Risk Of Colitis-associated Colon Cancer Research Articles

Animal models of inflammatory bowel disease: novel experiments for revealing pathogenesis of colitis, fibrosis, and colitis-associated colon cancer.

Inflammatory bowel disease (IBD), comprising Crohn's disease and ulcerative colitis, is a lifelong disease that manifests with chronic intestinal inflammation, sequential fibrosis, and an increased risk of colitis-associated colon cancer (CAC). The combined effects of genetic, immunological, environmental, and microbial factors render it difficult to determine the specific mechanism underlying the induction and perpetuation of IBD. Various animal models of IBD have contributed enormously to the understanding of IBD pathogenesis in terms of genomics, transcriptomics, proteomics, microbiome, and drug development of novel therapeutics. Although comprehensive research on IBD has been enabled by advanced technologies, such as genetically engineered models, there is a great need to develop relevant in vivo models of colitis and fibrosis. Here, we review 4 categories of animal models of acute and chronic intestinal inflammation, fibrosis, and CAC: chemically induced, genetically engineered, T cell transfer, and spontaneous gene mutation models.

Modulation of Gut Microbiota Combined with Upregulation of Intestinal Tight Junction Explains Anti-Inflammatory Effect of Corylin on Colitis-Associated Cancer in Mice.

Inflammatory bowel disease (IBD) involves chronic inflammation, loss of epithelial integrity, and gastrointestinal microbiota dysbiosis, resulting in the development of a colon cancer known as colitis-associated colorectal cancer (CAC). In this study, we evaluated the effects of corylin in a mouse model of dextran sodium sulfate (DSS)-induced colitis. The results showed corylin could improved the survival rate and colon length, maintained body weight, and ameliorated the inflammatory response in the colon. Then, we further identified the possible antitumor effects after 30-day treatment of corylin on an azoxymethane (AOM)/DSS-induced CAC mouse model. Biomarkers associated with inflammation, the colon tissue barrier, macrophage polarization (CD11c, CCR7, CD163, and CD206), and microbiota dysbiosis were monitored in the AOM/DSS group versus corylin groups. Corylin downregulated pro-inflammatory cytokines (TNF-α, IFN-γ, IL-1β, and IL-6) mRNA expression and inflammatory signaling-associated markers (TLR4, MyD88, AP-1, CD11b, and F4/80). In addition, a colon barrier experiment revealed that epithelial cell proliferation of the mucus layer (Lgr5, Cyclin D1, and Olfm4) was downregulated and tight junction proteins (claudin-1 and ZO-1) were upregulated. Furthermore, the Firmicutes/Bacteroidetes ratio changed with corylin intervention, and the microbial diversity and community richness of the AOM/DSS mice were improved by corylin. The comparative analysis of gut microbiota revealed that Bacteroidetes, Patescibacteria, Candidatus Saccharimonas, Erysipelatoclostridium, and Enterorhabdus were significantly increased but Firmicutes, Turicibacter, Romboutsia, and Blautia decreased after corylin treatment. Altogether, corylin administration showed cancer-ameliorating effects by reducing the risk of colitis-associated colon cancer via regulation of inflammation, carcinogenesis, and compositional change of gut microbiota. Therefore, corylin could be a novel, potential health-protective, natural agent against CAC.

Extracellular vesicles derived from inflamed murine colorectal tissue induce fibroblast proliferation via epidermal growth factor receptor.

Inflammatory bowel diseases (IBDs), such as Crohn's disease and ulcerative colitis, are chronic inflammatory disorders of the gastrointestinal tract. Although IBDs increase the risk of colitis-associated colon cancer, the underlying mechanisms are not fully understood. Extracellular vesicles (EVs) are lipid-bound sacs that transport proteins, RNA, and lipids between cells and are key mediators of cellular communication in both physiological and pathological settings. EVs have been implicated in many cancer hallmarks, including uncontrolled tumor growth and metastasis. In this study, we investigated the effects of colon-derived EVs on the proliferation of fibroblasts. We used comparative proteomics to characterize protein profiles of colorectal EVs isolated from healthy mice (Con-EVs) and those with dextran sulfate sodium-induced colitis (IBD-EVs). The results showed that 109 proteins were upregulated in IBD-EVs. Notably, expression of epidermal growth factor receptor (EGFR), which plays important roles in cell proliferation and development, was increased in IBD-EVs. We then examined the effect of EVs on murine NIH3T3 fibroblasts and found that IBD-EVs significantly promoted cell proliferation in EGFR- and ERK-dependent manner. Our findings suggest that inflamed colon-derived EVs promote tumor development thorough activation of fibroblasts.

Cancer-protective effect of a synbiotic combination between Lactobacillus gasseri 505 and a Cudrania tricuspidata leaf extract on colitis-associated colorectal cancer

ABSTRACT Previously, a synbiotic combination of probiotic Lactobacillus gasseri 505 (LG) and a new prebiotic, Cudrania tricuspidata leaf extract (CT) in fermented milk, designated FCT, showed an in vitro immunomodulatory effect and antioxidant activity. Although synbiotic combination might have cancer-protective effects, these activities have not been fully validated in vivo. Ten-week treatment of LG, CT, or FCT to azoxymethane (AOM)/dextran sodium sulfate (DSS)-induced colitis-associated colorectal cancer (CAC) mouse model reduced both the incidence of colonic tumors and damage to the colonic mucosa effectively, suggesting a cancer-protective effect. To understand these, biomarkers associated with inflammation, colon barrier, apoptosis, and cancer cell proliferation were monitored in AOM/DSS group versus LG/CT/FCT groups. A synbiotic combination (FCT) down-regulated pro-inflammatory cytokines (TNF-α, IFN-γ, IL-1β, and IL-6) and inflammation-associated enzymes (iNOS and COX-2), and up-regulated anti-inflammatory cytokines (IL-4 and IL-10). In addition, colon barrier experiment revealed that biomarkers of mucus layer (MUC-2 and TFF3) and tight junction (occludin and ZO-1) were up-regulated. Subsequent apoptosis experiment showed that pro-apoptotic factors (p53, p21, and Bax) were up-regulated and anti-apoptotic factors (Bcl-2 and Bcl-xL) were down-regulated. Furthermore, comparative metagenome analysis of gut microbiota revealed that Staphylococcus decreased but Lactobacillus, Bifidobacterium, and Akkermansia increased, supporting their protective effects, accompanied by increased short-chain fatty acids (SCFAs). Taken together, the FCT administration showed cancer-protective effects by reducing the risk of colitis-associated colon cancer via regulation of inflammation, carcinogenesis, and compositional change of gut microbiota. Consequently, the synbiotic combination (FCT) could be a novel potential health-protective natural agent against CAC.

Psychosocial predisposing factors for infantile colic.

To study associations between characteristics of families during the first pregnancy and after childbirth and the development of infantile colic. Randomised, stratified cluster sampling. Follow up from the first visit to a maternity health care clinic during pregnancy to three months after birth with confidential semistructured questionnaires. Maternity health care clinics in primary health care centres in Finland. 1443 nulliparous women and 1407 partners. Altogether 1333 women and 1279 men returned the questionnaires. When the infants were 3 months old 1208 women and 1115 men returned questionnaires. Marital relationship; personal and social behaviour of parents during the pregnancy and their coping with the pregnancy; mothers' physical health and events, symptoms, and experiences in relation to pregnancy; self confidence and experiences of mothers and fathers in relation to childbirth; and parents' sociodemographic and educational variables. Measure of colic when the infant was 3 months old. Experience of stress and physical symptoms during the pregnancy, dissatisfaction with the sexual relationship, and negative experiences during childbirth were associated with the development of colic in the baby. None of the sociodemographic factors was associated with colic. Early preventive health work during pregnancy should attempt to improve parents' tolerance of symptoms of stress and ability to cope and increase their confidence in parenting abilities.