Characteristic dysbiosis in gout and the impact of a uric acid-lowering treatment, febuxostat on the gut microbiota

Lin, Suxian; Zhang, Tao; Zhu, Lingxiao; Pang, Kun; Lu, Saisai; Liao, Xin; Ying, Senhong; Zhu, Lixia; Xu, Xin; Wu, Jinyu; Wang, Xiaobing

doi:10.1016/j.jgg.2021.06.009

Cited by 29 publications

(48 citation statements)

References 46 publications

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“…Recent studies have shown that in addition to improving UA symptoms, these drugs have positive effects in regulating the gut microbiota. A restriction of gut microbiota biodiversity was detected in untreated gout patients, and febuxostat partially restored this alteration ( Lin et al., 2021 ). Biochemical metabolic indices involved in liver and kidney metabolism were significantly correlated with the composition of the gut microbiota in patients with gout.…”

Section: Gut Microbiota As a Potential Therapeutic Target In Hua And ...mentioning

confidence: 99%

“…After the treatment of HUA with allopurinol and benzbromarone, the intestinal microbiota of rats changed. Both drugs could lead to an increase in Bifidobacterium and Collinsella and a decrease in Adlercreutzia and Anaerostipes after the reduction in UA ( Lin et al., 2021 ). In addition, Bilophila , Morganella , and Desulfovibrio decreased after allopurinol treatment, while Butyricimonas and Ruminococcus decreased and Proteus increased after benzbromarone treatment ( Lin et al., 2021 ).…”

Section: Gut Microbiota As a Potential Therapeutic Target In Hua And ...mentioning

confidence: 99%

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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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Section: Gut Microbiota As a Potential Therapeutic Target In Hua And ...mentioning

confidence: 99%

Section: Gut Microbiota As a Potential Therapeutic Target In Hua And ...mentioning

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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“…In healthy people, UA is primarily cleared via the kidneys, though ~30% is excreted via the intestine ( Sorensen and Levinson, 1975 ) where it can be further degraded by the gut microbiota ( Chu et al, 2021 ). In line, recent studies have shown that the gut microbial community composition is significantly altered in rat models of hyperuricemia ( Liu et al, 2020 ; Pan et al, 2020 ) or in patients with gout ( Chu et al, 2021 ; Lin et al, 2021 ). The gastrointestinal tract may therefore constitute a promising therapeutic target for hyperuricemia, for instance using oral probiotic strains, a concept supported by recent in vivo studies with microbial uricase ( Szczurek et al, 2017 ) or uricolytic bacterial strains ( García-Arroyo et al, 2018 ; Wu et al, 2021 ) that showed reduced serum UA levels in hyperuricemic rodent models.…”

Section: Introductionmentioning

confidence: 53%

Optimized UV-Spectrophotometric Assay to Screen Bacterial Uricase Activity Using Whole Cell Suspension

et al. 2022

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Uricase catalyzes the conversion of uric acid into allantoin with concomitant reduction of molecular oxygen to hydrogen peroxide. In humans, uricase is not functional, thereby predisposing individuals to hyperuricemia, a metabolic disturbance associated with gout, chronic kidney disorders, and cardiovascular diseases. The efficacy of current therapies to treat hyperuricemia is limited, and novel approaches are therefore desired, for instance using uricase-expressing probiotic strains. Here, we evaluated UV-spectrophotometric and H2O2-based fluorescent assays to enable the rapid identification of uricase activity in a broad panel of lactobacilli, Bacillus, and Bifidobacterium species. We highlighted abiotic (medium composition and mode of sterilization) and biotic (H2O2-producing strains) factors impacting the measurements’ accuracy, and reported on the stepwise optimization of a simple, fast, and robust high-throughput UV-spectrophotometric method to screen uricase activity using whole bacterial suspension, thereby assessing both cell-associated and extracellular activity. The validity of the optimized assay, based on the monitoring of uric acid degradation at 300 nm, was confirmed via liquid chromatography. Finally, a panel of 319 Qualified Presumption of Safety (QPS) strains of lactobacilli (18 species covering nine genera), Bacillus (three species), and Bifidobacterium (four species) were screened for uricase activity using the optimized method. All 319 strains, but the positive control Bacillus sp. DSM 1306, were uricase-negative, indicating that this activity is rare among these genera, especially in isolates from food or feces. Altogether, the UV-spectrophotometric high-throughput assay based on whole bacterial suspension reported here can be used to rapidly screen large microbial collections, by simultaneously detecting cell-associated and extracellular uricase activity, thereby accelerating the identification of uricolytic strains with therapeutic potential to treat hyperuricemia.

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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 ). Bacteroides possess an enrichment of the enzyme 5-hydroxysourate hydrolase, pivotal in gut uricolysis, and hence could regulate serum urate concentrations ( 30 ).…”

Section: Discussionmentioning

confidence: 99%

“…Using an experimental murine model of gout, and introducing a high-fat diet known to induce elevated levels of SCFAs, an accelerated resolution of the inflammatory response was observed, inferring a role for SCFAs in HUA-related inflammation ( 26 ). The proliferation of those salutary bacterial members may be reduced by HUA, which possibly contributes to the development of gout ( 9 ).…”

Section: Discussionmentioning

confidence: 99%

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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Characteristic dysbiosis in gout and the impact of a uric acid-lowering treatment, febuxostat on the gut microbiota

Cited by 29 publications

References 46 publications

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

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

Optimized UV-Spectrophotometric Assay to Screen Bacterial Uricase Activity Using Whole Cell Suspension

Altered Gut Microbiota in Children With Hyperuricemia

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