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?

Inflammatory bowel disease (IBD) encompasses various pathological conditions similar but distinct that share a multifactorial etiology, including involvement of the intestinal barrier function, the immune system, and intestinal microorganisms. Hsp60 is a chaperonin component of the chaperoning system, present in all cells and tissues, including the intestine. It plays important roles in cell physiology outside and inside mitochondria, its canonical place of residence. However, Hsp60 can also be pathogenic in many conditions, the Hsp60 chaperonopathies, possibly including IBD. The various clinico-pathological types of IBD have a complicated mix of causative factors, among which Hsp60 can be considered a putatively important driver of events and could play an etiopathogenic role. This possibility is discussed in this review. We also indicate that Hsp60 can be a biomarker useful in disease diagnosing and monitoring and, if found active in pathogenesis, should become a target for developing new therapies. The latter are particularly needed to alleviate patient suffering and to prevent complications, including colon cancer.

This study assessed the effect of catechin in modulating the inflammation of colitis. Thirty rats were randomized into three groups: Group I: chemically induced with colitis and received no treatment, Group II: chemically induced with colitis and received daily injection of EGCG, Group III: control group provided with water only. In groups I and II, colitis was induced by TNBS solution. Rats were sacrificed on days 3, 10 and 17 and biopsies of distal colons were assessed by histology and molecular techniques for ROS and changes in cytokines like IL-6 and IL1-β. Colitis induced by TNBS and non-treated with EGCG group, showed high inflammatory scores resulting in colonic mucosa and submucosa damage, necrosis, absence of goblet cells, infiltration of inflammatory cells, crypt abscesses and granulomas. Infiltration of inflammatory cells and tissue damage peaked at day 17 after the induction. At day 3 and day 10, the treated rats with EGCG showed amelioration in the severity of inflammation, but at day 17, the state of the colonic crypts and goblet cells was close to normal. The number of mast cells in the colon of treated rats decreased by more than 30% at day 17 compared to the non- treated rats. In addition, the expression of ROS decreased significantly. IL-1B and IL-6 expressions decrease with time by 50% in the treated group. Our data confirmed the anti-inflammatory effect of EGCG in TNBS-induced colitis and provided a clue to a potential therapeutic agent.

There is increasing evidence that (-)-epigallocatechin-3-gallate (EGCG) inhibits carcinogenesis and inflammation among other properties. However, its mechanism is not fully elucidated.To investigate the mechanism of action of EGCG in improving experimental colitis. 35 male Sprague-Dawley rats were randomly divided into 4 groups: Normal control group (n=5), EGCG group (n=9), TNBS group (n=9), and TNBS+EGCG group (n=12). For both, TNBS treated group and EGCG group, 1 mg/Kg EGCG was administered daily by intraperitoneal injection, starting one week before the induction. At days 3, 10 and 17, rats were sacrificed and the descending colon was collected. The score of histological alterations of the colonic mucosa was evaluated. The mast cells were assessed by toluidine blue staining. The mRNA expression of Tumor Necrosis Factor-α (TNF-α), and nuclear factor (NF-KB) was measured and ROS was tested by immunofluorescence. EGCG decreased significantly the erosions and the inflammatory cellular infiltration of the mucosa and submucosa. In addition, the mast cells were markedly reduced in number and degranulation. The increased levels NF-KB and TNF-α after TNBS administration were significantly and concurrently reduced in colonic scrapings after EGCG treatment at all the time points and did ROS. EGCG probably prevented the transcription of inflammatory genes by stabilizing mast cells and reducing its secretory pro-inflammatory factors such as TNF-α.