Abstract
Small intestinal bacterial overgrowth (SIBO) has a high incidence in dogs and, as in humans, is difficult to diagnose. The aim of this study was to determine the diagnostic significance of serum unconjugated bile acid concentrations in dogs with bacterial overgrowth. Fasting sera were obtained from 23 dogs: 10 with culture-proven SIBO, 8 with indirectly diagnosed SIBO (normal pancreatic function but small intestinal disease associated with subnormal serum cobalamin and supranormal folate concentrations), and 5 healthy controls. Unconjugated bile acids were determined using gas chromatography–mass spectrometry after isolation by liquid–solid extraction and anion-exchange chromatography. Mean serum unconjugated bile acid concentrations were significantly elevated in dogs with SIBO (mean ± sd: 0.91 ± 1.03 μmol/liter), and in dogs with indirectly diagnosed SIBO (2.11 ± 2.20 μmol/liter) compared to clinically healthy dogs (0.015 ± 0.015 μmol/liter, P < 0.005). Cholic acid was the predominant unconjugated bile acid in the serum of dogs with SIBO. In conclusion serum unconjugated bile acid concentrations of healthy dogs are significantly lower than reported values for humans, and this fraction represents a relatively small proportion (0–2.3%; mean 0.8%) of the total bile acids in dogs. Unconjugated bile acids increased 10- to 20-fold in dogs with SIBO indicating the clinical utility of serum unconjugated bile acids for diagnosis of intestinal bacterial overgrowth in dogs.
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REFERENCES
Russell DW, Setchell KDR: Bile acid biosynthesis. Biochemistry 31:4737-4749, 1992
Kilenberg PG: Measurement and subcelluler distributin of choloyl-CoA synthetase and liver bile acid CoA:amino acid N-acyltransferase activitites in rat liver. J Lipid Res 19:24-31, 1978
Falany CN, Johnson MR, Barnes S, Diasio RB: Glycine and taurine conjugation of bile acids by a single enzyme. Molecular cloning and expression of human liver bile acid CoA:amino acid N-acyltransferase. J Biol Chem 269:19375-19379, 1994
Sjovall J: Dietary glycine and taurine on bile acid conjugation in man. Bile acids and steroids 75. Proc Soc Exp Biol Med 100:676-678, 1959
Haslewood GAD: The biological importance of Bile Salts. Amsterdam, North Holland 1978
Setchell KDR, Dumaswala R, Colombo C, Ronchi M: Hepatic bile acid metabolism during early development revealed from the analysis of human fetal gallbaldder bile. J Biol Chem 263:16637-16644, 1988
Suchy FJ, Courchene SM, Balistreri WF: Ontogeny of hepatic bile acid conjugation in the rat. Pediatr Res 19(1):97-101, 1985
Rabin B, Nicolosi RJ, Hayes KC: Dietary influence on bile acid conjugation in the cat. J Nutr 106:1241-1246, 1976
O'Maille ERL, Richards TG, Short AH: Acute taurine depletion and maximal rates of hepatic conjugation and secretion of cholic acid in the dog. J Physiol 180:76-79, 1965
Matoba N, Une M, Hoshita T: Identification of unconjugated bile acids in human bile. J Lipid Res 27:1154-1162, 1986
Crosignani A, Podda M, Battezzati PM, Bertolini E, Zuin M, Watson D, Setchell KDR: Changes in bile acid composition in patients with primary biliary cirrhosis induced by ursodeoxycholic acid administration. Hepatology 14:1000-1007, 1991
Hofmann AF: The enterohepatic circulation of bile acids in man. Clin Gastroenterol 6:3-24, 1977
Hylemon PB: Metabolism of bile acids in intestinal microflora. In Sterols and Bile Acids. H Danielsson, J Sjovall (eds). Amsterdam, Elsevier, 1985, pp 331-343
Setchell KDR, Street JM, Sjovall J: Fecal bile acids. In The Bile Acids. Physiology and Metabolism, Vol 4. KDR Setchell, PP Nair, D Kritchevsky (eds). New York, Plenum Press, 1988, pp 441-570
Folch MH, Gersengoren W, Elliot S, Spiro HM: Bile acid exhibition of the intestinal microflora-a function for simple bile acids? Gastroenterology 61:228-233, 1971
Mekhjian HS, Philips SF, Hofmann AF: Colonic absorption of unconjugated bile acids. Perfusion studies in man. Dig Dis Sci 24:545-550, 1979
Schiff ER, Small NC, Dietschy JM: Characteristics of the kinetics of the passive and active transport mechanisms for bile acid absorption in the small intestine and colon of the rat. J Clin Invest 51:1351-1362, 1972
Makino I, Nakagawa S, Mashimo K: Conjugated and unconjugated serum bile acid levels in patients with hepatobiliary diseases. Gastroenterology 56:1033-1039, 1969
Setchell KDR, Lawson AM, Blackstock EJ, Murphy GM: Diurnal changes in serum unconjugated bile acids in normal man. Gut 23:637-642, 1982
Setchell KDR, Harrison DL, Gilbert JM, Murphy GM: Serum unconjugated bile acids: Qualitative and quantitative profiles in ileal resection and bacterial overgrowth. Clin Chim Acta 152:297-306, 1985
Lewis B, Panaveliwalla AD, Tabaqchali S, Wootton IPD: Serum bile acids in the stagnant-loop syndrome. Lancet 1:219-220, 1969
Tangerman A, van Schaik A, van der Hoek EW: Analysis of conjugated and unconjugated bile acids in serum and jejunal fluid of normal subjects. Clin Chim Acta 159:123-132, 1986
Bolt MJG, Stellaard F, Paumgartner G: Serum unconjugated bile acids in patients with small bowel bacterial overgrowth. Clin Chim Acta 181:87-102, 1989
Masclee A, Tangerman A, van Schaik A, van der Hoek EW, Van Tongeran JHM: Unconjugated serum bile acid as a marker of small intestinal bacterial overgrowth. Eur J Clin Invest 19:384-389, 1989
Batt RM, Needham JR, Carter MW: Bacterial overgrowth associated with a naturally occurring enteropathy in the German shepherd dog. Res Vet Sci 35:42-46, 1983
Williams DA, Batt RM, McLean L: Bacterial overgrowth in the duodenum of dogs with exocrine pancreatic insufficiency. J Am Vet Med Assoc 191:201-206, 1987
Westermarck E, Myllys V, Aho M: Intestinal bacterial overgrowth in dogs with exocrine pancreatic insufficiency. Effect of enzyme replacement and antibiotic therapy. J Vet Intern Med 5:131, 1991 (abstract)
Batt RM, Hall EJ, McLean L, Simpson KW: Small intestinal bacterial overgrowth and enhanced intestinal permeability in healthy Beagles. Am J Vet Res 53:1935-1940, 1992
Willard MD: Chronic intestinal bacterial overgrowth. In Current Veterinary Therapy. Small Animal Practice. 10th ed. RW Kirk, JD Bonagura (eds). Philadelphia, WB Saunders, 1989, pp 933-938
Rutgers HC, Batt RM, Elwood CM, Lamport A: Small intestinal bacterial overgrowth in dogs with chronic intestinal disease. J Am Vet Med Assoc 206:187-193, 1995
Rutgers HC, Lamport A, Simpson KW, Elwood CE, Batt RM: Bacterial overgrowth in dogs with chronic intestinal disease. J Vet Intern Med 7:133, 1993 (abstract)
Dill-Macky E, Williams DA: Breath [14CO2] output following oral administration of [14C]D-xylose to healthy dogs. J Vet Intern Med 3:132, 1989 (abstract)
Batt RM, Morgan JO: Role of serum folate and vitamin B12 concentrations in the differentiation of small intestinal abnormalities in the dog. Res Vet Sci 32:17-22, 1982
Rodrigues MP, Setchell KDR: Performance characteristics of reversed-phase bonded silica cartridges for serum bile acid extraction. Biomedical chromatography 10:1-5, 1996
Alme B, Bremmelgaard A, Sjovall J, Thomassen P: Analysis of metabolic profiles of bile acids in urine using a lipophilic anion exchanger and computerized gas-liquid chromatography-mass spectrometry. J Lipid Res 18:339-362, 1977
Setchell KDR, Matsui A: Serum bile acid analysis. Clin Chim Acta 127:1-17, 1983
Hirano Y, Miyazaki H, Higashidate S, Nakayama F: Analysis of 3-sulfated and nonsulfated bile acids by one-step solvolysis and high performance liquid chromatography. Journal of lipid research 28:1524-1529, 1987
Nair PP, Garcia CC: A modified gas-liquid chromatography procedure for the rapid determination of bile acids in biological fluids. Anal Biochem 29:164-166, 1969
Blau K, King G (eds): Handbook of Derivatives for Chromatography. London, Heyden & Son, 1978
Setchell KD: Liquid-solid extraction, lipophilic gel chromatography and capillary column gas chromatography in the analysis of bile acids from biological samples. In Bile acids in Gastroenterology. L Barabara, RH Dowiling, AF Hofman, E Roda (eds). Lancaster, UK, MTP Press Ltd, 1983, pp 1-18
Lawson AM, Setchell KDR: Mass spectrometry of bile acids. In The Bile Acids. Physiology and Metabolism, Vol 4. KDR Setchell, PP Nair, D Kritchevsky (eds). New York Plenum Press, 1988, pp 167-268
Setchell KDR, Heubi JE, O'Connell NC, Hofmann AF, Lavine JE: Identification of a unique inborn error in bile acid conjugation involving a deficiency in amidation. In Bile Acids in Hepatobiliary Disease. Basic and Clinical Applications. G Paumgartner, A Stiehl, W Gerok (eds). Dordrecht, Kluwer Academic, 1997, pp 43-37
Rosenberg IH, Hardison WG, Bull DM: Abnormal bile-salt patterns and intestinal bacterial overgrowth associated with malabsorption. N Engl J Med 276:1391-1397, 1967
King CE, Toskes PP: Small intestine bacterial overgrowth. Gastroenterology 76:1035-1055, 1979
Fromm H, Hofmann AF: Breath test for altered bile acid metabolism. Lancet 11:621-625, 1971
King CE, Toskes PP, Spivey JC, Lorenz E, Welkos S: Detection of small intestine bacterial overgrowth by means of a [14C]-D-xylose breath test. Gastroenterology 77:79-82, 1979
Metz G, Gassull MA, Drasar BS, Jenkins DJA, Blendis LM: Breath hydrogen test for small-intestinal bacterial colonization. Lancet 1:668-669, 1976
Drasar BS, Hill MJ, Shiner M: The deconjugation of bile salts by human intestinal bacteria. Lancet 1:1237-1238, 1966
Northfield TC, Drasar BS, Wright JT: Value of small intestinal bile acid analysis in the diagnosis of stagnant loop syndrome. Gut 14:341-347, 1973
Donaldson RM Jr: Studies on the pathogenesis of steatorrhea in the blind-loop syndrome. J Clin Invest 44:1815-1825, 1965
Tabaquali S, Booth CC: Jejunal bacteriology and bile-salt metabolism in patients with intestinal malabsorption. Lancet 11:12-15, 1966
Angelin B, Bjorkhem I, Einarsson K, Ewerth S: Hepatic uptake of bile acids in man. J Clin Invest 70:724-731, 1982
O'Maille ERL, Richards TG, Short AH: The influence of conjugation of cholic acid on its uptake and secretion: Hepatic extraction of taurocholate and cholate in the dog. J Physiol 189:350-357, 1967
van Berge-Henegouwen GP, Hofmann AF: Systemic spill-over of bile acids. Eur J Clin Invest 13:433-437, 1983
Hoenig M: Intestinal malabsorption attributed to bacterial overgrowth in a dog. J Am Vet Med Assoc 176:533-535, 1980
Thompson MB, Chappell JD, Kunze DJ, Blair PC: Bile acid profile in a dog with cholangiocarcinoma. Vet Pathol 26:75-78, 1989
Washizu T, Tomoda I, Kaneko JJ: Serum bile acid composition of the dog, cow, horse and human. J. Vet Med Sci 53:81-86, 1990
Hepner GWA, Hofmann AF, Thomas PJ: Metabolism of steroid and amino acid moieties of conjugated bile acids in man. I: Cholylglycine. J Clin Invest 51:1889-1897, 1972
Hepner GWA, Hofmann AF, Thomas PJ: Metabolism of steroid and amino acid moieties of conjugated bile acids in man. II: Glycine-conjugated dihydroxy bile acids. J Clin Invest 51:1898-1905, 1972
Huijghebaert SM, Hofmann AF: Influence of the amino acid moiety on deconjugation of bile acid amidates by cholylglycine hydrolase or human fecal cultures. J Lipid Res 27:742-752, 1986
Bernstein LH, Gutstein S, Efron G, Wager G: Experimental production of elevated serum folate in dogs with intestinal blind loops: Relationship of serum levels to location of the blind loop. Gastroenterology 63:815-819, 1972
Bernstein LH, Gutstein S, Efron G, Wager G: Experimental production of elevated serum folate in dogs with intestinal blind loops II: Nature of bacterially produced folate coenzymes in blind loop fluid. Am J Clin Nutr 28:925-929, 1975
Horadagoda NU, Batt RM: Lysosomal localization of cobalamin during absorption by the ileum of the dog. Biochim Biophys Acta 838:206-210, 1985
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Melgarejo, T., Williams, D.A., O'connell, N.C. et al. Serum Unconjugated Bile Acids as a Test for Intestinal Bacterial Overgrowth in Dogs. Dig Dis Sci 45, 407–414 (2000). https://doi.org/10.1023/A:1005493416946
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DOI: https://doi.org/10.1023/A:1005493416946