|
1
|
Black CJ, Ford AC. An evidence-based update on the diagnosis and management of irritable bowel syndrome. Expert Rev Gastroenterol Hepatol 2025:1-16. [PMID: 39835671 DOI: 10.1080/17474124.2025.2455586] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/08/2024] [Accepted: 01/15/2025] [Indexed: 01/22/2025]
Abstract
INTRODUCTION Irritable bowel syndrome (IBS) is a disorder of gut-brain interaction affecting 5% of the population. The cardinal symptoms are abdominal pain and altered stool form or frequency. AREAS COVERED Diagnosis and management of IBS. We searched the literature for diagnostic accuracy studies, randomized controlled trials, and meta-analyses. A positive diagnosis of IBS, alongside testing to exclude celiac disease, is recommended. Exhaustive investigation has a low yield. Patients should be offered traditional dietary advice. If response is incomplete, specialist dietetic guidance should be considered. Probiotics may be beneficial, but quality of evidence is poor. First-line treatment of constipation is with laxatives, with secretagogues used where these are ineffective. Anti-diarrheal drugs should be used first-line for diarrhea, with second-line drugs including 5-hydroxytryptamine-3 antagonists, eluxadoline, or rifaximin, where available. First-line treatment of abdominal pain should be with antispasmodics, with gut-brain neuromodulators prescribed second-line. Low-dose tricyclic antidepressants, such as amitriptyline, are preferred. Brain-gut behavioral therapies are effective and have evidence for efficacy in patients refractory to standard therapies. EXPERT OPINION Despite substantial advances, there remains scope for improvement in terms of both the diagnosis and management of IBS. Reinforcement of positive diagnostic strategies for the condition and novel treatment paradigms are required.
Collapse
Affiliation(s)
- Christopher J Black
- Leeds Gastroenterology Institute, St. James's University Hospital, Leeds, UK
- Leeds Institute of Medical Research at St. James's, University of Leeds, Leeds, UK
| | - Alexander C Ford
- Leeds Gastroenterology Institute, St. James's University Hospital, Leeds, UK
- Leeds Institute of Medical Research at St. James's, University of Leeds, Leeds, UK
| |
Collapse
|
|
2
|
Venge P, Tejera VC, Petersson C, Xu S, Larsson A, Simrén M, Öhman L, Törnblom H. Elevated Fecal Biomarkers of Colo-Rectal Epithelial Cell Activity in Irritable Bowel Syndrome. Neurogastroenterol Motil 2024:e14984. [PMID: 39688084 DOI: 10.1111/nmo.14984] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/29/2024] [Revised: 11/18/2024] [Accepted: 12/03/2024] [Indexed: 12/18/2024]
Abstract
BACKGROUND Irritable bowel syndrome (IBS) is a common functional gastro-intestinal disorder characterized by discomfort with constipation and/or diarrhea with unclear pathophysiology. We aimed to determine the activities of colorectal eosinophils, neutrophils and epithelial cells by biomarkers in feces reflecting these activities. METHODS Fecal samples were collected from 185 patients with IBS before and after 8 weeks of placebo or mesalazine treatment and from 40 healthy subjects. Calprotectin, eosinophil derived neurotoxin (EDN), eosinophil cationic protein (ECP), human neutrophil lipocalin (HNL) (pab/765) or dimer, human phospholipase BII-precursor (HPLBII-P) and myeloperoxidase (MPO) were measured by ELISA. Symptom scores were evaluated by diaries. RESULTS HPLBII-P, HNL (pab/765) and EDN, proteins secreted by intestinal epithelial cells, were elevated in IBS patients as compared to healthy subjects (p < 0.0001-p = 0.008). In contrast, the neutrophil proteins calprotectin, MPO and HNL dimer were unaltered. The eosinophilic protein ECP was lower in IBS (p = 0.001). HNL (pab/765) (p = 0.01) and EDN (p = 0.004) increased in IBS patients after mesalazine treatment. Colo-rectal mucosa showed strong staining of HPLBII-P and western blotting of fecal extracts showed the presence of mainly monomeric, epithelial-associated HNL. CONCLUSIONS The absence of signs of involvement of neutrophils and eosinophils in IBS suggests that activity of local epithelial cells rather than inflammation may be a major determinant of the disease. The measurements of EDN, HNL (pab/765), and HPLBII-P may serve as potential fecal biomarkers in the study and monitoring of IBS.
Collapse
Affiliation(s)
- Per Venge
- Department of Medical Sciences, Uppsala University and Diagnostics Development, Uppsala, Sweden
- Diagnostics Development, Uppsala, Sweden
| | - Valeria Castro Tejera
- Department of Molecular and Clinical Medicine, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden
| | - Christer Petersson
- Department of Medical Sciences, Uppsala University and Diagnostics Development, Uppsala, Sweden
| | - Shengyuan Xu
- Department of Medical Sciences, Uppsala University and Diagnostics Development, Uppsala, Sweden
| | - Anders Larsson
- Department of Medical Sciences, Uppsala University and Diagnostics Development, Uppsala, Sweden
| | - Magnus Simrén
- Department of Molecular and Clinical Medicine, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden
- Center for Functional GI and Motility Disorders, University of North Carolina-Chapel Hill, Chapel Hill, North Carolina, USA
| | - Lena Öhman
- Department of Microbiology and Immunology, Institute of Biomedicine, University of Gothenburg, Gothenburg, Sweden
| | - Hans Törnblom
- Department of Molecular and Clinical Medicine, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden
| |
Collapse
|
|
3
|
Pastras P, Aggeletopoulou I, Triantos C. Impact of Enteric Nervous Cells on Irritable Bowel Syndrome: Potential Treatment Options. Microorganisms 2024; 12:2036. [PMID: 39458345 PMCID: PMC11510338 DOI: 10.3390/microorganisms12102036] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/26/2024] [Revised: 10/04/2024] [Accepted: 10/05/2024] [Indexed: 10/28/2024] Open
Abstract
Irritable bowel syndrome (IBS) is a condition that significantly impacts the lifestyle, health, and habits of numerous individuals worldwide. Its diagnosis and classification are based on the Rome criteria, updated periodically to reflect new research findings in this field. IBS can be classified into different types based on symptoms, each with distinct treatment approaches and some differences in their pathophysiology. The exact pathological background of IBS remains unclear, with many aspects still unknown. Recent research developments suggest that disorders in the brain-gut-microbiota axis are key contributors to the symptoms and severity of IBS. The central nervous system (CNS) interacts bidirectionally with intestinal processes within the lumen and the intestinal wall, with the autonomic nervous system, particularly the vagus nerve, playing an important role. However, the enteric nervous system (ENS) is also crucial in the pathophysiological pathway of IBS. The apeline-corticotropin-releasing factor (CRF)-toll-like receptor 4 (TLR4) signaling route via enteric glia and serotonin production in enteroendocrine cells at the enteric barrier are among the most well-understood new findings that affect IBS through the ENS. Additionally, the microbiota regulates neuronal signals, modifying enteric function by altering the number of enteric bacteria and other mechanisms. Given the limited therapeutic options currently available, it is essential to identify new treatment targets, with the brain-gut axis, particularly the enteric nervous system, being a promising focus. This study aims to delineate the molecular mechanisms that induce IBS and to suggest potential targets for future research and treatment of this potentially debilitating disease.
Collapse
Affiliation(s)
| | - Ioanna Aggeletopoulou
- Division of Gastroenterology, Department of Internal Medicine, University Hospital of Patras, 26504 Patras, Greece; (P.P.); (C.T.)
| | | |
Collapse
|
|
4
|
Lo SW, Hung TH, Lin YT, Lee CS, Chen CY, Fang CJ, Lai PC. Clinical efficacy and safety of faecal microbiota transplantation in the treatment of irritable bowel syndrome: a systematic review, meta-analysis and trial sequential analysis. Eur J Med Res 2024; 29:464. [PMID: 39289768 PMCID: PMC11409544 DOI: 10.1186/s40001-024-02046-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/19/2024] [Accepted: 08/30/2024] [Indexed: 09/19/2024] Open
Abstract
BACKGROUND The aim of this study is to evaluate the efficacy and safety of faecal microbiota transplantation (FMT) for the treatment of irritable bowel syndrome (IBS). METHODS We searched four databases for randomised controlled trials (RCTs) that compared FMT with a control intervention in patients with IBS. The revised Cochrane risk-of-bias (RoB) tool was chosen for appraisal. Meta-analysis with trial sequential analysis (TSA) was conducted. Grading of Recommendations Assessment Development and Evaluation (GRADE) methodology was used to assess the certainty of evidence (CoE). RESULTS We included 12 RCTs with a total of 615 participants. Meta-analyses showed no significant difference between the FMT and control groups in terms of clinical responses (relative risk [RR] = 1.44, 95% confidence interval [CI] 0.88-2.33) and changes in IBS Severity Scoring System (IBS-SSS) scores (standardised mean difference [SMD] = - 0.31, 95% CI - 0.72 to 0.09) and IBS Quality of Life (IBS-QOL) scores (SMD = 0.30, 95% CI - 0.09 to 0.69). Subgroup analysis revealed that in studies with low RoB and using endoscopy, nasojejunal tube and rectal enema delivery, FMT led to a significant improvement in clinical responses and changes in IBS-SSS and IBS-QOL scores. TSA suggested that the current evidence is inconclusive and that the CoE is very low. CONCLUSION This study suggests that patients with IBS may benefit from FMT especially when it is administered via endoscopy, nasojejunal tube or rectal enema. However, the certainty of evidence is very low. Further research is needed to confirm the efficacy and safety of FMT for IBS treatment. TRIAL REGISTRATION PROSPERO registration number CRD42020211002.
Collapse
Affiliation(s)
- Shao-Wei Lo
- Education Centre, College of Medicine, National Cheng Kung University Hospital, National Cheng Kung University, No.138, Sheng Li Road, Tainan, 704, Taiwan
| | - Tsung-Hsuan Hung
- Education Centre, College of Medicine, National Cheng Kung University Hospital, National Cheng Kung University, No.138, Sheng Li Road, Tainan, 704, Taiwan
| | - Yen-Tsen Lin
- Education Centre, College of Medicine, National Cheng Kung University Hospital, National Cheng Kung University, No.138, Sheng Li Road, Tainan, 704, Taiwan
| | - Chun-Shen Lee
- Education Centre, College of Medicine, National Cheng Kung University Hospital, National Cheng Kung University, No.138, Sheng Li Road, Tainan, 704, Taiwan
| | - Chiung-Yu Chen
- Education Centre, College of Medicine, National Cheng Kung University Hospital, National Cheng Kung University, No.138, Sheng Li Road, Tainan, 704, Taiwan
- Department of Internal Medicine, College of Medicine, National Cheng Kung University Hospital, National Cheng Kung University, Tainan, Taiwan
| | - Ching-Ju Fang
- Medical Library, National Cheng Kung University, Tainan, Taiwan
- Department of Secretariat, College of Medicine, National Cheng Kung University Hospital, National Cheng Kung University, Tainan, Taiwan
| | - Pei-Chun Lai
- Education Centre, College of Medicine, National Cheng Kung University Hospital, National Cheng Kung University, No.138, Sheng Li Road, Tainan, 704, Taiwan.
- Department of Paediatrics, College of Medicine, National Cheng Kung University Hospital, National Cheng Kung University, Tainan, Taiwan.
| |
Collapse
|
|
5
|
Law M, Schamberg G, Gharibans A, Sebaratnam G, Foong D, Varghese C, Fitt I, Daker C, Ho V, Du P, Andrews CN, O'Grady G, Calder S. Short- and long-term reproducibility of body surface gastric mapping using the Gastric Alimetry® system. Neurogastroenterol Motil 2024; 36:e14812. [PMID: 38689428 DOI: 10.1111/nmo.14812] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/23/2023] [Revised: 04/03/2024] [Accepted: 04/15/2024] [Indexed: 05/02/2024]
Abstract
BACKGROUND Many diagnostic tests for gastroduodenal symptoms, such as gastric emptying scintigraphy (GES), gastric emptying breath tests (GEBT), and electrogastrography (EGG) show variable intra-individual reproducibility over time. This study investigated the short- and long-term reproducibility of body surface gastric mapping (BSGM), a non-invasive test for assessing gastric function, in controls and patients with chronic gastroduodenal disorders. METHODS Participants completed three standardized BSGM tests using Gastric Alimetry® (Alimetry, New Zealand). The test encompassed a fasting baseline (30 min), a 482 kCal standard meal, and a 4 h postprandial recording. The first two tests were >6 months apart and the last occurred ~1 week after the second test, to evaluate long and short-term reproducibility. RESULTS Fourteen patients with upper gastrointestinal symptoms and 14 healthy controls were recruited. There were no significant differences in any BSGM metrics between the tests at short and long term (all p > 0.180). Lin's concordance correlation coefficients (CCC) for the primary metrics were high, ranging from 0.58 to 0.96, with intra-individual coefficients of variance (CVintra) ranging from 0.2% to 1.9%. Reproducibility was higher, and intra-individual variation lower, than in previous studies of GES (CCC = 0.54-0.83, CVintra = 3%-77%), GEBT (CVintra = 8%-11%), and EGG (CVintra = 3%-78%). CONCLUSIONS BSGM spectral metrics demonstrate high reproducibility and low intra-individual variation at both short and long term, with superior results to comparable tests. The high reproducibility of Gastric Alimetry supports its role as a diagnostic aid for gastric dysfunction and a reliable tool for evaluating treatment outcomes and disease progression over time.
Collapse
Affiliation(s)
- Mikaela Law
- The Department of Surgery, The University of Auckland, Auckland, New Zealand
- Alimetry Ltd., Auckland, New Zealand
| | - Gabriel Schamberg
- The Department of Surgery, The University of Auckland, Auckland, New Zealand
- Alimetry Ltd., Auckland, New Zealand
| | - Armen Gharibans
- The Department of Surgery, The University of Auckland, Auckland, New Zealand
- Alimetry Ltd., Auckland, New Zealand
- Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA
| | | | - Daphne Foong
- Alimetry Ltd., Auckland, New Zealand
- School of Medicine, Western Sydney University, Sydney, New South Wales, Australia
| | - Chris Varghese
- The Department of Surgery, The University of Auckland, Auckland, New Zealand
| | - India Fitt
- The Department of Surgery, The University of Auckland, Auckland, New Zealand
| | - Charlotte Daker
- Alimetry Ltd., Auckland, New Zealand
- Department of Gastroenterology, Te Whatu Ora-Waitematā, Auckland, New Zealand
| | - Vincent Ho
- School of Medicine, Western Sydney University, Sydney, New South Wales, Australia
- Department of Gastroenterology and Hepatology, Campbelltown Hospital, Campbelltown, New South Wales, Australia
| | - Peng Du
- Alimetry Ltd., Auckland, New Zealand
- Auckland Bioengineering Institute, The University of Auckland, Auckland, New Zealand
| | - Christopher N Andrews
- Alimetry Ltd., Auckland, New Zealand
- Division of Gastroenterology, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada
| | - Greg O'Grady
- The Department of Surgery, The University of Auckland, Auckland, New Zealand
- Alimetry Ltd., Auckland, New Zealand
| | - Stefan Calder
- The Department of Surgery, The University of Auckland, Auckland, New Zealand
- Alimetry Ltd., Auckland, New Zealand
| |
Collapse
|
|
6
|
Hidayat AA, Waskito LA, Sugihartono T, Aftab H, Rezkitha YAA, Vilaichone RK, Miftahussurur M. Diagnostic strategy of irritable bowel syndrome: a low- and middle-income country perspective. Intest Res 2024; 22:286-296. [PMID: 38528371 PMCID: PMC11309822 DOI: 10.5217/ir.2023.00199] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/20/2023] [Revised: 02/06/2024] [Accepted: 02/15/2024] [Indexed: 03/27/2024] Open
Abstract
Irritable bowel syndrome (IBS) is a highly prevalent gastrointestinal disorder associated with substantial impairment which considerably burdens healthcare systems worldwide. Research on IBS has largely been conducted in high-income countries posing barriers to the application of diagnostic strategies in low- and middle-income countries (LMICs) due to differences in disease characteristics, healthcare resources, and socioeconomic factors. This review discusses the diagnostic issues associated with LMICs. We present a concise overview of the relevant approaches and propose a diagnostic strategy based on the latest evidence. A positive diagnostic strategy that relies on appropriate symptom-based criteria is crucial within the diagnostic framework. A combination of complete blood count, fecal occult blood test, and complete stool test may reliably identify individuals with suspected IBS who are more likely to have organic diseases, thus justifying the necessity for a colonoscopy. Eventually, we developed a diagnostic algorithm based on a limited setting perspective that summarizes the available evidence and may be applied in LMICs.
Collapse
Affiliation(s)
- Amal Arifi Hidayat
- Department of Internal Medicine, Faculty of Medicine, Universitas Airlangga, Surabaya, Indonesia
| | - Langgeng Agung Waskito
- Department of Physiology and Biochemistry, Faculty of Medicine, Universitas Airlangga, Surabaya, Indonesia
- Helicobacter pylori and Microbiota Study Group, Institute Tropical Disease, Universitas Airlangga, Surabaya, Indonesia
| | - Titong Sugihartono
- Division of Gastroentero-Hepatology, Department of Internal Medicine, Faculty of Medicine, Universitas Airlangga, Surabaya, Indonesia
| | - Hafeza Aftab
- Department of Gastroenterology, Dhaka Medical College and Hospital, Dhaka, Bangladesh
| | - Yudith Annisa Ayu Rezkitha
- Helicobacter pylori and Microbiota Study Group, Institute Tropical Disease, Universitas Airlangga, Surabaya, Indonesia
- Department of Internal Medicine, Universitas Muhammadiyah Surabaya, Surabaya, Indonesia
| | - Ratha-korn Vilaichone
- Division of Gastroentero-Hepatology, Department of Internal Medicine, Faculty of Medicine, Universitas Airlangga, Surabaya, Indonesia
- Center of Excellence in Digestive Diseases and Gastroenterology Unit, Department of Medicine, Thammasat University, Pathumthani, Thailand
| | - Muhammad Miftahussurur
- Helicobacter pylori and Microbiota Study Group, Institute Tropical Disease, Universitas Airlangga, Surabaya, Indonesia
- Division of Gastroentero-Hepatology, Department of Internal Medicine, Faculty of Medicine, Universitas Airlangga, Surabaya, Indonesia
| |
Collapse
|
|
7
|
Khasawneh M, Shaikh FA, Ng CE, Black CJ, Goodoory VC, Ford AC. Utility of irritable bowel syndrome subtypes and most troublesome symptom in predicting disease impact and burden. Neurogastroenterol Motil 2024; 36:e14756. [PMID: 38321517 DOI: 10.1111/nmo.14756] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/27/2023] [Revised: 01/20/2024] [Accepted: 01/23/2024] [Indexed: 02/08/2024]
Abstract
BACKGROUND Little is known about the characteristics of individuals with irritable bowel syndrome (IBS) according to stool subtype or the most troublesome symptom reported by the individual, or whether these are useful in predicting the impact of IBS. METHODS We collected demographic, gastrointestinal, and psychological symptoms, healthcare usage and direct healthcare costs, impact on work and activities of daily living, and quality of life data from individuals with Rome IV-defined IBS. KEY RESULTS We recruited 752 people with Rome IV IBS. Individuals with IBS-D reported a poorer disease-specific quality of life than those with IBS-C or IBS-M (mean (SD) IBS-QOL 45.3 (23.0) for IBS-D, vs. 52.3 (19.9) for IBS-C, vs. 49.4 (22.0) for IBS-M, p = 0.005). Mean (SD) IBS-QOL scores were also lower amongst those who reported diarrhea (44.8 (22.3)) or urgency (44.6 (22.3)) as their most troublesome symptom, compared with those reporting abdominal pain (52.2 (22.9)), constipation (49.5 (21.8)), or abdominal bloating or distension (50.4 (21.3)). However, there were no differences in mean EQ-5D scores, IBS severity, levels of anxiety, depression, somatoform symptom-reporting, or gastrointestinal symptom-specific anxiety. Direct healthcare costs of IBS were similar across all subtypes and all most troublesome symptom groups, although some differences in work productivity and social leisure activities were detected. CONCLUSIONS AND INFERENCES There appears to be limited variation in the characteristics of individuals with Rome IV IBS based on both stool subtypes and most troublesome symptom reported, suggesting that gastrointestinal symptoms alone have limited ability to predict disease impact and burden.
Collapse
Affiliation(s)
- Mais Khasawneh
- Leeds Institute of Medical Research at St. James's, University of Leeds, Leeds, UK
- Leeds Gastroenterology Institute, St. James's University Hospital, Leeds, UK
| | - Fahad Ali Shaikh
- Leeds Gastroenterology Institute, St. James's University Hospital, Leeds, UK
| | - Cho Ee Ng
- County Durham and Darlington NHS Foundation Trust, Durham, UK
| | - Christopher J Black
- Leeds Institute of Medical Research at St. James's, University of Leeds, Leeds, UK
- Leeds Gastroenterology Institute, St. James's University Hospital, Leeds, UK
| | - Vivek C Goodoory
- Leeds Institute of Medical Research at St. James's, University of Leeds, Leeds, UK
- Leeds Gastroenterology Institute, St. James's University Hospital, Leeds, UK
| | - Alexander C Ford
- Leeds Institute of Medical Research at St. James's, University of Leeds, Leeds, UK
- Leeds Gastroenterology Institute, St. James's University Hospital, Leeds, UK
| |
Collapse
|
|
8
|
Chiarelli M, De Simone M, Cioffi G, Cioffi U. New paradigm of oral rehydration in patients affected by irritable bowel syndrome with chronic diarrhea. World J Gastrointest Pharmacol Ther 2024; 15:90933. [PMID: 38590832 PMCID: PMC10999031 DOI: 10.4292/wjgpt.v15.i1.90933] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/18/2023] [Revised: 01/20/2024] [Accepted: 02/28/2024] [Indexed: 03/18/2024] Open
Abstract
Irritable bowel syndrome with diarrhea is a very frequent clinical condition characterized by disabling intestinal symptoms. This disease presents with daily abdominal pain for at least 3 months related to defecation and associated with a change in the frequency of bowel movements and the shape of the stool. International surveys about this disease report a global prevalence of about 1.5%. A new amino acid based electrolyte solution has recently been commercialized for oral rehydration in diarrhea. It is composed of water, electrolytes, and five selected amino acids that function as sodium co-transporters without containing glucose. In recent years, some studies explored the effectiveness of the amino acid based electrolyte beverage in oncologic patients with gastrointestinal mucositis, reporting good results. Recently, a prospective study to evaluate the clinical impact of the amino acid based medical beverage was conducted in patients with diarrhea predominant irritable bowel syndrome. The research was based on a real-life methodology minimizing the disruption of the routine care. One hundred patients suffering from irritable bowel syndrome with diarrhea drank a solution based on selected amino acids twice a day for 2 wk. Each enrolled patient completed the study and showed a significant response rate with regard to stool consistency and pain reduction. Based on this data, we can hypothesize that the amino acid based oral rehydration solution could be a valid tool in the treatment of patients affected by irritable bowel syndrome with diarrhea. It is certainly necessary to plan high-quality clinical trials comparing glucose based oral solutions and amino acid based solutions in patients with persisting diarrhea. Probably in the near future all oral rehydration solutions will contain amino acids.
Collapse
Affiliation(s)
- Marco Chiarelli
- Department of Emergency and Robotic Surgery, A. Manzoni Hospital–ASST Lecco, Lecco 23900, Italy
| | - Matilde De Simone
- Department of Surgery, University of Milan, Via F. Sforza 35, 20122 Milano, Milano 20122, Italy
| | - Gerardo Cioffi
- Department of Sciences and Technologies, Unisannio, Benevento 82100, Italy
| | - Ugo Cioffi
- Department of Surgery, University of Milan, Milano 20122, Italy
| |
Collapse
|
|
9
|
Baart AM, Mensink M, Witteman BJM. The impact of running on gastrointestinal symptoms in patients with irritable bowel syndrome. Neurogastroenterol Motil 2024; 36:e14707. [PMID: 37964184 DOI: 10.1111/nmo.14707] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/26/2023] [Revised: 10/13/2023] [Accepted: 10/25/2023] [Indexed: 11/16/2023]
Abstract
INTRODUCTION Physical activity has been suggested to alleviate gastrointestinal (GI) symptoms in patients with irritable bowel syndrome (IBS); however, evidence is scarce. Running has become increasingly popular and may be beneficial for patients with IBS. To obtain more insight in the potential application of running as therapy, we aimed to explore the impact of running and its intensity on GI symptoms in patients with IBS. METHODS Data from a large observational study in runners were used for this nested case-control study, which included 153 runners with IBS and 153 controls. All participants had completed a questionnaire on personal characteristics, running characteristics and GI symptoms. Regarding GI symptoms, the severity of nine symptoms was asked, both at rest and during and/or shortly (up to 3 h) after running. Each symptom could be scored on a scale from 0 (not bothersome) to 100 (very bothersome), resulting in a maximum total score of 900 points. KEY RESULTS The prevalence and total severity score of GI symptoms were higher in runners with IBS than in controls, both at rest and during running. Among runners with IBS, the median (25th-75th percentile) total severity score during/after running was significantly lower than at rest (118 [50-200] vs. 150 [90-217]), while in controls no significant difference between running and rest was observed. Analyses stratified for running intensity revealed that the beneficial effect in runners with IBS was present when their most intensive training session was moderately intensive or intensive but not very intensive. CONCLUSIONS & INFERENCES Running, particularly on moderate intensity, could have a beneficial effect on GI symptoms in patients with IBS.
Collapse
Affiliation(s)
- A Mireille Baart
- Division of Human Nutrition and Health, Wageningen University & Research, Wageningen, The Netherlands
- Sports Valley, Department of Sports Medicine, Gelderse Vallei Hospital, Ede, The Netherlands
| | - Marco Mensink
- Division of Human Nutrition and Health, Wageningen University & Research, Wageningen, The Netherlands
| | - Ben J M Witteman
- Division of Human Nutrition and Health, Wageningen University & Research, Wageningen, The Netherlands
- Department of Gastroenterology and Hepatology, Gelderse Vallei Hospital, Ede, The Netherlands
| |
Collapse
|
|
10
|
Zarei D, Saghazadeh A, Rezaei N. Subtyping irritable bowel syndrome using cluster analysis: a systematic review. BMC Bioinformatics 2023; 24:478. [PMID: 38102564 PMCID: PMC10724977 DOI: 10.1186/s12859-023-05567-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/29/2023] [Accepted: 11/13/2023] [Indexed: 12/17/2023] Open
Abstract
BACKGROUND Irritable bowel syndrome (IBS) is a common chronic functional gastrointestinal disorder associated with a wide range of clinical symptoms. Some researchers have used cluster analysis (CA), a group of non-supervised learning methods that identifies homogenous clusters within different entities based on their similarity. OBJECTIVE AND METHODS This literature review aims to identify published articles that apply CA to IBS patients. We searched relevant keywords in PubMed, Embase, Web of Science, and Scopus. We reviewed studies in terms of the selected variables, participants' characteristics, data collection, methodology, number of clusters, clusters' profiles, and results. RESULTS Among the 14 articles focused on the heterogeneity of IBS, eight of them utilized K-means Cluster Analysis (K-means CA), four employed Hierarchical Cluster Analysis, and only two studies utilized Latent Class Analysis. Seven studies focused on clinical symptoms, while four articles examined anocolorectal functions. Two studies were centered around immunological findings, and only one study explored microbial composition. The number of clusters obtained ranged from two to seven, showing variation across the studies. Males exhibited lower symptom severity and fewer psychological findings. The association between symptom severity and rectal perception suggests that altered rectal perception serves as a biological indicator of IBS. Ultra-slow waves observed in IBS patients are linked to increased activity of the anal sphincter, higher anal pressure, dystonia, and dyschezia. CONCLUSION IBS has different subgroups based on different factors. Most IBS patients have low clinical severity, good QoL, high rectal sensitivity, delayed left colon transit time, increased systemic cytokines, and changes in microbial composition, including increased Firmicutes-associated taxa and depleted Bacteroidetes-related taxa. However, the number of clusters is inconsistent across studies due to the methodological heterogeneity. CA, a valuable non-supervised learning method, is sensitive to hyperparameters like the number of clusters and random initialization of cluster centers. The random nature of these parameters leads to diverse outcomes even with the same algorithm. This has implications for future research and practical applications, necessitating further studies to improve our understanding of IBS and develop personalized treatments.
Collapse
Affiliation(s)
- Diana Zarei
- School of Medicine, Iran University of Medical Science, Tehran, Iran
- Systematic Review and Meta-Analysis Expert Group (SRMEG), Universal Scientific Education and Research Network (USERN), Tehran, Iran
| | - Amene Saghazadeh
- Research Center for Immunodeficiencies, Children's Medical Center, Tehran University of Medical Sciences, Dr. Qarib St, Keshavarz Blvd, Tehran, 14194, Iran
- Integrated Science Association (ISA), Universal Scientific Education and Research Network (USERN), Tehran, Iran
| | - Nima Rezaei
- Research Center for Immunodeficiencies, Children's Medical Center, Tehran University of Medical Sciences, Dr. Qarib St, Keshavarz Blvd, Tehran, 14194, Iran.
- Integrated Science Association (ISA), Universal Scientific Education and Research Network (USERN), Tehran, Iran.
- Department of Immunology and Biology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran.
| |
Collapse
|
|
11
|
Tian J, Li T, Zhao J, Li D, Sun J, Li Z, Shi R. Efficacy of different courses of acupuncture for diarrhea irritable bowel syndrome: A protocol for systematic review and meta-analysis. PLoS One 2023; 18:e0295077. [PMID: 38096158 PMCID: PMC10721030 DOI: 10.1371/journal.pone.0295077] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/07/2023] [Accepted: 11/14/2023] [Indexed: 12/17/2023] Open
Abstract
Irritable Bowel Syndrome (IBS) is the most common functional gastrointestinal disorder. As one of the most common subtypes of IBS, IBS-D can impair the patients' quality of life (QOL) and decreased work productivity. Acupuncture may be a potential treatment for patients with IBS-D. However, the treatment course of acupuncture was diverse. It is unclear what is the optimal acupuncture treatment courses for acupuncture. The efficacy and safety of different courses of acupuncture for IBS-D have not been systematically evaluated yet. The purpose of this study is to evaluate effectiveness of Acupuncture of different courses in the treatment of IBS-D and provide sufficient evidence for clinical recommendations for IBS-D. We will follow the Preferred reporting items for systematic reviews and meta-analysis protocols (PRISMA-P) guidelines to design the protocol of a systematic review and meta-analysis. This systematic review is registered in PROSPERO (CRD42023418846). We will include randomized controlled trials (RCTs) in which the efficacy of Acupuncture is compared with a placebo, sham acupuncture or Pinaverium bromide in the treatment of IBS-D with no language restrictions. The outcomes of interest will be efficiency rate and the Symptoms Severity Score. RCTs will be searched in the electronic database and Clinical Trials Registry Platform from inception to April 2023. Two independent reviewers will independently select studies, extract data from the included studies, and assess the risk of bias using the Cochrane tool. We will choose a random or fixed-effects model based on the heterogeneity index. We will use the relative risk and mean difference to estimate data with 95% CI. A stratified meta-analysis was conducted to evaluate the effect of different treatment courses of Acupuncture: 2weeks, 4weeks(or 1 months), 6 weeks, and 8 weeks. If there is significant clinical and methodological heterogeneity, we will look for the reason for heterogeneity and perform a subgroup analysis. According to the Grading of Recommendations Assessment, Development and Evaluation (GRADE), we will evaluate the evidence quality and provide the recommendation's strength.
Collapse
Affiliation(s)
- Junjian Tian
- School of Acupuncture-Moxibustion and Tuina, Beijing University of Chinese Medicine, Beijing, China
| | - Ting Li
- School of Acupuncture-Moxibustion and Tuina, Beijing University of Chinese Medicine, Beijing, China
| | - Jun Zhao
- School of Acupuncture-Moxibustion and Tuina, Beijing University of Chinese Medicine, Beijing, China
| | - Da Li
- Beijing University of Chinese Medicine Affiliated Dongzhimen Hospital, Beijing, China
| | - Jingwen Sun
- School of Acupuncture-Moxibustion and Tuina, Beijing University of Chinese Medicine, Beijing, China
| | - Zhigang Li
- School of Acupuncture-Moxibustion and Tuina, Beijing University of Chinese Medicine, Beijing, China
| | | |
Collapse
|
|
12
|
Khasawneh M, Craig OF, Gracie DJ, Black CJ, Ford AC. A Diagnosis of Irritable Bowel Syndrome Using Rome IV Criteria and Limited Investigations is Durable in Secondary Care. Clin Gastroenterol Hepatol 2023; 21:3397-3404.e1. [PMID: 37302448 DOI: 10.1016/j.cgh.2023.05.022] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/21/2023] [Revised: 03/30/2023] [Accepted: 05/22/2023] [Indexed: 06/13/2023]
Abstract
BACKGROUND & AIMS Irritable bowel syndrome (IBS) is a positive diagnosis, made using symptom-based criteria and limited, judicious, investigation. However, this may lead to uncertainty on the part of clinicians regarding potential for a missed diagnosis of organic gastrointestinal disease. Few studies have examined durability of a diagnosis of IBS, and none have used the current gold standard to diagnose IBS, the Rome IV criteria. METHODS We collected complete symptom data from 373 well-characterized adults meeting Rome IV criteria for IBS referred to a single UK clinic between September 2016 and March 2020. All patients underwent relatively standardized work-up to exclude relevant organic disease before diagnosis. We followed these individuals up to December 2022, assessing rates of rereferral, reinvestigation, and missed organic gastrointestinal disease. RESULTS During a mean follow-up of 4.2 years per patient (total follow-up in all patients, 1565 years), 62 (16.6%) patients were rereferred. Of these, 35 (56.5%) were rereferred for IBS and 27 (43.5%) for other gastrointestinal symptoms. Among the 35 rereferred with IBS this was caused by a change in symptoms in only 5 (14.3%). Reinvestigation was undertaken in 21 (60.0%) of 35 rereferred with IBS and 22 (81.5%) of 27 rereferred with other symptoms (P = .12). Only 4 (9.3% of those reinvestigated and 1.1% of the entire cohort) new cases of relevant organic disease, which may have been responsible for IBS symptoms at baseline, were identified (1 case of chronic calcific pancreatitis among those rereferred with IBS and 1 case each of inflammatory bowel disease-unclassified, moderate bile acid diarrhea, and small bowel obstruction among those rereferred with other gastrointestinal symptoms). CONCLUSIONS Despite rereferral for gastrointestinal symptoms among 1 in 6 patients overall, with almost 10% rereferred with ongoing IBS symptoms, and substantial reinvestigation rates, missed organic gastrointestinal disease occurred in only 1%. A diagnosis of Rome IV IBS after limited investigation is safe and durable.
Collapse
Affiliation(s)
- Mais Khasawneh
- Leeds Gastroenterology Institute, St. James's University Hospital, Leeds, United Kingdom
| | - Orla F Craig
- Leeds Gastroenterology Institute, St. James's University Hospital, Leeds, United Kingdom
| | - David J Gracie
- Leeds Gastroenterology Institute, St. James's University Hospital, Leeds, United Kingdom
| | - Christopher J Black
- Leeds Gastroenterology Institute, St. James's University Hospital, Leeds, United Kingdom; Leeds Institute for Medical Research at St. James's, University of Leeds, Leeds, United Kingdom
| | - Alexander C Ford
- Leeds Gastroenterology Institute, St. James's University Hospital, Leeds, United Kingdom; Leeds Institute for Medical Research at St. James's, University of Leeds, Leeds, United Kingdom.
| |
Collapse
|
|
13
|
Ford AC, Wright-Hughes A, Alderson SL, Ow PL, Ridd MJ, Foy R, Bianco G, Bishop FL, Chaddock M, Cook H, Cooper D, Fernandez C, Guthrie EA, Hartley S, Herbert A, Howdon D, Muir DP, Nath T, Newman S, Smith T, Taylor CA, Teasdale EJ, Thornton R, Farrin AJ, Everitt HA. Amitriptyline at Low-Dose and Titrated for Irritable Bowel Syndrome as Second-Line Treatment in primary care (ATLANTIS): a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet 2023; 402:1773-1785. [PMID: 37858323 DOI: 10.1016/s0140-6736(23)01523-4] [Citation(s) in RCA: 50] [Impact Index Per Article: 25.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/03/2023] [Revised: 06/30/2023] [Accepted: 07/20/2023] [Indexed: 10/21/2023]
Abstract
BACKGROUND Most patients with irritable bowel syndrome (IBS) are managed in primary care. When first-line therapies for IBS are ineffective, the UK National Institute for Health and Care Excellence guideline suggests considering low- dose tricyclic antidepressants as second-line treatment, but their effectiveness in primary care is unknown, and they are infrequently prescribed in this setting. METHODS This randomised, double-blind, placebo-controlled trial (Amitriptyline at Low-Dose and Titrated for Irritable Bowel Syndrome as Second-Line Treatment [ATLANTIS]) was conducted at 55 general practices in England. Eligible participants were aged 18 years or older, with Rome IV IBS of any subtype, and ongoing symptoms (IBS Severity Scoring System [IBS-SSS] score ≥75 points) despite dietary changes and first-line therapies, a normal full blood count and C-reactive protein, negative coeliac serology, and no evidence of suicidal ideation. Participants were randomly assigned (1:1) to low-dose oral amitriptyline (10 mg once daily) or placebo for 6 months, with dose titration over 3 weeks (up to 30 mg once daily), according to symptoms and tolerability. Participants, their general practitioners, investigators, and the analysis team were all masked to allocation throughout the trial. The primary outcome was the IBS-SSS score at 6 months. Effectiveness analyses were according to intention-to-treat; safety analyses were on all participants who took at least one dose of the trial medication. This trial is registered with the ISRCTN Registry (ISRCTN48075063) and is closed to new participants. FINDINGS Between Oct 18, 2019, and April 11, 2022, 463 participants (mean age 48·5 years [SD 16·1], 315 [68%] female to 148 [32%] male) were randomly allocated to receive low-dose amitriptyline (232) or placebo (231). Intention-to-treat analysis of the primary outcome showed a significant difference in favour of low-dose amitriptyline in IBS-SSS score between groups at 6 months (-27·0, 95% CI -46·9 to -7·10; p=0·0079). 46 (20%) participants discontinued low-dose amitriptyline (30 [13%] due to adverse events), and 59 (26%) discontinued placebo (20 [9%] due to adverse events) before 6 months. There were five serious adverse reactions (two in the amitriptyline group and three in the placebo group), and five serious adverse events unrelated to trial medication. INTERPRETATION To our knowledge, this is the largest trial of a tricyclic antidepressant in IBS ever conducted. Titrated low-dose amitriptyline was superior to placebo as a second-line treatment for IBS in primary care across multiple outcomes, and was safe and well tolerated. General practitioners should offer low-dose amitriptyline to patients with IBS whose symptoms do not improve with first-line therapies, with appropriate support to guide patient-led dose titration, such as the self-titration document developed for this trial. FUNDING National Institute for Health and Care Research Health Technology Assessment Programme (grant reference 16/162/01).
Collapse
Affiliation(s)
- Alexander C Ford
- Leeds Institute of Medical Research at St James's, University of Leeds, Leeds, UK; Leeds Gastroenterology Institute, St James's University Hospital, Leeds, UK.
| | - Alexandra Wright-Hughes
- Clinical Trial Research Unit, Leeds Institute of Clinical Trials Research, University of Leeds, Leeds, UK
| | - Sarah L Alderson
- Clinical Trial Research Unit, Leeds Institute of Clinical Trials Research, University of Leeds, Leeds, UK
| | - Pei-Loo Ow
- Clinical Trial Research Unit, Leeds Institute of Clinical Trials Research, University of Leeds, Leeds, UK
| | - Matthew J Ridd
- Population Health Sciences, Bristol Medical School, University of Bristol, Bristol, UK
| | - Robbie Foy
- Leeds Institute of Health Sciences, School of Medicine, University of Leeds, Leeds, UK
| | - Gina Bianco
- Clinical Trial Research Unit, Leeds Institute of Clinical Trials Research, University of Leeds, Leeds, UK
| | - Felicity L Bishop
- Centre for Clinical and Community Applications of Health Psychology, School of Psychology, University of Southampton, Southampton, UK
| | | | - Heather Cook
- Clinical Trial Research Unit, Leeds Institute of Clinical Trials Research, University of Leeds, Leeds, UK
| | - Deborah Cooper
- Leeds Institute of Health Sciences, School of Medicine, University of Leeds, Leeds, UK
| | - Catherine Fernandez
- Clinical Trial Research Unit, Leeds Institute of Clinical Trials Research, University of Leeds, Leeds, UK
| | - Elspeth A Guthrie
- Leeds Institute of Health Sciences, School of Medicine, University of Leeds, Leeds, UK
| | - Suzanne Hartley
- Clinical Trial Research Unit, Leeds Institute of Clinical Trials Research, University of Leeds, Leeds, UK
| | - Amy Herbert
- Population Health Sciences, Bristol Medical School, University of Bristol, Bristol, UK
| | - Daniel Howdon
- Leeds Institute of Health Sciences, School of Medicine, University of Leeds, Leeds, UK
| | - Delia P Muir
- Clinical Trial Research Unit, Leeds Institute of Clinical Trials Research, University of Leeds, Leeds, UK
| | - Taposhi Nath
- Clinical Trial Research Unit, Leeds Institute of Clinical Trials Research, University of Leeds, Leeds, UK
| | - Sonia Newman
- Primary Care Research Centre, Faculty of Medicine, University of Southampton, Southampton, UK
| | - Thomas Smith
- Clinical Trial Research Unit, Leeds Institute of Clinical Trials Research, University of Leeds, Leeds, UK
| | - Christopher A Taylor
- Clinical Trial Research Unit, Leeds Institute of Clinical Trials Research, University of Leeds, Leeds, UK
| | - Emma J Teasdale
- Centre for Clinical and Community Applications of Health Psychology, School of Psychology, University of Southampton, Southampton, UK
| | - Ruth Thornton
- Primary Care Research Centre, Faculty of Medicine, University of Southampton, Southampton, UK
| | - Amanda J Farrin
- Clinical Trial Research Unit, Leeds Institute of Clinical Trials Research, University of Leeds, Leeds, UK
| | - Hazel A Everitt
- Primary Care Research Centre, Faculty of Medicine, University of Southampton, Southampton, UK
| |
Collapse
|
|
14
|
Jamshidi P, Farsi Y, Nariman Z, Hatamnejad MR, Mohammadzadeh B, Akbarialiabad H, Nasiri MJ, Sechi LA. Fecal Microbiota Transplantation in Irritable Bowel Syndrome: A Systematic Review and Meta-Analysis of Randomized Controlled Trials. Int J Mol Sci 2023; 24:14562. [PMID: 37834010 PMCID: PMC10573019 DOI: 10.3390/ijms241914562] [Citation(s) in RCA: 7] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/26/2023] [Revised: 09/05/2023] [Accepted: 09/15/2023] [Indexed: 10/15/2023] Open
Abstract
Irritable bowel syndrome (IBS) poses a significant challenge due to its poorly understood pathogenesis, substantial morbidity, and often inadequate treatment outcomes. The role of fecal microbiota transplantation (FMT) in managing IBS symptoms remains inconclusive. This systematic review and meta-analysis aimed to ascertain the effectiveness of FMT in relieving symptoms in IBS patients. A thorough search was executed on PubMed/Medline and Embase databases until 14 June 2023, including all studies on FMT use in IBS patients. We examined the efficiency of FMT in reducing patients' symptoms overall and in particular subgroups, classified by placebo preparation, FMT preparation, frequency, and route of administration. Among 1015 identified studies, seven met the inclusion criteria for the meta-analysis. The overall symptomatology of FMT-treated IBS patients did not significantly differ from the control group (Odds Ratio (OR) = 0.99, 95% Confidence Interval (CI) 0.39-2.5). Multiple doses of FMT compared with non-FMT placebo, or single-donor FMT therapy compared with autologous FMT placebo also showed no significant benefit (OR = 0.32, 95%CI (0.07-1.32), p = 0.11, and OR = 1.67, 95%CI (0.59-4.67), p = 0.32, respectively). However, a single dose of multiple-donor FMT administered via colonoscopy (lower gastrointestinal (GI) administration) significantly improved patient symptoms compared with autologous FMT placebo (OR = 2.54, 95%CI (1.20-5.37), p = 0.01, and OR = 2.2, 95%CI (1.20-4.03), p = 0.01, respectively). The studies included in the analysis showed a low risk of bias and no publication bias. In conclusion, lower GI administration of a single dose of multiple-donor FMT significantly alleviates patient complaints compared with the autologous FMT used as a placebo. The underlying mechanisms need to be better understood, and further experimental studies are desired to fill the current gaps.
Collapse
Affiliation(s)
- Parnian Jamshidi
- Department of Microbiology, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran 1985717443, Iran or (P.J.)
| | - Yeganeh Farsi
- School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran 1985717443, Iran
| | - Zahra Nariman
- Student Research Committee, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran 1985717443, Iran
| | - Mohammad Reza Hatamnejad
- Basic and Molecular Epidemiology of Gastrointestinal Disorders Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran 1985717413, Iran
| | - Benyamin Mohammadzadeh
- Department of Microbiology, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran 1985717443, Iran or (P.J.)
| | - Hossein Akbarialiabad
- NVH Global Health Academy, Nuvance Health, Danbury, CT 06810, USA
- St George and Sutherland Clinical School, UNSW Medicine, Sydney, NSW 2217, Australia
| | - Mohammad Javad Nasiri
- Department of Microbiology, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran 1985717443, Iran or (P.J.)
| | - Leonardo A. Sechi
- Department of Biomedical Sciences, University of Sassari, 07100 Sassari, Italy
- SC Microbiologia e Virologia, Azienda Ospedaliera Universitaria, 07100 Sassari, Italy
| |
Collapse
|
|
15
|
D’Amico V, Gänzle M, Call L, Zwirzitz B, Grausgruber H, D’Amico S, Brouns F. Does sourdough bread provide clinically relevant health benefits? Front Nutr 2023; 10:1230043. [PMID: 37545587 PMCID: PMC10399781 DOI: 10.3389/fnut.2023.1230043] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/27/2023] [Accepted: 06/27/2023] [Indexed: 08/08/2023] Open
Abstract
During the last decade, scientific interest in and consumer attention to sourdough fermentation in bread making has increased. On the one hand, this technology may favorably impact product quality, including flavor and shelf-life of bakery products; on the other hand, some cereal components, especially in wheat and rye, which are known to cause adverse reactions in a small subset of the population, can be partially modified or degraded. The latter potentially reduces their harmful effects, but depends strongly on the composition of sourdough microbiota, processing conditions and the resulting acidification. Tolerability, nutritional composition, potential health effects and consumer acceptance of sourdough bread are often suggested to be superior compared to yeast-leavened bread. However, the advantages of sourdough fermentation claimed in many publications rely mostly on data from chemical and in vitro analyzes, which raises questions about the actual impact on human nutrition. This review focuses on grain components, which may cause adverse effects in humans and the effect of sourdough microbiota on their structure, quantity and biological properties. Furthermore, presumed benefits of secondary metabolites and reduction of contaminants are discussed. The benefits claimed deriving from in vitro and in vivo experiments will be evaluated across a broader spectrum in terms of clinically relevant effects on human health. Accordingly, this critical review aims to contribute to a better understanding of the extent to which sourdough bread may result in measurable health benefits in humans.
Collapse
Affiliation(s)
- Vera D’Amico
- Department of Food Science and Technology, BOKU–University of Natural Resources and Life Sciences, Vienna, Austria
| | - Michael Gänzle
- Department of Agricultural, Food and Nutritional Science, University of Alberta, Edmonton, AB, Canada
| | - Lisa Call
- Department of Crop Sciences, BOKU–University of Natural Resources and Life Sciences, Tulln, Austria
| | - Benjamin Zwirzitz
- Department of Food Science and Technology, BOKU–University of Natural Resources and Life Sciences, Vienna, Austria
| | - Heinrich Grausgruber
- Department of Crop Sciences, BOKU–University of Natural Resources and Life Sciences, Tulln, Austria
| | - Stefano D’Amico
- Institute for Animal Nutrition and Feed, AGES–Austrian Agency for Health and Food Safety, Vienna, Austria
| | - Fred Brouns
- Department of Human Biology, School for Nutrition and Translational Research in Metabolism, Maastricht University, Maastricht, Netherlands
| |
Collapse
|
|
16
|
Wang M, Xie X, Zhao S, Ma X, Wang Z, Zhang Y. Fecal microbiota transplantation for irritable bowel syndrome: a systematic review and meta-analysis of randomized controlled trials. Front Immunol 2023; 14:1136343. [PMID: 37275867 PMCID: PMC10234428 DOI: 10.3389/fimmu.2023.1136343] [Citation(s) in RCA: 15] [Impact Index Per Article: 7.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/02/2023] [Accepted: 04/27/2023] [Indexed: 06/07/2023] Open
Abstract
Objective Whether fecal microbiota transplantation (FMT) in patients with irritable bowel syndrome (IBS) is effective in improving outcomes remains controversial. We assessed the safety and efficacy of FMT for patients with IBS. Methods In this systematic review and meta-analysis, we searched PubMed, Embase, Web of Science, the Cochrane Library, the clinicaltrials.gov and International Clinical Trials Registry Platform (ICTRP) up to February 25, 2022, updated to March 28, 2023. Randomized controlled trials (RCTs) compared the stool and capsule FMT with placebo in patients with IBS were included. Two authors independently assessed study eligibility, extracted the data, and assessed risk of bias. We did meta-analysis with RevMan, and the Stata software was used for sensitivity analysis and meta-regression. The GRADE system was used to assess the quality of evidences. Mean difference (MD) or standardized Mean difference (SMD) with 95% CI for continuous data, and risk ratios (RR) with 95% CI for dichotomous data were used with random-effects models. The primary outcomes included the clinical response rate and IBS-SSS score. This study is registered with PROSPERO: CRD42022328377. Results Nineteen reports from nine RCTs were included finally. Compared with the placebo, a single stool FMT could significantly decrease the IBS-SSS score at 1 month (MD=-65.75, 95%CI [-129.37, -2.13]), 3 months (MD=-102.11, 95% CI [-141.98, -62.24]), 6 months (MD=-84.38, 95%CI [-158.79, -9.97]), 24 months (MD=-110.41, 95%CI [-145.37, -75.46]), and 36 months (MD=-104.71, 95%CI [-137.78, -71.64]). It also could improve the clinical response rate at 3 months (RR=1.91, 95% [1.12, 3.25]), 24 months (RR=2.97, 95% [1.94, 4.54]), and 36 months (RR=2.48, 95% [1.65, 3.72]), and increase the IBS-QoL score at 3 months, 24 months, and 36 months. FMT did not increase the serious adverse event. The risk of bias was low, and the quality of evidence based on GRADE system was moderate in the stool FMT group. However, we did not find positive effect of capsule FMT on patients with IBS based on the current available data. Conclusion A single stool FMT is effective and safe for patients with IBS. However, some factors may affect the effectiveness of FMT, and the relationship between the gut microbiome and the effect of FMT for IBS is still unclear. Systematic review registration https://www.crd.york.ac.uk/prospero/, identifier CRD42022328377.
Collapse
Affiliation(s)
- Mancai Wang
- Department of General Surgery, Lanzhou University Second Hospital, Lanzhou, China
| | - Xiaofeng Xie
- Department of Histology and Embryology, Medical College of Northwest Minzu University, Lanzhou, China
| | - Songbo Zhao
- Department of General Surgery, Lanzhou University Second Hospital, Lanzhou, China
| | - Xiaojuan Ma
- Department of Histology and Embryology, Medical College of Northwest Minzu University, Lanzhou, China
| | - Zheyuan Wang
- Department of General Surgery, Lanzhou University Second Hospital, Lanzhou, China
| | - Youcheng Zhang
- Department of General Surgery, Lanzhou University Second Hospital, Lanzhou, China
| |
Collapse
|
|
17
|
Konstantis G, Efstathiou S, Pourzitaki C, Kitsikidou E, Germanidis G, Chourdakis M. Efficacy and safety of probiotics in the treatment of irritable bowel syndrome: A systematic review and meta-analysis of randomised clinical trials using ROME IV criteria. Clin Nutr 2023; 42:800-809. [PMID: 37031468 DOI: 10.1016/j.clnu.2023.03.019] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/03/2022] [Revised: 03/18/2023] [Accepted: 03/25/2023] [Indexed: 04/03/2023]
Abstract
BACKGROUND Irritable Bowel Syndrome (IBS) is a functional gastrointestinal disorder which affects a great number of patients globally. Clinical trials and meta-analyses have evaluated different therapies for IBS. Some of them have shown that probiotics play a significant role in the management of IBS-patients. Nevertheless, results are controversial, and the efficacy of the administration of probiotics remains to be confirmed, especially in regard to which type of probiotic-strains are beneficial. AIM The aim of the present meta-analysis is to assess the efficacy and safety of the administration of probiotics to IBS-patients with a diagnosis based on Rome IV criteria, which is performed for the first time. METHODS Electronic databases (Pubmed, Scopus and Cochrane) were searched until 26.01.2023 for randomized controlled trials (RCTs) studying the administration of probiotics in adult IBS-patients, who were categorized according to the Rome IV criteria. The risk of bias was assessed using the Cochrane Risk of Bias tool (ROB) 2.0. Weighted and standardized mean difference with the 95% confidence intervals were used for the synthesis of the results. Primary outcomes were the decrease of IBS-Symptom Severity Score (IBS-SSS) and decrease of abdominal pain. The secondary outcomes were the improvement in quality of life (QoL) and the decrease of bloating. Lastly, the adverse effects of probiotics were evaluated. The protocol of the study has been registered at protocols.io (DOI dx.doi.org/10.17504/protocols.io.14egn218yg5d/v1). RESULTS Six double-blind (N = 970) placebo-control RCTs fulfilled the inclusion criteria and overall, nine different strains of probiotics were examined. No significant reduction in IBS-SSS (WMD -43.2, 95% CI -87.5 to 1.0, I2 = 82.9%) was demonstrated, whereas a significant decrease regarding abdominal pain (SMD -0.94, 95% CI -1.53 to -0.35, I2 = 92,2) was shown. Furthermore, no correlation between improvement of QoL and the use of probiotics (SMD -0.64, 95% CI -1.27 to 0.00, I2 = 93,9%) was shown. However, probiotics were associated with a significant reduction in bloating (SMD -0.28, 95% CI -0.47 to -0.09, I2 = 36,0%). A qualitative synthesis was conducted about adverse events and showed that the use of probiotics' is safe without severe adverse events. CONCLUSIONS The administration of probiotics to IBS-patients demonstrated a positive effect on pain and bloating, but due to significant heterogeneity and confounding factors, that were not examined in the included studies, a definitive statement cannot be made. Moreover, probiotics did not lead to an improvement in other parameters. There is a need for larger RCTs in IBS-patients diagnosed according to Rome IV (not III) criteria and especially it is essential to be conducted RCTs which examine the administration of specific strains and have similar methodological characteristics.
Collapse
Affiliation(s)
- Georgios Konstantis
- Clinical Pharmacology, Faculty of Medicine, School of Health Sciences, Aristotle University of Thessaloniki, Thessaloniki, Greece; Department of Gastroenterology, Hepatology and Transplant Medicine, Medical Faculty, University of Duisburg-Essen, Essen, Germany
| | - Stylianos Efstathiou
- Clinical Pharmacology, Faculty of Medicine, School of Health Sciences, Aristotle University of Thessaloniki, Thessaloniki, Greece
| | - Chryssa Pourzitaki
- Clinical Pharmacology, Faculty of Medicine, School of Health Sciences, Aristotle University of Thessaloniki, Thessaloniki, Greece.
| | - Elisavet Kitsikidou
- Department of Internal Medicine, Evangelical Hospital Dusseldorf, Dusseldorf, Germany
| | - Georgios Germanidis
- Division of Gastroenterology and Hepatology, 1st Department of Internal Medicine, AHEPA University Hospital, School of Medicine, Faculty of Health Sciences, Aristotle University of Thessaloniki, Thessaloniki, Greece
| | - Michail Chourdakis
- Laboratory of Hygiene, Social & Preventive Medicine and Medical Statistics, School of Medicine, Faculty of Health Sciences, Aristotle University of Thessaloniki, Thessaloniki, Greece
| |
Collapse
|
|
18
|
Shin A, Xu H, Imperiale TF. The Prevalence, Humanistic Burden, and Health Care Impact of Irritable Bowel Syndrome Among United States Veterans. Clin Gastroenterol Hepatol 2023; 21:1061-1069.e1. [PMID: 35964894 PMCID: PMC9918609 DOI: 10.1016/j.cgh.2022.08.005] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/11/2022] [Revised: 08/01/2022] [Accepted: 08/04/2022] [Indexed: 01/13/2023]
Abstract
BACKGROUND & AIMS Irritable bowel syndrome (IBS) in veterans is understudied. This study sought to investigate (1) prevalence of IBS; (2) phenotypic, environmental, and psychosocial factors associated with IBS; and (3) associations of IBS with health-related quality of life and health care use. METHODS From June 2018 to April 2020, we invited veterans to complete the Rome IV IBS questionnaire; Short Form-12; posttraumatic stress disorder (PTSD) checklist; Hospital Anxiety and Depression Scale; and questionnaires on general health, antibiotic use, infectious enteritis (IE), and health care use. RESULTS Among 858 veteran respondents, 244 (28.4%) met Rome IV IBS criteria (47.5% IBS with diarrhea, 16.8% IBS with constipation, 33.6% mixed IBS). IBS was associated with greater anxiety and depression and lower quality of life (all P < .001). Provisional PTSD, IE, and bowel problems after antibiotics were more common in IBS (all P < .001) as were multiple doctor visits (P < .01) and hospitalizations (P = .04). Comparisons across non-IBS and IBS subgroups revealed overall associations of psychological comorbidities (P < .01), multiple doctor visits (P < .01), hospitalizations (P = .03), IE (P < .01), and bowel problems after IE (P = .03) or antibiotics (P < .01) with subgroup. Highest anxiety and depression scores, PTSD, multiple doctor visits, hospitalizations, and bowel problems after IE were observed in IBS with constipation. In adjusted analyses, IBS was associated (all P < .001) with anxiety (odds ratio [OR], 3.47), depression (OR, 2.88), lower quality of life, PTSD (OR, 3.09), IE (OR, 4.44), bowel problems after antibiotics (OR, 1.84), multiple doctor visits (OR, 2.08), and hospitalizations (OR, 1.78). CONCLUSIONS IBS is prevalent among veterans and has a measurable impact on individuals and health care resources. Veterans with IBS may experience significant psychological impairment.
Collapse
Affiliation(s)
- Andrea Shin
- Division of Gastroenterology and Hepatology, Department of Medicine, Indiana University School of Medicine, Indianapolis, Indiana.
| | - Huiping Xu
- Department of Biostatistics and Health Data Science, Indiana University School of Medicine, Indianapolis, Indiana
| | - Thomas F Imperiale
- Division of Gastroenterology and Hepatology, Department of Medicine, Indiana University School of Medicine, Indianapolis, Indiana
| |
Collapse
|
|
19
|
Wang Z, Peng Y, Chen M, Peng L, Huang Y, Lin W. The Prevalence of Irritable Bowel Syndrome after Severe Acute Respiratory Syndrome Coronavirus 2 Infection and Their Association: A Systematic Review and Meta-Analysis of Observational Studies. J Clin Med 2023; 12:jcm12051865. [PMID: 36902651 PMCID: PMC10003507 DOI: 10.3390/jcm12051865] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/09/2023] [Revised: 02/19/2023] [Accepted: 02/20/2023] [Indexed: 03/02/2023] Open
Abstract
AIM Investigate the prevalence of irritable bowel syndrome (IBS) after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and assess the association between IBS and SARS-CoV-2 infection. METHODS A systematic literature search for PubMed, Web of Science, Embase, Scopus, and the Cochrane Library was performed to identify all reports published before 31 December 2022. The confidence interval (CI), estimation effect (ES) of prevalence, and risk ratios (RR) were calculated to evaluate the prevalence of IBS after SARS-CoV-2 infection and their association. Individual results were pooled by the random-effects (RE) model. Subgroup analyses conducted a further investigation of the results. We employed funnel plots, Egger's test, and Begg's test to evaluate publication bias. Sensitivity analysis was performed for the assessment of the robustness of the result. RESULTS The data on IBS prevalence after SARS-CoV-2 infection were extracted from two cross-sectional studies and ten longitudinal studies from nineteen countries with 3950 individuals. The IBS prevalence after SARS-CoV-2 infection ranges from 3% to 91% in different countries, and the overall pooled prevalence of IBS following SARS-CoV-2 infection is 15% (ES: 0.15; 95% CI, 0.11-0.20; p = 0.000). The data on the association between IBS and SARS-CoV-2 infection were extracted from six cohort studies from fifteen countries with 3595 individuals. The risk of IBS increased following SARS-CoV-2 infection but was not significant (RR: 1.82; 95% CI, 0.90-3.69; p = 0.096). CONCLUSIONS In conclusion, the overall pooled prevalence of IBS following SARS-CoV-2 infection was 15%, and SARS-CoV-2 infection increased the overall risk of IBS but was not statistically significant. Further extra high-quality epidemiological evidence and studies to clarify the underlying mechanism of IBS following SARS-CoV-2 infection are needed.
Collapse
Affiliation(s)
- Ziyan Wang
- Department of Gastroenterology, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou 510120, China
- The First Clinical School, Guangzhou Medical University, Guangzhou 510120, China
| | - Yinglong Peng
- School of Medicine, South China University of Technology, Guangzhou 510006, China
- Correspondence: (Y.P.); (L.P.)
| | - Minshan Chen
- The First Clinical School, Guangzhou Medical University, Guangzhou 510120, China
| | - Liang Peng
- Department of Gastroenterology, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou 510120, China
- Correspondence: (Y.P.); (L.P.)
| | - Yongzhen Huang
- First Clinical Medical School, Southern Medical University, Guangzhou 510515, China
| | - Wei Lin
- School of Pediatrics, Guangzhou Medical University, Guangzhou 510182, China
| |
Collapse
|
|
20
|
Breen-Lyles M, Decuir M, Byale A, Smith K, Grover M. Impact of Rome IV criteria on the prevalence of post-infection irritable bowel syndrome. Neurogastroenterol Motil 2023; 35:e14532. [PMID: 36633303 DOI: 10.1111/nmo.14532] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/13/2022] [Revised: 12/20/2022] [Accepted: 01/01/2023] [Indexed: 01/13/2023]
Abstract
BACKGROUND The Rome IV irritable bowel syndrome (IBS) criteria include changes to the description and frequency of abdominal pain. Existing studies have demonstrated a lower prevalence and greater severity in IBS patients identified using Rome IV than Rome III criteria. Our aim was to investigate the prevalence of post-infection IBS (PI-IBS) using Rome IV criteria in a population-based cohort of laboratory-confirmed C. jejuni infection cases. METHODS The Minnesota Department of Health (MDH) requires notification of Campylobacter cases and interviews patients to gather information on clinical symptoms. For this study, the Rome IV diagnostic questionnaire was utilized 6-9 months after infection to determine the development of PI-IBS. The survey responses were analyzed for the prevalence of IBS and symptom severity. KEY RESULTS Surveys were completed by 391 participants (31% response rate). Twenty-three patients had pre-existing IBS, and 18 did not complete enough questions to categorize their case status. Of the 350 remaining participants, 58 (17%) met Rome IV criteria. An additional 47 patients would have met the Rome III IBS criteria for pain frequency, driving the cumulative prevalence to 30%. The mean IBS Symptom Severity Score (IBS-SSS) in Rome IV patients was significantly higher than in Rome III (p < 0.05). With Rome IV, IBS-diarrhea was the most common subtype. CONCLUSIONS & INFERENCES Rome IV criteria resulted in a 19% lower prevalence of PI-IBS than earlier reported Rome III-based prevalence in a similar population. Rome IV defined PI-IBS patients have greater symptom severity but similar distribution of IBS subtypes.
Collapse
Affiliation(s)
- Margaret Breen-Lyles
- Department of Gastroenterology and Hepatology, Enteric Neuroscience Program, Mayo Clinic, Rochester, Minnesota, USA
| | - Marijke Decuir
- Minnesota Department of Health, St. Paul, Minnesota, USA
| | - Anjali Byale
- Department of Gastroenterology and Hepatology, Enteric Neuroscience Program, Mayo Clinic, Rochester, Minnesota, USA
| | - Kirk Smith
- Minnesota Department of Health, St. Paul, Minnesota, USA
| | - Madhusudan Grover
- Department of Gastroenterology and Hepatology, Enteric Neuroscience Program, Mayo Clinic, Rochester, Minnesota, USA
| |
Collapse
|
|
21
|
Wang X, Shi X, Lv J, Zhang J, Huo Y, Zuo G, Lu G, Liu C, She Y. Acupuncture and related therapies for the anxiety and depression in irritable bowel syndrome with diarrhea (IBS-D): A network meta-analysis of randomized controlled trials. Front Psychiatry 2022; 13:1067329. [PMID: 36620677 PMCID: PMC9816906 DOI: 10.3389/fpsyt.2022.1067329] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/11/2022] [Accepted: 12/07/2022] [Indexed: 12/25/2022] Open
Abstract
Objective A growing number of clinical studies have suggested the value of acupuncture-related therapies for patients with irritable bowel syndrome with diarrhea (IBS-D), and the patient's mental state plays an important role, but there are many types of acupuncture-related therapies involved. This study aimed to evaluate the mental status, efficacy and safety of the different acupuncture-related therapies for IBS-D patients. Methods We searched seven databases to collect randomized controlled trials of acupuncture-related therapies for IBS-D. After independent literature screening and data extraction, the quality of the final included literature was evaluated. Hamilton anxiety rating scale (HAMA), hamilton depression rating scale (HAMD), self-rating anxiety scale (SAS), and self-rating depression scale (SDS) was used as the primary outcome indicator. And the network meta-analysis (NMA) was performed by using Revman 5.4, Stata 15.0 and WinBUGS 1.4.3 software, and the surface under the cumulative ranking curve was conducted to rank the included interventions. Results We analyzed 24 eligible studies with 1,885 patients, involving eight types of acupuncture and related therapies along with comprehensive therapies. The NMA result shows that: for SAS scores, combined therapies were more efficacious than anti-diarrheal or antispasmodic (western medicine, WM) (SMD: -8.92; 95% CI: -15.30, -2.47); for SDS scores, combined therapies were more efficacious than WM (SMD: -8.45; 95% CI: -15.50, -1.41). For HAMA scores, moxibustion (MOX) was more efficacious than placebo (SMD: -8.66; 95% CI: -16.64, -0.38). For HAMD scores, MOX was more efficacious than all other included interventions. For response rate, MOX was more efficacious than the following interventions: acupuncture (ACU) (SMD:0.29; 95% CI:0.08,0.93), Chinese herb medicine (CH) (SMD:0.09; 95% CI:0.02,0.36), combined therapies (SMD:0.23; 95% CI:0.06, 0.85), electroacupuncture (EA) (SMD:0.06; 95% CI:0.01,0.33), warm acupuncture (WA) (SMD:22.16; 95% CI:3.53,148.10), WM (SMD:15.59; 95% CI:4.68,61.21), and placebo (SMD:9.80; 95% CI:2.90,45.51). Combined therapies were more efficacious than the following interventions: CH (SMD:0.39; 95% CI:0.19,0.80), WA (SMD:4.96; 95% CI:1.30,21.62), and WM (SMD:3.62; 95% CI:2.35,5.66). The comprehensive ranking results show that MOX, ACU, combined therapies, and EA had high SUCRA rankings involving different outcome indicators. Conclusion MOX, ACU, combined therapies, and EA better alleviate anxiety and depression among IBS-D patients, and with a higher safety level, may be the optimal therapies. In addition, combining acupuncture-related treatments and other therapies also delivers a higher global benefit level. Systematic review registration [https://www.crd.york.ac.uk/], identifier [CRD42022364560].
Collapse
Affiliation(s)
- Xuesong Wang
- School of Acupuncture-Moxibustion and Tuina, Hebei University of Chinese Medicine, Shijiazhuang, Hebei, China
| | - Xuliang Shi
- School of Acupuncture-Moxibustion and Tuina, Hebei University of Chinese Medicine, Shijiazhuang, Hebei, China
- Hebei International Joint Research Center for Dominant Diseases in Chinese Medicine and Acupuncture, Hebei University of Chinese Medicine, Shijiazhuang, Hebei, China
| | - Jing Lv
- School of Acupuncture-Moxibustion and Tuina, Hebei University of Chinese Medicine, Shijiazhuang, Hebei, China
- Hebei International Joint Research Center for Dominant Diseases in Chinese Medicine and Acupuncture, Hebei University of Chinese Medicine, Shijiazhuang, Hebei, China
| | - Juncha Zhang
- School of Acupuncture-Moxibustion and Tuina, Hebei University of Chinese Medicine, Shijiazhuang, Hebei, China
- Hebei International Joint Research Center for Dominant Diseases in Chinese Medicine and Acupuncture, Hebei University of Chinese Medicine, Shijiazhuang, Hebei, China
| | - Yongli Huo
- Department of Spleen and Stomach, Hebei Province Hospital of Chinese Medicine, Shijiazhuang, Hebei, China
| | - Guang Zuo
- School of Acupuncture-Moxibustion and Tuina, Hebei University of Chinese Medicine, Shijiazhuang, Hebei, China
| | - Guangtong Lu
- School of Acupuncture-Moxibustion and Tuina, Hebei University of Chinese Medicine, Shijiazhuang, Hebei, China
| | - Cunzhi Liu
- School of Acupuncture-Moxibustion and Tuina, Beijing University of Chinese Medicine, Beijing, China
| | - Yanfen She
- School of Acupuncture-Moxibustion and Tuina, Hebei University of Chinese Medicine, Shijiazhuang, Hebei, China
- Hebei International Joint Research Center for Dominant Diseases in Chinese Medicine and Acupuncture, Hebei University of Chinese Medicine, Shijiazhuang, Hebei, China
| |
Collapse
|
|
22
|
Black CJ, Houghton LA, Ford AC. Latent class analysis does not support the existence of Rome IV functional bowel disorders as discrete entities. Neurogastroenterol Motil 2022; 34:e14391. [PMID: 35531932 PMCID: PMC9788160 DOI: 10.1111/nmo.14391] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/07/2022] [Revised: 04/20/2022] [Accepted: 04/25/2022] [Indexed: 12/30/2022]
Abstract
BACKGROUND Previously, we used latent class analysis (LCA) to identify novel subgroups in people with irritable bowel syndrome (IBS). There are four other functional bowel disorders that, although characterized as discrete disorders, overlap considerably with, and fluctuate to, IBS. These might instead be conceptualized as a milder form of IBS. We explored this hypothesis using LCA in a cohort of people with non-IBS functional bowel disorders. METHODS We collected demographic, symptom, and psychological health data from 1375 adults in the community who self-identified as having IBS and identified individuals meeting Rome IV criteria for any non-IBS functional bowel disorder. We performed LCA to identify specific subgroups (clusters). We followed participants up at 12 months to reassess gastrointestinal and psychological heath and also gather data about healthcare utilization and impact of symptoms. KEY RESULTS 811 people met Rome IV criteria for IBS and 558 Rome IV criteria for another functional bowel disorder (76 (5.5%) functional constipation; 198 (14.5%) functional diarrhea; 129 (9.5%) functional abdominal bloating or distension; and 155 (11.4%) unspecified functional bowel disorder). LCA in these 558 people identified five clusters defined by a combination of gastrointestinal symptoms and the extent of psychological co-morbidity. However, correlation between these clusters and the Rome IV functional bowel disorder diagnoses was poor and 75% of people were classified as having mild IBS using our previous IBS-derived model. By 12 months, one-third of people had fluctuated and met criteria for IBS. Clusters with high psychological burden had a poorer prognosis, with higher rates of medical consultation, medication use, and greater impact of symptoms on daily life. CONCLUSIONS AND INFERENCES The functional bowel disorders may be better characterized as a spectrum of IBS rather than separate disorders. Adopting this pragmatic stance may help to simply diagnosis, treatment, and recruitment of patients to research trials.
Collapse
Affiliation(s)
- Christopher J. Black
- Leeds Institute of Medical Research at St. James’sUniversity of LeedsLeedsUK,Leeds Gastroenterology InstituteSt. James’s University HospitalLeedsUK
| | - Lesley A. Houghton
- Leeds Institute of Medical Research at St. James’sUniversity of LeedsLeedsUK
| | - Alexander C. Ford
- Leeds Institute of Medical Research at St. James’sUniversity of LeedsLeedsUK,Leeds Gastroenterology InstituteSt. James’s University HospitalLeedsUK
| |
Collapse
|
|
23
|
van der Geest AM, Schukking I, Brummer RJM, van de Burgwal LHM, Larsen OFA. Comparing probiotic and drug interventions in irritable bowel syndrome: a meta-analysis of randomised controlled trials. Benef Microbes 2022; 13:183-194. [PMID: 35848115 DOI: 10.3920/bm2021.0123] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
Clinical decisions made by health professionals to recommend either drug or probiotic interventions for irritable bowel syndrome (IBS) should be supported by proper knowledge of the efficacy rates of both types of interventions. In this article, we performed a systematic review and meta-analysis to examine the efficacy of both probiotic- and drug interventions in IBS. Medline was searched between January 2015 - January 2021. Randomised controlled trials (RCT) recruiting participants > 18 years old with IBS and examining the effect of probiotics or drugs were eligible for inclusion. The data of the primary outcome, i.e. the persistence of IBS symptoms (dichotomous symptom data), were pooled to obtain a relative risk (RR), with a 95% confidence interval (CI). Secondary outcomes, abdominal pain- and bloating scores (continuous data), were pooled using a standardised mean difference with a 95% CI. The search identified 269 citations of which 32 RCTs were eligible. Our meta-analysis indicated that both probiotic and drug interventions are able to improve the persistence of IBS symptoms (RR 0.60 [0.51; 0.92] versus 0.87 [0.81; 0.92], respectively) and abdominal pain scores (standardised mean difference (SMD) -0.35 [-0.56; -0.14] versus -0.10 [-0.20; 0.00], respectively). However, determining the overall efficacy of both intervention types is inherently complex and such results should be interpreted with care, due to the large diversity of probiotic- and drug types and doses, which is also complicated by variety in IBS subtypes. Hence, as a first step, more large scale randomised double blind placebo-controlled trials focussing on a specific IBS subtype targeted with specific probiotic strains or specific pharmaceutical modalities should be executed, enabling a more proper comparison between trials.
Collapse
Affiliation(s)
- A M van der Geest
- Vrije Universiteit Amsterdam, Athena Institute, De Boelelaan 1085, 1081 HV Amsterdam, the Netherlands
| | - I Schukking
- Vrije Universiteit Amsterdam, Athena Institute, De Boelelaan 1085, 1081 HV Amsterdam, the Netherlands
| | - R J M Brummer
- Örebro University, School of Medical Sciences, Faculty of Medical and Health Sciences, Fakultetsgatan 1, 70182 Örebro, Sweden
| | - L H M van de Burgwal
- Vrije Universiteit Amsterdam, Athena Institute, De Boelelaan 1085, 1081 HV Amsterdam, the Netherlands
| | - O F A Larsen
- Vrije Universiteit Amsterdam, Athena Institute, De Boelelaan 1085, 1081 HV Amsterdam, the Netherlands
| |
Collapse
|
|
24
|
Associations between Abnormal Eating Styles and Irritable Bowel Syndrome: A Cross-Sectional Study among Medical School Students. Nutrients 2022; 14:nu14142828. [PMID: 35889787 PMCID: PMC9319336 DOI: 10.3390/nu14142828] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/07/2022] [Revised: 07/02/2022] [Accepted: 07/08/2022] [Indexed: 02/05/2023] Open
Abstract
(1) Background: Few studies have investigated the association between eating styles and IBS. This study aimed to explore the association between abnormal eating styles and irritable bowel syndrome (IBS). (2) Methods: This cross-sectional study investigated students in China Medical University and Shenyang Medical College. Eating styles were evaluated by the Dutch Eating Behavior Questionnaire (DEBQ), and IBS was diagnosed according to Rome III criteria. Logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs). (3) Results: A total of 335 students were diagnosed with IBS. Students with the total scores in tertile 2 and 3 had 1.29 times and 2.75 times higher risk of IBS than students with the total scores in tertile 1, respectively. Simultaneously, the risk of IBS in the tertile 3 of external eating, emotional eating, and restraint eating trends was 3.87 times, 2.71 times, and 3.82 times higher than that of tertile 1, respectively. (4) Conclusions: this study showed that a high score in both total eating styles and each eating style was associated with the odds of having IBS and suggested that the psychological factors behind eating styles may play a critical role in controlling the IBS.
Collapse
|
|
25
|
Tornkvist NT, Törnblom H. European guidelines on functional bowel disorders with diarrhoea: United European Gastroenterology (UEG) and European Society for neurogastroenterology and motility (ESNM) statements and recommendations. United European Gastroenterol J 2022; 10:615-616. [PMID: 35765230 PMCID: PMC9486482 DOI: 10.1002/ueg2.12270] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/09/2022] Open
Affiliation(s)
- Navkiran T Tornkvist
- Department of Molecular and Clinical Medicine, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden
| | - Hans Törnblom
- Department of Molecular and Clinical Medicine, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden
| |
Collapse
|
|
26
|
Sayuk GS, North CS, Pollio DE, Gott BM, Alpers DH. Episodic Memories Among Irritable Bowel Syndrome (IBS) Patients: An Important Aspect of the IBS Symptom Experience. FRONTIERS IN PAIN RESEARCH 2022; 3:892313. [PMID: 35782224 PMCID: PMC9243497 DOI: 10.3389/fpain.2022.892313] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/08/2022] [Accepted: 05/20/2022] [Indexed: 11/21/2022] Open
Abstract
Objective: Some IBS patients possess detailed memories of the events surrounding their bowel symptom onset (“episodic memories”). In this exploratory study we sought to: (1) examine memory relationship with gastrointestinal (GI) symptom severity, extraintestinal symptoms, and mood; (2) qualitatively explore memory valence and content in IBS patients with or without episodic memories. Methods Referral IBS patients n = 29; age 47.0± 2.2 years, 79.3% female) enrolled in this cross-sectional, mixed methods research study. Participants completed validated specific memory instruments [Autobiographical Memory Test (AMT), Sentence Completion for Events from the Past Test (SCEPT)] and relevant questionnaires [IBS symptoms 10-cm visual analog scale); SF-36 Health-related quality of life (HRQOL); Perley-Guze and PHQ-15/12: somatization; Beck Depression/Anxiety Inventories). Qualitative analysis examined the content and valence of general memories. Results 14/29 (48.3%) of IBS subjects endorsed episodic memories of IBS symptom onset, often GI infections/enteritis (35.7%). Recall of the exact year (69%) and month (60%) of symptom onset were common. Episodic memories were associated with greater IBS symptom severity/bother, higher anxiety/depression, and poorer HRQOL. Though AMT and SCEPT memory specificity were not different based on episodic memories, overgeneralization to negatively-valenced cues in the AMT was associated with more severe IBS in those without episodic memory. Qualitative analysis revealed no observable differences in topic focus of IBS patients with and without episodic memories. Conclusions IBS patients often endorse episodic memories associated with symptom onset, and this recall seems to associate with more severe symptoms. Overgeneralization responses to negative stimuli may lead to worse bowel symptoms in those without episodic memories. IBS memory specificity may associate with qualitative differences in processing psychosocial experiences and might be important to IBS pathophysiology.
Collapse
Affiliation(s)
- Gregory S. Sayuk
- Division of Gastroenterology, Washington University School of Medicine, St. Louis, MO, United States
- Department of Psychiatry, Washington University School of Medicine, St. Louis, MO, United States
- St. Louis Veterans Affairs Medical Center, St. Louis, MO, United States
- *Correspondence: Gregory S. Sayuk
| | - Carol S. North
- The Altshuler Center for Education & Research, Metrocare Services, Dallas, TX, United States
- Department of Psychiatry, The University of Texas Southwestern Medical Center, Dallas, TX, United States
| | | | - Britt M. Gott
- Department of Psychiatry, Washington University School of Medicine, St. Louis, MO, United States
| | - David H. Alpers
- Division of Gastroenterology, Washington University School of Medicine, St. Louis, MO, United States
| |
Collapse
|
|
27
|
Savarino E, Zingone F, Barberio B, Marasco G, Akyuz F, Akpinar H, Barboi O, Bodini G, Bor S, Chiarioni G, Cristian G, Corsetti M, Di Sabatino A, Dimitriu AM, Drug V, Dumitrascu DL, Ford AC, Hauser G, Nakov R, Patel N, Pohl D, Sfarti C, Serra J, Simrén M, Suciu A, Tack J, Toruner M, Walters J, Cremon C, Barbara G. Functional bowel disorders with diarrhoea: Clinical guidelines of the United European Gastroenterology and European Society for Neurogastroenterology and Motility. United European Gastroenterol J 2022; 10:556-584. [PMID: 35695704 PMCID: PMC9278595 DOI: 10.1002/ueg2.12259] [Citation(s) in RCA: 70] [Impact Index Per Article: 23.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/21/2022] [Accepted: 05/20/2022] [Indexed: 11/23/2022] Open
Abstract
Irritable bowel syndrome with diarrhoea (IBS‐D) and functional diarrhoea (FDr) are the two major functional bowel disorders characterized by diarrhoea. In spite of their high prevalence, IBS‐D and FDr are associated with major uncertainties, especially regarding their optimal diagnostic work‐up and management. A Delphi consensus was performed with experts from 10 European countries who conducted a literature summary and voting process on 31 statements. Quality of evidence was evaluated using the grading of recommendations, assessment, development, and evaluation criteria. Consensus (defined as >80% agreement) was reached for all the statements. The panel agreed with the potential overlapping of IBS‐D and FDr. In terms of diagnosis, the consensus supports a symptom‐based approach also with the exclusion of alarm symptoms, recommending the evaluation of full blood count, C‐reactive protein, serology for coeliac disease, and faecal calprotectin, and consideration of diagnosing bile acid diarrhoea. Colonoscopy with random biopsies in both the right and left colon is recommended in patients older than 50 years and in presence of alarm features. Regarding treatment, a strong consensus was achieved for the use of a diet low fermentable oligo‐, di‐, monosaccharides and polyols, gut‐directed psychological therapies, rifaximin, loperamide, and eluxadoline. A weak or conditional recommendation was achieved for antispasmodics, probiotics, tryciclic antidepressants, bile acid sequestrants, 5‐hydroxytryptamine‐3 antagonists (i.e. alosetron, ondansetron, or ramosetron). A multinational group of European experts summarized the current state of consensus on the definition, diagnosis, and management of IBS‐D and FDr.
Collapse
Affiliation(s)
- Edoardo Savarino
- Gastroenterology Unit, Department of Surgery, Oncology and Gastroenterology, University of Padua, Padua, Italy
| | - Fabiana Zingone
- Gastroenterology Unit, Department of Surgery, Oncology and Gastroenterology, University of Padua, Padua, Italy
| | - Brigida Barberio
- Gastroenterology Unit, Department of Surgery, Oncology and Gastroenterology, University of Padua, Padua, Italy
| | - Giovanni Marasco
- Division of Internal Medicine, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy.,Department of Medical and Surgical Sciences, University of Bologna, Bologna, Italy
| | - Filiz Akyuz
- Department of Gastroenterology, İstanbul University İstanbul School of Medicine, İstanbul, Turkey
| | - Hale Akpinar
- Department of Internal Medicine, Dokuz Eylül University School of Medicine, Izmir, Turkey
| | - Oana Barboi
- Department of Gastroenterology, 'Grigore T. Popa' University of Medicine and Pharmacy, Iasi, Romania.,Institute of Gastroenterology and Hepatology, 'Saint Spiridon' Hospital, Iasi, Romania
| | - Giorgia Bodini
- Gastrointestinal Unit, Department of Internal Medicine, University of Genoa, Genoa, Italy
| | - Serhat Bor
- Division of Gastroenterology, Ege University School of Medicine, Izmir, Turkey
| | | | - Gheorghe Cristian
- Fundeni Clinical Institute Center of Gastroenterology and Hepatology, Carol Davila University of Medicine and Pharmacy, Bucharest, Romania
| | - Maura Corsetti
- National Institute for Health Research, Nottingham Biomedical Research Centre, Nottingham University Hospitals NHS Trust, Nottingham, UK.,Nottingham Digestive Diseases Centre, School of Medicine, University of Nottingham, Nottingham, UK
| | - Antonio Di Sabatino
- First Department of Internal Medicine, IRCCS San Matteo Hospital Foundation, University of Pavia, Pavia, Italy
| | - Anca Mirela Dimitriu
- Center of Gastroenterology and Hepatology, Fundeni Clinical Institute, University of Medicine and Pharmacy, Bucharest, Romania
| | - Vasile Drug
- Department of Gastroenterology, 'Grigore T. Popa' University of Medicine and Pharmacy, Iasi, Romania.,Institute of Gastroenterology and Hepatology, 'Saint Spiridon' Hospital, Iasi, Romania
| | - Dan L Dumitrascu
- 2nd Department of Internal Medicine, 'Iuliu Hatieganu' University of Medicine and Farmacy, Cluj-Napoca, Romania
| | - Alexander C Ford
- Leeds Gastroenterology Institute, Leeds Teaching Hospitals NHS Trust, Leeds, UK.,Leeds Institute of Medical Research at St. James's Sciences, University of Leeds, Leeds, UK
| | - Goran Hauser
- Department of Gastroenterology, Clinical Hospital Center Rijeka, Faculty of Medicine, University of Rijeka, Rijeka, Croatia
| | - Radislav Nakov
- Department of Gastroenterology, Tsaritsa Yoanna University Hospital, Medical University of Sofia, Sofia, Bulgaria
| | - Nisha Patel
- Imperial College Healthcare NHS Trust, Institute of Global Health Innovation, St Mary's Hospital Campus, London, UK
| | - Daniel Pohl
- Department of Gastroenterology, University Hospital Zurich, Zurich, Switzerland
| | - Cătălin Sfarti
- Department of Gastroenterology, 'Grigore T. Popa' University of Medicine and Pharmacy, Iasi, Romania.,Institute of Gastroenterology and Hepatology, 'Saint Spiridon' Hospital, Iasi, Romania
| | - Jordi Serra
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Badalona, Spain.,Digestive System Research Unit, University Hospital Vall d'Hebron, Barcelona, Spain.,Department of Medicine, Autonomous University of Barcelona, Badalona, Spain
| | - Magnus Simrén
- Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden
| | - Alina Suciu
- Center of Gastroenterology and Hepatology, Fundeni Clinical Institute, University of Medicine and Pharmacy, Bucharest, Romania
| | - Jan Tack
- Translational Research Center for Gastrointestinal Disorders, University of Leuven, Leuven, Belgium
| | - Murat Toruner
- Department of Gastroenterology, Ankara University School of Medicine, Ankara, Turkey
| | - Julian Walters
- Division of Digestive Diseases, Department of Metabolism, Digestion, and Reproduction, Faculty of Medicine, Imperial College London, London, UK.,Department of Gastroenterology, Division of Medicine and Integrated Care, Imperial College Healthcare NHS Trust, London, UK
| | - Cesare Cremon
- Division of Internal Medicine, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy.,Department of Medical and Surgical Sciences, University of Bologna, Bologna, Italy
| | - Giovanni Barbara
- Division of Internal Medicine, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy.,Department of Medical and Surgical Sciences, University of Bologna, Bologna, Italy
| |
Collapse
|
|
28
|
Barberio B, Savarino EV, Black CJ, Ford AC. Adverse events in trials of licensed drugs for irritable bowel syndrome with constipation or diarrhea: Systematic review and meta-analysis. Neurogastroenterol Motil 2022; 34:e14279. [PMID: 34672052 DOI: 10.1111/nmo.14279] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/21/2021] [Revised: 09/21/2021] [Accepted: 09/27/2021] [Indexed: 12/14/2022]
Abstract
BACKGROUND Nocebo effects occurring in patients receiving placebo frequently impact on adverse events reported in randomized controlled trials (RCTs) in irritable bowel syndrome (IBS). Therefore, we conducted a systematic review and meta-analysis to assess the proportion of patients randomized to placebo or active drug experiencing any adverse event in trials of licensed drugs for IBS with constipation (IBS-C) or diarrhea (IBS-D), and to estimate the risk of developing adverse events among patients randomized to placebo. METHODS We searched MEDLINE, EMBASE CLASSIC and EMBASE, and the Cochrane central register of controlled trials (through June 2021) to identify RCTs comparing licensed drugs with placebo in adults with IBS-C or IBS-D. We generated Forest plots of pooled adverse event rates in both active drug and placebo arms and pooled risk differences (RDs) with 95% confidence intervals (CIs). KEY RESULTS There were 21 RCTs of licensed drugs versus placebo in IBS-C (5953 patients placebo) and 17 in IBS-D (3854 patients placebo). Overall, 34.9% and 46.9% of placebo patients in IBS-C and IBS-D trials, respectively, developed at least one adverse event, with a statistically significantly higher risk of any adverse event and withdrawal due to an adverse event with active drug. In IBS-C and IBS-D trials, rates of each individual adverse event were generally higher with active drug. However, in IBS-C trials, only diarrhea or headache was significantly more common with active drug (RD 0.066 (95% CI 0.043-0.088) and RD 0.011 (95% CI 0.002-0.021), respectively), and in IBS-D trials only constipation, nausea, or abdominal pain (RD 0.096 (95% CI 0.054-0.138), 0.014 (95% CI 0.002-0.027), and 0.018 (95% CI 0.002-0.034), respectively). CONCLUSIONS & INFERENCES Patients with IBS randomized to placebo have a high risk of reporting adverse events, which might relate to both nocebo and non-nocebo factors. Although patients' expectations and psychosocial factors may be involved, further understanding of the mechanisms are important to control or optimize these effects in RCTs, as well as in clinical practice.
Collapse
Affiliation(s)
- Brigida Barberio
- Department of Surgery, Oncology and Gastroenterology (DISCOG), Gastroenterology Unit, University of Padova-Azienda Ospedaliera di Padova, Padova, Italy
| | - Edoardo V Savarino
- Department of Surgery, Oncology and Gastroenterology (DISCOG), Gastroenterology Unit, University of Padova-Azienda Ospedaliera di Padova, Padova, Italy
| | - Christopher J Black
- Leeds Gastroenterology Institute, St. James's University Hospital, Leeds, UK.,Leeds Institute of Medical Research at St. James's, University of Leeds, Leeds, UK
| | - Alexander C Ford
- Leeds Gastroenterology Institute, St. James's University Hospital, Leeds, UK.,Leeds Institute of Medical Research at St. James's, University of Leeds, Leeds, UK
| |
Collapse
|
|
29
|
Goodoory VC, Houghton LA, Black CJ, Ford AC. Characteristics of, and natural history among, individuals with Rome IV functional bowel disorders. Neurogastroenterol Motil 2022; 34:e14268. [PMID: 34532930 DOI: 10.1111/nmo.14268] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/08/2021] [Revised: 08/19/2021] [Accepted: 08/31/2021] [Indexed: 12/27/2022]
Abstract
BACKGROUND Little is known about the natural history of functional bowel disorders using Rome IV criteria. We examined these issues in a longitudinal follow-up study. METHODS We collected complete demographic, gastrointestinal symptom, and psychological comorbidity data at baseline from 1372 adults who met Rome IV criteria for one of the five functional bowel disorders. At 12 months, we collected data regarding gastrointestinal symptoms, psychological comorbidity, consultation behavior, and treatment commenced. We examined prognosis and stability of all five functional bowel disorders. KEY RESULTS At baseline, 811 (59.1%) individuals met Rome IV criteria for irritable bowel syndrome (IBS), 76 (5.5%) functional constipation (FC), 199 (14.5%) functional diarrhea (FDr), 130 (9.5%) functional abdominal bloating or distension (FABD), and 156 (11.4%) unspecified functional bowel disorder (UFBD). In total, 782 (57.0%) were successfully followed up. Individuals with IBS at baseline were significantly more likely to report symptoms compatible with anxiety, depression, or somatoform-type behavior (p < 0.001 for all analyses) at baseline and follow-up compared with those with the other four functional bowel disorders. IBS was the most stable functional bowel disorder; 319 (70.6%) of 452 participants still met criteria for IBS at 12 months, compared with 14 (34.1%) of 41, 43 (35.5%) of 121, 26 (33.8%) of 77, and 37 (40.7%) of 91 for FC, FDr, FABD, and UFBD, respectively (p < 0.001). CONCLUSIONS AND INFERENCES Individuals with Rome IV-defined IBS exhibited higher levels of anxiety, depression, or somatoform-type symptom reporting. IBS was the most stable and the likeliest disorder that the other four functional bowel disorders would fluctuate to.
Collapse
Affiliation(s)
- Vivek C Goodoory
- Leeds Institute of Medical Research at St. James's, University of Leeds, Leeds, UK.,Leeds Gastroenterology Institute, St. James's University Hospital, Leeds, UK
| | - Lesley A Houghton
- Leeds Institute of Medical Research at St. James's, University of Leeds, Leeds, UK
| | - Christopher J Black
- Leeds Institute of Medical Research at St. James's, University of Leeds, Leeds, UK.,Leeds Gastroenterology Institute, St. James's University Hospital, Leeds, UK
| | - Alexander C Ford
- Leeds Institute of Medical Research at St. James's, University of Leeds, Leeds, UK.,Leeds Gastroenterology Institute, St. James's University Hospital, Leeds, UK
| |
Collapse
|
|
30
|
Goodoory VC, Houghton LA, Yiannakou Y, Black CJ, Ford AC. Natural History and Disease Impact of Rome IV Vs Rome III Irritable Bowel Syndrome: A Longitudinal Follow-Up Study. Clin Gastroenterol Hepatol 2022; 20:569-577.e3. [PMID: 33957271 DOI: 10.1016/j.cgh.2021.04.043] [Citation(s) in RCA: 14] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/16/2021] [Revised: 04/21/2021] [Accepted: 04/27/2021] [Indexed: 02/07/2023]
Abstract
BACKGROUND & AIMS Irritable bowel syndrome (IBS) is a chronic functional bowel disorder diagnosed using the Rome criteria, which have evolved since their original description 30 years ago. Little is known about the effects on the natural history of IBS of moving to the latest iteration, Rome IV, from the previous Rome III criteria. We conducted a 12-month longitudinal follow-up study to examine this. METHODS We collected complete demographic, symptom, mood, and psychological health data at baseline from 1097 adults who self-identified as having IBS and met either Rome IV or Rome III criteria. At 12 months, we collected data regarding IBS symptom severity and impact, consultation behavior, treatments commenced, and psychological health. We examined whether subsequent disease behavior in Rome IV- or Rome III-defined IBS differed. RESULTS At 12 months, 638 (58.2%) of the 1097 participants were followed up successfully. Of these, 452 met Rome IV criteria and 186 met Rome III criteria at baseline. During the 12-month study period, individuals with Rome IV IBS were significantly more likely to have seen a primary care physician (44.7% vs 28.5%; P < .001) or a gastroenterologist (26.3% vs 12.4%; P < .001) for their IBS symptoms, were significantly more likely to have commenced a new treatment (73.0% vs 60.2%; P = .001), and cycled through significantly more treatments (P = .007), for their IBS compared with those with Rome III IBS. At follow-up evaluation, individuals with Rome IV IBS had more severe symptoms, which had a significantly greater impact on activities of daily living, were more likely to report continuous abdominal pain, and a higher proportion showed poor psychological health, compared with those with Rome III IBS (P < .001 for all analyses). CONCLUSIONS The natural history of IBS defined according to Rome IV criteria is more severe than that of Rome III-defined IBS. This has important implications for future treatment trials in IBS.
Collapse
Affiliation(s)
- Vivek C Goodoory
- Leeds Institute of Medical Research, Leeds, United Kingdom; Leeds Gastroenterology Institute, St. James's University Hospital, Leeds, United Kingdom
| | | | - Yan Yiannakou
- Gastroenterology Department, County Durham and Darlington National Health Service Foundation Trust, Durham, United Kingdom
| | - Christopher J Black
- Leeds Institute of Medical Research, Leeds, United Kingdom; Leeds Gastroenterology Institute, St. James's University Hospital, Leeds, United Kingdom
| | - Alexander C Ford
- Leeds Institute of Medical Research, Leeds, United Kingdom; Leeds Gastroenterology Institute, St. James's University Hospital, Leeds, United Kingdom.
| |
Collapse
|
|
31
|
Barberio B, Yiannakou Y, Houghton LA, Black CJ, Savarino EV, Ford AC. Overlap of Rome IV Irritable Bowel Syndrome and Functional Dyspepsia and Effect on Natural History: A Longitudinal Follow-Up Study. Clin Gastroenterol Hepatol 2022; 20:e89-e101. [PMID: 33839276 DOI: 10.1016/j.cgh.2021.04.011] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/08/2021] [Revised: 03/05/2021] [Accepted: 04/03/2021] [Indexed: 02/07/2023]
Abstract
OBJECTIVES Disorders of gut-brain interaction, such as irritable bowel syndrome (IBS) and functional dyspepsia (FD), frequently overlap, but the impact of this on the natural history is unknown. We examined this issue in a longitudinal follow-up study conducted in a large cohort of individuals. METHODS We collected complete demographic, symptom, mood, and psychological health data from 1374 adults who self-identified as having IBS. We applied the Rome IV criteria to examine what proportion met criteria for IBS and FD, as well as the degree of overlap between them. At 12 months, we collected data regarding IBS symptom severity and impact, consultation behavior, treatments commenced, and psychological health according to degree of overlap between IBS and FD. RESULTS Overall, 807 individuals met the Rome IV criteria for IBS at baseline and provided complete data. At study entry, overlap of FD occurred in 446 (55.3%) people who met Rome IV criteria for IBS. At 12 months, 451 (55.9%) individuals were successfully followed up. The proportion of individuals consulting their primary care physician (P = .001) or a gastroenterologist (P < .001) because of their IBS was significantly higher in those with overlap of IBS and FD, and the number of new IBS treatments commenced was significantly higher (P = .007). Those with overlap of IBS and FD reported significantly more severe IBS symptoms (P < .001), continuous abdominal pain, and that their IBS symptoms limited normal daily activities ≥50% of the time. Finally, those with overlap were more likely to report abnormal anxiety and depression scores at 12 months compared with those with IBS alone, and to have higher levels of somatization (P < .001 for all analyses). CONCLUSIONS The natural history of people with IBS with overlap FD defined according to Rome IV criteria is more severe than those with IBS alone. This has important implications for future treatment trials in IBS.
Collapse
Affiliation(s)
- Brigida Barberio
- Gastroenterology Unit, Department of Surgery, Oncology and Gastroenterology, University of Padova-Azienda Ospedaliera di Padova, Padova, Italy
| | - Yan Yiannakou
- Department of Gastroenterology, County Durham and Darlington NHS Foundation Trust, Durham, United Kingdom
| | - Lesley A Houghton
- Leeds Institute of Medical Research at St. James's, University of Leeds, Leeds, United Kingdom
| | - Christopher J Black
- Leeds Institute of Medical Research at St. James's, University of Leeds, Leeds, United Kingdom; Leeds Gastroenterology Institute, St. James's University Hospital, Leeds, United Kingdom
| | - Edoardo V Savarino
- Gastroenterology Unit, Department of Surgery, Oncology and Gastroenterology, University of Padova-Azienda Ospedaliera di Padova, Padova, Italy
| | - Alexander C Ford
- Leeds Institute of Medical Research at St. James's, University of Leeds, Leeds, United Kingdom; Leeds Gastroenterology Institute, St. James's University Hospital, Leeds, United Kingdom.
| |
Collapse
|
|
32
|
Shiha MG, Aziz I. Review article: Physical and psychological comorbidities associated with irritable bowel syndrome. Aliment Pharmacol Ther 2021; 54 Suppl 1:S12-S23. [PMID: 34927759 DOI: 10.1111/apt.16589] [Citation(s) in RCA: 18] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/15/2021] [Revised: 08/10/2021] [Accepted: 08/17/2021] [Indexed: 12/11/2022]
Abstract
Irritable bowel syndrome (IBS) is one of the most common gastrointestinal disorders encountered by physicians in primary and secondary care. Patients with IBS commonly present with various extraintestinal complaints, which account for a substantial clinical and economic burden. The common extraintestinal comorbidities associated with IBS include anxiety, depression, somatisation, fibromyalgia, chronic fatigue syndrome, chronic pelvic pain, interstitial cystitis, sexual dysfunction and sleep disturbance. The presence of comorbidity in IBS poses a diagnostic and therapeutic challenge with patients frequently undergoing unnecessary investigations and interventions, including surgery. This review discusses the different physical and psychological comorbidities associated with IBS, the shared pathophysiological mechanisms and potential management strategies.
Collapse
Affiliation(s)
- Mohamed G Shiha
- Academic Unit of Gastroenterology, Sheffield Teaching Hospitals, Sheffield, UK
| | - Imran Aziz
- Academic Unit of Gastroenterology, Sheffield Teaching Hospitals, Sheffield, UK.,Department of Infection, Immunity and Cardiovascular Disease, University of Sheffield, Sheffield, UK
| |
Collapse
|
|
33
|
Sperber AD. Review article: epidemiology of IBS and other bowel disorders of gut-brain interaction (DGBI). Aliment Pharmacol Ther 2021; 54 Suppl 1:S1-S11. [PMID: 34927754 DOI: 10.1111/apt.16582] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/29/2021] [Revised: 08/12/2021] [Accepted: 08/12/2021] [Indexed: 12/15/2022]
Abstract
The disorders of gut-brain interactions (DGBI) are a spectrum of gastrointestinal (GI) disorders that involve the entire GI tract and are usually categorised into four major anatomic GI regions, oesophageal, gastroduodenal, bowel and anorectal. Irritable bowel syndrome (IBS), a bowel DGBI, is one of the most researched DGBI and has been the subject of copious epidemiological studies. Prevalence rates are based on diagnostic criteria. In the case of IBS, there are three central obstacles to attaining a clear picture of prevalence: the absence of biomarkers, the multitude of diagnostic criteria used over the years, and the heterogeneous nature of the methodology used in epidemiologic surveys. When the results of multiple studies, conducted over a long period of time, using different diagnostic criteria and different research methodology, and involving different study populations are pooled to determine a single summary prevalence rate it is difficult to interpret the results and to determine their reliability and significance. This pitfall is insufficiently recognised and unfortunate because prevalence rates are important for understanding the burden of disease, for allocating healthcare and research resources, and for incentivising and prioritising new treatments. The aims of the present paper are to highlight our knowledge and understanding of IBS epidemiology within the context of other DGBI, and to present strategies to improve epidemiological research, especially in advance of the new Rome V criteria, to be published in 2026.
Collapse
Affiliation(s)
- Ami D Sperber
- Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer-Sheva, Israel
| |
Collapse
|
|
34
|
Vasant DH, Paine PA, Black CJ, Houghton LA, Everitt HA, Corsetti M, Agrawal A, Aziz I, Farmer AD, Eugenicos MP, Moss-Morris R, Yiannakou Y, Ford AC. British Society of Gastroenterology guidelines on the management of irritable bowel syndrome. Gut 2021; 70:1214-1240. [PMID: 33903147 DOI: 10.1136/gutjnl-2021-324598] [Citation(s) in RCA: 254] [Impact Index Per Article: 63.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/06/2021] [Revised: 03/30/2021] [Accepted: 04/06/2021] [Indexed: 12/11/2022]
Abstract
Irritable bowel syndrome (IBS) remains one of the most common gastrointestinal disorders seen by clinicians in both primary and secondary care. Since publication of the last British Society of Gastroenterology (BSG) guideline in 2007, substantial advances have been made in understanding its complex pathophysiology, resulting in its re-classification as a disorder of gut-brain interaction, rather than a functional gastrointestinal disorder. Moreover, there has been a considerable amount of new evidence published concerning the diagnosis, investigation and management of IBS. The primary aim of this guideline, commissioned by the BSG, is to review and summarise the current evidence to inform and guide clinical practice, by providing a practical framework for evidence-based management of patients. One of the strengths of this guideline is that the recommendations for treatment are based on evidence derived from a comprehensive search of the medical literature, which was used to inform an update of a series of trial-based and network meta-analyses assessing the efficacy of dietary, pharmacological and psychological therapies in treating IBS. Specific recommendations have been made according to the Grading of Recommendations Assessment, Development and Evaluation system, summarising both the strength of the recommendations and the overall quality of evidence. Finally, this guideline identifies novel treatments that are in development, as well as highlighting areas of unmet need for future research.
Collapse
Affiliation(s)
- Dipesh H Vasant
- Neurogastroenterology Unit, Gastroenterology, Wythenshawe Hospital, Manchester University NHS Foundation Trust, Manchester, UK.,Division of Diabetes, Endocrinology and Gastroenterology, University of Manchester, Manchester, UK
| | - Peter A Paine
- Division of Diabetes, Endocrinology and Gastroenterology, University of Manchester, Manchester, UK.,Gastroenterology, Salford Royal Foundation Trust, Salford, UK
| | - Christopher J Black
- Leeds Gastroenterology Institute, Leeds Teaching Hospitals NHS Trust, Leeds, UK.,Leeds Institute of Medical Research at St James's, University of Leeds, Leeds, UK
| | - Lesley A Houghton
- Leeds Institute of Medical Research at St James's, University of Leeds, Leeds, UK.,Gastroenterology and Hepatology, Mayo Clinic, Jacksonville, Florida, USA
| | - Hazel A Everitt
- Primary Care and Population Sciences, University of Southampton, Southampton, UK
| | - Maura Corsetti
- Nottingham Digestive Diseases Biomedical Research Unit, University of Nottingham, Nottingham, UK
| | - Anurag Agrawal
- Gastroenterology, Doncaster and Bassetlaw Hospitals NHS Trust, Armthorpe Road, Doncaster, UK
| | - Imran Aziz
- Academic Unit of Gastroenterology, Sheffield Teaching Hospitals NHS Foundation Trust, Sheffield, UK.,Department of Infection, Immunity and Cardiovascular Disease, University of Sheffield, Sheffield, UK
| | - Adam D Farmer
- Department of Gastroenterology, University Hospitals of North Midlands NHS Trust, Stoke-on-Trent, UK.,School of Medicine, Keele University, Keele, UK
| | - Maria P Eugenicos
- Department of Gastroenterology, University of Edinburgh, Western General Hospital, Edinburgh, UK
| | - Rona Moss-Morris
- Department of Psychology, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK
| | - Yan Yiannakou
- Department of Gastroenterology, County Durham and Darlington NHS Foundation Trust, Durham, UK
| | - Alexander C Ford
- Leeds Gastroenterology Institute, Leeds Teaching Hospitals NHS Trust, Leeds, UK .,Leeds Institute of Medical Research at St James's, University of Leeds, Leeds, UK
| |
Collapse
|
|
35
|
Impact of Psychological Comorbidity on the Prognosis of Irritable Bowel Syndrome. Am J Gastroenterol 2021; 116:1485-1494. [PMID: 33840729 DOI: 10.14309/ajg.0000000000001247] [Citation(s) in RCA: 25] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/28/2020] [Accepted: 02/26/2021] [Indexed: 12/11/2022]
Abstract
INTRODUCTION Psychological comorbidities are associated with irritable bowel syndrome (IBS), but little is known about their cumulative effect on its prognosis. We examined this issue in a longitudinal 12-month follow-up study. METHODS We collected complete demographic, symptom, and psychological comorbidity data (anxiety, depression, somatic symptom disorder, perceived stress, and gastrointestinal symptom-specific anxiety) at baseline from 807 adults who met Rome IV criteria for IBS. At 12 months, we collected data regarding IBS symptom severity and impact, consultation behavior, and treatments commenced from 452 individuals successfully followed up. We examined the cumulative effects of psychological comorbidities at baseline on subsequent IBS disease behavior. RESULTS At baseline, among the 807 participants, 177 (21.9%) had 1, 139 (17.2%) 2, 103 (12.8%) 3, 89 (11.0%) 4, and 54 (6.7%) 5 psychological comorbidities. IBS symptom severity at baseline increased significantly with the number of psychological comorbidities (72.2% of those with 5 psychological comorbidities reported severe symptoms, vs 29.1% of those with none, P < 0.001). Among 452 (56.0%) participants followed up at 12 months, those with a higher number of psychological comorbidities at baseline were significantly more likely to have seen a gastroenterologist (33.3% of those with 5 psychological comorbidities, vs 21.4% of those with none, P = 0.001), cycle through more treatments (P < 0.0001), to report more severe IBS symptoms (66.7% with 5, vs 24.4% with none, P < 0.001) and continuous abdominal pain (22.1% with none, vs 61.9% with 5, P < 0.001), and to report that symptoms impacted on daily activities ≥50% of the time (90.5% with 5, vs 41.2% with none, P < 0.001). DISCUSSION The prognosis of individuals with Rome IV-defined IBS worsens according to incremental increases in psychological comorbidity. This has important clinical and research implications.
Collapse
|
|
36
|
Black CJ, Yiannakou Y, Guthrie E, West R, Houghton LA, Ford AC. Longitudinal follow-up of a novel classification system for irritable bowel syndrome: natural history and prognostic value. Aliment Pharmacol Ther 2021; 53:1126-1137. [PMID: 33705578 DOI: 10.1111/apt.16322] [Citation(s) in RCA: 14] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/25/2021] [Revised: 02/08/2021] [Accepted: 02/23/2021] [Indexed: 12/15/2022]
Abstract
BACKGROUND Conventionally, irritable bowel syndrome (IBS) is subgrouped using predominant stool form, yet it is a complex disorder, with multiple biopsychosocial contributors. We previously derived and validated a latent class model subgrouping people with IBS into seven clusters based on gastrointestinal and extraintestinal symptoms and psychological profile. AIMS To conduct longitudinal follow-up examining the natural history and prognostic value of these clusters. METHODS Participants completed a 12-month follow-up questionnaire. We applied our model to these data, comparing cluster membership between the two time points in those still meeting Rome IV criteria at follow-up, including stratifying the analysis by predominant stool pattern, and level of psychological burden, at baseline. We examined whether baseline cluster predicted the course of IBS, and whether starting new treatment was associated with changing cluster. RESULTS Eight hundred and eleven participants met Rome IV criteria for IBS at baseline, of whom 452 (55.7%) responded, and 319 (70.6%) still met Rome IV criteria for IBS at follow-up. Of these, 172 (53.9%) remained in the same IBS cluster as at baseline and 147 changed cluster. Cluster membership stratified according to psychological comorbidity was more stable; 84% of those in a cluster with high psychological burden at baseline remained in such a cluster at follow-up. People in clusters with high psychological burden at baseline had more severe symptoms (P < 0.001), received a higher mean number of subsequent treatments (P < 0.001), and were more likely to consult a doctor than people in clusters with low psychological burden (P < 0.001). There was no significant association between starting a new treatment and changing cluster at follow-up. CONCLUSIONS Longitudinal follow-up demonstrated little transition between clusters with respect to psychological burden, and these appeared to predict disease course. Directing treatment according to cluster, including earlier use of psychological therapies, and exploring how this approach influences outcomes in IBS, should be examined.
Collapse
Affiliation(s)
- Christopher J Black
- Leeds Institute of Medical Research at St. James's, University of Leeds, Leeds, UK.,Leeds Gastroenterology Institute, St. James's University Hospital, Leeds, UK
| | - Yan Yiannakou
- County Durham and Darlington NHS Foundation Trust, Durham, UK
| | - Elspeth Guthrie
- Leeds Institute of Health Research, University of Leeds, Leeds, UK
| | - Robert West
- Leeds Institute of Health Research, University of Leeds, Leeds, UK
| | - Lesley A Houghton
- Leeds Institute of Medical Research at St. James's, University of Leeds, Leeds, UK
| | - Alexander C Ford
- Leeds Institute of Medical Research at St. James's, University of Leeds, Leeds, UK.,Leeds Gastroenterology Institute, St. James's University Hospital, Leeds, UK
| |
Collapse
|
|
37
|
Black CJ, Ford AC. Irritable bowel syndrome: a spotlight on future research needs. Lancet Gastroenterol Hepatol 2021; 6:419-422. [PMID: 33882271 DOI: 10.1016/s2468-1253(21)00131-x] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/29/2021] [Accepted: 03/29/2021] [Indexed: 12/18/2022]
Affiliation(s)
- Christopher J Black
- Leeds Institute of Medical Research at St James's, University of Leeds, Leeds, UK; Leeds Gastroenterology Institute, St James's University Hospital, Leeds, UK
| | - Alexander C Ford
- Leeds Institute of Medical Research at St James's, University of Leeds, Leeds, UK; Leeds Gastroenterology Institute, St James's University Hospital, Leeds, UK.
| |
Collapse
|