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Porphyromonas gingivalis aggravates colitis via a gut microbiota-linoleic acid metabolism-Th17/Treg cell balance axis

Author

Listed:
  • Lu Jia

    (Capital Medical University)

  • Yiyang Jiang

    (Capital Medical University)

  • Lili Wu

    (Capital Medical University)

  • Jingfei Fu

    (Capital Medical University)

  • Juan Du

    (Capital Medical University)

  • Zhenhua Luo

    (Capital Medical University)

  • Lijia Guo

    (Capital Medical University)

  • Junji Xu

    (Capital Medical University)

  • Yi Liu

    (Capital 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.

Suggested Citation

  • Lu Jia & Yiyang Jiang & Lili Wu & Jingfei Fu & Juan Du & Zhenhua Luo & Lijia Guo & Junji Xu & Yi Liu, 2024. "Porphyromonas gingivalis aggravates colitis via a gut microbiota-linoleic acid metabolism-Th17/Treg cell balance axis," Nature Communications, Nature, vol. 15(1), pages 1-18, December.
  • Handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-45473-y
    DOI: 10.1038/s41467-024-45473-y
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    1. Mingming Zhang & Lixing Zhou & Yuejie Xu & Min Yang & Yilai Xu & Garrison Paul Komaniecki & Tatsiana Kosciuk & Xiao Chen & Xuan Lu & Xiaoping Zou & Maurine E. Linder & Hening Lin, 2020. "A STAT3 palmitoylation cycle promotes TH17 differentiation and colitis," Nature, Nature, vol. 586(7829), pages 434-439, October.
    2. Wenjing Yang & Tianming Yu & Xiangsheng Huang & Anthony J. Bilotta & Leiqi Xu & Yao Lu & Jiaren Sun & Fan Pan & Jia Zhou & Wenbo Zhang & Suxia Yao & Craig L. Maynard & Nagendra Singh & Sara M. Dann & , 2020. "Intestinal microbiota-derived short-chain fatty acids regulation of immune cell IL-22 production and gut immunity," Nature Communications, Nature, vol. 11(1), pages 1-18, December.
    3. Saiyu Hang & Donggi Paik & Lina Yao & Eunha Kim & Jamma Trinath & Jingping Lu & Soyoung Ha & Brandon N. Nelson & Samantha P. Kelly & Lin Wu & Ye Zheng & Randy S. Longman & Fraydoon Rastinejad & A. Slo, 2019. "Bile acid metabolites control TH17 and Treg cell differentiation," Nature, Nature, vol. 576(7785), pages 143-148, December.
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