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The relationship between nitro group reduction and the intestinal microflora.

L A Wheeler, F B Soderberg, P Goldman

    The Journal of Pharmacology and Experimental Therapeutics
    |July 1, 1975
    PubMed
    Summary

    The gut microbiome significantly impacts how rats metabolize p-nitrobenzoic acid (PNBA) into p-aminobenzoic acid (PABA). Introducing specific gut bacteria increased this conversion, highlighting the microflora's crucial role in drug metabolism.

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    Area of Science:

    • Microbiology
    • Pharmacology
    • Gastroenterology

    Background:

    • The metabolic fate of xenobiotics, such as p-nitrobenzoic acid (PNBA), is influenced by host factors and microbial activity.
    • Previous studies noted discrepancies in PNBA reduction in rats that did not correlate with liver enzyme activity.

    Purpose of the Study:

    • To investigate the role of the intestinal microflora in the reduction of p-nitrobenzoic acid (PNBA) to p-aminobenzoic acid (PABA) in rats.
    • To determine the contribution of specific gut bacteria to this metabolic conversion.

    Main Methods:

    • Quantification of urinary p-aminobenzoic acid (PABA) and its conjugates after administering PNBA to germfree and conventional rats.
    • Colonization of germfree rats with specific cecal bacteria (Lactobacillus plantarum, Clostridium sp., Streptococcus faecalis) and assessment of PNBA reduction.

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  • Evaluation of the effect of cecectomy on PNBA reduction capacity in conventional rats.
  • Similar experiments were conducted with p-nitrobenzenesulfonamide.

    • Main Results:

    • Germfree rats showed minimal PNBA to PABA conversion (approx. 1%), while conventional rats exhibited significant conversion (approx. 25%).
    • Association of germfree rats with Lactobacillus plantarum increased conversion to 3.9%, and further association with Clostridium sp. and Streptococcus faecalis raised it to approx. 12%.
    • A positive correlation was observed between the in vitro PNBA-reducing capacity of microflora constituents and their effect when associated with germfree rats. Cecectomy reduced PNBA reduction capacity.

    Conclusions:

    • The intestinal microflora, not liver enzymes, is primarily responsible for the reduction of the nitro group in PNBA and similar compounds in rats.
    • Specific bacterial species within the gut microbiome play a significant role in the metabolism of xenobiotics.
    • Understanding the microbial contribution to xenobiotic metabolism is crucial for explaining physiological and pharmacological observations.