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

Abstract

Background 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. Methods 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. Results 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 pathogens Escherichia‐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. Conclusions F. nucleatum promotes gut inflammation, epithelial barrier dysfunction, microbiota dysbiosis and dysmetabolism to aggravate UC.

Association between periodontitis and uric acid levels in blood and oral fluids: A systematic review and meta-analysis

“…Given that ubiquitous xanthine oxidoreductase was sensitive to in ammation and oxidative stress [57], a low-grade systemic in ammation induced by periodontitis might accelerate purine catabolism in distant organs. For instance, periodontal infection is associated with increased UA content in liver and feces in rodents [58,59]. However, it should be noted that the present study only supported a positive association between blood UA and periodontitis in the context of normouricemia.…”

Distinct characteristics of the gut virome in patients with osteoarthritis and gouty arthritis

“…Fusobacterium is an important pro-inflammatory bacterium in the human gut that may induce inflammation and suppress host immunity [ 36 ] and contribute to the development of colorectal adenomas and carcinomas [ 36 , 50 ]. It is also significantly enriched in the gut of patients with other systemic diseases such as chronic kidney disease [ 51 ] and ulcerative colitis [ 52 ]. Therefore, the enrichment of Fusobacterium phages in the gut of OA and GA patients may indicate harmful effects that need further validation.…”

Lactobacillus plantarum surface-displayed FomA (Fusobacterium nucleatum) protein generally stimulates protective immune responses in mice

“…We used a DSS solution and F. nucleatum to construct an experimental model in mice (Lin et al, 2022 ). Studies suggest that the co-infection of DSS and F. nucleatum can exacerbate IBD, leading to intestinal structure destruction and abnormal cytokine secretion (Yu et al, 2020 ; Yamashita et al, 2021 ).…”