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The gut microbiome and metabolic pathways of recurrent kidney stone patients and their non-stone-forming live-in partners Choy, Wai Ho
Abstract
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.
Item Metadata
Title |
The gut microbiome and metabolic pathways of recurrent kidney stone patients and their non-stone-forming live-in partners
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Creator | |
Publisher |
University of British Columbia
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Date Issued |
2018
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Description |
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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Genre | |
Type | |
Language |
eng
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Date Available |
2018-08-27
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Provider |
Vancouver : University of British Columbia Library
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Rights |
Attribution-NonCommercial-NoDerivatives 4.0 International
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DOI |
10.14288/1.0371254
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URI | |
Degree | |
Program | |
Affiliation | |
Degree Grantor |
University of British Columbia
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Graduation Date |
2018-09
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Campus | |
Scholarly Level |
Graduate
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Rights URI | |
Aggregated Source Repository |
DSpace
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Rights
Attribution-NonCommercial-NoDerivatives 4.0 International