Porphyromonas gingivalis aggravates colitis via a gut microbiota-linoleic acid metabolism-Th17/Treg cell balance axis
Jia L, Jiang Y, Wu L, Fu J, Du J, Luo Z, Guo L, Xu J, Liu Y
Nature communications · 161 citations
How it was studied
- Design
- Animal study (classified by our AI screen)
- Studied in
- Animals
- Main outcome
- Health markers and function
Who paid for it
- Funding
- Independent funding
- Government
- National Natural Science Foundation of China
- University or hospital
- Capital Medical University
- Government
- Beijing Municipal Administration of Hospitals Clinical Medicine Development of Special Funding Support
- Government
- Beijing Municipal Administration of Hospitals
- Government
- National Natural Science Foundation of China (National Science Foundation of China)
- Grants
- National Natural Science Foundation of China (81974149); National Natural Science Foundation of China (82101009); National Natural Science Foundation of China (DFL20181501); Beijing Municipal Administration of Hospitals (81991504); Beijing Municipal Administration of Hospitals Clinical Medicine Development of Special Funding Support (81991504); National Natural Science Foundation of China (QML20181501); Beijing Municipal Administration of Hospitals Clinical Medicine Development of Special Funding Support (QML20181501); National Natural Science Foundation of China (82122015); Beijing Municipal Administration of Hospitals Clinical Medicine Development of Special Funding Support (DFL20181501); Beijing Municipal Administration of Hospitals (DFL20181501); National Natural Science Foundation of China (2022YFC2504200); Beijing Municipal Administration of Hospitals (81974149); Beijing Municipal Administration of Hospitals Clinical Medicine Development of Special Funding Support (81974149); Beijing Municipal Administration of Hospitals Clinical Medicine Development of Special Funding Support (ZYLX202121); National Natural Science Foundation of China (81991504); Beijing Municipal Administration of Hospitals (QML20181501)
Based on 5 listed funder(s) and full-text disclosure statement.
Publication
- Published
- 2024-02-22 · Nat Commun · vol. 15 · issue 1 · p. 1617
- Publisher
- Nature Portfolio
- Cited
- 199 citations · more than 100% of similar papers · 35.2× the field average
- Impact
- Top 10% most cited in its field
- References
- 69 works
- Access
- Open access (journal) · CC-BY
- Research areas
- Gut microbiota and health · Immune Response and Inflammation · Oral microbiology and periodontitis research
- Keywords
- Porphyromonas gingivalis, Gut flora, Dysbiosis, Colitis, Immunology, Periodontitis, Inflammation, Microbiome, Biology, Immune system, Medicine, Internal medicine, Bioinformatics
- MeSH
- animals, mice, inbred c57bl, humans, mice, porphyromonas gingivalis, colitis, inflammatory bowel diseases, periodontitis, inflammation, linoleic acid, t-lymphocytes, regulatory, th17 cells, gastrointestinal microbiome
9 authors
From CN, PL
- Jia LüCapital Medical University
- Yiyang JiangCapital Medical University
- Lili WuCapital Medical University
- Jingfei FuCapital Medical University
- Juan DuCapital Medical University
- Zhenhua LuoCapital Medical University
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.
Abstract via Europe PMC. Copyright remains with the authors or publisher (CC BY).
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