Periodontitis promotes intestinal inflammation through gut microbiota-mediated suppression of GPR109A

To determine whether periodontitis promotes intestinal inflammation through gut microbiota-mediated suppression of the GPR109A receptor.

Periodontitis was induced by ligatures in C57BL/6J mice under normal chow or high-fructose diet. Periodontal destruction was evaluated by micro-computed tomography and hematoxylin and eosin staining. Colonic GPR109A expression, intestinal epithelial integrity, as well as intestinal and systemic inflammation were assessed by histology and immunostaining, quantitative polymerase chain reaction (qPCR) and enzyme-linked immunosorbent assay (ELISA). Short-chain fatty acids (SCFAs) in colonic contents were quantified by GC-MS/MS. Further, the probiotic strain CBM588 was supplemented to two groups of mice (CP/LP group) to alleviate periodontitis-induced inflammation, and GPR109A expression was detected. To investigate the role of periodontitis-associated gut microbiota, fecal microbiota from control (GF-CON) and ligatured (GF-LIG) mice were transplanted into germ-free recipients, and colonic GPR109A levels and inflammatory responses were analyzed. Finally, GPR109A function was modulated by administration of GSK256073 and mepenzolate bromide in ligatured mice, and corresponding changes in tight junctional integrity as well as intestinal and systemic inflammation were evaluated.

Periodontitis significantly downregulated the expression of colonic GPR109A and disrupted the localization of ZO-1 and Occludin. Probiotic supplementation restored GPR109A expression and rescued ZO-1 distribution. Fecal microbiota transplantation from periodontitis donors led to GPR109A suppression, tight junction impairment, and inflammatory upregulation in germ-free mice, confirming a microbiota-dependent mechanism. Activation of GPR109A reversed barrier disruption and reduced pro-inflammatory cytokine levels.

Periodontitis promotes colonic inflammation by gut microbiota-induced suppression of GPR109A receptor, leading to the destruction of the epithelial barrier. Activation of GPR109A restores barrier function and attenuates inflammation.