Gastric cancer (GC) is the fifth most common cancer in the world and the fourth leading cause of cancer death (Sung et al., 2021). In the future, although the incidence rate of GC may show a downward trend, for some countries, incidence and mortality increases have been predicted in people below the age of 50 (Arnold et al., 2020; Qi et al., 2023; Teng et al., 2023). Helicobacter pylori (H. pylori) is considered a major risk factor for GC and has been classified as a Class I carcinogen. The birth-cohort pattern revealed an epidemic of H. pylori in gastrointestinal disease (Sonnenberg, 2022). The sequential development model of GC suggests that H. pylori colonizes the gastric mucosa, inducing continuous chronic gastric inflammation, then causes cascade pathogenesis: atrophic gastritis (AG), in which H. pylori plays a role, and then intestinal metaplasia (IM), dysplasia, and finally GC (Correa, 1988, 1992). However, the decreasing prevalence of H. pylori has been histologically observed with the increasing severity of AG (Correa, 1992; Kuipers, 1998; Liu et al., 2022), and some clinical studies have shown that H. pylori eradication in patients with advanced lesions does not eliminate the risk of carcinogenesis (Wong et al., 2004; Rugge et al., 2019), indicating that further progression of precancerous conditions may be independent of H. pylori colonization. With the prevalence of H. pylori infection decreasing (Li et al., 2023), these facts draw attention to gastric microorganisms other than H. pylori.

The gastrointestinal microbiota is the largest and most complex microbial ecosystem in the human body, among which bacteria form major communities. However, given its highly acidic environment, which makes it difficult for general bacteria to colonize, the stomach was considered sterile until H. pylori was isolated from the gastric mucosa. With the development of molecular techniques, 128 phylotypes of microorganisms have been identified through phylogenetic analysis from gastric endoscopy biopsy samples, most of which belong to Proteobacteria, Firmicutes, Bacteroidetes, Actinobacteria, and Fusobacteria, and 10 main genera have been classified (Bik et al., 2006; Liu et al., 2022). Multiple case–control studies based on gastric mucosal tissue biopsies have confirmed changes in bacterial diversity during the progression of intestinal-type GC. From non-atrophic gastritis (NAG) to IM and then to GC, the bacterial diversity steadily decreased (p = 0.004), and the gastric flora abundance changed continuously during this process (Aviles-Jimenez et al., 2014; Liu et al., 2022). Some studies have put forward different views: compared with functional dyspepsia, the richness and diversity of bacterial flora in GC tissue increased, but their uniformity did not increase. In addition, the serological status of H. pylori has a significant impact on the composition and diversity of the gastric microbiome (Castano-Rodriguez et al., 2017). Evidence from germ-free insulin–gastrin (INS-GAS) and human gastric microbiota transplant mouse models further supports the potential causality of the microbiota in gastric carcinogenesis (Lofgren et al., 2011; He C. et al., 2022; Kwon et al., 2022). Accordingly, some researchers have used combinations of genera of gastric flora as microbial markers for the non-invasive diagnosis of GC (Chen et al., 2023).

Bibliometrics combines mathematics, statistics, and literature to explore the structural characteristics and hot trends of disciplines through the quantitative analysis of vast amounts of publications and evaluates and predicts the results. It has been widely applied in various fields of medicine (Dracos and Cognetti, 1995; Chen et al., 2012; Kokol et al., 2021). Compared to traditional systematic reviews, the application of bibliometrics in a research field can help new researchers or researchers in other fields to grasp the development process and status of the field based on cluster labels or topics, rather than reading hundreds of unfamiliar studies to obtain limited information. It might also be limited to reading reviews because they often focus on only one research theme (Donthu et al., 2021). For small data samples, synthetic knowledge synthesis can also be applied to extract, synthesize, and multidimensionally structure the corpus of scholarship (Kokol et al., 2022). At present, scholars are increasingly reporting on GC and the gastric microbiota. However, to the best of our knowledge, there is currently no intuitive visual analysis that explores the hotspots and trends in this field. Therefore, we adopted bibliometric methods to conduct a systematic review of this field. By performing quantitative and qualitative analyses of the relevant literature and utilizing visualization tools, the research status, hotspots, and future trends in this field were analyzed.

This article is the first to identify the current research status, research hotspots, and trends in the field of gastric flora and gastric cancer based on bibliometric methods. The application of bibliometric analysis and visualization can display various topics and trends in basic or clinical research in order for researchers to carry out their work. In addition, our research shows that this research field has broad prospects and that there are still many clinical problems left to be solved.

While the annual cumulative number of papers has shown an exponential growth trend, in the past 3 years, the annual publications in this field have continued to grow rapidly, which suggests that the topic of gastric microbiota and GC has become popular. The analysis of funding showed that many countries are increasing capital input in this field, especially those that are productive. It can be predicted that in the future, the number of publications in this field will continue to grow exponentially, and funding support may also increase, making this field attractive for researchers.

Among the countries that published articles from 2013 to 2023, the total number of articles published by the top eight countries accounted for more than 90% of all articles published in this field, indicating that these countries were the main contributors to research in this field. Developed countries such as the United States and Germany published papers earlier, and their research results also had a relatively prominent influence. These countries often have advanced medical research institutions, outstanding scientific researchers, and sufficient financial support. As a developing country, China has been increasing its publication volume significantly since 2015, and the total number of articles quickly exceeded that of other countries. This may be due to the large population base, the large number of H. pylori infections and GC patients, and the popularization of endoscopic biopsy technology (Fan et al., 2021; Wang et al., 2022), as well as the rapid growth of national GDP and increased investment in scientific research (Lei et al., 2020; Zhou et al., 2021). However, although China is an important representative with respect to investment in this field, China’s betweenness centrality was not outstanding enough, indicating that Chinese researchers need to improve the quality of their research. The institutions that contributed the most to this field were mainly universities, mostly from the United States and European countries. Among them, Baylor College of Medicine has made prominent contributions and is considered one of the most outstanding medical schools in the United States. Through the analysis of authors and institutions, it can be seen that Fox JG and Wilson KT from Vanderbilt University, Figueiredo C and Ferreira RM from Universidade do Porto, have made great contributions in this field and published a series of highly influential articles, as well as actively participating in follow-up research. In recent years, with the largest number of publications, China’s output mainly came from Zhejiang University and Nanchang University. However, most researchers in this field currently tend to collaborate with domestic research institutions or within research groups in the same institution, even in productive countries. This might be due to the fact that this research field is only in its infancy. Therefore, as the number of publications increases, countries and institutions need to strengthen cooperation to promote the exchange of academic ideas and innovative development in the research field, which will also help to expand their influence.

In terms of journal analysis, the impact factor (IF) of a journal to some extent represents the influence of research in the field and the quality of the research results. The reference source journals have high IFs, indicating that the research foundation in this field is reliable. Gut was the most cited journal, indicating that the results published in this journal have an important influence in this research field, with an IF of 24.5. Helicobacter was the main journal publishing research in this field, with an IF of 4.4. Recently, journals such as Frontiers in Microbiology, Scientific Reports, and Gut Microbes have published numerous articles, among which the IF of Gut Microbes reached 12.2. However, compared to the cited literature, the current IFs of publications in this field are still lower in general. This may be due to the fact that research in this field has not attracted widespread attention, suggesting that researchers need to improve the quality of their research through reasonable experimental design and advanced research technology to produce more influential products and propose more novel perspectives.

A large number of studies have taken various directions, leading to pathogenesis research and clinical practical applications. By reading the key literature identified via the historiograph of citing documents, the research progression can be revealed. After identifying differences in the gastric microbiota characteristics between GC patients and those with dyspepsia, as the technique developed, the gradual shifting of the gastric microbiota in Correa’s cascade was confirmed, and genotoxic colonies were finally identified. In this process, the correlations between the gastric microbiota, gastric cancer, and specific pathogenic bacteria were gradually identified. The application of specific microbiota in the clinical identification of GC patients was gradually supported. Subsequently, through PICRUSt analysis and other means, the role of different gastric microorganisms in the progression of GC was gradually revealed. The article published by Ferreira RM et al. in Gut in 2018 (doi: 10.1136/gutjnl-2017-314205) had the highest citation frequency and the highest LCS and GCS, indicating that it was widely recognized by researchers as an important research basis. The researchers conducted a retrospective analysis of the gastric microbiota of patients with GC and chronic gastritis. They found that the diversity of the gastric microbiota was reduced in GC patients, and other bacterial genera, mainly intestinal commensal bacteria, were enriched, showing community characteristics different from chronic gastritis patients. This article revealed that gastric microbiota dysbiosis is related to GC and proved that the microbial dysbiosis index (MDI) can be used to identify GC, with the area under the curve (AUC) being 0.91 and 0.89, respectively (Ferreira et al., 2018). “Mucosal microbiome dysbiosis in gastric carcinogenesis,” published by Coker OO et al. (doi: 10.1136/gutjnl-2017-314281) close to the same period, also proved that there are differences in the gastric microbial composition and bacterial interactions during the progression from chronic gastritis to GC, and the correlation strengths between enriched groups and reduced groups increased (p < 0.001; Coker et al., 2018).

The visualization and clustering of keywords also reveal the evolution of the research topic. The timeline graph and thematic evolution analysis showed that although many important keywords such as “Helicobacter pylori” and “gastric cancer” have emerged in the early years, this research field is still developing and the topics described by these keywords are still being studied. In addition, topics that have begun to receive attention in recent years, such as “tumor microenvironment” and “stomach microbiota”, may be the focus of future research. In this research field, H. pylori, as a major member of the gastric microbiota, receives constant attention. Keyword analysis showed that “helicobacter-pylori”, “infection”, “eradication”, “proton pump inhibitors”, “regulatory T cells”, “CagA”, etc. were important keywords. As H. pylori is associated with GC and has a high infection rate in the general population, the diagnostic approaches, eradication methods, and carcinogenesis mechanisms for H. pylori have been extensively studied (Yang et al., 2014; Ansari and Yamaoka, 2022). However, current H. pylori eradication therapies face challenges involving antibiotic resistance (Ansari and Yamaoka, 2022; Suzuki et al., 2022), dysbiosis (Gotoda et al., 2018, 2020), the potential danger of long-term PPI use, and other shortcomings (Kuipers et al., 1996; Xu et al., 2013; Jiang et al., 2019; McCarthy, 2020; Seo et al., 2021; Arai et al., 2023). Recent studies have shown that H. pylori eradication regimens based on Vonoprazan (VPZ) are effective and safe (Kakiuchi et al., 2023) and have a higher H. pylori eradication rate than PPI-containing triple or quadruple therapy (Chey et al., 2022). The dual therapy consisting of VPZ and amoxicillin has a low incidence of adverse reactions and can also avoid unnecessary use of antibiotics, reducing the incidence of dysbiosis of the intestinal microbiota (Ouyang et al., 2022; Zhang J. et al., 2023). The dosage regimen of VPZ and the adverse events associated with its strong acid-suppressive effect still need further evaluation (Hu et al., 2022; Arai et al., 2023). In addition, the eradication of H. pylori might not be necessary for children because infection by H. pylori has a protective effect against asthma and inflammatory bowel disease via the systemic immune tolerance induced by dendritic cells (DCs) and regulatory T cells (Treg cells; Ravikumara, 2023). Helicobacter pylori infection or seropositivity have a detrimental impact on the efficacy of cancer immunotherapies, and the eradication of H. pylori infection by antibiotherapy does not revert the H. pylori-induced hyporesponsiveness to cancer immunotherapy (Che et al., 2022; Oster et al., 2022a,b; Gong et al., 2023). However, another meta-analysis has suggested that GC patients with H. pylori infection may respond better to PD-1/PD-L1 blockade therapy (Zhu et al., 2023). These divergent findings may be explained by differences in patients and treatment characteristics, as well as potential confounding factors. Thus, many experts are calling for a more individualized eradication approach in the context of additional risk factors rather than unconditionally eradicating H. pylori in every case. Clarifying the pathogenesis of H. pylori is still an important task. Helicobacter pylori infection triggers complex chronic immune responses, leading to the occurrence of a variety of diseases. Helicobacter pylori virulence factors such as cytotoxin-associated gene A (CagA), vacuolating cytotoxin A (VacA), and Helicobacter pylori neutrophil-activating protein (HP-NAP) significantly affect the function of DCs in tumor microenvironment or bone marrow-derived DCs and play an important role in the induction of GC (Fu and Lai, 2023; Raspe et al., 2023; Yuan et al., 2023). The Treg cell-mediated inflammatory response caused by H. pylori infection (Bagheri et al., 2016, 2018; Owyang et al., 2020) and the genome instability caused by CagA (Bagheri et al., 2018; Takahashi-Kanemitsu et al., 2020; Alipour, 2021; Imai et al., 2021; Murata-Kamiya and Hatakeyama, 2022; Marshall, 2023) have been extensively studied. Recent research has shown that H. pylori can inhibit miRNA-375 expression in the stomach. Downregulated miR-375 activates the JAK2-STAT3 pathway, which then promotes the secretion of IL-6, IL-10, and VEGF, leading to the immature differentiation of DCs and the induction of GC (Zhang et al., 2021). Notch signaling regulates the function and phenotype of DCs, thus mediating the differentiation of CD4⁺ T cells during H. pylori infection (Liu et al., 2023).

As 16 s rRNA sequencing techniques developed and gut microbiome research boomed with the confirmation of the relationship between the gastric microbiota and gastric carcinogenesis, researchers began to turn their attention to the study of the gastric microbiota. In this respect, “gut microbiota”, “colonization”, “16 s rRNA sequencing”, “risk”, “atrophic gastritis”, and “intestinal metaplasia” are important keywords, indicating that the clinical application of gastric microbiota in GC risk assessment and treatment are also current hotspots. As H. pylori is a bacterium that affects and is affected by the gastric microbiota, it is closely related to other bacteria in the progression of GC. Non-H. pylori microorganisms interact with H. pylori in gastric carcinogenesis (Guo et al., 2023). Successful H. pylori eradication can reverse gastric microbiota dysbiosis (Guo et al., 2020; Guo Q. et al., 2022), and its high eradication rate is related to specific flora members (Niu et al., 2021). The intestinal microbiota of H. pylori-positive GC patients is also transformed, and this may further contribute to GC (Gao et al., 2018; Dash et al., 2019; Seol et al., 2019; Iino and Shimoyama, 2021). Modulation of the gastrointestinal microbiota is beneficial to the eradication of H. pylori and the treatment of gastric diseases related to microbial dysbiosis (Viazis et al., 2022; Musazadeh et al., 2023; Zhang L. et al., 2023). The study of specific strains or pathogenic pathways of non-H. pylori bacteria in GC progression is helpful in identifying relevant treatment measures accordingly. Using 16 s rRNA sequencing technology to analyze gastric epithelial bacteria at different stages of GC progression, it was found that some bacterial taxa, such as Peptostreptococcus stomatis, Streptococcus anginosus, Parvimonas micra, etc., were significantly enriched in GC patients and could be used to identify precancerous lesions and GC (Coker et al., 2018; Liu et al., 2022). Microbial taxonomic features (MTFs) can be used to predict early gastric neoplasia (EGN; Png et al., 2022) and may improve the accuracy of the polygenic risk score (PRS) model in predicting GC (Wang et al., 2023). As for the mechanism, many studies have revealed that non-H. pylori microorganisms promote GC by inducing inflammation, modulating the immune response, triggering DNA damage, and promoting epithelial–mesenchymal transformation (Yang et al., 2022; Liao et al., 2023). Gastric non-H. pylori microorganisms may participate in the progression of GC by affecting host DNA methylation (Yue et al., 2023). Different bacterial taxa are related to certain types of infiltrating immune cells (Liao et al., 2023). In the gastric microbiota associated with atrophy/intestinal metaplasia, functional pathways such as amino acid metabolism and inositol phosphate metabolism are enriched, while folate biosynthesis and NOD-like receptor signaling are reduced, which may explain the ongoing progression of precancerous conditions even after H. pylori eradication (Sung et al., 2020). Research on the intestinal microbiota continuously activating host immunity and producing a variety of metabolites has illuminated its effect on GC (Nasr et al., 2020; Guo Y. et al., 2022), while the GC microflora can modulate macrophages and enhance gastric tumor development by suppressing antitumor immunity, activating oncogenic signaling pathways, and producing protumor metabolites (Zhang W. et al., 2023).

Through emergent analysis, we can speculate that the role of Fusobacterium nucleatum (F. nucleatum) in the Correa cascade of GC development may become a research hotspot in the future. Fusobacterium nucleatum, which exists in the oral cavity and gastrointestinal tract of humans, is an opportunistic pathogen causing systematic diseases, for example, gastrointestinal cancers (Chen et al., 2022; He Z. et al., 2022). A number of studies have demonstrated the potential pathogenic role of F. nucleatum in colorectal cancer (CRC; Lee et al., 2019). Fusobacterium nucleatum causes CRC by adhering and forming biofilm, invading host cells, producing metabolites, and releasing vesicles (Chen et al., 2022). Fusobacterium nucleatum promotes CRC metastasis through M2 polarization of macrophages in the tumor microenvironment (Chen et al., 2018; Xu et al., 2021). However, its roles in GC are not so clear. In a study using Clostridium and Fusobacterium nucleatum in biopsy tissue to diagnose GC, the sensitivity reached 100%, the specificity was 68.8%, and the AUC was 0.875 (Hsieh et al., 2018). The combined colonization of F. nucleatum and Helicobacter pylori has also been associated with a poor survival rate in late-stage GC patients treated with gastrectomy, suggesting that it may promote the progression or metastasis of GC by synergizing with H. pylori (Hsieh et al., 2021, 2023). Fusobacterium nucleatum has strong interactions with Porphyromonas, Prevotella, etc., which may lead to shortened survival (Nie et al., 2021; Lehr et al., 2023). A bioinformatic analysis suggested that neutrophil transcriptional activation induced by F. nucleatum may be implicated in the occurrence of GC through several candidate genes, including DNAJB1, EHD1, IER2, CANX, and PH4B. Functional analysis showed that membrane-bound organelle dysfunction, intracellular trafficking, transcription factors ER71 and Sp1, and miR580 and miR155 were other candidate mechanisms (Zhou et al., 2022). The metabolic function analysis showed that F. nucleatum-positive GC tissues were significantly enriched in the biosynthesis of lysine, peptidoglycan, and tRNA metabolic functions (Nie et al., 2021). These results await further verification. Existing studies have demonstrated the role of F. nucleatum in the ERBB2-PIK3-AKT–mTOR pathway and the miR-885-3p/EphB2/PI3K/AKT axis (Hsieh et al., 2023; Xin et al., 2023). However, some researchers have questioned the actual role of F. nucleatum in gastric carcinogenesis. An F. nucleatum-positive result was associated with poor prognosis in patients with Lauren’s diffuse type GC but had no association with the prognosis of intestinal-type GC. These results still remain to be confirmed (Boehm et al., 2020; Nie et al., 2021). Fusobacterium nucleatum may promote carcinogenesis via Fusobacterium adhesionA (FadA), which binds to E-cadherin, activating Wnt/β-catenin signaling and various inflammatory and oncogenic properties of the cells (Rubinstein et al., 2013, 2019). Since the diffuse type of GC is strongly associated with E-cadherin deregulation, one may speculate on the potential molecular mimicry and specific prognostic relevance of F. nucleatum to the diffuse type of GC (Boehm et al., 2020). Furthermore, the interaction of F. nucleatum with non-H. pylori gastric microorganisms also requires more explanation.

This study has some limitations. Only relevant studies published by WoSCC were included in this study; cutting-edge research with high quality from other databases such as PubMed and Scopus might have been ignored. Second, the language was restricted to English, which may have excluded high-quality literature in other languages. In addition, the co-citation frequency of the literature is time-dependent, and since the research in this field is still in the developing stage, the number of citations cannot accurately reflect the importance of the document, especially important documents published in recent years. With the exponential growth of publications in this field, our research needs to be constantly updated to keep up with the latest research developments. Finally, due to missing keywords reported by Biblioshiny in some literature, the outcome of the CiteSpace keyword analysis might be a little inaccurate; however, we used different bibliometric software to conduct our analysis and verify the results.

To the best of our knowledge, this study is the first to use visualization software and data mining methods to conduct a bibliometric analysis of publications in the field of gastric microbiota and gastric cancer and to determine the research status, hotspots, and development trends in this field. Research in this field has mainly focused on the eradication therapy and pathogenic mechanisms of Helicobacter pylori, as well as the utilization of gastric microbiota in the evaluation and treatment of gastric cancer. Future research hotspots may include the use of the gastric microorganisms represented by Fusobacterium nucleatum in the diagnosis of and for therapeutic effects on gastric cancer. Their mechanisms of action need to be further explored in order to provide a theoretical basis for clinical application. Relevant researchers or researchers outside this field can use this study to improve their awareness and understanding of the field and to gain some perspectives for further research.

All data used for our research is available through our retrieval query. Further inquiries can be directed to the corresponding author.

YK: Data curation, Formal analysis, Investigation, Visualization, Writing – original draft. CT: Data curation, Formal analysis, Investigation, Visualization, Writing – original draft. JZ: Formal analysis, Investigation, Methodology, Writing – review & editing. WD: Conceptualization, Methodology, Writing – review & editing.