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. 2021 Apr 7;27(13):1341–1353. doi: 10.3748/wjg.v27.i13.1341

Global research trends in the microbiome related to irritable bowel syndrome: A bibliometric and visualized study

Sa'ed H Zyoud 1,2,3, Simon Smale 4, W Stephen Waring 5, Waleed Sweileh 6, Samah W Al-Jabi 7
PMCID: PMC8015301  PMID: 33833487

Abstract

BACKGROUND

Irritable bowel syndrome (IBS) is a common functional gastrointestinal disorder. Dysregulation of the gut–brain axis plays a central role in the pathophysiology of IBS. It is increasingly clear that the microbiome plays a key role in the development and normal functioning of the gut–brain axis.

AIM

To facilitate the identification of specific areas of focus that may be of relevance to future research. This study represents a bibliometric analysis of the literature pertaining to the microbiome in IBS to understand the development of this field.

METHODS

The data used in our bibliometric analysis were retrieved from the Scopus database. The terms related to IBS and microbiome were searched in titles or abstracts within the period of 2000–2019. VOSviewer software was used for data visualization.

RESULTS

A total of 13055 documents related to IBS were retrieved at the global level. There were 1872 scientific publications focused on the microbiome in IBS. There was a strong positive correlation between publication productivity related to IBS in all fields and productivity related to the microbiome in IBS (r = 0.951, P < 0.001). The United States was the most prolific country with 449 (24%) publications, followed by the United Kingdom (n = 176, 9.4%), China (n = 154, 8.2%), and Italy (n = 151, 8.1%). The h-index for all retrieved publications related to the microbiome in IBS was 138. The hot topics were stratified into four clusters: (1) The gut–brain axis related to IBS; (2) Clinical trials related to IBS and the microbiome; (3) Drug-mediated manipulation of the gut microbiome; and (4) The role of the altered composition of intestinal microbiota in IBS prevention.

CONCLUSION

This is the first study to evaluate and quantify global research productivity pertaining to the microbiome in IBS. The number of publications regarding the gut microbiota in IBS has continuously grown since 2013. This finding suggests that the future outlook for interventions targeting the gut microbiota in IBS remains promising.

Keywords: Irritable bowel syndrome, Bibliometric, Microbiota, Microbiome, Scopus, Brain gut axis

Core Tip: This is the first study to evaluate and quantify the global research productivity pertaining to the microbiome in irritable bowel syndrome (IBS). We present a holistic picture of this emerging topic and explore future research directions. A number of abnormalities have been described within the microbiome of patients with IBS. The relationships of these abnormalities to the causality of dysfunction and associated symptomatology have not been clearly elucidated. Our finding, while preliminary, suggests that the future outlook for interventions targeting the gut microbiota in IBS remains promising.

INTRODUCTION

Irritable bowel syndrome (IBS) is a term used to describe a group of symptoms, including abdominal pain and altered bowel habits, that arises because of disturbances of the interactions between the diet, the brain, the gut, and the microbiome. IBS poses a significant disease burden, with 20% of adults estimated to develop IBS symptoms in any given year. Symptoms arise as a consequence of abnormal visceral sensation and or motility as a result of abnormalities within the enteric or central nervous systems, or both[1]. This usually occurs in the absence of ‘organic’ disease, but the association with other gastrointestinal diseases is common. Many patients experiencing gastrointestinal inflammation due to infection or inflammatory bowel disease develop IBS symptoms[2]. Nearly a quarter of patients with IBS without identifiable ‘organic’ disease appear to have low-grade intestinal inflammation as judged by faecal inflammatory markers (calprotectin)[3]. Inflammation may lead to sensitization of peripheral nerves. Most inflammation within the gastrointestinal tract settles, but in susceptible individuals sensitization of peripheral afferents may persist. Such sensitization may be driven by ongoing mast cell activation and increased epithelial permeability associated with low-level inflammation[4].

The onset of symptoms in IBS is often associated with psychological stressors. A high proportion of people with IBS have psychological comorbidities. Chronic stress is associated with stress-induced hyperalgesia. This hyperalgesia is mediated via corticotrophin-releasing hormone and the hypothalamic–pituitary axis (HPA)[5]. Dysfunction within these systems is well documented in patients with functional gastrointestinal disorders and other chronic pain syndromes. Furthermore, many patients have histories of traumatic events in early life. These events may result in changes that profoundly affect the microbiome and brain development, predisposing patients to visceral pain syndromes[6-8]. In addition to direct effects on neurons proximal to the bowel, bacteria and their products have a profound effect on the development and activity of the central nervous system and, consequently, upon the psychological state and behaviors[9]. Within the enteric nervous system, certain bacterial strains may directly promote sensitization or downregulation of peripheral afferents. Of note, low-grade inflammation seen in a proportion of patients with IBS may result from the ability of specific bacteria to enhance the production and the effects of proinflammatory cytokines. Bacteria may also be able to transmit signals via the enteric nervous and immune systems to the central nervous system[10].

Although several bibliometric studies have been conducted to evaluate research productivity regarding various research aspects in the medical field[11-18], and some bibliometric studies have focused on microbiota science[19-25], there has not been an assessment of the research output regarding the microbiome in IBS. This study undertakes a bibliometric analysis of the literature within this field to understand the development of the literature pertaining to the microbiome in IBS and to facilitate the identification of specific areas of focus that may be of relevance to future research. This study evaluates data that will help to address the research gaps in this field. The current bibliometric study plays a significant role for researchers interested in the relationship between the microbiome and IBS, because it offers a quick reference guide for interdisciplinary researchers to know how this field has been assessed by scientific experts in previous years.

MATERIALS AND METHODS

The data used in our bibliometric analysis were retrieved from Scopus, which is a multidisciplinary database owned by Elsevier and is considered the largest and most widely used database[26-28]. Most of the publications in this field were published between 2000 and 2019. The following term combinations were searched in the title or abstract within this period: Terms related to IBS, i.e., ‘adaptive colitis’ OR ‘colon spasm’ OR ‘functional bowel disease’ OR ‘irritable bowel’ OR ‘irritable colon’ OR ‘membranous colitis’ OR ‘mucous colitis’ OR ‘spastic colitis’ OR ‘spastic colon’ OR ‘spastic bowel’ OR ‘functional colonic disease’ OR ‘colon irritable’ OR ‘colon neurosis’ OR ‘bowel neurosis’ OR ‘functional colopathy’ OR ‘functional colonopathy’ OR ‘chronic catarrhal colitis’ OR ‘colica mucosa’ OR ‘colonic enterospasm’ OR ‘dyskinesia of the colon’ OR ‘dyssynergia of the colon’ OR ‘functional enterocolonopathy’ OR ‘functional diarrhea’ OR ‘Glarry enteritis’ OR ‘glutinous diarrhea’ OR ‘intestinal croup’ OR ‘irritable gut syndrome’ OR ‘lienteric diarrhea’ OR ‘Membranous catarrh of the intestine’ OR ‘mucomembranous colic’ OR ‘myxoneurosis’ OR ‘nervous diarrhea’ OR ‘neurogenic mucous’ OR ‘nonspecific diarrhea’ OR ‘tubular diarrhea’ OR ‘unhappy colon’ OR ‘unstable colon’, and terms related to microbiome, i.e., ‘microbiome’ OR ‘microflora’ OR ‘microbiota’ OR ‘flora’ OR ‘probiotic’ OR ‘Saccharomyces’ OR ‘Lactobacillus’ OR ‘Bifidobacterium’ OR ‘Escherichia coli’. The terms were selected from related reviews on IBS[29,30] and the microbiome[19,20,31-33].

Data analysis

Microsoft Excel was used to analyze the retrieved data to calculate frequencies and percentages. The current bibliometric study included quantitative data about document types, language, country of the publications with their h-index and collaboration pattern, authors of the publications, journals that published papers on IBS, microbiome documents, and citation reports. In addition, we used the Statistical Package for the Social Sciences 16.0 software for Windows to assess the correlation between yearly quantitative distributions of publications related to IBS in all fields and publications related to the microbiome in IBS by using the Pearson correlation test. Analysis with P < 0.05 is considered statistically significant. In addition, the VOSviewer program[34,35] was used for mapping and clustering terms according to their occurrence in both titles and abstracts to determine hot topics in this field. Furthermore, network visualization maps for collaboration among the most productive countries and the most prolific authors in this field were prepared using VOSviewer.

RESULTS

A total of 13055 documents related to IBS in titles and abstracts were retrieved over the period of 2000–2019 at the global level. There were 1872 scientific publications focused on the microbiome in IBS. The research findings showed that English was the main research language of documents indexed in Scopus, accounting for 48.8% of the documents, followed by German (3.9%) and Chinese (2.9%). Articles were the main type of document for publications related to the microbiome and IBS, accounting for 51.9% of documents, followed by reviews (35.3%).

The number of publications related to the microbiome in IBS has increased year by year. The quantity of documents has increased each year, from 9 documents in 2000, to 84 documents in 2009, to 219 documents in 2019 (Figure 1). Published papers during the last 5 years (2015 to 2019) accounted for 47.0% of the total publications. There was a strong positive correlation between the publication productivity related to IBS in all fields and the productivity related to the microbiome in IBS (r = 0.951, P < 0.001).

Figure 1.

Figure 1

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The annual number of publications related to irritable bowel syndrome and the microbiome from 2000 to 2019. IBS: Irritable bowel syndrome.

In total, authors from 105 countries published their work on the microbiome and IBS topics. Table 1 lists the top 10 most prolific countries. The United States was the most prolific country with 449 (24%) publications, followed by the United Kingdom (n = 176, 9.4%), China (n = 154, 8.2%), and Italy (n = 151, 8.1%). The h-index for all retrieved publications related to the microbiome in IBS was 138. Figure 2 shows the network visualization map for the collaboration among the 40 most productive countries. This includes countries that published more than 5 papers on microbiome and IBS research according to the number of publications in the last two decades (2000–2019). The United States and the United Kingdom can be referred to as central countries for this network because they published research in collaboration with 40 and 31 countries, respectively. In total, 5960 authors published their work on the microbiome and IBS topics. Figure 3 shows the network visualization map for the collaboration among the 32 most productive authors (authors who published more than 10 papers) on the microbiome in IBS research according to the number of publications in the last two decades (2000–2019). EMM Quigley (United States), G Barbara (Italy), JF Cryan (Ireland), and TG Dinan (Ireland) can be considered the prolific authors of this network due to the fact that they published 61, 25, 25, and 23 documents, respectively.

Table 1.

Top 10 most productive countries on the microbiome in irritable bowel syndrome research, ranked by the total number of publications in the last two decades (2000-2019)

SCR
Country
Number of documents
%
1st United States 449 24.0
2nd United Kingdom 176 9.4
3rd China 154 8.2
4th Italy 151 8.1
5th France 116 6.2
6th Germany 107 5.7
7th Canada 103 5.5
8th Ireland 102 5.4
9th Australia 72 3.8
10th Spain 69 3.7
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SCR: Standard competition ranking.

Figure 2.

Figure 2

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Network visualization map for the collaboration among the 40 most productive countries on the microbiome in irritable bowel syndrome research according to the number of publications in the last two decades (2000–2019).

Figure 3.

Figure 3

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Network visualization map for the collaboration among the 32 most productive authors on the microbiome in irritable bowel syndrome research according to the number of publications in the last two decades (2000–2019).

Terms were extracted from the titles and abstracts of all retrieved publications related to the microbiome in IBS and analyzed by the VOSviewer software to identify the current state and hot topics in this field. Terms appearing more than 10 times were included in the map (Figure 4) and were stratified into four clusters: IBS related to the gut–brain axis (yellow cluster), clinical trials related to IBS and the microbiome (red cluster), drug-mediated manipulation of the gut microbiome (blue cluster), and the role of the altered composition of intestinal microbiota in IBS prevention (green cluster).

Figure 4.

Figure 4

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Network visualization map for the terms with high co-occurrence frequencies, based on the titles and abstracts of documents related to the microbiome in irritable bowel syndrome research published in the last two decades (2000–2019).

The top 10 journals accounted for 19.98% of all articles (Table 2). The four journals that published the most studies related to microbiome and IBS were World Journal of Gastroenterology (n = 70), Alimentary Pharmacology and Therapeutics (n = 54), Neurogastroenterology and Motility (n = 52), and the Journal of Clinical Gastroenterology (n = 39).

Table 2.

Top 10 most productive journals on the microbiome in irritable bowel syndrome research, ranked by the total number of publications in the last two decades (2000-2019)

SCR1
Journal
Frequency
%
IF2
1st World Journal of Gastroenterology 70 3.74 3.665
2nd Alimentary Pharmacology and Therapeutics 54 2.88 7.515
3rd Neurogastroenterology and Motility 52 2.78 2.946
4th Journal of Clinical Gastroenterology 39 2.08 2.973
5th American Journal of Gastroenterology 34 1.82 10.171
6th Gastroenterology 33 1.76 17.373
7th Current Opinion in Gastroenterology 27 1.44 3.225
8th PLoS One 24 1.28 2.740
9th Nutrients 21 1.12 4.546
10th Gut Microbes 20 1.07 7.740
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1

Equal journals have the same ranking number, and then a gap is left in the ranking numbers.

2

Impact factors based on Journal Citation Reports 2019 from Clarivate Analytics.

SCR: Standard competition ranking; IF: Impact factor.

The sample presents an average citation rate of 42 citations per publication. However, 16.6% of the publications have never been cited. Table 3 lists the information on the top ranking of publications in terms of the highest number of citations[36-55]. The article ‘Prebiotic Effects: Metabolic and Health Benefits” is the most cited article with 1147 citations; it was authored by Roberfroid et al[49] and published in the British Journal of Nutrition in 2010. This study reported that a substantial number of studies about human intervention have shown that dietary intake of food products/ingredients/ supplements results in statistically important improvements in the faecal gut microbiota composition. The second most highly cited article is ‘Lactobacillus and Bifidobacterium in IBS: Symptom Responses and Relationship to Cytokine Profiles’ by O'Mahony et al[44] and published in Gastroenterology in 2005. This study showed that intake of Bifidobacterium infantis over 8 wk was associated with symptomatic improvement in IBS.

Table 3.

Top 20 most cited articles on the microbiome in irritable bowel syndrome research in the last two decades (2000-2019)

SCR
Ref.
Title
Year
Source title
Cited by
1st Roberfroid et al[49] "Prebiotic effects: Metabolic and health benefits" 2010 British Journal of Nutrition 1147
2nd O'Mahony et al[44] "Lactobacillus and Bifidobacterium in irritable bowel syndrome: Symptom responses and relationship to cytokine profiles" 2005 Gastroenterology 1042
3rd Claesson et al[37] "Composition, variability, and temporal stability of the intestinal microbiota of the elderly" 2011 Proceedings of the National Academy of Sciences of the United States of America 836
4th Collins et al[38] "The interplay between the intestinal microbiota and the brain” 2012 Nature Reviews Microbiology 735
5th Kassinen et al[40] "The fecal microbiota of irritable bowel syndrome patients differs significantly from that of healthy subjects” 2007 Gastroenterology 684
6th Pimentel et al[46] "Rifaximin therapy for patients with irritable bowel syndrome without constipation" 2011 New England Journal of Medicine 659
7th Rinttilä et al[48] "Development of an extensive set of 16S rDNA-targeted primers for quantification of pathogenic and indigenous bacteria in faecal samples by real-time PCR" 2004 Journal of Applied Microbiology 658
8th O'Mahony et al[45] "Early life stress alters behavior, immunity, and microbiota in rats: implications for irritable bowel syndrome and psychiatric illnesses " 2009 Biological Psychiatry 634
9th Rolfe[50] “The role of probiotic cultures in the control of gastrointestinal health” 2000 Journal of Nutrition 584
10h Carabotti et al[36] “The gut-brain axis: Interactions between enteric microbiota, central and enteric nervous systems" 2015 Annals of Gastroenterology 580
11th De Vrese and Schrezenmeir[39] "Probiotics, prebiotics, and synbiotics" 2008 Advances in Biochemical Engineering/Biotechnology 575
12th Rajilić-Stojanović et al[47] "Global and deep molecular analysis of microbiota signatures in fecal samples from patients with irritable bowel syndrome" 2011 Gastroenterology 545
13th Whorwell et al[55] "Efficacy of an encapsulated probiotic Bifidobacterium infantis 35624 in women with irritable bowel syndrome" 2006 American Journal of Gastroenterology 541
13th Swidsinski et al[54] "Spatial organization and composition of the mucosal flora in patients with inflammatory bowel disease" 2005 Journal of Clinical Microbiology 541
15th Malinen et al[41] "Analysis of the fecal microbiota of irritable bowel syndrome patients and healthy controls with real-time PCR" 2005 American Journal of Gastroenterology 523
16th Mayer et al[42] "Gut/brain axis and the microbiota" 2015 Journal of Clinical Investigation 519
17th Simrén et al[52] "Intestinal microbiota in functional bowel disorders: A Rome foundation report" 2013 Gut 510
18th Spiller and Garsed[53] "Postinfectious irritable bowel syndrome " 2009 Gastroenterology 508
19th Rousseaux et al[51] "Lactobacillus acidophilus modulates intestinal pain and induces opioid and cannabinoid receptors" 2007 Nature Medicine 500
20th Nobaek et al[43] "Alteration of intestinal microflora is associated with reduction in abdominal bloating and pain in patients with irritable bowel syndrome" 2000 American Journal of Gastroenterology 498
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Table 4 presents the top 10 most productive institutions on the microbiome in IBS research, ranked by the total number of publications. The four institutions that have published the most studies related to microbiome and IBS are the University College Cork (n = 87), APC Microbiome Ireland (n = 84), McMaster University (n = 45), the Mayo Clinic (n = 32), and Alma Mater Studiorum Università di Bologna (n = 38) (Table 4).

Table 4.

Top 10 most productive institutions on the microbiome in irritable bowel syndrome research, ranked by the total number of publications in the last two decades (2000-2019)

SCR1
Institute
Country
n
%
1st University College Cork Ireland 87 4.65
2nd APC Microbiome Ireland Ireland 84 4.49
3rd McMaster University Canada 45 2.40
4th Alma Mater Studiorum Università di Bologna Italy 38 2.03
5th Helsingin Yliopisto Finland 36 1.92
5th Mayo Clinic United States 36 1.92
7th Inserm (Institut national de la santé et de la recherche médicale) France 30 1.60
8th Baylor College of Medicine United States 27 1.44
9th Göteborgs Universitet Sweden 27 1.44
10th The University of North Carolina at Chapel Hill United States 27 1.44
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1

Equal institutes have the same ranking number, and then a gap is left in the ranking numbers.

SCR: Standard competition ranking.

DISCUSSION

This bibliometric study was carried out using data from Scopus for the period of 2000–2019. It presents a comprehensive review of research progress on the microbiome and IBS, identifies hot topics within this field, and indicates potential directions for future research. It is apparent that the research productivity in this field has progressively increased due to the increasing recognition of the role of the gut microbiota[56,57]. In addition, this increase is probably linked to the growing number of researchers who are interested in the fields of neurology and gastroenterology [e.g., EMM Quigley (the United States), JF Cryan (Ireland), TG Dinan (Ireland), G Barbara (Italy), Y Ringel (the United States), M Simrén (Sweden), M Camilleri (the United States), A Palva (Finland), M Pimentel (Canada), NJ Talley (Australia), and others]. Over the last two decades, advances in our understanding of the enteric and central nervous systems have led to an evolving understanding of their interactions and how the gastrointestinal microbiome influences their function. Disturbances in the gastrointestinal microbiome have been identified in patients with functional gastrointestinal disease, like IBS, and it is often the case that symptoms may be triggered by events that lead to changes in the microbiome, where the emotional context and the enteric nervous system function in tandem[1].

The results of this study indicate that the United States has been the most prolific country in this field. These findings are consistent with many previous bibliometric studies[12,58]. Research productivity in the United States is likely associated with overwhelming support in terms of research, the wide range of researchers with an interest within this field, several well-resourced research environments, and greater availability of a well-trained workforce. In addition, the economic strength of the United States has led to a substantial amount of financial support for researchers and has enhanced the mobility of researchers[59,60]. Furthermore, in 2013, the United States launched an exceptional research project on the gut microbiota–brain axis[61], thus contributing to the increasing number of publications regarding the microbiome in IBS.

Our study demonstrates that the gut–brain axis has become the most prolific area for research within IBS and the microbiome globally, and several studies in a range of journals are proof of this emerging trend. According to these data, we can infer that central pain amplification occurs through a wide variety of mechanisms within the central nervous system and mediates the effects of mood, emotional context, and environmental circumstances upon our central pain perception. Functional magnetic resonance imaging (fMRI) studies have demonstrated that patients with IBS often display an exaggerated response of arousal circuits associated with the HPA and activation of endogenous pain pathways in response to visceral stimulation. Similarly, studies have shown enhanced anticipation of pain in response to conditioning stimuli in patients with functional gastrointestinal disease[62]. Neuro-immune activation within the central nervous system is associated with altered astrocyte and microglial activity that further enhances central sensitisation.

Early deprivation in patients with IBS can have profound effects on the microbiome, and researchers recognise that these factors may predispose susceptible individuals to more severe IBS[8,63-66]. Changes in central nervous system function arise as a result of microbial products, which then influence astrocyte, microglial, and central nervous system inflammatory responses[67]. Certain bacterial strains, possibly as a result of being able to modulate these effects, may influence behaviour. Offspring of mice fed a high-fat diet display disordered behaviour and socialisation. These behavioural changes appear to be manifested by alterations in the microbiome. Correction of ‘bacterial deficits’ or their metabolic sequelae leads to improvements in behaviour. Specific bacterial strains have been demonstrated to increase resilience in individuals with anxiety, and these behavioural changes have neurological correlates in fMRI studies. Those factors known to provoke IBS have profound effects on the microbiome function; gastroenteritis can deplete the microbiome, and psychological stress can lead to significant changes in the representation of different phyla within the microbial flora. These potentially detrimental changes may facilitate feedback from the gut and, consequently, permit the gut to have effects on mood, behaviour, and cognitive functions.

Limitations

There are some limitations in our study that are similar to previous bibliometric studies. First, although Scopus is the most recognized and the largest database for peer-reviewed literature, our study is restricted to only the Scopus database as a source of data collection. Second, some authors or institutions have different name formats in the Scopus database, and their research count might be scattered; therefore, their names might not show in the active list. Despite these limitations, we still consider that the findings of our analysis were adequate to characterize accurately the state of IBS and microbiome research at the global level.

CONCLUSION

This is the first study to evaluate and quantify the global research productivity pertaining to the microbiome in IBS to present a holistic picture of this emerging topic and explore future research directions. The number of publications regarding the gut microbiota in IBS has continuously grown since 2013. The United States, the United Kingdom, Italy, and Ireland have been the most productive regions. Currently, the main hot topics regarding the gut microbiota in IBS are the gut–brain axis related to IBS, clinical trials related to IBS and the microbiome, drug-mediated manipulation of the gut microbiome, and the role of the altered composition of intestinal microbiota in IBS prevention. A number of abnormalities have been described within the microbiome of patients with IBS. The relationship between these abnormalities and the causality of dysfunction and associated symptomatology have yet to be clearly elucidated. Our findings, while preliminary, suggest that the future outlook for interventions targeting the gut microbiota in IBS remains promising.

ARTICLE HIGHLIGHTS

Research background

The ability of specific bacteria to boost the development and the effects of proinflammatory cytokines can result in low-grade inflammation seen in a proportion of patients with irritable bowel syndrome (IBS).

Research motivation

The current bibliometric analysis plays an important role for researchers interested in the relationship between the microbiome and IBS. It provides a simple reference guide for interdisciplinary researchers to learn how scientific experts have examined this area in previous years.

Research objectives

This study aimed to carry out a bibliometric review of the IBS and the microbiome literature to explain the growth of this field and assist the identification of unique focus areas that may be important for future research.

Research methods

The information used in our bibliometric research was derived from the Scopus database. Terms related to IBS and the microbiome were searched in titles or abstracts during the period of 2000–2019. For data visualization, VOSviewer software was used.

Research results

Since 2013, the number of publications on gut microbiota in IBS has continuously increased. This result indicates that the future outlook remains optimistic for treatments targeting the gut microbiota in IBS.

Research conclusions

This is the first study to analyze and measure the global research productivity of IBS and microbiome research to provide a holistic view of this evolving subject and explore future research directions. It is evident that, due to the growing understanding of the role of the gut microbiota, research productivity in this area has steadily increased. Currently, the key hot topics are the gut–brain axis related to IBS, clinical trials related to IBS and the microbiome, drug-mediated modulation of the gut microbiome, and the role of the altered composition of the intestinal microbiome in the prevention of IBS.

Research perspectives

Our results indicate that the future outlook for IBS therapies targeting the intestinal microbiota remains promising.

Footnotes

Conflict-of-interest statement: The authors have no financial disclosures or conflicts of interest to declare.

PRISMA 2009 Checklist statement: The authors have read the PRISMA 2009 Checklist, and the manuscript was prepared and revised according to the PRISMA 2009 Checklist.

Manuscript source: Invited manuscript

Peer-review started: November 18, 2020

First decision: December 27, 2020

Article in press: March 16, 2021

Specialty type: Gastroenterology and hepatology

Country/Territory of origin: Palestine

Peer-review report’s scientific quality classification

Grade A (Excellent): 0

Grade B (Very good): B

Grade C (Good): 0

Grade D (Fair): 0

Grade E (Poor): 0

P-Reviewer: Gazouli M S-Editor: Fan JR L-Editor: A P-Editor: Li JH

Contributor Information

Sa'ed H Zyoud, Poison Control and Drug Information Center (PCDIC), College of Medicine and Health Sciences, An-Najah National University, Nablus 44839, West Bank, Palestine. saedzyoud@yahoo.com; Department of Clinical and Community Pharmacy, College of Medicine and Health Sciences, An-Najah National University, Nablus 44839, West Bank, Palestine; Department of Clinical Research Centre, An-Najah National University Hospital, Nablus 44839, West Bank, Palestine.

Simon Smale, Department of Gastroenterology, York Hospital, York Teaching Hospital NHS Foundation Trust, York YO31 8HE, United Kingdom.

W Stephen Waring, Acute Medical Unit, York Teaching Hospitals NHS Foundation Trust, York YO31 8HE, United Kingdom.

Waleed Sweileh, Department of Pharmacology and Toxicology, College of Medicine and Health Sciences, An-Najah National University, Nablus 44839, West Bank, Palestine.

Samah W Al-Jabi, Department of Clinical and Community Pharmacy, College of Medicine and Health Sciences, An-Najah National University, Nablus 44839, West Bank, Palestine.

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