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Uric acid-inducible genes in bacteria from the human gut microbiome

ABSTRACT: Uric acid-inducible genes in bacteria from the human gut microbiome

PROVIDER: PRJNA850627 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR19744338.fastq.gz	Fastqsanger.gz
	SRR19744339.fastq.gz	Fastqsanger.gz
	SRR19744340.fastq.gz	Fastqsanger.gz
	SRR19744341.fastq.gz	Fastqsanger.gz
	SRR19744342.fastq.gz	Fastqsanger.gz

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Uric acid-inducible genes in bacteria from the human gut microbiome

Project description:Approximately 15% of US adults have circulating levels of uric acid above its solubility limit, which is causally linked to the inflammatory disease gout. In most mammals, uric acid elimination is facilitated by the enzyme uricase. However, human uricase is a pseudogene, having been inactivated early in hominid evolution. Though it has long been known that a substantial amount of uric acid is eliminated in the gut, the role of the gut microbiota in hyperuricemia has not been studied. Here we identify a gene cluster, widely distributed in the gut microbiome, that encodes a pathway for uric acid degradation. Stable isotope tracing demonstrates that gut bacteria metabolize uric acid to xanthine or short chain fatty acids such as acetate, lactate and butyrate. Ablation of the microbiota in uricase-deficient mice causes profound hyperuricemia, and anaerobe-targeted antibiotics increase the risk of gout in humans. These data reveal a role for the gut microbiota in uric acid excretion and highlight the potential for microbiome-targeted therapeutics in hyperuricemia.

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Project description:Uric acid stored in the fat body of cockroaches is a nitrogen reservoir mobilized in times of scarcity. The discovery of urease in Blattabacterium cuenoti, the primary endosymbiont of cockroaches, suggests that the endosymbiont may participate in cockroach nitrogen economy. However, bacterial urease may only be one piece in the entire nitrogen recycling process from insect uric acid. Thus, in addition to the uricolytic pathway to urea, there must be glutamine synthetase assimilating the released ammonia by the urease reaction to enable the stored nitrogen to be metabolically usable. None of the Blattabacterium genomes sequenced to date possess genes encoding for those enzymes. To test the host's contribution to the process, we have sequenced and analysed Blattella germanica transcriptomes from the fat body. We identified transcripts corresponding to all genes necessary for the synthesis of uric acid and its catabolism to urea, as well as for the synthesis of glutamine, asparagine, proline and glycine, i.e. the amino acids required by the endosymbiont. We also explored the changes in gene expression with different dietary protein levels. It appears that the ability to use uric acid as a nitrogen reservoir emerged in cockroaches after its age-old symbiotic association with bacteri

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Project description:Uric acid (UA) is the final product of purine metabolism and plays an important role as a physiological antioxidant. In recent years, several different groups have reported a correlation between decreased UA in Parkinson’s disease (PD) and clinical progression and stage of PD. However, little is known about the molecular mechanisms of decreased UA under oxidative stress. We used our systematic functional annotation pipeline for silkworm genes to identify a novel UA metabolic pathway regulator under oxidative stress in a UA metabolism mutant silkworm Bombyx mori model. Gene expression was measured in 3day of fifth instar larvae of abnormal uric acid synthesis Bombyx mori mutant of op.

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The cockroach Blattella germanica obtains nitrogen from uric acid through a metabolic pathway shared with its bacterial endosymbiont

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Gene expression of abnormal uric acid synthesis animal model of silk worm Bombyx mori.

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Project description:Milk urea concentration is an indicator for dietary nitrogen (N)-supply and urinary nitrogen excretion. Dairy cows with high (HMU) compared to low milk urea (LMU) concentration have greater plasma urea, creatinine and uric acid concentrations, but if the liver metabolism accounts for these differences is unknown. Eighteen HMU and 18 LMU cows were fed either a diet with a low (LP) and normal (NP) crude protein concentration. An N-balance study was performed and a 13C-urea bolus was administered followed by a series of blood samplings. Liver samples were analysed by 2D-gel-based proteomics and real-time RT-PCR. Although HMU cows had a higher urea pool, plasma urea, uric acid, and hippuric acid concentrations, these differences were not associated with increased activation of the hepatic urea cycle or non-urea nitrogen metabolite pathways. Instead, HMU cows had a higher oxidative stress level. Conclusively, other factors than hepatic urea metabolism account for the milk urea concentration. Despite higher plasma urea concentrations on the LP diet, urea cycle mRNA expression was not affected, indicating it is not controlled at transcriptional level. Feeding the LP diet resulted in higher expressions of enzymes catabolizing fatty acids, which is likely due to diminished microbial growth and insufficient energy supply.

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