Fusobacterium nucleatum aggravates ulcerative colitis through promoting gut microbiota dysbiosis and dysmetabolism.

Abstract

The correlation between periodontitis and ulcerative colitis (UC) has drawn widespread attention recently. Fusobacterium nucleatum (F. nucleatum) as a periodontal pathogen also has reservoirs in gut and may play a role in intestinal diseases. However, its role in the pathogenesis of UC is unclear. Mice were orally given dextran sulphate sodium (DSS) solution and F. nucleatum to construct experimental models. The survival rate, weight, and disease activity index (DAI) of mice were monitored. Alveolar bone loss, abundance of F. nucleatum in colon, colon length, histopathological assessment, and inflammatory cytokines were detected. Apoptosis of intestinal epithelial cells (IECs) were evaluated by TUNEL assay and pro-apoptotic gene Bax. The epithelial barrier function was assessed by tight junction proteins. By 16S rRNA gene sequencing and LC-MS-based methods, the composition of the intestinal microbiota and metabolites in mice were analyzed. F. nucleatum facilitated alveolar bone loss and colonized only in infected colon tissue. Mice fed with DSS showed destruction of gut structure, increased expressions of interleukin one-beta (IL-1β) and tumor necrosis factor alpha (TNF-α), decreased expression of IL-10, higher apoptosis of IECs, microbiota dysbiosis and bile acid dysmetabolism compared to healthy ones. F. nucleatum further aggravated intestinal inflammation and epithelial barrier damage. Probiotics such as Bifidobacterium and Faecalibacterium decreased, opportunistic pathogensEscherichia-Shigella increased and the differential microorganisms highly associated with inflammatory parameters and metabolites. Meanwhile, level of uric acid involving in the purine metabolism significantly elevated compared to UC mice. F. nucleatum promotes gut inflammation, epithelial barrier dysfunction, microbiota dysbiosis and dysmetabolism to aggravate UC.