Structural and Functional Alterations of Gut Microbiota in Males With Hyperuricemia and High Levels of Liver Enzymes

Sheng, Shifeng; Chen, Jingfeng; Zhang, Yuheng; Qin, Qian; Li, Weikang; Su, Yan; Wang, Youxiang; Li, Tiantian; Gao, Xinxin; Tang, Lin; Li, Ang; Ding, Shuzhe

doi:10.3389/fmed.2021.779994

Cited by 22 publications

(23 citation statements)

References 61 publications

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“…Besides the diversity of the gut microbiota in our HUA subjects, the community of the gut microbiota also differed between the two groups, a finding concordant to that of Sheng S ( 13 ). Patients with gout have abundant Bacteroides in their gut microbiomes compared to healthy individuals ( 9 – 11 ).…”

Section: Discussionsupporting

confidence: 80%

“…In a prior report, the taxonomic gut microbiota of adult gout patients had richness indices including Chao1, observed species and ACE that were significantly decreased compared to controls, while Shannon and Simpson diversity indices and beta-diversity were similar between the study groups ( 29 ). Conversely, another study ( 13 ) reported significant alpha- and beta-diversity in the HUA group compared with controls. In our study, despite no significant difference in alpha-diversity of the gut microbiota in those with HUA, the beta-diversity was significantly reduced.…”

Section: Discussionmentioning

confidence: 88%

“…Compositional bacterial alterations could plausibly contribute to the advancement of UA ( 8 – 11 ) and thereby be a potential therapeutic target ( 12 ). Several studies regarding the gut microbiota have been reported in adults with gout; however, only one study in clinically healthy HUA adult male patients involved the structural and functional alterations of gut microbiota ( 13 ). Exploring the seminal pathogenesis of HUA in the microbiome of children may provide insights into its targeted treatment ( 14 ).…”

Section: Introductionmentioning

confidence: 99%

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Altered Gut Microbiota in Children With Hyperuricemia

et al. 2022

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BackgroundIn adults, gut dysbiosis may contribute to the pathogenesis of gout. However, the characteristics of gut microbiota in children with hyperuricemia (HUA) in the absence of clinical gout have not been explored.ObjectiveThis present study analyzed the gut microbiota in children with HUA as compared to controls (Con) and explored bacterial associations that may account for differences.MethodsA total of 80 children were enrolled in this study; they were divided into HUA and Con according to the level of serum uric acid (UA). The composition of gut microbiota was investigated by 16S rRNA high-throughput sequencing.ResultsPrincipal coordinate analysis revealed that gut microbiota of the HUA group was clustered together and separated partly from the Con group. There was no difference in alpha-diversity between the two groups. However, Spearman’s correlation analysis revealed that serum UA level positively correlated with genera Actinomyces, Morganella, and Streptococcus, and negatively associated with the producers of short-chain fatty acids (SCFAs), such as Alistipes, Faecalibacterium, and Oscillospira, and the sulfidogenic bacteria Bilophila. The members of the genera Alistipes and Bilophila in the Con group were significantly more prevalent than the HUA subjects. Compared to the Con cohort, metabolic pathway predictions found that the superpathways of purine nucleotide de novo biosynthesis were decreased in HUA subjects, whereas the superpathway of purine deoxyribonucleoside de gradation was increased.ConclusionThe composition of the gut microbiota in children with HUA differs from Con. Although causality cannot be established, modification in the microbiota that produces SCFA and sulfide may promote HUA.

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Section: Discussionsupporting

confidence: 80%

Section: Discussionmentioning

confidence: 88%

Section: Introductionmentioning

confidence: 99%

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Altered Gut Microbiota in Children With Hyperuricemia

et al. 2022

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“…Especially the Megamonas species had highly positive correlations with the pathways responsible for the biosynthesis of amine, polyamine, and putrescine, such as POLYAMSYN-PWY, ARG+POLYAMINE-SYN, and PWY-6305 in this study. Studies have shown that the relative abundance of Fusobacterium ulcerans in hyperuricemia (Sheng et al, 2021) and post colorectal cancer surgery (Schmitt et al, 2021) was higher than that in the control group. As is known to all, K. pneumoniae, a Gram-negative pathogen bacterium of, is related to lots of opportunistic community-acquired infections.…”

Section: Discussionmentioning

confidence: 91%

Gut microbiome is associated with metabolic syndrome accompanied by elevated gamma-glutamyl transpeptidase in men

Sheng

Su²,

Chen³

et al. 2022

Front. Cell. Infect. Microbiol.

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It is predicted that by 2035, metabolic syndrome (MS) will be found in nearly more than half of our adult population, seriously affecting the health of our body. MS is usually accompanied by the occurrence of abnormal liver enzymes, such as elevated gamma-glutamyl transpeptidase (GGT). More and more studies have shown that the gut microbiota is involved in MS; however, the correlation between gut microbiota and MS with elevated GGT has not been studied comprehensively. Especially, there are few reports about its role in the physical examination of the population of men with MS and elevated GGT. By using the whole-genome shotgun sequencing technology, we conducted a genome-wide association study of the gut microbiome in 66 participants diagnosed as having MS accompanied by high levels of GGT (case group) and 66 participants with only MS and normal GGT level (control group). We found that the number of gut microbial species was reduced in participants in the case group compared to that of the control group. The overall microbial composition between the two groups is of significant difference. The gut microbiota in the case group is characterized by increased levels of “harmful bacteria” such as Megamonas hypermegale, Megamonas funiformis, Megamonas unclassified, Klebsiella pneumoniae, and Fusobacterium mortiferum and decreased levels of “beneficial bacteria” such as Faecalibacterium prausnitzii, Eubacterium eligens, Bifidobacterium longum, Bifidobacterium pseudocatenulatum, Bacteroides dorei, and Alistipes putredinis. Moreover, the pathways of POLYAMSYN-PWY, ARG+POLYAMINE-SYN, PWY-6305, and GOLPDLCAT-PWY were also increased in the case group, which may play a role in the elevation of GGT by producing amine, polyamine, putrescine, and endogenous alcohol. Taken together, there are apparent changes in the composition of the gut microbiome in men with MS and abnormal GGT levels, and it is high time to discover specific gut microbiome as a potential therapeutic target in that population. More in-depth studies of relevant mechanism could offer some new methods for the treatment of MS with elevated GGT.

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“…Several transporters promoting UA secretion have been identified in the intestine (6). Gut microbiota and its metabolites have been proven to directly or indirectly participate in the metabolism of purine and UA (7)(8)(9). The complex interactions between intestinal microbiota and the host provide crucial insight into the pathogenesis of many inflammatory diseases including gout (5,10).…”

Section: Introductionmentioning

confidence: 99%

Alteration of Gut Microbiome and Correlated Amino Acid Metabolism Contribute to Hyperuricemia and Th17-Driven Inflammation in Uox-KO Mice

et al. 2022

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Although gut dysbiosis had been demonstrated to be an important factor affecting hyperuricemia (HUA) and gout, little is known for its potential mechanistic connections. In this study, Uox-KO mice model that with spontaneously developed pronounced HUA and urate nephropathy was used to explore the pathophysiologic mechanism of microbiota alterations in HUA and gout with integrated multi-omics analysis. 16S rRNA gene sequencing was performed to characterize the characteristic bacteria, and untargeted LC/MS analysis was applied to reveal the featured metabolites. Our results showed there was a significant shift in gut microbiota composition and function in Uox-KO mice compared to WT mice and apparent metabolomics differences between the two groups. Among them, amino acids metabolism appears to play a critical role. Correlation analysis further revealed that the characteristic metabolites were strongly influenced by the discrepant bacterial genera. Furthermore, impairment of intestinal integrity and profound alterations in the profile of solute carrier family resulted in dysregulation of amino acids transportation, which subsequently impacted serum uric acid level and CD4+ Th17 driven inflammation. Together, these data indicate that gut dysbiosis promotes purine metabolism disorder and inflammation in Uox-KO mice. Remodeling the gut microbiota is a promising strategy to combat HUA and gout.

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Structural and Functional Alterations of Gut Microbiota in Males With Hyperuricemia and High Levels of Liver Enzymes

Cited by 22 publications

References 61 publications

Altered Gut Microbiota in Children With Hyperuricemia

Altered Gut Microbiota in Children With Hyperuricemia

Gut microbiome is associated with metabolic syndrome accompanied by elevated gamma-glutamyl transpeptidase in men

Alteration of Gut Microbiome and Correlated Amino Acid Metabolism Contribute to Hyperuricemia and Th17-Driven Inflammation in Uox-KO Mice

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