Conjugated bile acid replacement therapy for short-bowel syndrome

Gruy-Kapral, Christine; Little, Katherine H.; Fordtran, John S.; Meziere, Tom L.; Hagey, Lee R.; Hofmann, Alan F.

doi:10.1016/s0016-5085(99)70223-4

Cited by 76 publications

(31 citation statements)

References 32 publications

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“…Cholylsarcosine was shown to be as effective as desiccated ox bile in improving fat malabsorption in a patient with short bowel syndrome who lacked a colon. With continued administration of cholylsarcosine, the patient gained weight [97].…”

Section: Bile Acid Replacementmentioning

confidence: 99%

Bile Acids: Chemistry, Pathochemistry, Biology, Pathobiology, and Therapeutics

Hofmann

Hagey

2008

Cell. Mol. Life Sci.

729

565

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Bile acids and bile alcohols in the form of their conjugates are amphipathic end products of cholesterol metabolism with multiple physiological functions. The great variety of bile acids and bile alcohols that are present in vertebrates are tabulated. Bile salts have an enterohepatic circulation resulting from efficient vectorial transport of bile salts through the hepatocyte and the ileal enterocyte; such transport leads to the accumulation of a pool of bile salts that cycles between the liver and intestine. Bile salt anions promote lipid absorption, enhance tryptic cleavage of dietary proteins, and have antimicrobial effects. Bile salts are signaling molecules, activating nuclear receptors in the hepatocyte and ileal enterocyte, as well as an increasing number of G-protein coupled receptors. Bile acids are used therapeutically to correct deficiency states, to decrease the cholesterol saturation of bile, or to decrease the cytotoxicity of retained bile acids in cholestatic liver disease.

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Section: Bile Acid Replacementmentioning

confidence: 99%

Bile Acids: Chemistry, Pathochemistry, Biology, Pathobiology, and Therapeutics

Hofmann

Hagey

2008

Cell. Mol. Life Sci.

729

565

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“…This, plus the decreased surface area and rapid transit time, leads to severe fat malabsorption. A synthetic bile acid analogue, cholyl-Nmethylglycine (cholylsarcosine) has been shown 48 to increase lipid absorption in a patient with shortbowel syndrome. Cholylsarcosine is resistant to deconjugation and dehydroxylation, and might also be useful in patients with bacterial proliferation in the small intestine.…”

Section: Replacement Therapymentioning

confidence: 99%

The Continuing Importance of Bile Acids in Liver and Intestinal Disease

1999

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Bile acids, the water-soluble, amphipathic end products of cholesterol metabolism, are involved in liver, biliary, and intestinal disease. Formed in the liver, bile acids are absorbed actively from the small intestine, with each molecule undergoing multiple enterohepatic circulations before being excreted. After their synthesis from cholesterol, bile acids are conjugated with glycine or taurine, a process that makes them impermeable to cell membranes and permits high concentrations to persist in bile and intestinal content. The relation between the chemical structure and the multiple physiological functions of bile acids is reviewed. Bile acids induce biliary lipid secretion and solubilize cholesterol in bile, promoting its elimination. In the small intestine, bile acids solubilize dietary lipids promoting their absorption. Bile acids are cytotoxic when present in abnormally high concentrations. This may occur intracellularly, as occurs in the hepatocyte in cholestasis, or extracellularly, as occurs in the colon in patients with bile acid malabsorption. Disturbances in bile acid metabolism can be caused by (1) defective biosynthesis from cholesterol or defective conjugation, (2) defective membrane transport in the hepatocyte or ileal enterocyte, (3) defective transport between organs or biliary diversion, and (4) increased bacterial degradation during enterohepatic cycling. Bile acid therapy involves bile acid replacement in deficiency states or bile acid displacement by ursodeoxycholic acid, a noncytotoxic bile acid. In cholestatic liver disease, administration of ursodeoxycholic acid decreases hepatocyte injury by retained bile acids, improving liver tests, and slowing disease progression. Bile acid malabsorption may lead to high concentrations of bile acids in the colon and impaired colonic mucosal function; bile acid sequestrants provide symptomatic benefit for diarrhea. A knowledge of bile acid physiology and the perturbations of bile acid metabolism in liver and digestive disease should be useful for the internist.

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“…This process may damage specific components of bile. It has been suggested that the alcohol used during the preparation of powdered bile results in the precipitation of particular components (inorganic electrolytes, proteins, and biliary lipids) (18). Also, in order to reconstitute powdered bile in water, the solution must be heated to high temperatures, which may result in hydrolysis of bile acids.…”

mentioning

confidence: 99%

Investigation of the Mechanisms by WhichListeria monocytogenesGrows in Porcine Gallbladder Bile

et al. 2011

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The food-borne pathogen Listeria monocytogenes is known to colonize the lumen of the gallbladder in infected mice and to grow rapidly in this environment (J. Hardy et al., Science 303:851-853, 2004). However, relatively little is known about the mechanisms utilized by the pathogen to survive and grow in this location. We utilized gallbladder bile (GB bile) isolated directly from porcine gallbladders as an ex vivo model of gallbladder growth. We demonstrate that GB bile is generally nontoxic for bacteria and can readily support growth of a variety of bacterial species including L. monocytogenes, Lactococcus lactis, Salmonella enterica serovar Typhimurium, and Escherichia coli. Significantly, L. monocytogenes grew at the same rate as the nonpathogenic species Listeria innocua, indicating that the pathogen does not possess specialized mechanisms that enable growth in this environment. However, when we reduced the pH of GB bile to pH 5.5 in order to mimic the release of bile within the small intestine, the toxicity of GB bile increased significantly and specific resistance mechanisms (Sigma B, BSH, and BilE) were essential for survival of the pathogen under these conditions. In order to identify genetic loci that are necessary for growth of L. monocytogenes in the gallbladder, a mariner transposon bank was created and screened for mutants unable to replicate in GB bile. This led to the identification of mutants in six loci, including genes encoding enzymes involved in purine metabolism, amino acid biosynthesis, and biotin uptake. Although GB bile does not represent a significant impediment to bacterial growth, specific metabolic processes are required by L. monocytogenes in order to grow in this environment.

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Conjugated bile acid replacement therapy for short-bowel syndrome

Cited by 76 publications

References 32 publications

Bile Acids: Chemistry, Pathochemistry, Biology, Pathobiology, and Therapeutics

Bile Acids: Chemistry, Pathochemistry, Biology, Pathobiology, and Therapeutics

The Continuing Importance of Bile Acids in Liver and Intestinal Disease

Investigation of the Mechanisms by WhichListeria monocytogenesGrows in Porcine Gallbladder Bile

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