Ulcerative colitis-driven gut dysbiosis exacerbates periodontal bone loss through the gut–oral axis /Th17/Treg imbalance

Ulcerative colitis (UC) and periodontitis, both microbial dysbiosis-driven chronic inflammatory disorders, coexist and mutually exacerbate, but the causal mechanisms remain unclear. Using ligature-induced periodontitis plus DSS-colitis mice, we found UC doubles alveolar bone loss, heightens systemic inflammation, oxidative stress, and osteoclastogenesis. 16S rRNA and LC-MS metabolomics showed UC enriches oral pathogens, depletes gut Firmicutes, expands Bacteroides, and correlates with suppressed amino-acid/bile-acid biosynthesis. Fecal microbiota transplantation (FMT) from DSS donors into antibiotic-pretreated periodontitis-prone mice replicated aggravated bone loss, systemic inflammation, gut-barrier leakage, and Th17/Treg imbalance, while healthy-donor FMT protected. GC-MS revealed 35-60% reductions in acetate, propionate, and butyrate; keystone taxa Parabacteroides and Muribaculum inversely correlated with SCFAs and host inflammatory genes. Collectively, UC-driven gut dysbiosis is a transmissible causal factor that simultaneously remodels oral and intestinal biofilms, erodes epithelial barriers, and amplifies osteoclastic bone resorption. SCFAs-producing microbes or supplementation may be potential therapeutics for UC-associated periodontitis patients.