Kinase Signaling in Colitis-Associated Colon Cancer and Inflammatory Bowel Disease.

Colorectal cancer is a known complication of chronic inflammation of the colon ("colitis-associated colon cancer"). Inflammatory bowel disease (IBD) is a chronic inflammatory disorder of the gastrointestinal tract. Patients with IBD are at increased risk of colon cancer compared to the general population. Kinase signaling pathways play critical roles in both the inflammation and regulating cellular processes such as proliferation and survival that contribute to cancer development. Here we review the interplay of kinase signaling pathways (mitogen-activated protein kinases, cyclin-dependent kinases, autophagy-activated kinases, JAK-STAT, and other kinases) and their effects on colitis-associated colon cancer. We also discuss the role of JAK-STAT signaling in the pathogenesis of IBD and the therapeutic landscape of JAK inhibitors for the treatment of IBD.

Dietary Exposures and Interventions in Inflammatory Bowel Disease: Current Evidence and Emerging Concepts.

Diet is intimately linked to the gastrointestinal (GI) tract and has potent effects on intestinal immune homeostasis. Inflammatory bowel disease (IBD) is characterized by chronic inflammation of the GI tract. The therapeutic implications of diet in patients with IBD have received significant attention in recent years. In this review, we provide a contemporary and comprehensive overview of dietary exposures and interventions in IBD. Epidemiological studies suggest that ultra-processed foods, food additives, and emulsifiers are associated with a higher incidence of IBD. Exclusion and elimination diets are associated with improved symptoms in patients with IBD, but no effects on objective markers of inflammation. Specific dietary interventions (e.g., Mediterranean, specific carbohydrate, high fiber, ketogenic, anti-inflammatory diets) have been shown to reduce symptoms, improve inflammatory biomarkers, and quality of life metrics to varying degrees, but these studies are limited by study design, underpowering, heterogeneity, and confounding. To date, there is no robust evidence that any dietary intervention alone may replace standard therapies in patients with IBD. However, diet may play an adjunct role to induce or maintain clinical remission with standard IBD therapies. The results of novel dietary trials in IBD such as personalized fiber, intermittent fasting, and time-restricted diets are eagerly awaited.

Gut Microbiome in Inflammatory Bowel Disease: Role in Pathogenesis, Dietary Modulation, and Colitis-Associated Colon Cancer.

The gut microbiome has increasingly been recognized as a critical and central factor in inflammatory bowel disease (IBD). Here, we review specific microorganisms that have been suggested to play a role in the pathogenesis of IBD and the current state of fecal microbial transplants as a therapeutic strategy in IBD. We discuss specific nutritional and dietary interventions in IBD and their effects on gut microbiota composition. Finally, we examine the role and mechanisms of the gut microbiome in mediating colitis-associated colon cancer.