Pancreatic cancer (PC) is a prevalent and highly aggressive malignancy of the digestive system, with a dismal 5-year survival rate of merely 11% (Khalaf et al., 2021). While various risk factors—such as age, obesity, genetic predisposition, alcohol use, smoking, chronic pancreatitis, and diabetes—have been identified, the exact etiology of PC remains unclear (Klein, 2021; Zanini et al., 2021; Bennett et al., 2022; Amri et al., 2023; Michalak and Malecka-Wojciesko, 2023; Conway et al., 2024). Owing to its subtle early symptoms and the absence of specific detection indicators, PC is often not diagnosed until advanced stages. Consequently, research has increasingly focused on early diagnosis, tumorigenesis mechanisms, and anti-tumor therapy.

The gut microbiota (GM), comprising trillions of microorganisms, exhibits a complex relationship with cancer (Aykut et al., 2019; Dong et al., 2021; Hashimoto et al., 2023; Seo and Wargo, 2023). Advances in targeted 16S rRNA pyrophosphate sequencing and metagenomics have shown that abnormal GM contribute to chronic metabolic diseases like chronic pancreatitis, obesity, inflammatory bowel disease (IBD), and nonalcoholic fatty liver disease (NAFLD), as well as tumors (Jandhyala et al., 2015; Jandhyala et al., 2017; Riquelme et al., 2019; Talukdar et al., 2021; Zhao et al., 2022; Feng et al., 2023; Ma et al., 2023). Emerging evidence indicates that gut dysbiosis is significantly linked to PC (Yu et al., 2022; Chen T. et al., 2023). Researchers have identified several mechanisms by which the GM influences PC, including modulation of the microbe-immune system tumor axis, alteration of the tumor microenvironment, impact on metabolite production, promotion of cancer-related inflammation, and effects on chemotherapy efficacy (Aykut et al., 2019; Dong et al., 2021; Li et al., 2022; Zhang and Tang, 2022; Hashimoto et al., 2023; Seo and Wargo, 2023). Obviously, these findings highlight the complex relationship between GM and PC, functioning as a carcinogenic factor while also representing a promising therapeutic target (Kartal et al., 2022).

Bibliometric analysis has emerged as a key method for assessing the credibility, quality, and impact of scholarly work by analyzing and visualizing research trends in the era of big data (Jiang et al., 2022; Mirhashemi et al., 2022; Sun et al., 2022). Unlike traditional systematic reviews, bibliometric analysis offers a quantitative approach to assess academic literature, enabling the identification of key research findings, contextual development, and summarization of research trends (Kokol, 2021; Ge et al., 2022). To the best of our knowledge, only one study has quantitatively analyzed the literature on the relationship between GM and PC (Wu et al., 2023). However, previous study failed to adequately reflect the current research status and hotspots in the relationship between GM and PC. Constrained by research timelines and methodological limitations, some pivotal and emerging studies may have been omitted in the previous study. Furthermore, the exclusion of investigational hotspots that lack established feasibility would compromise the comprehensiveness of emerging trends mapping.

In contrast, this study incorporated data from the most recent years (updated to November, 2023). In an era defined by the rapid evolution of big data, one-year new data may lead to groundbreaking high-impact papers, new research directions, and shifts in the landscape of leading countries and institutions. Furthermore, our study covered a longer time span (dating back to 2000), allowing us to better analyze the evolution of research hotspots and future direction rather than merely focusing on current trends. By refining our search terms, we have generated a literature set that is more focused on the core relationship between GM and PC, thereby enhancing the accuracy and relevance of our analysis. This approach would more effectively reveal the “historical patterns” of development in the field.

In recent years, an increasing number of studies have explored the relationship between GM and PC, particularly in the last decade. Notably, some researches have shown a close link between GM dysfunction and PC (Pushalkar et al., 2018; Riquelme et al., 2019; da Cruz et al., 2025). This bibliometric analysis provided a comprehensive mapping of the knowledge structure and evolutionary trends in the research linking the GM to PC by analyzing highly productive countries, institutions, core journals, core literature, key authors, keyword clusters, and emerging research topics and future directions.

In this study, a total of 763 publications from January 1, 2000, to November 18, 2023, were analyzed to delineate research trends and identify potential future hotspots in this field over the past 23 years. The results indicate that interest in the association between GM and PC has steadily increased since 2014. The significant rise in literature over the last decade reflects a growing recognition of the impact of gut microbiota on PC. Regarding the country analysis, studies from 63 countries/regions were enrolled in this study. The analysis identified the USA and China as the two leading countries in this field, together accounting for 55.99% of all research (Table 5). The USA maintained a commanding lead over all other countries in total publications, H-index, and total citations, leading by a wide margin. Obviously, the USA’s status as the undisputed leader in this domain is likely underpinned by its robust research ecosystem, characterized by stable funding, deep expertise, and significant human capital. A striking contrast is presented by China, as a developing country, while the total publication volume and H-index were far ahead of other developed countries to rank second, but the average number of cited articles was relatively low. This phenomenon highlights the urgent need for increased investment and emphasis on fundamental science and original research. Additionally, institutions between countries should strengthen their cooperation, especially in developing countries. Although the USA and China had the closest interaction in the country collaboration, there was little close cooperation and communication among academic institutions in various nations (Figure 4B), with the majority of institutional cooperation was only within countries.

Regarding the institutional analysis, the ten leading organizations were distributed across four countries: the USA, China, Sweden, and Italy (Table 1). Among them, more than half of the top ten funded institutions came from the USA. Notably, there were 3 institutions from China in the top ten, including Zhejiang University, Shanghai Jiao Tong University and Peking Union Medical College. This reality further underscores the profound impact of economic investment and capacity on scientific advancement. Interestingly, although National Cancer Institute only ranked 10th in total papers, it ranked third in terms of average number of citations, which demonstrated that focusing on cutting-edge and major research topics yields highly innovative and influential outcomes. The multi-perspective analysis not only uncovered dense collaborative networks among institutions but also provides a valuable reference for researchers seeking suitable partners.

Regarding in the core journal analysis, those top ten journals published 18.48% of relevant articles, categorized into gastrointestinal cancer journals, general interest publications, and microbiological journals (Table 3). Notably, gastrointestinal cancer journals published the most articles, highlighting the gut microbiota’s significance in pancreatic cancer research. Analysis of the top 10 productive authors, Dominique S. Michaud (Brown University) was the most prolific author, contributing 160 publications, ahead of Florencia McAllister (88) and George Miller (76). Regarding scholarly impact, Richard B. Hayes and Jiyoung Ahn shared the highest citation counts (total: 1,464; average: 292.8). Hayes alone attained the highest H-index of 100. Based on this analysis, we can infer that research quality is a key driver of professional citation and engagement.

The top 10 core literatures with the highest citations on the association between GM and PC in Table 4. In this field, the first most cited article was written by Gopalakrishnan et al (Kokol, 2021). This article established that the structure and function of gut microbiota significantly affected outcomes of PD-1 inhibitor therapy, uncovering the microbiome’s impact on immune checkpoint blockade and paving the way for subsequent research into gut microbiota in PC The second most cited article was a review by McGuckin et al (Ge et al., 2022). This review focused on the interactions between intestinal pathogens and mucins, and the strategies pathogens employ to disrupt and circumvent the mucosal barrier, offering key insights for future investigations into the GM-PC mechanism. Notably, studies conducted by Pushalkar et al (Chen H. et al., 2023). dedicated to investigating the microbiome’s influence on development and PC prognosis. However, the exact role of the GM in PC pathogenesis remains unclear. Based on this analysis, we can infer that the current research focuses primarily on three themes: 1) how the gut microbiota influences immune regulation; 2) the mechanisms by which the gut microbiota contributes to tumorigenesis; and 3) the interactions among the microbiota, metabolism and cancer.

To better investigate and describe the evolution of research topics and frontiers on the link between GM and PC, this study employed timeline visualizations of co-cited references and keywords. These visualizations, particularly the timeline view of co-cited references shown in Figures 7B and 8B, intuitively depict the temporal dynamics and shifts in research focus. The timeline view of co-cited references reveals a clear shift in research focus over time (Figure 7B). Recent studies have centered primarily on two areas: anticancer and metabolic pathway. Through the timeline visualizations of keywords and theme trend and thematic map, we found that the keywords “Gut Microbiota”, “Pancreatic Cancer”, “Cancer”, “Sequence” “Microbiome” and “Tumor Microbiome” may be hot research topics for the future.

Although the association between GM and PC has not been fully elucidated, considerable progress has been achieved in mechanistic research, paving the way for a deeper understanding. For one thing, Guo et al (Huang et al., 2023). found that the tumorigenicity of PDAC xenograft was higher in microbiota-intact mice than that in microbiota-depleted mice. Similarly, the study of Thomas et al (Thomas et al., 2018). demonstrated that complete PC mouse model was tended to develop carcinogenesis, compared with intestinal aseptic PC mouse model after the ABX cocktail therapy. These results indicated that the underlying reason may be related to the suppression of the host’s immune regulation by the gut microbiota. And, chronic inflammation in pancreatic tissue can trigger KRAS mutations in pancreatic endocrine cells ultimately leading to pancreatic epithelial tumors and PDAC, which was reported by Gidecel Friedlander et al (Gopalakrishnan et al., 2018). and Guerra et al (McGuckin et al., 2011). For another, established research demonstrated that specific microbes such as Bifidobacterium, Collinsella aerofaciens and Enterococcus faecalis can suppress regulatory T cells to enhance immune responses during cancer therapy (Zhang et al., 2020). Listeria monocytogenes was identified to promote the repolarization of macrophages from the immunosuppressive M2 phenotype to the antitumor M1 phenotype. Meanwhile, probiotics have been reported to inhibit PC development by producing anti-tumor mediator or enhancing the apoptosis of tumor cells (Kita et al., 2020; Konishi et al., 2021). Besides that, intestinal microbial may enhance the efficacy of conventional chemotherapy through drug metabolism, biological transformation. In the study conducted by Nicola Gaglian et al (Tintelnot et al., 2023). the microbiota-derived tryptophan metabolite indole-3-acetic acid (3-IAA) was enriched in patients who respond positively to chemotherapy through shotgun metagenomic sequencing and metabolomic screening. Simultaneously, fecal microbiota transplantation(FMT)was observed to increase the efficacy of chemotherapy in humanized gnotobiotic mouse models of PDAC, one of which may be involved in downregulation of the reactive oxygen species (ROS)-degrading enzymes (Riquelme et al., 2019). By searching clinical trial registration websites, we found that a relevant clinical trial NCT04975217(Fecal Microbial Transplants for the Treatment of Pancreatic Cancer) is underway. This study is focusing on the safety, tolerability, and feasibility of FMT in resectable PDAC patients, which is sponsored by M.D. Anderson Cancer Center.

This study has several limitations. Firstly, it only included publications from the Web of Science, a widely recognized database, which may have excluded some relevant works not indexed there. Actually, we previously considered merging data from multiple databases, such as Scopus, Medline, and Cochrane, to enhance literature coverage, but encountered several significant challenges during implementation. For more comprehensive results, those databases could be adopted in further studies. Secondly, our study was restricted to publications in English, which may have resulted in the exclusion of non-English studies and consequently limited the breadth of our findings. Thirdly, the specific search terms used potentially introduced selection bias by failing to capture all pertinent literature. Fourth, in this study, review articles account for nearly half of the total, which may introduce bias into the citation analysis of keywords. Lastly, given the rapidly evolving nature of microbiome research, some important and landmark studies may have been omitted and some hotspots that researchers are working on that have not been proven feasible may be missed, resulting in some new hotspots not being included. Obviously, it is subject to the inherent time lag in the Web of Science indexing process. It is hoped that these limitations will be addressed in future research.

In conclusion, we conducted a bibliometric analysis to thoroughly investigate the relationship between GM and PC, providing an overview of the topic and identifying future research directions in this field. The association between GM and PC has attracted increasing research interest, prompting more comprehensive investigations into this relationship. Based on this bibliometric analysis, we have revealed that GM plays a pivotal role in both the pathogenesis of PC and its therapeutic interventions.