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An In Vitro System to Study Effects of Low Dose Antimicrobials on the Human Intestinal Microflora


<p>To use an in vitro chemostat culture system that mimics the human intestinal tract to determine the concentrations of antibiotic residues in food that produce no adverse effect on the human intestinal microflora.</p>

<p>The adverse effects to be evaluated include:</p>

<li>Changes in numbers of selected organisms;</li>
<li>Changes in the metabolic activity of the fecal flora relating to metabolism of endogenous and exogenous compounds;</li>
<li>Development of antimicrobial-resistant strains; and</li>
<li>Disruption of colonization resistance of pathogenic microorganisms.</li>


More information

FY 2000 Accomplishments: <ol> <li>Antibiotics are used both therapeutically and as growth promoters in animals destined for human consumption. Residues of the antibiotics may remain in the animal tissues when they are brought to market. A pre-validation study was conducted on a method to test the effect on the human intestinal microflora, of low level antibiotic residues in food.
<li>Using a series of chemostats to model the bacteria population of the human large intestine, selected bacterial species were monitored for an increase in antibiotic resistance upon the addition of different levels of ciprofloxacin.
<li>The normal population of bacteria in the human intestines serves as a natural barrer to colonization of the gut by pathogenic bacteria. Using the chemostat system, tested the effect of low levels of ciprofloxacin on the ability of the normal intestinal microflora to resist colonization by a Salmonella species.
<li>The results of our ciprofloxacin studies were presented to an international task force on microbial safety, where both the in vitro and an in vivo method for addressing the issue of antibiotic residues in food were evaluated.</ol>
FY 2001 Plans: <ol> <li>Submit a research protocol through the NCTR protocol review and approval system for continued work using the chemostat system to measure the effect of low-level antibiotic residues on the human intestinal microflora.
<li>Continue analysis of the samples collected during the exposure of the chemostats to ciprofloxacin,examining metabolic enzyme activity, volatile fatty acid concentrations,and bile acid metabolism as alternative endpoints for system perturbation by low-level antibiotic residues.
<li>Using the information and experience gained during the ciprofloxacin experiment, intitiate a new chemostat experiment for testing a veterinary fluoroquinolone antibiotic such as enrofloxacin or danofloxacin.
<li>Prepare a topic paper on normal variations in human intestinal microflora for the microbial safety task force, which will be used to recommend procedures for preparing fecal inocula for in vitro or in vivo testing.</ol> </p>

Erickson, Bruce
DHHS/FDA - National Center for Toxicological Research
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