Colitis Modulates L. Johnsonii-Cla-Bone Homeostasis Axis Exacerbating Periodontitis

To explore how colitis exacerbates periodontitis through gut microbiota dysbiosis and key metabolite interactions, focusing on Lactobacillus johnsonii and conjugated linoleic acid (CLA). DSS-induced colitis and ligation-induced periodontitis were established as models to assess periodontal inflammation and bone resorption. 16s rDNA sequencing and metabolomics were used to screen key flora and metabolites. L. johnsonii supplementation and CLA administration were employed to assess reversibility. PPARγ agonists/antagonists and osteoclast/osteoblast assays elucidated mechanistic roles. Colitis aggravated periodontitis phenotypes and alveolar bone loss via gut dysbiosis. L. johnsonii depletion was critical in exacerbating periodontitis, while its supplementation reversed bone resorption. Dysregulated linoleic acid (LA)-CLA conversion by L. johnsonii impaired bone homeostasis. CLA restoration suppressed osteoclastogenesis and enhanced osteogenesis by inhibiting PPARγ activation. CLA’s anti-resorptive effect persisted despite PPARγ agonism, counteracting drug-induced osteoporosis. Colitis disrupts L. johnsonii-dependent LA-CLA metabolism, exacerbating periodontitis via PPARγ-mediated osteoclast activation. CLA supplementation rescues bone homeostasis, offering therapeutic potential against periodontitis and PPARγ agonist-associated osteoporosis.