Porphyromonas gingivalis aggravates colitis via a gut microbiota-linoleic acid metabolism-Th17/Treg cell balance axis
Abstract Periodontitis is closely related to inflammatory bowel disease (IBD). An excessive and non-self-limiting immune response to the dysbiotic microbiome characterizes the two. However, the underlying mechanisms that overlap still need to be clarified. We demonstrate that the critical periodonta...
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| Format: | Article |
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Nature Portfolio
2024-02-01
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| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-024-45473-y |
| _version_ | 1797273908146077696 |
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| author | Lu Jia Yiyang Jiang Lili Wu Jingfei Fu Juan Du Zhenhua Luo Lijia Guo Junji Xu Yi Liu |
| author_facet | Lu Jia Yiyang Jiang Lili Wu Jingfei Fu Juan Du Zhenhua Luo Lijia Guo Junji Xu Yi Liu |
| author_sort | Lu Jia |
| collection | DOAJ |
| description | Abstract Periodontitis is closely related to inflammatory bowel disease (IBD). An excessive and non-self-limiting immune response to the dysbiotic microbiome characterizes the two. However, the underlying mechanisms that overlap still need to be clarified. We demonstrate that the critical periodontal pathogen Porphyromonas gingivalis (Pg) aggravates intestinal inflammation and Th17/Treg cell imbalance in a gut microbiota-dependent manner. Specifically, metagenomic and metabolomic analyses shows that oral administration of Pg increases levels of the Bacteroides phylum but decreases levels of the Firmicutes, Verrucomicrobia, and Actinobacteria phyla. Nevertheless, it suppresses the linoleic acid (LA) pathway in the gut microbiota, which was the target metabolite that determines the degree of inflammation and functions as an aryl hydrocarbon receptor (AHR) ligand to suppress Th17 differentiation while promoting Treg cell differentiation via the phosphorylation of Stat1 at Ser727. Therapeutically restoring LA levels in colitis mice challenged with Pg exerts anti-colitis effects by decreasing the Th17/Treg cell ratio in an AHR-dependent manner. Our study suggests that Pg aggravates colitis via a gut microbiota-LA metabolism-Th17/Treg cell balance axis, providing a potential therapeutically modifiable target for IBD patients with periodontitis. |
| first_indexed | 2024-03-07T14:50:51Z |
| format | Article |
| id | doaj.art-be9e20d140194e1fa1dc1bc86746c81e |
| institution | Directory Open Access Journal |
| issn | 2041-1723 |
| language | English |
| last_indexed | 2024-03-07T14:50:51Z |
| publishDate | 2024-02-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Nature Communications |
| spelling | doaj.art-be9e20d140194e1fa1dc1bc86746c81e2024-03-05T19:43:46ZengNature PortfolioNature Communications2041-17232024-02-0115111810.1038/s41467-024-45473-yPorphyromonas gingivalis aggravates colitis via a gut microbiota-linoleic acid metabolism-Th17/Treg cell balance axisLu Jia0Yiyang Jiang1Lili Wu2Jingfei Fu3Juan Du4Zhenhua Luo5Lijia Guo6Junji Xu7Yi Liu8Laboratory of Tissue Regeneration and Immunology and Department of Periodontics, Beijing Key Laboratory of Tooth Regeneration and Function Reconstruction, School of Stomatology, Capital Medical UniversityLaboratory of Tissue Regeneration and Immunology and Department of Periodontics, Beijing Key Laboratory of Tooth Regeneration and Function Reconstruction, School of Stomatology, Capital Medical UniversityLaboratory of Tissue Regeneration and Immunology and Department of Periodontics, Beijing Key Laboratory of Tooth Regeneration and Function Reconstruction, School of Stomatology, Capital Medical UniversityLaboratory of Tissue Regeneration and Immunology and Department of Periodontics, Beijing Key Laboratory of Tooth Regeneration and Function Reconstruction, School of Stomatology, Capital Medical UniversityLaboratory of Tissue Regeneration and Immunology and Department of Periodontics, Beijing Key Laboratory of Tooth Regeneration and Function Reconstruction, School of Stomatology, Capital Medical UniversityLaboratory of Tissue Regeneration and Immunology and Department of Periodontics, Beijing Key Laboratory of Tooth Regeneration and Function Reconstruction, School of Stomatology, Capital Medical UniversityDepartment of Orthodontics School of Stomatology, Capital Medical UniversityLaboratory of Tissue Regeneration and Immunology and Department of Periodontics, Beijing Key Laboratory of Tooth Regeneration and Function Reconstruction, School of Stomatology, Capital Medical UniversityLaboratory of Tissue Regeneration and Immunology and Department of Periodontics, Beijing Key Laboratory of Tooth Regeneration and Function Reconstruction, School of Stomatology, Capital Medical UniversityAbstract Periodontitis is closely related to inflammatory bowel disease (IBD). An excessive and non-self-limiting immune response to the dysbiotic microbiome characterizes the two. However, the underlying mechanisms that overlap still need to be clarified. We demonstrate that the critical periodontal pathogen Porphyromonas gingivalis (Pg) aggravates intestinal inflammation and Th17/Treg cell imbalance in a gut microbiota-dependent manner. Specifically, metagenomic and metabolomic analyses shows that oral administration of Pg increases levels of the Bacteroides phylum but decreases levels of the Firmicutes, Verrucomicrobia, and Actinobacteria phyla. Nevertheless, it suppresses the linoleic acid (LA) pathway in the gut microbiota, which was the target metabolite that determines the degree of inflammation and functions as an aryl hydrocarbon receptor (AHR) ligand to suppress Th17 differentiation while promoting Treg cell differentiation via the phosphorylation of Stat1 at Ser727. Therapeutically restoring LA levels in colitis mice challenged with Pg exerts anti-colitis effects by decreasing the Th17/Treg cell ratio in an AHR-dependent manner. Our study suggests that Pg aggravates colitis via a gut microbiota-LA metabolism-Th17/Treg cell balance axis, providing a potential therapeutically modifiable target for IBD patients with periodontitis.https://doi.org/10.1038/s41467-024-45473-y |
| spellingShingle | Lu Jia Yiyang Jiang Lili Wu Jingfei Fu Juan Du Zhenhua Luo Lijia Guo Junji Xu Yi Liu Porphyromonas gingivalis aggravates colitis via a gut microbiota-linoleic acid metabolism-Th17/Treg cell balance axis Nature Communications |
| title | Porphyromonas gingivalis aggravates colitis via a gut microbiota-linoleic acid metabolism-Th17/Treg cell balance axis |
| title_full | Porphyromonas gingivalis aggravates colitis via a gut microbiota-linoleic acid metabolism-Th17/Treg cell balance axis |
| title_fullStr | Porphyromonas gingivalis aggravates colitis via a gut microbiota-linoleic acid metabolism-Th17/Treg cell balance axis |
| title_full_unstemmed | Porphyromonas gingivalis aggravates colitis via a gut microbiota-linoleic acid metabolism-Th17/Treg cell balance axis |
| title_short | Porphyromonas gingivalis aggravates colitis via a gut microbiota-linoleic acid metabolism-Th17/Treg cell balance axis |
| title_sort | porphyromonas gingivalis aggravates colitis via a gut microbiota linoleic acid metabolism th17 treg cell balance axis |
| url | https://doi.org/10.1038/s41467-024-45473-y |
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