The co-occurrence of the three disease entities, inflammatory bowel disease (IBD), colorectal cancer (CRC), type 2diabetes mellitus (T2DM) along with inflammation and dismicrobism has been frequently reported. Some authors have even suggested that dysbiosis could be the link through a molecular crosstalk of multiple inflammatory loops including TGFβ, NFKB, TNFα and ROS among others.This review focuses on the inflammatory process along with the role of microbiota in the pathophysiology of the three diseases.The etiology of IBD is multifactorial, and like CRC and T2DM, it is associated with a widespread and sustained GI inflammation and dismicrobism, whereby an array of pro-inflammatory mediators and other related biomolecules are up-regulated, both locally and systematically. Such a persistent or an inadequately resolved chronic inflammation may be a causative agent, in the presence other factors, leading to several pathologies such as IBD, CRC and T2DM.TGFβ plays a crucial role in pancreatic β cell malfunctioning as glucotoxicity stimulates its signaling cascade through smad 3, IL-6 and epithelial to mesenchymal transition. Such a cascade could lead to macrophages and other cells recruitment, inflammation, then IBD and CRC.NFkB is also another key regulator in the crosstalk among the pathways leading to the three disease entities. It plays a major role in linking inflammation to cancer development through its ability to up regulate several inflammatory and tumor promoting cytokines like: IL-6, IL-1 α and TNF α, as well as genes like BCL2 and BCLXL. It activates JAK/STAT signaling network via STAT3 transcription factors and promotes epithelial to mesenchymal transition. It also increases the risk for T2DM in obese people. In brief, NFKB is a matchmaker between inflammation, IBD, cancer and diabetes.In addition, TNFα plays a pivotal role in systemic inflammation. It is increased in the mucosa of IBD patients and has a central role in its pathogenesis. It also activates other signaling pathways like NFKB and MAPK leading to CRC. It is also overexpressed in the adipose tissues of obese patients thus linking it to T2DM, chronic inflammation and consequently CRC.On the other hand, increasing evidence suggests that dysbiosis plays a role in initiating, maintaining and determining the severity of IBD. Actually, among its functions, it modulates genotoxic metabolites which are able to induce CRC, a fact proven to be sustained by stool transfer from patients with CRC. Probiotics, however, may actively prevent CRC as well as IBD and results in a significant decrease in fasting glycemia in T2DM patients.In conclusion, IBD, CRC and T2DM are commonly occurring interrelated clinical problems. They share a common basis influenced by an inflammatory process, an imbalance in intestinal microbiota, and a crosstalk between various signaling pathways. Would probiotics interrupt the crosstalk or orient it in the physiological direction?

IntroductionColorectal cancer (CRC) is a multifactorial disease; genetic epigenetic and environmental factors as well as oxidative stress could be responsible for its onset and progression. Several studies have documented the importance of natural antioxidants in countering oxidative stress and thus preventing colorectal carcinogenesis.ObjectiveThis study aimed to test the protective effect of a mixture of antioxidants against CRC progression in a colorectal cancer mouse model at cellular, microscopic and macroscopic levels.MethodsMale C57BL/6 mice were divided into 4 groups, Group 1 given the mixture (M) which contains Curcumin, Resveratrol, Quercetin, EGCG and Cruciferex PB (0.1 mg/mL + DSS (1.5%) + AOM (10mg/kg)). Group 2, M (1 mg/mL + DSS (1.5%) + AOM (10mg/kg)). Group 3, M (1 mg/mL) and Group 4, (DSS (1.5%) + AOM (10mg/kg)). Body weight, intake of drinking water and diet were recorded every day. Two sacrifices were made (week 7 & 14) and biopsies of the liver, small intestine, colon and kidneys were collected and processed for histology and histochemistry.ResultsThe mixture (M) improved the clinical signs and symptoms of the animals after the DSS cycle by decreasing the bleeding, diarrhea, inflammation and regaining the weight lost during the past week. Macroscopically, PB was able to decrease the formation of intestinal polyps, vessels vasodilation, inflammation and necrosis of the colon with respect to the controls. Microscopically, PB at both concentrations was able to decrease the infiltration of inflammatory cells, including mast cells and the formation of polyps, compared to the controls.ConclusionThe mixture (M) seems to have an effect in halting the progression of CRC at the macroscopical and microscopical levels. Further studies are needed to validate its effect at the molecular level.