Introduction

Gout is one of the most frequent arthritic diseases characterized by recurrent episodes of pronounced acute inflammatory attacks. It results from the deposition of monosodium urate crystals in joints, tendons, and other tissues caused by abnormally elevated urate levels in blood circulation. Due to its prevalence globally, gout is responsible for considerable disability, health loss, and economic burden [1, 2]. So far, numerous researchers have studied gout from various perspectives, including epidemiological investigation, pathological research, pharmaceutical development, diagnostic technique, and clinical treatment. Therefore, a comprehensive and systematic knowledge map of gout research is necessary.

Bibliometric analysis is a quantitative method that can track the development process of a research field over a definite time. Furthermore, the bibliometric analysis also can predict the hotspots and trends within a specific research area through information visualization [3, 4]. It focuses on the influences of articles, contribution and cooperation of authors/institutions/countries, and development of topics in the research field and has been applied in much scientific literature [5, 6]. To our knowledge, a study performed the bibliometric analysis of gout research from 1990 to 2012 [7]. However, it only focused on the most contributive authors, institutions, and journals, and identified the most successful international and national cooperation, but did not track the topic’s development of gout research. For nearly 10 years, there have great processes in the research field of gout. For instance, gene polymorphisms of gout-associated transporters, mainly including glucose transporter 9 (Glut9) and ABCG2 (ATP binding cassette subfamily G member 2), have been identified by genome-wide association studies and drawn widespread attention from gout researchers [8, 9]. The management guideline of gout from the American College of Rheumatology (ACR) published in 2020 also put forward several subversive cognitions [10]. Such as, it is recommended to initiate the urate-lowering therapy during the gout flare time instead of the resolved period of a gout flare. In addition, the USA Food and Drug Administration announced a black box warning for febuxostat in 2019, and thus, the ACR recommended that allopurinol be the preferred first-line agent for starting any urate-lowering therapy [11]. Accordingly, it is necessary to perform a comprehensive bibliometric analysis of gout research literature over the latest decade.

In the present study, we conducted a comprehensive bibliometric analysis of gout research publications from 2012 to 2021, considering the analysis and visualization of annual publications, countries/regions, institutions, authors, journals, funding agencies, keywords, co-cited references, and academic cooperation with multi-levels. In addition, we illustrated the development process of gout and explored its research hotspots over the past decade at a global level. We hope this study will provide new perspectives for investigators’ future work in the gout field.

Materials and methods

Data sources and search strategy

The Web of Science (WOS) is one of the most influential databases of scientific literature. Related publications from January 1, 2012, to December 31, 2021, were retrieved from the Science Citation Index Expanded (SCI-E) through the Web of Science Core Collection (WoSCC) via the library website of the Beijing University of Chinese Medicine. Records from 2022 were not considered for the incomplete data acquisition at the time of analysis. The retrieval strategy was TS = gout. Non-English language, non-article, and non-review publications were excluded. All data, including titles, author information, abstracts, keywords, journals, and references, were downloaded on the same day (May 1, 2022). This query yielded 5535 records, which were acquired for further analysis in this study. The particular retrieval procedure is illustrated in Fig. 1. Data involving full records and cited references were downloaded in txt format. Microsoft Excel Office 2019 was applied to manage data.

Fig. 1
figure 1

Flowchart of data filtration processing and excluding publications

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Bibliometric and visualized analysis

The number of publications and citations per year, funding agencies, and subject categories of gout research were analyzed by the online data analysis function (“Analyze Results”) of the WoSCC and visualized with Microsoft Excel Office 2019. R-bibliometrix version R 4.1.2, VOSviewer version 1.6.17, and CiteSpace version 5.8.R3 were further employed for literature analysis and bibliometric visualization. These prevailing bibliometric tools provide diverse and objective perspectives on gout research.

R-bibliometrix is an open-source tool designed by Massimo Ariaa and Corrado Cuccurullo for performing comprehensive science mapping analysis [12]. R-bibliometrix package was used in the present study for quantitative analyses in the map of geographical collaboration, trend topics, and thematic map of keywords.

VOSviewer is developed by Nees Jan van Eck and Ludo Waltman at the Centre for Science and Technology Studies of Leiden University [13]. It focuses on building bibliometrics networks of co-authorship, co-citation, and co-occurrence. In the present study, we applied VOSviewer to construct the co-authorship network with overlay figures to analyze the academic collaboration between different countries/regions, institutions, and authors. Besides, VOSviewer was also used to cluster keywords with high co-occurrence frequencies to identify core terms. On the VOSviewer maps, each circle represents the observed subject (a country/region, an institution, an author, or a keyword), while the size of the bubble represents the number of publications or co-occurrence frequency. The thickness of connecting lines reflects the strength of the relationship between the observed subjects, and the color represents a cluster with similar attributes in the network. VOSviewer parameters were set as follows: the counting method was full counting, and the threshold (T) depended on the corresponding observed subject.

CiteSpace, created by Prof. Chaomei Chen, is a piece of application visualizing networks among documents citation, collaboration relationships, and research hotspots [3, 14]. In the present study, CiteSpace performed the burst analysis of categories, keywords, and co-cited references and constructed the cluster and timeline view of co-cited references. The parameters of CiteSpace were as follows: link retaining factor (LRF = 5), look back years (LBY = 8), e for top N (e = 2), time span (2012–2021), years per slice (1), selection criteria (Top N: top 100), and pruning (pathfinder + pruning sliced network + pruning the merged network). The clusters in the timeline view of co-citation were labeled by keywords, and the log-likelihood rate (LLR) was employed as the clustering algorithm.

In addition, a comprehensive description of various publishing characteristics is provided, including the Hirsch index (H-index) and the impact factor (IF). H-index, introduced by Hirsch, is a comprehensive score to quantify the significance and broad impact of scientists, institutions, or countries based on their cumulative research [15, 16]. IF, devised by Eugene Garfield, is a crucial marker of journals’ influence in its scientific field, and it is calculated from the frequency of citation by other publications [17]. IF used in the present study was obtained from the 2020 Journal Citation Reports (JCR) (Clarivate Analytics, Philadelphia, USA). Q1 represents the top 25% of the IF distribution, Q2 between the 50th percentile and 25th percentile, and Q3 between the 75th percentile and 50th percentile.

The present study is a bibliometric analysis of existing publications, and it does not require ethical approval.

Results

Analysis of the basic situation of the extracted publications concerning gout

Trends and annual publications

According to the screening criteria, a total of 5535 publications (4617 articles and 918 reviews) concerning gout research from 2012 to 2021 were ultimately included in the present study and are shown in Fig. 1. Based on the WoSSC database, the 5535 publications were cited 108,213 times, and each publication has cited an average of 19.55 times. Figure 2 shows the steady growth trend of the annual publications, from 326 in 2012 to 799 in 2021, indicating the sustained attention to gout in recent years. At the same time, the rapidly growing number of citations, from 314 in 2012 to 26,618 in 2021, also suggested a strong interest of gout research from researchers.

Fig. 2
figure 2

Annual number of publications and citations in gout research from 2012 to 2021

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Contribution of countries/regions

Totally, 124 countries/regions contributed to gout-related publications between 2012 and 2021. Figure 3 presents the global distribution of all the included papers and the top 10 most productive countries/regions in terms of the number of publications and citations. China produced the most gout-related articles with 1642 publications in the survey period, followed by the USA (n = 1414), New Zealand (n = 393), the UK (n = 351), Japan (n = 347), South Korea (n = 283), Germany (n = 257), Italy (n = 255), Australia (n = 242), and France (207). Besides, publications from China also displayed the largest number of citations (n = 31,549), followed by the USA (n = 19,113), New Zealand (n = 6,342), the UK (n = 6114), Japan (n = 5270), Germany (n = 4450), France (3454), Italy (n = 3334), Australia (n = 3199), and South Korea (n = 3015). Of the leading 10 productive countries/regions, 4 are situated in Europe, 3 in Asia, 2 in Oceania, and 1 in North America. In addition, 9 of the top 10 productive countries/regions are developed countries. And China is also in a period of rapid economic growth. Combining the epidemiological studies that the well-off diets with high purine and high fat usually contribute to gout incidence, it partly indicates a positive relationship between the economy and gout research in a country/region [18, 19].

Fig. 3
figure 3

Countries/regions distribution on gout publications. A Geographical distribution of gout research. B, C The top 10 most productive countries in the publication of gout research and their number of citations

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Contribution of institutions and authors

The most productive institutions and authors were evaluated in our study. A total of 6032 institutions and 25,976 authors have contributed to the research field of gout during the latest decade.

As shown in Table 1, with 268 papers published, the University of Auckland was the most productive institution and followed by the University of Otago (n = 231), the University of Alabama at Birmingham (n = 164), China Medical University (n = 108), Harvard Medical School (n = 99), Boston University (n = 97), Qingdao University (n = 89), University of Paris (n = 69), Lariboisière Hospital (n = 67), and Mayo Clinic (n = 67). Of the top 10 productive institutions, 4 came from the USA, 2 from New Zealand, 2 from French, and 2 from China.

Table 1 The top 10 productive institutions in gout research
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To find the most impactful scholars in the research field of gout during the past 10 years, we ranked all the authors based on their publication number and the H-index. Figure 4A depicts the top 10 productive authors. Dalbeth Nicola from the University of Auckland is the most productive author with 241 publications and an H-index of 46. In addition, as shown in Fig. 4B, Singh Jasvinder A. from The University of Alabama at Birmingham published 14 articles and obtained the highest number of total citations of 491.5 in 2017, indicating an outstanding contribution that received wide attention at the specific time. By literature scanning, we further understand the research achievements of the top 5 productive authors, who are dominant in publication number and H-index value. Professor Dalbeth Nicola is an internationally respected gout specialist and researcher who focuses on understanding the impact, mechanisms, and treatment of gout. As the first author, she has published four highly cited papers that rank in the top 1% of the gout field, and her excellent research in both pharmacological and non-pharmacological treatments has been incorporated into international gout management guidelines [20,21,22,23]. Stamp Lisa K is a medicine professor and rheumatologist from the University of Otago. She specializes in the pathophysiology and management of gout and has closely cooperated with professor Dalbeth Nicola. Singh Jasvinder A is a rheumatologist from the University of Alabama Birmingham. He focuses on epidemiological research of gout and pays more attention to gout comorbidities and the gout treatments in the clinic [24]. Professor Merriman Tony R is from the University of Otago and is particularly interested in the genetics behind gout and hyperuricemia [25].

Fig. 4
figure 4

The productive authors in gout research. A The top 10 most productive authors and their H-index. B The annual production number of the top 5 most productive authors

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Choi Hyon K is a professor of Medicine from Harvard Medical School focusing on simple, safe, cost-effective prevention strategies for gout. In recent years, he has extended to explore the gene-environment interactions of gout and investigate the potential of dual-energy computed tomography in visualizing uric acid crystals in articular and extra-articular tissue [26, 27].

Academic collaboration

Academic collaboration between different countries/regions, institutions, and authors usually promotes knowledge communication and broadens the vision of the research field. Analysis of academic collaboration could reveal the central cooperative relationship in gout research from multiple levels.

The geographical map in Fig. 5A clearly exhibits widespread cooperation among different countries. The darker the blue, the more publications. The red lines symbolized cooperation between countries/regions. It shows that the USA was the country most frequently involved in international cooperation. Figure 5B more detailly displays that the USA, Germany, and Netherlands had the higher number of collaborations with other countries. Fifty-four countries/regions that owned more than ten publications meet the threshold of a minimum of four documented collaborations. The top 10 most productive countries all have high collaboration with others.

Fig. 5
figure 5

Academic collaboration between different countries/regions, institutions, and authors in gout research. A, B Geographical map and collaboration of countries/regions. C Collaboration of institutions. D Collaboration of authors

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The partnership between institutions is another effective way to evaluate collaboration. As shown in Fig. 5C, eighty-four institutions were screened out with the threshold of more than ten publications and three thousand citation times. The University of Auckland, University of Otago, The University of Alabama at Birmingham, Harvard Medical School, and Boston University are not only in the group of top 10 productive institutions but also ranked in the top 5 most extensive cooperation in the research field of gout. During the latest 10 years, the University of Auckland cooperated with almost all influential scientific institutions in gout research.

The co-authorship analysis was performed among authors with more than 20 publications. Finally, 56 authors were formed six clusters in Fig. 5D. There was a strong cooperation intensity among the top 10 most productive authors in gout research. It is worth mentioning that Dalbeth Nicola is the key node of the collaboration network, indicating her significant contribution to the field of gout research.

Contribution of funding agencies

The crucial role of funding agencies in research subjects and directions should be understood. A total of 3724 publications, which accounted for 67.28% of included papers, obtained funding support in the present study. Table 2 listed the top 10 agencies that provided the funds to gout research during the survey period, contributing to 66.68% of fund-supported publications. National Natural Science Foundation of China sponsored 682 papers (18.31% of fund-supported publications) and ranked first as the sole agency, consistent with the high number of publications from China. Three US research funding agencies supported 1100 documents, which accounted for 29.54% of fund-supported publications. Three agencies from Japan sponsored 328 papers (8.81% of fund-supported publications). Furthermore, European Commission placed fifth with 141 publications (3.79% of fund-supported publications). The Health Research Council of New Zealand ranked seventh with 117 publications (3.14% of fund-supported publications). A total of 115 papers were sponsored by AstraZeneca, a global biopharmaceutical business company, with a proportion of 3.09% of fund-supported publications and ranked eighth.

Table 2 The top 10 prime funding agencies in gout research
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Contribution of journals

In the present study, characteristics of journals that publish gout research were revealed, including journal titles, countries, total publication, total citations, H-index, IF (2020), and quartile in category (2020). A total of 1328 journals contributed to the research field of gout during the survey time. The top 10 active journals, which published 1057 papers and accounted for 19.10% of the total publications, are displayed in Table 3. Half of the top 10 journals came from the UK, three journals originated from the USA, and the remaining two journals were from Germany and Canada, respectively. Among them, Clinical Rheumatology (n = 149), Rheumatology (n = 142), and Arthritis Research & Therapy (n = 138) were the top 3 productive journals in terms of the number of publications on gout research. Annals of the Rheumatic Diseases, the Journal of Rheumatology, and Rheumatology occupied the top 3 highest citations (11,355 vs. 5202 vs. 4679 citations, respectively). Annals of the Rheumatic Diseases, Rheumatology, and Arthritis Research & Therapy had the top 3 highest H-index (49 vs. 32 vs. 32, respectively). The highest IF (2020) was 19.103, which belonged to Annals of the Rheumatic Diseases. Rheumatology, Annals of the Rheumatic Diseases, and Scientific Reports were classified as Q1 according to the JCR 2020 standards. Among the top 10 active journals, Annals of the Rheumatic Diseases showed the most excellent comprehensive strength indicating its leading role in gout research. The top 10 high-cited publications are listed in Table 4, including two practice guidelines, two reviews, and six research articles.

Table 3 The top 10 active journals that published articles of gout research
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Table 4 The top 10 high-cited published articles in gout research
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Analysis of the basic contents of extracted publications

Category analysis

The subject categories concerning gout research were analyzed among all the publications. The treemap in Fig. 6A illustrates the top 10 categories and their number of corresponding articles. The darker the blue, the more publications. The top three categories account for nearly 50% of all the publications, which include Rheumatology with 1473 papers (26.61%), Pharmacology Pharmacy with 698 papers (12.61%), and Medicine General Internal with 509 papers (9.20%).

Fig. 6
figure 6

Analysis of subject category in gout research. A Distribution of subject category. B Burst analysis of subject category

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Bursts mention the sudden growth in publications during a period, reflecting the evolution trend in the field. The category bursts over the last 10 years were analyzed with CiteSpace. Figure 6B displays the top 20 subject categories ranked with the burst strength from 2.09 to 9.16. The duration ranged from 2 to 4 years. The blue and red lines present the time span and the burst period, respectively. The strongest citation burst occurred in Urology & Nephrology from 2012 to 2013, suggesting a vital concern in the relationship between gout and renal diseases. Infectious diseases, materials science and multidisciplinary, engineering and chemical, and materials science were the four categories emerging in 2018 and lasted recently, indicating a multidisciplinary focus on gout research beside medicine.

Keyword detection and burst analysis

The keywords can reflect the hotspots and frontiers in a specific field. A total of 99 keywords with a threshold over 20 were selected, and five clusters were screened out by co-occurrence clustering analysis using VOSviewer in Fig. 7A. The top 10 keywords with the most frequent occurrence were as follows: gout (1832), hyperuricemia (744), uric acid (536), allopurinol (277), febuxostat (212), xanthine oxidase (207), inflammation (186), colchicine (134), urate (121), chronic kidney disease (114), and arthritis (108). The five clusters represented by different colors were as follows: (1) the relevant diseases and diagnosis of gout in red: gout, rheumatoid arthritis, osteoarthritis, chondrocalcinosis, ultrasonography, dual-energy computed tomography, and imaging. (2) Mechanism concerning gouty inflammation in green: xanthine oxidase, inflammation, NLRP3 inflammasome, interleukin-1β, and cytokines. (3) Mechanism concerning uric acid, the biochemical basis of gout, in blue: uric acid, ABCG2, SLC2A9, URAT1, and genetics. (4) Medication management of gout in purple: allopurinol, benzbromarone, colchicine, febuxostat, and lesinurad. (5) Epidemiology of gout in yellow: cohort study, incidence, prevalence, risk factors, and mortality.

Fig. 7
figure 7

Keywords analysis in gout research. A Co-occurrence analysis of keywords with a threshold over 20. B Burst analysis of the top 20 keywords. C Trend topics map of keywords from 2012 to 2021. D Thematic map in gout research

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A burst analysis of keywords was performed to unravel the fastest growing topics in recent years. As shown in Fig. 7B, the strength of the top 20 keywords with bursts varied from 8.67 to 14.47. The duration ranged from 1 to 5 years. The term gene owned the highest burst strength and lasted for 5 years, and its relevant terms, susceptibility and SLC2A9, also lasted for multiple years, suggesting a continuous research focus in gout research. The most recent hotspot with the highest burst strength was heart failure.

The trend topics of keywords during the lasted 10 years were analyzed by R-bibliometrix. As shown in Fig. 7C, the horizontal and vertical axis represented the year and the major keyword, respectively. Each node represents a keyword, and its size indicates the keyword occurrence frequency. The horizontal line displays the time span of the keyword occurrence. The keyword gout showed the highest frequency from 2015 to 2020. Gout research’s most recent trend topics were gut microbiota, chicken, anxiety, monosodium urate, and COVID-19.

R-bibliometrix also can be used to analyze the thematic evolution based on density and centrality. Figure 7D shows the thematic map in gout research. The relative locations of the concepts symbolized the development of the theme: (1) the well-developed and essential topics in the upper right region (gout, arthritis, epidemiology), (2) the isolated and highly developed themes in the upper left region (inflammation, gouty arthritis, inflammasome), (3) the emerging or declining themes in the lower left region (urate, ABCG, polymorphism), and (4) the basic and transversal themes in the lower right region (hyperuricemia, medicines (allopurinol, febuxostat, and colchicine)).

Co-citation analysis

The co-citation relationship is established with two or more papers cited by one more later publication at the same time. A strong co-citation relationship may indicate a high similarity among these cited papers, and thus, a common topic would be speculated. CiteSpace was employed to analyze the bursts and clusters of co-cited references. Figure 8A displays the top 10 references with the strongest co-citation bursts. More detailed information is shown in Table 5. A publication authored by Richette P et al. in Annals of the Rheumatic Diseases in 2017 obtained the strongest burst (strength = 45.09) and a high number of co-citation (n = 192). Kuo C et al. published a paper in Nature Reviews Rheumatology in 2015 that acquired the highest number of co-citation (n = 209) and a strong burst (strength = 40.57). Zhang W was an author who produced two papers in Annals of the Rheumatic Diseases in 2006 with co-citation number of 112 and 64, and burst strength of 38.59 and 21.92, respectively. Choi HK was another author who also published two papers. One of them got the co-citation number of 43 and the burst strength of 20.04, published in Annals of Internal medicine in 2005. The other one owned the co-citation number of 69 with the burst strength of 18.19, published in Circulation in 2007. In addition, in Lancet, the top journal, Dalbeth N published an article with a co-citation number of 141 and a burst strength of 32.16. Martinon F was another author who published the paper with a co-citation number of 87 and a burst strength of 29.89 in a leading journal, Nature. In general, these authors achieve the high co-citation all worthy of attention in gout research.

Fig. 8
figure 8

Co-citation analysis in gout research. A Burst analysis in top 10 co-cited references. B Timeline view of co-citation

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Table 5 The top 10 references with the strongest co-citation bursts in gout research
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The timeline view of co-citation, which could trace the temporal relationship of hot themes by analyzing included papers’ co-cited references, is a featured function of CiteSpace software. Figure 8B illustrates a timeline view of the top 10 critical clusters that were based on the log-likelihood ratio algorithm. It could further export the research frontiers following a chronological point. The modularity Q and silhouette value are two parameters to evaluate the structure significance and robustness of clusters, respectively. In our study, the modularity Q (0.8718 > 0.3) and mean silhouette value (0.9563 > 0.7) were considered highly significant in cluster structure and convincing in cluster results. Along the dashed line to each tag representing a reference, the occurrence position means its firstly cited time, circles with a larger radius mean higher citations, and darker colored lines stand for the later publication dates. By default, a reference with the highest citation frequency will be displayed every year. The hot themes in gout research have changed over time. Specifically, the clusters with lighter color were relatively early research hotspots, containing ultrasonography (cluster #0), hypertension (cluster #3), uricase (cluster #6), canakinumab (cluster #7), and slc2a9 (cluster #8). The others with the darker color may be the current research focus, involving abcg2 (cluster #1), mobile apps (cluster #2), lesinurad (cluster #4), nlrp3 inflammasome (cluster #5), and xanthine oxidase (cluster #9). More detailed information on the top clusters is listed in Table 6.

Table 6 The top 10 largest clusters of co-cited references in gout research
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Discussion

Bibliometrics is a scientific method first used by Alan Pritchard in 1969 [28]. It contributes to tracking data correlation and making predictions about future frontiers. Bibliometrics analysis and its visualization can efficiently support information integration to enable researchers to understand the range of related research. In this study, we perform a comprehensive bibliometric analysis of global publications concerning gout research from 2012 to 2021.

General trends, influential countries/institutions/authors, and academic collaboration in gout research

The number of publications and their citations in a certain research area can mirror the productive abilities and development trends in the field over time [29]. A total of 5535 publications with 108,213 citations were published globally in the latest decade (Fig. 2). Compared to annual publications in 2012, doubled growth was observed in 2021. These results demonstrated the sustained attention and interest of researchers in gout research.

The number of publications in a research field is also a vital index for evaluating the research level of a country, an institution, or a researcher [30, 31]. China and the USA were the two countries that both owned the most publications and citations concerning gout in the survey period (Fig. 3), indicating their great impact on the research field of gout. The University of Auckland in New Zealand and its famous scholar Dalbeth Nicola were the most productive institution and the author of gout research, respectively, between 2012 and 2021 (Table 1 and Fig. 4). Meanwhile, four of the top ten productive authors in gout research were from New Zealand. The high research enthusiasm for gout in New Zealand may relate to its high prevalence of gout, especially in Māori [32, 33]. Funding supports can also reflect a country’s emphasis on a specific field. China, the USA, and Japan exhibited the strongest support for gout research by providing funding (Table 2), indicating an elevated incidence trend of gout among different countries in recent years [34,35,36].

Journal analysis from bibliometric analysis would provide a reliable reference for searching articles or submitting manuscripts. Clinical Rheumatology was the journal that published the most gout-related papers, while Annals of the Rheumatic Diseases, a leading journal with Q1 of IF distribution in the rheumatology category, showed the most excellent comprehensive strength with the most citations and the highest H-index value (Table 3). This result is consistent with the category analysis that rheumatology was the main subject category of included gout-related papers (Fig. 6).

Academic collaborations, especially worldwide, will support innovation as well as address unmet challenges to the greatest extent [37]. The widespread cooperation among different countries, institutions, and authors was observed in our study (Fig. 5). The USA performed the highest partnership globally. Besides the term of paper production, the University of Auckland and Dalbeth Nicola were also in the central place of the collaboration network, which confirms their significant contribution to gout research during the latest decade.

Topics evolution and future outlook in gout research

The co-occurrence analysis and burst analysis of keywords and co-cited references are widely accepted for determining research hotspots and predicting research frontiers [38, 39]. In the present study, we tracked the topic evolution and future outlook concerning gout research with various visualization from multiple perspectives. The burst analysis of keywords showed heart failure was the strong burst term among gout research in 2020 (Fig. 7B). The trend topics, drawn from keywords, indicated that gut microbiota ranked first in the gout research’s most recent issues (Fig. 7C). The thematic map suggested that urate, ABCG, and polymorphism might be the emerging themes in gout research (Fig. 7D). The timeline view of co-citation illustrated NLRP3 inflammasome, xanthine oxidase, and ABCG2 represent the recent research focus on gout (Fig. 8B). In general, the pathological mechanism remains the hotspot in gout research, and its future research frontiers may be as follows:

  1. 1)

    Gout and heart failure

Gout is chronic inflammatory arthritis characterized by monosodium urate crystals deposition, secondary to hyperuricemia [22]. Evidence showed that hyperuricemia, an abnormally increased uric acid in the body, was a risk factor for cardiovascular diseases, including stroke, myocardial infarction, and heart failure [40, 41]. Recent research also reported that gout was associated with an increased risk for incident heart failure but not for incident coronary heart disease, incident stroke, or all-cause mortality [42]. In clinics, patients with chronic heart failure are always required to the routine blood testing of uric acid concentration. It is not only due to the stronger relationship between gout and heart failure than other cardiovascular diseases but also related to the use of diuretics by patients with heart failure to reduce fluid retention, which often increases uric acid levels and leads to gout. Moreover, several studies confirmed that allopurinol, a uric acid-lowering agent, can effectively treat chronic heart failure by improving blood flow, peripheral vasodilator capacity, and endothelial dysfunction. But not all research report that urate-lowering therapy would contribute to cardiovascular benefit. It may associate with the duration a patient received allopurinol [43, 44]. Accordingly, hyperuricemia may be the critical charge of the pathological connection between gout and heart failure. The pathological mechanism and drug treatment of gout patients with heart failure require investigation in future studies.

  1. 2)

    Gout and gut microbiota

Gut microbiota, the complex and dynamic population of microorganisms habited in the gastrointestinal tract, influences the host during homeostasis and disease. Gut microbiota under the physiological status may benefit the host’s health via a range of functions, including intestinal integrity improvement, pathogens clearance, and immunity regulation [45,46,47]. Several studies have reported that gut microbiota in gout patients were distinguished from healthy humans. For instance, gout patients showed enrichment of Bacteroides caccae and Bacteroides xylanisolvens as well as a depletion of Faecalibacterium prausnitzii and Bifidobacterium pseudocatenulatum [48]. A large metagenomics study, concerning the functional signature identification of gut microbiome in China people, also found that species belonging to the Bacteroides, Prevotella, and Fusobacterium genera were more enriched in gout patients than healthy ones [49]. At the same time, prebiotics, the live bacteria and yeasts that can replenish beneficial bacteria in the digestive tract, were reported to have a positive effect on treatments of gout and hyperuricemia [50]. Accordingly, there was a close relationship between gout and gut microbiota, which had been focused on by many researchers. So far, inflammatory response, abnormal urate metabolism, and excessive lipopolysaccharide release resulting from dysbacteriosis in the intestine were the main directions for clarifying the mechanism of the pathological relationship between gout and gut microbiota [48, 51, 52]. Due to the numerous amounts of gut microbiota and its complicated function to hosts, it is challenging to identify gout-specific microbiota in the intestine. Nevertheless, deeply exploring the role of gut microbiota in gout is necessary for a new sight for gout therapy.

  1. 3)

    Gout and NLRP3 inflammasome

NLRP3 inflammasome is a complex composed of NLRP3 sensors, ASC adaptor protein, and caspase-1 enzymes [53]. Upon the leucine-rich repeats domain of NLRP3 was stimulated by a foreign agonist, the NLRP3 molecule would be induced assembly by recruiting ASC adaptor and pro-caspase-1, and further cleave the pro-caspase-1 to produce active caspase-1, which would result in the mature and secretion of IL-1β and IL-18 cytokine [54]. It is recognized that gouty inflammation is a consequence of activating a cytokine cascade with IL-1β as the central controller [55]. Nowadays, the activation of the NLRP3-IL-1β axis in gout research has got to a common view from scholars. And based on this pathological pathway, much mechanism research concerning anti-gout agents has been carried out widely [56, 57]. While the role of NLRP3 inflammasome activation in gout research has been relatively well-established, its upstream pathways are not yet fully clarified.

  1. 4)

    Gout and xanthine oxidase

Xanthine oxidase is a vital enzyme that can catalyze the oxidation of hypoxanthine into xanthine and further oxidate xanthine to uric acid [58]. Due to the definite regulation of xanthine oxidase on uric acid in the process of hyperuricemia and gout, the inhibitors targeted on xanthine oxidase have been developed widespread, including allopurinol and febuxostat. The result of the co-citation analysis that xanthine oxidase was the research focus between 2012 and 2020 may relate to the controversy concerning the increased risk of heart-related death caused by febuxostat [11, 59]. In addition, recent research reported that using xanthine oxidase inhibitors in pre-dialysis patients with cardiovascular risks might reduce cardiovascular events, which may indicate a direct relationship between xanthine oxidase and cardiovascular diseases [60]. Therefore, the role of xanthine oxidase in gout research may call for a new perspective.

  • 5) Gout and urate-transporter ABCG2

Genetics research concerning gout and hyperuricemia has been widely carried out over the latest decade [9, 61]. Genome-wide association studies have identified 28 loci that will interfere with the gene encoding of urate transporters and result in hyperuricemia, and further lead to gout [62]. The stable uric acid level in the body always depends on the balance of urate synthesis and urate excretion. Urate transporters are responsible for the urate excretion via renal and intestinal pathways. Among those urate transporters, ABCG2 is a vital transporter expressed in both the gut and kidney. Evidences showed that the decreased expression of ABCG2 or deficiency in ABCG2 would contribute to the dysfunction of urate excretion and further cause hyperuricemia [63, 64]. It is noteworthy that most recent research reported that ABCG2 might be important in gout beyond its established role in elevating urate levels [65]. And another study also pointed out that variation in ABCG2 function may play a role in developing tophaceous disease under the independence of serum urate concentrations and disease duration [66]. Moving forward, learning more regulative details of ABCG2 and its gout-related variants will shed light on the pathophysiology exploration of gout.

Limitations

The present bibliometric analysis of gout provided a comprehensive overview of the global status and trends in gout research during the latest decade. However, several inevitable limitations in the bibliometric study should be considered. Firstly, the prevailing bibliometric software only can analyze literature from one database. Although the WOSCC is the most commonly used database, there are many other databases worthy of attention, such as PubMed and Sciencedirect. Secondly, we just analyzed publication in English writes, which may lead to the omission of essential research. Last but not least, due to a high degree of informatization and intricate cooperation, the actual contribution of different authors or institutions could not be wholly distinguished with bibliometric applications.

Conclusion

In conclusion, the annual number of publications on gout research grew in the latest decade between 2012 and 2021. China owned the most publications, while the USA was the country most frequently involved in international cooperation. The University of Auckland in New Zealand was the most contribute institution and achieved the leading place in research collaboration. Furthermore, Dalbeth Nicola made significant contributions to this research field. The analysis of keywords and co-citation suggested that the exploration of the pathological mechanism remains the future hotspot in gout research. The forward directions may involve gout connection with gut microbiota, urate-transporter ABCG2, NLRP3 inflammasome, xanthine oxidase, and heart failure. The present study would provide valuable research references and frontier directions for later researchers in the gout field.