Evolution of proton pump inhibitor research in reflux esophagitis: a Web of Science-based global bibliometric assessment [1990–2026]

Abstract

Background

Reflux esophagitis remains a prevalent acid-related disorder with an increasing global burden, yet the growing challenges of refractory disease and the transition toward newer acid-suppressing agents highlight critical knowledge gaps. This study aimed to analyze the global research trends and identify emerging hotspots in proton pump inhibitors (PPIs) treatment for reflux esophagitis through a Web of Science-based bibliometric analysis [1990–2026].

Methods

A systematic search was conducted in the Web of Science Core Collection (WoSCC) on June 18, 2026, using MeSH-derived terms. Only English-language original research articles were included. Two independent researchers manually screened all records for relevance. The analysis was performed using VOSviewer, CiteSpace, and the “bibliometrix” package of R.

Results

A total of 338 articles were included. Publications showed an overall upward trend with an annual growth rate of 2%. Japan emerged as the leading country (111 publications), followed by the United States [59] and China [38]. The American Journal of Gastroenterology and the Journal of Gastroenterology were the most influential journals. Keyword co-occurrence analysis identified five major research clusters spanning clinical assessment, pathophysiological mechanisms, disease classification, pharmacological evaluation, and comparative clinical trials, with research evolving from early PPI efficacy studies [1991–2005] to disease mechanisms [2005–2015] and to patient-centered outcomes [2015–2026].

Conclusions

Three distinct research phases were identified in PPI treatment for reflux esophagitis. Current research insufficiently addresses the long-term impact of PPIs on gut microbiome and the comparative effectiveness of emerging potassium-competitive acid blockers (P-CABs). Future research should prioritize pharmacogenetic optimization, real-world evidence generation for novel therapeutic agents, and enhanced international collaboration.

Highlight box.

Key findings

• Publications on proton pump inhibitors (PPIs) for reflux esophagitis have grown steadily at an annual rate of 2% [1990–2026]. Japan, the United States, and China are the most prolific contributors.

• Five major research clusters were identified: clinical assessment, pathophysiological mechanisms, disease classification, pharmacological evaluation, and comparative clinical trials.

• The field has evolved through three distinct phases: establishing PPIs as standard care [1991–2005], exploring disease mechanisms [2005–2015], and shifting toward comprehensive management and diagnostic precision [2015–2026].

What is known and what is new?

• PPIs are the cornerstone of reflux esophagitis management, with well-documented efficacy and established treatment guidelines.

• This study provides the first comprehensive bibliometric mapping of the field, revealing the temporal evolution of research priorities—from clinical efficacy to mechanistic understanding and, most recently, to patient-centered approaches—along with key contributors, collaborations, and emerging thematic shifts.

What is the implication, and what should change now?

• The shift toward patient-centered outcomes highlights a growing need to integrate long-term safety, personalized therapy, and quality of life considerations into clinical practice and future research.

• Researchers and funding bodies should prioritize pharmacogenetic optimization of acid suppression therapy, comparative effectiveness studies of emerging potassium-competitive acid blockers, and real-world evidence generation in diverse populations to address current gaps identified in the evolving research landscape.

Introduction

Reflux esophagitis is a common inflammatory condition of the esophagus resulting from gastroesophageal reflux disease (GERD), characterized by heartburn, regurgitation, and various complications that significantly impact patients’ quality of life (1). The global burden of GERD has increased substantially over the past three decades, with approximately 825.6 million prevalent cases worldwide in 2021 and projections indicating continued upward trends (2). The pathogenesis involves complex mechanisms, including reduced lower esophageal sphincter pressure and compromised esophageal clearance, leading to prolonged exposure of the esophageal mucosa to gastric contents (3,4).

Proton pump inhibitors (PPIs) have become the mainstay treatment for reflux esophagitis since their introduction in the late 1980s, demonstrating superior efficacy compared to H2-receptor antagonists (5). However, approximately 20–42% of patients remain symptomatic despite standard PPI therapy, constituting the growing challenge of refractory GERD (6). The recent introduction of potassium-competitive acid blockers (P-CABs) such as vonoprazan (7), combined with emerging concerns regarding the long-term impact of PPIs on the gut microbiome (8), have generated a rapidly expanding and increasingly complex body of literature.

Bibliometric analysis is a quantitative methodology that evaluates the structural metadata of scientific literature, including publication patterns, citation networks, and the temporal evolution of research themes (9). It is fundamentally distinct from other evidence synthesis approaches: systematic reviews and meta-analyses evaluate the direction and strength of clinical effects, and scoping reviews map available literature to identify knowledge gaps, whereas bibliometric analysis uniquely examines the macro-level architecture of a research field by analyzing its scholarly metadata rather than the substantive findings of individual studies (10). This methodological distinction enables bibliometric analysis to address questions that are inaccessible through traditional review methodologies, such as identifying influential research networks, detecting temporal shifts in research priorities through citation burst analysis, and visualizing thematic clusters that reveal the intellectual structure of a discipline.

While several bibliometric studies have examined broader gastroenterological research trends, none has specifically analyzed the intersection of PPIs and reflux esophagitis treatment. Previous studies have either focused on GERD as a broader condition (11,12) or on P-CABs in acid-related diseases (13), leaving a notable gap given the central role of PPIs in reflux esophagitis management and the continuous evolution of treatment strategies. Therefore, the purpose of this study is to conduct a comprehensive bibliometric analysis of the scientific literature regarding PPIs treatment for reflux esophagitis, aiming to map the global research landscape, identify key contributors and collaboration networks, delineate the temporal evolution of research hotspots, and provide evidence-based guidance for future research priorities in this field. We present this article in accordance with the BIBLIO reporting checklist (available at https://jtd.amegroups.com/article/view/10.21037/jtd-2026-0946/rc).

Methods

Data source and search strategy

A comprehensive literature search was conducted in the Web of Science Core Collection (WoSCC) database on June 18, 2026. The WoSCC was selected as the sole data source because of its comprehensive coverage of high-quality peer-reviewed journals, robust citation indexing system, and full compatibility with established bibliometric visualization tools such as VOSviewer and CiteSpace. This single-database approach is consistent with the methodological standards adopted by the majority of published bibliometric studies (14). The citation indices selected were the Science Citation Index Expanded (SCI-EXPANDED) and the Social Sciences Citation Index (SSCI). No temporal restriction was imposed on the starting year of the search; the earliest publication identified in the dataset was from 1990, and the search extended to the retrieval date. The search strategy combined terms related to reflux esophagitis and PPIs: TS = [(“Peptic Esophagitis” OR “Esophagitides, Peptic” OR “Peptic Esophagitides” OR “Reflux Esophagitis” OR “Esophagitis, Reflux” OR “Esophagitides, Reflux” OR “Reflux Esophagitides”) AND (“proton pump inhibitor*” OR “Proton Pump Inhibitor” OR “Inhibitors, Proton Pump” OR “Inhibitor, Proton Pump” OR “Pump Inhibitor, Proton”)]. The search terms were derived from Medical Subject Headings (MeSH) thesauri and supplemented with synonymous terms to maximize retrieval sensitivity while avoiding highly ambiguous abbreviations (e.g., “PPI”) that could introduce irrelevant records from unrelated disciplines.

Inclusion and exclusion criteria

Only original research articles published in English were eligible for inclusion. We excluded reviews, meeting abstracts, proceeding papers, editorial materials, letters, retracted publications, meeting summaries, non-English publications, and other document types. Following the removal of ineligible document types, two independent researchers manually screened all remaining records by reviewing titles and abstracts to assess relevance to the study topic of PPI therapy in reflux esophagitis. Discrepancies between reviewers were resolved through discussion and final adjudication by the corresponding author. Articles judged to be irrelevant to the research topic were further excluded. This manual screening protocol was implemented in compliance with the BIBLIO (Bibliometric Reviews of the Biomedical Literature) reporting guidelines, specifically addressing the requirement for transparent data refinement procedures (15). All bibliographic data were exported from WoSCC using the “Full Record and Cited References” format in plain text, including comprehensive information about publications, authors, citations, references, and journal metrics.

Data analysis and visualization

For the bibliometric analysis, we employed three complementary analytical tools: VOSviewer (version 1.6.20) (16), CiteSpace (version 6.3.R1) (17), and “bibliometrix” package of R (version 4.3.3) (18). An online bibliometric platform (https://bibliometric.com/) was also employed as an auxiliary analytical tool. Additionally, Microsoft Excel was used to identify and calculate basic bibliometric indicators, including annual publication volume, citation frequency, journal impact factor (IF), and author productivity metrics. VOSviewer was primarily utilized for visualizing bibliometric networks and analyzing collaboration patterns (16). Keyword co-occurrence analysis was performed in VOSviewer using “Keywords Plus” as the data source, with a minimum occurrence threshold of 5, which identified 107 qualifying keywords. Keywords Plus was selected over Author Keywords because comparison of both sources indicated that Keywords Plus provided more standardized results for co-occurrence mapping. CiteSpace was employed to conduct temporal analysis and detect emerging trends in the field (17). We configured the software with 1-year time slices spanning 1991 to 2026. The top 5 most cited items per slice were selected for analysis. The node type was set to “Keyword”. Pruning was performed using Pathfinder and pruned merged network approaches. This configuration enabled the generation of keyword timeline visualizations and citation burst detection for identifying emerging research frontiers. The “bibliometrix” package of R was used for comprehensive statistical analysis and the generation of supplementary visualizations (18). To evaluate research impact, we utilized several established bibliometric indicators (Table S1). At the author level, we employed the h-index, which measures both productivity and citation impact (19); the g-index, which gives greater weight to highly-cited articles (20); and the m-index, which normalizes the h-index by the number of years since an author’s first publication (21). For journal evaluation, we considered the IF from Journal Citation Reports (JCR), and JCR Quartile rankings (22).

Results

Overview of publications

A total of 631 studies were initially identified from the WoSCC. After applying language and document-type restrictions in WoSCC, 455 English-language original articles remained. Subsequently, two independent researchers manually screened all records by reviewing titles and abstracts. A total of 117 articles judged to be irrelevant to the research topic were excluded, yielding a final dataset of 338 articles for this bibliometric analysis (Figure 1). Overall, the 338 articles were contributed by 1,970 authors from 1,188 institutions across 47 countries and published in 136 journals, citing 8,329 references. The average number of co-authors per document was 7.12, and the international co-authorship rate was 13.31%. Depicting the annual publication trend from 1991 to 2026, the annual publication count demonstrated fluctuations over time, reaching peaks of 16 and 20 publications in 2010 and 2012, respectively, with an overall upward trend and an annual growth rate of 2% (Figure 2). The most cited article (364 citations), published in the American Journal of Gastroenterology (IF =8.5) in 2003, reported a five-way crossover study comparing gastric acid control among five PPI agents, including esomeprazole, lansoprazole, omeprazole, pantoprazole, and rabeprazole (23). This study provided critical pharmacodynamic evidence that established differential acid suppression profiles among available PPIs, informing subsequent clinical decision-making regarding drug selection.

Figure 1.

A flowchart visually represents the systematic procedure for screening the literature. TS, topic search.

Figure 2.

Trend analysis of academic publications.

Analysis of countries and institutions

The bibliometric analysis revealed significant geographic and institutional contributions to research on PPI therapy in reflux esophagitis. Our analysis identified research contributions from 47 countries across 1,188 institutions, with distinct patterns of productivity and collaboration.

Among all contributing nations, Japan emerged as the leading contributor with 111 publications (32.8% of total publications) and 2,470 citations, demonstrating the highest impact in the field. The United States followed with 59 publications (17.5%) and 2,874 citations, while China ranked third with 38 publications (11.2%) and 521 citations. European countries also showed substantial contributions, with Germany (25 publications, 997 citations) and the Netherlands (11 publications, 836 citations) demonstrating particularly strong citation impact relative to their publication volume (Figure 3A and Table S2).

Figure 3.

Investigation of global scientific collaboration trends. (A) Distribution of corresponding authors’ publications across countries. (B) Network visualization of country collaborations. (C) Top ten institutions by article count and rank. (D) Collaboration network map depicting the relationships among institutions. MCP, multiple country publication; SCP, single country publication.

Analysis of international collaboration patterns revealed varying levels of research cooperation among countries. The United States demonstrated the highest level of international engagement with 35 collaborative connections, followed by Germany (28 connections) and Sweden (22 connections) (Figure 3B). Among leading nations, Germany showed strong international engagement with 8 of its 25 publications involving international collaboration (multiple country publication, MCP =8). Similarly, Belgium had 1 international collaborative publication out of 2 total publications (MCP =1), while Brazil demonstrated the highest MCP ratio with all 2 of its publications involving international collaboration (MCP =2). The United States demonstrated notable international collaboration with 9 multi-country publications out of 59 total (MCP =9). In contrast, Japan, despite having the highest publication volume (111 papers), had relatively few international collaborations (MCP =1). Spain showed moderate international engagement with 2 collaborative papers out of 6 total publications (MCP =2) (Table S2).

At the institutional level, the top ten institutions by article count were identified through R bibliometrix analysis. The United States Department of Veterans Affairs and Veterans Health Administration emerged as the most productive institutions, each contributing 25 publications. Among academic institutions, Shimane University led with 24 publications, followed by Tohoku University (20 publications) and Saga University (18 publications) (Figure 3C). The analysis of institutional collaboration networks (Figure 3D) revealed that Hyogo College of Medicine demonstrated the strongest collaborative ties, maintaining 56 institutional collaborations, followed by Shimane University (48 total link strength, TLS) and Gunma University Hospital (47 TLS).

Analysis of authors

The bibliometric analysis identified 1,970 authors contributing to research on PPI therapy in reflux esophagitis, with varying patterns of productivity, impact, and collaboration networks. Kinoshita Yoshikazu emerged as the most prolific author, with the highest publication count of 15 articles and an h-index of 10 and g-index of 15, accumulating 452 citations. His work, spanning from 2006, demonstrated consistent productivity with an m-index of 0.48, indicating sustained impact in the field. Hongo Michio ranked second in h-index (10) and g-index (13), contributing 13 publications with 525 total citations since 2008. Fujimoto Kazuma and Haruma Ken shared similar h-index values (h-index =8), though their publication patterns differed. Fujimoto Kazuma’s work showed higher total citations [530] with 13 publications, while Haruma Ken contributed 10 publications with 330 citations (Table S3).

The analysis of author collaboration networks revealed interesting patterns among the 75 authors with at least three publications. Fujimoto Kazuma demonstrated the highest degree of collaboration, maintaining 78 TLS, followed by Kusano Motoyasu and Miwa Hiroto with 70 TLS each (Figure 4).

Figure 4.

Visualization of author collaboration network.

Analysis of journals

Our bibliometric analysis identified 136 journals that published research on PPIs and reflux esophagitis between 1990 and 2026. The American Journal of Gastroenterology emerged as the most productive and influential journal in this field with 21 publications and the highest h-index (17), accounting for approximately 6.2% of all publications. This journal also ranked second in total citations [889] with an IF of 8.5. The Journal of Gastroenterology followed closely with 19 publications, an h-index of 12, and 307 total citations (IF =5.7). Alimentary Pharmacology & Therapeutics ranked third with 18 publications, an h-index of 13, and 830 citations (IF =6.8). Among the high-impact journals in this field, Gastroenterology had the highest IF (29.7) though it published only 6 articles on this topic. The Journal of Gastroenterology and Hepatology (IF =3.5) also showed substantial publication volume with 17 articles and an h-index of 12 (Table S4).

The journal co-occurrence network analysis (Figure 5A) revealed strong interconnections among specialized gastroenterology journals. The three key journals with the highest TLS in co-occurrence networks were the Journal of Gastroenterology [65], American Journal of Gastroenterology [44], and the Journal of Gastroenterology and Hepatology [37]. In the coupling networks analysis (Figure 5B), which assesses the extent to which journals share common references, the Journal of Gastroenterology demonstrated the highest link strength [1,784], followed by the American Journal of Gastroenterology [1,336] and the Journal of Gastroenterology and Hepatology [1,328].

Figure 5.

Journal co-occurrence and coupling networks. (A) Co-occurrence network of journals. (B) Coupling network of journals.

Analysis of keywords

A comprehensive keyword analysis of the selected articles was performed using “Keywords Plus” provided by VOSviewer. In total, 107 keywords with a minimum of 5 occurrences were identified. The keyword “omeprazole” had the highest occurrence [115] and TLS [564], followed by “disease” (83 occurrences, 415 TLS), “reflux esophagitis” (70 occurrences, 307 TLS), and “ranitidine” (48 occurrences, 288 TLS).

The keyword co-occurrence network visualization identified five major research clusters (Figure 6A). Cluster 1 (34 items) focused on clinical assessment, epidemiology, and management strategies, including keywords such as “disease”, “efficacy”, “diagnosis”, “symptoms”, “prevalence”, “quality-of-life”, “guidelines”, “management”, and “clinical characteristics”. This cluster represents the broadest thematic area encompassing clinical evaluation, treatment effectiveness measurement, and evidence-based management approaches. Cluster 2 (29 items) concentrated on pathophysiological mechanisms and related conditions, featuring keywords such as “omeprazole”, “helicobacter-pylori”, “acid-secretion”, “gastric-mucosa”, “atrophic gastritis”, “duodenal-ulcer”, “infection”, and “expression”. This cluster reflects the biological basis of treatment approaches and the complex interplay between acid-related disorders. Cluster 3 (19 items) emphasized diagnostic classification and functional disorders, containing terms such as “acid reflux”, “classification”, “functional dyspepsia”, “gastroesophageal reflux disease”, “motility”, and “natural-history”, highlighting the importance of disease phenotyping and differential diagnosis. Cluster 4 (13 items) represented pharmacological aspects and drug-specific research, including “lansoprazole”, “acid suppression”, “H2-receptor antagonists”, “intragastric pH”, “metabolism”, “pharmacokinetics”, and “safety”, demonstrating the emphasis on comparative pharmacology and drug development. Cluster 5 (12 items) specifically addressed comparative clinical trials and therapeutic evaluation, including “double-blind”, “erosive esophagitis”, “competitive acid blocker”, “esomeprazole 40 mg”, “pantoprazole”, “rabeprazole”, and “randomized clinical-trial” (Table S5).

Figure 6.

Analysis of research themes and trends. (A) Network visualization of keyword co-occurrence analysis identifying five major clusters. (B) Top 20 keywords with the most significant citation bursts.

The analysis of keyword bursts revealed significant temporal shifts in research focus over the studied period [1991–2026] (Figure 6B). The earliest and strongest citation burst belonged to “ranitidine” (strength =11, 1993–2003), reflecting the critical transition period from H2-receptor antagonists to PPIs as the primary treatment for reflux esophagitis. This period also saw significant bursts in “duodenal ulcer” (strength =6.27, 1994–2000) and “double blind” (strength =4.25, 1994–1997), highlighting the emphasis on comparative clinical trials and the establishment of PPIs as the standard of care. The burst pattern of “helicobacter pylori” (strength =5.55, 1998–2010) further indicated growing interest in understanding the relationship between H. pylori infection and reflux esophagitis during this transitional period.

The middle period was characterized by bursts in “efficacy” (strength =3.97, 2002–2005) and “intragastric pH” (strength =3.68, 1999–2006), indicating continued focus on treatment effectiveness evaluation and acid suppression monitoring. The emergence of specific PPIs names such as “rabeprazole” (strength =3.12, 2006–2021) reflected ongoing comparative drug studies.

Recent developments show a clear evolution toward patient-centered outcomes and comprehensive disease understanding. Strong bursts in “prevalence” (strength =5.36, 2007–2023), “symptoms” (strength =3.9, 2007–2016), and “disease” (strength =5.08, 2009–2024) reflect increasing attention to epidemiological patterns and clinical manifestations. The bursts in “quality of life” (strength =4.24, 2009–2017) and “erosive esophagitis” (strength =4.77, 2012–2018) demonstrate growing emphasis on patient experience and disease severity classification. The most recent and currently active citation bursts belong to “management” (strength =7.98, 2019–2026) and “diagnosis” (strength =3.29, 2020–2026), suggesting an ongoing shift toward comprehensive treatment strategies, diagnostic precision, and personalized medicine approaches in the treatment of reflux esophagitis.

Discussion

This bibliometric analysis provided a comprehensive overview of global research trends in PPI therapy for reflux esophagitis from 1990 to 2026. Our analysis revealed significant contributions from diverse geographical regions, institutions, and researchers, reflecting the global importance of this therapeutic area.

The dominance of high-impact gastroenterology journals, particularly the American Journal of Gastroenterology and the Journal of Gastroenterology, in publishing research on PPI therapy for reflux esophagitis reflects the clinical significance of this topic. These journals have historically shown strong interest in acid-related disorders and therapeutic innovations (24). Notably, the Journal of Gastroenterology demonstrated the highest TLS in both co-occurrence [65] and coupling [1,784] network analyses, indicating its central role as an intellectual hub connecting diverse research streams within this field. The prominence of the Journal of Gastroenterology and Hepatology in both networks further reflects the strong interconnection between gastroenterology and hepatology research in the context of acid-related disorders.

The geographical distribution of research output shows interesting patterns, with Japan, the United States, and China emerging as major contributors. Japan’s leadership in this field, contributing 32.8% of all publications, can be attributed to several interrelated factors. The declining prevalence of Helicobacter pylori infection in Japan, which has decreased substantially since the introduction of national eradication policies in 2000 and 2013 (25), has been associated with a paradoxical increase in GERD prevalence, as reduced H. pylori colonization leads to restored gastric acid secretion capacity (26). This epidemiological shift has stimulated substantial clinical research interest in acid suppression therapy. Furthermore, Japan’s pioneering role in the development and clinical adoption of P-CABs, particularly vonoprazan, which was first approved for clinical use in Japan in 2015, has generated a unique research trajectory that distinguishes its scholarly output from Western nations (27). Additionally, Japan’s strong tradition of endoscopic innovation and its well-established national gastroenterology research infrastructure have facilitated large-scale multicenter studies that are prominently represented in our dataset (28).

In contrast, the United States, despite having fewer total publications than Japan (59 vs. 111), demonstrated markedly higher average citations per article (48.7 vs. 22.3), indicating greater per-article influence. This disparity may reflect the United States’ strength in conducting large-scale randomized controlled trials and developing clinical practice guidelines that serve as international reference standards. Germany and the Netherlands similarly showed high citation impact relative to their publication volumes, reflecting the influential nature of European multicenter collaborative research. However, the analysis also revealed concerning patterns of limited international collaboration, particularly for Japan (MCP ratio =0.009) and China (MCP ratio =0.026), suggesting that research in East Asian countries remains largely domestically oriented despite the increasing global relevance of their findings.

The analysis of author contributions reveals the evolution of research focus over time. Key contributors such as Kinoshita Yoshikazu and Hongo Michio have shaped the field through pioneering work in PPIs efficacy studies and the development of treatment guidelines (29). Their research teams have particularly contributed to understanding Asian-specific aspects of reflux esophagitis treatment, addressing the unique pathophysiological characteristics and treatment responses in Asian populations (30).

Research hotspots and frontier trends

The keyword co-occurrence network identified five major research clusters, revealing a thematic architecture that spans from fundamental clinical assessment to advanced pharmacological evaluation. The largest cluster (Cluster 1, 34 items) encompassed the broadest range of clinical research themes, integrating epidemiology, symptom assessment, management strategies, and treatment outcomes. The convergence of keywords such as “prevalence”, “quality-of-life”, “guidelines”, and “management” within a single cluster reflects the field’s maturation toward evidence-based, patient-centered clinical practice. The second cluster (29 items) centered on pathophysiological mechanisms and comorbid acid-related conditions, highlighting the persistent research interest in the interplay between H. pylori infection, gastric acid secretion, and esophageal mucosal injury. This thematic grouping underscores the importance of mechanistic understanding in informing therapeutic strategies, particularly in populations with variable H. pylori prevalence.

Clusters 3 through 5 demonstrated increasing specificity, progressing from disease classification and differential diagnosis (Cluster 3) to pharmacokinetic evaluation and drug safety (Cluster 4), and finally to head-to-head clinical trial comparisons among specific PPI agents (Cluster 5). The inclusion of “competitive acid blocker” in Cluster 5, alongside established PPIs such as esomeprazole, pantoprazole, and rabeprazole, reflects the emerging presence of P-CABs in the comparative effectiveness literature.

The keyword burst analysis revealed significant temporal shifts in research priorities that can be organized into three distinct periods. The early period [1991–2005] was characterized by the transition from H2-receptor antagonists to PPIs as the primary treatment for reflux esophagitis, with the strongest burst belonging to “ranitidine” (strength =11, 1993–2003). This period also saw substantial bursts in “duodenal ulcer” and “double blind”, reflecting the emphasis on rigorous comparative clinical trials that established PPIs as the standard of care. The therapeutic paradigm shift during this period was comprehensively documented by Vakil et al., whose Montreal consensus paper established a global evidence-based definition of GERD and formalized PPIs as the cornerstone therapy (24).

The middle period [2005–2015] demonstrated a shift toward understanding disease mechanisms and long-term treatment outcomes. The prolonged burst of “helicobacter pylori” [1998–2010] indicated growing recognition of the complex bidirectional relationship between H. pylori infection and reflux esophagitis, with studies demonstrating that infection patterns influence gastric acid secretion differently depending on the affected gastric region (31). This period also witnessed increasing attention to treatment effectiveness evaluation, as evidenced by the burst in “efficacy” [2002–2005]. Notably, the growing clinical burden of refractory GERD, in which standard PPI therapy fails to achieve complete mucosal healing or symptom resolution in approximately 20–42% of patients (6), has become a major clinical challenge driving research during and beyond this period.

The most recent period [2015–2026] shows a clear evolution toward patient-centered outcomes and comprehensive disease management. The currently active and strongest burst belongs to “management” (strength =7.98, 2019–2026), reflecting the shift toward integrated treatment algorithms that incorporate both pharmacological and non-pharmacological approaches (32). The concurrent burst in “diagnosis” [2020–2026] suggests growing interest in diagnostic precision and phenotypic classification, aligning with updated clinical guidelines that emphasize individualized management strategies (33). Earlier bursts in “quality of life” [2009–2017] and “erosive esophagitis” [2012–2018] further demonstrate the field’s transition from efficacy-driven research to assessments of patient-reported outcomes and disease severity grading. The emergence of vonoprazan, a first-in-class P-CAB, has represented a paradigmatic advance in this field, with randomized controlled trials demonstrating its superiority over conventional PPIs in healing and maintenance of healing of erosive esophagitis, particularly in severe cases (7). This therapeutic innovation, initially developed and approved in Japan before gaining regulatory approval in the United States and other markets, highlights how regional research priorities can generate globally transformative advances.

These evolving research trajectories also point to several critical knowledge gaps and emerging frontiers. The impact of long-term PPIs use on the gut microbiome has attracted growing attention, with studies demonstrating that prolonged acid suppression alters intestinal microbial composition, reduces diversity, and enriches potentially pathogenic taxa (8). These microbiome perturbations may contribute to adverse outcomes including enteric infections, intestinal inflammation, and nutrient malabsorption (34). Additionally, the pharmacogenetic optimization of PPI therapy, particularly through CYP2C19 genotype-guided dosing, represents a promising approach toward personalized treatment that may improve outcomes in patients with variable drug metabolism (35).

Strengths and limitations

Our study represented the first comprehensive bibliometric analysis specifically focusing on PPI therapy in reflux esophagitis. The analysis spans over three decades, providing a longitudinal perspective on research evolution. The use of multiple complementary analytical tools enabled robust validation of findings through different methodological approaches. Furthermore, a rigorous manual screening protocol with independent dual-reviewer assessment was implemented to ensure the relevance and quality of included publications, in accordance with the BIBLIO reporting guidelines.

However, several limitations should be acknowledged. First, our analysis was restricted to the WoSCC, which, although widely recognized as the gold standard database for bibliometric analysis due to its comprehensive citation indexing and compatibility with visualization tools, may potentially miss relevant publications indexed exclusively in other databases. This limitation may particularly underrepresent contributions from regional databases, including Chinese-language publications, which is notable given China’s position as the third-largest contributor to this field. Future bibliometric studies may incorporate multi-database search strategies to improve coverage and further reduce potential database-related bias. Second, the analysis included only English-language publications, which may further underrepresent contributions from non-English speaking regions. Third, the inherent delay in citation accumulation means that the impact of recent publications may be underestimated.

Conclusions

This bibliometric analysis revealed significant trends in PPI therapy for reflux esophagitis research from 1990 to 2026, with a clear shift from efficacy-focused studies to patient-centered outcomes and precision medicine approaches. The keyword burst analysis identified three distinct research phases: establishment of PPIs as standard care [1991–2005], exploration of disease mechanisms and long-term outcomes [2005–2015], and evolution toward comprehensive management strategies and diagnostic precision [2015–2026]. The most recent and currently active bursts in “management” and “diagnosis” underscore the field’s ongoing transition toward individualized therapeutic approaches. The key emerging research frontiers include the impact of long-term PPIs use on gut microbiome, the clinical adoption of P-CABs such as vonoprazan, and pharmacogenetic optimization of acid suppression therapy. This study provides valuable insights for researchers, clinicians, and funding agencies by identifying both established research areas and emerging frontiers to guide future research priorities and international collaboration opportunities.

Supplementary

The article’s supplementary files as

Ethical Statement: The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.