A systems-level analysis of bile acids effects on rat colon epithelial cells.

Bile acid diarrhea is a chronic condition caused by increased delivery of bile acids to the colon. The underlying mechanisms remain to be elucidated. To investigate genes involved in bile acid diarrhea, systems-level analyses were used on a rat bile acid diarrhea model. Twelve male Wistar Munich rats, housed in metabolic cages, were fed either control or bile acid-mixed (1% wt/wt) diets for 10 days. Food intake, water intake, urine volume, body weight, and fecal output were monitored daily. After euthanasia, colonic epithelial cells were isolated using calcium chelation and processed for systems-level analyses, that is, RNA-sequencing transcriptomics and mass spectrometry proteomics. Bile acid-fed rats suffered diarrhea, indicated by increased drinking, feces weight, and fecal water content compared with control rats. Urine output was unchanged. With bile acid feeding, RNA-sequencing revealed 204 increased and 401 decreased mRNAs; mass spectrometry revealed 183 increased and 111 decreased proteins. Among the altered genes were genes associated with electrolyte and water transport (including Slc12a7, Clca4, and Aqp3) and genes associated with bile acid transport (Slc2b1, Abcg2, Slc51a, Slc51b, and Fabps). Correlation analysis showed a significant positive correlation (Pearson's r = 0.28) between changes in mRNA expression and changes in protein expression. However, caution must be exercised in making a direct correlation between experimentally determined transcriptomes and proteomes. Genes associated with bile acid transport responded to bile acid feeding, suggesting that colonic bile acid transport also occur by regulated protein facilitated mechanisms in addition to passive diffusion. In summary, the study provides annotated rat colonic epithelial cell transcriptome and proteome with response to bile acid feeding.NEW & NOTEWORTHY Feeding rats with a bile acid caused changes in fecal output, underlining this bile acid diarrhea model's usefulness. Colonic epithelial expression of genes associated with facilitated transport of bile acids was altered during bile acid feeding. The study raises the possibility of regulated colonic transepithelial transport of bile acids in response to luminal bile acids. In addition, this study provides annotated rat colonic epithelial cell transcriptome and proteome with response to bile acid feeding.

Expression, regulation and function of Aquaporin-3 in colonic epithelial cells.

The human colon balances water and electrolyte absorption and secretion while also forming a barrier protecting the body from the entry of harmful components. Aquaporin-3 (AQP3) is a water, glycerol and H2O2 transporting channel expressed in colonic epithelia. Although expression of colonic epithelial AQP3 is altered in several intestinal disorders, such as inflammatory bowel disease and irritable bowel syndrome, the regulation and specific roles of AQP3 remain to be fully defined. In this mini-review, we summarize the current understanding of the expression, regulation, and biological functions of AQP3 protein in colonic epithelia concerning intestinal absorption, secretion and barrier function.

Chronic diarrhoea following surgery for colon cancer-frequency, causes and treatment options.

PURPOSE: The growing population of survivors after colon cancer warrants increased attention to the long-term outcome of surgical treatment. The change in bowel anatomy after resection disrupts normal gastrointestinal function and may cause symptoms. Thus, many patients surviving colon cancer have to cope with bowel dysfunction for the rest of their lives. We here aim to provide an overview of the literature on this topic. METHODS: We review long-term functional outcomes of surgical treatment for colon cancer, the underlying pathology, and treatment options. RESULTS: Common symptoms include constipation, urge for defecation and diarrhoea. Causes of diarrhoea after colon cancer surgery are sparsely studied, but they probably include bile acid malabsorption, small intestinal bacterial overgrowth and disruption of the ileal brake. Specific diagnosis should be made to allow individual treatment based on the underlying pathology. Studies on treatment of functional problems after surgery for colon cancer are extremely few, but some lessons can be drawn from the treatment of other patient groups having undergone colon surgery. CONCLUSION: Diarrhoea is likely a common long-term complication after colon cancer surgery. Attention to this complication and a specific diagnosis will aid the targeted treatment of patients suffering from this complication.

Characterization of AQPs in Mouse, Rat, and Human Colon and Their Selective Regulation by Bile Acids.

In normal individuals, the epithelium of the colon absorbs 1.5-2 l of water a day to generate dehydrated feces. However, in the condition of bile acid malabsorption (BAM), an excess of bile acids in the colon results in diarrhea. Several studies have attempted to address the mechanisms contributing to BAM induced by various bile acids. However, none have addressed a potential dysregulation of aquaporin (AQP) water channels, which are responsible for the majority of transcellular water transport in epithelial cells, as a contributing factor to the onset of diarrhea and the pathogenesis of BAM. In this study, we aimed to systematically analyze the expression of AQPs in colonic epithelia from rat, mouse, and human and determine whether their expression is altered in a rat model of BAM. Mass spectrometry-based proteomics, RT-PCR, and western blotting identified various AQPs in isolated colonic epithelial cells from rats (AQP1, 3, 4, 7, 8) and mice (AQP1, 4, 8). Several AQPs were also detected in human colon (AQP1, 3, 4, 7-9). Immunohistochemistry localized AQP1 to the apical plasma membrane of epithelial cells in the bottom of the crypts, whereas AQP3 (rat, human) and AQP4 (mice, human) were localized predominantly in the basolateral plasma membrane. AQP8 was localized intracellularly and at the apical plasma membrane of epithelial cells. Rats fed sodium cholate for 72 h had significantly increased fecal water content, suggesting development of BAM-associated diarrhea. Colonic epithelial cells isolated from this model had significantly altered levels of AQP3, 7, and 8, suggesting that these AQPs may be involved in the pathogenesis of bile acid-induced diarrhea.