Cluster analysis of research hotspots and trends in probiotics for constipation: A comprehensive bibliometric analysis (1977–2024)

Abstract

Background:

Probiotics are increasingly recognized as a promising therapeutic approach for managing constipation, sparking widespread interest in their effects on gastrointestinal health. This study conducts a cluster analysis to systematically map global research trends and hotspots in probiotics for constipation from 1977 to 2024.

Methods:

Relevant publications were retrieved from the Web of Science Core Collection. Bibliometric tools, including VOSviewer, CiteSpace, and R, were applied for cluster analysis, network visualization, and trend mapping.

Results:

A total of 519 publications were included in the analysis. China led in publication volume, while the United States demonstrated the highest academic influence. Key institutions, such as the University of California System and Harvard University, were identified as major contributors. High-impact journals, including Nutrients, World Journal of Gastroenterology, and Digestive Diseases and Sciences, played central roles in disseminating research. Quigley Eamonn M. M. indicated significant influence in the field. Cluster analysis of keywords revealed 6 principal research hotspots: microbial diversity and mechanisms, gut microbiota–host interaction and pathophysiology, dietary factors and microbiome analysis techniques, epidemiology, prevalence, and population health, clinical management and therapeutic efficacy, and clinical trials and study design. Citation burst analysis indicated a recent research focus shift toward mechanisms, personalized interventions, and gut microbiome modulation.

Conclusion:

This bibliometric study based on cluster analysis identified 6 major research hotspots in probiotics for constipation, reflecting the evolving trends and collaborative networks of the field. These findings provide a comprehensive perspective on current research priorities and can guide future studies toward innovative and evidence-based clinical applications.

1. Introduction

Constipation is a common gastrointestinal disorder characterized by difficult bowel movements, infrequent defecation, and hard stools.^[1] According to the Rome III criteria, chronic constipation is diagnosed when patients experience at least 2 or more related symptoms for a minimum of 12 weeks over the past year.^[2] Its prevalence varies by region, age, and gender, with a global average of approximately 20%, rising to as high as 40% among the elderly.^[3] Women are 2.2 times more likely than men to experience constipation.^[4,5] The etiology of constipation is multifactorial, including inadequate dietary habits, impaired gastrointestinal motility, lifestyle factors, and psychological stress.^[6,7] Beyond physical discomfort, constipation significantly affects quality of life, increases healthcare utilization, and imposes notable economic burdens.^[8,9] Thus, effective management strategies are crucial for alleviating the disease burden.

Current management of constipation encompasses pharmacological treatments, dietary modifications, surgical interventions, noninvasive nerve stimulation, and complementary therapies. Laxatives, such as polyethylene glycol and stimulant agents, are commonly used as first-line pharmacological options.^[10] For opioid-induced constipation, peripheral μ-opioid receptor antagonists like naldemedine have shown efficacyand safety.^[11,12] Dietary interventions, including supplementation with xylooligosaccharides and dietary fiber, have demonstrated benefits for gut microbiota composition and symptom relief.^[13,14] Surgical intervention is sometimes necessary in cases complicated by malnutrition or refractory symptoms,^[15] while noninvasive vagus nerve stimulation offers novel therapeutic possibilities.^[16] Nevertheless, significant challenges persist, such as reliance on specialized diagnostic procedures, adverse effects from long-term medication use, and inconsistent patient adherence.^[17,18] As a result, complementary approaches – particularly probiotics – have gained attention for their potential benefits in increasing spontaneous bowel movements and improving constipation-related symptoms.^[19,20]

Probiotics are live microorganisms that confer health benefits to the host, primarily by colonizing the gut and promoting microecological balance.^[7,21] Common strains include Clostridium butyricum, Lactobacillus spp., Bifidobacterium spp., and Lactobacillus acidophilus.^[19,22] Probiotics may alleviate constipation through several mechanisms, such as modulating gut microbiota composition, enhancing intestinal motility via organic acid production, and strengthening gut immunity by promoting mucosal immunoglobulin synthesis.^[22–25] While the application of probiotics in constipation has attracted wide interest, their efficacy remains debated, with clinical outcomes influenced by factors like baseline microbiota, probiotic strain, dosage, and patient characteristics.^[26–29]

Bibliometric analysis, which quantitatively assesses published literature using mathematical and statistical methods, provides valuable insights into research categories, co-authorship networks, keyword trends, and influential journals.^[30–32] Recent years have witnessed the application of bibliometric techniques to various fields of gut health, including functional gastrointestinal disorders (FGID),^[33] gut microbiota,^[34] and probiotics in irritable bowel syndrome (IBS).^[35] However, systematic bibliometric studies specifically focusing on probiotics for constipation are lacking, and existing analyses rarely employ cluster analysis to map major research hotspots and thematic trends in this area.

Therefore, this study aims to fill this gap by conducting a cluster analysis-based bibliometric investigation of global research on probiotics for constipation. By identifying key research clusters, influential contributors, and evolving hotspots, this study provides a comprehensive mapping of the field and offers guidance for future research directions and clinical applications.

2. Methods

2.1. Ethical considerations

This study is a bibliometric analysis based exclusively on data retrieved from the public Web of Science Core Collection (WoSCC) database. As the research did not involve human participants, animal subjects, or access to private patient data, institutional review board approval and informed consent were not required.

2.2. Literature search and data compilation

A comprehensive literature search was conducted using the WoSCC, a widely recognized multidisciplinary database indexing over 12,000 high-impact journals. The search was performed on November 18, 2024, focusing on the intersection of “constipation” and “probiotics.” To focus exclusively on human-related studies with clinical relevance, we excluded studies focusing on animal models, in vitro experiments, and veterinary research through the NOT operator. The search strategy was defined as follows: ((TS = (constipation OR “gastrointestinal transit” OR “functional constipation” OR “chronic constipation” OR “idiopathic constipation” OR “colonic inertia” OR dyschezia)) AND TS = (probiotic* OR bacteria OR synbiotic* OR prebiotics OR “escherichia coli” OR lactobacillus OR bifidobacterium OR bifidobacteria OR acidophilus OR saccharomyces OR bacillus OR “microbial cell preparation*” OR “fermented milk*”)) NOT TS = (animal* OR cell OR in vitro OR rat* OR dog* OR mice OR mouse OR pig* OR horse* OR monkey* OR veterinary). Only articles written in English were included to ensure linguistic uniformity. Editorial materials, meeting abstracts, non-English publications, and other non-article documents were excluded. Data were exported in both “Full record and cited references” and “plain text” formats. Key bibliometric data extracted included publication year, citation metrics, author affiliations, geographic distribution, journal titles, and keywords. This bibliometric analysis was conducted and reported in accordance with the Guideline for Reporting Bibliometric Reviews of the Biomedical Literature (BIBLIO).^[36]

2.3. Statistical analysis

The bibliometric analysis employed 3 specialized tools: R (version 4.3.3), VOSviewer (version 1.6.20), and CiteSpace (version 6.3.R1), each serving distinct analytical purposes. The Bibliometrix R package was used for quantitative analysis, extracting and analyzing bibliometric indicators such as publication counts, citation metrics, and keyword frequencies. Descriptive analyses, including publication growth trends and distributions across geographic and institutional levels, were also performed. Additionally, key bibliometric indices such as the H-index, G-index, and M-index were calculated to assess author productivity and research impact.^[37,38] The impact factor (IF) was obtained from information published in the latest version of Journal Citation Reports released in 2023 to 2024. Additionally, the online bibliometric platform (https://bibliometric.com/) was employed to visualize the distributions.

VOSviewer facilitated the construction and visualization of co-authorship and keyword co-occurrence networks. By applying clustering algorithms, the tool revealed collaborative patterns among countries, authors and institutions while identifying thematic groupings of keywords. The time-overlay feature provided insights into the temporal evolution of research topics, highlighting emerging trends over the study period.

CiteSpace enabled the detection of citation bursts and the mapping of academic knowledge structures. This tool identified influential references and keywords with strong citation bursts, providing a temporal perspective on shifts in research focus.

3. Results

3.1. Temporal dynamics of publications and citations: growth and impact over decades

The screening and selection process is visualized in Figure 1. An initial search retrieved 906 studies. After applying inclusion criteria and excluding editorials, and non-research documents, a total of 519 studies were retained for bibliometric analysis. This study encompassed articles with a steady annual growth rate of 8.94% between 1977 and 2024, encompassing the contributions of 3266 authors, with a notable 17.53% of the documents involving international co-authorship. Moreover, the average number of citations per document is 39.14, underscoring impact of these publications within the research community (Fig. 2A). The data also indicate a robust collaboration among researchers, with an average of 6.74 coauthors per document, emphasizing the collective efforts driving advancements in this domain. The trend in the number of publications (Fig. 2B) reveals a marked growth trajectory, particularly after 2010. Before 2005, the number of publications remained below 5 annually. While a sharp increase began in the subsequent years, reaching a peak of 56 publications in 2024. This upward trend reflects the growing academic focus on this field and its relevance in recent years.

Figure 1.

Flowchart of the literature screening process.

Figure 2.

Publications overview from 1977 to 2024. (A) Collected studies overview. (B) Annual number of publications and trend.

3.2. Landmark publications: insights from highly cited articles

The mostly cited article is “Short chain fatty acids and gut microbiota differ between patients with Parkinson disease (PD) and age-matched controls,” published in the Parkinsonism & Related Disorders (IF = 3.1) in 2016 and accumulated a total of 769 citations.^[39] The second mostly cited article, titled “An IBS subtype defined by species-specific alterations in fecal microbiota,” was published in the Gut (IF = 23.0) in 2012 and accumulated a total of 631 citations.^[40] The third mostly cited article is “Analysis of the fecal microbiota of IBS patients and healthy controls with real-time PCR,” published in the American Journal of Gastroenterology (IF = 8.0) in 2005 and accumulated a total of 537 citations.^[41] The top 50 articles are listed in the Table S1 (Supplemental Digital Content, https://links.lww.com/MD/R754).

3.3. Global research landscape: contributions from leading countries and institutions

The global distribution of publications demonstrates significant contributions from leading countries (Table S2, Supplemental Digital Content, https://links.lww.com/MD/R754 and Fig. 3A). China led with the highest number of articles (95), accounting for 18.3% of the total publications, followed by the USA (81 articles, 15.6%) and Japan (50 articles, 9.6%). These 3 countries exhibited varying levels of international collaboration, with multiple-country publication (MCP) ratios of 0.084 for China, 0.210 for the USA, and 0.100 for Japan. In terms of total citations, the USA ranked first with 4099 citations, reflecting its strong academic influence, while China ranked second with 1889 citations. Finland stood out with the highest average citations per document (119.8), indicating the high impact of its contributions despite its smaller publication volume. Other notable countries include Belgium (MCP ratio = 0.700) and Spain (MCP ratio = 0.571) demonstrated a high proportion of multi-country collaborations. The international collaboration network (Fig. 3B) highlights the USA and China as central nodes with extensive connections to other countries. The USA had the highest number of collaborations (total link strength = 59), followed by the United Kingdom (total link strength = 34) and Italy (total link strength = 29). European countries such as Germany, France, and Belgium formed dense regional clusters, while smaller clusters included countries like Brazil and Mexico.

Figure 3.

Analysis of countries. (A) Global distributions of countries. (B) Visualization map depicting the collaboration among different countries.

Institutional analysis highlights the dominance of major universities and research centers in the field (Fig. 4A). The University of California System and the University of London lead with 30 publications each, followed closely by Harvard University (28) and Jiangnan University (27). Other prominent contributors include the Mayo Clinic (22), University College London (16), and University of Helsinki (15). Collaboration patterns further emphasize the importance of these institutions in fostering partnerships (Fig. 4B). The Mayo Clinic led with the highest number of collaborations (19), followed by University of California, Los Angeles (15) and Harvard Medical School (15). In addition, the institutional collaborations highlight regional clusters, with European institutions such as the University of Helsinki, University of Bologna, and University of Naples Federico II respectively forming cohesive networks.

Figure 4.

Analysis of institutions. (A) Top ten institutions by article count and rank. (B) Institutions’ publications and collaborations visual analysis.

3.4. Authorial footprints and collaborative synergies in probiotics research

A total of 3266 authors have contributed to this field of research, reflecting its collaborative and interdisciplinary nature. Table S3 (Supplemental Digital Content, https://links.lww.com/MD/R754) highlights the profiles of high-impact authors, with Quigley Eamonn M. M. achieving the highest total citations (1283) and a notable G-index of 5, indicating significant influence in the field. Other prominent contributors include Szajewska Hania (297 citations) and Ouwehand Arthur C. (275 citations). Authors such as Chen Wei, Zhang Hao, and Tian Fengwei demonstrate sustained productivity and influence, as reflected in their m-index values and recent contributions.

The co-authorship network (Fig. 5) visually illustrates the collaboration dynamics among authors, revealing 4 distinct clusters of research activity. The red cluster, dominated by Zhang Hao, Tian Fengwei, and Chen Wei, shows the strongest interconnections, reflecting active international collaboration (24 collaborations each). The green cluster, led by Ma Jianxia, highlights dense regional collaborations in applied clinical studies, with contributors such as Pan Yiru and Wang Ke forming strong connections. The blue cluster, featuring Huang Zhenyu, Yang Zhenyu, and Peng Yuanping, emphasizes foundational and emerging research with strong interdisciplinary ties. Lastly, the yellow cluster, including Theis Stephan, Raes Jeroen, and Savino Francesco, represents emerging microbiome-related topics with smaller but meaningful collaborations. These patterns underscore the strong collaborative efforts and thematic diversity within the field.

Figure 5.

Visualization map depicting the collaboration among different authors.

3.5. Scholarly dissemination: journal networks and their influence on research progression

The collected papers are distributed across 272 journals, reflecting the interdisciplinary nature of the research field. Ranking the top journals based on H-index (Table S4, Supplemental Digital Content, https://links.lww.com/MD/R754), Nutrients leads with an H-index of 12, followed by the World Journal of Gastroenterology (H-index = 11) and Digestive Diseases and Sciences (H-index = 9). Other notable journals include the International Journal of Food Sciences and Nutrition (H-index = 8) and the American Journal of Gastroenterology (H-index = 7). Among the top-ranked journals, Gut has the highest IF (23, 2023), followed by Gut Microbes (12.2, 2023) and the American Journal of Gastroenterology (8, 2023). Journals such as Alimentary Pharmacology & Therapeutics (IF = 6.6, 2023) and Clinical Nutrition (IF = 6.6, 2023) also play significant roles, reflecting their contributions to advancing research in gastroenterology and nutrition. From the perspective of publication volume, Nutrients leads with the highest total number of publications (TP = 23), followed by the World Journal of Gastroenterology (TP = 11) and Digestive Diseases and Sciences (TP = 9). Other journals with notable contributions include Beneficial Microbes (TP = 9), International Journal of Food Sciences and Nutrition (TP = 9), and the American Journal of Gastroenterology (TP = 8).

The co-occurrence network analysis (Fig. 6A) reveals 79 journals with at least 2 occurrences, highlighting their interconnectedness in the citation network. Journals such as the World Journal of Gastroenterology, Nutrition Journal, and Nutrients exhibit the highest total link strengths (91, 44, and 43, respectively), signifying their central roles in shaping the research landscape. The coupling network analysis (Fig. 6B) provides further insights into the relationships between journals based on shared references. Nutrients, World Journal of Gastroenterology, and American Journal of Gastroenterology demonstrate the highest link strengths (1848, 1508, and 1476, respectively), emphasizing their shared intellectual foundations and influence within the field. Journals such as Gut and Alimentary Pharmacology & Therapeutics also exhibit high co-citation frequencies, underscoring their prominence in the research network.

Figure 6.

Network analysis of journals. (A) Co-occurrence networks of journals, reflecting thematic or topical connections based on co-citations. (B) Coupling networks of journals, illustrating shared intellectual foundations through common references.

3.6. Cluster analysis of keyword hotspots in probiotics for constipation

The keyword analysis reveals key research trends and focal points in the field (Table S5, Supplemental Digital Content, https://links.lww.com/MD/R754), with terms such as “double-blind” (95 occurrences, total link strength: 451), “probiotics” (84 occurrences, total link strength: 407), and “irritable-bowel-syndrome” (63 occurrences, total link strength: 331) dominating the landscape. These keywords emphasize the field’s focus on clinical trials and the therapeutic potential of probiotics for gastrointestinal disorders. Other frequently occurring terms, including “symptoms,” “constipation,” and “quality-of-life,” underscore a strong interest in patient outcomes and treatment efficacy. Across the network, 146 keywords with at least 5 occurrences were identified, forming distinct clusters that represent different areas of research.

The keyword co-occurrence network analysis (Fig. 7A) identified 6 distinct thematic clusters, each representing a central research focus within the domain of probiotics and constipation. Cluster 1 (Red): Microbial Diversity and Mechanisms. This cluster focuses on the foundational understanding of gut microbiota composition and the mechanistic roles of bacteria in gastrointestinal health. Core keywords such as “bacteria,” “diversity,” “microbiota,” “fermentation,” “fiber,” and “fatty-acids” illustrate research dedicated to exploring bacterial diversity, metabolic activity, and their effects on gut function. The high frequency and strong link strength of these terms underscore the centrality of microbial mechanisms in constipation and probiotic action. Cluster 2 (Green): Gut Microbiota–Host Interaction and Pathophysiology. This cluster encapsulates research into the dynamic interplay between gut microbiota and host factors. Dominant keywords include “gut microbiota,” “constipation,” “chronic constipation,” “colonic transit,” “inflammation,” and “fecal microbiota,” reflecting an emphasis on how shifts in microbial communities, host metabolism, and inflammation contribute to the development and management of constipation. Cluster 3 (Blue): Dietary Factors and Microbiome Analysis Techniques. This cluster highlights studies examining the influence of nutrition and analytical methodologies on the gut microbiome. Keywords such as “dietary fiber,” “bifidobacteria,” “colonization,” “intestinal microflora,” “16s ribosomal-rna,” and “oligosaccharides” indicate a focus on both dietary interventions and advanced techniques for profiling and manipulating the intestinal microbiome. Cluster 4 (Yellow): Epidemiology, Prevalence, and Population Health. This cluster is centered on epidemiological and population-based research. Frequently occurring terms like “prevalence,” “adults,” “children,” “health,” “risk,” and “prevention” emphasize efforts to map the distribution of constipation, identify at-risk populations, and develop preventive strategies at the public health level. Cluster 5 (Purple): Clinical Management and Therapeutic Efficacy. This cluster synthesizes research on clinical outcomes, therapeutic interventions, and evidence-based management. Prominent keywords such as “efficacy,” “management,” “metaanalysis,” “controlled-trial,” “microbiome,” and “synbiotics” reflect the evaluation of treatment modalities, safety, and clinical guidelines for probiotics in constipation and related disorders. Cluster 6 (Cyan): Clinical Trials and Study Design. This cluster highlights methodological rigor and clinical research design. High-frequency and highly interconnected keywords such as “double-blind,” “irritable-bowel-syndrome,” “clinical-trial,” “symptoms,” “functional constipation,” and “quality-of-life” demonstrate the field’s emphasis on randomized controlled trials (RCTs) and robust evaluation of probiotic efficacy and safety.

Figure 7.

Visual analysis of keywords. (A) Keyword co-occurrence network analysis of clusters. (B) Keyword co-occurrence network analysis (timeline).

The temporal evolution of research priorities is further illustrated in Figure 7B, with earlier studies addressing foundational topics such as “bacteria” and “dietary fiber,” while recent studies have shifted toward terms like “gut microbiota,” “functional constipation,” and “mechanisms.” Recent keywords of particular significance include “gut microbiome” (2021), “functional gastrointestinal disorders” (2022), and “mechanisms” (2022), which signify a growing emphasis on understanding gut health mechanisms and clinical applications in FGID.

The top 20 keywords with the strongest citation bursts reflect the dynamic shifts in research focus over time (Fig. 8). “Gut microbiota” exhibits the strongest burst (Strength: 9.45, 2022–2024), underscoring its pivotal role in current research. Other significant terms include “functional gastrointestinal disorders” (Strength: 5.03, 2022–2024), “mechanisms” (Strength: 3.44, 2022–2024), and “functional constipation” (Strength: 4.26, 2019–2024), all of which highlight emerging areas of focus. Earlier bursts, such as “fecal microbiota” (Strength: 4.39, 2014–2021), reflect sustained interest in microbiota-based interventions, while more recent terms signal a shift toward mechanistic studies and clinical applications.

Figure 8.

Top 20 keywords with the strongest citation bursts.

4. Discussion

This study conducted a bibliometric analysis of publications related to probiotics and constipation from 1977 to 2024, uncovering critical insights into research trends, major contributors, and emerging themes. The findings reveal a consistent growth in academic interest, with a significant increase in publications and collaborative efforts over the past 2 decades.

The geographic distribution of publications highlights a strong research presence in China and the United States, with China leading in publication volume and the United States demonstrating the highest academic influence, as evidenced by its total citations. This aligns with findings from other bibliometric studies, where the USA consistently exhibits a high impact in medical and nutritional research due to its robust research funding and interdisciplinary focus.^[42,43] Notably, Japan, Italy, and the United Kingdom also emerge as key contributors, reflecting their growing interest in probiotic-based interventions for gastrointestinal health. Institutional analysis underscores the prominence of major research hubs in driving advancements in the field. Institutions like the University of California System, Harvard University, and Jiangnan University have made substantial contributions, with the University of California System and Harvard University prominently involved in international collaborations. These finding echoes previous bibliometric studies, which highlight the role of leading institutions in fostering interdisciplinary and multinational partnerships. The Mayo Clinic, University of London, and University of Helsinki also stand out for their impactful contributions, particularly in clinical applications and foundational research on gut microbiota and probiotics.

Influential researchers such as Quigley Eamonn M. M., Szajewska Hania, and Ouwehand Arthur C. have not only advanced our understanding of probiotics’ therapeutic roles but also shaped the research agenda in gastrointestinal health. For example, Quigley’s work has been pivotal in elucidating the relationship between gut microbiota and motility disorders, providing a strong foundation for clinical applications of probiotics.^[44] Szajewska’s research, on the other hand, has focused on the efficacy of probiotics in pediatric populations, emphasizing evidence-based approaches in clinical practice.^[45] Ouwehand’s studies have contributed to understanding strain-specific effects, addressing critical challenges in the standardization of probiotic interventions.^[46] Beyond individual achievements, the collaborative nature of this field is evident in the co-authorship networks, which highlight the integration of applied and foundational research. Researchers like Zhang Hao and Tian Fengwei have contributed to bridging mechanistic studies with clinical applications, reflecting a trend toward translational research that prioritizes patient outcomes. This shift is particularly relevant as the field moves from general probiotic use to more personalized approaches, considering factors like individual gut microbiota composition and lifestyle.^[47] Moreover, the emerging collaborations among foundational researchers, such as Raes Jeroen and Theis Stephan, suggest a growing advances in sequencing technologies and computational biology to explore the interplay between probiotics and the broader gut microbiome, offering novel insights into the mechanisms underlying constipation.

The analysis of journals reveals that Nutrients, the World Journal of Gastroenterology, and Digestive Diseases and Sciences serve as pivotal platforms for disseminating research on probiotics and constipation. These journals’ interdisciplinary focus on nutrition, gastroenterology, and food sciences provides a valuable avenue for researchers to reach diverse and specialized audiences. Similar to findings in related bibliometric analyses, high-impact journals such as Gut and American Journal of Gastroenterology play a critical role in shaping the research landscape by publishing groundbreaking studies on the gut microbiota and its implications for gastrointestinal health. For emerging researchers, these journals offer not only visibility but also allow engagement with cutting-edge findings in the field.

Keyword analysis revealed distinct thematic areas in probiotics and constipation, focusing on clinical trials, mechanisms, and therapeutic applications. These clusters provide insights into the evolution of research priorities and the interconnectedness of topics within this field.

4.1. Microbial diversity and mechanisms (red cluster)

The prominence of this cluster highlights the foundational role of complex gut microbial communities and their metabolic interactions in the context of constipation and probiotic therapy. Accumulating evidence indicates that alterations in microbial diversity and metabolic activity, particularly the production of short-chain fatty acids (SCFAs), are crucial in regulating intestinal motility and maintaining mucosal health.^[48,49] For instance, Pan et al demonstrated that specific probiotics, such as Bifidobacterium bifidum and Lactobacillus rhamnosus GG, can modulate serotonergic pathways and Toll-like receptor signaling, leading to improved gastrointestinal transit and symptom relief in constipation.^[48] Furthermore, fermentation byproducts like butyrate and other SCFAs have been shown to enhance epithelial barrier function and exert anti-inflammatory effects.^[50,51] However, not all probiotic strains produce equivalent effects, and factors such as baseline microbial diversity and the presence of specific bacterial taxa may influence individual responsiveness to supplementation.^[52–54] Looking ahead, future research should focus on identifying strain-specific and patient-specific responses to probiotic interventions through advanced microbiome profiling and mechanistic studies. There is also a pressing need to investigate the role of host genetics, diet, and lifestyle in modulating probiotic efficacy, paving the way for precision, individualized probiotic therapies for constipation.

4.2. Gut microbiota–host interaction and pathophysiology (green cluster)

This cluster encapsulates the growing recognition that dynamic host–microbe cross-talk, mediated through immune, metabolic, and neuroendocrine pathways, is central to the pathogenesis and management of constipation.^[22,23] Inflammation, altered mucosal immunity, and dysregulated microbial metabolism are increasingly implicated in gastrointestinal dysmotility and persistent symptoms.^[50] Research has shown that strains such as Lactobacillus paracasei and Bifidobacterium animalis can modulate cytokine production and strengthen barrier function, reducing inflammation and improving stool consistency.^[52] Moreover, the role of the microbiota–gut–brain axis is gaining attention, as microbial metabolites can influence both central and enteric nervous system signaling, directly affecting colonic motility and patient quality of life.^[54] Advances in metagenomic profiling have allowed for a more nuanced understanding of these interactions, revealing that individual differences in host genetics, diet, and baseline microbiota composition can significantly influence therapeutic outcomes.^[26,27] Future research should integrate multi-omics approaches and longitudinal cohort studies to unravel the complex bidirectional interactions between host and microbiome. Additionally, the development of predictive models based on host and microbial features may enable more effective, personalized interventions for constipation.

4.3. Dietary factors and microbiome analysis techniques (blue cluster)

Research within this cluster underscores the central role of diet and advanced analytical tools in shaping the gut microbiome and evaluating interventions for constipation.^[13,14] Dietary fibers, prebiotics, and oligosaccharides have consistently been shown to increase the abundance of beneficial taxa such as bifidobacteria and lactobacilli, promoting SCFA production and improving bowel habits.^[14,24] For example, supplementation with xylooligosaccharides and inulin-type fructans has been associated with enhanced microbial diversity and improved stool frequency in constipated individuals.^[13,24] Methodological innovations, including 16S rRNA sequencing and metagenomic analysis, have facilitated the identification of microbial signatures linked to therapeutic response, thus supporting more targeted dietary and probiotic interventions.^[31] With the ability to connect dietary patterns and interventions to specific microbial pathways, future research should prioritize personalized nutrition strategies and the development of functional foods tailored to individual microbiome profiles.^[27,31] Employing machine learning and advanced analytics to integrate dietary, clinical, and microbiome data could enable predictive modeling and optimization of dietary interventions. Well-designed intervention trials are also needed to validate the synergistic effects of dietary and probiotic treatments for constipation.

4.4. Epidemiology, prevalence, and population health (yellow cluster)

This cluster emphasizes the importance of large-scale studies in elucidating the distribution, determinants, and societal impact of constipation, as well as identifying populations most likely to benefit from probiotic interventions.^[3,4] Recent global meta-analyses have shown substantial variation in constipation prevalence by age, sex, and region, with elderly individuals and women at higher risk.^[3] These epidemiological insights are critical for designing preventive strategies and tailoring interventions to specific demographic groups.^[4,5] Additionally, population-based studies have begun to link constipation with comorbidities such as cardiovascular and neurological diseases, as well as modifiable lifestyle factors including diet and physical activity.^[8,9] The integration of microbiome data into epidemiological research is an emerging trend, facilitating the identification of microbiota-based risk markers for targeted interventions.^[29] Future research should focus on global, multicenter studies to harmonize data collection, development of microbiota-based risk scores, and assessment of the cost-effectiveness of population-level interventions. Implementing community-based, preventive programs that incorporate microbiome education and dietary guidance may also yield significant public health benefits.

4.5. Clinical management and therapeutic efficacy (purple cluster)

This cluster is defined by a critical mass of research evaluating the effectiveness, safety, and clinical application of probiotics and related interventions in constipation.^[7,19] Numerous RCTs and meta-analyses have demonstrated that specific strains, including Bifidobacterium lactis HN019 and Lactobacillus reuteri DSM 17938, are effective at increasing stool frequency and improving consistency across various populations.^[19,55] Nevertheless, heterogeneity in study design, probiotic formulations, and patient demographics persists, underscoring the need for standardized clinical protocols and comparative effectiveness research.^[55–57] Additional studies focusing on special populations, such as the elderly and patients with neurological comorbidities, suggest that probiotics may provide added benefits, including reduced bloating, enhanced quality of life, and even modulation of disease progression in conditions like PD.^[58–60] Looking forward, research should emphasize large-scale, strain-specific and dose-response studies, direct head-to-head comparisons with standard therapies, and long-term follow-up of safety and sustainability. Incorporating patient-centered outcomes and mechanistic endpoints, such as microbiome and metabolome changes, will be critical in translating research findings into clinical practice and developing individualized management strategies.

4.6. Clinical trials and study design (cyan cluster)

This cluster reflects the field’s methodological maturation, with a strong emphasis on randomized, double-blind, placebo-controlled trials as the gold standard for evaluating probiotic efficacy.^[26] Keywords such as “double-blind,” “clinical-trial,” and “quality-of-life” underscore the commitment to rigorous clinical research, with recent trials examining the effects of various probiotic strains on clinical endpoints in both functional constipation and irritable bowel syndrome (IBS-C).^[50,51] The centrality of this cluster in the keyword network aligns with consensus guidelines that highlight the need for well-powered, high-quality RCTs to clarify strain-specific effects, optimal dosing, and long-term safety.^[61,62] Recent literature also stresses the importance of standardizing patient selection, endpoints, and incorporating microbiome and metabolomic data to improve the interpretability and translational value of clinical studies.^[31] Future research should continue to refine trial methodologies, develop and validate advanced biomarkers for stratification and outcome assessment, and adopt pragmatic and adaptive trial designs to better reflect real-world effectiveness. Collaboration, data sharing, and meta-analytic approaches will be essential for synthesizing evidence and informing robust clinical recommendations for probiotic use in constipation.

The keyword burst analysis provides valuable insights into the temporal dynamics of research priorities, shedding light on the emergence and decline of key themes over time. By analyzing the progression of keywords, we can trace the field’s evolution and predict future research directions. In the early phases, keywords like “gut microbiota,” “clinical trial,” and “SCFAs” dominated the field, reflecting foundational studies on the mechanisms of probiotics in modulating gut health. These early investigations laid the groundwork for understanding probiotics’ role in restoring microbial balance, enhancing SCFA production, and improving colonic motility. Studies during this period primarily focused on experimental models and small-scale clinical trials. As the field matured, keywords such as “functional constipation,” “IBS,” and “immune modulation” gained prominence, indicating a shift toward exploring the therapeutic applications of probiotics in clinical settings. This phase saw an increase in RCTs investigating strain-specific effects on stool frequency, consistency, and gastrointestinal motility. The emergence of keywords like “double-blind” and “RCT” highlights the field’s growing emphasis on evidence-based practices and clinical validation.

Recent keyword bursts, such as “personalized medicine,” “gut-brain axis,” and “PD,” reflect the field’s shift toward more specialized and interdisciplinary research. The growing interest in personalized approaches underscores the need to tailor probiotic therapies based on individual microbiota profiles and clinical conditions.^[63,64] Additionally, the emerging focus on the gut-brain axis and its role in FGIDs and neurodegenerative diseases, such as PD, suggests a promising avenue for future exploration. Keywords like “inflammation” and “microbiota modulation” further highlight the importance of understanding the complex interactions between probiotics, immune responses, and systemic health.

The most recent keyword bursts, including “gut-brain axis” and “PD,” point to emerging research hotspots that are likely to dominate future investigations. These findings suggest that probiotics may play a broader role beyond gastrointestinal health, potentially influencing systemic conditions through microbiota modulation. Future research should prioritize high-quality, longitudinal studies to validate these emerging applications and establish evidence-based guidelines for their use.^[65–67]

4.7. Limitations

Despite its contributions, this study has limitations that should be acknowledged. The reliance on a single database may have excluded relevant literature from other sources, potentially limiting the scope of the analysis. Moreover, the exclusion of books, editorials, and gray literature might overlook important contributions that could provide additional perspectives. Finally, variations in keyword terminology, despite efforts to standardize terms, may have led to the omission of some relevant concepts.

5. Conclusion

This bibliometric study based on cluster analysis identified 6 major research hotspots in probiotics for constipation: microbial diversity and mechanisms, gut microbiota–host interaction and pathophysiology, dietary factors and microbiome analysis techniques, epidemiology, prevalence, and population health, clinical management and therapeutic efficacy, and clinical trials and study design. Citation burst analysis revealed a recent shift in research focus toward mechanisms, personalized interventions, and modulation of the gut microbiome. These findings comprehensively map the evolving landscape of probiotics research in constipation and provide valuable guidance for future investigations and clinical applications.

Author contributions

Conceptualization: Yirong Shen, Zhaoxiang Wang, Fengyan Tang.

Data curation: Yirong Shen, Zhaoxiang Wang, Xia Cheng, Songxian Rao.

Formal analysis: Yirong Shen, Xia Cheng, Fengyan Tang.

Writing – original draft: Yirong Shen, Zhaoxiang Wang, Xia Cheng, Fengyan Tang, Songxian Rao, Danni Zhang.

Writing – review & editing: Yirong Shen, Zhaoxiang Wang, Xia Cheng, Fengyan Tang, Songxian Rao, Danni Zhang.

Supplementary Material

medi-105-e48338-s001.pdf ^{(499.7KB, pdf)}