Abstract: SA-OR028

Understanding the Metatranscriptome and Metagenome Regulating Oxalate Metabolism in the Human Gut

Session Information

Category: Mineral Disease

  • 1204 Mineral Disease: Nephrolithiasis

Authors

  • Nazzal, Lama, New York University School Of Medicine, New York, New York, United States
  • Battaglia, Tom W, New York University School Of Medicine, New York, New York, United States
  • Liu, Menghan, New York University School Of Medicine, New York, New York, United States
  • Goldfarb, David S., New York Harbor VAMC, Hastings on Hudson, New York, United States
  • Ruggles, Kelly, New York University School Of Medicine, New York, New York, United States
  • Blaser, Martin J., New York University School Of Medicine, New York, New York, United States
Background

Multiple bacterial species are capable of degrading oxalate in vitro. Certain taxa degrade oxalate as their sole source of energy and carbon (e.g. Oxalobacter formigenes), whereas others use oxalate as an auxiliary carbon source. For oxalate metabolism, it is not yet well-understood how genomic potential relates to transcriptional regulation. We asked whether the human gut could have a community of oxalate-degrading taxa working synergistically to diminish the effects of this toxic metabolite. Our hypothesis is that oxalate metabolism is regulated by a multi-organism oxalate-degrading community (oxalobiome) that is dominated by specialist oxalate degraders.

Methods

We used data from 2 public databases: (i)8 healthy subjects in the USA; and (ii)471 healthy subjects in the Netherlands as part of the Human Functional Genomic Project (HFGP). Both collected fecal samples for metagenomic and/or metatranscriptomic high throughput sequencing. Using HUMAnN2 with customized settings, we profiled the metabolic activity of oxalate-degrading bacterial species. Output from these analyses was expressed as Reads per Kilobase per Million mapped reads (RPKM).

Results

We identified the oxalate degradation pathway (ODP) in the metagenome and metatranscriptome of all 8 subjects. Mean ODP is 35.3+28.1 and 90.1+43.5 RPKM in the metagenome and the metatranscriptome, respectively, indicating active expression. O. formigenes, E. coli, and unclassified bacteria were present in metagenomic and metatranscriptomic reads. B. dentium had detectable ODP in its genome but was not transcribing it.
In the HFGP database, we identified ODP in 328 subjects of the 471 tested (70%) (Mean=18.1±2.1 RPKM). ODP was detected in B. animalis, B. dentium, B. pseudocatenulatum, E.coli/Shigella, L. acidophilus, L. gasseri, L. mucosae, O. formigenes and unclassified bacteria. ODP was examined in the metagenome of 265 females (Mean ODP= 21.7+3.3) and 200 males (Mean ODP=13.3+1.9 RPKM; p=0.04 by unpaired t test).

Conclusion

We have identified a community of bacteria with the potential to degrade oxalate in healthy humans and species actively transcribing ODP. These include E.coli, which might be a common contributor of oxalate degradation in humans. The sex differences in ODP is consistent with the ~ 2:1 male/female incidence and prevalence of calcium oxalate stones.

Funding

  • NIDDK Support