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Zhao X, Zheng I, Huang W, Tang D, Zhao M, Hou R, Huang Y, Shi Y, Zhu W, Wang S. Research Progress on the Mechanism of Bile Acids and Their Receptors in Depression. Int J Mol Sci 2025; 26:4023. [PMID: 40362260 PMCID: PMC12071821 DOI: 10.3390/ijms26094023] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/21/2025] [Revised: 04/17/2025] [Accepted: 04/23/2025] [Indexed: 05/15/2025] Open
Abstract
Depression, a highly prevalent mental disorder worldwide, arises from multifaceted interactions involving neurotransmitter imbalances, inflammatory responses, and gut-brain axis dysregulation. Emerging evidence highlights the pivotal role of bile acids (BAs) and their receptors, including farnesoid X receptor (FXR), Takeda G protein-coupled receptor 5 (TGR5), and liver X receptors (LXRs) in depression pathogenesis through modulation of neuroinflammation, gut microbiota homeostasis, and neural plasticity. Clinical investigations demonstrated altered BA profiles in depressed patients, characterized by decreased primary BAs (e.g., chenodeoxycholic acid (CDCA)) and elevated secondary BAs (e.g., lithocholic acid (LCA)), correlating with symptom severity. Preclinical studies revealed that BAs ameliorate depressive-like behaviors via dual mechanisms: direct CNS receptor activation and indirect gut-brain signaling, regulating neuroinflammation, oxidative stress, and BDNF/CREB pathways. However, clinical translation faces challenges including species-specific BA metabolism, receptor signaling complexity, and pharmacological barriers (e.g., limited blood-brain barrier permeability). While FXR/TGR5 agonists exhibit neuroprotective and anti-inflammatory potential, their adverse effects (pruritus, dyslipidemia) require thorough safety evaluation. Future research should integrate multiomics approaches and interdisciplinary strategies to develop personalized BA-targeted therapies, advancing novel treatment paradigms for depression.
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Affiliation(s)
- Xue Zhao
- Research Center of Experimental Acupuncture Science, Tianjin University of Traditional Chinese Medicine, Tianjin 301617, China; (X.Z.); (I.Z.); (W.H.); (D.T.); (M.Z.); (R.H.); (Y.H.)
| | - Iin Zheng
- Research Center of Experimental Acupuncture Science, Tianjin University of Traditional Chinese Medicine, Tianjin 301617, China; (X.Z.); (I.Z.); (W.H.); (D.T.); (M.Z.); (R.H.); (Y.H.)
| | - Wenjing Huang
- Research Center of Experimental Acupuncture Science, Tianjin University of Traditional Chinese Medicine, Tianjin 301617, China; (X.Z.); (I.Z.); (W.H.); (D.T.); (M.Z.); (R.H.); (Y.H.)
| | - Dongning Tang
- Research Center of Experimental Acupuncture Science, Tianjin University of Traditional Chinese Medicine, Tianjin 301617, China; (X.Z.); (I.Z.); (W.H.); (D.T.); (M.Z.); (R.H.); (Y.H.)
| | - Meidan Zhao
- Research Center of Experimental Acupuncture Science, Tianjin University of Traditional Chinese Medicine, Tianjin 301617, China; (X.Z.); (I.Z.); (W.H.); (D.T.); (M.Z.); (R.H.); (Y.H.)
- School of Acupuncture & Moxibustion and Tuina, Tianjin University of Traditional Chinese Medicine, Tianjin 301617, China
- National Clinical Research Center for Chinese Medicine Acupuncture and Moxibustion, Tianjin 300381, China
| | - Ruiling Hou
- Research Center of Experimental Acupuncture Science, Tianjin University of Traditional Chinese Medicine, Tianjin 301617, China; (X.Z.); (I.Z.); (W.H.); (D.T.); (M.Z.); (R.H.); (Y.H.)
| | - Ying Huang
- Research Center of Experimental Acupuncture Science, Tianjin University of Traditional Chinese Medicine, Tianjin 301617, China; (X.Z.); (I.Z.); (W.H.); (D.T.); (M.Z.); (R.H.); (Y.H.)
| | - Yun Shi
- Hebei Key Laboratory of Early Life Health Promotion, Hebei Medical University, Shijiazhuang 050031, China;
| | - Weili Zhu
- National Institute on Drug Dependence and Beijing Key Laboratory of Drug Dependence Research, Peking University, Beijing 100191, China
| | - Shenjun Wang
- Research Center of Experimental Acupuncture Science, Tianjin University of Traditional Chinese Medicine, Tianjin 301617, China; (X.Z.); (I.Z.); (W.H.); (D.T.); (M.Z.); (R.H.); (Y.H.)
- School of Acupuncture & Moxibustion and Tuina, Tianjin University of Traditional Chinese Medicine, Tianjin 301617, China
- National Clinical Research Center for Chinese Medicine Acupuncture and Moxibustion, Tianjin 300381, China
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Lenti MV, Hammer HF, Tacheci I, Burgos R, Schneider S, Foteini A, Derovs A, Keller J, Broekaert I, Arvanitakis M, Dumitrascu DL, Segarra-Cantón O, Krznarić Ž, Pokrotnieks J, Nunes G, Hammer J, Pironi L, Sonyi M, Sabo CM, Mendive J, Nicolau A, Dolinsek J, Kyselova D, Laterza L, Gasbarrini A, Surdea-Blaga T, Fonseca J, Lionis C, Corazza GR, Di Sabatino A. European Consensus on Malabsorption-UEG & SIGE, LGA, SPG, SRGH, CGS, ESPCG, EAGEN, ESPEN, and ESPGHAN: Part 2: Screening, Special Populations, Nutritional Goals, Supportive Care, Primary Care Perspective. United European Gastroenterol J 2025. [PMID: 40088199 DOI: 10.1002/ueg2.70011] [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: 10/27/2024] [Revised: 02/14/2025] [Accepted: 02/18/2025] [Indexed: 03/17/2025] Open
Abstract
Malabsorption is a complex and multifaceted condition characterised by the defective passage of nutrients into the blood and lymphatic streams. Several congenital or acquired disorders may cause either selective or global malabsorption in both children and adults, such as cystic fibrosis, exocrine pancreatic insufficiency (EPI), coeliac disease (CD) and other enteropathies, lactase deficiency, small intestinal bacterial overgrowth (SIBO), autoimmune atrophic gastritis, Crohn's disease, and gastric or small bowel resections. Early recognition of malabsorption is key for tailoring a proper diagnostic work-up for identifying the cause of malabsorption. Patient's medical and pharmacological history are essential for identifying risk factors. Several examinations like endoscopy with small intestinal biopsies, non-invasive functional tests, and radiologic imaging are useful in diagnosing malabsorption. Due to its high prevalence, CD should always be looked for in case of malabsorption with no other obvious explanations and in high-risk individuals. Nutritional support is key in management of patients with malabsorption; different options are available, including oral supplements, enteral or parenteral nutrition. In patients with short bowel syndrome, teduglutide proved effective in reducing the need for parenteral nutrition, thus improving the quality of life of these patients. Primary care physicians have a central role in early detection of malabsorption and should be involved into multidisciplinary teams for improving the overall management of these patients. In this European consensus, involving 10 scientific societies and several experts, we have dissected all the issues around malabsorption, including the definitions and diagnostic testing (Part 1), high-risk categories and special populations, nutritional assessment and management, and primary care perspective (Part 2).
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Affiliation(s)
- Marco Vincenzo Lenti
- Department of Internal Medicine and Medical Therapeutics, University of Pavia, Pavia, Italy
- First Department of Internal Medicine, Fondazione IRCCS San Matteo, Pavia, Italy
| | - Heinz Florian Hammer
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Medical University, Graz, Austria
| | - Ilja Tacheci
- 2nd Department of Internal Medicine - Gastroenterology, University Hospital Hradec Králové, Charles University, Faculty of Medicine in Hradec Králové, Hradec Kralove, Czech Republic
| | - Rosa Burgos
- Endocrinology and Nutrition Department, Hospital Universitari Vall d'Hebron, Diabetes and Metabolism Research Unit, Vall d'Hebron Institut de Recerca (VHIR), Universitat Autonoma de Barcelona, Barcelona, Spain
| | - Stephane Schneider
- Gastroenterology and Nutrition, Centre Hospitalier Universitaire de Nice, Université Côte d'Azur, Nice, France
| | - Anastasiou Foteini
- 4th Local Primary Care Team, Municipality Practice and Academic Practice of Heraklion, University of Crete, Crete, Greece
| | - Aleksejs Derovs
- Department of Internal Diseases, Rīga Stradiņš University, Riga, Latvia
| | - Jutta Keller
- Israelitic Hospital, Academic Hospital University of Hamburg, Hamburg, Germany
| | - Ilse Broekaert
- Department of Paediatrics, Faculty of Medicine and University Hospital Cologne, University of Cologne, Cologne, Germany
| | - Marianna Arvanitakis
- Department of Gastroenterology, Digestive Oncology and Hepatopancreatology, HUB Hôpital Erasme, Université Libre de Bruxelles, Brussels, Belgium
| | - Dan Lucian Dumitrascu
- 2nd Department of Internal Medicine, Iuliu Hatieganu University of Medicine and Pharmacy, Cluj-Napoca, Romania
- 2nd Medical Department, Emergency Clinical County Hospital, Cluj-Napoca, Romania
| | - Oscar Segarra-Cantón
- Paediatric Gastroenterology and Clinical Nutrition Unit, Vall d'Hebron Hospital Universitari, Vall d'Hebron Barcelona Hospital Campus, Barcelona, Spain
| | - Željko Krznarić
- Department of Gastroenterology, Hepatology and Nutrition, University of Zagreb, Zagreb School of Medicine, University Hospital Centre Zagreb, Zagreb, Croatia
| | - Juris Pokrotnieks
- Department of Internal Diseases, Rīga Stradiņš University, Riga, Latvia
- Centre of Gastroenterology, Hepatology and Nutrition, Pauls Stradiņš Clinical University Hospital, Riga, Latvia
| | - Gonçalo Nunes
- Gastroenterology Department, Hospital Garcia de Orta, Almada, Portugal
- Egas Moniz Center for Interdisciplinary Research (CiiEM), Egas Moniz School of Health & Science, Almada, Portugal
| | - Johann Hammer
- Department of Gastroenterology and Hepatology, Medical University of Vienna, Vienna, Austria
| | - Loris Pironi
- Department of Medical and Surgical Sciences, University of Bologna, Bologna, Italy
- Centre for Chronic Intestinal Failure, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy
| | - Marc Sonyi
- Clinic for General Medicine, Gastroenterology, and Infectious Diseases, Augustinerinnen Hospital, Cologne, Germany
| | - Cristina Maria Sabo
- 2nd Department of Internal Medicine, Iuliu Hatieganu University of Medicine and Pharmacy, Cluj-Napoca, Romania
- 2nd Medical Department, Emergency Clinical County Hospital, Cluj-Napoca, Romania
| | - Juan Mendive
- La Mina Primary Health Care Academic Centre, Catalan Health Institute, University of Barcelona, Barcelona, Spain
| | - Adrien Nicolau
- Gastroenterology and Nutrition, Centre Hospitalier Universitaire de Nice, Université Côte d'Azur, Nice, France
| | - Jernej Dolinsek
- Pediatric Gastroenterology, Hepatology and Nutrition Unit, Pediatric Department, University Medical Center Maribor, Maribor, Slovenia
- Faculty of Medicine, University of Maribor, Maribor, Slovenia
| | - Denisa Kyselova
- Department of Hepatogastroenterology, IKEM, Prague, Czech Republic
| | - Lucrezia Laterza
- Department of Translational Medicine and Surgery, Università Cattolica del Sacro Cuore, Rome, Italy
- CEMAD, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy
| | - Antonio Gasbarrini
- Department of Translational Medicine and Surgery, Università Cattolica del Sacro Cuore, Rome, Italy
- CEMAD, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy
| | - Teodora Surdea-Blaga
- 2nd Department of Internal Medicine, Iuliu Hatieganu University of Medicine and Pharmacy, Cluj-Napoca, Romania
- 2nd Medical Department, Emergency Clinical County Hospital, Cluj-Napoca, Romania
| | - Jorge Fonseca
- Gastroenterology Department, Hospital Garcia de Orta, Almada, Portugal
- Egas Moniz Center for Interdisciplinary Research (CiiEM), Egas Moniz School of Health & Science, Almada, Portugal
| | - Christos Lionis
- Laboratory of Health and Society, School of Medicine, University of Crete, Heraklion, Greece
| | - Gino Roberto Corazza
- Department of Internal Medicine and Medical Therapeutics, University of Pavia, Pavia, Italy
- First Department of Internal Medicine, Fondazione IRCCS San Matteo, Pavia, Italy
| | - Antonio Di Sabatino
- Department of Internal Medicine and Medical Therapeutics, University of Pavia, Pavia, Italy
- First Department of Internal Medicine, Fondazione IRCCS San Matteo, Pavia, Italy
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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.
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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
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Schiepatti A, Bossert I, Cincotta M, Zanini CA, Maimaris S, D'Ambrosio D, Trifirò G, Biagi F. Comparison between SeHCAT test and clinical response to cholestyramine in patients with chronic diarrhea and high suspicion of bile acid malabsorption: A single-center prospective study. J Dig Dis 2024; 25:279-284. [PMID: 38973129 DOI: 10.1111/1751-2980.13289] [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: 01/09/2024] [Revised: 04/29/2024] [Accepted: 05/16/2024] [Indexed: 07/09/2024]
Abstract
OBJECTIVES We aimed to evaluate the clinical response to cholestyramine in patients with functional chronic diarrhea and a high clinical suspicion of bile-acid diarrhea (BAD) investigated with 75-selenium homocholic acid taurine (SeHCAT) test. METHODS Adult patients attending our outpatient clinic between January and December 2021 for chronic diarrhea with suspicion of BAD were proposed SeHCAT testing and a therapeutic trial of cholestyramine 4-8 g daily. Clinical response to cholestyramine was evaluated at 1, 3, 6, and 12 months. Clinical and demographic data were analyzed according to SeHCAT test results. RESULTS Among the 50 patients with chronic diarrhea and clinical suspicion of BAD, 13 (26.0%) refused either SeHCAT testing or cholestyramine therapy. Finally, 37 patients (31 females, age 44 ± 14 years) agreed to undergo SeHCAT and were started on cholestyramine (median follow-up 14 months [interquartile range 6-16 months]). Initial response to cholestyramine was similar in patients with positive and negative SeHCAT test results, but improved over time in those with a positive test result. Long-term response (100% vs 65.2%, P = 0.02) and necessity of maintenance therapy for symptom control were more common in those with positive SeHCAT test result (71.4% vs 26.1%, P = 0.02). However, response to cholestyramine was also frequent in patients with a negative test result. CONCLUSIONS The SeHCAT test accurately identifies patients with BAD who benefit from long-term cholestyramine treatment. Nevertheless, cholestyramine may be also effective in patients with chronic diarrhea but negative SeHCAT test result.
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Affiliation(s)
- Annalisa Schiepatti
- Department of Internal Medicine and Medical Therapy, University of Pavia, Pavia, Italy
- Gastroenterology Unit of Pavia Institute, Istituti Clinici Scientifici Maugeri IRCCS, Pavia, Italy
| | - Irene Bossert
- Nuclear Medicine Unit, Istituti Clinici Scientifici Maugeri SpA SB IRCCS, Pavia, Italy
| | - Marta Cincotta
- Department of Internal Medicine and Medical Therapy, University of Pavia, Pavia, Italy
- Gastroenterology Unit of Pavia Institute, Istituti Clinici Scientifici Maugeri IRCCS, Pavia, Italy
| | | | - Stiliano Maimaris
- Department of Internal Medicine and Medical Therapy, University of Pavia, Pavia, Italy
| | - Daniela D'Ambrosio
- Medical Physics Unit, Istituti Clinici Scientifici Maugeri SpA SB IRCCS, Pavia, Italy
| | - Giuseppe Trifirò
- Nuclear Medicine Unit, Istituti Clinici Scientifici Maugeri SpA SB IRCCS, Pavia, Italy
| | - Federico Biagi
- Department of Internal Medicine and Medical Therapy, University of Pavia, Pavia, Italy
- Gastroenterology Unit of Pavia Institute, Istituti Clinici Scientifici Maugeri IRCCS, Pavia, Italy
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Zhao J, Tian L, Xia B, Mi N, He Q, Yang M, Wang D, Wu S, Li Z, Zhang S, Zhang X, Yue P, Lin Y, Zhao H, Zhang B, Ma Z, Jiang N, Li M, Yuan J, Nie P, Lu L, Meng W. Cholecystectomy is associated with a higher risk of irritable bowel syndrome in the UK Biobank: a prospective cohort study. Front Pharmacol 2023; 14:1244563. [PMID: 38143491 PMCID: PMC10749201 DOI: 10.3389/fphar.2023.1244563] [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: 06/22/2023] [Accepted: 11/28/2023] [Indexed: 12/26/2023] Open
Abstract
Background: Recent studies have shown that bile acids are essential in irritable bowel syndrome (IBS) pathology, and cholecystectomy has direct effects on bile acid metabolism. However, whether cholecystectomy increases the risk of IBS remains unclear. We aimed to investigate the association between cholecystectomy and IBS risk in the UK Biobank (UKB). Methods: This study is a prospective analysis of 413,472 participants who were free of IBS, inflammatory bowel disease, cancer, or common benign digestive tract diseases. We identified incidents of IBS through self-reporting or links to primary healthcare and hospitalization data. We evaluated hazard ratios (HRs) adjusted for sociodemographic characteristics, health behaviours, comorbidities, and medications. Results: During a median follow-up period of 12.7 years, we observed 15,503 new cases of IBS. Participants with a history of cholecystectomy had a 46% higher risk of IBS than those without (HR = 1.46, 95% CI: 1.32-1.60), and further subtype analysis showed that the risk of IBS with diarrhoea was significantly higher than the risk of IBS without diarrhoea (HR = 1.71, 95% CI: 1.30-2.25 vs. HR = 1.42, 95% CI: 1.28-1.58). The overall covariate-adjusted HRs for IBS were similar between the group with both cholecystectomy and gallstones (HR = 1.45, 95% CI: 1.32-1.58) and the group with cholecystectomy without gallstones (HR = 1.50, 95% CI: 1.36-1.67) when the group without both cholecystectomy and gallstones was used as a reference. The overall covariate-adjusted HR was not significantly different in the group without cholecystectomy with gallstones (HR = 1.18, 95% CI: 0.95-1.47). The positive association of cholecystectomy with IBS risk did not change when stratifying the data based on age, sex, BMI, smoking, alcohol consumption, healthy diet, quality sleep, physical activity, type 2 diabetes, hypertension, hyperlipidaemia, mental illness, NSAID intake, or acid inhibitor intake. Sensitivity analyses, including propensity score matching analysis and lagging the exposure for two or four years, indicated that the effects were robust. Conclusion: Cholecystectomy was associated with a higher risk of IBS, especially IBS with diarrhoea. Additional prospective randomized controlled and experimental studies are warranted to further validate the association and to explore the relevant biological mechanisms.
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Affiliation(s)
- Jinyu Zhao
- The First Clinical Medical School, Lanzhou University, Lanzhou, Gansu, China
- Department of General Surgery, The First Hospital of Lanzhou University, Lanzhou, Gansu, China
| | - Liang Tian
- The First Clinical Medical School, Lanzhou University, Lanzhou, Gansu, China
- Department of General Surgery, The First Hospital of Lanzhou University, Lanzhou, Gansu, China
| | - Bin Xia
- Scientific Research Center, Big Data Center, The Seventh Affiliated Hospital, Sun Yat-Sen University, Shenzhen, Guangdong, China
- Clinical Research Center, The Seventh Affiliated Hospital, Sun Yat-Sen University, Shenzhen, Guangdong, China
- Guangdong Provincial Key Laboratory of Gastroenterology, Center for Digestive Disease, The Seventh Affiliated Hospital, Sun Yat-Sen University, Shenzhen, Guangdong, China
| | - Ningning Mi
- The First Clinical Medical School, Lanzhou University, Lanzhou, Gansu, China
- Department of General Surgery, The First Hospital of Lanzhou University, Lanzhou, Gansu, China
| | - Qiangsheng He
- Scientific Research Center, Big Data Center, The Seventh Affiliated Hospital, Sun Yat-Sen University, Shenzhen, Guangdong, China
- Clinical Research Center, The Seventh Affiliated Hospital, Sun Yat-Sen University, Shenzhen, Guangdong, China
- Guangdong Provincial Key Laboratory of Gastroenterology, Center for Digestive Disease, The Seventh Affiliated Hospital, Sun Yat-Sen University, Shenzhen, Guangdong, China
| | - Man Yang
- Guangdong Provincial Key Laboratory of Gastroenterology, Center for Digestive Disease, The Seventh Affiliated Hospital, Sun Yat-Sen University, Shenzhen, Guangdong, China
| | - Danni Wang
- Scientific Research Center, Big Data Center, The Seventh Affiliated Hospital, Sun Yat-Sen University, Shenzhen, Guangdong, China
| | - Siqing Wu
- School of Medicine, Shenzhen Campus of Sun Yat-Sen University, Shenzhen, China
| | - Zijun Li
- Evidence Based Social Science Research Center, School of Public Health, Lanzhou University, Lanzhou, China
| | - Shiyong Zhang
- Department of Joint Surgery, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, Guangdong, China
| | - Xianzhuo Zhang
- The First Clinical Medical School, Lanzhou University, Lanzhou, Gansu, China
- Department of General Surgery, The First Hospital of Lanzhou University, Lanzhou, Gansu, China
| | - Ping Yue
- Department of General Surgery, The First Hospital of Lanzhou University, Lanzhou, Gansu, China
| | - Yanyan Lin
- Department of General Surgery, The First Hospital of Lanzhou University, Lanzhou, Gansu, China
| | - Haitong Zhao
- Evidence Based Social Science Research Center, School of Public Health, Lanzhou University, Lanzhou, China
| | - Baoping Zhang
- The First Clinical Medical School, Lanzhou University, Lanzhou, Gansu, China
- Department of General Surgery, The First Hospital of Lanzhou University, Lanzhou, Gansu, China
| | - Zelong Ma
- The First Clinical Medical School, Lanzhou University, Lanzhou, Gansu, China
- Department of General Surgery, The First Hospital of Lanzhou University, Lanzhou, Gansu, China
| | - Ningzu Jiang
- The First Clinical Medical School, Lanzhou University, Lanzhou, Gansu, China
- Department of General Surgery, The First Hospital of Lanzhou University, Lanzhou, Gansu, China
| | - Matu Li
- The First Clinical Medical School, Lanzhou University, Lanzhou, Gansu, China
- Department of Gastroenterology, The First Hospital of Lanzhou University, Lanzhou, Gansu, China
| | - Jinqiu Yuan
- Scientific Research Center, Big Data Center, The Seventh Affiliated Hospital, Sun Yat-Sen University, Shenzhen, Guangdong, China
- Clinical Research Center, The Seventh Affiliated Hospital, Sun Yat-Sen University, Shenzhen, Guangdong, China
- Guangdong Provincial Key Laboratory of Gastroenterology, Center for Digestive Disease, The Seventh Affiliated Hospital, Sun Yat-Sen University, Shenzhen, Guangdong, China
| | - Peng Nie
- Department of Gastric Surgery, Gansu Wuwei Tumour Hospital, Wuwei Academy of Medical Science, Wuwei, Gansu, China
| | - Linzhi Lu
- Wuwei Oncology Hospital, Wuwei, Gansu, China
| | - Wenbo Meng
- The First Clinical Medical School, Lanzhou University, Lanzhou, Gansu, China
- Department of General Surgery, The First Hospital of Lanzhou University, Lanzhou, Gansu, China
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Chen S, Shao Q, Chen J, Lv X, Ji J, Liu Y, Song Y. Bile acid signalling and its role in anxiety disorders. Front Endocrinol (Lausanne) 2023; 14:1268865. [PMID: 38075046 PMCID: PMC10710157 DOI: 10.3389/fendo.2023.1268865] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/28/2023] [Accepted: 11/06/2023] [Indexed: 12/18/2023] Open
Abstract
Anxiety disorder is a prevalent neuropsychiatric disorder that afflicts 7.3%~28.0% of the world's population. Bile acids are synthesized by hepatocytes and modulate metabolism via farnesoid X receptor (FXR), G protein-coupled receptor (TGR5), etc. These effects are not limited to the gastrointestinal tract but also extend to tissues and organs such as the brain, where they regulate emotional centers and nerves. A rise in serum bile acid levels can promote the interaction between central FXR and TGR5 across the blood-brain barrier or activate intestinal FXR and TGR5 to release fibroblast growth factor 19 (FGF19) and glucagon-like peptide-1 (GLP-1), respectively, which in turn, transmit signals to the brain via these indirect pathways. This review aimed to summarize advancements in the metabolism of bile acids and the physiological functions of their receptors in various tissues, with a specific focus on their regulatory roles in brain function. The contribution of bile acids to anxiety via sending signals to the brain via direct or indirect pathways was also discussed. Different bile acid ligands trigger distinct bile acid signaling cascades, producing diverse downstream effects, and these pathways may be involved in anxiety regulation. Future investigations from the perspective of bile acids are anticipated to lead to novel mechanistic insights and potential therapeutic targets for anxiety disorders.
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Affiliation(s)
| | | | | | | | | | - Yan Liu
- College of Traditional Chinese Medicine, Beijing University of Chinese Medicine, Beijing, China
| | - Yuehan Song
- College of Traditional Chinese Medicine, Beijing University of Chinese Medicine, Beijing, China
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Lindberg G, Mohammadian G. Loose ends in the differential diagnosis of IBS-like symptoms. Front Med (Lausanne) 2023; 10:1141035. [PMID: 37484861 PMCID: PMC10357384 DOI: 10.3389/fmed.2023.1141035] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/09/2023] [Accepted: 05/30/2023] [Indexed: 07/25/2023] Open
Abstract
Two thirds of the patients we believed to have IBS in the 1970's have since been possible to diagnose with treatable conditions like bile acid diarrhea, inflammatory bowel disease, microscopic colitis, celiac disease, disaccharide malabsorption, exocrine pancreatic insufficiency, or rare genetic variants. Despite advances in diagnostic techniques a substantial proportion of patients continue suffering from IBS-like symptoms that cannot be explained by current knowledge. Although it is likely that further research will reveal small but important subgroups of patients with treatable mechanisms for IBS-like symptoms, we propose that only two large groups remain for being addressed in the clinic: those with connective tissue disorders such as Ehlers-Danlos syndrome or hypermobility spectrum disorders and those with autism spectrum disorders. Patients with connective tissue disorders exhibit identifiable disturbances of gut motor function and possibly increased gut permeability as underlying mechanisms for IBS-like symptoms. Autism spectrum disorders pose a much more difficult problem in the clinic. Disturbances of perception combined with anxiety and excessive worry about signals from the gut can lead to an endless but futile search for something being wrong. The search can involve large numbers of care givers, no one understanding the patient's suffering. Others may try to change their diet to lessen symptoms, only to find that almost all foods may cause worrying perceptions from the gut. Early recognition of autism spectrum disorders is essential for finding better ways to help patients with gastrointestinal and, as is often the case, extraintestinal symptoms.
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Affiliation(s)
- Greger Lindberg
- Department of Medicine at Huddinge, Karolinska Institutet, Stockholm, Sweden
- Neurogastroenterology Unit, Division of Gastroenterology, Department of Gastroenterology, Dermatovenereology and Rheumatology, Karolinska University Hospital, Stockholm, Sweden
| | - Ghazaleh Mohammadian
- Department of Medicine at Huddinge, Karolinska Institutet, Stockholm, Sweden
- Neurogastroenterology Unit, Division of Gastroenterology, Department of Gastroenterology, Dermatovenereology and Rheumatology, Karolinska University Hospital, Stockholm, Sweden
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8
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Zhou Q, Yang L, Verne ML, Zhang BB, Fields J, Verne GN. Catechol-O-Methyltransferase Loss Drives Cell-Specific Nociceptive Signaling via the Enteric Catechol-O-Methyltransferase/microRNA-155/Tumor Necrosis Factor α Axis. Gastroenterology 2023; 164:630-641.e34. [PMID: 36623778 PMCID: PMC10038873 DOI: 10.1053/j.gastro.2022.12.041] [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: 08/16/2020] [Revised: 12/21/2022] [Accepted: 12/27/2022] [Indexed: 01/11/2023]
Abstract
BACKGROUND & AIMS The etiology of abdominal pain in postinfectious, diarrhea-predominant irritable bowel syndrome (PI-IBS-D) is unknown, and few treatment options exist. Catechol-O-methyltransferase (COMT), an enzyme that inactivates and degrades biologically active catecholamines, plays an important role in numerous physiologic processes, including modulation of pain perception. Our objective was to determine the mechanism(s) of how decreased colonic COMT in PI-IBS-D patients contributes to the chronic abdominal pain phenotype after enteric infections. METHODS Colon neurons, epithelial cells, and macrophages were procured with laser capture microdissection from PI-IBS-D patients to evaluate cell-specific colonic COMT, microRNA-155 (miR-155), and tumor necrosis factor (TNF) α expression levels compared to recovered patients (infection cleared: did not develop PI-IBS-D) and control individuals. COMT-/-, colon-specific COMT-/-, and miR-155-/- mice and human colonoids were used to model phenotypic expression of COMT in PI-IBS-D patients and to investigate signaling pathways linking abdominal pain. Citrobacter rodentium and trinitrobenzene sulfonic acid animal models were used to model postinflammatory changes seen in PI-IBS-D patients. RESULTS Colonic COMT levels were significantly decreased and correlated with increased visual analog scale abdominal pain ratings in PI-IBS-D patients compared to recovered patients and control individuals. Colonic miR-155 and TNF-α were increased in PI-IBS-D patients with diminished colonic COMT. COMT-/- mice had significantly increased expression of miR-155 and TNF-α in both colon tissues and dorsal root ganglia. Introduction of cV1q antibody (anti-TNF-α) into mice reversed visceral hypersensitivity after C rodentium and trinitrobenzene sulfonic acid. CONCLUSIONS Decreased colonic COMT in PI-IBS-D patients drives abdominal pain phenotypes via the COMT/miR-155/TNF-α axis. These important findings will allow new treatment paradigms and more targeted and personalized medicine approaches for gastrointestinal disorders after enteric infections.
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Affiliation(s)
- QiQi Zhou
- Department of Medicine, University of Tennessee Health Science Center, Memphis, Tennessee; Memphis Veterans Affairs Medical Center, Research Service, Memphis, Tennessee
| | - Liuqing Yang
- Department of Medicine, University of Tennessee Health Science Center, Memphis, Tennessee
| | - Meghan L Verne
- Department of Medicine, University of Tennessee Health Science Center, Memphis, Tennessee
| | - Benjamin B Zhang
- Department of Medicine, University of Tennessee Health Science Center, Memphis, Tennessee
| | - Jeremy Fields
- Department of Medicine, University of Tennessee Health Science Center, Memphis, Tennessee
| | - George Nicholas Verne
- Department of Medicine, University of Tennessee Health Science Center, Memphis, Tennessee; Memphis Veterans Affairs Medical Center, Research Service, Memphis, Tennessee.
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9
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Pohl D, Vavricka S, Fox M, Madisch A, Studerus D, Wiesel P, Heinrich H, Linas I, Schoepfer A, Schwizer A, Wildi S. [Frequent Gastro-Intestinal Disorders: Management of Functional Dyspepsia and Irritable Bowel Syndrome in Clinical Practice]. PRAXIS 2023; 112:304-316. [PMID: 37042398 DOI: 10.1024/1661-8157/a003988] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/19/2023]
Abstract
Frequent Gastro-Intestinal Disorders: Management of Functional Dyspepsia and Irritable Bowel Syndrome in Clinical Practice Abstract: Functional dyspepsia (FD) and irritable bowel syndrome (IBS), two common gastrointestinal entities with overlapping symptoms, should be diagnosed according to Rome IV criteria. This includes one or more of the following symptoms: in FD, postprandial fullness, early satiation, epigastric pain or burning; in IBS, recurrent abdominal pain associated with defecation, change in frequency of stool or form of stool. To exclude structural diseases, attention should be paid to alarm symptoms. As far as treatment is concerned, a stepwise scheme proves to be effective for both diseases. Step 1: doctor-patient discussion with explanation of diagnosis and prognosis as well as clarification of therapy goals; lifestyle adaptations; use of phytotherapeutics; step 2: symptom-oriented medication: for FD, PPIs or prokinetics; for IBS, antispasmodics, secretagogues, laxatives, bile acid sequestrants, antidiarrheals, antibiotics, probiotics; step 3: visceral analgesics (antidepressants).
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Affiliation(s)
- Daniel Pohl
- Klinik für Gastroenterologie und Hepatologie, Universitätsspital Zürich, Schweiz
| | | | - Mark Fox
- Zentrum für Integrative Gastroenterologie, Klinik Arlesheim, Schweiz
| | | | | | - Paul Wiesel
- Gastro-entérologie, Centre Médical d'Epalinges, Epalinges, Schweiz
| | | | - Ioannis Linas
- Gastroenterologische Gruppenpraxis, Hirslanden Campus Bern, Schweiz
| | - Alain Schoepfer
- Service de gastro-entérologie et hépatologie, Centre hospitalier universitaire vaudois CHUV, Lausanne, Schweiz
| | - Alexandra Schwizer
- Klinik für Gastroenterologie und Hepatologie, Kantonsspital St. Gallen, St. Gallen, Schweiz
| | - Stephan Wildi
- Klinik für Gastroenterologie und Hepatologie, Kantonsspital St. Gallen, St. Gallen, Schweiz
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10
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Goodoory VC, Ng CE, Black CJ, Ford AC. Prevalence and impact of faecal incontinence among individuals with Rome IV irritable bowel syndrome. Aliment Pharmacol Ther 2023; 57:1083-1092. [PMID: 36914979 DOI: 10.1111/apt.17465] [Citation(s) in RCA: 11] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/15/2023] [Revised: 02/24/2023] [Accepted: 02/25/2023] [Indexed: 03/16/2023]
Abstract
BACKGROUND Little is known about faecal incontinence (FI) in individuals with irritable bowel syndrome (IBS). AIMS To compare characteristics of people with IBS reporting FI, compared with people with IBS who do not report FI. METHODS We collected demographic, gastrointestinal and psychological symptoms, healthcare usage, direct healthcare costs, impact on work and activities of daily living, and quality of life data from individuals with Rome IV-defined IBS. We asked participants about FI, assigning presence or absence according to Rome-IV criteria. RESULTS Of 752 participants with Rome IV IBS, 202 (26.9%) met Rome IV criteria for FI. Individuals with FI were older (p < 0.001), more likely to have IBS-D (47.0% vs. 39.0%, p = 0.008), and less likely to have attained a university or postgraduate level of education (31.2% vs. 45.6%, p < 0.001), or to have an annual income of ≥£30,000 (18.2% vs. 32.9%, p < 0.001). They were more likely to report urgency (44.6% vs. 19.1%, p < 0.001) as their most troublesome symptom and a greater proportion had severe IBS symptom scores, abnormal depression scores, higher somatic symptom-reporting scores or higher gastrointestinal symptom-specific anxiety scores (p < 0.01 for trend for all analyses). Mean health-related quality of life scores were significantly lower among those with, compared with those without, FI (p < 0.001). Finally, FI was associated with higher IBS-related direct healthcare costs (p = 0.002). CONCLUSIONS Among individuals with Rome IV IBS, one-in-four repo rted FI according to Rome IV criteria. Physicians should ask patients with IBS about FI routinely.
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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
| | - Cho E 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
| | - 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
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11
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Biomarkers for Bile Acid Malabsorption in Diarrhea-predominant Irritable Bowel Syndrome: A Systematic Review and Meta-analysis. J Clin Gastroenterol 2023; 57:451-458. [PMID: 36867517 DOI: 10.1097/mcg.0000000000001841] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 03/04/2023]
Abstract
BACKGROUND AND AIM A clear relationship of biological indexes between bile acid malabsorption (BAM) and diarrhea-predominant irritable bowel syndrome (IBS-D) has not been well analyzed. This meta-analysis aimed to establish a more convenient method to diagnose BAM in IBS-D patients by comparing the differences in biomarkers between IBS-D patients and healthy people. METHODS Multiple databases were searched for relevant case-control studies. Indicators used to diagnose BAM included 75Se-homocholic acid taurine (SeHCAT), 7α-hydroxy-4-cholesten-3-one(C4), fibroblast growth factor-19 and 48-hour fecal bile acid (48FBA). The rate of BAM (SeHCAT) was calculated by using a random-effect model. The levels of C4, FGF19, and 48FBA were compared, and the overall effect size was combined by a fixed effect model. RESULTS The search strategy identified 10 relevant studies comprising 1034 IBS-D patients and 232 healthy volunteers. The pooled rate of BAM in IBS-D patients was 32% (according to SeHCAT; 95% CI: 24%-40%). The level of C4 in IBS-D patients was significantly higher than that in the control group (2.86 ng/mL; 95% CI: 1.09, 4.63); The level of FGF19 was significantly lower than that in the control group (-33.97 pg/mL; 95% CI: -51.13, -16.82); The level of 48FBA was significantly higher than that in the control group (0.059; 95% CI: 0.41, 0.77). CONCLUSIONS The results mainly concluded serum C4 and FGF19 levels in IBS-D patients. Most of the studies have different normal cutoff points of serum C4 and FGF19 levels; the performance of each test should be further estimated. By comparing the levels of these biomarkers, BAM in patients with IBS-D could be identified more accurately, which would lead to more effective treatment.
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12
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Zhou Q, Verne GN. Epigenetic modulation of visceral nociception. Neurogastroenterol Motil 2022; 34:e14443. [PMID: 35950237 PMCID: PMC9787514 DOI: 10.1111/nmo.14443] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/26/2022] [Accepted: 07/29/2022] [Indexed: 12/30/2022]
Abstract
Epigenetics is a process that alters gene activity or phenotype without any changes in the underlying DNA sequence or genotype. These biological changes may have deleterious effects and can lead to various human diseases. Ongoing research is continuing to illuminate the role of epigenetics in a variety of pathophysiologic processes. Several categories of epigenetic mechanisms have been studied including chromatin remodeling, DNA methylation, histone modification, and non-coding RNA mechanisms. These epigenetic changes can have a long-term effect on gene expression without any underlying changes in the DNA sequences. The underlying pathophysiology of disorders of brain-gut interaction and stress-induced visceral pain are not fully understood and the role of epigenetic mechanisms in these disorders are starting to be better understood. Current work is underway to determine how epigenetics plays a role in the neurobiology of patients with chronic visceral pain and heightened visceral nociception. More recently, both animal models and human studies have shown how epigenetic regulation modulates stress-induced visceral pain. While much more work is needed to fully delineate the mechanistic role of epigenetics in the neurobiology of chronic visceral nociception, the current study by Louwies et al., in Neurogastroenterology and Motility provides additional evidence supporting the involvement of epigenetic alterations in the central nucleus of the amygdala in stress-induced visceral hypersensitivity in rodents.
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Affiliation(s)
- QiQi Zhou
- Department of MedicineUniversity of Tennessee College of MedicineMemphisTennesseeUSA
- Memphis VA Medical CenterResearch ServiceMemphisTennesseeUSA
| | - George Nicholas Verne
- Department of MedicineUniversity of Tennessee College of MedicineMemphisTennesseeUSA
- Memphis VA Medical CenterResearch ServiceMemphisTennesseeUSA
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13
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Vijayvargiya P, Breen-Lyles M, Nord SL, Maselli D, Busciglio I, Boinpally R, Muslin A, Carrothers TJ, Camilleri M. Safety and Efficacy of Eluxadoline in Patients with Irritable Bowel Syndrome-Diarrhea With or Without Bile Acid Diarrhea: Open-Label Study. Dig Dis Sci 2022; 67:3911-3921. [PMID: 35122592 DOI: 10.1007/s10620-022-07379-x] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/23/2021] [Accepted: 11/04/2021] [Indexed: 12/28/2022]
Abstract
BACKGROUND Eluxadoline, a peripherally acting, mixed µ- and κ-opioid receptor (OR) agonist and δ-OR antagonist, is approved for treatment of adults with irritable bowel syndrome-diarrhea (IBS-D). About a third of IBS-D patients has bile acid diarrhea (BAD); opioids may stimulate TGR5 (bile acid) receptors. AIM To evaluate eluxadoline's efficacy on altered bowel functions and safety in IBS-D patients with or without BAD. METHODS In a single-center, phase 4, parallel-group, open-label study, patients with IBS-D (cohort 1) and patients with BAD were treated with eluxadoline, 100 mg tablets BID, with food for 4 weeks. Patients recorded bowel functions by electronic daily diary. BAD was based on fasting serum 7αC4 (> 52.5 ng/mL) or concurrent criteria of increased total or primary fecal BAs excreted in 48 h. We assessed efficacy on treatment compared to baseline in the two cohorts. Primary outcome measures were changes from baseline in average stool consistency Bristol Stool Form Scale (BSFS) score (range 1-7) and safety. RESULTS Mean changes from baseline in cohorts 1 and 2 (data presented in this order) were similar for: BSFS score averaged over 4 weeks' treatment (- 1.25 and - 1.09); daily bowel movement frequency (- 1.48 and - 0.79); daily urgent bowel movements (- 0.52 and - 0.80); IBS-QoL (5.9 and 13.6); serum 7αC4 (- 5.59 and - 8.78 ng/mL). There were no deaths, serious treatment-emergent adverse events, or discontinuations due to adverse events during the study. CONCLUSION Eluxadoline is similarly efficacious in the treatment of IBS-D and BAD, and it appears to be safe and efficacious as documented in large clinical trials.
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Affiliation(s)
- Priya Vijayvargiya
- Clinical Enteric Neuroscience Translational and Epidemiological Research (CENTER), Division of Gastroenterology and Hepatology, Mayo Clinic, 200 First St. S.W., Charlton Building, Rm. 8-110, Rochester, MN, 55905, USA
| | - Margaret Breen-Lyles
- Clinical Enteric Neuroscience Translational and Epidemiological Research (CENTER), Division of Gastroenterology and Hepatology, Mayo Clinic, 200 First St. S.W., Charlton Building, Rm. 8-110, Rochester, MN, 55905, USA
| | - Sara Linker Nord
- Clinical Enteric Neuroscience Translational and Epidemiological Research (CENTER), Division of Gastroenterology and Hepatology, Mayo Clinic, 200 First St. S.W., Charlton Building, Rm. 8-110, Rochester, MN, 55905, USA
| | - Daniel Maselli
- Clinical Enteric Neuroscience Translational and Epidemiological Research (CENTER), Division of Gastroenterology and Hepatology, Mayo Clinic, 200 First St. S.W., Charlton Building, Rm. 8-110, Rochester, MN, 55905, USA
| | - Irene Busciglio
- Clinical Enteric Neuroscience Translational and Epidemiological Research (CENTER), Division of Gastroenterology and Hepatology, Mayo Clinic, 200 First St. S.W., Charlton Building, Rm. 8-110, Rochester, MN, 55905, USA
| | - Ramesh Boinpally
- Clinical Enteric Neuroscience Translational and Epidemiological Research (CENTER), Division of Gastroenterology and Hepatology, Mayo Clinic, 200 First St. S.W., Charlton Building, Rm. 8-110, Rochester, MN, 55905, USA.,AbbVie Inc, Madison, NJ, USA
| | - Anna Muslin
- Clinical Enteric Neuroscience Translational and Epidemiological Research (CENTER), Division of Gastroenterology and Hepatology, Mayo Clinic, 200 First St. S.W., Charlton Building, Rm. 8-110, Rochester, MN, 55905, USA.,AbbVie Inc, Madison, NJ, USA
| | | | - Michael Camilleri
- Clinical Enteric Neuroscience Translational and Epidemiological Research (CENTER), Division of Gastroenterology and Hepatology, Mayo Clinic, 200 First St. S.W., Charlton Building, Rm. 8-110, Rochester, MN, 55905, USA.
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14
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Goodoory VC, Craig OF, Gracie DJ, Black CJ, Ford AC. Prognosis of patients with Rome IV-defined versus physician-diagnosed irritable bowel syndrome: Longitudinal follow-up study. Neurogastroenterol Motil 2022; 34:e14282. [PMID: 34612560 DOI: 10.1111/nmo.14282] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/07/2021] [Revised: 09/19/2021] [Accepted: 09/27/2021] [Indexed: 12/20/2022]
Abstract
INTRODUCTION Little is known about the differences between patients diagnosed with irritable bowel syndrome (IBS) by a physician who meet the Rome IV criteria for IBS and those who do not. We conducted a longitudinal follow-up study examining this. METHODS We collected complete gastrointestinal, extraintestinal, and psychological symptom data from 577 consecutive adult patients with suspected IBS in a single UK gastroenterology clinic. We compared baseline characteristics between patients who met Rome IV criteria for IBS, and those who had IBS according to a physician's diagnosis but who did not meet Rome IV criteria, as well as examining whether meeting Rome IV criteria at baseline influenced evolution of symptoms under therapy. KEY RESULTS Of 455 patients diagnosed with IBS by a physician, 375 (82.4%) met Rome IV criteria and 80 (17.4%) did not. Those who met Rome IV criteria were more likely to report severe symptoms (67.6%, vs. 30.0%, p < 0.001) and that symptoms limited activities ≥50% of the time (63.0%, vs. 37.5%, p < 0.001). Patients with Rome IV IBS were more likely to have abnormal anxiety scores (50.8%, vs. 35.9%, p = 0.007) and higher levels of somatoform symptom-reporting (29.4%, vs. 12.5%, p < 0.001). Despite this, during longitudinal follow-up, there was no significant difference in mean number of appointments required subsequently, or IBS symptom severity. CONCLUSIONS AND INFERENCES Although patients who met the Rome IV criteria had more severe symptoms at baseline and were more likely to exhibit psychological comorbidity, they did not appear to have a worse prognosis than those with physician-diagnosed IBS.
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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
| | - Orla F Craig
- Leeds Institute of Medical Research at St. James's, University of Leeds, Leeds, UK
| | - David J Gracie
- 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
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15
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Gu Y, Li L, Yang M, Liu T, Song X, Qin X, Xu X, Liu J, Wang B, Cao H. Bile acid-gut microbiota crosstalk in irritable bowel syndrome. Crit Rev Microbiol 2022; 49:350-369. [PMID: 35389754 DOI: 10.1080/1040841x.2022.2058353] [Citation(s) in RCA: 10] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
Abstract
Irritable bowel syndrome (IBS) is a common disorder of gut-brain interaction with an increasing prevalence, and its precise aetiology remains unclear. Gut microbiota dysbiosis has been found to be associated with IBS pathogenesis. In addition, a high incidence of bile acid diarrhoea and disturbed bile acid metabolism has been observed in IBS patients. The abundant microorganisms inhabited in human gut have essential functions in bile acid biotransformation, and can immensely affect the size and constitution of bile acid pool. Meanwhile, the alterations of bile acid profile can inversely interfere with the gut microbiota. This review discussed the role of intricate correlations between bile acids and gut microbiota in IBS pathogenesis and delineated the possible molecular mechanisms, mainly the signalling induced by farnesoid X receptor and transmembrane G protein-coupled receptor 5. Besides, some biomarkers for identifying bile acid diarrhoea in IBS population were listed, assisting the diagnosis and classification of IBS. Moreover, it also assessed some therapeutic strategies for IBS that regulate the bile acid-gut microbiota axis, such as dietary modulation, probiotics/prebiotics, faecal microbiota transplantation, and antibiotics. Collectively, this article illustrated the relationship between bile acids and gut microbiota in IBS pathophysiology and might offer some novel therapeutic options for IBS.
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Affiliation(s)
- Yu Gu
- Department of Gastroenterology and Hepatology, Tianjin Medical University General Hospital, Tianjin, China
| | - Lingfeng Li
- Department of Gastroenterology and Hepatology, Tianjin Medical University General Hospital, Tianjin, China
| | - Min Yang
- Department of Gastroenterology and Hepatology, Tianjin Medical University General Hospital, Tianjin, China
| | - Tianyu Liu
- Department of Gastroenterology and Hepatology, Tianjin Medical University General Hospital, Tianjin, China
| | - Xueli Song
- Department of Gastroenterology and Hepatology, Tianjin Medical University General Hospital, Tianjin, China
| | - Xiali Qin
- Department of Gastroenterology and Hepatology, Tianjin Medical University General Hospital, Tianjin, China
| | - Xin Xu
- Department of Gastroenterology and Hepatology, Tianjin Medical University General Hospital, Tianjin, China
| | - Jinghua Liu
- Department of Gastroenterology, Tianjin TEDA hospital, Tianjin, China
| | - Bangmao Wang
- Department of Gastroenterology and Hepatology, Tianjin Medical University General Hospital, Tianjin, China
| | - Hailong Cao
- Department of Gastroenterology and Hepatology, Tianjin Medical University General Hospital, Tianjin, China
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16
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Kindt S, Louis H, De Schepper H, Arts J, Caenepeel P, De Looze D, Gerkens A, Holvoet T, Latour P, Mahler T, Mokaddem F, Nullens S, Piessevaux H, Poortmans P, Rasschaert G, Surmont M, Vafa H, Van Malderen K, Vanuytsel T, Wuestenberghs F, Tack J. Belgian consensus on irritable bowel syndrome. Acta Gastroenterol Belg 2022; 85:360-382. [PMID: 35709780 DOI: 10.51821/85.2.10100] [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] [Indexed: 11/11/2022]
Abstract
BACKGROUND Irritable bowel syndrome (IBS) is characterised by recurrent abdominal pain related to defaecation or associated with altered stool frequency or consistency. Despite its prevalence, major uncertainties in the diagnostic and therapeutic management persist in clinical practice. METHODS A Delphi consensus was conducted by 20 experts from Belgium, and consisted of literature review and voting process on 78 statements. Grading of recommendations, assessment, development and evaluation criteria were applied to evaluate the quality of evidence. Consensus was defined as > 80 % agreement. RESULTS Consensus was reached for 50 statements. The Belgian consensus agreed as to the multifactorial aetiology of IBS. According to the consensus abdominal discomfort also represents a cardinal symptom, while bloating and abdominal distension often coexist. IBS needs subtyping based on stool pattern. The importance of a positive diagnosis, relying on history and clinical examination is underlined, while additional testing should remain limited, except when alarm features are present. Explanation of IBS represents a crucial part of patient management. Lifestyle modification, spasmolytics and water-solube fibres are considered first-line agents. The low FODMAP diet, selected probiotics, cognitive behavioural therapy and specific treatments targeting diarrhoea and constipation are considered appropriate. There is a consensus to restrict faecal microbiota transplantation and gluten-free diet, while other treatments are strongly discouraged. CONCLUSIONS A panel of Belgian gastroenterologists summarised the current evidence on the aetiology, symptoms, diagnosis and treatment of IBS with attention for the specificities of the Belgian healthcare system.
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Affiliation(s)
- S Kindt
- Department of gastroenterology and Hepatology, Universitair Ziekenhuis Brussel, Vrije Universiteit Brussel, Brussel, Belgium
| | - H Louis
- Department of Gastroenterology, Hepatopancreatology and Digestive Oncology, Erasme University Hospital, Université Libre de Bruxelles, Route de Lennik 808, 1070 Brussels, Belgium
| | - H De Schepper
- Department of Gastroenterology and Hepatology, University Hospital Antwerp, Antwerp, Belgium
| | - J Arts
- Department of Gastroenterology and Hepatology, University Hospitals Leuven, Leuven, Belgium
- Department of Gastroenterology, AZ Sint-Lucas, Brugge, Belgium
| | - P Caenepeel
- Department of Gastroenterology and Hepatology, University Hospitals Leuven, Leuven, Belgium
- Department of Gastroenterology, Ziekenhuis Oost-Limburg, Campus Sint-Jan, Genk, Belgium
- UHasselt, Hasselt, Belgium
| | - D De Looze
- Department of Gastroenterology and Hepatology, University Hospital Ghent, Gent, Belgium
| | - A Gerkens
- Boitsfort Medical Center, Brussels, Belgium
| | - T Holvoet
- Department of Gastroenterology and Hepatology, University Hospital Ghent, Gent, Belgium
- Department of Gastroenterology, AZ Nikolaas, Sint Niklaas, Belgium
| | - P Latour
- Department of Gastroenterology, Hepatology and Digestive Oncology, Centre Hospitalier Universitaire de Liège, Liège, Belgium
| | - T Mahler
- Department of Pediatrics, Universitair Ziekenuis Brussel, Brussel, Belgium
| | - F Mokaddem
- Department of Gastroenterology and Hepatology, Vivalia-Centre Sud Luxembourg, Arlon, Belgium
| | - S Nullens
- Department of Gastroenterology and Hepatology, University Hospital Antwerp, Antwerp, Belgium
| | - H Piessevaux
- Department of Hepato-gastroenterology, Cliniques universitaires St-Luc, Université catholique de Louvain, Brussels, Belgium
| | - P Poortmans
- Department of gastroenterology and Hepatology, Universitair Ziekenhuis Brussel, Vrije Universiteit Brussel, Brussel, Belgium
| | - G Rasschaert
- Department of gastroenterology and Hepatology, Universitair Ziekenhuis Brussel, Vrije Universiteit Brussel, Brussel, Belgium
| | - M Surmont
- Department of gastroenterology and Hepatology, Universitair Ziekenhuis Brussel, Vrije Universiteit Brussel, Brussel, Belgium
| | - H Vafa
- Department of Gastroenterology and Hepatology, Chirec-Site Delta, Brussels, Belgium
| | - K Van Malderen
- Department of Gastroenterology and Hepatology, University Hospital Antwerp, Antwerp, Belgium
| | - T Vanuytsel
- Department of Gastroenterology and Hepatology, University Hospitals Leuven, Leuven, Belgium
| | - F Wuestenberghs
- Department of Gastroenterology and Hepatology, CHU UCL Namur, Université catholique de Louvain, Yvoir, Belgium
| | - J Tack
- Department of Gastroenterology and Hepatology, University Hospitals Leuven, Leuven, Belgium
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17
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Tao E, Zhu Z, Hu C, Long G, Chen B, Guo R, Fang M, Jiang M. Potential Roles of Enterochromaffin Cells in Early Life Stress-Induced Irritable Bowel Syndrome. Front Cell Neurosci 2022; 16:837166. [PMID: 35370559 PMCID: PMC8964523 DOI: 10.3389/fncel.2022.837166] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/16/2021] [Accepted: 02/09/2022] [Indexed: 12/04/2022] Open
Abstract
Irritable bowel syndrome (IBS) is one of the most common functional gastrointestinal disorders, also known as disorders of the gut–brain interaction; however, the pathophysiology of IBS remains unclear. Early life stress (ELS) is one of the most common risk factors for IBS development. However, the molecular mechanisms by which ELS induces IBS remain unclear. Enterochromaffin cells (ECs), as a prime source of peripheral serotonin (5-HT), play a pivotal role in intestinal motility, secretion, proinflammatory and anti-inflammatory effects, and visceral sensation. ECs can sense various stimuli and microbiota metabolites such as short-chain fatty acids (SCFAs) and secondary bile acids. ECs can sense the luminal environment and transmit signals to the brain via exogenous vagal and spinal nerve afferents. Increasing evidence suggests that an ECs-5-HT signaling imbalance plays a crucial role in the pathogenesis of ELS-induced IBS. A recent study using a maternal separation (MS) animal model mimicking ELS showed that MS induced expansion of intestinal stem cells and their differentiation toward secretory lineages, including ECs, leading to ECs hyperplasia, increased 5-HT production, and visceral hyperalgesia. This suggests that ELS-induced IBS may be associated with increased ECs-5-HT signaling. Furthermore, ECs are closely related to corticotropin-releasing hormone, mast cells, neuron growth factor, bile acids, and SCFAs, all of which contribute to the pathogenesis of IBS. Collectively, ECs may play a role in the pathogenesis of ELS-induced IBS. Therefore, this review summarizes the physiological function of ECs and focuses on their potential role in the pathogenesis of IBS based on clinical and pre-clinical evidence.
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Affiliation(s)
- Enfu Tao
- Endoscopy Center and Gastrointestinal Laboratory, Children’s Hospital, Zhejiang University School of Medicine, National Clinical Research Center for Child Health, National Children’s Regional Medical Center, Hangzhou, China
- Wenling Maternal and Child Health Care Hospital, Wenling, China
| | - Zhenya Zhu
- Endoscopy Center and Gastrointestinal Laboratory, Children’s Hospital, Zhejiang University School of Medicine, National Clinical Research Center for Child Health, National Children’s Regional Medical Center, Hangzhou, China
| | - Chenmin Hu
- Endoscopy Center and Gastrointestinal Laboratory, Children’s Hospital, Zhejiang University School of Medicine, National Clinical Research Center for Child Health, National Children’s Regional Medical Center, Hangzhou, China
| | - Gao Long
- Endoscopy Center and Gastrointestinal Laboratory, Children’s Hospital, Zhejiang University School of Medicine, National Clinical Research Center for Child Health, National Children’s Regional Medical Center, Hangzhou, China
| | - Bo Chen
- Endoscopy Center and Gastrointestinal Laboratory, Children’s Hospital, Zhejiang University School of Medicine, National Clinical Research Center for Child Health, National Children’s Regional Medical Center, Hangzhou, China
| | - Rui Guo
- Endoscopy Center and Gastrointestinal Laboratory, Children’s Hospital, Zhejiang University School of Medicine, National Clinical Research Center for Child Health, National Children’s Regional Medical Center, Hangzhou, China
| | - Marong Fang
- Institute of Neuroscience and Gastrointestinal Laboratory, Children’s Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | - Mizu Jiang
- Department of Gastroenterology, Children’s Hospital, Zhejiang University School of Medicine, National Clinical Research Center for Child Health, National Children’s Regional Medical Center, Hangzhou, China
- *Correspondence: Mizu Jiang,
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18
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Poon D, Law GR, Major G, Andreyev HJN. A systematic review and meta-analysis on the prevalence of non-malignant, organic gastrointestinal disorders misdiagnosed as irritable bowel syndrome. Sci Rep 2022; 12:1949. [PMID: 35121775 PMCID: PMC8817019 DOI: 10.1038/s41598-022-05933-1] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/05/2021] [Accepted: 12/21/2021] [Indexed: 12/16/2022] Open
Abstract
Treatable gastrointestinal disorders in patients with symptoms typical for irritable bowel syndrome (IBS) may be overlooked. The prevalence of five gastrointestinal conditions-bile acid diarrhoea (BAD), carbohydrate malabsorption (CM), microscopic colitis (MC), pancreatic exocrine insufficiency (PEI) and small intestinal bacterial overgrowth (SIBO) was systematically assessed from studies including consecutive patients meeting diagnostic criteria for IBS. 4 databases were searched from 1978 to 2020. Studies were included if they evaluated the prevalence of these conditions in secondary healthcare setting. Estimated pooled rates were calculated and statistical heterogeneity between studies was evaluated using Q and I2 statistics. Seven studies (n = 597) estimated the pooled prevalence for BAD as 41% (95% CI 29-54). 17 studies (n = 5068) estimated that of MC as 3% (95% CI 2-4%). Two studies (n = 478) suggested a rate of 4.6% (range: 1.8-6.1%) for PEI. Using breath testing, 26 studies (n = 6700) and 13 studies (n = 3415) estimated the prevalence of lactose and fructose malabsorption as 54% (95% CI 44-64%) and 43% (95% CI 23-62%); 36 studies (n = 4630) and 22 studies (n = 2149) estimated that of SIBO as 49% (95% CI 40-57%) with lactulose and 19% (95% CI 13-27%) with glucose. Rates of all conditions were significantly higher than in healthy controls. A significant proportion of patients presenting to secondary care with IBS have an organic condition which may account for their symptoms. Failure to exclude such conditions will deny patients effective treatment.
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Affiliation(s)
- Dennis Poon
- Department of Gastroenterology, Lincoln County Hospital, Greetwell Road, Lincoln, LN2 5QY, UK
| | - Graham R Law
- Community and Health Research Unit, School of Health and Social Care, University of Lincoln, Lincoln, LN6 7TS, UK
| | - Giles Major
- NIHR Nottingham Biomedical Research Centre, Nottingham University Hospitals NHS Trust and the University of Nottingham, Nottingham, UK
- Queens Medical Centre Campus, Derby Road, Nottingham, NG7 2UH, UK
| | - H Jervoise N Andreyev
- Department of Gastroenterology, Lincoln County Hospital, Greetwell Road, Lincoln, LN2 5QY, UK.
- NIHR Nottingham Biomedical Research Centre, Nottingham University Hospitals NHS Trust and the University of Nottingham, Nottingham, UK.
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19
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Asghar Z, Thoufeeq M, Kurien M, Ball AJ, Rej A, David Tai FW, Afify S, Aziz I. Diagnostic Yield of Colonoscopy in Patients With Symptoms Compatible With Rome IV Functional Bowel Disorders. Clin Gastroenterol Hepatol 2022; 20:334-341.e3. [PMID: 32882424 DOI: 10.1016/j.cgh.2020.08.062] [Citation(s) in RCA: 21] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/03/2020] [Revised: 08/25/2020] [Accepted: 08/26/2020] [Indexed: 02/07/2023]
Abstract
BACKGROUND & AIMS There is little data on the diagnostic yield of colonoscopy in patients with symptoms compatible with functional bowel disorders (FBDs). Previous studies have only focused on diagnostic outcomes of colonoscopy in those with suspected irritable bowel syndrome using historic Rome I-III criteria, whilst having partially assessed for alarm features and shown markedly conflicting results. There is also no colonoscopy outcome data for other FBDs, such as functional constipation or functional diarrhea. Using the contemporaneous Rome IV criteria we determined the diagnostic yield of colonoscopy in patients with symptoms compatible with a FBD, stratified diligently according to the presence or absence of alarm features. METHODS Basic demographics, alarm features, and bowel symptoms using the Rome IV diagnostic questionnaire were collected prospectively from adults attending out-patient colonoscopy in 2019. Endoscopists were blinded to the questionnaire data. Organic disease was defined as the presence of inflammatory bowel disease, colorectal cancer, or microscopic colitis. RESULTS 646 patients fulfilled symptom-based criteria for the following Rome IV FBDs: IBS (56%), functional diarrhea (27%) and functional constipation (17%). Almost all had alarm features (98%). The combined prevalence of organic disease was 12%, being lowest for functional constipation and IBS-constipation (∼6% each), followed by IBS-mixed (∼9%), and highest amongst functional diarrhea and IBS-diarrhea (∼17% each); p = .005. The increased prevalence of organic disease in diarrheal versus constipation disorders was accounted for by microscopic colitis (5.7% vs. 0%, p < .001) but not inflammatory bowel disease (7.2% vs. 4.0%, p = .2) or colorectal cancer (4.2% vs. 2.3%, p = .2). However, 1-in-4 chronic diarrhea patients - conceivably at risk for microscopic colitis - did not have colonic biopsies taken. Finally, only 11 of 646 (2%) patients were without alarm features, in whom colonoscopy was normal. CONCLUSIONS Most patients with symptoms of FBDs who are referred for colonoscopy have alarm features. The presence of organic disease is significantly higher in diarrheal versus constipation disorders, with microscopic colitis largely accounting for the difference whilst also being a missed diagnostic opportunity. In those patients without alarm features, the diagnostic yield of colonoscopy was nil.
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Affiliation(s)
- Zohaib Asghar
- Academic Department of Gastroenterology, Sheffield Teaching Hospitals, Sheffield, United Kingdom; Department of Infection, Immunity and Cardiovascular Disease, University of Sheffield, Sheffield, United Kingdom
| | - Mo Thoufeeq
- Academic Department of Gastroenterology, Sheffield Teaching Hospitals, Sheffield, United Kingdom
| | - Matthew Kurien
- Academic Department of Gastroenterology, Sheffield Teaching Hospitals, Sheffield, United Kingdom; Department of Infection, Immunity and Cardiovascular Disease, University of Sheffield, Sheffield, United Kingdom
| | - Alex J Ball
- Academic Department of Gastroenterology, Sheffield Teaching Hospitals, Sheffield, United Kingdom
| | - Anupam Rej
- Academic Department of Gastroenterology, Sheffield Teaching Hospitals, Sheffield, United Kingdom
| | - Foong Way David Tai
- Academic Department of Gastroenterology, Sheffield Teaching Hospitals, Sheffield, United Kingdom
| | - Shima Afify
- Academic Department of Gastroenterology, Sheffield Teaching Hospitals, Sheffield, United Kingdom
| | - Imran Aziz
- Academic Department of Gastroenterology, Sheffield Teaching Hospitals, Sheffield, United Kingdom; Department of Infection, Immunity and Cardiovascular Disease, University of Sheffield, Sheffield, United Kingdom.
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20
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Ghadaksaz A, Nodoushan SM, Sedighian H, Behzadi E, Fooladi AAI. Evaluation of the Role of Probiotics As a New Strategy to Eliminate Microbial Toxins: a Review. Probiotics Antimicrob Proteins 2022; 14:224-237. [PMID: 35031968 DOI: 10.1007/s12602-021-09893-2] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 12/15/2021] [Indexed: 01/17/2023]
Abstract
Probiotics are living microorganisms that have favorable effects on human and animal health. The most usual types of microorganisms recruited as probiotics are lactic acid bacteria (LAB) and bifidobacteria. To date, numerous utilizations of probiotics have been reported. In this paper, it is suggested that probiotic bacteria can be recruited to remove and degrade different types of toxins such as mycotoxins and algal toxins that damage host tissues and the immune system causing local and systemic infections. These microorganisms can remove toxins by disrupting, changing the permeability of the plasma membrane, producing metabolites, inhibiting the protein translation, hindering the binding to GTP binding proteins to GM1 receptors, or by preventing the interaction between toxins and adhesions. Here, we intend to review the mechanisms that probiotic bacteria use to eliminate and degrade microbial toxins.
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Affiliation(s)
- Abdolamir Ghadaksaz
- Department of Biology, Science and Research Branch, Islamic Azad University, Tehran, Iran
| | - Somayeh Mousavi Nodoushan
- Applied Microbiology Research Center, Systems Biology and Poisonings Institute, Baqiyatallah University of Medical Sciences, Vanak Sq. Molasadra St, Tehran, Iran
| | - Hamid Sedighian
- Applied Microbiology Research Center, Systems Biology and Poisonings Institute, Baqiyatallah University of Medical Sciences, Vanak Sq. Molasadra St, Tehran, Iran
| | - Elham Behzadi
- Department of Microbiology, College of Basic Sciences, Shahr-E-Qods Branch, Islamic Azad University, Tehran, Iran
| | - Abbas Ali Imani Fooladi
- Applied Microbiology Research Center, Systems Biology and Poisonings Institute, Baqiyatallah University of Medical Sciences, Vanak Sq. Molasadra St, Tehran, Iran.
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21
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Purssell H, Whorwell PJ, Athwal VS, Vasant DH. Non-alcoholic fatty liver disease in irritable bowel syndrome: More than a coincidence? World J Hepatol 2021; 13:1816-1827. [PMID: 35069992 PMCID: PMC8727221 DOI: 10.4254/wjh.v13.i12.1816] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/17/2021] [Revised: 08/01/2021] [Accepted: 10/27/2021] [Indexed: 02/06/2023] Open
Abstract
Irritable bowel syndrome (IBS) and non-alcoholic fatty liver disease (NAFLD) are amongst the most common gastrointestinal and liver conditions encountered in primary and secondary care. Recently, there has been interest in the apparent co-incidence of NAFLD in patients with IBS mainly driven by improved understanding of their shared risk factors and pathophysiology. In this paper we summarize the shared risk factors which include; overlapping nutritional and dietary factors as well as shared putative mechanisms of pathophysiology. These include changes in the gut microbiome, gut permeability, immunity, small bowel bacterial overgrowth and bile acid metabolism. This paper describes how these shared risk factors and etiological factors may have practical clinical implications for these highly prevalent conditions. It also highlights some of the limitations of current epidemiological data relating to estimates of the overlapping prevalence of the two conditions which have resulted in inconsistent results and, therefore the need for further research. Early recognition and management of the overlap could potentially have impacts on treatment outcomes, compliance and morbidity of both conditions. Patients with known IBS who have abnormal liver function tests or significant risk factors for NAFLD should be investigated appropriately for this possibility. Similarly, IBS should be considered in patients with NAFLD and symptoms of abdominal pain associated with defecation, an altered bowel habit and bloating.
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Affiliation(s)
- Huw Purssell
- Hepatology, Manchester University NHS Foundation Trust, Manchester M23 9LT, United Kingdom
- Division of Diabetes, Endocrinology and Gastroenterology, University of Manchester, Manchester M23 9LT, United Kingdom
| | - Peter J Whorwell
- Division of Diabetes, Endocrinology and Gastroenterology, University of Manchester, Manchester M23 9LT, United Kingdom
- Neurogastroenterology Unit, Wythenshawe Hospital, Manchester University NHS Foundation Trust, Manchester M23 9LT, United Kingdom
| | - Varinder S Athwal
- Hepatology, Manchester University NHS Foundation Trust, Manchester M23 9LT, United Kingdom
- Division of Diabetes, Endocrinology and Gastroenterology, University of Manchester, Manchester M23 9LT, United Kingdom
| | - Dipesh H Vasant
- Division of Diabetes, Endocrinology and Gastroenterology, University of Manchester, Manchester M23 9LT, United Kingdom
- Neurogastroenterology Unit, Department of Gastroenterology, Manchester University NHS Foundation Trust, Wythenshawe Hospital, Manchester M23 9LT, United Kingdom.
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22
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Hou JJ, Wang X, Wang YM, Wang BM. Interplay between gut microbiota and bile acids in diarrhoea-predominant irritable bowel syndrome: a review. Crit Rev Microbiol 2021; 48:696-713. [PMID: 34936854 DOI: 10.1080/1040841x.2021.2018401] [Citation(s) in RCA: 13] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
Irritable bowel syndrome (IBS) is a common functional gastrointestinal disease that disturbs the physiology and psychology of patients and increases the burden on families, the healthcare system, society, and economic development, affecting more and more people around the world. Despite the multiple factors that account for IBS remaining incompletely studied, emerging evidence demonstrated the abnormal changes in gut microbiota and bile acids (BAs) metabolism closely associated with IBS. Moreover, microbiota drives significant modifications for BAs, consisting of deconjugation, 7α-dehydroxylation, oxidation, epimerization, desulfation, esterification, and so on, while BAs, in turn, affect the microbiota directly or indirectly. In light of the complex connection among gut microbiota, BAs, and IBS, it is urgent to review the latest research progress in this field. In this review, we described the disorders of intestinal microecology and BAs profiles in IBS-D and also highlighted the cross-talk between gut microbiota and BAs in the context of IBS-D. Integrating these, we suggest that new therapeutic strategies targeting the microbiota-BAs axis for IBS-D, even for other related diseases caused by bacteria-bile acid dysbiosis should be expected.
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Affiliation(s)
- Jun-Jie Hou
- Department of Gastroenterology and Hepatology, Tianjin Medical University General Hospital, Tianjin, China.,Tianjin Institute of Digestive Disease, Tianjin Medical University General Hospital, Tianjin, China.,Tianjin Key Laboratory of Digestive Disease, Tianjin Medical University General Hospital, Tianjin, China
| | - Xin Wang
- Department of Gastroenterology and Hepatology, Tianjin Medical University General Hospital, Tianjin, China.,Tianjin Institute of Digestive Disease, Tianjin Medical University General Hospital, Tianjin, China.,Tianjin Key Laboratory of Digestive Disease, Tianjin Medical University General Hospital, Tianjin, China
| | - Yu-Ming Wang
- Department of Gastroenterology and Hepatology, Tianjin Medical University General Hospital, Tianjin, China.,Tianjin Institute of Digestive Disease, Tianjin Medical University General Hospital, Tianjin, China.,Tianjin Key Laboratory of Digestive Disease, Tianjin Medical University General Hospital, Tianjin, China
| | - Bang-Mao Wang
- Department of Gastroenterology and Hepatology, Tianjin Medical University General Hospital, Tianjin, China.,Tianjin Institute of Digestive Disease, Tianjin Medical University General Hospital, Tianjin, China.,Tianjin Key Laboratory of Digestive Disease, Tianjin Medical University General Hospital, Tianjin, China
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23
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Black CJ. Review article: Diagnosis and investigation of irritable bowel syndrome. Aliment Pharmacol Ther 2021; 54 Suppl 1:S33-S43. [PMID: 34927756 DOI: 10.1111/apt.16597] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/19/2021] [Revised: 08/22/2021] [Accepted: 08/24/2021] [Indexed: 12/17/2022]
Abstract
Irritable bowel syndrome (IBS) is a common disorder of gut-brain interaction. It is defined by the Rome criteria as the presence of abdominal pain, related to defaecation, associated with a change in stool form and/or frequency. The approach to diagnosis and investigation of suspected IBS varies between clinicians and, due in part to the uncertainty that can surround the diagnosis, many still consider it to be a diagnosis of exclusion. However, exhaustive investigation is both unnecessary and costly, and may also be counterproductive. Instead, physicians should aim to make a positive diagnosis, based on their clinical assessment of symptoms, and limit their use of investigations. The yield of routine blood tests in suspected IBS is low overall, but normal inflammatory markers may be reassuring. All patients should have serological testing for coeliac disease, irrespective of their predominant stool form. Routine testing of stool microbiology or faecal elastase is unnecessary; however, all patients with diarrhoea aged <45 should have a faecal calprotectin or a similar marker measured which, if positive, should lead to colonoscopy to exclude possible inflammatory bowel disease. Colonoscopy should also be undertaken in any patient reporting alarm symptoms suggestive of colorectal cancer, and in those whose presentation raises suspicion for microscopic colitis. Testing for bile acid diarrhoea should be considered for patients with IBS with diarrhoea where available. Hydrogen breath tests for lactose malabsorption or small intestinal bacterial overgrowth have no role in the routine assessment of suspected IBS. Adopting a standardised approach to the diagnosis and investigation of IBS will help to promote high-quality and high-value care for patients overall.
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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
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24
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Shiha MG, Asghar Z, Thoufeeq M, Kurien M, Ball AJ, Rej A, Tai FWD, Afify S, Aziz I. Increased psychological distress and somatization in patients with irritable bowel syndrome compared with functional diarrhea or functional constipation, based on Rome IV criteria. Neurogastroenterol Motil 2021; 33:e14121. [PMID: 33719130 DOI: 10.1111/nmo.14121] [Citation(s) in RCA: 12] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/30/2020] [Revised: 02/02/2021] [Accepted: 02/19/2021] [Indexed: 12/13/2022]
Abstract
BACKGROUND The Rome IV criteria for disorders of gut-brain interaction define irritable bowel syndrome (IBS) as a functional bowel disorder associated with frequent abdominal pain of at least 1 day per week. In contrast, functional diarrhea (FD) and functional constipation (FC) are relatively painless. We compared differences in mood and somatization between Rome IV IBS and FC/FD. METHODS A total of 567 patients with Rome IV defined IBS or FD/FC completed a baseline questionnaire on demographics, abdominal pain frequency, mood (hospital anxiety and depression scale, HADS), and somatization (patient health questionnaire, PHQ-12). The primary analysis compared differences in mood and somatization between IBS and FC/FD, and the relative influence of abdominal pain frequency on these extra-intestinal symptoms. The secondary analysis evaluated differences across individual IBS subtypes, and also between FC and FD. KEY RESULTS Patients with IBS-in comparison to those with FC/FD-had significantly higher mean PHQ-12 somatization scores (9.1 vs. 5.4), more somatic symptoms (6.0 vs. 4.3), abnormally high somatization levels (16% vs. 3%), higher HADS score (15.0 vs. 11.7), and clinically abnormal levels of anxiety (38% vs. 20%) and depression (17% vs. 10%). Increasing abdominal pain frequency correlated positively with PHQ-12, number of somatic symptoms, and HADS; p < 0.001. No differences in mood and somatization scores were seen between individual IBS subtypes, and nor between FC and FD. CONCLUSION & INFERENCES Based on the Rome IV criteria, IBS is associated with increased levels of psychological distress and somatization compared with FD or FC. Patients reporting frequent abdominal pain should be comprehensively screened for psychosomatic disorders, with psychological therapies considered early in the disease course.
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Affiliation(s)
- Mohamed G Shiha
- Academic Department of Gastroenterology, Sheffield Teaching Hospitals, Sheffield, UK
| | - Zohaib Asghar
- Academic Department of Gastroenterology, Sheffield Teaching Hospitals, Sheffield, UK.,Department of Infection, Immunity and Cardiovascular Disease, University of Sheffield, Sheffield, UK
| | - Mo Thoufeeq
- Academic Department of Gastroenterology, Sheffield Teaching Hospitals, Sheffield, UK
| | - Matthew Kurien
- Academic Department of Gastroenterology, Sheffield Teaching Hospitals, Sheffield, UK.,Department of Infection, Immunity and Cardiovascular Disease, University of Sheffield, Sheffield, UK
| | - Alex J Ball
- Academic Department of Gastroenterology, Sheffield Teaching Hospitals, Sheffield, UK
| | - Anupam Rej
- Academic Department of Gastroenterology, Sheffield Teaching Hospitals, Sheffield, UK
| | - Foong Way David Tai
- Academic Department of Gastroenterology, Sheffield Teaching Hospitals, Sheffield, UK
| | - Shima Afify
- Academic Department of Gastroenterology, Sheffield Teaching Hospitals, Sheffield, UK
| | - Imran Aziz
- Academic Department of Gastroenterology, Sheffield Teaching Hospitals, Sheffield, UK.,Department of Infection, Immunity and Cardiovascular Disease, University of Sheffield, Sheffield, UK
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25
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Abstract
Irritable bowel syndrome (IBS) is among the most common diagnoses made by medical providers and its symptoms are common causes for health care consultation. IBS is characterized by abdominal pain associated with abnormal stool consistency and/or frequency and is widely considered a diagnosis of exclusion, despite abundant evidence contradicting such an approach. A positive diagnosis is achieved through application of symptom-based clinical criteria, careful history and physical examination, evaluation for alarm sign/symptoms, and judicious use of diagnostic testing. This article reviews the symptom-based criteria for IBS and utility of diagnostic tests commonly included in the evaluation of IBS symptoms.
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Affiliation(s)
- Ryan S Goldstein
- Gastroenterology, Hepatology and Nutrition, UT Health Science Center at Houston, 6431 Fannin Street, MSB 4.234, Houston, TX 77030, USA
| | - Brooks D Cash
- Gastroenterology, Hepatology and Nutrition, UT Health Science Center at Houston, 6431 Fannin Street, MSB 4.234, Houston, TX 77030, USA.
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26
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Videlock EJ, Chang L. Latest Insights on the Pathogenesis of Irritable Bowel Syndrome. Gastroenterol Clin North Am 2021; 50:505-522. [PMID: 34304785 DOI: 10.1016/j.gtc.2021.04.002] [Citation(s) in RCA: 12] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/18/2022]
Abstract
The pathogenesis of irritable bowel syndrome is multifactorial and complex. Our understanding of its pathophysiology has evolved, but remains incompletely understood. Symptoms result from a dysregulation of brain-gut interactions. Evidence has identified alterations in central and peripheral (gut) mechanisms in irritable bowel syndrome and the bidirectional communication between the brain and the gut. Pertinent mechanisms include disturbed gut motility, visceral hypersensitivity, altered mucosal and immune function, altered gut microbiota, and altered central nervous system processing. This review addresses factors that increase the risk of irritable bowel syndrome and the central and peripheral mechanisms thought to underlie its symptoms.
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Affiliation(s)
- Elizabeth J Videlock
- Vatche and Tamar Manoukian Division of Digestive Diseases, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA
| | - Lin Chang
- Vatche and Tamar Manoukian Division of Digestive Diseases, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA.
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27
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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: 269] [Impact Index Per Article: 67.3] [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.
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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
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Black CJ, Craig O, Gracie DJ, Ford AC. Comparison of the Rome IV criteria with the Rome III criteria for the diagnosis of irritable bowel syndrome in secondary care. Gut 2021; 70:1110-1116. [PMID: 32973070 DOI: 10.1136/gutjnl-2020-322519] [Citation(s) in RCA: 43] [Impact Index Per Article: 10.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/12/2020] [Revised: 08/25/2020] [Accepted: 09/02/2020] [Indexed: 12/11/2022]
Abstract
OBJECTIVES Despite being proposed 4 years ago, there has been no independent validation study of the Rome IV criteria for IBS. We assessed their performance for the diagnosis of IBS in secondary care and compared them with the previous iteration, the Rome III criteria. DESIGN We collected complete symptom data from consecutive adult patients with suspected IBS referred to a single UK clinic. All subjects underwent relatively standardised workup, with assessors blinded to symptom status. The reference standard used to confirm IBS was the presence of lower abdominal pain or discomfort in association with altered stool form or frequency, in a patient with no evidence of organic gastrointestinal disease after investigation. Sensitivity, specificity and positive and negative likelihood ratios (LRs), with 95% CIs, were calculated for each of the diagnostic criteria. RESULTS The level of agreement between the Rome IV and Rome III criteria was good (kappa=0.65). Compared with the reference standard, sensitivity and specificity of the Rome IV criteria in 572 patients (431 (75.3%) women, mean age 36.5 years) were 82.4% and 82.9%, respectively. Positive and negative LRs for the Rome IV criteria were 4.82 (95% CI 3.30 to 7.28) and 0.21 (95% CI 0.17 to 0.26), respectively. The Rome IV criteria performed best in those with IBS with constipation or mixed bowel habits. In 471 patients (350 (74.3%) women, mean age 36.7 years), compared with the reference standard, the sensitivity and specificity of the Rome III criteria were 85.8% and 65.0%; positive and negative LRs were 2.45 (95% CI 1.90 to 3.27) and 0.22 (0.16 to 0.29), respectively. Incorporating mood and extraintestinal symptom reporting into diagnostic criteria did not improve their performance significantly. CONCLUSIONS The Rome IV criteria performed significantly better than the Rome III criteria in diagnosing IBS in this single centre secondary care study, although the clinical relevance of this is uncertain.
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Affiliation(s)
- 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
| | - Orla Craig
- Leeds Gastroenterology Institute, Leeds Teaching Hospitals NHS Trust, Leeds, UK
| | - David J Gracie
- Leeds Gastroenterology Institute, Leeds Teaching Hospitals NHS Trust, Leeds, 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
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Flores V, Martínez-Lozano H, Bighelli F, Orcajo J, García-Lledó J, Alonso-Farto JC, Menchén L. Prevalence of biliary acid malabsorption in patients with chronic diarrhoea of functional characteristics: a prospective study. BMC Gastroenterol 2021; 21:56. [PMID: 33563227 PMCID: PMC7871394 DOI: 10.1186/s12876-021-01637-4] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/04/2020] [Accepted: 02/02/2021] [Indexed: 12/22/2022] Open
Abstract
Background Bile acid malabsorption occurs in up to one third of patients with chronic diarrhoea of functional characteristics. The gold standard test for its diagnosis is the 75Selenium homocholic acid taurine (75SeHCAT) test. The aim of this work is to confirm previous data suggesting that bile acid malabsorption, diagnosed by 75Se-HCAT test, is the underlying cause of diarrhoea in a significant proportion of patients previously diagnosed with a functional disorder. In addition, we have analysed the clinical response of bile acid sequestrants in those patients with a bile acid diarrhoea diagnosis. Methods This is a prospective, single-centre study including consecutive adult patients diagnosed with chronic diarrhoea of unknown origin and with functional characteristics; systematic rule out of common causes of chronic diarrhoea was performed before bile acid malabsorption evaluation by 75SeHCAT scanning. A retention percentage less than 10% was considered positive. Clinical response to cholestyramine was further evaluated in those patients with a positive diagnosis of bile acid diarrhoea Results 38 patients (20 male, mean age 37.5 years) were finally included. Twenty (52.6%) patients included had a positive 75SeHCAT test. Median body mass index was significantly higher in those patients. We did not find significant differences in other clinical or biochemical variables 75SeHCAT-positive and 75SeHCAT-negative groups. Only 6 of 17 (35.3%) patients responded to cholestyramine treatment; 10 patients did not have response or withdraw the drug due to adverse events. Logistic regression analysis showed that none of the included variables was a predictor of clinical response to cholestyramine. Conclusions Bile acid malabsorption occurs in a high proportion of patients suffering from chronic diarrhoea with functional characteristics. Systematic investigation of bile acid malabsorption should be included in the diagnostic algorithms of patients with chronic watery diarrhoea in the routine clinical practice. Absence of response to cholestyramine does not rule out bile acid diarrhoea.
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Affiliation(s)
- Virginia Flores
- Servicio de Aparato Digestivo, Hospital General Universitario Gregorio Marañón - Instituto de Investigación Sanitaria Gregorio Marañón, C/ Dr. Esquerdo 46, 28007, Madrid, Spain
| | - Helena Martínez-Lozano
- Servicio de Aparato Digestivo, Hospital General Universitario Gregorio Marañón - Instituto de Investigación Sanitaria Gregorio Marañón, C/ Dr. Esquerdo 46, 28007, Madrid, Spain
| | - Federico Bighelli
- Servicio de Aparato Digestivo, Hospital General Universitario Gregorio Marañón - Instituto de Investigación Sanitaria Gregorio Marañón, C/ Dr. Esquerdo 46, 28007, Madrid, Spain
| | - Javier Orcajo
- Servicio de Medicina Nuclear, Hospital General Universitario Gregorio Marañón - Instituto de Investigación Sanitaria Gregorio Marañón, Madrid, Spain
| | - Javier García-Lledó
- Servicio de Aparato Digestivo, Hospital General Universitario Gregorio Marañón - Instituto de Investigación Sanitaria Gregorio Marañón, C/ Dr. Esquerdo 46, 28007, Madrid, Spain
| | - Juan Carlos Alonso-Farto
- Servicio de Medicina Nuclear, Hospital General Universitario Gregorio Marañón - Instituto de Investigación Sanitaria Gregorio Marañón, Madrid, Spain
| | - Luis Menchén
- Servicio de Aparato Digestivo, Hospital General Universitario Gregorio Marañón - Instituto de Investigación Sanitaria Gregorio Marañón, C/ Dr. Esquerdo 46, 28007, Madrid, Spain. .,Departamento de Medicina, Centro de Investigación Biomédica en Red de Enfermedades Hepáticas Y Digestivas (CIBEREHD), Universidad Complutense de Madrid, Madrid, Spain. .,Centro de Investigación Biomédica en Red de Enfermedades Hepáticas Y Digestivas (CIBEREHD), Madrid, Spain.
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The overlap between irritable bowel syndrome and organic gastrointestinal diseases. Lancet Gastroenterol Hepatol 2021; 6:139-148. [DOI: 10.1016/s2468-1253(20)30212-0] [Citation(s) in RCA: 27] [Impact Index Per Article: 6.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/24/2020] [Revised: 06/15/2020] [Accepted: 06/22/2020] [Indexed: 12/13/2022]
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Costa S, Gattoni S, Nicolardi ML, Costetti M, Maimaris S, Schiepatti A, Biagi F. Prevalence and clinical features of bile acid diarrhea in patients with chronic diarrhea. J Dig Dis 2021; 22:108-112. [PMID: 33438795 DOI: 10.1111/1751-2980.12969] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/19/2020] [Revised: 01/04/2021] [Accepted: 01/10/2021] [Indexed: 12/11/2022]
Abstract
OBJECTIVE Bile acid diarrhea is a form of chronic diarrhea caused by excessive bile reaching the colon. Conditions involving the terminal ileum and cholecystectomy are predisposing factors but an idiopathic form of bile acid diarrhea has also been described. In this study we aimed to evaluate the prevalence of bile acid diarrhea in patients consecutively evaluated for chronic diarrhea in an Outpatient Gastroenterology Clinic. METHODS Medical records of all patients admitted for chronic diarrhea (>4 weeks) between June 2018 and April 2019 were retrospectively reviewed. Bile acid diarrhea was suspected in patients with ileal disease, cholecystectomy or post-prandial diarrhea. Patients' age at diagnosis, sex, presenting symptoms, results of main test and examinations, final diagnoses and date of last follow-up visit were also collected. Exclusion of chronic diarrhea of other causes and a 6-month clinical improvement with cholestyramine treatment confirmed the diagnosis of bile acid diarrhea. RESULTS In total, 139 patients aged 46 ± 20 years (76 women and 63 men) were included. Diarrhea due to an organic cause was diagnosed in 16 patients. A clinical response to cholestyramine persisting for more than 6 months led to a diagnosis of bile acid diarrhea in 39 (aged 52 ± 19 years) out of the remaining 123 patients with functional forms of diarrhea. Therefore, the prevalence of bile acid diarrhea was 28.1% (95% confidence interval 19.9%-38.4%) in patients with chronic diarrhea. CONCLUSIONS Bile acid diarrhea is a very common, yet under-recognized cause of chronic functional diarrhea. A therapeutic trial of cholestyramine is a valid diagnostic strategy.
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Affiliation(s)
- Stefania Costa
- Gastroenterology Unit of Pavia Institute, Istituti Clinici Scientifici Maugeri, University of Pavia, Pavia, Italy
| | - Serena Gattoni
- Gastroenterology Unit of Pavia Institute, Istituti Clinici Scientifici Maugeri, University of Pavia, Pavia, Italy
| | - Maria Luisa Nicolardi
- Gastroenterology Unit of Pavia Institute, Istituti Clinici Scientifici Maugeri, University of Pavia, Pavia, Italy
| | - Martina Costetti
- Gastroenterology Unit of Pavia Institute, Istituti Clinici Scientifici Maugeri, University of Pavia, Pavia, Italy
| | - Stiliano Maimaris
- Gastroenterology Unit of Pavia Institute, Istituti Clinici Scientifici Maugeri, University of Pavia, Pavia, Italy
| | - Annalisa Schiepatti
- Gastroenterology Unit of Pavia Institute, Istituti Clinici Scientifici Maugeri, University of Pavia, Pavia, Italy
| | - Federico Biagi
- Gastroenterology Unit of Pavia Institute, Istituti Clinici Scientifici Maugeri, University of Pavia, Pavia, Italy
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Abstract
PURPOSE OF REVIEW Irritable bowel syndrome (IBS) is a very common disorder whose clinical presentation varies considerably between patients as well as within the same individual over time. Many of its symptoms, such as pain, diarrhea, constipation and bloating, may be manifestations of a host of other gastrointestinal diseases; some accompanied by increased mortality. This presents the clinician with a real dilemma: how to sensibly investigate the patient in which one suspects IBS but there is a nagging doubt that 'it could be something else'? Could one miss 'something serious'? This short review attempts to provide both an evidence-based response to these vexing questions and a practical guide to detecting alternative diagnoses in the subject with IBS-type symptoms. RECENT FINDINGS Clinical features, patient demographics and the clinical context can help to significantly narrow the differential diagnosis of the individual with IBS-type symptoms and may permit a positive diagnosis of IBS. The advent of noninvasive serological and stool tests has greatly facilitated differentiation from celiac disease and inflammatory bowel disease, respectively. In the older, female diarrhea sufferer microscopic colitis should be considered. The role of bile acid diarrhea in the individual with diarrhea-predominant IBS is emphasized; the status of small intestinal bacterial overgrowth in IBS remain uncertain. SUMMARY Attention to detail in the clinical evaluation of the individual with IBS-like symptoms will facilitate a selective and targeted approach to investigation. Wherever indicated, widely available serological and fecal tests will serve to bolster the diagnosis by excluding other options. Proceeding to more invasive testing should be dictated by clinical presentation and scenario with the threshold for intervention being generally lower among those with prominent diarrhea.
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Muehler A, Slizgi JR, Kohlhof H, Groeppel M, Peelen E, Vitt D. Clinical relevance of intestinal barrier dysfunction in common gastrointestinal diseases. World J Gastrointest Pathophysiol 2020; 11:114-130. [PMID: 33362939 PMCID: PMC7739114 DOI: 10.4291/wjgp.v11.i6.114] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/21/2020] [Revised: 10/07/2020] [Accepted: 10/27/2020] [Indexed: 02/06/2023] Open
Abstract
The intestinal barrier is a complex and well-controlled physiological construct designed to separate luminal contents from the bowel wall. In this review, we focus on the intestinal barrier’s relationship with the host’s immune system interaction and the external environment, specifically the microbiome. The bowel allows the host to obtain nutrients vital to survival while protecting itself from harmful pathogens, luminal antigens, or other pro-inflammatory factors. Control over barrier function and the luminal milieu is maintained at the biochemical, cellular, and immunological level. However, disruption to this highly regulated environment can cause disease. Recent advances to the field have progressed the mechanistic understanding of compromised intestinal barrier function in the context of gastrointestinal pathology. There are numerous examples where bowel barrier dysfunction and the resulting interaction between the microbiome and the immune system has disease-triggering consequences. The purpose of this review is to summarize the clinical relevance of intestinal barrier dysfunction in common gastrointestinal and related diseases. This may help highlight the importance of restoring barrier function as a therapeutic mechanism of action in gastrointestinal pathology.
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Wei W, Wang HF, Zhang Y, Zhang YL, Niu BY, Yao SK. Altered metabolism of bile acids correlates with clinical parameters and the gut microbiota in patients with diarrhea-predominant irritable bowel syndrome. World J Gastroenterol 2020; 26:7153-7172. [PMID: 33362374 PMCID: PMC7723672 DOI: 10.3748/wjg.v26.i45.7153] [Citation(s) in RCA: 52] [Impact Index Per Article: 10.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/17/2020] [Revised: 09/21/2020] [Accepted: 10/13/2020] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Bile acids (BAs) have attracted attention in the research of irritable bowel syndrome with predominant diarrhea (IBS-D) due to their ability to modulate bowel function and their tight connection with the gut microbiota. The composition of the fecal BA pool in IBS-D patients is reportedly different from that in healthy populations. We hypothesized that BAs may participate in the pathogenesis of IBS-D and the altered BA profile may be correlated with the gut microbiome. AIM To investigate the role of BAs in the pathogenesis of IBS-D and the correlation between fecal BAs and gut microbiota. METHODS Fifty-five IBS-D patients diagnosed according to the Rome IV criteria and twenty-eight age-, sex-, and body mass index-matched healthy controls (HCs) were enrolled in this study at the gastroenterology department of China-Japan Friendship Hospital. First, clinical manifestations were assessed with standardized questionnaires, and visceral sensitivity was evaluated via the rectal distension test using a high-resolution manometry system. Fecal primary BAs including cholic acid (CA) and chenodeoxycholic acid (CDCA), secondary BAs including deoxycholic acid (DCA), lithocholic acid (LCA), and ursodeoxycholic acid (UDCA) as well as the corresponding tauro- and glyco-BAs were examined by ultraperformance liquid chromatography coupled to tandem mass spectrometry. The gut microbiota was analyzed using 16S rRNA gene sequencing. Correlations between fecal BAs with clinical features and gut microbiota were explored. RESULTS Fecal CA (IBS-D: 3037.66 [282.82, 6917.47] nmol/g, HC: 20.19 [5.03, 1304.28] nmol/g; P < 0.001) and CDCA (IBS-D: 1721.86 [352.80, 2613.83] nmol/g, HC: 57.16 [13.76, 1639.92] nmol/g; P < 0.001) were significantly increased, while LCA (IBS-D: 1621.65 [58.99, 2396.49] nmol/g, HC: 2339.24 [1737.09, 2782.40]; P = 0.002] and UDCA (IBS-D: 8.92 [2.33, 23.93] nmol/g, HC: 17.21 [8.76, 33.48] nmol/g; P = 0.025) were significantly decreased in IBS-D patients compared to HCs. Defecation frequency was positively associated with CA (r = 0.294, P = 0.030) and CDCA (r = 0.290, P = 0.032) and negatively associated with DCA (r = -0.332, P = 0.013) and LCA (r = -0.326, P = 0.015) in IBS-D patients. In total, 23 of 55 IBS-D patients and 15 of 28 HCs participated in the visceral sensitivity test. The first sensation threshold was negatively correlated with CDCA (r = -0.459, P = 0.028) in IBS-D patients. Furthermore, the relative abundance of the family Ruminococcaceae was significantly decreased in IBS-D patients (P < 0.001), and 12 genera were significantly lower in IBS-D patients than in HCs (P < 0.05), with 6 belonging to Ruminococcaceae. Eleven of these genera were negatively correlated with primary BAs and positively correlated with secondary BAs in all subjects. CONCLUSION The altered metabolism of BAs in the gut of IBS-D patients was associated with diarrhea and visceral hypersensitivity and might be ascribed to dysbiosis, especially the reduction of genera in Ruminococcaceae.
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Affiliation(s)
- Wei Wei
- Graduate School, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing 100730, China
- Department of Gastroenterology, China-Japan Friendship Hospital, Beijing 100029, China
| | - Hui-Fen Wang
- Department of Gastroenterology, China-Japan Friendship Hospital, Beijing 100029, China
| | - Yu Zhang
- Graduate School, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing 100730, China
- Department of Gastroenterology, China-Japan Friendship Hospital, Beijing 100029, China
| | - Yan-Li Zhang
- Department of Gastroenterology, China-Japan Friendship Hospital, Beijing 100029, China
| | - Bing-Yu Niu
- Department of Gastroenterology, China-Japan Friendship Hospital, Beijing 100029, China
- Graduate School, Beijing University of Chinese Medicine, Beijing 100029, China
| | - Shu-Kun Yao
- Department of Gastroenterology, China-Japan Friendship Hospital, Beijing 100029, China
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Monasterio C, Hartl C, Hasselblatt P. Akute und chronische Durchfallerkrankungen: Differenzialdiagnose und Therapie. Dtsch Med Wochenschr 2020; 145:1325-1336. [DOI: 10.1055/a-0944-8523] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/23/2022]
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Shiha MG, Ashgar Z, Fraser EM, Kurien M, Aziz I. High prevalence of primary bile acid diarrhoea in patients with functional diarrhoea and irritable bowel syndrome-diarrhoea, based on Rome III and Rome IV criteria. EClinicalMedicine 2020; 25:100465. [PMID: 32954237 PMCID: PMC7486326 DOI: 10.1016/j.eclinm.2020.100465] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/28/2020] [Revised: 06/29/2020] [Accepted: 07/03/2020] [Indexed: 12/14/2022] Open
Abstract
BACKGROUND A high prevalence of primary bile acid diarrhoea (BAD) has been reported for Rome III defined irritable bowel syndrome (IBS)-diarrhoea and functional diarrhoea. We determined whether this still applies under the contemporaneous Rome IV criteria, given that the latter characterises IBS-diarrhoea as having more frequent abdominal pain compared with previous iterations, whilst no longer recognising abdominal discomfort. METHODS Patients referred for a 75SeHCAT test completed a baseline questionnaire comprising, i) demographic data, ii) risk factors for BAD (inflammatory bowel disease, bowel resection, cholecystectomy, microscopic colitis, celiac disease, abdominal-pelvic radiotherapy), iii) the Rome III and IV bowel disorder questionnaire, and iv) mood and somatisation scores. A diagnosis of BAD constituted a 75SeHCAT of ≤15%, with moderate to severe disease being defined as ≤10% and ≤5%, respectively. FINDINGS Of 300 patients with complete dataset, 184 had no risk factors for BAD and fulfilled criteria for either IBS-diarrhoea or functional diarrhoea. The prevalence of primary BAD was 38% (n = 70/184), with almost half having moderate (n = 16) to severe (n = 17) disease. Using the Rome III criteria, the prevalence of primary BAD was 36% in IBS-diarrhoea (n = 63/173) and 64% (n = 7/11) in functional diarrhoea; p = 0.11. Using the Rome IV criteria, the prevalence of primary BAD was 38% (n = 53/139) in IBS-diarrhoea and 38% (n = 17/45) in functional diarrhoea; p = 0.97. Patients with primary BAD experienced more frequent loose stools (p = 0.01) and had a higher body mass index (p<0.0001) compared to those without BAD, but otherwise no significant differences were seen in age, gender, mood, somatisation, or abdominal pain. The presence of primary BAD in patients classified as overweight or obese was approximately 40% and 60%, respectively. INTERPRETATION Over a third of patients with Rome IV IBS-diarrhoea or functional diarrhoea have primary BAD, similar to Rome III. We therefore recommend that, in secondary care settings, generic testing for primary BAD should be considered in patients presenting with chronic diarrhoea of presumed functional origin regardless of concomitant abdominal pain. Centres that lack tests for primary BAD, and who empirically treat instead, may consider targeting patients who are overweight or obese.
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Affiliation(s)
- Mohamed G. Shiha
- Academic Department of Gastroenterology, Sheffield Teaching Hospitals, Sheffield, United Kingdom
| | - Zohaib Ashgar
- Academic Department of Gastroenterology, Sheffield Teaching Hospitals, Sheffield, United Kingdom
- Department of Infection, Immunity and Cardiovascular Disease, University of Sheffield, Sheffield, United Kingdom
| | - Ellen M. Fraser
- Academic Department of Gastroenterology, Sheffield Teaching Hospitals, Sheffield, United Kingdom
| | - Matthew Kurien
- Academic Department of Gastroenterology, Sheffield Teaching Hospitals, Sheffield, United Kingdom
- Department of Infection, Immunity and Cardiovascular Disease, University of Sheffield, Sheffield, United Kingdom
| | - Imran Aziz
- Academic Department of Gastroenterology, Sheffield Teaching Hospitals, Sheffield, United Kingdom
- Department of Infection, Immunity and Cardiovascular Disease, University of Sheffield, Sheffield, United Kingdom
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Black CJ, Ford AC. Rational investigations in irritable bowel syndrome. Frontline Gastroenterol 2020; 11:140-147. [PMID: 32133113 PMCID: PMC7043084 DOI: 10.1136/flgastro-2019-101211] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/17/2019] [Revised: 05/08/2019] [Accepted: 05/18/2019] [Indexed: 02/06/2023] Open
Abstract
Irritable bowel syndrome (IBS) is a common functional gastrointestinal disorder which accounts for a substantial proportion of a gastroenterologist's time in the outpatient clinic. However, there is variability in approaches to diagnosis and investigation between physicians, dependent on expertise. Many patients express disappointment over the lack of a patient-centred approach. Consequently, there have been calls for the care of patients with IBS to be standardised, a process which aims to promote high-quality and high-value care. Making an early diagnosis, based on a clinical assessment of symptoms, while limiting use of investigations, are key tenets of this process. Exhaustive investigation to exclude all organic pathology is unnecessary, and may be counterproductive. Routine blood tests in suspected IBS have low yield, but are an acceptable part of routine practice. All patients should have coeliac serology tested, regardless of their predominant stool form. Patients with diarrhoea should have a faecal calprotectin measured, and should proceed to colonoscopy to exclude inflammatory bowel disease (IBD) if this is positive. Beyond this, the need for investigations should be made on a case-by-case basis, contingent on the reporting of known risk factors for organic pathology. Colonoscopy should be considered in any patient with alarm features for colorectal cancer, and in those whose clinical features are suggestive of microscopic colitis. A 23-seleno-25-homotaurocholic acid (SeHCAT) scan should be considered in patients with IBS-D, a third of whom may actually have bile acid diarrhoea. There is no role for routine hydrogen breath tests for lactose malabsorption or small intestinal bacterial overgrowth.
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Affiliation(s)
- Christopher J Black
- Leeds Gastroenterology Institute, St. James's University Hospital, Leeds, UK
| | - Alexander C Ford
- Leeds Gastroenterology Institute, St. James's University Hospital, Leeds, UK
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Sadowski DC, Camilleri M, Chey WD, Leontiadis GI, Marshall JK, Shaffer EA, Tse F, Walters JRF. Canadian Association of Gastroenterology Clinical Practice Guideline on the Management of Bile Acid Diarrhea. Clin Gastroenterol Hepatol 2020; 18:24-41.e1. [PMID: 31526844 DOI: 10.1016/j.cgh.2019.08.062] [Citation(s) in RCA: 41] [Impact Index Per Article: 8.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/09/2019] [Accepted: 08/28/2019] [Indexed: 02/07/2023]
Abstract
BACKGROUND & AIMS Chronic diarrhea affects about 5% of the population overall. Altered bile acid metabolism is a common but frequently undiagnosed cause. METHODS We performed a systematic search of publication databases for studies of assessment and management of bile acid diarrhea (BAD). The certainty (quality) of evidence and strength of recommendations were rated according to the Grading of Recommendation Assessment, Development and Evaluation approach. Patient population, intervention, comparator, and outcome questions were developed through an iterative process and were voted on by a group of specialists. RESULTS The certainty of evidence was generally rated as very low. Therefore, 16 of 17 recommendations are conditional. In patients with chronic diarrhea, consideration of risk factors (terminal ileal resection, cholecystectomy, or abdominal radiotherapy), but not additional symptoms, was recommended for identification of patients with possible BAD. The group suggested testing using 75selenium homocholic acid taurine (where available) or 7α-hydroxy-4-cholesten-3-one, including patients with irritable bowel syndrome with diarrhea, functional diarrhea, and Crohn's disease without inflammation. Testing was suggested over empiric bile acid sequestrant therapy (BAST). Once remediable causes are managed, the group suggested cholestyramine as initial therapy, with alternate BAST when tolerability is an issue. The group suggested against BAST for patients with extensive ileal Crohn's disease or resection and suggested alternative antidiarrheal agents if BAST is not tolerated. Maintenance BAST should be given at the lowest effective dose, with a trial of intermittent, on-demand administration, concurrent medication review, and reinvestigation for patients whose symptoms persist despite BAST. CONCLUSIONS Based on a systematic review, BAD should be considered for patients with chronic diarrhea. For patients with positive results from tests for BAD, a trial of BAST, initially with cholestyramine, is suggested.
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Affiliation(s)
- Daniel C Sadowski
- Division of Gastroenterology, Royal Alexandra Hospital, Edmonton, Alberta, Canada.
| | - Michael Camilleri
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota
| | - William D Chey
- Division of Gastroenterology, University of Michigan Health System, Ann Arbor, Michigan
| | - Grigorios I Leontiadis
- Division of Gastroenterology, Farncombe Family Digestive Health Research Institute, McMaster University, Hamilton, Ontario, Canada
| | - John K Marshall
- Division of Gastroenterology, Farncombe Family Digestive Health Research Institute, McMaster University, Hamilton, Ontario, Canada
| | - Eldon A Shaffer
- Division of Gastroenterology, University of Calgary, Calgary, Alberta, Canada
| | - Frances Tse
- Division of Gastroenterology, Farncombe Family Digestive Health Research Institute, McMaster University, Hamilton, Ontario, Canada
| | - Julian R F Walters
- Division of Digestive Diseases, Imperial College London, London, United Kingdom
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Ticho AL, Malhotra P, Dudeja PK, Gill RK, Alrefai WA. Intestinal Absorption of Bile Acids in Health and Disease. Compr Physiol 2019; 10:21-56. [PMID: 31853951 PMCID: PMC7171925 DOI: 10.1002/cphy.c190007] [Citation(s) in RCA: 140] [Impact Index Per Article: 23.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
The intestinal reclamation of bile acids is crucial for the maintenance of their enterohepatic circulation. The majority of bile acids are actively absorbed via specific transport proteins that are highly expressed in the distal ileum. The uptake of bile acids by intestinal epithelial cells modulates the activation of cytosolic and membrane receptors such as the farnesoid X receptor (FXR) and G protein-coupled bile acid receptor 1 (GPBAR1), which has a profound effect on hepatic synthesis of bile acids as well as glucose and lipid metabolism. Extensive research has focused on delineating the processes of bile acid absorption and determining the contribution of dysregulated ileal signaling in the development of intestinal and hepatic disorders. For example, a decrease in the levels of the bile acid-induced ileal hormone FGF15/19 is implicated in bile acid-induced diarrhea (BAD). Conversely, the increase in bile acid absorption with subsequent overload of bile acids could be involved in the pathophysiology of liver and metabolic disorders such as fatty liver diseases and type 2 diabetes mellitus. This review article will attempt to provide a comprehensive overview of the mechanisms involved in the intestinal handling of bile acids, the pathological implications of disrupted intestinal bile acid homeostasis, and the potential therapeutic targets for the treatment of bile acid-related disorders. Published 2020. Compr Physiol 10:21-56, 2020.
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Affiliation(s)
- Alexander L. Ticho
- Department of Physiology and Biophysics, College of Medicine, University of Illinois at Chicago, Chicago, Illinois, USA
| | - Pooja Malhotra
- Division of Gastroenterology & Hepatology, Department of Medicine, College of Medicine, University of Illinois at Chicago, Chicago, Illinois, USA
| | - Pradeep K. Dudeja
- Division of Gastroenterology & Hepatology, Department of Medicine, College of Medicine, University of Illinois at Chicago, Chicago, Illinois, USA
- jesse Brown VA Medical Center, Chicago, Illinois, USA
| | - Ravinder K. Gill
- Division of Gastroenterology & Hepatology, Department of Medicine, College of Medicine, University of Illinois at Chicago, Chicago, Illinois, USA
| | - Waddah A. Alrefai
- Division of Gastroenterology & Hepatology, Department of Medicine, College of Medicine, University of Illinois at Chicago, Chicago, Illinois, USA
- jesse Brown VA Medical Center, Chicago, Illinois, USA
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Sadowski DC, Camilleri M, Chey WD, Leontiadis GI, Marshall JK, Shaffer EA, Tse F, Walters JRF. Canadian Association of Gastroenterology Clinical Practice Guideline on the Management of Bile Acid Diarrhea. J Can Assoc Gastroenterol 2019; 3:e10-e27. [PMID: 32010878 PMCID: PMC6985689 DOI: 10.1093/jcag/gwz038] [Citation(s) in RCA: 20] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/07/2023] Open
Abstract
Background and Aims Chronic diarrhea affects about 5% of the population overall. Altered bile acid metabolism is a common but frequently undiagnosed cause. Methods We performed a systematic search of publication databases for studies of assessment and management of bile acid diarrhea (BAD). The certainty (quality) of evidence and strength of recommendations were rated according to the Grading of Recommendation Assessment, Development and Evaluation approach. Patient population, intervention, comparator and outcome questions were developed through an iterative process and were voted on by a group of specialists. Results The certainty of evidence was generally rated as very low. Therefore, 16 of 17 recommendations are conditional. In patients with chronic diarrhea, consideration of risk factors (terminal ileal resection, cholecystectomy or abdominal radiotherapy), but not additional symptoms, was recommended for identification of patients with possible BAD. The group suggested testing using 75selenium homocholic acid taurine (where available) or 7α-hydroxy-4-cholesten-3-one, including patients with irritable bowel syndrome with diarrhea, functional diarrhea and Crohn's disease without inflammation. Testing was suggested over empiric bile acid sequestrant therapy (BAST). Once remediable causes are managed, the group suggested cholestyramine as initial therapy, with alternate BAST when tolerability is an issue. The group suggested against BAST for patients with extensive ileal Crohn's disease or resection and suggested alternative antidiarrheal agents if BAST is not tolerated. Maintenance BAST should be given at the lowest effective dose, with a trial of intermittent, on-demand administration, concurrent medication review and reinvestigation for patients whose symptoms persist despite BAST. Conclusions Based on a systematic review, BAD should be considered for patients with chronic diarrhea. For patients with positive results from tests for BAD, a trial of BAST, initially with cholestyramine, is suggested.
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Affiliation(s)
- Daniel C Sadowski
- Division of Gastroenterology, Royal Alexandra Hospital, Edmonton, Alberta, Canada
| | - Michael Camilleri
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota, USA
| | - William D Chey
- Division of Gastroenterology, University of Michigan Health System, Ann Arbor, Michigan, USA
| | - Grigorios I Leontiadis
- Division of Gastroenterology, Farncombe Family Digestive Health Research Institute, McMaster University, Hamilton, Ontario, Canada
| | - John K Marshall
- Division of Gastroenterology, Farncombe Family Digestive Health Research Institute, McMaster University, Hamilton, Ontario, Canada
| | - Eldon A Shaffer
- Division of Gastroenterology, University of Calgary, Calgary, Alberta, Canada
| | - Frances Tse
- Division of Gastroenterology, Farncombe Family Digestive Health Research Institute, McMaster University, Hamilton, Ontario, Canada
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Munjal A, Dedania B, Cash BD. Current and emerging pharmacological approaches for treating diarrhea-predominant irritable bowel syndrome. Expert Opin Pharmacother 2019; 21:63-71. [PMID: 31738621 DOI: 10.1080/14656566.2019.1691524] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
Abstract
Introduction: Irritable bowel syndrome with diarrhea (IBS-D) is among the most common functional gastrointestinal (GI) disorders and is associated with impaired quality of life, increased health-care utilization, and significant costs to patients and society. The treatment of IBS is typically hierarchal with initial therapies consisting of dietary and lifestyle modifications. Pharmacotherapy with over-the-counter and prescription medications is also commonly used for symptomatic control in the course of therapy.Areas covered: Three medications are approved by the United States Food and Drug Administration (FDA) for IBS-D, with all of them demonstrating efficacy in randomized, placebo-controlled trials. In this review, the authors discuss the clinical trial data applicable to the current FDA approved IBS-D therapies as well as review data related to new and emerging therapies for this condition.Expert opinion: Clinicians should be familiar with emerging therapies for IBS-D as they may provide benefit to some IBS-D patients. The exact mechanisms of action of many of the emerging agents for IBS-D remain unknown. Despite substantial differences and limitations in the design and quality of supporting studies, there is an increasing body of evidence suggesting that emerging agents may promote meaningful symptom improvement in patients with IBS-D.
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Affiliation(s)
- Akhil Munjal
- Division of Internal Medicine, University of Texas Health Science Center, McGovern Medical School, Houston, TX, USA
| | - Bhavtosh Dedania
- Division of Gastroenterology, University of Texas Health Science Center, McGovern Medical School, Houston, TX, USA
| | - Brooks D Cash
- Division of Gastroenterology, University of Texas Health Science Center, McGovern Medical School, Houston, TX, USA
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Lim SJ, Gracie DJ, Kane JS, Mumtaz S, Scarsbrook AF, Chowdhury FU, Ford AC, Black CJ. Prevalence of, and predictors of, bile acid diarrhea in outpatients with chronic diarrhea: A follow-up study. Neurogastroenterol Motil 2019; 31:e13666. [PMID: 31225936 DOI: 10.1111/nmo.13666] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/15/2019] [Revised: 06/04/2019] [Accepted: 06/10/2019] [Indexed: 02/08/2023]
Abstract
BACKGROUND 23-seleno-25-homo-tauro-cholic acid (SeHCAT) scanning to rule out bile acid diarrhea (BAD) in patients with chronic diarrhea has a high yield. Our previous study showed that patients with terminal ileal (TI) Crohn's disease, TI resection, or cholecystectomy were highly likely to have an abnormal scan. As a result, we encouraged clinicians to use a therapeutic trial of a bile acid sequestrant in these patients, instead of scanning. This may have reduced diagnostic yield of the test, so we examined this issue, as well as factors predicting an abnormal scan, in a large cohort of patients referred subsequently. METHODS We retrospectively identified 1,071 consecutive patients with chronic diarrhea undergoing SeHCAT scanning at Leeds Teaching Hospitals Trust from 2012 to 2016. We reviewed electronic patient records to obtain information on presenting gastrointestinal symptoms and any proposed risk factors for BAD. BAD was categorized according to subtype and severity. KEY RESULTS As expected, indications for scanning changed between 2012 and 2016, with a significant reduction in referrals with TI Crohn's disease or resection year-on-year (P < 0.001). Despite this, 457 (42.7%) patients had BAD and there was no downward trend in yield of SeHCAT during the 5 year period (P = 0.39). Overall, 51.6% had type II BAD, 36.1% type III, and 12.3% type I. BAD was mild in 31.7%, moderate in 34.4%, and severe in 33.9%. In total, 653 (61.0%) patients had no known risk factors, other than chronic diarrhea, but 233 (35.7%) of these individuals had BAD, and in 143 (61.4%), this was moderate or severe. CONCLUSIONS AND INFERENCES Despite reduced referrals for SeHCAT scanning in those with clear risk factors for BAD, the yield remained > 40%. One-third of those without known risk factors had BAD.
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Affiliation(s)
- Shujing Jane Lim
- Leeds Gastroenterology Institute, St. James's University Hospital, Leeds, UK
| | - David J Gracie
- Leeds Gastroenterology Institute, St. James's University Hospital, Leeds, UK.,Leeds Institute of Medical Research at St. James's, University of Leeds, Leeds, UK
| | - John S Kane
- Leeds Gastroenterology Institute, St. James's University Hospital, Leeds, UK
| | - Saqib Mumtaz
- Leeds Gastroenterology Institute, St. James's University Hospital, Leeds, UK
| | | | - Fahmid U Chowdhury
- Department of Nuclear Medicine, St. James's University Hospital, 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
| | - 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
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Zamani M, Alizadeh-Tabari S, Zamani V. Systematic review with meta-analysis: the prevalence of anxiety and depression in patients with irritable bowel syndrome. Aliment Pharmacol Ther 2019; 50:132-143. [PMID: 31157418 DOI: 10.1111/apt.15325] [Citation(s) in RCA: 268] [Impact Index Per Article: 44.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/28/2019] [Revised: 04/25/2019] [Accepted: 05/08/2019] [Indexed: 12/09/2022]
Abstract
BACKGROUND Irritable bowel syndrome (IBS) is a common and potential disabling functional gastrointestinal disorder. Studies have revealed a possible association between IBS and psychological problems, such as anxiety and depression. Existing systematic reviews have addressed only the levels of anxiety or depression in patients with IBS. AIM To investigate systematically the prevalence of anxiety or depression in IBS patients METHODS: A literature search was conducted using the related keywords from the bibliographic databases of Embase, PubMed, Scopus, Web of Science and POPLINE published until 1 January 2019 with no language restriction. Studies reporting the prevalence of anxiety/depressive symptoms/disorders in adult (≥15 years) IBS patients were evaluated. The pooled prevalence, odds ratio (OR) and 95% CI were calculated using stata software. RESULTS A total of 14 926 articles were initially screened, and finally 73 papers were included. The prevalence rates of anxiety symptoms and disorders in IBS patients were 39.1% (95% CI: 32.4-45.8) and 23% (95% CI: 17.2-28.8) respectively. The ORs for anxiety symptoms and disorders in IBS patients compared with healthy subjects were 3.11 (95% CI: 2.43-3.98) and 2.52 (95% CI: 1.99-3.20) respectively. The prevalence estimates of depressive symptoms and disorders in IBS patients were 28.8% (95% CI: 23.6-34) and 23.3% (95% CI: 17.2-29.4) respectively. The ORs for depressive symptoms and disorders in IBS patients compared to healthy subjects were 3.04 (95% CI: 2.37-3.91) and 2.72 (95% CI: 2.45-3.02) respectively. CONCLUSION Patients with IBS have a three-fold increased odds of either anxiety or depression, compared to healthy subjects.
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Affiliation(s)
- Mohammad Zamani
- Student Research Committee, School of Medicine, Babol University of Medical Sciences, Babol, Iran
- Cancer Research Center, Health Research Institute, Babol University of Medical Sciences, Babol, Iran
| | | | - Vahid Zamani
- Vice-Chancellery for Health, Babol University of Medical Sciences, Babol, Iran
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Abstract
PURPOSE OF REVIEW Chronic diarrhoea remains a diagnostic challenge, with numerous causes and few effective symptomatic treatments. This review focuses on new methods for diagnosis of common disorders and alerts readers to rarer causes through a systematic approach to the underlying mechanisms. RECENT FINDINGS New strategies are emerging to stratify the need for endoscopic investigation. Faecal immunochemical testing, combined with standard blood tests, shows promise in excluding colorectal cancers, adenoma and inflammatory bowel disease, challenging the current use of faecal calprotectin. Serum analysis for markers of bile acid synthesis has been refined, potentially streamlining diagnostic pathways of bile acid malabsorption for those who are unable to access nuclear medicine scans, but the positive predictive value of faecal elastase in low prevalence populations has been questioned. Novel markers such as volatile organic compounds and stool DNA analyses continue to develop. SUMMARY A systematic approach to investigation of chronic diarrhoea will ensure all relevant causes are considered and minimize the chance of a missed diagnosis. Combination of clinical features with noninvasive testing supports a judicious approach to endoscopic investigations but further innovation will be needed to resolve the diagnostic challenge that diarrhoea poses.
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Camilleri M. Management Options for Irritable Bowel Syndrome. Mayo Clin Proc 2018; 93:1858-1872. [PMID: 30522596 PMCID: PMC6314474 DOI: 10.1016/j.mayocp.2018.04.032] [Citation(s) in RCA: 68] [Impact Index Per Article: 9.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/04/2017] [Revised: 04/23/2018] [Accepted: 04/27/2018] [Indexed: 02/07/2023]
Abstract
Irritable bowel syndrome (IBS) is associated with diverse pathophysiologic mechanisms. These mechanisms include increased abnormal colonic motility or transit, intestinal or colorectal sensation, increased colonic bile acid concentration, and superficial colonic mucosal inflammation, as well as epithelial barrier dysfunction, neurohormonal up-regulation, and activation of secretory processes in the epithelial layer. Novel approaches to treatment include lifestyle modification, changes in diet, probiotics, and pharmacotherapy directed to the motility, sensation, and intraluminal milieu of patients with IBS. Despite recent advances, there is a need for development of new treatments to relieve pain in IBS without deleterious central or other adverse effects.
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Affiliation(s)
- Michael Camilleri
- Clinical Enteric Neuroscience Translational and Epidemiological Research (C.E.N.T.E.R.) Program and Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN.
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Simrén M, Tack J. New treatments and therapeutic targets for IBS and other functional bowel disorders. Nat Rev Gastroenterol Hepatol 2018; 15:589-605. [PMID: 29930260 DOI: 10.1038/s41575-018-0034-5] [Citation(s) in RCA: 83] [Impact Index Per Article: 11.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
Functional bowel disorders (FBDs) are a spectrum of disorders characterized by combinations of symptoms attributable to the lower gastrointestinal tract. Most current first-line therapies for IBS and other FBDs target the predominant symptom and mainly affect one symptom in the symptom complex. Additional broadly effective treatment alternatives targeting the entire symptom complex are needed. New drugs for FBDs (such as lubiprostone, linaclotide, plecanatide, prucalopride, eluxadoline and rifaximin) target key mechanisms in the pathophysiology of these disorders and improve both the abnormal bowel habit and other key symptoms, such as abdominal pain and bloating. The current development of new treatment alternatives is focusing on different aspects of the complex pathophysiology of IBS and other FBDs: gut microenvironment (via diet and modulation of gut microbiota), enterohepatic circulation of bile acids, gastrointestinal secretion, motility and sensation, gut-brain interactions, gut barrier function and the immune system within the gastrointestinal tract. Studies also suggest that personalized treatment of IBS and other FBDs is possible using various diagnostic markers.
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Affiliation(s)
- Magnus Simrén
- Department of Internal Medicine and Clinical Nutrition, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
- Center for Functional Gastrointestinal and Motility Disorders, University of North Carolina, Chapel Hill, NC, USA.
| | - Jan Tack
- Translational Research Center for Gastrointestinal Disorders (TARGID), Department of Clinical and Experimental Medicine, KU Leuven, Leuven, Belgium
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van de Peppel IP, Doktorova M, Berkers G, de Jonge HR, Houwen RHJ, Verkade HJ, Jonker JW, Bodewes FAJA. IVACAFTOR restores FGF19 regulated bile acid homeostasis in cystic fibrosis patients with an S1251N or a G551D gating mutation. J Cyst Fibros 2018; 18:286-293. [PMID: 30279125 DOI: 10.1016/j.jcf.2018.09.001] [Citation(s) in RCA: 27] [Impact Index Per Article: 3.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/24/2018] [Revised: 08/30/2018] [Accepted: 09/06/2018] [Indexed: 12/21/2022]
Abstract
OBJECTIVE Disruption of the enterohepatic circulation of bile acids (BAs) is part of the gastrointestinal phenotype of cystic fibrosis (CF). Ivacaftor (VX-770), a cystic fibrosis transmembrane conductance regulator (CFTR) potentiator, improves pulmonary function in CF patients with class III gating mutations. We studied the effect of ivacaftor on the enterohepatic circulation by assessing markers of BA homeostasis and their changes in CF patients. METHODS In CF patients with an S1251N mutation (N = 16; age 9-35 years S125N study/NTR4873) or a G551D mutation (N = 101; age 10-24 years; GOAL study/ NCT01521338) we analyzed plasma fibroblast growth factor 19 (FGF19) and 7α-hydroxy-4-cholesten-3-one (C4) levels, surrogate markers for intestinal BA absorption and hepatic synthesis, respectively, before and after treatment with ivacaftor. RESULTS At baseline, median FGF19 was lower (52% and 53%, P < .001) and median C4 higher (350% and 364%, P < .001), respectively, for the S1251 N and G551D mutation patient groups compared to healthy controls. Treatment with ivacaftor significantly increased FGF19 and reduced C4 levels towards normalization in both cohorts but this did not correlate with CFTR function in other organs, as measured by sweat chloride levels or pulmonary function. CONCLUSIONS We demonstrate that patients with CFTR gating mutations display interruption of the enterohepatic circulation of BAs reflected by lower FGF19 and elevated C4 levels. Treatment with ivacaftor partially restored this disruption of BA homeostasis. The improvement did not correlate with established outcome measures of CF, suggesting involvement of modulating factors of CFTR correction in different organs.
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Affiliation(s)
- Ivo P van de Peppel
- Section of Molecular Metabolism and Nutrition, Department of Pediatrics, University of Groningen, Beatrix Children's Hospital - University Medical Center Groningen, PO Box 30001, 9700 RB Groningen, the Netherlands; Pediatric Gastroenterology and Hepatology, Department of Pediatrics, University of Groningen, Beatrix Children's Hospital - University Medical Center Groningen, PO Box 30001, 9700 RB Groningen, the Netherlands
| | - Marcela Doktorova
- Section of Molecular Metabolism and Nutrition, Department of Pediatrics, University of Groningen, Beatrix Children's Hospital - University Medical Center Groningen, PO Box 30001, 9700 RB Groningen, the Netherlands; Pediatric Gastroenterology and Hepatology, Department of Pediatrics, University of Groningen, Beatrix Children's Hospital - University Medical Center Groningen, PO Box 30001, 9700 RB Groningen, the Netherlands
| | - Gitte Berkers
- Department of Pediatric Pulmonology, Wilhelmina Children's Hospital, University Medical Center Utrecht, Utrecht University, Utrecht, the Netherlands
| | - Hugo R de Jonge
- Department of Gastroenterology and Hepatology, Erasmus University Medical Center, Rotterdam, the Netherlands
| | - Roderick H J Houwen
- Department of Pediatric Gastroenterology, Wilhelmina Children's Hospital, University Medical Center Utrecht, Utrecht University, Utrecht, the Netherlands
| | - Henkjan J Verkade
- Section of Molecular Metabolism and Nutrition, Department of Pediatrics, University of Groningen, Beatrix Children's Hospital - University Medical Center Groningen, PO Box 30001, 9700 RB Groningen, the Netherlands; Pediatric Gastroenterology and Hepatology, Department of Pediatrics, University of Groningen, Beatrix Children's Hospital - University Medical Center Groningen, PO Box 30001, 9700 RB Groningen, the Netherlands
| | - Johan W Jonker
- Section of Molecular Metabolism and Nutrition, Department of Pediatrics, University of Groningen, Beatrix Children's Hospital - University Medical Center Groningen, PO Box 30001, 9700 RB Groningen, the Netherlands
| | - Frank A J A Bodewes
- Pediatric Gastroenterology and Hepatology, Department of Pediatrics, University of Groningen, Beatrix Children's Hospital - University Medical Center Groningen, PO Box 30001, 9700 RB Groningen, the Netherlands.
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Kane JS, Irvine AJ, Derwa Y, Rotimi O, Ford AC. High prevalence of irritable bowel syndrome-type symptoms in microscopic colitis: implications for treatment. Therap Adv Gastroenterol 2018; 11:1756284818783600. [PMID: 29977339 PMCID: PMC6024332 DOI: 10.1177/1756284818783600] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/01/2018] [Accepted: 05/21/2018] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Patients with microscopic colitis (MC) often present with abdominal pain and diarrhoea, and previous data suggest that there may be overlap between MC and irritable bowel syndrome (IBS). We evaluated the prevalence of IBS-type symptoms in patients with MC, and assess the impact of these symptoms on psychological health and quality of life. METHODS We conducted a cross-sectional survey of individuals with a histological diagnosis of MC, collecting demographic data, Rome III IBS-type symptoms, and mood, somatization, and quality of life data. RESULTS In total, 151 (31.6%) of 478 individuals with a new diagnosis of MC completed questionnaires, 52 (34.4%) of whom reported IBS-type symptoms. The commonest histological subtype was collagenous colitis (51.7%, n = 78), followed by lymphocytic colitis (39.1%, n = 59). Individuals with IBS-type symptoms had significantly higher levels of anxiety [Hospital Anxiety and Depression Scale (HADS) anxiety score 8.6 versus 5.1, p < 0.001], depression (HADS depression score 6.2 versus 3.6, p = 0.001), and somatoform-type behaviour (Patient Health Questionnaire 15 score 12.7 versus 8.0, p < 0.001) compared with individuals who did not. Those with IBS-type symptoms scored significantly worse across all domains of the 36-item Short Form questionnaire, except for physical functioning. CONCLUSIONS More than one third of individuals with MC reported IBS-type symptoms, although whether this is due to ongoing inflammation is unclear. These individuals had higher levels of anxiety, depression, and somatization, and impaired quality of life. Identifying concomitant IBS in individuals with MC may have important implications for management decisions.
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Affiliation(s)
- John S. Kane
- Leeds Gastroenterology Institute, 4th Floor, Bexley Wing, St James’s University Hospital, Beckett Street, Leeds LS9 7TF, UK
| | - Andrew J. Irvine
- Leeds Gastroenterology Institute, St James’s University Hospital, Leeds, UK
| | - Yannick Derwa
- Leeds Gastroenterology Institute, St James’s University Hospital, Leeds, UK
| | - Olorunda Rotimi
- Department of Histopathology, St James’s University Hospital, Leeds, UK
| | - Alexander C. Ford
- Leeds Gastroenterology Institute, St James’s University Hospital, Leeds, UK Leeds Institute of Biomedical and Clinical Sciences, University of Leeds, Leeds, UK
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Kurien M, Thurgar E, Davies A, Akehurst R, Andreyev J. Challenging current views on bile acid diarrhoea and malabsorption. Frontline Gastroenterol 2018; 9:92-97. [PMID: 29588835 PMCID: PMC5868445 DOI: 10.1136/flgastro-2017-100808] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/05/2017] [Revised: 04/05/2017] [Accepted: 05/06/2017] [Indexed: 02/04/2023] Open
Abstract
BACKGROUND In 2012, the National Institute for Health and Care Excellence (NICE) assessed guidance (DG7) on the use of tauroselcholic (75selenium) acid (also known as SeHCAT) for the investigation of diarrhoea due to bile acid malabsorption (BAM) in patients with IBS-D and in patients with Crohn's disease who have not had an ileal resection. NICE concluded that tauroselcholic (75selenium) acid was recommended for use in research only. NICE will be reviewing the decision to update the guidance for tauroselcholic (75selenium) acid, for these populations, in March 2017. AIM Our aim is to summarise advances in BAM, also known as bile acid diarrhoea (BAD), and encourage clinicians to re-evaluate their understanding of this disorder. APPROACH We review the prevalence, diagnosis and treatment of BAD/BAM. We describe the new evidence available since the original NICE review in 2012, and discuss the economic issues associated with failure to diagnose or to treat BAD/BAM accurately. EVIDENCE UPDATE There is new and compelling evidence available since DG7, which shows that tauroselcholic (75selenium) acid scanning is a powerful tool in the diagnosis of BAD/BAM. We summarise published prevalence data (approximately 1% prevalence in the UK, as suggested by clinical practice diagnosis rates), and highlight that the true prevalence of BAD/BAM could be far greater than this. CONCLUSION We present evidence that challenges current opinion about this disorder, and we commend both clinicians and health technology assessment (HTA) agencies for being open to arguments and new evidence in any future HTAs.
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Affiliation(s)
- Matthew Kurien
- Academic Unit of Gastroenterology, Department of Infection, Immunity and Cardiovascular Sciences, University of Sheffield, Sheffield, UK
| | | | | | | | - Jervoise Andreyev
- The GI and Nutrition Team, The Royal Marsden NHS Foundation Trust, London, UK
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Holtmann G, Shah A, Morrison M. Pathophysiology of Functional Gastrointestinal Disorders: A Holistic Overview. Dig Dis 2018; 35 Suppl 1:5-13. [PMID: 29421808 DOI: 10.1159/000485409] [Citation(s) in RCA: 99] [Impact Index Per Article: 14.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/02/2023]
Abstract
Background and Summary: Traditionally, functional gastrointestinal disorders (FGID), including functional dyspepsia or irritable bowel syndrome (IBS), are defined by more or less specific symptoms and the absence of structural or biochemical abnormalities that cause these symptoms. This concept is now considered to be outdated; if appropriate tests are applied, structural or biochemical abnormalities that explain or cause the symptoms may be found in many patients. Another feature of FGID are the highly prevalent psychiatric comorbidities, such as depression and anxiety. It is implied that mood disorders "cause" gastrointestinal symptoms. In fact, epidemiological data now provide strong evidence that in subsets of cases, gastrointestinal (GI) symptoms arise first and mood disorders occur later, while in other patients the reverse appears to happen. Possible mechanisms for gut-brain dysfunction have been identified, with systemic minimal inflammation as a causal factor in at least some subjects. Other mechanisms that play a role in FGID include chronic infections, intestinal microbiota, low-grade mucosal inflammation including the increase of eosinophils, systemic immune activation, altered intestinal permeability, in diarrhea predominant IBS altered bile salt metabolism, abnormalities in the serotonin metabolism and genetic factors. All these factors might be modulated by environmental factors such as diet. Key Messages: While a number of factors can be linked to specific symptoms (e.g., pain or diarrhea), it is evident that the symptom-based categorization of patients will not allow targeted treatments that specifically address the underlying pathophysiology.
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Affiliation(s)
- Gerald Holtmann
- Department of Gastroenterology and Hepatology, Princess Alexandra Hospital, Woolloongabba, Queensland, Australia.,Faculty of Medicine and Falty of Health and Behavioural Sciences, University of Queensland, Queensland, Queensland, Australia
| | - Ayesha Shah
- Department of Gastroenterology and Hepatology, Princess Alexandra Hospital, Woolloongabba, Queensland, Australia
| | - Mark Morrison
- Diamantina Institute, University of Queensland, Queensland, Queensland, Australia
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