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

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.

Global research trends in microbiome-gut-brain axis during 2009-2018: a bibliometric and visualized study.

BACKGROUND: The pathways and mechanism by which associations between the gut microbiome and the brain, termed the microbiome-gut-brain axis (MGBA), are manifest but remain to be fully elucidated. This study aims to use bibliometric analysis to estimate the global activity within this rapidly developing field and to identify particular areas of focus that are of current relevance to the MGBA during the last decade (2009-2018). METHODS: The current study uses the Scopus for data collection. We used the key terms "microbiome-gut-brain axis" and its synonyms because we are concerned with MGBA per se as a new concept in research rather than related topics. A VOSviewer version 1.6.11 was used to visualize collaboration pattern between countries and authors, and evolving research topics by analysis of the term co-occurrence in the title and abstract of publications. RESULTS: Between 2009 and 2018, there were 51,504 published documents related to the microbiome, including 1713 articles related to the MGBA: 829 (48.4%) original articles, 658(38.4%) reviews, and 226 (13.2%) other articles such as notes, editorials or letters. The USA took the first place with 385 appearances, followed by Ireland (n = 161), China (n = 155), and Canada (n = 144).The overall citation h-index was 106, and the countries with the highest h-index values were the USA (69), Ireland (58), and Canada (43). The cluster analysis demonstrated that the dominant fields of the MGBA include four clusters with four research directions: "modeling MGBA in animal systems", "interplay between the gut microbiota and the immune system", "irritable bowel syndrome related to gut microbiota", and "neurodegenerative diseases related to gut microbiota". CONCLUSIONS: This study demonstrates that the research on the MGBA has been becoming progressively more extensive at global level over the past 10 years. Overall, our study found that a large amount of work on MGBA focused on immunomodulation, irritable bowel syndrome, and neurodevelopmental disorders. Despite considerable progress illustrating the communication between the gut microbiome and the brain over the past 10 years, many issues remain about their relevance for therapeutic intervention of many diseases.

Validation of a care pathway for the use of faecal calprotectin in monitoring patients with Crohn's disease.

INTRODUCTION: We have previously published an evidence-based care pathway for the use of faecal calprotectin (FC) to monitor patients with Crohn's disease established on therapy. Patients are treated as low, intermediate or high risk of continuing Crohn's disease activity based on their FC, whatever their phenotype and surgical status are. Low-risk patients (FC <100 µg/g) are offered 12 monthly follow-ups or step down of therapy if asymptomatic or initial expectant symptomatic treatment. Intermediate-risk patients (FC 100-250 µg/g) are reviewed at 6 months with a repeat FC. High-risk patients (two consecutive FCs >250 µg/g) are flagged up to the responsible clinician as likely having an active Crohn's disease. METHODS: To validate this care pathway over a 2-year period, by determining its negative predictive value (NPV) and positive predictive value (PPV). RESULTS: 123 patients were managed by means of the care pathway for a mean of 24.4 months. The NPV and PPV were 0.97 (CI 0.93 to 0.98) and 0.85 (CI 0.80 to 0.94), respectively (sensitivity: 0.92 (0.83 to 0.96) and specificity: 0.95 (0.92 to 0.98)). Importantly 69% of patients with FC >250 µg/g were in clinical remission, the care pathway identifying patients who would benefit from presymptomatic disease modification. CONCLUSIONS: This validation of a pragmatic clinical care pathway demonstrates a safe and effective mechanism by which to use FC to monitor risk of disease activity in patients with Crohn's disease established on therapy. It provides a framework for prioritising follow-up and for identifying patients at risk of continuing disease activity or those in whom therapy could be stepped down.

Prevalence and mechanism of nonsteroidal anti-inflammatory drug-induced clinical relapse in patients with inflammatory bowel disease.

BACKGROUND & AIMS: It has been variably suggested that nonselective NSAIDs and cyclooxygenase (COX)-2 selective inhibitors aggravate or ameliorate clinical disease activity in patients with inflammatory bowel disease. We assessed the effect of these drugs in patients with inflammatory bowel disease (n = 209) and the possible mechanisms. METHODS: First, patients with quiescent Crohn's disease and ulcerative colitis received the non-NSAID analgesic acetaminophen (n = 26) and the conventional NSAIDs naproxen (n = 32), diclofenac (n = 29), and indomethacin (n = 22) for 4 weeks. The Harvey-Bradshaw index was used to define relapse. Second, to assess the mechanism of relapse, intestinal inflammation was quantitated (fecal calprotectin) before and during treatment (20 patients/group) with acetaminophen, naproxen (topical effect, COX-1 and -2 inhibitor), nabumetone (COX-1 and -2 inhibitor), nimesulide (selective COX-2 inhibitor), and low-dose aspirin (selective COX-1 inhibition). RESULTS: Nonselective NSAIDs were associated with a 17%-28% relapse rate within 9 days of ingestion. No patient had an early relapse on acetaminophen, nimesulide, or aspirin, whereas those on naproxen and nabumetone (20%) experienced relapse. These clinical relapses were associated with escalating intestinal inflammatory activity. CONCLUSIONS: NSAID ingestion is associated with frequent and early clinical relapse of quiescent inflammatory bowel disease, and the mechanism appears to be due to dual inhibition of the COX enzymes. Selective COX-2 inhibition with nimesulide and COX-1 inhibition with low-dose aspirin appear to be well-tolerated in the short-term.

Determining small bowel integrity following drug treatment.

Intestinal integrity is maintained by a delicate balance between mucosal defence and luminal aggressors that cause damage if exposed to the mucosa. The intestinal barrier function appears to be the gatekeeper for controlling this balance. It is becoming increasingly clear that if the intestinal barrier is disrupted the consequences are low grade intestinal inflammation which carry with it the risk of significant blood and protein loss both of which may cause clinical management problems. We review the strength and weaknesses of methods for assessing small bowel function that are useful for assessing drug-induced intestinal toxicity. There are a number of imaging methods for assessing intestinal integrity but these do not provide functional information. Intestinal permeability measurements have been optimized for specificity and there are now ways of measuring intestinal permeability regionally, but marker analyses continue to be cumbersome. Recent developments of faecal inflammatory markers make it a matter of routine to assess this in any routine chemical pathology laboratory. Bleeding, protein loss and other complications of inflammation can also be measured with good specificity, but again the methods are cumbersome. Using a combination of functional and imaging techniques it is now possible to characterize and define with precision, the small bowel side-effects of drugs, the best example being the small bowel side-effects of nonsteroidal anti-inflammatory drugs (NSAIDs).