes Gomez de Agüero Leticia Abecia Juan Anguita Héctor Rodríguez |
| author_facet | Janire Castelo Sarai Araujo-Aris Diego Barriales Samuel Tanner Pasco Iratxe Seoane Ainize Peña-Cearra Ainhoa Palacios Carolina Simó Virginia Garcia-Cañas Muthita Khamwong Itziar Martín-Ruiz Monika Gonzalez-Lopez Laura Barcena José Ezequiel Martín Rodríguez José Luís Lavín Naiara Gutiez Raquel Marcos Estibaliz Atondo Arantza Cobela Laura Plaza-Vinuesa Adrián Plata Eneko Santos-Fernandez Alberto Fernandez-Tejada Mari Carmen Villarán José Miguel Mancheño Juana Maria Flores Ana María Aransay Aize Pellón Blanca de las Rivas Rosario Muñoz Abelardo Margolles Patricia Ruas-Madiedo Maria Victoria Selma Mercedes Gomez de Agüero Leticia Abecia Juan Anguita Héctor Rodríguez |
| author_sort | Janire Castelo |
| collection | DOAJ |
| description | Phloroglucinol is a key byproduct of gut microbial metabolism that has been widely used as a treatment for irritable bowel syndrome. Here, we demonstrate that phloroglucinol tempers macrophage responses to pro-inflammatory pathogens and stimuli. In vivo, phloroglucinol administration decreases gut and extraintestinal inflammation in murine models of inflammatory bowel disease and systemic infection. The metabolite induces modest modifications in the microbiota. However, the presence of an active microbiota is required to preserve its anti-inflammatory activity. Remarkably, the protective effect of phloroglucinol lasts partially at least 6 months. Single-cell transcriptomic analysis of bone marrow progenitors demonstrates the capacity of the metabolite to induce long-lasting innate immune training in hematopoietic lineages, at least partially through the participation of the receptor and transcription factor, aryl hydrocarbon receptor (AhR). Phloroglucinol induces alterations in metabolic and epigenetic pathways that are most prevalent in upstream progenitors as hallmarks of central trained immunity. These data identify phloroglucinol as a dietary-derived compound capable of inducing central trained immunity and modulating the response of the host to inflammatory insults. |
| format | Article |
| id | doaj-art-b34810a018fb4213be0c1f08a497b946 |
| institution | Kabale University |
| issn | 1949-0976 1949-0984 |
| language | English |
| publishDate | 2024-12-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| series | Gut Microbes |
| spelling | doaj-art-b34810a018fb4213be0c1f08a497b9462024-12-16T07:51:45ZengTaylor & Francis GroupGut Microbes1949-09761949-09842024-12-0116110.1080/19490976.2024.2438829The microbiota metabolite, phloroglucinol, confers long-term protection against inflammationJanire Castelo0Sarai Araujo-Aris1Diego Barriales2Samuel Tanner Pasco3Iratxe Seoane4Ainize Peña-Cearra5Ainhoa Palacios6Carolina Simó7Virginia Garcia-Cañas8Muthita Khamwong9Itziar Martín-Ruiz10Monika Gonzalez-Lopez11Laura Barcena12José Ezequiel Martín Rodríguez13José Luís Lavín14Naiara Gutiez15Raquel Marcos16Estibaliz Atondo17Arantza Cobela18Laura Plaza-Vinuesa19Adrián Plata20Eneko Santos-Fernandez21Alberto Fernandez-Tejada22Mari Carmen Villarán23José Miguel Mancheño24Juana Maria Flores25Ana María Aransay26Aize Pellón27Blanca de las Rivas28Rosario Muñoz29Abelardo Margolles30Patricia Ruas-Madiedo31Maria Victoria Selma32Mercedes Gomez de Agüero33Leticia Abecia34Juan Anguita35Héctor Rodríguez36CIC bioGUNE, Basque Research and Technology Alliance (BRTA), Derio, SpainCIC bioGUNE, Basque Research and Technology Alliance (BRTA), Derio, SpainCIC bioGUNE, Basque Research and Technology Alliance (BRTA), Derio, SpainCIC bioGUNE, Basque Research and Technology Alliance (BRTA), Derio, SpainCIC bioGUNE, Basque Research and Technology Alliance (BRTA), Derio, SpainCIC bioGUNE, Basque Research and Technology Alliance (BRTA), Derio, SpainCIC bioGUNE, Basque Research and Technology Alliance (BRTA), Derio, SpainMolecular Nutrition and Metabolism, Institute of Food Science Research (CIAL), Spanish National Research Council (CSIC), Madrid, SpainMolecular Nutrition and Metabolism, Institute of Food Science Research (CIAL), Spanish National Research Council (CSIC), Madrid, SpainWürzburg Institute of Systems Immunology, Max-Planck Research Group at the Julius-Maximilians Universität, Würzburg, GermanyCIC bioGUNE, Basque Research and Technology Alliance (BRTA), Derio, SpainCIC bioGUNE, Basque Research and Technology Alliance (BRTA), Derio, SpainCIC bioGUNE, Basque Research and Technology Alliance (BRTA), Derio, SpainCIC bioGUNE, Basque Research and Technology Alliance (BRTA), Derio, SpainApplied Mathematics Department - Bioinformatics Unit, NEIKER-BRTA, Derio, SpainCIC bioGUNE, Basque Research and Technology Alliance (BRTA), Derio, SpainDepartamento de Microbiología y Bioquímica, Instituto de Productos Lácteos de Asturias, CSIC, Villaviciosa, SpainCIC bioGUNE, Basque Research and Technology Alliance (BRTA), Derio, SpainCIC bioGUNE, Basque Research and Technology Alliance (BRTA), Derio, SpainDepartamento de PRocesos Tecnológicos y Biotecnología, Instituto de Ciencia y Tecnología de Alimentos y Nutrición (ICTAN), CSIC, Madrid, SpainCIC bioGUNE, Basque Research and Technology Alliance (BRTA), Derio, SpainCIC bioGUNE, Basque Research and Technology Alliance (BRTA), Derio, SpainCIC bioGUNE, Basque Research and Technology Alliance (BRTA), Derio, SpainÁrea de Alimentación Saludable, Tecnalia-BRTA, Miñano, SpainDepartment of Crystallography and Structural Biology, Institute of Physical Chemistry Blas Cabrera (IQF), CSIC, Madrid, SpainDepartment of Animal Medicine and Surgery, Veterinary Faculty, Universidad Complutense de Madrid, Madrid, SpainCIC bioGUNE, Basque Research and Technology Alliance (BRTA), Derio, SpainCIC bioGUNE, Basque Research and Technology Alliance (BRTA), Derio, SpainDepartamento de PRocesos Tecnológicos y Biotecnología, Instituto de Ciencia y Tecnología de Alimentos y Nutrición (ICTAN), CSIC, Madrid, SpainDepartamento de PRocesos Tecnológicos y Biotecnología, Instituto de Ciencia y Tecnología de Alimentos y Nutrición (ICTAN), CSIC, Madrid, SpainDepartamento de Microbiología y Bioquímica, Instituto de Productos Lácteos de Asturias, CSIC, Villaviciosa, SpainDepartamento de Microbiología y Bioquímica, Instituto de Productos Lácteos de Asturias, CSIC, Villaviciosa, SpainLaboratory of Food & Health, Research Group on Quality, Safety and Bioactivity of Plant Foods, CEBAS-CSIC, Murcia, SpainWürzburg Institute of Systems Immunology, Max-Planck Research Group at the Julius-Maximilians Universität, Würzburg, GermanyCIC bioGUNE, Basque Research and Technology Alliance (BRTA), Derio, SpainCIC bioGUNE, Basque Research and Technology Alliance (BRTA), Derio, SpainCIC bioGUNE, Basque Research and Technology Alliance (BRTA), Derio, SpainPhloroglucinol is a key byproduct of gut microbial metabolism that has been widely used as a treatment for irritable bowel syndrome. Here, we demonstrate that phloroglucinol tempers macrophage responses to pro-inflammatory pathogens and stimuli. In vivo, phloroglucinol administration decreases gut and extraintestinal inflammation in murine models of inflammatory bowel disease and systemic infection. The metabolite induces modest modifications in the microbiota. However, the presence of an active microbiota is required to preserve its anti-inflammatory activity. Remarkably, the protective effect of phloroglucinol lasts partially at least 6 months. Single-cell transcriptomic analysis of bone marrow progenitors demonstrates the capacity of the metabolite to induce long-lasting innate immune training in hematopoietic lineages, at least partially through the participation of the receptor and transcription factor, aryl hydrocarbon receptor (AhR). Phloroglucinol induces alterations in metabolic and epigenetic pathways that are most prevalent in upstream progenitors as hallmarks of central trained immunity. These data identify phloroglucinol as a dietary-derived compound capable of inducing central trained immunity and modulating the response of the host to inflammatory insults.https://www.tandfonline.com/doi/10.1080/19490976.2024.2438829Microbiota byproductsphenolic derivativescentral trained immunityinflammation |
| spellingShingle | Janire Castelo Sarai Araujo-Aris Diego Barriales Samuel Tanner Pasco Iratxe Seoane Ainize Peña-Cearra Ainhoa Palacios Carolina Simó Virginia Garcia-Cañas Muthita Khamwong Itziar Martín-Ruiz Monika Gonzalez-Lopez Laura Barcena José Ezequiel Martín Rodríguez José Luís Lavín Naiara Gutiez Raquel Marcos Estibaliz Atondo Arantza Cobela Laura Plaza-Vinuesa Adrián Plata Eneko Santos-Fernandez Alberto Fernandez-Tejada Mari Carmen Villarán José Miguel Mancheño Juana Maria Flores Ana María Aransay Aize Pellón Blanca de las Rivas Rosario Muñoz Abelardo Margolles Patricia Ruas-Madiedo Maria Victoria Selma Mercedes Gomez de Agüero Leticia Abecia Juan Anguita Héctor Rodríguez The microbiota metabolite, phloroglucinol, confers long-term protection against inflammation Gut Microbes Microbiota byproducts phenolic derivatives central trained immunity inflammation |
| title | The microbiota metabolite, phloroglucinol, confers long-term protection against inflammation |
| title_full | The microbiota metabolite, phloroglucinol, confers long-term protection against inflammation |
| title_fullStr | The microbiota metabolite, phloroglucinol, confers long-term protection against inflammation |
| title_full_unstemmed | The microbiota metabolite, phloroglucinol, confers long-term protection against inflammation |
| title_short | The microbiota metabolite, phloroglucinol, confers long-term protection against inflammation |
| title_sort | microbiota metabolite phloroglucinol confers long term protection against inflammation |
| topic | Microbiota byproducts phenolic derivatives central trained immunity inflammation |
| url | https://www.tandfonline.com/doi/10.1080/19490976.2024.2438829 |
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