The effect of physiological concentrations of bile acids on in vitro growth of Mycobacterium tuberculosis.
BACKGROUND
Intestinal tuberculosis occurs mainly in the terminal ileum and caecum, where the concentration of bile acids is lowest, and rarely in the upper digestive tract.


OBJECTIVE
We examined the effect of physiological concentrations of bile acids on the in vitro growth of Mycobacterium tuberculosis (MTB).


METHODS
The 4 major bile acids, lithocolic acid, cholic acid, deoxycholic acid and chenodeoxycholic acid, were added to individual Lowenstein-Jensen (LJ) culture media at physiological concentrations. A combined LJ medium was also prepared using all 4 bile acids. These were double-diluted 4 times by the addition of LJ media. Each culture medium was inoculated with the H37Rv strain of MTB and incubated at 37°C for 8 weeks. MTB growth was measured at 2 and 8 weeks in a semiquantitative fashion using cut-offs of >5, >10, >20, >100 colony-forming units.


RESULTS
All lithocolic acid cultures showed uninhibited TB growth at 2 and 8 weeks. Chenodeoxycholic acid, deoxycholic acid and cholic acid alone, and in combination, showed concentration-dependent inhibition of MTB growth at 2 and 8 weeks. Four cultures were lost to contamination.


CONCLUSIONS
Certain bile acids alone and in combination, at physiological concentrations, inhibit the growth of MTB in vitro. This might explain why intestinal TB occurs in the ileocaecum in the majority of cases and why gallbladder TB is very rare.
Division of Gastroenterology, Department of Medicine, University of Cape Town, Cape Town. david@gastro-enterology.co.za
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Epstein
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Mistry
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Whitelaw
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Watermeyer
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Pettengell
D002635:Chenodeoxycholic Acid / Q000378:metabolism / Q000494:pharmacology; D019826:Cholic Acid / Q000378:metabolism / Q000494:pharmacology; D002793:Cholic Acids / Q000378:metabolism* / Q000494:pharmacology; D006801:Humans; D008095:Lithocholic Acid / Q000378:metabolism / Q000494:pharmacology; D009169:Mycobacterium tuberculosis / Q000187:drug effects / Q000254:growth & development*; D014385:Tuberculosis, Gastrointestinal / Q000382:microbiology*
D002793:Cholic Acids; D002635:Chenodeoxycholic Acid; D008095:Lithocholic Acid; D019826:Cholic Acid