Interrogation of the perturbed gut microbiota in gouty arthritis patients through in silico metabolic modeling

Henson, Michael A.

doi:10.1002/elsc.202100003

Cited by 15 publications

(30 citation statements)

References 74 publications

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“…In this study, we found that the genus Clostridium, Veillonella , and Streptococcus were more prevalent in HUA subjects than Con, consistent with a prior study in which Clostridium and Veillonella positively correlated with serum UA ( 31 ). The genus Clostridium is considered as an obese-associated genus in both Chinese ( 43 ) and Danish ( 44 ) populations.…”

Section: Discussionsupporting

confidence: 92%

“…Bacteroides possess an enrichment of the enzyme 5-hydroxysourate hydrolase, pivotal in gut uricolysis, and hence could regulate serum urate concentrations ( 30 ). On the other hand, elevated Bacteroides abundance may be a consequence of gout disease per se ( 31 ). Regardless, there are scant studies of asymptomatic individuals with HUA and their gut flora, which could provide prescient insight into the pathogenesis of the HUA.…”

Section: Discussionmentioning

confidence: 99%

“…Regarding butyrate-producing bacteria Alistipes and sulfidogenic bacteria Bilophila , both can affect the host immune system in an antithetical fashion ( 39 ). The hypothesis that loss of gut butyrate producers may be altered in gout was buttressed by computational predictions ( 31 ). Furthermore, elevated H 2 S production consequent to sulfur-rich L-cysteine feeding from Faecalibacterium may play a role in promoting disease.…”

Section: Discussionmentioning

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: 92%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Altered Gut Microbiota in Children With Hyperuricemia

et al. 2022

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“…A reduced species abundance of Enterobacteriaceae was associated with amino acid metabolism and environmental perception, which together resulted in increased serum UA and C-reactive protein levels in gout patients ( Chu et al., 2021 ). After metagenomics and cluster analysis of feces from gout patients and healthy people, the samples were divided into high gout clusters dominated by Bacteroides and low gout clusters with increased Faecalibacterium ( Henson, 2021 ). The high gout cluster exhibited increased synthesis of the amino acids D-alanine and L-alanine and by-products of branched-chain amino acid catabolism, while the low gout cluster exhibited increased the production of butyrate, the sulfur-containing amino acids L-cysteine and L-methionine, and the L-cysteine catabolite H 2 S ( Henson, 2021 ).…”

Section: The Gut Microbiota In the Pathogenesis Of Hua And Goutmentioning

confidence: 99%

Gut microbiota remodeling: A promising therapeutic strategy to confront hyperuricemia and gout

Wang

Liao

et al. 2022

Front. Cell. Infect. Microbiol.

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The incidence of hyperuricemia (HUA) and gout continuously increases and has become a major public health problem. The gut microbiota, which colonizes the human intestine, has a mutually beneficial and symbiotic relationship with the host and plays a vital role in the host’s metabolism and immune regulation. Structural changes or imbalance in the gut microbiota could cause metabolic disorders and participate in the synthesis of purine-metabolizing enzymes and the release of inflammatory cytokines, which is closely related to the occurrence and development of the metabolic immune disease HUA and gout. The gut microbiota as an entry point to explore the pathogenesis of HUA and gout has become a new research hotspot. This review summarizes the characteristics of the gut microbiota in patients with HUA and gout. Meanwhile, the influence of different dietary structures on the gut microbiota, the effect of the gut microbiota on purine and uric acid metabolism, and the internal relationship between the gut microbiota and metabolic endotoxemia/inflammatory factors are explored. Moreover, the intervention effects of probiotics, prebiotics, and fecal microbial transplantation on HUA and gout are also systematically reviewed to provide a gut flora solution for the prevention and treatment of related diseases.

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“…The gut microbiota is not only significantly related to diabetes but also its cause ( Vangipurapu et al., 2020 ; Zhang et al., 2021 ). The gut microbiota participates in purine and uric acid metabolism ( Henson, 2021 ). The kidneys excrete two-thirds of the human body’s uric acid, and the rest is mainly removed through the intestine ( Richette and Bardin, 2010 ).…”

Section: Introductionmentioning

confidence: 99%

Variation of Serum Uric Acid Is Associated With Gut Microbiota in Patients With Diabetes Mellitus

Zhang

Wang

Guo

et al. 2022

Front. Cell. Infect. Microbiol.

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Diabetes mellitus is a metabolic disease closely related to a disordered gut microbiome. Diabetic patients usually suffer from various metabolic disorders, such as increased serum uric acid levels. Although serum uric acid levels depend partially on intestine excretion, the relationship between uric acid and gut microbiome in diabetic patients remains unknown. We collected a total of 126 fecal samples from diabetic patients for 16S ribosomal RNA gene amplicon sequencing and recorded clinical data. We analyzed the correlation between clinical indicators and gut microbiota of diabetic patients using Spearman analysis. Since uric acid was the most prominent one, we classified diabetic patients based on their uric acid levels to find the microbiome associated with uric acid disturbance. We constructed Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway profiles using Phylogenetic Investigation of Communities by Reconstruction of Unobserved States (PICRUSt) to identify variations between the different groups. Among all the clinical indicators, uric acid had the strongest correlation with gut microbiota. First, we divided the patients into three groups according to their uric acid levels. The two low uric acid groups were similar, while the elevated uric acid group had significant differences in gut microbiota and metabolic pathways. The elevated uric acid group had a significantly lower gut microbiota diversity. At the genus level, this group had remarkably higher Escherichia–Shigella amounts and notably lower Faecalibacterium, Oscillospiraceae_UCG−002, and Oscillospiraceae_UCG−005 amounts. The gut microbiota of the high uric acid group was predicted to be enriched in metabolism, human diseases, and lipopolysaccharide biosynthesis. Since the two low uric acid groups were similar, we regrouped and matched the abnormal uric acid patients with normal uric acid patients. The differences in gut microbiota and metabolic pathways related to nucleotide metabolism became more significant. The serum uric acid levels were associated with gut microbiome changes. This might be related to uric acid metabolism by gut microbes. Our study indicates that targeting the gut microbiome could help manage elevated uric acid levels.

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Interrogation of the perturbed gut microbiota in gouty arthritis patients through in silico metabolic modeling

Cited by 15 publications

References 74 publications

Altered Gut Microbiota in Children With Hyperuricemia

Altered Gut Microbiota in Children With Hyperuricemia

Gut microbiota remodeling: A promising therapeutic strategy to confront hyperuricemia and gout

Variation of Serum Uric Acid Is Associated With Gut Microbiota in Patients With Diabetes Mellitus

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