UBC Theses and Dissertations
The gut microbiome and metabolic pathways of recurrent kidney stone patients and their non-stone-forming live-in partners Choy, Wai Ho
Background: Metabolism-associated kidney stones such as oxalate, uric acid and cystine stones are caused by over-accumulation or under-excretion of their associated metabolites in the human body. Although the kidney is the primary excretion site for these metabolites, the intestine is an important alternative site of excretion. Intestinal bacterial community members contribute to the breakdown, transport and assimilation of stone-associated metabolites including oxalate, uric acid, cystine and butyrate. To better diagnose and prevent the formation of metabolic kidney stones, the intestinal microbiome should be examined at the level of bacterial communities and interconnected metabolic pathways. Experimental approach: This study examines the differences in bacterial communities and metabolic pathways between the intestinal microbiomes of recurrent kidney stone patients and non-stone-forming controls. Fecal samples were collected from 17 recurrent kidney stone patients and 17 controls with no stone-forming history. Bacterial DNA was then extracted from the fecal samples. To examine bacterial taxonomy, specific variable regions of the 16S rRNA gene were sequenced from the DNA and aligned to a bacterial gene database to identify and quantify the bacteria present. To examine metabolic pathways, metagenomic DNA libraries were sequenced, assembled and aligned to a metabolic gene database to identify and quantify the metabolic genes present. Results: Bacterial populations in patient microbiomes appear to be less diverse than those in control microbiomes. At the bacterial species level, we found that patient microbiomes had lower abundance of Oxalobacter formigenes, a well-known oxalate-degrading bacterium. At the metabolic pathway level, patient microbiomes were found to contain a lower abundance of genes important for the production of butyrate, a fatty acid that promotes overall intestinal integrity and has been found to upregulate the expression of oxalate transporters in the gut. Conclusions: This study verifies previous findings that a majority of recurrent kidney stone formers lack O. formigenes in their intestinal microbiomes. Additionally, analysis into metabolic genes in the gut uncovered an additional deficiency in the butyrate metabolism pathway that could influence overall gut homeostasis. Reduced bacterial diversity in recurrent stone formers also suggest patient microbiomes may be dysbiotic, a state common to many intestinal diseases.
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