Gut bacteria

Rifaximin Rifamycin Antibiotic Gut bacteria Enteric infection Diarrhea, infectious Hepatic encephalopathy Small intestine bacterial overgrowth Inflammatory bowel disease Colonic diverticular disease Irritable bowel syndrome Constipation Clostridium difficile infection Helicobacter pylori infection Colorectal surgery Bowel decontamination, selective Pancreatitis, acute Bacterial peritonitis, spontaneous Nonsteroidal anti-inflammatory drug enteropathy... 

An indirect proof of the role exerted by gut bacteria in the pathogenesis of NSAID enteropathy is represented by the similarities between indomethacin-induced intestinal damage and Crohn s disease [234, 246], Not only are these lesions anatomically (both macro- and microscopically) similar [246], but also sensitive to the same drugs, e.g. sulfasalazine [234,247], steroids [234,247], immunosuppressive compounds [248], and antibiotics [234-237],... 

As shown in table 7, there are established and potential clinical indications for this peculiar drug. In all these conditions, many of which share SIBO as a common feature, gut bacteria represent the specific target of rifaximin. The drug can be used alone (like, for instance, in the treatment of infectious diarrhea) or as add-on medication (as in the management of IBD) and given short-term (single course of treatment) or long-term (repeated courses of therapy, i.e. cyclically). 

Runyon BA, Squier SU, Borzio M Transloca-tion of gut bacteria in rats with cirrhosis to mesenteric lymph nodes partially explains the pathogenesis of spontaneous bacterial peritonitis. J Hepatol 1994 21 792-796. 

Yurdaydin C, Walsh TJ, Howard DE, Ha J, Li Y, Jones EA, Basile AS Gut bacteria provide precursors of benzodiazepine receptor ligands in a rat model of hepatic encephalopathy. Brain Res 1995 679 42-48. 

Dasarathy S Role of gut bacteria in the therapy of hepatic encephalopathy with lactulose and antibiotics. Indian J Gastroenterol 2003 22(suppl 2) S50-S53. 

Due to its excellent activity against a broad range of enteropathogens as well as its lack of absorption after oral administration the first topical application of rifaximin was within the GI tract [1, 2]. The appreciation of the pathogenic role of gut bacteria in several organic and functional GI diseases [6, 7] has broadened its clinical use, which now goes beyond the original indication, i.e. GI infections. 

Although hydrolytic enzymes, esterases and amidases, are named after their major substrates, the same enzyme can often hydrolyze esters, thioesters, and amides therefore, the differentiation between esterases and amidases is sometimes artificial. The highest hydrolytic activity is in the liver, but the enzyme pseudocholinesterase is found in the serum. Gut bacteria also contain hydrolytic enzymes. 

Brauman A, Kane MD, Labat M, Breznak JA. 1992. Genesis of acetate and methane by gut bacteria of nutritionally diverse termites. Science 257 1384-7. 

Maefarlane, G.T., Hay, S., and Gibson, G.R., Influence of mucin on glycosidase, protease and arylamidase activities of human gut bacteria grown in a 3-stage continuous culture system, J. Appl. Bacteriol., 66 407-417 (1989). 

Long-term, low-level feeding of penicillin and the tetracyclines promotes, by natural selection from the pool of normal intestinal flora, those enteric (gut) bacteria that contain R-plasmids. R-plasmids, also known as R-factors, are extrachromosomal genetic material which confer antibiotic resistance to host bacteria. These plamids can be transferred between various kinds of bacteria through cell-to-cell contact (conjugation). Simultaneous resistance to several unrelated antibiotics is commonly carried on a single plasmid and therefore is simultaneously transferred from one bacterium to another. 

Vitamin K promotes the hepatic y-car-boxylation of glutamate residues on the precursors of factors II, VII, IX, and X, as well as that of other proteins, e.g., protein C, protein S, or osteocalcin. Carboxyl groups are required for Ca +-mediat-ed binding to phospholipid surfaces (p, 142). There are several vitamin K derivatives of different origins Ichlorophyllous plants I<2 from gut bacteria and I<3 (menadione) synthesized chemically. All are hydrophobic and require bile acids for absorption. 

Diphenolmethane derivatives (p. 177) were developed from phenolphthalein, an accidentally discovered laxative, use of which had been noted to result in rare but severe allergic reactions. Bisac-odyl and sodium picosulfate are converted by gut bacteria into the active colon-irritant principle. Given by the enteral route, bisacodyl is subject to hydrolysis of acetyl residues, absorption, conjugation in liver to glucuronic acid (or also to sulfate, p. 38), and biliary secretion into the duodenum. Oral administration is followed after approx. 6 to 8 h by discharge of soft formed stooL When given by suppository, bisacodyl produces its effect within 1 h. 

Bone E, Tamm A, Hill M. 1976. The production of urinary phenols by gut bacteria and their possible role in the causation of large bowel cancer. Am J Clin Nutr 29 1448-1454. 

In some well-documented cases given oral antibiotics, contraception has failed - presumably because gut bacteria have been killed and the recycled component of oestrogen lost with a consequent fall in plasma oestrogen. It is possible to be pregnant on the pill in this case ... 

Coumarins are competitive inhibitors of vitamin K, which is required for the formation in the liver of the amino acid, gamma-carboxyglutamic acid. This is necessary for the synthesis of prothrombin and factors VII, IX and X (Figure 17.1). After starting treatment the anticoagulant effect is delayed until the concentration of normal coagulation factors falls (36-72 h). The effects can be reversed by vitamin K (slow maximum effect only after 3-6 h) or by whole blood or plasma (fast). Gut bacteria synthesise vitamin K and thus are an important source of this vitamin. Consequently, antibiotics can cause excessive prolongation of the prothrombin time in patients otherwise adequately controlled on warfarin. 

Despite the lack of agreed guidelines for the tests involved, tests do exist and they comprise studies in human volunteers, studies in germ-free rats the intestines of which harbor human gut bacteria, and in vitro studies with bacterial populations. However, the selection of the most appropriate test system remains an open question. All tests investigate minimum inhibitory concentrations (MICs) that can be used in ADI calculations however, such ADI calculations tend to... 

Apart from influencing the absorption of foreign compounds, the environment of the gastrointestinal tract may also affect the compound itself, making it more or less toxic. For example, gut bacteria may enzymically alter the compound, and the pH of the tract may affect its chemical structure. 

The natural-occurring carcinogen cycasin, which is a glycoside of methylazoxymethanol (Fig. 1.1), is hydrolyzed by the gut bacteria after oral administration. The product of the hydrolysis is methylazoxymethanol, which is absorbed from the gut and which is the compound responsible for the carcinogenicity. Given by other routes, cycasin is not carcinogenic, as it is not hydrolyzed. 

The gut bacteria may also reduce nitrates to nitrites, which can cause methemoglobinemia or may react with secondary amines in the acidic environment of the gut, giving rise to carcinogenic nitrosamines. 

There are three main sites of absorption skin (large surface area poorly vascularized not readily permeable) gastrointestinal tract (major site well vascularized variable pH large surface area transport processes food gut bacteria) lungs (very large surface area well vascularized readily permeable). Compounds may be administered by direct injection (i.p., i.m., s.c., i.v.). 

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