Colon bacteria

Lactulose. 4-O-P -D-Galactopyranosyl-4-D-fmctofuranose [4618-18-2] (Chronolac) (12) may be made from lactose using the method described in Reference 9. It is a synthetic disaccharide that is not hydroly2ed by gastrointestinal enzymes in the small intestine, but is metabolized by colonic bacteria to short-chain organic acids. The increased osmotic pressure of these nonabsorbable organic acids results in an accumulation of fluid in the colon. Lactulose may not be tolerated by patients because of an extremely sweet taste. It frequently produces flatulence and intestinal cramps. 

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). 

Although vitamin K is a fat soluble vitamin, only little stores are found in the body which have to be refilled permanently via dietary input. The role of vitamin K derived from bacteria in the colon is controversely discussed, as the concentration of biliary acids for the resorption the fatsoluble vitamin K is very low in the colon. In addition, only diseases of the small intestine lead to a deficit in vitamin K concentration which cannot be restored by K2 production of colonic bacteria. However, watersoluble vitamin Ks can be resorbed by the colonic mucosa. Maybe because of the little stores for vitamin K, the process of vitamin K-dependent carboxylation of proteins is part of a cycle with several steps during which vitamin K normally is regenerated (see Fig. 1) and thus can be used several times. 

When sorbitol is administered intravenously, it is converted to fructose rather than to glucose. It is poorly absorbed in the small intestine, and much is fermented by colonic bacteria to short-chain fatty acids, CO2, and Hj, leading to abdominal pain and diarrhea (sorbitol intolerance). 

Fig. 4.1 Sinigrin is an aliphatic glucosinolate that occurs at significant levels in the human diet, notably in mustard and Brussels sprouts. When brought into contact with myrosinase, derived either from plant cells or from colonic bacteria, it is broken down to yield a variety of products including the acrid, volatile, biologically active compoimd...

In some cases pectinolytic enzymes have been associated with virulence and it is generally accepted that pectinolysis by these bacteria facilitates their entry and spread in plant tissue. In Rhizohium, these enzymes may play a role in the root infection process that precedes nodule formation (Hubbell et al 1978). A. irakense has never been reported to be pathogenic on plants. It can therefore be speculated that moderate and strictly regulated pectinolysis of A. irakense facilitates entry in the outer cortex of plants roots, since A. irakense has been isolated from surface-sterilized roots. It is likely that breakdown of plant polysaccharides by root colonizing bacteria can provide them with extra carbon source. 

Gout is caused by an abnormality in uric acid metabolism. Uric acid is a waste product of the breakdown of purines contained in the DNA of degraded body cells and dietary protein. Uric acid is water soluble and excreted primarily by the kidneys, although some is broken down by colonic bacteria and excreted via the gastrointestinal tract. 

Normal flora Normal colonizing bacteria of a human host. 

Gibson G.R. and Wang X. (1994). Inhibitory effects of bifidobacteria on other colonic bacteria . J Appl Bacteriol, 77, 412-420. 

Table 5. Parenterally administered antimicrobial agents which can be used alone or combined to provide effective coverage of the mixed aerobic-anaerobic infections arising from human colonic bacteria for patients requiring preventive therapy...

About two-thirds of the uric acid produced each day is excreted in the urine. The remainder is eliminated through the GI tract after enzymatic degradation by colonic bacteria. A decline in the urinary excretion of uric acid to a level below the rate of production leads to hyperuricemia and an increased miscible pool of sodium urate. 

Pancreatic infection may result from increased intestinal permeability and translocation of colonic bacteria. 

Due to fermentation of hitherto undigested carbohydrates by the cecal and colonic bacteria (the large bowel contains concentrations of bacteria of up to 10lo-1012 bacteria/ mL), the pH in the proximal colon is usually lower than that of the ileum. This is reflected in the composition of SCoF, which is essentially an acetate buffer. The use of acetate is appropriate as it is known that the products of carbohydrate fermentation include very short chain acids (acetate, propionate, and butyrate are typical). 

Recent developments involve utilization of cyclodextrins that are absorbed only in minor quantities in the small intestine but are fermented by the colonic bacteria. In a recent study [56,57], the use of biphenyl acetic acid conjugates of P-cylcodextrins was described. The ester conjugate released the drug preferentially when incubated with rat cecal contents, and almost no release was observed on incubation with the contents of the stomach or the small intestine. 

Macleod et al. [92] have studied the potential of pectin-chitosan-hydroxypropyl methylcellulose films for colonic drug delivery [92]. The results showed that in all cases the tablets were able to pass through the stomach and small intestine intact. The tablets started to break up once they were in the colon, due to degradation of the coat by colonic bacteria. 

Friend, D.R., and Chang, G.W., A colon-speciflc drug delivery system based on drug glycosides and glycosidases of colonic bacteria, J. Med. Chem., 27 261-266 (1984). 

Veervort, L., and Kinget, R., In vitro degradation by colonic bacteria of insulin-HP ineorpo-rated in Eudragit RS films, Int J. Pharm., 129 185-190 (1996). 

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). 

Deconjugation and dehydroxylation reactions occur in the colon, leading to the formation of dozens of new distinct BAs, by the action of the colonic bacteria. The final products enter the enterohepatic circulation and reach the liver where they are reconjugated mostly to either glycine or taurine. Some lithocholic acid, the most toxic substance produced in the body and a known carcinogen, enters the liver where it is sulfated or esterified to glucuronic acid and excreted. 

D. Stamp, Antibiotic therapy may induce cancers in the colon and breasts through a mechanism involving bile acids and colonic bacteria. Medical Hypotheses, 2004, 63, 555-556. 

Osmotic laxative effects are also produced by the polyhydric alcohols, mannitol and sorbitol, which unlike glucose cannot be transported through the intestinal mucosa, as well as by the non-hydrolyzable disaccharide, lactubse. Fermentation of lactulose by colon bacteria results in acidification of bowel contents and microfloral damage. Lactulose is used in hepatic failure in order to prevent bacterial production of ammonia and its subsequent absorption (absorbable NH3 nonabsorbable NH4+), so as to forestall hepatic coma. 

Pharmacology Olsalazine sodium is a sodium salt of a salicylate compound that is effectively bioconverted to 5-aminosalicylic acid (mesalamine 5-ASA), which has anti-inflammatory activity in ulcerative colitis. Approximately 98% to 99% of an oral dose will reach the colon, where each molecule is rapidly converted into 2 molecules of 5-ASA by colonic bacteria. The liberated 5-ASA is absorbed slowly, resulting in very high local concentrations in the colon. 

Sulfasalazine is a prodrug of which 70% is converted by colon bacteria to two active metabolites, sulfapyri-dine and 5-aminosalicylic acid (mesalamine). Sulfa-pyridine has antibacterial activities, and 5-aminosali-... 

Osmotic laxatives (e.g., lactulose, sorbitol) are poorly absorbed or nonabsorbable compounds that draw additional fluid into the GI tract. Lumen osmolality increases, and fluid movement occurs secondary to osmotic pressure. Lactulose is a synthetic disaccharide that is poorly absorbed from the GI tract, since no mammalian enzyme is capable of hydrolyzing it to its monosaccharide components. It therefore reaches the colon unchanged and is metabolized by colonic bacteria to lactic acid and to small quantities of formic and acetic acids. Since lactulose does contain galactose, it is contraindicated in patients who require a galactose-free diet. Metabolism of lactulose by intestinal bacteria may result in increased formation of intraluminal gas and abdominal distention. Lactulose is also used in the treatment of hepatic encephalopathy. 

Couteau, D., McCartney, A.L., Gibson, G.R., Williamson, G., and Faulds, C.B., Isolation and characterization of human colonic bacteria able to hydrolyse chlorogenic acid, J. Appl. Microbiol, 90, 873, 2001. 

Following oral administration sodium picosulphate is not absorbed. In colon it is converted to the active metabolite BHPM, by the action of arylsulphatases secreted by the colonic bacteria. 

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