A high-fiber dietary pattern and subsequent consistent production of SCFAs and healthy gut microbiota are associated with a reduced risk of A-CRA. This trial was registered at www.chictr.org as ChiCTR-TRC-00000123.

Increasing evidence suggests long non-coding RNAs (lncRNAs) are frequently aberrantly expressed in cancers, however, few related lncRNA signatures have been established for prediction of cancer prognosis. We aimed to develop a lncRNA signature to improve prognosis prediction of colorectal cancer (CRC). Using a lncRNA-mining approach, we performed lncRNA expression profiling in large CRC cohorts from Gene Expression Ominus (GEO), including GSE39582 test series(N=436), internal validation series (N=117); and two independent validation series GSE14333 (N=197) and GSE17536(N=145). We established a set of six lncRNAs that were significantly correlated with the disease free survival (DFS) in the test series. Based on this six-lncRNA signature, the test series patients could be classified into high-risk and low-risk subgroups with significantly different DFS (HR=2.670; P<0.0001). The prognostic value of this six-lncRNA signature was confirmed in the internal validation series and another two independent CRC sets. Gene set enrichment analysis (GSEA) analysis suggested that risk score positively correlated with several cancer metastasis related pathways. Functional experiments demonstrated three dysregulated lncRNAs, AK123657, BX648207 and BX649059 were required for efficient invasion and proliferation suppression in CRC cell lines. Our results might provide an efficient classification tool for clinical prognosis evaluation of CRC.

ObjectiveFusobacterium nucleatum (F. nucleatum) has been reported to be enriched in patients with inflammatory bowel disease (IBD). This study aimed to explore the role of F. nucleatum in IBD and its pathogenic mechanism.MethodsSeveral bacteria that have been reported to be associated with IBD or colorectal cancer were measured in the fecal samples of 91 patients with IBD and 43 healthy individuals. Mice with dextran sulfate sodium (DSS)‐induced colitis and a Caco‐2 cell line were used to explore the pathogenicity of F. nucleatum. Barrier damage was evaluated by a transmission electron microscope, the permeability of fluorescein isothiocyanate‐dextran, transepithelial electrical resistance and immunofluorescence. Protein levels of the cell‐cell junction and activation of the STAT3 signaling pathway were detected by immunohistochemistry and immunoblot. Cytokine secretion and T‐cell differentiation were measured by quantitative real‐time polymerase chain reaction and flow cytometry.ResultsF. nucleatum was significantly enriched in the feces of patients with IBD and its abundance correlated with disease activity. Administration of F. nucleatum markedly exacerbated colitis in a DSS mouse model. Mechanistically, F. nucleatum damaged epithelial integrity and increased permeability by regulating the expression and distribution of tight junction proteins zonula occludens‐1 and occludin. Moreover, F. nucleatum promoted the secretion of cytokines (tumor necrosis factor‐α, interferon‐γ, interleukin [IL]‐1β, IL‐6, and IL‐17), activated the STAT3 signaling pathway, and induced CD4+T cell proliferation and Th1 and Th17 subset differentiations.ConclusionF. nucleatum can damage the intestinal barrier and induce aberrant inflammation, which exacerbates colitis.