Oxalobacter formigenes and its potential role in human health

Abstract

Oxalate degradation by the anaerobic bacterium Oxalobacter formigenes is important for human health, helping to prevent hyperoxaluria and disorders such as the development of kidney stones. Oxalate-degrading activity cannot be detected in the gut flora of some individuals, possibly because Oxalobacter is susceptible to commonly used antimicrobials. Here, clarithromycin, doxycycline, and some other antibiotics inhibited oxalate degradation by two human strains of O. formigenes. These strains varied in their response to gut environmental factors, including exposure to gastric acidity and bile salts. O. formigenes strains established oxalate breakdown in fermentors which were preinoculated with fecal bacteria from individuals lacking oxalate-degrading activity. Reducing the concentration of oxalate in the medium reduced the numbers of O. formigenes bacteria. Oxalate degradation was established and maintained at dilution rates comparable to colonic transit times in healthy individuals. A single oral ingestion of O. formigenes by adult volunteers was, for the first time, shown to result in (i) reduced urinary oxalate excretion following administration of an oxalate load, (ii) the recovery of oxalate-degrading activity in feces, and (iii) prolonged retention of colonization.

FIG. 1.

Effect of incubation at pH 6.8, 3, and 2 for 2 h upon survival of O. formigenes strains. Values are the averages of three separate incubations + SD (bars).

FIG. 2.

The effect of introduction of O. formigenes on oxalate concentrations in fermentor simulations of the human colon operated at different dilution rates. (a) Vessel V inoculated on day 0 with O. formigenes strain Va3; D = 0.015 h⁻¹. (b) Vessel H1 (○) inoculated on day 0 with O. formigenes strain HC1; D = 0.0625 h⁻¹. Also shown are data for vessel H2 (▴), inoculated on day 35 with the mixed population from vessel H1; D = 0.02 h⁻¹.

FIG. 3.

PCR-based detection of O. formigenes in fermentor samples. A genus-specific oligonucleotide probe was used that hybridizes to the PCR amplification product of the oxc gene. (A) Agarose gel electrophoresis of the PCR products. (B) Southern blotting performed on the same gel. Lanes 1, 2, and 3 are replicate samples from vessel H1 and lanes 4, 5, and 6 are replicate samples from vessel H2, 44 days after the start of perfusion with medium to which oxalate was not added. Lane +c, amplification of genomic DNA of the type strain OxB; lane −c, negative control; lane M, molecular size marker.