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| Main Authors: | , , , , , , , , , |
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| Format: | Artículo científico |
| Language: | en |
| Published: |
Proceedings of the National Academy of Sciences of the United States of America
2025
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| Subjects: | |
| Online Access: | https://pubmed.ncbi.nlm.nih.gov/40825123/ |
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| _version_ | 1868266165115027456 |
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| author | Park, Jong-Duk Lee, Seoung Rak Dhennezel, Catherine Taylor, Noel Dame, Andrea Kadoki, Motohiko Pishchany, Gleb Graham, Daniel B Xavier, Ramnik J Seyedsayamdost, Mohammad R |
| author_facet | Park, Jong-Duk Lee, Seoung Rak Dhennezel, Catherine Taylor, Noel Dame, Andrea Kadoki, Motohiko Pishchany, Gleb Graham, Daniel B Xavier, Ramnik J Seyedsayamdost, Mohammad R Park, Jong-Duk Lee, Seoung Rak Dhennezel, Catherine Taylor, Noel Dame, Andrea Kadoki, Motohiko Pishchany, Gleb Graham, Daniel B Xavier, Ramnik J Seyedsayamdost, Mohammad R |
| collection | PubMed - marine biology |
| contents | Elucidating the role of -derived indole metabolites in gut inflammation and immune modulation. Park, Jong-Duk Lee, Seoung Rak Dhennezel, Catherine Taylor, Noel Dame, Andrea Kadoki, Motohiko Pishchany, Gleb Graham, Daniel B Xavier, Ramnik J Seyedsayamdost, Mohammad R Indoles Animals Gastrointestinal Microbiome Campylobacter Mice Inflammation Humans Macrophages Cytokines Mice, Inbred C57BL Inflammatory Bowel Diseases The gut microbiota plays a pivotal role in maintaining human health with dysbiosis linked to a variety of diseases. Metagenome sequencing and robust statistical analysis have linked specific strains, including the gut bacterium , to Crohn's disease and ulcerative colitis, together known as inflammatory bowel disease (IBD). However, the roles of this and other strains in disease progression remain to be investigated. Herein, we assess the contribution of secondary metabolites to inflammation. Through untargeted metabolomics, we identified a diverse array of nineteen indole-containing metabolites produced by , including trisindoline, previously isolated from a marine bacterium. Collectively, these metabolites modulate inflammatory responses by significantly inducing the release of proinflammatory cytokines interleukin (IL)-1β, IL-6, IL-8, and MCP-1. The metabolites act through the aromatic hydrocarbon receptor arylhydrocarbon receptor and in vivo intravital imaging revealed a marked increase in the recruitment and activation of immune cells, specifically neutrophils and macrophages, following the administration of trisindoline. Several indole metabolites also exhibited antimicrobial activity against commensal strains that facilitate a proper immune response. Our study provides a possible rationale for the association of with IBD and underscores the complex interplay between gut bacteria and host immunity. The identification of indole-derived secondary metabolites as key modulators of inflammation offers new avenues for therapeutic intervention. |
| format | Artículo científico |
| id | pubmed_40825123 |
| institution | PubMed |
| language | en |
| publishDate | 2025 |
| publisher | Proceedings of the National Academy of Sciences of the United States of America |
| record_format | pubmed |
| spellingShingle | Elucidating the role of -derived indole metabolites in gut inflammation and immune modulation. Park, Jong-Duk Lee, Seoung Rak Dhennezel, Catherine Taylor, Noel Dame, Andrea Kadoki, Motohiko Pishchany, Gleb Graham, Daniel B Xavier, Ramnik J Seyedsayamdost, Mohammad R Indoles Animals Gastrointestinal Microbiome Campylobacter Mice Inflammation Humans Macrophages Cytokines Mice, Inbred C57BL Inflammatory Bowel Diseases Elucidating the role of -derived indole metabolites in gut inflammation and immune modulation. Park, Jong-Duk Lee, Seoung Rak Dhennezel, Catherine Taylor, Noel Dame, Andrea Kadoki, Motohiko Pishchany, Gleb Graham, Daniel B Xavier, Ramnik J Seyedsayamdost, Mohammad R Indoles Animals Gastrointestinal Microbiome Campylobacter Mice Inflammation Humans Macrophages Cytokines Mice, Inbred C57BL Inflammatory Bowel Diseases The gut microbiota plays a pivotal role in maintaining human health with dysbiosis linked to a variety of diseases. Metagenome sequencing and robust statistical analysis have linked specific strains, including the gut bacterium , to Crohn's disease and ulcerative colitis, together known as inflammatory bowel disease (IBD). However, the roles of this and other strains in disease progression remain to be investigated. Herein, we assess the contribution of secondary metabolites to inflammation. Through untargeted metabolomics, we identified a diverse array of nineteen indole-containing metabolites produced by , including trisindoline, previously isolated from a marine bacterium. Collectively, these metabolites modulate inflammatory responses by significantly inducing the release of proinflammatory cytokines interleukin (IL)-1β, IL-6, IL-8, and MCP-1. The metabolites act through the aromatic hydrocarbon receptor arylhydrocarbon receptor and in vivo intravital imaging revealed a marked increase in the recruitment and activation of immune cells, specifically neutrophils and macrophages, following the administration of trisindoline. Several indole metabolites also exhibited antimicrobial activity against commensal strains that facilitate a proper immune response. Our study provides a possible rationale for the association of with IBD and underscores the complex interplay between gut bacteria and host immunity. The identification of indole-derived secondary metabolites as key modulators of inflammation offers new avenues for therapeutic intervention. |
| title | Elucidating the role of -derived indole metabolites in gut inflammation and immune modulation. |
| topic | Indoles Animals Gastrointestinal Microbiome Campylobacter Mice Inflammation Humans Macrophages Cytokines Mice, Inbred C57BL Inflammatory Bowel Diseases |
| url | https://pubmed.ncbi.nlm.nih.gov/40825123/ |