Login to Access Video or Poster Abstract: MP12-15
Sources of Funding: NIH 1F32DK102277-01A1 _x000D_ Lerner Research Institute Seed funds

Introduction

The impact of a high oxalate content diet on the gastrointestinal microbiome is unknown. Our objective was to elucidate the changes to the microbial metagenome after exposure to high levels of dietary oxalate in vivo. _x000D_

Methods

The metagenomic effects of oxalate on the gut microbiota was studied in the wild mammalian herbivore, Neotoma albigula, a species that regularly consumes high levels of oxalate in the wild and harbors a highly effective oxalate-degrading gut microbiota. Four animals fed a 0.2% oxalate diet for six months prior to the experiment were gradually acclimated to a 6% oxalate diet over the course of nine days. Fecal samples were collected before addition of oxalate and at the end of a five-day period on a 6% oxalate diet for shotgun metagenomic sequencing on an Illumina HiSeq platform. Assembled sequencing data were annotated, normalized with a negative binomial Wald test (DeSeq2), and the differential abundance of genes were compared between the two oxalate diets.

Results

Over the course of the diet trial, animals maintained an oxalate-degrading capacity of nearly 100% of the dietary oxalate consumed. Sequencing effort resulted in 390 million sequence reads across four animals and two time points, with >50,000 unique protein-coding sequences. High oxalate exposure corresponded to a significant shift in the abundance of ~1% of genes identified within the metagenome. Affected genes included several involved in building cellular components, transmembrane transportation, nutrient assimilation, and others.

Conclusions

Our results show that oxalate exhibits broad stimulatory and inhibitory effects on the metagenome of the gut microbiota beyond just that of the oxalate-degrading bacteria. These results can inform the development of probiotics, synbiotics, and dietary strategies designed to maximize microbial oxalate metabolism, along with diagnostic biomarkers indicative of effective or poor microbial oxalate metabolism for patients with recurrent calcium oxalate stone episodes.

Funding

NIH 1F32DK102277-01A1 _x000D_ Lerner Research Institute Seed funds