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Query: UMLS:C0020500 (hyperoxaluria)
 912 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Hyperoxaluria can lead to multiple pathologic conditions such as recurrent urolithiasis, oxalosis, nephrocalcinosis and even renal failure, but there is no known oxalate-degrading pathway in the human body, and current therapeutic options for patients with hyperoxaluria are limited. Oxalyl-CoA decarboxylase and formyl-CoA transferase are the key enzymes in the oxalate catabolism of Oxalobacter formigenes which dwell in the intestine of vertebrates and have an important symbiotic relationship with their hosts. The aim of this study was to insert the oxalate-degrading enzyme genes into human embryo kidney (HEK) 293 cells and to evaluate if the oxalate-degrading enzymes could be expressed in these cells and keep their enzyme activity. We present here the cloning of the two genes from O. formigenes and their subsequent expression in HEK293 cells. The results showed that the expression of oxalyl-CoA decarboxylase and formyl-CoA transferase was confirmed by RT-PCR and Western blotting, and the proteins were located in the cytoplasm of transfected cells. Furthermore, the transfected cells were capable to a certain degree of degrading oxalate. These findings suggest that the transfer of oxalate-degrading enzyme genes into human cells is possibly a potential candidate for the gene therapy of hyperoxaluria.
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PMID:Stable expression of the oxc and frc genes from Oxalobacter formigenes in human embryo kidney 293 cells: implications for gene therapy of hyperoxaluria. 1778 82

Humans lack the enzymes needed to metabolize endogenous and dietary oxalate, a toxic compound causing hyperoxaluria and calcium oxalate urolithiasis. Oxalate in humans can be eliminated through (1) excretion in urine, (2) forming insoluble calcium oxalate and elimination in feces, or (3) oxalate degradation by gastrointestinal (GIT) microorganisms. In this article, anaerobic oxalate catabolism in gut bacteria is reviewed, and the possible use of these bacteria as probiotics for treating kidney stone disease is evaluated. Oxalobacter formigenes and Lactobacillus and Bifidobacterium species are the best studied in this regard, with oxalate degradation in the lactic acid bacteria being both species- and strain-specific. The GIT oxalate-degrading bacteria express the catabolic enzymes formyl-CoA transferase (Frc) and oxalyl-CoA decarboxylase (Oxc). The genes encoding these proteins are clustered on the genomes and show strong phylogenetic relationships. Clinical trials investigating reduced hyperoxaluria through administering O. formigenes or its enzymes show a promising trend, but the data need confirmation through larger scale, well-controlled trials. Similar studies using Lactobacillus and Bifidobacterium species also show in vivo oxalate reduction, but these data are still controversial. In particular, further investigations need to determine whether there is a direct link between the lack of oxalate-degrading bacteria and hyperoxaluria and whether their absence is a risk factor. Key experiments linking microbial numbers, functional oxalate degradation, molecular analysis of the regulation of the genes involved, and the ability of the bacteria to survive in the gut are crucial elements in identifying suitable probiotics for treating kidney stone disease.
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PMID:Oxalate-degrading bacteria of the human gut as probiotics in the management of kidney stone disease. 2060 88

Hyperoxaluria due to endogenously synthesized and exogenously ingested oxalates is a leading cause of recurrent oxalate stone formations. Even though, humans largely rely on gut microbiota for oxalate homeostasis, hyperoxaluria associated gut microbiota features remain largely unknown. Based on 16S rRNA gene amplicons, targeted metagenomic sequencing of formyl-CoA transferase (frc) gene and qPCR assay, we demonstrate a selective enrichment of Oxalate Metabolizing Bacterial Species (OMBS) in hyperoxaluria condition. Interestingly, higher than usual concentration of oxalate was found inhibitory to many gut microbes, including Oxalobacter formigenes, a well-characterized OMBS. In addition a concomitant enrichment of acid tolerant pathobionts in recurrent stone sufferers is observed. Further, specific enzymes participating in oxalate metabolism are found augmented in stone endures. Additionally, hyperoxaluria driven dysbiosis was found to be associated with oxalate content, stone episodes and colonization pattern of Oxalobacter formigenes. Thus, we rationalize the first in-depth surveillance of OMBS in the human gut and their association with hyperoxaluria. Our findings can be utilized in the treatment of hyperoxaluria associated recurrent stone episodes.
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PMID:Hyperoxaluria leads to dysbiosis and drives selective enrichment of oxalate metabolizing bacterial species in recurrent kidney stone endures. 2770 9