Colonocytes

Colon cancer Colonic cancer Colonocytes Colonoscopy... 

Fiber components are the principal energy source for colonic bacteria with a further contribution from digestive tract mucosal polysaccharides. Rate of fermentation varies with the chemical nature of the fiber components. Short-chain fatty acids generated by bacterial action are partiaUy absorbed through the colon waU and provide a supplementary energy source to the host. Therefore, dietary fiber is partiaUy caloric. The short-chain fatty acids also promote reabsorption of sodium and water from the colon and stimulate colonic blood flow and pancreatic secretions. Butyrate has added health benefits. Butyric acid is the preferred energy source for the colonocytes and has been shown to promote normal colonic epitheUal ceU differentiation. Butyric acid may inhibit colonic polyps and tumors. The relationships of intestinal microflora to health and disease have been reviewed (10). 

The CaR regulates numerous biological processes, including the expression of various genes (e.g., PTH) the secretion of hormones (PTH and calcitonin), cytokines (MCP-1), and calcium (e.g., into breast milk) the activities of channels (potassium channels) and transporters (aquaporin-2) cellular shape, motility (of macrophages), and migration cellular adhesion (of hematopoietic stem cells) and cellular proliferation (of colonocytes), differentiation (of keratinocytes), and apoptosis (of H-500 ley dig cancer cells) [3]. 

Although a portion of the nutrients released from feedstuff s is absorbed by diffusing across the apical membrane of enterocytes or through the junctional complexes of adjacent enterocytes (paracellular absorption), the majority of nutrients are absorbed from the lumen of the GIT by carrier proteins that are inserted into the apical membrane of enterocytes and colonocytes. 

Calonge, M. L. and Ilundain, A. A. (1998). HCO -dependent ion transport systems and intracellular pH regulation in colonocytes from the chick, Biochim. Biophys. Acta-Biomembranes, 1371, 232-240. 

Chu S, Montrose MH (1995) An Na+-independent short-chain fatty acid transporter contributes to intracellular pH regulation in murine colonocytes. J Gen Physiol 105 589-615... 

Gabor, F., Wirth, M., Jurkovich, B., Theyer, G., Walcher, G., Hamilton, G., Lectin-mediated bioadhesion Proteolytic stability and binding-characteristics of wheat germ agglutinin and Solanum tuberosum lectin on Caco-2, HT-29 and human colonocytes. J Control Release 49, 27-37 (1997). 

Ingestion of commercial preparations that contain digestion-resistant starches and bacteria (e.g. homolactic lactobacilli) increases volatile fatty acid formation in the colon. This provides more fuel for colonocytes it is claimed regular intake of these preparations improves intestinal function and hence mood, known sometimes as die feel good factor. 

Short-chain fatty acids (butyrate, propionate, acetate) free (unbound) microorganisms in colon colonocytes, liver... 

As well as providing fuel, butyrate (which contains four carbon atoms) can reduce the proliferation of colonocytes, which may reduce the risk of tumour development. This is one suggestion to explain how high-fibre diets protect against colon cancer (Chapter 21). 

These short-chain fatty acids are acetic, butyric, lactic and propionic acids, also known as volatile fatty acids, VFA. They are produced from fermentation of carbohydrate by microorganisms in the colon and oxidised by colonocytes or hepatocytes (see above and Chapter 4). Butyric acid is activated to produce butyryl-CoA, which is then degraded to acetyl-CoA by P-oxidation acetic acid is converted to acetyl-CoA for complete oxidation. Propionic acid is activated to form propionyl-CoA, which is then converted to succinate (Chapter 8). The fate of the latter is either oxidation or, conversion to glucose, via glu-coneogenesis in the liver. 

The two important fuels for colonocytes are glutamine and short-chain fatty acids. The oxidation of both fuels provides ATP for the cells, which is important not only to maintain digestive and absorptive functions but also to maintain membrane structure and hence the physical barrier between the lumen and the blood and peritoneal cavity. This barrier normally prevents significant rates of translocation of bacteria into the peritoneal cavity and thence into the blood. If this barrier is breached, translocation of pathogens and... 

In addition to synthesis, mnscle also stores glntamine. It is estimated that the total qnantity stored in aU the skeletal mnscles is about 80 g. The glutamine released by muscle can be utilised by the kidney, enterocytes in the small intestine, colonocytes, aU the immune cells and the cells in the bone marrow (Figure 8.24). Details of the pathways of utilisation by these tissues are discussed. 

Figure 10.1 Simple diagram of the sources of ammonia for the urea cycle. Sources are the Liver, bone marrow, immune cells, enterocytes, colonocytes and microorganisms. Numbers refer to list in text.

Conditions such as malnutrition, starvation, infection or trauma can reduce the fuels available for the colonocytes (glutamine, short chain fatty acids) so that the barrier is less effective. 

Starch. In general, the latter are favonred, despite the need for digestion, because they do not pose osmotic problems. Fibre is sometimes added for fermentation by the bacteria in the colon, which form short chain fatty acids that are used by the colonocytes (Chapter 4). 

Ui) Bacterial translocation from colon due to hypoxic damage Reperfusion damage to the colonocytes can impair the physical barrier between the contents of the colon and the blood. This leads to translocation of bacteria (some of which are pathogens (e.g. E. coli)), or lipopoly-saccharide (endotoxin) into the peritoneal cavity and evenmaUy into the bloodstream. Activation of the gut-associated immune system results in local inflammation which can also damage the barrier and hence increase bacterial translocation. This sets up a vicious circle, with the development of peritonitis and possible systemic sepsis (Figure 18.6). 

Dietary recommendations designed to rednce cancer risk are to eat abalanced diet containing frnit, vegetables and fibre (to provide colonic bacteria with fnel to prodnce short-chain fatty acids which may regnlate colonocyte proliferation) with limited alcohol and fat (in particnlar to avoid obesity). 

Figure 5.2 Therapeutic interventions for decreasing colorectal mucosal bile acid exposure as a CRC chemoprevention strategy. 1) Lifestyle modifications including reduction in dietary animal fat and increased fibre intake may, at least partly, be explained by reduction in luminal primary (cholic acid [CA] and chenodeoxycholic acid [CDCA]) and secondary (deoxycholic acid [DCA] and lithocholic acid [LCA]) bile acids. 2) Reduction of secondary bile acids, which are believed to have pro-carcinogenic activity could be obtained by decreased bacterial conversion from primary bile acids. 3) Alternatively, bile acids could be sequestered by chemical binding agents, e.g. aluminium hydroxide (Al(OH)3) or probiotic bacteria. 4) Exogenous ursodeoxycholic acid (UDCA) can reduce the luminal proportion of secondary bile acids and also has direct anti-neoplastic activity on colonocytes in vitro.

Qiao L, Kozoni V, Tsioulias GJ, et al. Selected eicosanoids increase the proliferation rate of human colon carcinoma cell lines and mouse colonocytes in vivo. Biochem Biophys Acta 1995 1258 215-223. 

Albuquerque FC Jr, Smith EH, Kellum JM. 5-HT induces cAMP production in crypt colonocytes at a 5-HT4 receptor. J Surg Res 1998 77 137-140. 

Bile acids that escape enterohepatic circulation and pass to the colon can be cytotoxic to colonocytes. Damaged cells undergo apoptosis and are shed into the lumen. To maintain cell homeostasis, new cells must be produced. This replacement can result in an increase in cell proliferation rate that can increase the risk of mutations in tumor-related genes and lead to carcinoma development. Moschetta et al. (2000) showed that sphingomyelin protected against bile acid-induced cytotoxicity in human CaCo-2 colon cancer cells, a common model for studying intestinal cell function. 

Uniquely, milk fat of ruminants contains butyric acid, which is an important anti-cancer agent. Butyric acid is best known for its action in the colon where it is generated, along with other short-chain acids, by bacterial fermentation of dietary fiber and starch. Colonocytes utilize a portion of this butyric acid as a primary energy source, with the remainder delivered to the portal circulation and transported to the liver where it is metabolized rapidly. 

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