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. 1991 Sep;32(9):1007–1010. doi: 10.1136/gut.32.9.1007

Effect of protein and lactulose on the production of gamma-aminobutyric acid by faecal Escherichia coli.

H al Mardini 1, B al Jumaili 1, C O Record 1, D Burke 1
PMCID: PMC1379039  PMID: 1916480

Abstract

The value of lactulose treatment in hepatic encephalopathy is widely recognised but its mode of action remains controversial. Much evidence supports a role for gamma-aminobutyric acid in hepatic encephalopathy, and lactulose could alter its bacterial production in the gut. Using the rat synaptic membrane assay and gas chromatography mass spectrometry, the production of gamma-aminobutyric acid by faecal Escherichia coli, with and without the addition of albumin, haemoglobin, whole blood, and lactulose under aerobic and anaerobic conditions was determined. Using an inorganic medium, maximal gamma-aminobutyric acid production occurred after a culture period of between 25 and 50 hours. The concentration after 30 hours of aerobic culture at 37 degrees C by a single strain was mean (SEM), 101 (5) mumol/l (99% confidence intervals 87-114 mumol/l; n = 8; interassay coefficient of variation 14.7%). gamma-aminobutyric acid production was significantly increased by the addition of albumin and haemoglobin. Under anerobic conditions, it was one fifth of that produced aerobically, but the addition of albumin and haemoglobin increased production by greater than 700%. Lactulose did not significantly attenuate gamma-aminobutyric acid production under aerobic or anaerobic conditions. gamma-aminobutyric acid determined by the rat synaptic membrane assay showed a highly significant correlation (r = 0.99) with that detected by gas chromatography mass spectrometry. These data confirm that gamma-aminobutyric acid is produced by faecal E coli and that protein enhances its production considerably, and suggest that lactulose does not exert its therapeutic effect by attenuating gamma-aminobutyric acid production.

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Selected References

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  1. Bassett M. L., Mullen K. D., Scholz B., Fenstermacher J. D., Jones E. A. Increased brain uptake of gamma-aminobutyric acid in a rabbit model of hepatic encephalopathy. Gastroenterology. 1990 Mar;98(3):747–757. doi: 10.1016/0016-5085(90)90298-f. [DOI] [PubMed] [Google Scholar]
  2. Bircher J., Müller J., Guggenheim P., Haemmerli U. P. Treatment of chronic portal-systemic encephalopathy with lactulose. Lancet. 1966 Apr 23;1(7443):890–892. doi: 10.1016/s0140-6736(66)91573-x. [DOI] [PubMed] [Google Scholar]
  3. Conn H. O., Floch M. H. Effects of lactulose and Lactobacillus acidophilus on the fecal flora. Am J Clin Nutr. 1970 Dec;23(12):1588–1594. doi: 10.1093/ajcn/23.12.1588. [DOI] [PubMed] [Google Scholar]
  4. Conn H. O., Leevy C. M., Vlahcevic Z. R., Rodgers J. B., Maddrey W. C., Seeff L., Levy L. L. Comparison of lactulose and neomycin in the treatment of chronic portal-systemic encephalopathy. A double blind controlled trial. Gastroenterology. 1977 Apr;72(4 Pt 1):573–583. [PubMed] [Google Scholar]
  5. Enna S. J., Snyder S. H. Properties of gamma-aminobutyric acid (GABA) receptor binding in rat brain synaptic membrane fractions. Brain Res. 1975 Dec 12;100(1):81–97. doi: 10.1016/0006-8993(75)90243-7. [DOI] [PubMed] [Google Scholar]
  6. Ferenci P., Schafer D. F., Kleinberger G., Hoofnagle J. H., Jones E. A. Serum levels of gamma-aminobutyric-acid-like activity in acute and chronic hepatocellular disease. Lancet. 1983 Oct 8;2(8354):811–814. doi: 10.1016/s0140-6736(83)90735-3. [DOI] [PubMed] [Google Scholar]
  7. Ferkany J. W., Smith L. A., Seifert W. E., Caprioli R. M., Enna S. J. Measurement of gamma-aminobutyric acid (GABA) in blood. Life Sci. 1978 Jun 19;22(23):2121–2128. doi: 10.1016/0024-3205(78)90456-3. [DOI] [PubMed] [Google Scholar]
  8. Laker M. F. Estimation of disaccharides in plasma and urine by gas-liquid chromatography. J Chromatogr. 1979 May 1;163(1):9–18. doi: 10.1016/s0378-4347(00)81163-9. [DOI] [PubMed] [Google Scholar]
  9. Levy L. J., Leek J., Losowsky M. S. Evidence for gamma-aminobutyric acid as the inhibitor of gamma-aminobutyric acid binding in the plasma of humans with liver disease and hepatic encephalopathy. Clin Sci (Lond) 1987 Nov;73(5):531–534. doi: 10.1042/cs0730531. [DOI] [PubMed] [Google Scholar]
  10. Minuk G. Y. Gamma-aminobutyric acid (GABA) production by eight common bacterial pathogens. Scand J Infect Dis. 1986;18(5):465–467. doi: 10.3109/00365548609032366. [DOI] [PubMed] [Google Scholar]
  11. Minuk G. Y., Winder A., Burgess E. D., Sarjeant E. J. Serum gamma-aminobutyric acid (GABA) levels in patients with hepatic encephalopathy. Hepatogastroenterology. 1985 Aug;32(4):171–174. [PubMed] [Google Scholar]
  12. Morgan M. Y., Alonso M., Stanger L. C. Lactitol and lactulose for the treatment of subclinical hepatic encephalopathy in cirrhotic patients. A randomised, cross-over study. J Hepatol. 1989 Mar;8(2):208–217. doi: 10.1016/0168-8278(89)90009-3. [DOI] [PubMed] [Google Scholar]
  13. Morgan M. Y., Hawley K. E., Stambuk D. Lactitol versus lactulose in the treatment of chronic hepatic encephalopathy. A double-blind, randomised, cross-over study. J Hepatol. 1987 Apr;4(2):236–244. doi: 10.1016/s0168-8278(87)80086-7. [DOI] [PubMed] [Google Scholar]
  14. Moroni F., Bianchi C., Tanganelli S., Moneti G., Beani L. The release of gamma-aminobutyric acid, glutamate, and acetylcholine from striatal slices: a mass fragmentographic study. J Neurochem. 1981 May;36(5):1691–1699. doi: 10.1111/j.1471-4159.1981.tb00420.x. [DOI] [PubMed] [Google Scholar]
  15. Mortensen P. B., Rasmussen H. S., Holtug K. Lactulose detoxifies in vitro short-chain fatty acid production in colonic contents induced by blood: implications for hepatic coma. Gastroenterology. 1988 Mar;94(3):750–754. doi: 10.1016/0016-5085(88)90250-8. [DOI] [PubMed] [Google Scholar]
  16. Patil D. H., Westaby D., Mahida Y. R., Palmer K. R., Rees R., Clark M. L., Dawson A. M., Silk D. B. Comparative modes of action of lactitol and lactulose in the treatment of hepatic encephalopathy. Gut. 1987 Mar;28(3):255–259. doi: 10.1136/gut.28.3.255. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Sahota S. S., Bramley P. M., Menzies I. S. The fermentation of lactulose by colonic bacteria. J Gen Microbiol. 1982 Feb;128(2):319–325. doi: 10.1099/00221287-128-2-319. [DOI] [PubMed] [Google Scholar]
  18. Schafer D. F., Fowler J. M., Jones E. A. Colonic bacteria: a source of gamma-aminobutyric acid in blood. Proc Soc Exp Biol Med. 1981 Jul;167(3):301–303. doi: 10.3181/00379727-167-41169. [DOI] [PubMed] [Google Scholar]
  19. Schafer D. F., Jones E. A. Hepatic encephalopathy and the gamma-aminobutyric-acid neurotransmitter system. Lancet. 1982 Jan 2;1(8262):18–20. doi: 10.1016/s0140-6736(82)92559-4. [DOI] [PubMed] [Google Scholar]
  20. van Berlo C. L., de Jonge H. R., van den Bogaard A. E., van Eijk H. M., Janssen M. A., Soeters P. B. gamma-Aminobutyric acid production in small and large intestine of normal and germ-free Wistar rats. Influence of food intake and intestinal flora. Gastroenterology. 1987 Sep;93(3):472–479. doi: 10.1016/0016-5085(87)90908-5. [DOI] [PubMed] [Google Scholar]

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