Colonic bacteria, action

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). 

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. 

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. 

GC data should be evaluated carefully. The main sterols of interest are cholesterol and lathosterol, the latter being a late-stage intermediate in cholesterol synthesis. Coprostanol is formed by the action of colonic bacteria on cholesterol and may vary considerably between mice. Peaks for coprostanol and other minor animal-derived sterols appear very close to, and may overlap with, that of cholesterol. Lathosterol is usually resolved between the cholesterol and the first phytosterol peak. Neutral sterol excretion should be reported as the sum of cholesterol, its precursors, and its derivatives. Evaluation excluding precursors is also appropriate. 

Q4 The colon contains large numbers of bacteria, which begin to colonize it soon after birth. What are the beneficial actions of colonic bacteria ... 

The sulfasalazine molecule comprises sulfa-piridine and 5-aminosalicylic acid linked by an azo-bond which is split by colonic bacteria, releasing the component parts. Sulfapiridine, as a sulphonamide, has an antifolate action which is believed to benefit rheumatoid arthritis, while it is the salicylate moiety that is thought to be effective in inflammatory bowel disease a fuller description appears on page 64. Sulfasalazine is used as a DMARD for rheumatoid arthritis, spondyloarthropathy with peripheral joint involvement, and psoriatic arthritis. 

Sulfasalazine (salicylazosulfapyridine, Salazopyrin) consists of two compounds, sulpha-pyridine and 5-aminosalicylic acid, joined by an azo-bond. Sulfasalazine is poorly absorbed from the small intestine and colonic bacteria split the azo-bond to release the component parts. The therapeutically active moiety is 5-aminosalicylic acid (5-ASA). Sulphapyridine is well absorbed, is acetylated in the liver and excreted in the urine it has no therapeutic action in colitis but contributes to a mechanism for delivering 5-ASA to the colon. 

Sodium picosulfate becomes active following metabolism by colonic bacteria so it has a relatively slow onset of action, usually within 10-14 hours. It can be used in young children. 

Because the mechanism of action of sulfasalazine is not related to the sulfapyridine component, and since sulfapyridine is believed to be responsible for many of the adverse reactions to sulfasalazine, mesalamine alone can be used. Mesalamine can be used topically as an enema for the treatment of proctitis, or given orally in slow-release formulations that deliver mesalamine to the small intestine and colon (Table 34—5 and Fig. 34-1). Slow-release oral formulations of mesalamine such as Pentasa release mesalamine from the duodenum to the ileum, with about 75% of the drug passing into the colon. Olsalazine is a dimer of two 5-aminosalicylate molecules linked by an azo bond. Mesalamine is released in the colon after colonic bacteria cleave olsalazine. Balsalazide is a mesalamine prodrug that is enzymatically cleaved in the colon to produce mesalamine. The recommended daily doses of the oral mesalamine derivatives are intended to approximate the molar equivalent of mesalamine present in 4 g of sulfasalazine. At present, snlfasalazine is nsed in preference to oral mesalamine derivatives, mainly becanse it costs mnch less. However, it is not tolerated as well as the mesalamine altematives. Becanse the oral mesalamine formulations are coated tablets or grannies, they should not be crushed or chewed. 

Sulfasalazine, a prodrug, is cleaved by bacteria in the colon into sulfapyridine and 5-aminosalicylic acid. It is believed that the sul-fapyridine moiety is responsible for the agent s antirheumatic properties, although the exact mechanism of action is not known. Once the colonic bacteria have cleaved sulfasalazine, sulfapyridine and 5-aminosalicylic acid are absorbed rapidly from the gastrointestinal tract. Sulfapyridine distributes rapidly throughout the body, but higher concentrations are found in certain tissues such as serous fluid, liver, and intestines. Both sulfasalazine and its metabolites are excreted in the urine. Antirheumatic effects should be seen within 2 months. 

CHEMISTRY, MECHANISM OF ACTION, AND PHARMACOLOGICAL PROPERTIES First-line therapy for mild-to-moderate ulcerative colitis generally involves mesalamine (5-aminosalicylic acid, or 5-ASA). The archetype for this class of medications is sulfasalazine (azulfidine), which consists of 5-ASA linked to sulfapyridine by an azo bond. Sulfasalazine represents one of the first examples of an oral drug that is delivered effectively to the distal GI tract. The azo linkage in sulfasalazine prevents absorption in the stomach and small intestine, and the individual components are not liberated for absorption until colonic bacteria cleave the bond. 5-ASA is now regarded as the therapeutic agent, with little, if any, contribution by sulfapyridine. 

Most of the bile acids which escape from the terminal ileum into the colon undergo under normal conditions a transformation to secondary bile acids via the action of colonic bacteria (1,4). The amount of primary bile acids in feces is thus negligible, if any, the mixture of fecal bile acids consisting of compounds with a wide range of polarity (38-41). However, in contrast to neutral sterols, bile acids are not degraded to any appreciable extent into undetectable metabolites during the intestinal passage (42). 

An indwelling catheter is commonly used in various health care settings, and is associated with UTIs. Bacteria may be introduced into the bladder via the catheter in several ways. These include direct infection introduction during catheterization (via colonization and subsequently traveling the length of the catheter through bacterial motility or capillary action). UTIs as a result of an indwelling catheter are common and occur at a rate of 5% per day of catheter presence.25... 

Mechanism of Action Asalicylicacidderivativethat isconvertedtomesalamineinthe colon by bacterial action. Blocks prostaglandin production in bowel mucosa. Therapeutic Effect Reduces colonic inflammation in inflammatory bowel disease. Pharmacokinetics Small amount absorbed. Protein binding 99%. Metabolized by bacteria in the colon. Minimal elimination in urine and feces. Half-life 0.9 hr. 

Anaerobic bacteria in the colon produce significant quantities of methanethiol along with hydrogen sulfide. Rodent studies indicate that these substances are detoxified to thiosulfate by the action of a specialized detoxification system that operates in the mucous layer of the colon lining.2 The failure of this system may contribute to some diseases of the colon, such as ulcerative colitis. 

Third, after contact with BAS the microorganisms become sensitive to the action of proteolytic enzymes and cationic and anionic SAS, such as bile acids and phospholipids that is to natural components of intestinal and gastric juices. The high affinity of BAS to microorganisms, and its influence on processes of vital activity of microorganisms, provides an explanation for mechanisms of its curative effect. The appearance of infectious diseases and their progress are directly dependent on the contagious dose and number of bacteria that are accumulated in an intestine in the course of colonization. 

Therefore, the colonic hydrolysis of lactose to glucose and galactose, the fermentation of these monosaccharides to various organic acids and alcohols and H2, and the further conversion of these end products to C02, and CH4 require the combined action of several types of bacteria. 

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