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Background: This study investigated the causal relationship between gut microbiota (GM), serum metabolome, and host transcriptome in the development of gout and hyperuricemia (HUA) using genome-wide association studies (GWAS) data and HUA mouse model experiments., Methods: Mendelian randomization (MR) analysis of GWAS summary statistics was performed using an inverse variance weighted (IVW) approach to determine or predict the causal role of the GM on gout. The HUA mouse model was used to characterize changes in the gut microbiome, host metabolome, and host kidney transcriptome by integrating cecal 16S rRNA sequencing, untargeted serum metabolomics, and host mRNA sequencing., Results: Our analysis demonstrated causal effects of seven GM taxa on gout, including genera of Ruminococcus, Odoribacter, and Bacteroides. Thirty eight immune cell traits were associated with gout. Dysbiosis of Dubosiella, Lactobacillus, Bacteroides, Alloprevotella, and Lachnospiraceae_NK4A136_group genera were associated with changes in the serum metabolites and kidney transcriptome of the HUA model mice. The changes in the gut microbiome of the HUA model mice correlated significantly with alterations in the levels of serum metabolites such as taurodeoxycholic acid, phenylacetylglycine, vanylglycol, methyl hexadecanoic acid, carnosol, 6-aminopenicillanic acid, sphinganine, p-hydroxyphenylacetic acid, pyridoxamine, and de-o-methylsterigmatocystin, and expression of kidney genes such as CNDP2, SELENOP, TTR, CAR3, SLC12A3, SCD1, PIGR, CD74, MFSD4B5, and NAPSA., Conclusion: Our study demonstrated a causal relationship between GM, immune cells, and gout. HUA development involved alterations in the vitamin B6 metabolism because of GM dysbiosis that resulted in altered pyridoxamine and pyridoxal levels, dysregulated sphingolipid metabolism, and excessive inflammation., (© 2024 The Author(s).)

Hyperuricemia (HUA) is a condition associated with a high concentration of uric acid (UA) in the bloodstream and can cause gout and chronic kidney disease. The gut microbiota of patients with gout and HUA is significantly altered compared to that of healthy people. This article focused on the complex interconnection between alterations in the gut microbiota and the development of this disorder. Some studies have suggested that changes in the composition, diversity, and activity of microbes play a key role in establishing and progressing HUA and gout pathogenesis. Therefore, we discussed how the gut microbiota contributes to HUA through purine metabolism, UA excretion, and intestinal inflammatory responses. We examined specific changes in the composition of the gut microbiota associated with gout and HUA, highlighting key bacterial taxa and the metabolic pathways involved. Additionally, we discussed the effect of conventional gout treatments on the gut microbiota composition, along with emerging therapeutic approaches that target the gut microbiome, such as the use of probiotics and prebiotics. We also provided insights into a study regarding the gut microbiota as a possible novel therapeutic intervention for gout treatment and dysbiosis-related diagnosis., Competing Interests: Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article., (©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.)

Goose astrovirus (GoAstV) is an emerging avian pathogen that induces gout in goslings with a mortality of up to 50%. Organ damage caused by GoAstV infection was considered the cause of gout, but it is still unclear whether other factors are involved. Human and murine studies have linked the gut microbiome-derived urate and gout, thus we hypothesized that gut microbiome may also play an important role in gout induced by GoAstV infection. This study tested the pathogenicity of our isolated GoAstV genotype 2 strain on goslings, while the appearance of clinical signs, histopathological changes, viral distribution and the blood level of cytokines were monitored for 18 d postinfection (dpi). The dynamics in the gut microbiome were profiled by 16S sequencing and then correlated with GoAstV infection. Results showed that this study successfully developed an experimental infection model for studying the pathogenicity of the GoAstV infection which induces typical symptoms of gout. GoAstV infection significantly altered the gut microbiome of goslings with the enrichment of potential proinflammatory bacteria and depletion of beneficial bacteria that can produce short-chain fatty acids. More importantly, the microbial pathway involved in urate production was significantly increased in goslings infected with GoAstV, suggesting that gut microbiome-derived urate may also contribute to the gout symptoms. Overall, this study demonstrated the role of gut microbiome in the pathogenesis of GoAstV infection, highlighting the potential of gut microbiome-based therapeutics against gout symptoms., Competing Interests: DISCLOSURES The authors declare no conflicts of interest., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Gut dysbiosis is suggested to play a critical role in the pathogenesis of gout. The aim of our study was to identify the characteristic dysbiosis of the gut microbiota in gout patients and the impact of a commonly used uric acid-lowering treatment, febuxostat on gut microbiota in gout. 16S ribosomal RNA sequencing and metagenomic shotgun sequencing was performed on fecal DNA isolated from 38 untreated gout patients, 38 gout patients treated with febuxostat, and 26 healthy controls. A restriction of gut microbiota biodiversity was detected in the untreated gout patients, and the alteration was partly restored by febuxostat. Biochemical metabolic indexes involved in liver and kidney metabolism were significantly associated with the gut microbiota composition in gout patients. Functional analysis revealed that the gut microbiome of gout patients had an enriched function on carbohydrate metabolism but a lower potential for purine metabolism, which was comparatively enhanced in the febuxostat treated gout patients. A classification microbial model obtained a high mean area under the curve up to 0.973. Therefore, gut dysbiosis characterizings gout could potentially serve as a noninvasive diagnostic tool for gout and may be a promising target of future preventive interventions., Competing Interests: Conflict of interest The authors declare that they have no conflict of interest., (Copyright © 2021 Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, and Genetics Society of China. Published by Elsevier Ltd. All rights reserved.)

Emerging evidence indicates an association between gut microbiome and arthritis diseases including gout. However, how and which gut bacteria affect host urate degradation and inflammation in gout remains unclear. Here we performed a metagenome analysis on 307 fecal samples from 102 gout patients and 86 healthy controls. Gout metagenomes significantly differed from those of healthy controls. The relative abundances of Prevotella, Fusobacterium, and Bacteroides were increased in gout, whereas those of Enterobacteriaceae and butyrate-producing species were decreased. Functionally, gout patients had greater abundances for genes in fructose, mannose metabolism and lipid A biosynthesis, and lower for genes in urate degradation and short chain fatty acid production. A three-pronged association between metagenomic species, functions and clinical parameters revealed that decreased abundances of species in Enterobacteriaceae were associated with reduced amino acid metabolism and environmental sensing, which together contribute to increased serum uric acid and C-reactive protein levels in gout. A random forest classifier based on three gut microbial genes showed high predictivity for gout in both discovery and validation cohorts (0.91 and 0.80 accuracy), with high specificity in the context of other chronic disorders. Longitudinal analysis showed that uric-acid-lowering and anti-inflammatory drugs partially restored gut microbiota after 24-week treatment. Comparative analysis with obesity, type 2 diabetes, ankylosing spondylitis and rheumatoid arthritis indicated that gout metagenomes were more similar to those of autoimmune than metabolic diseases. Our results suggest that gut dysbiosis was associated with dysregulated host urate degradation and systemic inflammation and may be used as non-invasive diagnostic markers for gout., (© 2021. The Author(s).)

Osteoarthritis (OA) is one of the most common medical conditions affecting > 300 million people globally which represents the formidable public health challenge. Despite its clinical and financial ramifications, there are currently no approved disease modifying OA drugs available and symptom palliation is the only alternative. Currently, the amount of data on the human intestinal microbiome is growing at a high rate, both in health and in various pathological conditions. With an increase in the amount of the accumulated data, there is an expanded understanding that the microbiome provides compelling evidence of a link between thegut microbiomeand development ofOA. The microbiota management tools of probiotics and/or prebiotics or symbiotic have been developed and indeed, commercialized over the past few decades with the expressed purpose of altering the microbiota within the gastrointestinal tract which could be a potentially novel intervention to tackle or prevent OA. However, the mechanisms how intestinal microbiota affects the OA pathogenesis are still not clear and further research targeting specific gut microbiota or its metabolites is still needed to advance OA treatment strategies from symptomatic management to individualized interventions of OA pathogenesis. This article provides an overview of the various preclinical and clinical studies using probiotics and prebiotics as plausible therapeutic options that can restore the gastrointestinal microbiota and its impact on the OA pathogenesis. May be in the near future the targeted alterations of gut microbiota may pave the way for developing new interventions to prevent and treat OA., (Copyright © 2021. Published by Elsevier B.V.)

The role of host microbes in the pathogenesis of several diseases has been established, and altered microbiomes have been related to diseases. However, the variability of the urinary microbiome in individuals with gout has not been evaluated to date. Therefore, we conducted the present prospective study to characterize the urinary microbiome and its potential relation to gout. Urine samples from 30 patients with gout and 30 healthy controls were analyzed by Illumina MiSeq sequencing of the 16S rRNA hypervariable regions, and the microbiomes were compared according to alpha-diversity indices, complexity (beta diversity) with principal component analysis, and composition with linear discriminant analysis effect size. The most significantly different taxa at the phylum and genus levels were identified, and their potential as biomarkers for discriminating gout patients was assessed based on receiver operating characteristic (ROC) curve analysis. Compared with the healthy controls, there was a dramatic decrease in microbial richness and diversity in the urine of gout patients. The phylum Firmicutes and its derivatives (Lactobacillus_iners, Family_XI, and Finegoldia), the phylum Actinobacteria and its derivatives (unidentified_Actinobacteria, Corynebacteriales, Corynebacteriale, Corynebacterium_1, and Corynebacterium_tuberculostearicum), and the genera Prevotella and Corynebacterium_1 were significantly enriched in the urine of gout patients. ROC analysis indicated that the top five altered microbial genera could be reliable markers for distinguishing gout patients from healthy individuals. These findings demonstrate that there are specific alterations in the microbial diversity of gout patients. Thus, further studies on the causal relationship between gout and the urinary microbiome will offer new prospects for diagnosing, preventing, and treating gout., (Copyright © 2020 Ning, Yang, Chen, Zhao, Qian, Liu, Chen and Shi.)

We investigated the gut-kidney interaction in goslings with gout and tried to decipher the probable mechanisms through which gut dysbiosis leads to the progression of renal injury and inflammation. A total of 15 goslings (Anser cygnoides), with typical visceral gout symptoms, were screened and compared with 15 healthy goslings. We determined the signatures of the microbiome in the cecum chyme of goslings in the 2 groups by 16S sequencing, and analyzed the changes in intestinal permeability, levels of serum lipopolysaccharide (LPS), and the induced inflammatory response of Toll-like receptors (TLRs). We found the existence of gut dysbiosis in goslings with gout as a result of interactions among the multitude of bacteria present in the gut, and the proliferation of a specific pathogenic genus, Proteobacteria, played a decisive role in this process. Moreover, the permeability increased not only in the intestinal epithelium but also in the renal endothelium, providing possibilities for gut-derived LPS to enter the blood circulation and damage the kidneys. The systemic LPS concentration was increased in the gout group and exhibited a positive correlation with the degree of renal injury. In addition, we also found that inflammatory disorders concurrently existed in the gut and kidney of goslings with gout, and the LPS/TLR4/MyD88 (Myeloid differentiation primary response gene 88) inflammatory signaling was activated. These results indicate that the loss of intestinal barrier as a result of gut dysbiosis causes the translocation of gut-derived LPS, which can play an important role in the development of gout in goslings through interference with kidney functions., (© 2019 Poultry Science Association Inc.)

Competing Interests: Competing interests: None declared.

Two male travelers with histories of gout and hazardous alcohol consumption, presented with a triad of severe culture-positive disseminated gonococcal infection, crystal-positive polyarticular gout, and gonococcal soft tissue collections, following unprotected sexual contact in The Philippines. Both men initially attributed symptoms to gout, since their usual joints were affected, but clinical deterioration occurred with self-administration of anti-inflammatory agents alone. The clinical courses were severe and protracted, requiring aggressive management of infection with prolonged intravenous antimicrobials and repeated surgery, and prolonged anti-inflammatory agents for gout. Joint symptom onset in each case occurred within a week of sexual exposure in conjunction with hazardous alcohol ingestion. We speculate that acute dissemination of infection to previously damaged joints triggered polyarticular gout, with progressive infection, exacerbated by unopposed anti-inflammatory agents and delayed antibiotics. Disseminated gonococcal infection can occur with polyarticular gout and delays in recognition and treatment, including while traveling, can lead to severe disease from both.

Tophaceous gout occurs years after recurrent attacks of acute inflammatory arthritis. The urate deposits are incriminated in the inflammatory process; however, their infection is exceptional. We report the observation of an infected gouty tophus of the pinky and the wrist of a 40-year-old man, presented as an excruciating inflammatory pain with buff-yellow swelling of the fifth right finger and wrist in a febrile context. As a matter of fact, the evolution was favourable after surgical excision and antibiotic therapy. The infection of a tophus is an exceptional complication of the gout. In daily practice, this diagnosis is really a difficult challenge for the clinician. The systematic bacteriological examination of the tophi with cutaneous fistulation is necessary to introduce prematurely an adapted treatment., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2018. No commercial re-use. See rights and permissions. Published by BMJ.)

Objective The aim of this study was to investigate the clinical characteristics of infectious ulceration over tophi in patients with gout. Methods Participants were recruited from the First Affiliated Hospital of Wenzhou Medical University. The clinical characteristics of the patients and wound characteristics were recorded. Results Of the 38 enrolled patients, 18 were found to have infectious ulceration over tophi. Staphylococcus aureus was the most common pathogen and was identified in nine patients. Patients with infection were significantly older (69.6 vs. 60.1 years) and had a worse quality of life than those without infection. Patients with infection also had a significantly longer ulcer duration (125.6 vs. 54.2 days), larger ulcer size (2.47 vs. 1.99 cm 2 ), a higher rate of tissue necrosis in the ulcer bed (55.6% vs. 20.0%), a lower rate of callus at the edge (27.8% vs. 70.0%), and a higher moisture level than did patients without infection. Additionally, patients with infection had significantly delayed wound healing (35.3 vs. 20.3 days) compared with patients without infection. Conclusions Older patients with a long ulcer duration and larger ulcer size are more susceptible to infection. Infection can lower patients' quality of life and delay wound healing.

Background/aims: Microbes reside in a number of body sites, including the oral cavity, and are associated with the progression of many systemic diseases. In this study, we aimed to investigate the effects of gout and hyperuricemia (HUA) on the composition of oral microbiomes., Methods: Analysis of the oral microbiota from 12 gout patients, 11 HUA patients, and 19 healthy control subjects was performed using a deep sequencing approach, and validation of significant changes in Prevotella intermedia and Serratia marcescens in new patient cohorts was performed using quantitative PCR (qPCR)., Results: Our analysis indicated that both gout and HUA significantly altered the composition of the oral microbiome in patients. Patients with gout or HUA had significantly greater levels of salivary Prevotella intermedia but significantly lower levels of Serratia marcescens than healthy control subjects., Conclusion: We demonstrated the association between the oral microbiome and gout and HUA for the first time. In particular, 16S sequencing and qPCR analysis revealed significantly higher levels of oral Prevotella intermedia in gout/HUA patients, which suggests that these patients might be at risk for the development of periodontitis., (© 2018 The Author(s). Published by S. Karger AG, Basel.)

Current blood-based approach for gout diagnosis can be of low sensitivity and hysteretic. Here via a 68-member cohort of 33 healthy and 35 diseased individuals, we reported that the intestinal microbiota of gout patients are highly distinct from healthy individuals in both organismal and functional structures. In gout, Bacteroides caccae and Bacteroides xylanisolvens are enriched yet Faecalibacterium prausnitzii and Bifidobacterium pseudocatenulatum depleted. The established reference microbial gene catalogue for gout revealed disorder in purine degradation and butyric acid biosynthesis in gout patients. In an additional 15-member validation-group, a diagnosis model via 17 gout-associated bacteria reached 88.9% accuracy, higher than the blood-uric-acid based approach. Intestinal microbiota of gout are more similar to those of type-2 diabetes than to liver cirrhosis, whereas depletion of Faecalibacterium prausnitzii and reduced butyrate biosynthesis are shared in each of the metabolic syndromes. Thus the Microbial Index of Gout was proposed as a novel, sensitive and non-invasive strategy for diagnosing gout via fecal microbiota.

To analyze the diversity of both Bacteroides and Clostridium in patients with primary gout and the difference from that of normal individuals. And to investigate the relationship between the primary gout and the intestinal flora. Fecal samples of 90 cases with the primary gout and 94 cases normal comparison group were selected, together with the cases that match the filter criteria. The DNA is extracted from the feces. 16S rRNA specific primers of both Bacteroides and Clostridium were adopted for the PCR amplification. The molecular fingerprints of Bacteroides and Clostridium in both the primary gout group and the normal control group were obtained through DGGE and subjected for further analysis on both the diversity and the similarity. Compared with normal individuals, the number of bands and Shannon-Weaver (H') of Bacteroides in patients with primary gout was not reduced, but significantly decreased in Clostridium. Furthermore, the intra-group and inter-group similarity of both Bacteroides and Clostridium were lower. The primary gout has caused the structural change of both Bacteroides and Clostridium, inducing the low similarity, especially for Clostridium. It has statistic significance. The gut predominant flora may play an important role in the development of primary gout.

Streptococcus iniae, a widely distributed fish pathogen, is known to cause rare cases of human infection. We describe 2 cases of invasive S. iniae infection, one with septic arthritis complicating chronic gout and the other with bacteremic cellulitis. Both patients were Chinese and have been regularly handling fresh fish for cooking. Both isolates were unidentified or misidentified by 3 commercially available identification system and were only identified by 16S rRNA gene sequencing. When compared with a clinical isolate of S. iniae from Canada, their colonies were larger, more beta-hemolytic, and microcoid. Although bacteremic cellulitis has been described as the most common infection associated with S. iniae, the bacterium has not been reported to cause exacerbations of gouty arthritis previously. Clinical laboratories should be aware of the possibility of different colony morphology of S. iniae from Asia. More accurate identification of nongroupable beta-hemolytic streptococci, especially from patients with epidemiologic linkage to fresh fish, may uncover more cases of S. iniae infection. The Asian population and handlers of fresh fish should be informed of the risk of acquiring S. iniae infection.

A 45-year-old man with severe gout was admitted to the hospital because of Staphylococcus aureus septicemia. He had also a biclonal dysglobulinemia, without signs of myeloma. An asymptomatic lytic lesion of the left pedicle of L5 was discovered on radiographs. Histologic examination of the biopsied lesion showed typical tophaceous gout.

Synovial needle biopsies, joint aspirates, and joint tissue obtained at open operation from 41 cases of rheumatoid arthritis were inoculated onto PPLO media, L-form medium, and cell cultures for the isolation of mycoplasmas, L-form bacteria, and viruses. Medium suitable for the isolation of 'T' strain mycoplasmas was not employed. No mycoplasmas, L-form bacteria, or cytopathogenic viruses were shown. Similar specimens from nine patients diagnosed as having Reiter's disease were examined in a like manner and yielded only one Mycoplasma hominis type 1 isolate from a knee joint biopsy. It is concluded that known strains of mycoplasma and bacterial L-forms do not play a direct role in early and established cases of rheumatoid arthritis. Some of the cell cultures used in this study contained mycoplasma contaminants. Bacterial contaminants were also encountered in occasional batches of L-form medium.