2. Academic Validation
  3. Periodontitis salivary microbiota exacerbates colitis by CXCL3 derived from gut microbiota-induced macrophages

Periodontitis salivary microbiota exacerbates colitis by CXCL3 derived from gut microbiota-induced macrophages

  • Microbiome. 2025 Dec 10;13(1):255. doi: 10.1186/s40168-025-02218-3.
Jun Qian # 1,  Qing Tao # 2 3,  Yue Shen # 1,  Lei Wang 4 5,  Min Wang 1,  Nannan Wang 1,  Qiao Liang 2,  Jiangyue Lu 6,  Yuezhen Huang 7,  Wenzheng Liao 1,  Rixin Chen 1,  Ruiyang Ge 1,  Zhiyao Yuan 1,  Yanfen Li 1,  Han Shen 8,  Qian Gao 9,  Fuhua Yan 10
Affiliations

Affiliations

  • 1 Nanjing Stomatological Hospital, Affiliated Hospital of Medical School, Institute of Stomatology, Nanjing University, Nanjing, China.
  • 2 Department of Laboratory Medicine, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, China.
  • 3 Center for Translational Medicine and Jiangsu Key Laboratory of Molecular Medicine, Medical School, Nanjing University, Nanjing, China.
  • 4 Department of Clinical Laboratory, Affiliated Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing, China.
  • 5 Jiangsu Province Academy of Traditional Chinese Medicine, Nanjing, China.
  • 6 Centre for Host Microbiome Interactions, King's College London, England, UK.
  • 7 Shanghai Engineering Research Center of Tooth Restoration and Regeneration & Tongji Research Institute of Stomatology & Department of Periodontitis, Shanghai Tongji Stomatological Hospital and Dental School, Tongji University, Shanghai, China.
  • 8 Department of Laboratory Medicine, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, China. [email protected].
  • 9 Center for Translational Medicine and Jiangsu Key Laboratory of Molecular Medicine, Medical School, Nanjing University, Nanjing, China. [email protected].
  • 10 Nanjing Stomatological Hospital, Affiliated Hospital of Medical School, Institute of Stomatology, Nanjing University, Nanjing, China. [email protected].
  • # Contributed equally.
PMID: 41373016 DOI: 10.1186/s40168-025-02218-3
Abstract

Background: Increasing research has focused on the role of the oral-gut axis in the development of colitis. Saliva contains a large number of oral bacteria that influence gut microbiota and colitis, but the underlying mechanisms remain unclear. In this study, we investigated the role and mechanisms of gut microbiota in salivary microbiota-affected colitis.

Results: We confirmed that periodontitis salivary microbiota (PSM) exacerbated colitis compared to healthy salivary microbiota (HSM). Antibiotics could reverse the effect of PSM in exacerbating colitis, suggesting that the altered gut microbiota was pathogenic. PSM resulted in the enrichment of pathogens, such as Escherichia coli, and lipopolysaccharide in the gut microbiota, and this gut microbiota was shown to be detrimental to colitis by C-X-C motif chemokine ligand 3(CXCL3) in our study. Mechanistically, PSM-derived gut microbiota significantly upregulated CXCL3 in the macrophages, and these Cxcl3 + macrophages contributed to colitis pathology by secreting CXCL3. The macrophages-derived CXCL3 exacerbated colitis via neutrophil chemotaxis and macrophage polarization. CXCL3 induced M2b-like polarization in macrophages, with functions related to immunomodulation and lipid catabolism. These macrophages exacerbated colitis in a gut microbiota-dependent manner. In terms of treatment, administration of Lactobacillus rhamnosus GG, a well-known probiotic, improved gut microbiota and CXCL3, and ameliorated the PSM-exacerbated colitis.

Conclusions: Gut microbiota was a key factor in PSM-exacerbated colitis, which was by activating macrophage to secrete CXCL3. Our study provides new insights into the role of gut microbiota with macrophages and chemokines in colitis, and the mechanism of oral disease affecting the distal organs systemically.

Keywords

Lactobacillus rhamnosus GG; C-X-C motif chemokine ligand 3; Colitis; Gut microbiota; Immune; Inflammatory bowel disease; Macrophage; Periodontitis; Probiotic; Saliva.

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