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Abstract
A newly synthesized conjugate of ursodeoxycholic acid with para-aminobenzoic acid (PAB A) was investigated to determine its suitability for evaluation of enteric bacteria. This compound, PABA-UDCA, was deconjugated by cholylglycine hydrolase to release free PABA, whereas it was completely resistant to deconjugation by pancreatic and intestinal mucosal enzymes. In bacteriologic experiments almost all the microorganisms that split glycocholic acid deconjugated PABA-UDCA. In rat experiments urinary excretions of PABA were measured during 6 h after oral administration of 10 mg PABA-UDCA (PABA-UDCA administration test). Ten control rats excreted 338.5 ± 13.8 μg (mean ± SE) of PABA; 10 rats with intestinal stagnant loop excreted more (673.6 ± 70.2 μg; P < 0.01); whereas 10 rats in each of 7 groups pretreated with oral administration of various antibiotics excreted less (P < 0.001; polymixin B + tinidazole, 14.0 ± 2.5 μg; polymixin B, 224.9 ± 23.5 μg; tinidazole, 42.7 ± 8.6 μg; kanamycin, 50.3 ± 5.8 μg; clindamycin, 57.4 ± 7.4 μg; vancomycin, 70.4 ± 8.5 μg; and paromomycin, 160.4 ± 16.4 μg). This result was reflected by the bacterial mean count of feces. In the PABA-UDCA administration test, after 2 months of feeding with different diets, rats with high-fiber diet (n = 10) excreted less PABA in urine (70.9 ± 15.9 μg; P < 0.001) than rats on a control diet (n = 10) and a high-protein-high-fat diet (n = 10) (288.9 ± 34.5 μg and 386.7 ± 61.2 μg, respectively). Fecal bacteriologic status was consistently altered. In human volunteers 250 mg PABA-UDCA was tested. Amounts of PABA excreted in urine during 6 h after dosing were 21.11 ± 2.02 mg in controls (n = 5) and 12.20 ± 1.01 mg in the group treated with polymixin B plus tinidazole (n = 5; P < 0.01). No adverse effect was observed. These basic studies indicate that this compound is likely to offer a simple and rapid method for evaluation of the intestinal microorganisms without use of radioisotopes or expensive, special equipment.