Secondary bile acids (BAs) and short chain fatty acids (SCFAs), two major types of bacterial metabolites in the colon, cause opposing effects on colonic inflammation at chronically high physiological levels. Primary BAs play critical roles in cholesterol metabolism, lipid digestion, and host–microbe interaction. Although BAs are reabsorbed via enterohepatic circulation, primary BAs serve as substrates for bacterial biotransformation to secondary BAs in the colon. High-fat diets increase secondary BAs, such as deoxycholic acid (DCA) and lithocholic acid (LCA), which are risk factors for colonic inflammation and cancer. In contrast, increased dietary fiber intake is associated with anti-inflammatory and anticancer effects. These effects may be due to the increased production of the SCFAs acetate, propionate, and butyrate during dietary fiber fermentation in the colon. Elucidation of the molecular events by which secondary BAs and SCFAs regulate colonic cell proliferation and inflammation will lead to a better understanding of the anticancer potential of dietary fiber in the context of high-fat diet-related colon cancer. This article reviews the current knowledge concerning the effects of secondary BAs and SCFAs on the proliferation of colon epithelial cells, inflammation, cancer, and the associated microbiome.

Human CD38 is a nonlineage-restricted type II transmembrane glycoprotein that has emerged as a multifunctional protein in recent years. It can serve as an ectoenzyme that catalyzes the synthesis and hydrolysis of cyclic ADP-ribose, a recently identified Ca2+ mobilizing agent that acts independently of inositol triphosphate. The enzymatic functions of CD38 probably contribute to an array of its immunoregulatory functions. The release of soluble CD38 and the ability of membrane-bound CD38 to become internalized in response to appropriate stimuli suggest that extracellular and intracellular roles for this protein are equally plausible. Ligation of CD38 with agonistic antibodies induces diverse effects in hematopoietic cells that range from growth stimulation to induction and prevention from apoptosis, induction of cytokines, activation of kinases, and phosphorylation of certain proteins. These observations suggest that CD38 may serve as receptor for an as yet unidentified ligand. Other molecules that share significant structural and functional homology to CD38 have been identified in humans and mice, suggesting that these molecules may represent a new family of proteins. Understanding the role of CD38 in certain pathological conditions such as myeloma, X-linked agammaglobulinemia, and HIV infection may provide insight into its physiological functions.

Self-renewal in the intestinal epithelia is fueled by a population of undifferentiated intestinal stem cells (ISCs) that give rise to daughter or progenitor cells, which can subsequently differentiate into the mature cell types required for normal gut function. The cellular signals that regulate self-renewal are poorly understood and the factors that mediate the transition from a stem cell to a progenitor cell in the gut are unknown. Recent studies have suggested that ISCs are located either at the crypt base interspersed between the Paneth cells (eg, Lgr-5+ve cells) or at or near position 4 within the intestinal crypt (eg, DCAMKL-1 or Bmi-1+ve cells). This raises the possibility that distinct stem cell regions exist in the crypts and that ISC's state of activation will determine how the self-renewal is regulated in the intestinal tract.

Inflammatory Bowel Disease (IBD) is a multifactorial disorder that conceptually occurs as a result of altered immune responses to commensal and/or pathogenic gut microbes in individuals most susceptible to the disease. During Crohn’s Disease (CD) or Ulcerative Colitis (UC), two components of the human IBD, distinct stages define the disease onset, severity, progression and remission. Epigenetic, environmental (microbiome, metabolome) and nutritional factors are important in IBD pathogenesis. While the dysbiotic microbiota has been proposed to play a role in disease pathogenesis, the data on IBD and diet are still less convincing. Nonetheless, studies are ongoing to examine the effect of pre/probiotics and/or FODMAP reduced diets on both the gut microbiome and its metabolome in an effort to define the healthy diet in patients with IBD. Knowledge of a unique metabolomic fingerprint in IBD could be useful for diagnosis, treatment and detection of disease pathogenesis.

Doublecortin-like kinase 1 (Dclk1) is overexpressed in many cancers including colorectal cancer (CRC) and it specifically marks intestinal tumor stem cells. However, the role of Dclk1 in intestinal tumorigenesis in Apc mutant conditions is still poorly understood. We demonstrate that Dclk1 expression and Dclk1+ cells are significantly increased in the intestinal epithelium of elderly ApcMin/+ mice compared to young ApcMin/+ mice and wild type mice. Intestinal epithelial cells of ApcMin/+ mice demonstrate increased pluripotency, self-renewing ability, and EMT. Furthermore, miRNAs are dysregulated, expression of onco-miRNAs are significantly increased with decreased tumor suppressor miRNAs. In support of these findings, knockdown of Dclk1 in elderly ApcMin/+ mice attenuates intestinal adenomas and adenocarcinoma by decreasing pluripotency, EMT and onco-miRNAs indicating that Dclk1 overexpression facilitates intestinal tumorigenesis. Knocking down Dclk1 weakens Dclk1-dependent intestinal processes for tumorigenesis. This study demonstrates that Dclk1 is critically involved in facilitating intestinal tumorigenesis by enhancing pluripotency and EMT factors in Apc mutant intestinal tumors and it also provides a potential therapeutic target for the treatment of colorectal cancer.