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

Periodontitis salivary microbiota (PSM) exacerbated colitis compared to healthy salivary microbiota (HSM).

• PSM and HSM were compared in a colitis model to assess differential effects on disease severity.
• PSM-treated animals showed worse colitis pathology than HSM-treated animals.
• The study confirmed that salivary microbiota composition, specifically from periodontitis patients, was sufficient to worsen colitis outcomes.

Antibiotic treatment reversed the exacerbating effect of PSM on colitis, implicating altered gut microbiota as the pathogenic mediator.

• Antibiotics were administered to deplete gut microbiota in PSM-treated animals.
• Reversal of colitis exacerbation by antibiotics indicated that the gut microbiota altered by PSM was responsible for worsening disease.
• This finding established gut microbiota as a key intermediary in the oral-gut axis mechanism.

PSM resulted in enrichment of pathogens, particularly Escherichia coli, and increased lipopolysaccharide (LPS) in the gut microbiota.

• Metagenomic or microbiota profiling revealed enrichment of E. coli and LPS in the gut following PSM administration.
• This pathogen-enriched gut microbiota was shown to be detrimental to colitis outcomes.
• LPS enrichment in the gut was identified as a downstream consequence of PSM-induced gut microbiota dysbiosis.

PSM-derived gut microbiota significantly upregulated CXCL3 expression in macrophages.

• CXCL3 (C-X-C motif chemokine ligand 3) was identified as a key chemokine upregulated in macrophages in response to PSM-altered gut microbiota.
• Cxcl3+ macrophages were found to contribute to colitis pathology by secreting CXCL3.
• The upregulation of CXCL3 in macrophages was dependent on the gut microbiota composition driven by PSM.

Macrophage-derived CXCL3 exacerbated colitis via neutrophil chemotaxis and macrophage polarization.

• CXCL3 promoted recruitment of neutrophils to the gut through chemotaxis.
• CXCL3 induced M2b-like polarization in macrophages.
• M2b-like polarized macrophages had functions related to immunomodulation and lipid catabolism.
• These M2b-like macrophages exacerbated colitis in a gut microbiota-dependent manner.

Administration of Lactobacillus rhamnosus GG (LGG) improved gut microbiota composition, reduced CXCL3 levels, and ameliorated PSM-exacerbated colitis.

• LGG is described as a 'well-known probiotic' used as a therapeutic intervention.
• LGG treatment improved gut microbiota dysbiosis induced by PSM.
• LGG administration was associated with reduced CXCL3 levels.
• The amelioration of colitis by LGG supports the gut microbiota–CXCL3–macrophage axis as a therapeutic target.

The study establishes a mechanistic link between oral disease (periodontitis) and distal organ pathology (colitis) through the gut microbiota–macrophage–CXCL3 axis.

• The proposed mechanism involves: PSM → gut microbiota dysbiosis (E. coli/LPS enrichment) → macrophage CXCL3 upregulation → neutrophil chemotaxis and M2b-like polarization → colitis exacerbation.
• The study provides evidence that gut microbiota is 'a key factor in PSM-exacerbated colitis, which was by activating macrophage to secrete CXCL3.'
• The findings offer '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.'