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Kendler KS, Ohlsson H, Neale M, van Loo H, Rosmalen JGM, Sundquist J, Sundquist K. A multivariate Swedish national twin-sibling study in women of major depression, anxiety disorder, fibromyalgia, and irritable bowel syndrome. Psychol Med 2025; 55:e125. [PMID: 40289642 DOI: 10.1017/s0033291725000923] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 04/30/2025]
Abstract
BACKGROUND Functional Somatic Disorders (FSD) and Internalizing Psychiatric Disorders (IPD) are frequently comorbid and likely share familial/genetic risk factors. METHODS We performed a Common Factor Multivariate Analysis of 2 FSDs, Fibromyalgia (FM) and Irritable Bowel Syndrome (IBS), and two IPDs, Major Depression (MD) and Anxiety Disorders (AD), in five kinds of Swedish female-female relative pairs: monozygotic (n = 8,052) dizygotic (n = 7216), full siblings (n = 712,762), half-siblings reared together (n = 23,623), and half-siblings reared apart (n = 53,873). Model fitting was by full information maximum likelihood using OpenMx. RESULTS The best-fit model included genetic, shared environmental, and unique environmental factors. The common factor, ~50% heritable with a small shared environmental effect, loaded more strongly on the two IPDs (~0.80) than the 2 FSDs (0.40). Disorder-specific genetic effects were larger for the 2 FSDs (~0.30) than the 2 IPDs (~0.03). Estimated genetic correlations were high for MD and AD (+0.91), moderate between IBS and IPDs (+0.62), and intermediate between FM and MD (+0.54), FM and AD (+0.28), and FM and IBS (+0.38). Shared environmental influences on all disorders were present but small. CONCLUSIONS In women, FSDs and IPDs shared a moderate proportion of their genetic risk factors, greater for IBS than for FM. However, the genetic sharing between IBS and FM was less than between MD and AD, suggesting that FSDs do not form a highly genetically coherent group of disorders. The shared environment made a modest contribution to the familial aggregation of FSDs and IPDs.
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Affiliation(s)
- Kenneth S Kendler
- Virginia Institute for Psychiatric and Behavioral Genetics, Virginia Commonwealth University, Richmond, VA, USA
- Department of Psychiatry, Virginia Commonwealth University, RichmondVA, USA
| | - Henrik Ohlsson
- Center for Primary Health Care Research, Lund University, Malmö, Sweden
| | - Michael Neale
- Virginia Institute for Psychiatric and Behavioral Genetics, Virginia Commonwealth University, Richmond, VA, USA
- Department of Psychiatry, Virginia Commonwealth University, RichmondVA, USA
| | - Hanna van Loo
- Department of Psychiatry, University Medical Center Groningen, Groningen, Netherlands
| | - Judith G M Rosmalen
- Department of Psychiatry, University Medical Center Groningen, Groningen, Netherlands
- Department of Internal Medicine, University Medical Center Groningen, Groningen, Netherlands
| | - Jan Sundquist
- Center for Primary Health Care Research, Lund University, Malmö, Sweden
- University Clinic Primary Care Skåne, Region Skåne, Malmö, Sweden
- Center for Community-Based Healthcare Research and Education (CoHRE), Department of Functional Pathology, School of Medicine, Shimane University, Japan
| | - Kristina Sundquist
- Center for Primary Health Care Research, Lund University, Malmö, Sweden
- University Clinic Primary Care Skåne, Region Skåne, Malmö, Sweden
- Center for Community-Based Healthcare Research and Education (CoHRE), Department of Functional Pathology, School of Medicine, Shimane University, Japan
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Roy S, Eva FN, Dev D, Roy S, Tipu SK, Chowdhury S, Medha MRB, Poonya PTH, Juthi IJ, Nowrin JH, J C E, Sumat T, Dey DM, Chowdhury S, Iktidar MA, Hawlader MDH. Prevalence and predictors of functional gastrointestinal disorder among the undergraduate students of Bangladesh. PLoS One 2024; 19:e0315687. [PMID: 39693324 DOI: 10.1371/journal.pone.0315687] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/12/2024] [Accepted: 11/29/2024] [Indexed: 12/20/2024] Open
Abstract
OBJECTIVE This study aimed to address this knowledge gap by investigating FGID prevalence and its predictors among undergraduate students in Bangladesh. DESIGN This cross-sectional study was conducted between 01 August 2023 and 31 January 2024 among 1,019 undergraduate students. Data were collected using a web-based survey containing questions on socio-demographics, the Rome IV questionnaire, the insomnia severity index, the perceived stress scale 4, the patient health questionnaire, and the smartphone addiction scale. Descriptive statistics, the chi-square test, the t-test, and the multivariable logistic regression model were used to report our study findings. RESULTS The overall prevalence of FGID was 38.24%, with functional constipation being the most common subtype (18.24%). The multivariate analysis revealed that college canteen meal (AOR: 1.593, CI: 1.068, 2.376), occasionally and regularly delayed meal (AOR: 1.663, CI: 1.031, 2.682; AOR: 1.872, CI: 1.061, 3.301), physical inactivity (AOR:0.41, CI: 1.061, 3.301), family history of FGID and GI disease (AOR: 4.7, CI: 2.55, 8.66; AOR: 2.42, CI: 1.47, 3.96), history of abdominal surgery (AOR: 2, CI: 1.08, 3.72), psychological trauma (AOR: 1.64, CI: 1.04, 2.57), dairy-product consumption (AOR: 1.64, CI: 1.04, 2.59), >3 meals/day (AOR: 1.89, CI: 1.2, 2.98), insomnia (AOR: 1.98, CI: 0.73, 5.40), and depression (AOR: 7.02, CI: 2.74, 17.98) were significantly associated with FGID. CONCLUSION The burden of FGIDs among Bangladeshi students is concerning. This study found significant factors contributing to their prevalence, including meal source and number of daily meals, delayed meals, family history of disease, physical activity, abdominal surgery, history of psychological trauma, depression, and insomnia. This study recommends further exploration and holistic healthcare approaches to better the well-being of young adults dealing with FGIDs.
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Affiliation(s)
- Simanta Roy
- Department of Public Health, North South University, Dhaka, Bangladesh
- School of Research, Chattogram, Bangladesh
- Public Health Promotion and Development Society (PPDS), Dhaka, Bangladesh
| | - Fahima Nasrin Eva
- Department of Public Health, North South University, Dhaka, Bangladesh
- School of Research, Chattogram, Bangladesh
- Public Health Promotion and Development Society (PPDS), Dhaka, Bangladesh
| | - Dipa Dev
- School of Research, Chattogram, Bangladesh
- Department of Medicine, Chittagong Medical College Hospital, Chittagong, Bangladesh
| | | | - Shafkat Kamal Tipu
- School of Research, Chattogram, Bangladesh
- Rangpur Medical College, Rangpur, Bangladesh
| | - Sristi Chowdhury
- School of Research, Chattogram, Bangladesh
- Department of Biochemistry and Molecular Biology, Noakhali Science and Technology University, Noakhali, Bangladesh
| | - Madhu Ritu Bhadra Medha
- Department of Public Health, North South University, Dhaka, Bangladesh
- School of Research, Chattogram, Bangladesh
| | - Purzia Tanaz Haque Poonya
- School of Research, Chattogram, Bangladesh
- Department of Medicine, Shaheed M. Monsur Ali Medical College, Sirajganj, Bangladesh
| | - Israt Jahan Juthi
- School of Research, Chattogram, Bangladesh
- Centre for Injury Prevention and Research, Dhaka, Bangladesh
| | - Jwearia Hoque Nowrin
- School of Research, Chattogram, Bangladesh
- Public Health Promotion and Development Society (PPDS), Dhaka, Bangladesh
| | - Eaasvar J C
- School of Research, Chattogram, Bangladesh
- Department of Medicine, Dhaka National Medical College, Dhaka, Bangladesh
| | - Tahsin Sumat
- School of Research, Chattogram, Bangladesh
- Department of Medicine, Cumilla Medical College Hospital, Cumilla, Bangladesh
| | - Disha Mony Dey
- School of Research, Chattogram, Bangladesh
- Department of Medicine, M Abdur Rahim Medical College, Dinajpur, Bangladesh
| | - Sreshtha Chowdhury
- Department of Public Health, North South University, Dhaka, Bangladesh
- School of Research, Chattogram, Bangladesh
- Department of Medicine, Chittagong Medical College Hospital, Chittagong, Bangladesh
| | - Mohammad Azmain Iktidar
- Department of Public Health, North South University, Dhaka, Bangladesh
- School of Research, Chattogram, Bangladesh
- Department of Medicine, Chittagong Medical College Hospital, Chittagong, Bangladesh
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Camilleri M, Jencks K. Pharmacogenetics in IBS: update and impact of GWAS studies in drug targets and metabolism. Expert Opin Drug Metab Toxicol 2024; 20:319-332. [PMID: 38785066 PMCID: PMC11139426 DOI: 10.1080/17425255.2024.2349716] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/28/2023] [Accepted: 04/26/2024] [Indexed: 05/25/2024]
Abstract
INTRODUCTION Medications are frequently prescribed for patients with irritable bowel syndrome (IBS) or disorders of gut brain interaction. The level of drug metabolism and modifications in drug targets determine medication efficacy to modify motor or sensory function as well as patient response outcomes. AREAS COVERED The literature search included PubMed searches with the terms: pharmacokinetics, pharmacogenomics, epigenetics, clinical trials, irritable bowel syndrome, disorders of gut brain interaction, and genome-wide association studies. The main topics covered in relation to irritable bowel syndrome were precision medicine, pharmacogenomics related to drug metabolism, pharmacogenomics related to mechanistic targets, and epigenetics. EXPERT OPINION Pharmacogenomics impacting drug metabolism [CYP 2D6 (cytochrome P450 2D6) or 2C19 (cytochrome P450 2C19)] is the most practical approach to precision medicine in the treatment of IBS. Although there are proof of concept studies that have documented the importance of genetic modification of transmitters or receptors in altering responses to medications in IBS, these principles have rarely been applied in patient response outcomes. Genome-wide association (GWAS) studies have now documented the association of symptoms with genetic variation but not the evaluation of treatment responses. Considerably more research, particularly focused on patient response outcomes and epigenetics, is essential to impact this field in clinical medicine.
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Affiliation(s)
- Michael Camilleri
- Clinical Enteric Neuroscience Translational and Epidemiological Research (CENTER), Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN, USA
| | - Kara Jencks
- Clinical Enteric Neuroscience Translational and Epidemiological Research (CENTER), Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN, USA
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Camargo Tavares L, Lopera-Maya EA, Bonfiglio F, Zheng T, Sinha T, Zanchetta Marques F, Zhernakova A, Sanna S, D'Amato M. Rome III Criteria Capture Higher Irritable Bowel Syndrome SNP-Heritability and Highlight a Novel Genetic Link With Cardiovascular Traits. Cell Mol Gastroenterol Hepatol 2024; 18:101345. [PMID: 38643935 PMCID: PMC11176963 DOI: 10.1016/j.jcmgh.2024.04.002] [Citation(s) in RCA: 3] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/04/2023] [Revised: 04/10/2024] [Accepted: 04/10/2024] [Indexed: 04/23/2024]
Abstract
BACKGROUND & AIMS Irritable bowel syndrome (IBS) shows genetic predisposition, and large-scale genome-wide association studies (GWAS) are emerging, based on heterogeneous disease definitions. We investigated the genetic architecture of IBS defined according to gold standard Rome Criteria. METHODS We conducted GWAS meta-analyses of Rome III IBS and its subtypes in 24,735 IBS cases and 77,149 asymptomatic control subjects from 2 independent European cohorts (UK Biobank and Lifelines). Single-nucleotide polymorphism (SNP)-based heritability (h2SNP) and genetic correlations (rg) with other traits were calculated. IBS risk loci were functionally annotated to identify candidate genes. Sensitivity and conditional analyses were conducted to assess impact of confounders. Polygenic risk scores were computed and tested in independent datasets. RESULTS Rome III IBS showed significant SNP-heritability (up to 13%) and similar genetic architecture across subtypes, including those with manifestations at the opposite ends of the symptom spectrum (rg = 0.48 between IBS-D and IBS-C). Genetic correlations with other traits highlighted commonalities with family history of heart disease and hypertension, coronary artery disease, and angina pectoris (rg = 0.20-0.45), among others. Four independent GWAS signals (P < 5×10-8) were detected, including 2 novel loci for IBS (rs2035380) and IBS-mixed (rs2048419) that had been previously associated with hypertension and coronary artery disease. Functional annotation of GWAS risk loci revealed genes implicated in circadian rhythm (BMAL1), intestinal barrier (CLDN23), immunomodulation (MFHAS1), and the cyclic adenosine monophosphate pathway (ADCY2). Polygenic risk scores allowed the identification of individuals at increased risk of IBS (odds ratio, 1.34; P = 1.1×10-3). CONCLUSIONS Rome III Criteria capture higher SNP-heritability than previously estimated for IBS. The identified link between IBS and cardiovascular traits may contribute to the delineation of alternative therapeutic strategies, warranting further investigation.
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Affiliation(s)
| | | | - Ferdinando Bonfiglio
- Department of Chemical, Materials and Production Engineering, University of Naples Federico II, Naples, Italy; CEINGE Biotecnologie Avanzate s.c.ar.l., Naples, Italy
| | - Tenghao Zheng
- School of Biological Sciences, Monash University, Clayton, Australia
| | - Trishla Sinha
- Department of Genetics, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands
| | - Francine Zanchetta Marques
- School of Biological Sciences, Monash University, Clayton, Australia; Heart Failure Research Group, Baker Heart and Diabetes Institute, Melbourne, Australia
| | - Alexandra Zhernakova
- Department of Genetics, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands
| | - Serena Sanna
- Department of Genetics, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands; Institute for Genetic and Biomedical Research, National Research Council, Cagliari, Italy
| | - Mauro D'Amato
- Gastrointestinal Genetics Lab, CIC bioGUNE - BRTA, Derio, Spain; Ikerbasque, Basque Foundation for Science, Bilbao, Spain; Department of Medicine and Surgery, LUM University, Casamassima, Italy
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Vu NTH, Quach DT, Miyauchi S, Luu MN, Yoshida M, Nguyen DTN, Yoshino A, Miyaka Y, Okamoto Y, Oka S, Hiyama T. Prevalence and associated factors of chronic constipation among Japanese university students. Front Public Health 2024; 12:1258020. [PMID: 38292906 PMCID: PMC10824902 DOI: 10.3389/fpubh.2024.1258020] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/13/2023] [Accepted: 01/02/2024] [Indexed: 02/01/2024] Open
Abstract
BACKGROUND Chronic constipation (CC) is one of the most frequently reported gastrointestinal disorders in the general population and a prominent problem among university students. The study aimed to evaluate the prevalence and the associated factors of CC among Japanese university students. METHODS This cross-sectional study was conducted among university students at Hiroshima University, Japan. Students answered the web questionnaire when making a web reservation for the health checkup (April 1 to May 31, 2023). The web questionnaire consisted of four sections, including baseline characteristics, lifestyle factors, family history of CC, and three scales to assess depression and eating disorders: the Beck Depression Inventory (BDI), Eating Attitudes Test (EAT)-26 and Bulimic Investigatory Test (BITE). CC was diagnosed using Rome IV criteria. The multivariate logistic regression model was used to determine CC-related factors. RESULTS Out of 10,500 individuals who participated in the annual health checkup, 7,496 participants answered the web questionnaire, of whom 5,386 answered all the survey questions. The mean age of the students was 21.1 ± 4.1 years. The male-to-female ratio was 1:1.17. The prevalence of CC was 13.7%. Factors significantly associated with CC in the multivariate model were first-degree family members with CC [Odd ratio (OR): 2.77, 95% confidence interval (CI): 2.31-3.31], severe depression according to BDI scale (OR: 2.59, 95% CI: 1.96-3.43), female sex (OR: 2.00, 95% CI: 1.69-2.36), and short sleep duration of 6 hours or less per day (OR: 1.28, 95% CI: 1.09-1.50). Lack of physical exercise tended to be associated with CC (OR: 1.19, 95% CI: 1.00-1.40). CONCLUSIONS CC is prevalent among Japanese university students. Significant risk factors for CC included the first-degree family history of CC, severe depression, female sex, and short sleep duration. Lack of physical exercise tended to be associated with CC. This may contribute to implementing suitable education health programs, health care professionals, and public health policies to identify individuals at risk for CC to prevent and treat CC effectively.
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Affiliation(s)
- Nhu Thi Hanh Vu
- Department of Internal Medicine, University of Medicine and Pharmacy at Ho Chi Minh City, Ho Chi Minh, Vietnam
- Department of Endoscopy, Hiroshima University Hospital, Hiroshima, Japan
| | - Duc Trong Quach
- Department of Internal Medicine, University of Medicine and Pharmacy at Ho Chi Minh City, Ho Chi Minh, Vietnam
| | - Shunsuke Miyauchi
- Health Service Center, Hiroshima University, Higashihiroshima, Japan
| | - Mai Ngoc Luu
- Department of Internal Medicine, University of Medicine and Pharmacy at Ho Chi Minh City, Ho Chi Minh, Vietnam
| | - Mahoko Yoshida
- Health Service Center, Hiroshima University, Higashihiroshima, Japan
| | - Doan Thi Nha Nguyen
- Department of Internal Medicine, University of Medicine and Pharmacy at Ho Chi Minh City, Ho Chi Minh, Vietnam
| | - Atsuo Yoshino
- Health Service Center, Hiroshima University, Higashihiroshima, Japan
| | - Yoshie Miyaka
- Health Service Center, Hiroshima University, Higashihiroshima, Japan
| | - Yuri Okamoto
- Health Service Center, Hiroshima University, Higashihiroshima, Japan
| | - Shiro Oka
- Department of Gastroenterology, Graduate School of Biomedical and Health Sciences, Hiroshima, Japan
| | - Toru Hiyama
- Health Service Center, Hiroshima University, Higashihiroshima, Japan
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Yang F, Wu Y, Hockey R, Doust J, Mishra GD, Montgomery GW, Mortlock S. Evidence of shared genetic factors in the etiology of gastrointestinal disorders and endometriosis and clinical implications for disease management. Cell Rep Med 2023; 4:101250. [PMID: 37909040 PMCID: PMC10694629 DOI: 10.1016/j.xcrm.2023.101250] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/16/2022] [Revised: 03/26/2023] [Accepted: 09/27/2023] [Indexed: 11/02/2023]
Abstract
In clinical practice, the co-existence of endometriosis and gastrointestinal symptoms is often observed. Using large-scale datasets, we report a genetic correlation between endometriosis and irritable bowel syndrome (IBS), peptic ulcer disease (PUD), gastro-esophageal reflux disease (GORD), and a combined GORD/PUD medicated (GPM) phenotype. Mendelian randomization analyses support a causal relationship between genetic predisposition to endometriosis and IBS and GPM. Identification of shared risk loci highlights biological pathways that may contribute to the pathogenesis of both diseases, including estrogen regulation and inflammation, and potential therapeutic drug targets (CCKBR; PDE4B). Higher use of IBS, GORD, and PUD medications in women with endometriosis and higher use of hormone therapies in women with IBS, GORD, and PUD, support the co-occurrence of these conditions and highlight the potential for drug repositioning and drug contraindications. Our results provide evidence of shared disease etiology and have important clinical implications for diagnostic and treatment decisions for both diseases.
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Affiliation(s)
- Fei Yang
- The Institute for Molecular Bioscience, The University of Queensland, Brisbane, QLD 4072, Australia
| | - Yeda Wu
- The Institute for Molecular Bioscience, The University of Queensland, Brisbane, QLD 4072, Australia
| | - Richard Hockey
- The University of Queensland, NHMRC Centre for Research Excellence on Women and Non-communicable Diseases (CREWaND), School of Public Health, Herston Road, Herston, QLD, Australia
| | - Jenny Doust
- The University of Queensland, NHMRC Centre for Research Excellence on Women and Non-communicable Diseases (CREWaND), School of Public Health, Herston Road, Herston, QLD, Australia
| | - Gita D Mishra
- The University of Queensland, NHMRC Centre for Research Excellence on Women and Non-communicable Diseases (CREWaND), School of Public Health, Herston Road, Herston, QLD, Australia
| | - Grant W Montgomery
- The Institute for Molecular Bioscience, The University of Queensland, Brisbane, QLD 4072, Australia
| | - Sally Mortlock
- The Institute for Molecular Bioscience, The University of Queensland, Brisbane, QLD 4072, Australia.
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Hung TH, Wang CY, Lee HF. Update in diagnosis and management of irritable bowel syndrome. Tzu Chi Med J 2023; 35:306-311. [PMID: 38035060 PMCID: PMC10683518 DOI: 10.4103/tcmj.tcmj_104_23] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/28/2023] [Revised: 06/13/2023] [Accepted: 08/09/2023] [Indexed: 12/02/2023] Open
Abstract
Irritable bowel syndrome (IBS) is a functional gastrointestinal disorder characterized by a lack of structural or biochemical abnormalities. The current diagnosis of IBS is based on the Rome IV criteria, and it is recommended to approach IBS patients using a multidimensional clinical profile (MDCP). The pathophysiology of IBS is multifactorial and involves motility disorders, genetic factors, immune responses, visceral hypersensitivity, brain-gut dysregulation, and altered intestinal microbiota. The management of IBS includes both nonpharmacologic and pharmacologic therapies. Nonpharmacologic therapy options include physical activity, low fermentable oligosaccharides, disaccharides, monosaccharides, and polyol diet, as well as cognitive behavioral therapy. Pharmacologic therapy options include probiotics, antidepressants, antispasmodics, and new agents. In clinical practice, a multidisciplinary strategy, including nonpharmacologic or/and pharmacologic treatment for IBS, is emphasized. Therefore, clinicians should carefully consider the underlying pathophysiology before selecting an appropriate therapeutic option for the treatment of IBS. In other words, individualized treatment plans are necessary for managing IBS.
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Affiliation(s)
- Tsung-Hsing Hung
- Division of Gastroenterology, Department of Medicine, Dalin Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Chiayi, Taiwan
- School of Medicine, Tzu Chi University, Hualien, Taiwan
| | - Chih-Ying Wang
- Department of Medical Research, Dalin Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Chiayi, Taiwan
| | - Hsing-Feng Lee
- Division of Gastroenterology, Department of Medicine, Dalin Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Chiayi, Taiwan
- School of Medicine, Tzu Chi University, Hualien, Taiwan
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Pan PY, Taylor MJ, Larsson H, Almqvist C, Lichtenstein P, Lundström S, Bölte S. Genetic and environmental contributions to co-occurring physical health conditions in autism spectrum condition and attention-deficit/hyperactivity disorder. Mol Autism 2023; 14:17. [PMID: 37085910 PMCID: PMC10122407 DOI: 10.1186/s13229-023-00548-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/08/2022] [Accepted: 04/13/2023] [Indexed: 04/23/2023] Open
Abstract
BACKGROUND Autism spectrum condition and attention-deficit/hyperactivity disorder (ADHD) are associated with a range of physical health conditions. The aim of this study was to examine the etiological components contributing to co-occurring physical health conditions in autism and ADHD. METHODS In this nationwide Child and Adolescent Twin Study in Sweden, we analyzed data from 10,347 twin pairs aged 9 and 12. Clinical diagnoses of autism, ADHD, and physical health conditions were identified through the Swedish National Patient Register. Subclinical phenotypes of autism and ADHD were defined by symptom thresholds on a standardized parent-interview, the Autism-Tics, ADHD, and Other Comorbidities inventory. Associations between physical health conditions and autism/ADHD phenotypes were examined using generalized estimating equations. Bivariate twin models were applied to estimate the extent to which genetic and environmental risk factors accounted for physical health comorbidities. RESULTS Similar patterns of association with physical health conditions were found in clinical and subclinical autism/ADHD, with odds ratios ranging from 1.31 for asthma in subclinical ADHD to 8.03 for epilepsy in clinical autism. The estimated genetic correlation (ra) with epilepsy was 0.50 for clinical autism and 0.35 for subclinical autism. In addition, a modest genetic correlation was estimated between clinical autism and constipation (ra = 0.31), functional diarrhea (ra = 0.27) as well as mixed gastrointestinal disorders (ra = 0.30). Genetic effects contributed 0.86 for mixed gastrointestinal disorders in clinical ADHD (ra = 0.21). Finally, subclinical ADHD shared genetic risk factors with epilepsy, constipation, and mixed gastrointestinal disorders (ra = 0.30, 0.17, and 0.17, respectively). LIMITATIONS Importantly, since medical records from primary care were not included in the registry data used, we probably identified only more severe rather than the full range of physical health conditions. Furthermore, it needs to be considered that the higher prevalence of physical health conditions among autistic children and children with ADHD could be associated with the increased number of medical visits. CONCLUSIONS Shared genetic effects contribute significantly to autism and ADHD phenotypes with the co-occurring physical health conditions across different organ systems, including epilepsy and gastrointestinal disorders. The shared genetic liability with co-occurring physical health conditions was present across different levels of autism and ADHD symptom severity.
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Affiliation(s)
- Pei-Yin Pan
- Center of Neurodevelopmental Disorders (KIND), Centre for Psychiatry Research; Department of Women's and Children's Health, Karolinska Institutet & Stockholm Health Care Services, Region Stockholm, Gävlegatan 22, 11330, Stockholm, Sweden.
| | - Mark J Taylor
- Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Berzelius Väg 8, Solna, 17165, Stockholm, Sweden
| | - Henrik Larsson
- Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Berzelius Väg 8, Solna, 17165, Stockholm, Sweden
| | - Catarina Almqvist
- Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Berzelius Väg 8, Solna, 17165, Stockholm, Sweden
- Lung and Allergy Unit, Astrid Lindgren Children's Hospital, Karolinska University Hospital, Eugeniavägen 23, Solna, 17164, Stockholm, Sweden
| | - Paul Lichtenstein
- Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Berzelius Väg 8, Solna, 17165, Stockholm, Sweden
| | - Sebastian Lundström
- Gillberg Neuropsychiatry Centre, University of Gothenburg, Kungsgatan 12, 41119, GothenburgGöteborg, Sweden
- Centre for Ethics, Law, and Mental Health, University of Gothenburg, Universitetsplatsen 1, 41124, Gothenburg, Sweden
| | - Sven Bölte
- Center of Neurodevelopmental Disorders (KIND), Centre for Psychiatry Research; Department of Women's and Children's Health, Karolinska Institutet & Stockholm Health Care Services, Region Stockholm, Gävlegatan 22, 11330, Stockholm, Sweden
- Child and Adolescent Psychiatry, Stockholm Health Care Services, Region Stockholm, Solnavägen 1E, 113 65, Stockholm, Sweden
- Curtin Autism Research Group, Curtin School of Allied Health, Curtin University, Kent Street, Bentley, Perth, WA, 6102, Australia
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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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Császár-Nagy N, Bókkon I. Hypnotherapy and IBS: Implicit, long-term stress memory in the ENS? Heliyon 2022; 9:e12751. [PMID: 36685398 PMCID: PMC9849985 DOI: 10.1016/j.heliyon.2022.e12751] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/12/2022] [Revised: 09/20/2022] [Accepted: 12/27/2022] [Indexed: 01/01/2023] Open
Abstract
The association between irritable bowel syndrome (IBS) and psychiatric and mood disorders may be more fundamental than was previously believed. Prenatal, perinatal, postnatal, and early-age conditions can have a key role in the development of IBS. Subthreshold mental disorders (SMDs) could also be a significant source of countless diverse diseases and may be a cause of IBS development. We hypothesize that stress-induced implicit memories may persist throughout life by epigenetic processes in the enteric nervous system (ENS). These stress-induced implicit memories may play an essential role in the emergence and maintenance of IBS. In recent decades, numerous studies have proven that hypnosis can improve the primary symptoms of IBS and also reduce noncolonic symptoms such as anxiety and depression and improve quality of life and cognitive function. These significant beneficial effects of hypnosis on IBS may be because hypnosis allows access to unconscious brain processes.
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Affiliation(s)
- N. Császár-Nagy
- National University of Public Services, Budapest, Hungary,Psychosomatic Outpatient Clinics, Budapest, Hungary
| | - I. Bókkon
- Psychosomatic Outpatient Clinics, Budapest, Hungary,Vision Research Institute, Neuroscience and Consciousness Research Department, Lowell, MA, USA,Corresponding author. H-1238, Budapest, Láng Endre 68, Hungary.
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11
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Grozić A, Coker K, Dussik CM, Sabir MS, Sabir Z, Bradley A, Zhang L, Park J, Yale S, Kaneko I, Hockley M, Harris LA, Lunsford TN, Sandrin TR, Jurutka PW. Identification of putative transcriptomic biomarkers in irritable bowel syndrome (IBS): Differential gene expression and regulation of TPH1 and SERT by vitamin D. PLoS One 2022; 17:e0275683. [PMID: 36264926 PMCID: PMC9584396 DOI: 10.1371/journal.pone.0275683] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/23/2022] [Accepted: 09/21/2022] [Indexed: 11/06/2022] Open
Abstract
Irritable bowel syndrome (IBS) is one of the most common gastrointestinal disorders and affects approximately 4% of the global population. The diagnosis of IBS can be made based on symptoms using the validated Rome criteria and ruling out commonly occurring organic diseases. Although biomarkers exist for "IBS mimickers" such as celiac disease and inflammatory bowel disease (IBD), no such test exists for IBS. DNA microarrays of colonic tissue have been used to identify disease-associated variants in other gastrointestinal (GI) disorders. In this study, our objective was to identify biomarkers and unique gene expression patterns that may define the pathological state of IBS. Mucosal tissue samples were collected from the sigmoid colon of 29 participants (11 IBS and 18 healthy controls). DNA microarray analysis was used to assess gene expression profiling. Extraction and purification of RNA were then performed and used to synthesize cDNA. Reverse transcriptase quantitative polymerase chain reaction (RT-qPCR) was employed to identify differentially expressed genes in patients diagnosed with IBS compared to healthy, non-IBS patient-derived cDNA. Additional testing probed vitamin D-mediated regulation of select genes associated with serotonergic metabolism. DNA microarray analyses led to the identification of 858 differentially expressed genes that may characterize the IBS pathological state. After screening a series of genes using a combination of gene ontological analysis and RT-qPCR, this spectrum of potential IBS biomarkers was narrowed to 23 genes, some of which are regulated by vitamin D. Seven putative IBS biomarkers, including genes involved in serotonin metabolism, were identified. This work further supports the hypothesis that IBS pathophysiology is evident within the human transcriptome and that vitamin D modulates differential expression of genes in IBS patients. This suggests that IBS pathophysiology may also involve vitamin D deficiency and/or an irregularity in serotonin metabolism.
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Affiliation(s)
- Aleksandra Grozić
- School of Mathematical and Natural Sciences, Arizona State University, Phoenix, AZ, United States of America
| | - Keaton Coker
- School of Mathematical and Natural Sciences, Arizona State University, Phoenix, AZ, United States of America
| | - Christopher M. Dussik
- School of Mathematical and Natural Sciences, Arizona State University, Phoenix, AZ, United States of America
| | - Marya S. Sabir
- School of Mathematical and Natural Sciences, Arizona State University, Phoenix, AZ, United States of America
| | - Zhela Sabir
- School of Mathematical and Natural Sciences, Arizona State University, Phoenix, AZ, United States of America
| | - Arianna Bradley
- School of Mathematical and Natural Sciences, Arizona State University, Phoenix, AZ, United States of America
| | - Lin Zhang
- School of Mathematical and Natural Sciences, Arizona State University, Phoenix, AZ, United States of America
| | - Jin Park
- Biodesign Institute, Arizona State University, Tempe, AZ, United States of America
| | - Steven Yale
- Department of Medicine, University of Central Florida College of Medicine, Orlando, FL, United States of America
| | - Ichiro Kaneko
- School of Mathematical and Natural Sciences, Arizona State University, Phoenix, AZ, United States of America
- Department of Basic Medical Sciences, University of Arizona College of Medicine, Phoenix, AZ, United States of America
| | - Maryam Hockley
- School of Mathematical and Natural Sciences, Arizona State University, Phoenix, AZ, United States of America
| | - Lucinda A. Harris
- Mayo Clinic Division of Gastroenterology & Hepatology, Alix School of Medicine, Mayo Clinic, Scottsdale, AZ, United States of America
| | - Tisha N. Lunsford
- Mayo Clinic Division of Gastroenterology & Hepatology, Alix School of Medicine, Mayo Clinic, Scottsdale, AZ, United States of America
| | - Todd R. Sandrin
- School of Mathematical and Natural Sciences, Arizona State University, Phoenix, AZ, United States of America
- Julie Ann Wrigley Global Futures Laboratory, Arizona State University, Tempe, AZ, United States of America
| | - Peter W. Jurutka
- School of Mathematical and Natural Sciences, Arizona State University, Phoenix, AZ, United States of America
- Department of Basic Medical Sciences, University of Arizona College of Medicine, Phoenix, AZ, United States of America
- * E-mail:
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12
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Kutschke J, Harris JR, Bengtson MB. The relationships between IBS and perceptions of physical and mental health-a Norwegian twin study. BMC Gastroenterol 2022; 22:266. [PMID: 35643443 PMCID: PMC9145077 DOI: 10.1186/s12876-022-02340-8] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/07/2022] [Accepted: 05/18/2022] [Indexed: 11/10/2022] Open
Abstract
BACKGROUND AND AIMS Poor quality of life is a main complaint among individuals with irritable bowel syndrome (IBS). Self-rated health (SRH) is a powerful predictor of clinical outcomes, and also reflects psychological and social aspects of life and an overall sense of well-being. This population-based twin study evaluates how IBS affects ratings of physical and mental health, and influences perceptions of hindrance of daily activity by physical or mental health. Further, we examine how IBS is related to these SRH measures. METHODS The sample included 5288 Norwegian twins aged 40-80, of whom 575 (10.9%) suffer from IBS. Hierarchical regressions were used to estimate the impact of IBS on perceptions of health, before and after accounting for other chronic physical and mental health conditions. Two dimensions of SRH, physical and mental, and two aspects of functional limitations, the extent to which physical or mental health interferes with daily activities, were included as outcomes in separate models. Co-twin control analyses were used to explore whether the relationships between IBS and the four measures of SRH are causal, or due to shared genetic or shared environment effects. RESULTS IBS was an independent predictor of poor self-rated physical health (OR = 1.82 [1.41; 2.33]), the size of this effect was comparable to that predicted by chronic somatic conditions. However, in contrast to somatic diseases, IBS was associated with the perception that poorer ratings of mental health (OR = 1.45 [1.02; 2.06]), but not physical health (OR = 1.23 [0.96; 1.58]), interfered with daily activity. The co-twin control analyses suggest that causal mechanisms best explain the relationships between IBS with self-rated physical health and with hindrance of daily activities. In contrast, the relationship between IBS and self-rated mental health was consistent with shared genetic effects. CONCLUSION IBS is predictive of poor self-rated physical health. The relationship between IBS and self-rated mental health is best explained by shared genetic effects which might partially explain why mental health interferes with daily activity to a larger degree among those with IBS.
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Affiliation(s)
| | - Jennifer R Harris
- Centre for Fertility and Health, The Norwegian Institute of Public Health, Oslo, Norway
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13
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A Breakthrough Point in Integrative Medical Research: Challenge of Treating Overlapping Symptoms in Functional Gastrointestinal Disorders. Chin J Integr Med 2022; 28:554-559. [PMID: 35610498 DOI: 10.1007/s11655-022-3534-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 03/03/2022] [Indexed: 11/03/2022]
Abstract
Functional gastrointestinal disorders (FGIDs) are common disorders that are characterized by persistent and recurring gastrointestinal symptoms. Many patients with FGIDs have overlapping symptoms, which impaired the quality of life and ability to work of patients, and left a considerable impact on health-care systems and society. Chinese medicines (CMs) are commonly utilized by many patients with FGIDs. This article discusses the current status of diagnosis and treatment of FGIDs, the advantages and characteristics of CM treatment, and how integrated medicine can make a breakthrough in FGIDs diagnosis and treatment.
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14
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Kutschke J, Harris JR, Bengtson M. How are perceptions of social strain and low support related to Irritable Bowel Syndrome?-A Norwegian twin study. Neurogastroenterol Motil 2021; 33:e14007. [PMID: 33030285 PMCID: PMC8047927 DOI: 10.1111/nmo.14007] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/04/2020] [Revised: 08/28/2020] [Accepted: 09/14/2020] [Indexed: 02/08/2023]
Abstract
BACKGROUND Social stress is related to symptom burden of irritable bowel syndrome (IBS). This study explores the associations between IBS and social strain or low support in close relationships, including spouse, friends, and family, in a Norwegian twin cohort. METHODS The sample included 5442 Norwegian twins aged 40-80, of whom 589 suffer from IBS. We used multivariate structural equation models to estimate genetic and environmental sources of variation and covariation underlying IBS liability, measures of social stress and the relationships between these. The co-twin control design was used to explore the nature of the associations between IBS and social strain or low support using models that test for causality. KEY RESULTS Genetic effects explained between 30% and 40% of the variation in IBS liability, social strain, and low support. The phenotypic correlations between IBS and social strain (0.20) and between IBS and low support (0.17) were primarily explained by shared genetic pathways. Surprisingly, all the genetic variation underlying the liability to develop IBS was shared with genetic influences underlying social strain and low support. In contrast, most of the nonshared environmental influences accounting for the variation of IBS risk were unique for IBS. The co-twin control analyses suggest that the relationships between IBS and the social measures reflect shared familial rather than causal effects. CONCLUSION & INFERENCES The genetic variation of IBS risk was fully shared with genetic effects for variation in the social measures, emphasizing the contribution of genes involved in central brain-gut mechanisms to genetic variation in IBS risk.
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Affiliation(s)
| | - Jennifer R. Harris
- Division of Health Data and DigitalisationThe Norwegian Institute of Public HealthOsloNorway
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15
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Harvey PR, Theron B, Smith SCL, Rastall P, Steves CJ, Harris J, Spector TD, Trudgill NJ. The association between low birth weight, childhood recollections of parental response to illness, and irritable bowel syndrome: a twin study. Neurogastroenterol Motil 2020; 32:e13939. [PMID: 32715594 DOI: 10.1111/nmo.13939] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/11/2019] [Revised: 06/06/2020] [Accepted: 06/16/2020] [Indexed: 12/16/2022]
Abstract
BACKGROUND The aetiology of irritable bowel syndrome (IBS) is multifactorial, including genetic and environmental factors. Previous studies have suggested that low birth weight and family environment during childhood are associated with developing IBS. METHODS A survey was sent to all individuals in a UK twin registry. Questions included IBS diagnosed by the Rome IV criteria and if a doctor had previously diagnosed them with IBS. Subjects were categorized as having IBS by Rome IV criteria, a medical diagnosis of IBS or no IBS. Further questions included subjects' recollections of their parents' responses to illness in both the respondent as a child and in the parents themselves. Information regarding birth weight and gestational age have been collected previously. KEY RESULTS 4258 subjects responded to the questionnaire (51.7%), mean age of 52 (SD 14) years, of whom 98.5% were white and 89.6% female. The mean birth weight was 2.4 (0.6) kg. 5.1% satisfied the Rome IV IBS criteria, the same prevalence as the UK population. However, 14.1% had a previous medical diagnosis of IBS. There was no association found between birth weight and IBS or a medical diagnosis of IBS. On multivariable regression analysis, including parental responses to illness, subjects recalling a parent responding to the parent's bowel symptoms by excusing themselves from household chores were associated with a Rome IV diagnosis of IBS (OR 2.19 (95% CI 1.17-4.10), P = .013). CONCLUSIONS AND INFERENCES There was no association between birth weight and IBS. However, observing their parents excuse themselves from household chores when they had bowel symptoms was associated with IBS in later life.
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Affiliation(s)
- Philip R Harvey
- Department of Gastroenterology, Sandwell & West Birmingham Hospitals NHS Trust, West Bromwich, UK
| | - Byron Theron
- Department of Gastroenterology, Sandwell & West Birmingham Hospitals NHS Trust, West Bromwich, UK
| | - Samuel C L Smith
- Department of Gastroenterology, Sandwell & West Birmingham Hospitals NHS Trust, West Bromwich, UK
| | - Paul Rastall
- Department of Gastroenterology, Sandwell & West Birmingham Hospitals NHS Trust, West Bromwich, UK
| | - Claire J Steves
- Department of Twin Research and Genetic Epidemiology, Kings College London, London, UK
| | - Julliette Harris
- Department of Twin Research and Genetic Epidemiology, Kings College London, London, UK
| | - Timothy D Spector
- Department of Twin Research and Genetic Epidemiology, Kings College London, London, UK
| | - Nigel J Trudgill
- Department of Gastroenterology, Sandwell & West Birmingham Hospitals NHS Trust, West Bromwich, UK
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16
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Koloski N, Holtmann G, Talley NJ. Is there a causal link between psychological disorders and functional gastrointestinal disorders? Expert Rev Gastroenterol Hepatol 2020; 14:1047-1059. [PMID: 32715790 DOI: 10.1080/17474124.2020.1801414] [Citation(s) in RCA: 34] [Impact Index Per Article: 6.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
Abstract
INTRODUCTION Psychological distress is associated with functional gastrointestinal disorders (FGIDs) including irritable bowel syndrome (IBS) and functional dyspepsia (FD) but only evidence from prospective longitudinal and treatment studies can indicate whether the link between FGIDs and psychological distress is causal. Emerging evidence suggests underlying biological mechanisms may explain the association of psychological distress with FGIDs. AREAS COVERED This review critically evaluates whether anxiety and/or depression and FGIDs are causally related including evidence for a temporal sequence, strength and specificity of the association, biological gradient, and biological plausibility. EXPERT OPINION Accumulating evidence suggests that psychological factors are causal for symptoms in a subset of FGID patients and not explained by health care seeking behavior (brain-gut disorder). In other cases, psychological factors may arise secondary to intestinal disease (gut-brain disorder). Prospective population-based studies are needed in FGIDs other than IBS and FD to determine if a similar brain-gut and gut-brain syndrome exists. Treatment studies have not phenotyped FGIDs according to brain-gut versus gut-brain origins which may be important in understanding true treatment efficacy. Future research needs to unravel biological mechanisms that may explain the link between psychological factors and FGIDs but promising data in the area of the brain-gut-immune-microbe axis is emerging.
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Affiliation(s)
- Natasha Koloski
- Faculty of Health and Medicine, University of Newcastle , Callaghan, Australia
- Australian Gastrointestinal Research Alliance (AGIRA)
- Department of Gastroenterology, Princess Alexandra Hospital , Woolloongabba, Australia
- School of Medicine, University of Queensland , St Lucia, Australia
| | - Gerald Holtmann
- Australian Gastrointestinal Research Alliance (AGIRA)
- Department of Gastroenterology, Princess Alexandra Hospital , Woolloongabba, Australia
- School of Medicine, University of Queensland , St Lucia, Australia
| | - Nicholas J Talley
- Faculty of Health and Medicine, University of Newcastle , Callaghan, Australia
- Australian Gastrointestinal Research Alliance (AGIRA)
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17
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Tappin D, Grzeda M, Joinson C, Heron J. Challenging the view that lack of fibre causes childhood constipation. Arch Dis Child 2020; 105:864-868. [PMID: 32156695 PMCID: PMC7456542 DOI: 10.1136/archdischild-2019-318082] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/14/2019] [Revised: 02/12/2020] [Accepted: 02/17/2020] [Indexed: 11/10/2022]
Abstract
OBJECTIVES To assess evidence supporting the view that 'low fibre causes childhood constipation'. DESIGN Triangulation integrated three approaches: a systematic review NICE guideline CG99 examining effectiveness of increasing fibre; a cohort study, Avon Longitudinal Study of Parents and Children (ALSPAC), to assess if constipation (or hard stools) can precede fibre intake at weaning; and a literature search for twin studies to calculate heredity. SETTING CG99 examined the literature regarding the effectiveness of increasing fibre. ALSPAC asked parents about: hard stools at 4 weeks, 6 months and 2.5 years and constipation at age 4-10 years, as well as fibre intake at 2 years. Twin studies and data from ALSPAC were pooled to calculate concordance of constipation comparing monozygotic and dizygous twin pairs. PARTICIPANTS CG99 reported six randomised controlled trials (RCTs). ALSPAC hard stool data from 6796 children at 4 weeks, 9828 at 6 months and 9452 at 2.5 years plus constipation data on 8401 at 4-10 years were compared with fibre intake at 2 years. Twin studies had 338 and 93 twin pairs and ALSPAC added a further 45. RESULTS Increasing fibre did not effectively treat constipation. Hard stools at 4 weeks predated fibre and at 6 months predicted lower fibre intake at 2 years (p=0.003). Heredity explained 59% of constipation. CONCLUSIONS RCTs indicate that increasing fibre is not an effective treatment for constipation in children. Hard stools can precede and predict later fibre intake. Genetic inheritance explains most childhood constipation. Extended treatment with stool softeners may improve fibre intake and limit long-term damaging sequelae of constipation.
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Affiliation(s)
- David Tappin
- Scottish Cot Death Trust, University of Glasgow, Glasgow, UK
| | - Mariusz Grzeda
- Population Health Sciences, University of Bristol, Bristol, UK
| | - Carol Joinson
- Population Health Sciences, University of Bristol, Bristol, UK,Centre for Child and Adolescent Health, University of Bristol, Bristol, UK
| | - Jon Heron
- Population Health Sciences, University of Bristol, Bristol, UK
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18
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El-Salhy M. Possible role of intestinal stem cells in the pathophysiology of irritable bowel syndrome. World J Gastroenterol 2020; 26:1427-1438. [PMID: 32308344 PMCID: PMC7152517 DOI: 10.3748/wjg.v26.i13.1427] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/03/2019] [Revised: 03/12/2020] [Accepted: 03/14/2020] [Indexed: 02/06/2023] Open
Abstract
The pathophysiology of irritable bowel syndrome (IBS) is not completely understood. However, several factors are known to play a role in pathophysiology of IBS such as genetics, diet, gut microbiota, gut endocrine cells, stress and low-grade inflammation. Understanding the pathophysiology of IBS may open the way for new treatment approaches. Low density of intestinal stem cells and low differentiation toward enteroendocrine cells has been reported recently in patients with IBS. These abnormalities are believed to be the cause of the low density of enteroendocrine cells seen in patients with IBS. Enteroendocrine cells regulate gastrointestinal motility, secretion, absorption and visceral sensitivity. Gastrointestinal dysmotility, abnormal absorption/secretion and visceral hypersensitivity are all seen in patients with IBS and haven been attributed to the low density the intestinal enteroendocrine cells in these patients. The present review conducted a literature search in Medline (PubMed) covering the last ten years until November 2019, where articles in English were included. Articles about the intestinal stem cells and their possible role in the pathophysiology of IBS are discussed in the present review. The present review discusses the assumption that intestinal stem cells play a central role in the pathophysiology of IBS and that the other factors known to contribute to the pathophysiology of IBS such as genetics, diet gut microbiota, stress, and low-grade inflammation exert their effects through affecting the intestinal stem cells. It reports further the data that support this assumption on genetics, diet, gut microbiota, stress with depletion of glutamine, and inflammation.
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Affiliation(s)
- Magdy El-Salhy
- Section for Gastroenterology, Department of Medicine, Stord Hospital, Stord 54 09, Norway
- Department of Clinical Medicine, University of Bergen, Bergen 50 21, Norway
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Mora-Ortiz M, Ibraheim H, Hermangild Kottoor S, Bowyer RCE, Metrustry S, Sanderson J, Powell N, D. Spector T, S. Small K, Steves CJ. Introducing ExHiBITT – Exploring Host microBIome inTeractions in Twins –, a colon multiomic cohort study. Wellcome Open Res 2020. [DOI: 10.12688/wellcomeopenres.15632.1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/20/2022] Open
Abstract
Background: The colon is populated by approximately 1012 microorganisms, but the relationships between this microbiome and the host health status are still not completely understood. Here, our objective is to present the cohort characteristics of ExHiBITT – Exploring Host microBIome inTeractions in Twins – including i) biomedical phenotypes, ii) environmental factors and ii) colonoscopic findings. Methods: Participants from the TwinsUK cohort were recruited to study the interactions between the microbiome and host adaptive immunity. In total, 205 monozygotic twins were recruited from the wider TwinsUK cohort. They completed health questionnaires, and provided saliva, blood, colon biopsies from three different locations, caecal fluid, and two faecal samples. Results: A significant proportion of this apparently normal cohort had colonic polyps (28%), which are of interest as potential precursors of colorectal cancer, and, as expected, the number of polyps found was significantly correlated with BMI and age. Hitherto undiagnosed diverticulosis was also not infrequently found during colonoscopy (26%) and was associated with changes in Hybrid Th1-17 cells in the colon. Twin proband co-occurrence rate for diverticulosis (82%) was much higher than for polyps (42%). Familial factors affecting morphology or tolerance may contribute to the ease of endoscopy, as both the time to reach the caecum and pain perceived were highly concordant (proband concordance: 85% and 56%, respectively). Conclusions: We found the expected positive relationship between BMI and colonoscopic anomalies such as diverticular disease and polyps in the whole population, but within twin pairs this association was reversed. This suggests that familial factors confound these associations. Host and microbial next generation sequencing and metabolomics of the samples collected are planned in this cohort.
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20
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Mahurkar-Joshi S, Chang L. Epigenetic Mechanisms in Irritable Bowel Syndrome. Front Psychiatry 2020; 11:805. [PMID: 32922317 PMCID: PMC7456856 DOI: 10.3389/fpsyt.2020.00805] [Citation(s) in RCA: 34] [Impact Index Per Article: 6.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/06/2020] [Accepted: 07/27/2020] [Indexed: 12/12/2022] Open
Abstract
Irritable bowel syndrome (IBS) is a brain-gut axis disorder characterized by abdominal pain and altered bowel habits. IBS is a multifactorial, stress-sensitive disorder with evidence for familial clustering attributed to genetic or shared environmental factors. However, there are weak genetic associations reported with IBS and a lack of evidence to suggest that major genetic factor(s) contribute to IBS pathophysiology. Studies on animal models of stress, including early life stress, suggest a role for environmental factors, specifically, stress associated with dysregulation of corticotropin releasing factor and hypothalamus-pituitary-adrenal (HPA) axis pathways in the pathophysiology of IBS. Recent evidence suggests that epigenetic mechanisms, which constitute molecular changes not driven by a change in gene sequence, can mediate environmental effects on central and peripheral function. Epigenetic alterations including DNA methylation changes, histone modifications, and differential expression of non-coding RNAs (microRNA [miRNA] and long non-coding RNA) have been associated with several diseases. The objective of this review is to elucidate the molecular factors in the pathophysiology of IBS with an emphasis on epigenetic mechanisms. Emerging evidence for epigenetic changes in IBS includes changes in DNA methylation in animal models of IBS and patients with IBS, and various miRNAs that have been associated with IBS and endophenotypes, such as increased visceral sensitivity and intestinal permeability. DNA methylation, in particular, is an emerging field in the realm of complex diseases and a promising mechanism which can provide important insights into IBS pathogenesis and identify potential targets for treatment.
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Affiliation(s)
- Swapna Mahurkar-Joshi
- G. Oppenheimer Center for Neurobiology of Stress and Resilience, Division of Digestive Diseases, Department of Medicine at UCLA, Los Angeles, CA, United States
| | - Lin Chang
- G. Oppenheimer Center for Neurobiology of Stress and Resilience, Division of Digestive Diseases, Department of Medicine at UCLA, Los Angeles, CA, United States
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21
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Diet in Irritable Bowel Syndrome (IBS): Interaction with Gut Microbiota and Gut Hormones. Nutrients 2019; 11:nu11081824. [PMID: 31394793 PMCID: PMC6723613 DOI: 10.3390/nu11081824] [Citation(s) in RCA: 88] [Impact Index Per Article: 14.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/23/2019] [Accepted: 08/05/2019] [Indexed: 12/15/2022] Open
Abstract
Diet plays an important role not only in the pathophysiology of irritable bowel syndrome (IBS), but also as a tool that improves symptoms and quality of life. The effects of diet seem to be a result of an interaction with the gut bacteria and the gut endocrine cells. The density of gut endocrine cells is low in IBS patients, and it is believed that this abnormality is the direct cause of the symptoms seen in IBS patients. The low density of gut endocrine cells is probably caused by a low number of stem cells and low differentiation progeny toward endocrine cells. A low fermentable oligo-, di-, monosaccharide, and polyol (FODMAP) diet and fecal microbiota transplantation (FMT) restore the gut endocrine cells to the level of healthy subjects. It has been suggested that our diet acts as a prebiotic that favors the growth of a certain types of bacteria. Diet also acts as a substrate for gut bacteria fermentation, which results in several by-products. These by-products might act on the stem cells in such a way that the gut stem cells decrease, and consequently, endocrine cell numbers decrease. Changing to a low-FODMAP diet or changing the gut bacteria through FMT improves IBS symptoms and restores the density of endocrine cells.
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22
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Qin D, Yue L, Xue B, Chen M, Tang TC, Zheng H. Pharmacological treatments for patients with irritable bowel syndrome: An umbrella review of systematic reviews and meta-analyses. Medicine (Baltimore) 2019; 98:e15920. [PMID: 31393342 PMCID: PMC6709044 DOI: 10.1097/md.0000000000015920] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/09/2019] [Accepted: 05/13/2019] [Indexed: 12/19/2022] Open
Abstract
INTRODUCTION Several pharmacological treatments are beneficial for patients with irritable bowel syndrome (IBS), and there are numbers of systematic reviews evaluating the effectiveness of these treatments. However, the overall quality of the evidence has not been quantitatively assessed. The aim of this study is to evaluate the possible biases in the published systematic reviews and determine the treatments with reliable evidence. METHODS AND ANALYSIS We will perform an umbrella review to identify eligible systematic reviews. A comprehensive literature search will be conducted in MEDLINE, EMBASE, and the Cochrane library for systematic reviews. We will describe the general information such as participants, interventions, outcome measurements, and conclusion. Additionally, the heterogeneity and inconsistency between trials will be assessed by the I statistical test and Cochrane Q test. We will assess risk of bias, and summarize the strength evidence. CONCLUSION The umbrella reviews will assess the reliability of the evidence so that doctors and patients can make better medical choices. PROSPERO REGISTRATION NUMBER CRD42018109597.
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Affiliation(s)
- Di Qin
- The 3 Hospital/Acupuncture and Tuina School
| | - Ling Yue
- The 3 Hospital/Acupuncture and Tuina School
| | - Bin Xue
- Acupuncture and Rehabilitation Department, Sichuan 2 Hospital of Traditional Chinese Medicine
| | - Min Chen
- Clinical Medicine College/Teaching Hospital, Chengdu University of Traditional Chinese Medicine, China
| | - Tai-Chun Tang
- Clinical Medicine College/Teaching Hospital, Chengdu University of Traditional Chinese Medicine, China
| | - Hui Zheng
- The 3 Hospital/Acupuncture and Tuina School
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23
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Waehrens R, Zöller B, Sundquist J, Sundquist K, Pirouzifard M. A Swedish national adoption study of risk of irritable bowel syndrome (IBS). BMJ Open Gastroenterol 2017; 4:e000156. [PMID: 29119001 PMCID: PMC5663268 DOI: 10.1136/bmjgast-2017-000156] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/27/2017] [Revised: 07/29/2017] [Accepted: 08/29/2017] [Indexed: 02/06/2023] Open
Abstract
Objectives Irritable bowel syndrome (IBS) clusters in families, but the familial risk of IBS has not been determined in adoptees. Studying adoptees and their biological and adoptive parents is a strong study design for separating genetic from environmental causes of familial clustering. This nationwide study aimed to separate the biological (genetic) and familial environmental contribution to the familial transmission of IBS. Methods We performed a family study for Swedish-born adoptees born from 1951 until 1995, and their biological and adoptive parents. The Swedish Multigeneration Register was linked to the Hospital Register (inpatients and outpatients) for the period 1964-2012 and the Swedish Outpatient Care Register for 2001-2012, and the Swedish Primary Healthcare register for 1989-2012. ORs for IBS were calculated for adoptees with an affected biological parent with IBS compared with adoptees without a biological parent with IBS. The OR for IBS was also determined in adoptees with an adoptive parent with IBS compared with adoptees without an adoptive parent with IBS. Heritability h2 (±SE) was also determined. Results The ORs for IBS were 1.67 in adoptees (95% CI 1.06 to 2.62) of biological parents diagnosed with IBS. The ORs for IBS were 0.88 in adoptees (95% CI 0.48 to 1.63) of adoptive parents diagnosed with IBS. The heritability was 19.5%±8.5%. Conclusions The present study indicates that biological (genetic) factors are important for the familial clustering of IBS. The heritability calculated is in the range from twin studies and suggests that heritability may be estimated in adoptees.
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Affiliation(s)
- Rasmus Waehrens
- Center for Primary Health Care Research, Lund University/Region SKåne, Malmö, Sweden
| | - Bengt Zöller
- Center for Primary Health Care Research, Lund University/Region SKåne, Malmö, Sweden
| | - Jan Sundquist
- Center for Primary Health Care Research, Lund University/Region SKåne, Malmö, Sweden
| | - Kristina Sundquist
- Center for Primary Health Care Research, Lund University/Region SKåne, Malmö, Sweden
| | - MirNabi Pirouzifard
- Center for Primary Health Care Research, Lund University/Region SKåne, Malmö, Sweden
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24
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O'Mahony SM, Clarke G, Dinan TG, Cryan JF. Irritable Bowel Syndrome and Stress-Related Psychiatric Co-morbidities: Focus on Early Life Stress. Handb Exp Pharmacol 2017; 239:219-246. [PMID: 28233180 DOI: 10.1007/164_2016_128] [Citation(s) in RCA: 42] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
Irritable bowel syndrome is a functional gastrointestinal disorder, with stress playing a major role in onset and exacerbation of symptoms such as abdominal pain and altered bowel movements. Stress-related disorders including anxiety and depression often precede the development of irritable bowel syndrome and vice versa. Stressor exposure during early life has the potential to increase an individual's susceptibility to both irritable bowel syndrome and psychiatric disease indicating that there may be a common origin for these disorders. Moreover, adverse early life events significantly impact upon many of the communication pathways within the brain-gut-microbiota axis, which allows bidirectional interaction between the central nervous system and the gastrointestinal tract. This axis is proposed to be perturbed in irritable bowel syndrome and studies now indicate that dysfunction of this axis is also seen in psychiatric disease. Here we review the co-morbidity of irritable bowel syndrome and psychiatric disease with their common origin in mind in relation to the impact of early life stress on the developing brain-gut-microbiota axis. We also discuss the therapeutic potential of targeting this axis in these diseases.
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Affiliation(s)
- Siobhain M O'Mahony
- Department of Anatomy and Neuroscience, University College Cork, Cork, Ireland. .,APC Microbiome Institute, University College Cork, Cork, Ireland.
| | - Gerard Clarke
- APC Microbiome Institute, University College Cork, Cork, Ireland.,Department of Psychiatry and Neurobehavioural Science, University College Cork, Cork, Ireland
| | - Timothy G Dinan
- APC Microbiome Institute, University College Cork, Cork, Ireland.,Department of Psychiatry and Neurobehavioural Science, University College Cork, Cork, Ireland
| | - John F Cryan
- Department of Anatomy and Neuroscience, University College Cork, Cork, Ireland.,APC Microbiome Institute, University College Cork, Cork, Ireland
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25
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Halawi H, Camilleri M. Pharmacogenetics and the treatment of functional gastrointestinal disorders. Pharmacogenomics 2017; 18:1085-1094. [PMID: 28686075 PMCID: PMC5591464 DOI: 10.2217/pgs-2017-0049] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/09/2017] [Accepted: 05/10/2017] [Indexed: 12/12/2022] Open
Abstract
The diagnosis and management of functional gastrointestinal disorders (FGIDs) remain very challenging. In the era of precision medicine, it is important to individualize the treatment of these conditions by providing targeted and effective therapies while minimizing the risk of medication side effects. By using genetic information that predicts and affects the responses to specific medications, it is anticipated that the science of pharmacogenetics in FGIDs will advance the practice of precision medicine. The pathophysiology of FGIDs is complex, involving the interaction between predisposing genetic and environmental factors. Studies have shown that genetic polymorphisms may contribute to the variable responses to specific medications among individuals with FGIDs. Genetic variations in the CYP450 system can affect the metabolism and, hence, the pharmacokinetics of drugs used to treat FGIDs. Polymorphisms in the genes controlling proteins that are involved in the direct action of medications targeting the serotonergic, cannabinoid, adrenergic and bile acid pathways can affect the pharmacologic effects of the medications. In this review, we summarize the published literature on the pharmacogenetics of FGIDs and address the potential clinical utility and future challenges in this field. Since it was the dominant topic in the majority of the articles relevant to FGIDs, our review will focus on irritable bowel syndrome.
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Affiliation(s)
- Houssam Halawi
- Clinical Enteric Neuroscience Translational & Epidemiological Research (C.E.N.T.E.R.), Division of Gastroenterology & Hepatology, Mayo Clinic, Rochester, MN 55905, USA
| | - Michael Camilleri
- Clinical Enteric Neuroscience Translational & Epidemiological Research (C.E.N.T.E.R.), Division of Gastroenterology & Hepatology, Mayo Clinic, Rochester, MN 55905, USA
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26
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El-Salhy M, Hausken T, Gilja OH, Hatlebakk JG. The possible role of gastrointestinal endocrine cells in the pathophysiology of irritable bowel syndrome. Expert Rev Gastroenterol Hepatol 2017; 11:139-148. [PMID: 27927062 DOI: 10.1080/17474124.2017.1269601] [Citation(s) in RCA: 24] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
The etiology of irritable bowel syndrome (IBS) is unknown, but several factors appear to play a role in its pathophysiology, including abnormalities of the gastrointestinal endocrine cells. The present review illuminates the possible role of gastrointestinal hormones in the pathophysiology of IBS and the possibility of utilizing the current knowledge in treating the disease. Areas covered: Research into the intestinal endocrine cells and their possible role in the pathophysiology of IBS is discussed. Furthermore, the mechanisms underlying the abnormalities in the gastrointestinal endocrine cells in IBS patients are revealed. Expert commentary: The abnormalities observed in the gastrointestinal endocrine cells in IBS patients explains their visceral hypersensitivity, gastrointestinal dysmotility, and abnormal intestinal secretion, as well as the interchangeability of symptoms over time. Clarifying the role of the intestinal stem cells in the pathophysiology of IBS may lead to new treatment methods for IBS.
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Affiliation(s)
- Magdy El-Salhy
- a Division of Gastroenterology, Department of Medicine , Stord Hospital , Stord , Norway.,b Division of Gastroenterology, Department of Clinical Medicine , University of Bergen , Bergen , Norway.,c National Centre for Functional Gastrointestinal Disorders, Department of Medicine , Haukeland University Hospital , Bergen , Norway
| | - Trygve Hausken
- b Division of Gastroenterology, Department of Clinical Medicine , University of Bergen , Bergen , Norway.,c National Centre for Functional Gastrointestinal Disorders, Department of Medicine , Haukeland University Hospital , Bergen , Norway
| | - Odd Helge Gilja
- b Division of Gastroenterology, Department of Clinical Medicine , University of Bergen , Bergen , Norway.,c National Centre for Functional Gastrointestinal Disorders, Department of Medicine , Haukeland University Hospital , Bergen , Norway.,d National Centre for Ultrasound in Gastroenterology, Department of Medicine , Haukeland University Hospital , Bergen , Norway
| | - Jan Gunnar Hatlebakk
- b Division of Gastroenterology, Department of Clinical Medicine , University of Bergen , Bergen , Norway.,c National Centre for Functional Gastrointestinal Disorders, Department of Medicine , Haukeland University Hospital , Bergen , Norway
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27
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Bhattarai Y, Muniz Pedrogo DA, Kashyap PC. Irritable bowel syndrome: a gut microbiota-related disorder? Am J Physiol Gastrointest Liver Physiol 2017; 312:G52-G62. [PMID: 27881403 PMCID: PMC5283907 DOI: 10.1152/ajpgi.00338.2016] [Citation(s) in RCA: 204] [Impact Index Per Article: 25.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/09/2016] [Revised: 11/07/2016] [Accepted: 11/16/2016] [Indexed: 01/31/2023]
Abstract
Irritable bowel syndrome (IBS) is one of the most common gastrointestinal (GI) disorders. Despite its prevalence, the pathophysiology of IBS is not well understood although multiple peripheral and central factors are implicated. Recent studies suggest a role for alterations in gut microbiota in IBS. Significant advances in next-generation sequencing technology and bioinformatics and the declining cost have now allowed us to better investigate the role of gut microbiota in IBS. In the following review, we propose gut microbiota as a unifying factor in the pathophysiology of IBS. We first describe how gut microbiota can be influenced by factors predisposing individuals to IBS such as host genetics, stress, diet, antibiotics, and early life experiences. We then highlight the known effects of gut microbiota on mechanisms implicated in the pathophysiology of IBS including disrupted gut brain axis (GBA), visceral hypersensitivity (VH), altered GI motility, epithelial barrier dysfunction, and immune activation. While there are several gaps in the field that preclude us from connecting the dots to establish causation, we hope this overview will allow us to identify and fill in the voids.
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Affiliation(s)
- Yogesh Bhattarai
- 1Enteric Neuroscience Program, Mayo Clinic, Rochester, Minnesota; and ,2Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota
| | - David A. Muniz Pedrogo
- 1Enteric Neuroscience Program, Mayo Clinic, Rochester, Minnesota; and ,2Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota
| | - Purna C. Kashyap
- 1Enteric Neuroscience Program, Mayo Clinic, Rochester, Minnesota; and ,2Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota
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28
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Shayto RH, Abou Mrad R, Sharara AI. Use of rifaximin in gastrointestinal and liver diseases. World J Gastroenterol 2016; 22:6638-6651. [PMID: 27547007 PMCID: PMC4970477 DOI: 10.3748/wjg.v22.i29.6638] [Citation(s) in RCA: 32] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/18/2016] [Revised: 06/17/2016] [Accepted: 07/06/2016] [Indexed: 02/06/2023] Open
Abstract
Rifaximin is a broad spectrum oral antibiotic with antimicrobial activity against Gram-positive and Gram-negative aerobic and anaerobic bacteria. It is poorly absorbed and thus has a highly favorable safety profile. Rifaximin has been shown to be effective in the treatment of traveler's diarrhea, functional bloating and irritable bowel syndrome, small bowel bacterial overgrowth and in the prevention of recurrent overt hepatic encephalopathy. In addition, there is emerging evidence for a possible beneficial effect of rifaximin in the treatment of uncomplicated diverticular disease and in the prevention of recurrent diverticulitis. The use of rifaximin is associated with a low incidence of development, or persistence of spontaneous bacterial mutants. Moreover, the development of important drug resistance among extra-intestinal flora during rifaximin therapy is unlikely because of minimal systemic absorption and limited cross-resistance of rifaximin with other antimicrobials. This review addresses the current and emerging role of rifaximin in the treatment of gastrointestinal and liver disorders.
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Abstract
The symptom-based diagnosis of irritable bowel syndrome (IBS) has not been established in everyday clinical practice, and the diagnosis of this disorder remains one of exclusion. It has been demonstrated that the densities of duodenal chromogranin A, rectal peptide YY and somatostatin cells are good biomarkers for the diagnosis of sporadic IBS, and low-grade mucosal inflammation is a promising biomarker for the diagnosis of postinfectious IBS. Genetic markers are not useful as biomarkers for IBS since the potential risk genes have yet to be validated, and the intestinal microbiota cannot be used because of the lack of an association between a specific bacterial species and IBS. Furthermore, gastrointestinal dysmotility and visceral hypersensitivity tests produce results that are too nonconsistent and noncharacteristic to be used in the diagnosis of IBS. A combination of symptom-based assessment, exclusion of overlapping gastrointestinal diseases and positive biomarkers appears to be the best way to diagnose IBS.
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Affiliation(s)
- Magdy El-Salhy
- a Department of Medicine, Section for Gastroenterology, Stord Hospital, Stord, Norway
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30
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Boeckxstaens G, Camilleri M, Sifrim D, Houghton LA, Elsenbruch S, Lindberg G, Azpiroz F, Parkman HP. Fundamentals of Neurogastroenterology: Physiology/Motility - Sensation. Gastroenterology 2016; 150:S0016-5085(16)00221-3. [PMID: 27144619 DOI: 10.1053/j.gastro.2016.02.030] [Citation(s) in RCA: 84] [Impact Index Per Article: 9.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/03/2016] [Accepted: 02/09/2016] [Indexed: 12/14/2022]
Abstract
The fundamental gastrointestinal functions include motility, sensation, absorption, secretion, digestion and intestinal barrier function. Digestion of food and absorption of nutrients normally occurs without conscious perception. Symptoms of functional gastrointestinal disorders are often triggered by meal intake suggesting abnormalities in the physiological processes are involved in the generation of symptoms. In this manuscript, normal physiology and pathophysiology of gastrointestinal function, and the processes underlying symptom generation are critically reviewed. The functions of each anatomical region of the digestive tract are summarized. The pathophysiology of perception, motility, mucosal barrier, and secretion in functional gastrointestinal disorders as well as effects of food, meal intake and microbiota on gastrointestinal motility and sensation are discussed. Genetic mechanisms associated with visceral pain and motor functions in health and functional gastrointestinal disorders are reviewed. Understanding the basis for digestive tract functions is essential to understand dysfunctions in the functional gastrointestinal disorders.
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Affiliation(s)
- Guy Boeckxstaens
- Department of Gastroenterology, Translational Research Center for Gastrointestinal Disorders (TARGID), University Hospital Leuven, KU Leuven, Leuven, Belgium
| | | | - Daniel Sifrim
- Wingate Institute of Neurogastroenterology, Bart's and the London School of Medicine, Queen Mary, University of London, London, UK
| | - Lesley A Houghton
- Division of Gastroenterology and Hepatology, Mayo Clinic, Jacksonville, FL, USA
| | - Sigrid Elsenbruch
- Institute of Medical Psychology and Behavioral Immunobiology, University Hospital Essen, University of Duisburg-Essen, Essen, Germany
| | - Greger Lindberg
- Department of Medicine, Karolinska Institutet, Karolinska University Hospital Huddinge, Stockholm, Sweden
| | - Fernando Azpiroz
- Digestive Diseases Department, University Hospital Vall D'Hebron, Autonomous University of Barcelona, Barcelona, Spain
| | - Henry P Parkman
- Department of Medicine, Temple University School of Medicine, Philadelphia, PA, USA.
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Gazouli M, Wouters MM, Kapur-Pojskić L, Bengtson MB, Friedman E, Nikčević G, Demetriou CA, Mulak A, Santos J, Niesler B. Lessons learned--resolving the enigma of genetic factors in IBS. Nat Rev Gastroenterol Hepatol 2016; 13:77-87. [PMID: 26726033 DOI: 10.1038/nrgastro.2015.206] [Citation(s) in RCA: 66] [Impact Index Per Article: 7.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
Abstract
IBS is the most prevalent functional gastrointestinal disorder and phenotypically characterized by chronic abdominal discomfort, pain and altered defecation patterns. The pathophysiology of IBS is multifactorial, albeit with a substantial genetic component. To date, studies using various methodologies, ranging from family and twin studies to candidate gene approaches and genome-wide association studies, have identified several genetic variants in the context of IBS. Yet, despite enlarged sample sizes, increased statistical power and meta-analyses in the past 7 years, positive associations are still scarce and/or have not been reproduced. In addition, epigenetic and pharmacogenetic approaches remain in their infancy. A major hurdle is the lack of large homogenized case-control cohorts recruited according to standardized and harmonized criteria. The COST Action BM1106 GENIEUR (GENes in Irritable Bowel Syndrome Research Network EURope) has been established to address these obstacles. In this Review, the (epi)genetic working group of GENIEUR reports on the current state-of-the-art in the field, highlights fundamental flaws and pitfalls in current IBS (epi)genetic research and provides a vision on how to address and improve (epi)genetic approaches in this complex disorder in the future.
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Affiliation(s)
- Maria Gazouli
- Department of Basic Sciences, Laboratory of Biology, School of Medicine, University of Athens, Michalakopoulou 176, 11527 Athens, Greece
| | - Mira M Wouters
- Translational Research Center for Gastrointestinal Disorders (TARGID), University Hospital Leuven, Herestraat 49, Leuven 3000, Belgium
| | - Lejla Kapur-Pojskić
- Institute for Genetic Engineering and Biotechnology, University of Sarajevo, Kemalbegova 10, 71.000 Sarajevo, Bosnia and Herzegovina
| | - May-Bente Bengtson
- Vestfold Hospital Trust, Tønsberg, Department of Internal Medicine, Division of Gastroenterology, P.O. Box 2168, 3103 Tønsberg, Norway
| | - Eitan Friedman
- The Suzanne Levy Gertner Oncogenetics Unit, Chaim Sheba Medical Centre, 52621 Tel-Hashomer, Israel
| | - Gordana Nikčević
- Laboratory for Molecular Biomedicine, Institute of Molecular Genetics and Genetic Engineering, University of Belgrade, Vojvode Stepe 444a, 23 11010 Belgrade, Serbia
| | - Christiana A Demetriou
- Department of Electron Microscopy / Molecular Pathology, The Cyprus Institute of Neurology and Genetics, P.O. Box 23462, 1683 Nicosia, Cyprus
| | - Agata Mulak
- Department of Gastroenterology and Hepatology, Wroclaw Medical University, Borowska 213, 50-556 Wroclaw, Poland
| | - Javier Santos
- Neuro-immuno-gastroenterology Lab, Digestive Diseases Research Unit, Vall d'Hebron Institut de Recerca. Department of Gastroenterology, Hospital Universitari Vall d'Hebron &Facultat de Medicina, Universitat Autònoma de Barcelona and Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas, Paseo Vall d'Hebron 119-129, 08035 Barcelona, Spain
| | - Beate Niesler
- Institute of Human Genetics, Department of Human Molecular Genetics, University of Heidelberg, Im Neuenheimer Feld 366, 69120 Heidelberg, Germany
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Makker J, Chilimuri S, Bella JN. Genetic epidemiology of irritable bowel syndrome. World J Gastroenterol 2015; 21:11353-11361. [PMID: 26525775 PMCID: PMC4616211 DOI: 10.3748/wjg.v21.i40.11353] [Citation(s) in RCA: 36] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/20/2015] [Revised: 06/16/2015] [Accepted: 08/25/2015] [Indexed: 02/06/2023] Open
Abstract
Irritable bowel syndrome (IBS) is the most common functional gastrointestinal disorder characterized by presence of abdominal pain or discomfort associated with altered bowel habits. It has three main subtypes - constipation predominant IBS (C-IBS), diarrhea predominant IBS (D-IBS) and IBS with mixed features of both diarrhea as well as constipation (M-IBS). Its pathophysiology and underlying mechanisms remain elusive. It is traditionally believed that IBS is a result of multiple factors including hypersensitivity of the bowel, altered bowel motility, inflammation and stress. Initial studies have shown familial aggregation of IBS suggesting shared genetic or environmental factors. Twin studies of IBS from different parts of world have shown higher concordance rates among monozygotic twins than dizygotic twins, and thus suggesting a genetic component to this disorder. Multiple studies have tried to link single-nucleotide polymorphisms (SNPs) to IBS but there is little evidence that these SNPs are functional. Various molecules have been studied and investigated by the researchers. Serotonin, a known neurotransmitter and a local hormone in the enteric nervous system, has been most extensively explored. At this time, the underlying gene pathways, genes and functional variants linked with IBS remain unknown and the promise of genetically-determined risk prediction and personalize medicine remain unfulfilled. However, molecular biological technologies continue to evolve rapidly and genetic investigations offer much promise in the intervention, treatment and prevention of IBS.
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El-Salhy M. Recent developments in the pathophysiology of irritable bowel syndrome. World J Gastroenterol 2015; 21:7621-7636. [PMID: 26167065 PMCID: PMC4491952 DOI: 10.3748/wjg.v21.i25.7621] [Citation(s) in RCA: 76] [Impact Index Per Article: 7.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/21/2015] [Revised: 03/31/2015] [Accepted: 05/21/2015] [Indexed: 02/06/2023] Open
Abstract
Irritable bowel syndrome (IBS) is a common gastrointestinal disorder, the pathophysiology of which is not completely known, although it has been shown that genetic/social learning factors, diet, intestinal microbiota, intestinal low-grade inflammation, and abnormal gastrointestinal endocrine cells play a major role. Studies of familial aggregation and on twins have confirmed the heritability of IBS. However, the proposed IBS risk genes are thus far nonvalidated hits rather than true predisposing factors. There is no convincing evidence that IBS patients suffer from food allergy/intolerance, with the effect exerted by diet seemingly caused by intake of poorly absorbed carbohydrates and fiber. Obesity is a possible comorbidity of IBS. Differences in the microbiota between IBS patients and healthy controls have been reported, but the association between IBS symptoms and specific bacterial species is uncertain. Low-grade inflammation appears to play a role in the pathophysiology of a major subset of IBS, namely postinfectious IBS. The density of intestinal endocrine cells is reduced in patients with IBS, possibly as a result of genetic factors, diet, intestinal microbiota, and low-grade inflammation interfering with the regulatory signals controlling the intestinal stem-cell clonogenic and differentiation activities. Furthermore, there is speculation that this decreased number of endocrine cells is responsible for the visceral hypersensitivity, disturbed gastrointestinal motility, and abnormal gut secretion seen in IBS patients.
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van Tilburg MAL, Levy RL, Walker LS, Von Korff M, Feld LD, Garner M, Feld AD, Whitehead WE. Psychosocial mechanisms for the transmission of somatic symptoms from parents to children. World J Gastroenterol 2015; 21:5532-41. [PMID: 25987776 PMCID: PMC4427675 DOI: 10.3748/wjg.v21.i18.5532] [Citation(s) in RCA: 47] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/22/2014] [Revised: 11/19/2014] [Accepted: 12/20/2014] [Indexed: 02/06/2023] Open
Abstract
AIM To examine familial aggregation of irritable bowel syndrome (IBS) via parental reinforcement/modeling of symptoms, coping, psychological distress, and exposure to stress. METHODS Mothers of children between the ages of 8 and 15 years with and without IBS were identified through the Group Health Cooperative of Puget Sound. Mothers completed questionnaires, including the Child Behavior Checklist (child psychological distress), the Family Inventory of Life Events (family exposure to stress), SCL-90R (mother psychological distress), and the Pain Response Inventory (beliefs about pain). Children were interviewed separately from their parents and completed the Pain Beliefs Questionnaire (beliefs about pain), Pain Response Inventory (coping) and Child Symptom Checklist [gastrointestinal (GI) symptoms]. In addition, health care utilization data was obtained from the automated database of Group Health Cooperative. Mothers with IBS (n = 207) and their 296 children were compared to 240 control mothers and their 335 children, while controlling for age and education. RESULTS Hypothesis 1: reinforcement of expression of GI problems is only related to GI symptoms, but not others (cold symptoms) in children. There was no significant correlation between parental reinforcement of symptoms and child expression of GI or other symptoms. Hypothesis 2: modeling of GI symptoms is related to GI but not non-GI symptom reporting in children. Children of parents with IBS reported more non-GI (8.97 vs 6.70, P < 0.01) as well as more GI (3.24 vs 2.27, P < 0.01) symptoms. Total health care visits made by the mother correlated with visits made by the child (rho = 0.35, P < 0.001 for cases, rho = 0.26, P < 0.001 for controls). Hypothesis 3: children learn to share the methods of coping with illness that their mothers exhibit. Methods used by children to cope with stomachaches differed from methods used by their mothers. Only 2/16 scales showed weak but significant correlations (stoicism rho = 0.13, P < 0.05; acceptance rho = 0.13, P < 0.05). Hypothesis 4: mothers and children share psychological traits such as anxiety, depression, and somatization. Child psychological distress correlated with mother's psychological distress (rho = 0.41, P < 0.001 for cases, rho= 0.38, P < 0.001 for controls). Hypothesis 5: stress that affects the whole family might explain the similarities between mothers and their children. Family exposure to stress was not a significant predictor of children's symptom reports. Hypothesis 6: the intergenerational transmission of GI illness behavior may be due to multiple mechanisms. Regression analysis identified multiple independent predictors of the child's GI complaints, which were similar to the predictors of the child's non-GI symptoms (mother's IBS status, child psychological symptoms, child catastrophizing, and child age). CONCLUSION Multiple factors influence the reporting of children's gastrointestinal and non-gastrointestinal symptoms. The clustering of illness within families is best understood using a model that incorporates all these factors.
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Czogalla B, Schmitteckert S, Houghton LA, Sayuk GS, Camilleri M, Olivo-Diaz A, Spiller R, Wouters MM, Boeckxstaens G, Bermejo JL, Niesler B. A meta-analysis of immunogenetic Case-Control Association Studies in irritable bowel syndrome. Neurogastroenterol Motil 2015; 27:717-27. [PMID: 25824902 DOI: 10.1111/nmo.12548] [Citation(s) in RCA: 37] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/02/2014] [Accepted: 02/18/2015] [Indexed: 12/17/2022]
Abstract
BACKGROUND To date, genetic-association studies of single nucleotide polymorphisms (SNP) in selected candidate genes with the symptom phenotype of irritable bowel syndrome (IBS) have typically involved hundreds to 2000 patients. SNPs in immune-related genes, such as cytokine and cytokine receptor encoding genes, have been reported to associate with IBS risk. METHODS We conducted two independent case-control studies on 16 SNPs in IL1R1, IL4, IL6, IL8, IL10, IL23R, TNFA, and TNFSF15, one from the UK (194 patients and 92 healthy volunteers) and one from the USA (137 patients and 96 healthy volunteers). The main aim was to examine the relationship between inherited immunological diversity and IBS risk in a meta-analysis which included 12 additional, earlier studies. The meta-analysis comprised a total of 2894 patients (839 IBS-C, 1073 IBS-D, 502 IBS-M), and 3138 healthy volunteers with self-reported Caucasian ancestry. KEY RESULTS The association of SNP rs4263839 (TNFSF15) was investigated in four studies and confirmed in the meta-analysis: IBS (OR 1.19, 95% CI 1.08-1.31), and IBS-C (OR 1.24, 95% CI 1.08-1.42). No additional SNPs residing in immunogenes associated with IBS symptom phenotypes. CONCLUSIONS & INFERENCES Our meta-analysis could not confirm a major role of most investigated SNPs, but a moderate association between rs4263839 TNFSF15 and IBS, in particular IBS-C. The analysis emphasizes the importance of definition and phenotype homogeneity, adequate study size and representativeness of the patient and control collective.
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Affiliation(s)
- B Czogalla
- Institute of Human Genetics, Department of Human Molecular Genetics, University of Heidelberg, Heidelberg, Germany
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Chang JY, Locke GR, Schleck CD, Zinsmeister AR, Talley NJ. Lack of familial aggregation in chronic constipation excluding irritable bowel syndrome: a population-based study. Dig Dis Sci 2015; 60:1358-65. [PMID: 25532498 PMCID: PMC4526026 DOI: 10.1007/s10620-014-3475-x] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/04/2014] [Accepted: 11/28/2014] [Indexed: 12/17/2022]
Abstract
BACKGROUND Despite strong evidence supporting a genetic and gene-environment interaction in the irritable bowel syndrome (IBS), the role of genes and early life in another common functional bowel disorder, chronic constipation (CC), have been little studied. AIM To determine whether familial aggregation occurs in CC and whether risk factors differed in those with family members. METHODS A randomly selected population-based cohort from Olmsted County, MN, was surveyed (n = 8,006); 3,831 completed questionnaires (response rate 48 %). Cases were identified based upon their responses to a validated questionnaire and meeting Rome criteria for CC. Controls were matched one to one by age and gender. IBS (by Rome II criteria) was excluded. Recruitment of case and control probands occurred in 2010-2011 by mailing a family information form; then, first-degree relatives (FDR) were mailed a questionnaire. All potential proband participants were not informed of CC status. RESULTS Overall 1,185 cases who met criteria for CC without symptoms of IBS and 1,185 controls were surveyed; 309 case and 336 control probands provided data. The proportion of family members having CC was not associated with case status, and the constipation status of FDR was not significantly associated with case-controls status of the respective probands. Symptom burden in FDR was associated with gender and SSC score, but not age or proband status. CONCLUSIONS No evidence of familial aggregation was observed in adults from the community with CC (excluding IBS). Our data suggest environmental factors in later life more likely account for adult CC.
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Affiliation(s)
- Joseph Y. Chang
- Department of Gastroenterology, Southlake Clinic, Renton, WA
| | - G. Richard Locke
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN
| | - Cathy D. Schleck
- Division of Biomedical Statistics and Informatics, Mayo Clinic, Rochester, MN
| | - Alan R. Zinsmeister
- Division of Biomedical Statistics and Informatics, Mayo Clinic, Rochester, MN
| | - Nicholas J. Talley
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN,Faculty of Health & Medicine, University of Newcastle, New Lambton, NSW, Australia
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Abstract
INTRODUCTION To assess the potential association between serotonin transporter gene insertion/deletion polymorphism and the cancer-related constipation phenotype. MATERIAL AND METHODS A total of 120 patients diagnosed with malignant solid tumors were subjected to genotyping. For the two groups - patients with constipation and constipation-free patients with non-gastrointestinal cancer, 60 cases in each group - we collected the peripheral venous blood. We extracted genomic DNA, and used polymerase chain reaction (PCR) to analyze the serotonin transporter (5-HT) link polymorphic region (5-HTTLPR) polymorphism of the serotonin transporter gene. RESULTS The frequency of S/S genotype in cancer patients with constipation was 66.67% (40/60), and the frequency of the S allele was 79.17% (95/120); the frequency of S/S genotype in cancer patients without constipation was 48.33% (29/60), and the frequency of the S allele was 65.83% (79/120). There was a significant difference between the two groups (p < 0.05). CONCLUSIONS The presence of 5-HTTLPRS/S genotype and the S allele in patients with cancers probably carry an increased risk of constipation. However, its role as a cause of cancer-related constipation needs to be further investigated.
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Bengtson MB, Aamodt G, Vatn MH, Harris JR. Co-occurrence of IBS and symptoms of anxiety or depression, among Norwegian twins, is influenced by both heredity and intrauterine growth. BMC Gastroenterol 2015; 15:9. [PMID: 25649866 PMCID: PMC4321711 DOI: 10.1186/s12876-015-0237-y] [Citation(s) in RCA: 33] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/20/2014] [Accepted: 01/20/2015] [Indexed: 12/15/2022] Open
Abstract
Background Environmental and genetic factors contribute to variation in irritable bowel syndrome (IBS), anxiety and depression. Comorbidity between these disorders is high. A previous investigation of our population-based twin cohort revealed that low birth weight increased the risk for development of IBS, with environmental influences in utero as the most relevant contributing factor. We hypothesise that both intrauterine and genetic factors influence the co-occurrence of IBS and symptoms of anxiety and depression. Methods A postal questionnaire sent to 12700 Norwegian twins born between 1967 and 1979 comprised a checklist of 31 illnesses and symptoms, including IBS and symptoms of anxiety and depression. The influence of genetic factors and intrauterine growth on comorbidity between these disorders were analysed in the full sample and compared to those based on only monozygotic (MZ) twin pairs discordant for IBS (95 pairs) in birth weight group < 2500 g and ≥ 2500 g. Results In the co-twin analyses restricted growth (birth weight < 2500 g) was significantly associated with anxiety and depression (average birth weight difference of 181.0 g (p <0.0001) and 249.9 g (p < 0.0001), respectively). The analysis of the full sample revealed that IBS was significantly associated with symptoms of anxiety (adjusted OR = 2.5, 95% CI: 1.9, 3.3) and depression (adjusted OR = 2.3. 95% CI: 1.8, 3.0). Analyses of MZ pairs discordant for IBS indicated significant associations between IBS and symptoms of anxiety (OR = 3.7, 95% CI: 1.3, 10.5) and between IBS and symptoms of depression (OR = 4.2, 95% CI: 1.7, 9.9) only in the birth weight group below 2500 g. Conclusion Our findings suggest that genetic factors partly explain the association between IBS and symptoms of anxiety and depression. In the low range of birth weight (<2500 g), restricted fetal growth seems to be a common contributing factor to the co-occurrence between these disorders.
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Affiliation(s)
- May-Bente Bengtson
- Medical Department, Vestfold Hospital Trust, PO Box 2168, 3103, Tønsberg, Norway. .,EpiGen-Institute, Faculty Division Akershus University Hospital, University of Oslo, Oslo, Norway.
| | - Geir Aamodt
- Norwegian University of Life Sciences, PO Box 5003, 1432, Ås, Norway.
| | - Morten H Vatn
- EpiGen-Institute, Faculty Division Akershus University Hospital, University of Oslo, Oslo, Norway.
| | - Jennifer R Harris
- Division of Epidemiology, The Norwegian Institute of Public Health, Oslo, Norway.
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Waehrens R, Ohlsson H, Sundquist J, Sundquist K, Zöller B. Risk of irritable bowel syndrome in first-degree, second-degree and third-degree relatives of affected individuals: a nationwide family study in Sweden. Gut 2015; 64:215-21. [PMID: 24694578 DOI: 10.1136/gutjnl-2013-305705] [Citation(s) in RCA: 40] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
OBJECTIVES IBS aggregates in families, but the familial risk of IBS has only been determined in first-degree relatives and spouses. This nationwide study aimed to determine the familial risk of IBS in first-degree, second-degree, and third-degree relatives and spouses of affected individuals in order to estimate the relative influences of genes and shared family environment. METHODS We performed a case-cohort study. The Swedish Multigeneration Register was linked to the Hospital Discharge Register for the period 1987-2010 and the Swedish Outpatient Care Register for 2001-2010. ORs for IBS were calculated for relatives of individuals who had been diagnosed with IBS compared with relatives of individuals unaffected by IBS as the reference group. ORs were also determined for IBS cases diagnosed in primary healthcare in four Swedish counties (2001-2007). RESULTS The ORs for IBS were 1.75 in siblings (95% CI 1.63 to 1.89), 1.82 in offspring (1.67 to 1.97), 1.90 in parents (1.76 to 2.05), 1.10 in maternal half-siblings (0.88 to 1.39), 1.78 in paternal half-siblings (1.48 to 2.15), 1.27 in nieces/nephews (1.18 to 1.38), 1.11 in cousins (1.04 to 1.18), and 1.51 in spouses (1.24 to 1.84) of probands diagnosed with IBS. The OR for probands diagnosed in primary healthcare was 1.82 in siblings (1.52 to 2.18), and 1.82 in offspring (1.49 to 2.21). CONCLUSIONS The increased IBS risk among first-degree relatives and also second-degree and third-degree relatives indicates a genetic component of the familial clustering of IBS. However, a non-genetic contribution is also suggested by the increased risk among spouses.
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Affiliation(s)
- Rasmus Waehrens
- Center for Primary Health Care Research, Lund University/Region Skåne, Malmö, Sweden
| | - Henrik Ohlsson
- Center for Primary Health Care Research, Lund University/Region Skåne, Malmö, Sweden
| | - Jan Sundquist
- Center for Primary Health Care Research, Lund University/Region Skåne, Malmö, Sweden Stanford Prevention Research Center, Stanford University School of Medicine, Palo Alto, California, USA
| | - Kristina Sundquist
- Center for Primary Health Care Research, Lund University/Region Skåne, Malmö, Sweden Stanford Prevention Research Center, Stanford University School of Medicine, Palo Alto, California, USA
| | - Bengt Zöller
- Center for Primary Health Care Research, Lund University/Region Skåne, Malmö, Sweden
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Chung HA, Lee SY, Lee HJ, Kim JH, Sung IK, Shim CS, Jin CJ, Park HS. G protein β3 subunit polymorphism and long-term prognosis of functional dyspepsia. Gut Liver 2014; 8:271-6. [PMID: 24827623 PMCID: PMC4026644 DOI: 10.5009/gnl.2014.8.3.271] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/01/2023] Open
Abstract
Background/Aims A link between G protein β3 (GNB3) polymorphism and functional dyspepsia (FD) has been suggested. The aim of this study was to determine the role of GNB3 polymorphism in the long-term prognosis of FD in Koreans. Methods FD patients and normal healthy controls were recruited from patients who visited our center between December 2006 and June 2007. All of the subjects completed Rome III questionnaires before undergoing upper gastrointestinal endoscopy and colonoscopy. Genomic DNA was extracted for GNB3 genotyping. After 5 years, the subjects were reevaluated using the same questionnaires. Results GNB3 825T carrier status was significantly related to FD in Koreans (p=0.04). After 5 years, 61.0% of the initial FD patients and 12.2% of the initial normal subjects were diagnosed with FD (odds ratio [OR], 11.7; 95% confidence interval [CI], 4.3 to 31.1; p<0.001). Regardless of the GNB3 genotype (p=0.798), female sex was strongly correlated with FD after 5 years (OR, 3.3; 95% CI, 1.2 to 9.1; p=0.017). Conclusions The T allele of GNB3 is linked to FD in Koreans but does not predict long-term prognosis. Female sex is related to a higher prevalence of FD after 5 years.
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Affiliation(s)
- Hyun Ah Chung
- Department of Internal Medicine, Konkuk University School of Medicine, Seoul, Korea
| | - Sun Young Lee
- Department of Internal Medicine, Konkuk University School of Medicine, Seoul, Korea
| | - Heon Jeong Lee
- Department of Psychiatry, Korea University College of Medicine, Seoul, Korea
| | - Jeong Hwan Kim
- Department of Internal Medicine, Konkuk University School of Medicine, Seoul, Korea
| | - In Kyung Sung
- Department of Internal Medicine, Konkuk University School of Medicine, Seoul, Korea
| | - Chan Sup Shim
- Department of Internal Medicine, Konkuk University School of Medicine, Seoul, Korea
| | - Choon Jo Jin
- Department of Internal Medicine, Konkuk University School of Medicine, Seoul, Korea
| | - Hyung Seok Park
- Department of Internal Medicine, Konkuk University School of Medicine, Seoul, Korea
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Shraim M, Blagojevic-Bucknall M, Mallen CD, Dunn KM. Repeated primary care consultations for non-specific physical symptoms in children in UK: a cohort study. BMC FAMILY PRACTICE 2014; 15:195. [PMID: 25477255 PMCID: PMC4261613 DOI: 10.1186/s12875-014-0195-4] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 09/04/2014] [Accepted: 11/12/2014] [Indexed: 02/02/2023]
Abstract
BACKGROUND Non-specific physical symptoms (NSPS), such as headache and abdominal pain, are common reasons for children to consult primary care. NSPS represent a significant burden not only on society, but also on health care services, through frequent physician consultations and referrals to secondary care. Research evidence suggests a positive relationship between health and consulting behavior of parents and their children, but research on whether repeated physician consultations for NSPS in children is influenced by parental consultations for NSPS is lacking. The aim was to measure the frequency of repeated physician consultations for NSPS in children, and investigate whether this is influenced by maternal consultations for NSPS. METHODS A cohort study of children registered with primary care practices contributing to the Consultation in Primary Care Archive database. Participants were child-mother pairs registered between January 2007 and December 2010. The cohort comprised all children (n = 1437) aged 2 to 16 years who consulted a physician for NSPS in 2009. Mothers' consultations for NSPS were measured between 2007 and 2008. Main outcome measures were repetition and frequency of consultations for NSPS in children (consultations for NSPS in both 2009 and 2010). RESULTS Overall, 27% of children had repeated consultations for NSPS. The three most common repeated consultations were for back pain, constipation and abdominal pain. Exposure to maternal consultation for NSPS was associated with 21% increase in consultation frequency for NSPS (adjusted incidence rate ratio 1.21; 95% CI 1.12, 1.31). After adjusting for child age and maternal age, maternal consultation for NSPS was associated with an increased risk of repeated consultations for NSPS in children (relative risk 1.41; 95% CI 1.16, 1.73). This association was also significant for specific NSPS groups including painful, gastrointestinal, and neurologic symptoms. CONCLUSIONS Repeated consultation for NSPS is common among children. It is important for primary care physicians and secondary care clinicians, managing children referred from primary care for NSPS, to be aware that consultation for NSPS in mothers is a risk factor for repeated consultations for NSPS among children. More research is needed to uncover exactly how parental health influences health and consulting behavior of children.
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Affiliation(s)
- Mujahed Shraim
- Arthritis Research UK Primary Care Centre, Keele University, Keele, UK. .,Work Environment Department, University of Massachusetts Lowell, Lowell, Massachusetts, USA. .,Center for Disability Research, Liberty Mutual Research Institute for Safety, Hopkinton, Massachusetts, USA.
| | | | | | - Kate M Dunn
- Arthritis Research UK Primary Care Centre, Keele University, Keele, UK.
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Srinath A, Young E, Szigethy E. Pain management in patients with inflammatory bowel disease: translational approaches from bench to bedside. Inflamm Bowel Dis 2014; 20:2433-49. [PMID: 25208108 DOI: 10.1097/mib.0000000000000170] [Citation(s) in RCA: 65] [Impact Index Per Article: 5.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
Abdominal pain is a common symptom in patients with inflammatory bowel disease (IBD) that negatively affects quality of life and can lead to increased health-seeking behavior. Although abdominal pain has been traditionally attributed to inflammation, there is growing literature demonstrating the existence of functional abdominal pain in patients with IBD, of which there are a variety of potential causes. Thus, when approaching a patient with IBD who has abdominal pain, in addition to IBD-related complications (e.g., inflammation/stricture), it is important to screen for related contributors, including peripheral factors (visceral hypersensitivity, bacterial overgrowth, and bowel dysmotility) and centrally mediated neurobiological and psychosocial underpinnings. These central factors include psychological symptoms/diagnoses, sleep disturbance, and stress. Opioid-induced hyperalgesia (e.g., narcotic bowel syndrome) is also growing in recognition as a potential central source of abdominal pain. This review draws from clinical studies and animal models of colitis and abdominal pain to consider how knowledge of these potential etiologies can be used to individualize treatment of abdominal pain in patients with IBD, including consideration of potential novel treatment modalities for the future. Accurate assessment of the source(s) of pain in patients with IBD can help guide appropriate diagnostic workup and use of disease-modifying therapy.
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Affiliation(s)
- Arvind Srinath
- *Department of Pediatric Gastroenterology, Children's Hospital of UPMC, Pittsburgh, Pennsylvania; †Department of Anesthesiology, University of Pittsburgh, Pittsburgh, Pennsylvania; and ‡Department of Psychiatry, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania
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Shraim M, Blagojevic-Bucknall M, Mallen CD, Dunn KM. The association between GP consultations for non-specific physical symptoms in children and parents: a case-control study. PLoS One 2014; 9:e108039. [PMID: 25251344 PMCID: PMC4176724 DOI: 10.1371/journal.pone.0108039] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/06/2014] [Accepted: 08/25/2014] [Indexed: 11/19/2022] Open
Abstract
BACKGROUND Non-specific physical symptoms (NSPS) such as abdominal pain, headache and musculoskeletal pain are widespread in the community, and are common reasons for visiting a general practitioner (GP). Causes of NSPS are multifactorial, but may include parental influences. OBJECTIVE To investigate associations between GP consultations for NSPS in parents and their children. METHODS Matched case-control study using GP consultation data from 12 GP practices in the United Kingdom. Participants were 1328 children who consulted a GP for NSPS in 2009 (cases), 3980 controls who consulted a GP in 2009 but not for NSPS, plus parents of cases and controls (n = 8354). PRIMARY OUTCOME MEASURE child consultation status for NSPS. RESULTS Maternal consultation for NSPS was associated with significantly increased odds of their child consulting for NSPS (odds ratio (OR) 1.51, 95% confidence intervals (CI) 1.33, 1.73); there was no significant association with paternal consultations (OR 0.87, 95% CI 0.71, 1.08). Each additional maternal consultation for NSPS was associated with an increase in the rate ratio for number of consultations for NSPS in the child by 1.03 (95% CI 1.01, 1.05). This overall association was clearest in maternal-child consultations for painful NSPS and for specific bodily systems including gastrointestinal, musculoskeletal and neurologic symptoms. CONCLUSIONS Maternal GP consultation for NSPS is associated with increased odds of GP consultations for NSPS in children. This study included a large sample of children and parents and used medical records data which is not subject to recall bias. However, analysis was based on medical records, thus the presence of NSPS not leading to consultations is unknown. Medical practitioners managing children with NSPS need to be aware of this association.
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Affiliation(s)
- Mujahed Shraim
- Arthritis Research UK Primary Care Centre, Keele University, Keele, United Kingdom
- Work Environment Department, University of Massachusetts Lowell, Lowell, Massachusetts, United States of America
- Center for Disability Research, Liberty Mutual Research Institute for Safety, Hopkinton, Massachusetts, United States of America
| | | | - Christian D. Mallen
- Arthritis Research UK Primary Care Centre, Keele University, Keele, United Kingdom
| | - Kate M. Dunn
- Arthritis Research UK Primary Care Centre, Keele University, Keele, United Kingdom
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EL-SALHY MAGDY, GILJA ODDHELGE, GUNDERSEN DORIS, HATLEBAKK JANG, HAUSKEN TRYGVE. Interaction between ingested nutrients and gut endocrine cells in patients with irritable bowel syndrome (review). Int J Mol Med 2014; 34:363-71. [PMID: 24939595 PMCID: PMC4094590 DOI: 10.3892/ijmm.2014.1811] [Citation(s) in RCA: 27] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/31/2013] [Accepted: 02/10/2014] [Indexed: 12/15/2022] Open
Abstract
Several endocrine cell abnormalities have been reported in different segments of the gastrointestinal tract of patients with irritable bowel syndrome (IBS). These cells have specialized microvilli that project into the lumen; they function as sensors for the gut contents and respond to luminal stimuli (mostly ingested nutrients) by releasing hormones into the lamina propria, where they exert their effects via a paracrine/endocrine mode of action. Certain food items trigger the symptoms experienced by IBS patients, including those rich in fermentable oligo-, di- and monosaccharides, and polyols (FODMAPs). In this review, we present the argument that the effects of both FODMAPs and the proportional intake of proteins, fats and carbohydrates on IBS symptoms may be caused by an interaction with the gut endocrine cells. Since the gut hormones control and regulate gastrointestinal motility and sensation, this interaction may be responsible for abnormal gastrointestinal motility and the visceral hypersensitivity observed in these patients. There is no consistent evidence that IBS patients suffer from food allergy. The role of gluten intolerance in the development of IBS symptoms in these patients remains a matter of controversy. Individual guidance on food management, which includes restrictions in the intake of FODMAP-rich foods and testing diets with different proportions of proteins, fats and carbohydrates has been found to reduce the symptoms, improve the quality of life, and make the habitual diet of IBS patients more healthy.
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Affiliation(s)
- MAGDY EL-SALHY
- Section of Gastroenterology, Department of Medicine, Stord Helse-Fonna Hospital, University of Bergen, Bergen, Norway
- Section of Gastroenterology, Department of Clinical Medicine, University of Bergen, Bergen, Norway
| | - ODD HELGE GILJA
- Section of Gastroenterology, Department of Clinical Medicine, University of Bergen, Bergen, Norway
- National Centre for Ultrasound in Gastroenterology, Department of Medicine, Haukeland University Hospital, Bergen, Norway
| | | | - JAN G. HATLEBAKK
- Section of Gastroenterology, Department of Clinical Medicine, University of Bergen, Bergen, Norway
| | - TRYGVE HAUSKEN
- Section of Gastroenterology, Department of Clinical Medicine, University of Bergen, Bergen, Norway
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Dai F, Liu Y, Shi H, Ge S, Song J, Dong L, Yang J. Association of genetic variants in GNβ3 with functional dyspepsia: a meta-analysis. Dig Dis Sci 2014; 59:1823-30. [PMID: 24557575 PMCID: PMC4119519 DOI: 10.1007/s10620-014-3057-y] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/08/2013] [Accepted: 02/05/2014] [Indexed: 02/08/2023]
Abstract
BACKGROUND Functional dyspepsia (FD) is a functional upper gastrointestinal disorder. The etiology and pathogenesis of FD remain unclear, with genetic factors playing an important role. Previous studies investigated the association of C825T in GNβ3 with FD, with conflicting results reported. AIMS The aim of this meta-analysis is to assess the association of genetic variants in GNβ3 with FD. METHODS We performed a systematic literature search in PubMed, Cochrane Library, Google Scholar, and Web of Knowledge, and conducted a meta-analysis to assess the association of C825T in GNβ3 with FD. For sensitivity analysis, we analyzed the association between C825T and subtypes of FD. We also performed meta-analyses separately for individual ethnic groups/countries of origin. RESULTS A total of eight studies met the eligibility criteria and were included in our analyses. Our meta-analysis finds no association between 825CC and FD (OR 1.19, 95% CI 0.84-1.67, p = 0.328). However, the association is significant under an additive model (OR 0.59, 95% CI 0.38-0.92, p = 0.018). Sensitivity analysis indicated a significant association of C825T with FD in participants from Korea but not in those from Japan, Europe, or the United States. We also detected a significant association of this SNP with dysmotility. CONCLUSIONS The genetic variant C825T in GNβ3 is significantly associated with FD under an additive model and the association is race-specific. Further studies with larger samples sizes are needed to validate our findings and to explore the potential mechanism underlying the association.
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Affiliation(s)
- Fei Dai
- Division of Gastroenterology, Second Affiliated Hospital, Medical College of Xi’an Jiaotong University, Xi’an, Shaanxi 710004, China
| | - Yaping Liu
- Division of Gastroenterology, First Affiliated Hospital, Medical College of Xi’an Jiaotong University, Xi’an, Shaanxi 710061, China
| | - Haitao Shi
- Division of Gastroenterology, Second Affiliated Hospital, Medical College of Xi’an Jiaotong University, Xi’an, Shaanxi 710004, China
| | - Shuqiong Ge
- Division of Gastroenterology, Second Affiliated Hospital, Medical College of Xi’an Jiaotong University, Xi’an, Shaanxi 710004, China
| | - Jun Song
- Division of Gastroenterology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430022, China
| | - Lei Dong
- Division of Gastroenterology, Second Affiliated Hospital, Medical College of Xi’an Jiaotong University, Xi’an, Shaanxi 710004, China
| | - Jingyun Yang
- Rush Alzheimer’s Disease Center & Department of Neurological Sciences, Rush University Medical Center, Chicago, IL 60612, USA
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Wouters MM, Lambrechts D, Knapp M, Cleynen I, Whorwell P, Agréus L, Dlugosz A, Schmidt PT, Halfvarson J, Simrén M, Ohlsson B, Karling P, Van Wanrooy S, Mondelaers S, Vermeire S, Lindberg G, Spiller R, Dukes G, D'Amato M, Boeckxstaens G. Genetic variants in CDC42 and NXPH1 as susceptibility factors for constipation and diarrhoea predominant irritable bowel syndrome. Gut 2014; 63:1103-11. [PMID: 24041540 DOI: 10.1136/gutjnl-2013-304570] [Citation(s) in RCA: 48] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
OBJECTIVE The complex genetic aetiology underlying irritable bowel syndrome (IBS) needs to be assessed in large-scale genetic studies. Two independent IBS cohorts were genotyped to assess whether genetic variability in immune, neuronal and barrier integrity genes is associated with IBS. DESIGN 384 single nucleotide polymorphisms (SNPs) covering 270 genes were genotyped in an exploratory cohort (935 IBS patients, 639 controls). 33 SNPs with Puncorrected<0.05 were validated in an independent set of 497 patients and 887 controls. Genotype distributions of single SNPs were assessed using an additive genetic model in IBS and clinical subtypes, IBS-C and IBS-D, both in individual and combined cohorts. Trait anxiety (N=614 patients, 533 controls), lifetime depression (N=654 patients, 533 controls) and mRNA expression in rectal biopsies (N=22 patients, 29 controls) were correlated with SNP genotypes. RESULTS Two SNPs associated independently in the exploratory and validation cohort: rs17837965-CDC42 with IBS-C (ORexploratory=1.59 (1.05 to 1.76); ORvalidation=1.76 (1.03 to 3.01)) and rs2349775-NXPH1 with IBS-D (ORexploratory=1.28 (1.06 to 1.56); ORvalidation=1.42 (1.08 to 1.88)). When combining both cohorts, the association of rs2349775 withstood post hoc correction for multiple testing in the IBS-D subgroup. Additionally, three SNPs in immune-related genes (rs1464510-LPP, rs1881457-IL13, rs2104286-IL2RA), one SNP in a neuronal gene (rs2349775-NXPH1) and two SNPs in epithelial genes (rs245051-SLC26A2, rs17837965-CDC42) were weakly associated with total-IBS (Puncorrected<0.05). At the functional level, rs1881457 increased IL13 mRNA levels, whereas anxiety and depression scores did not correlate with rs2349775-NXPH1. CONCLUSIONS Rs2349775 (NXPH1) and rs17837965 (CDC42) were associated with IBS-D and IBS-C, respectively, in two independent cohorts. Further studies are warranted to validate our findings and to determine the mechanisms underlying IBS pathophysiology.
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Affiliation(s)
- Mira M Wouters
- Translational Research Center for Gastrointestinal Disorders, Leuven University, Leuven, Belgium
| | - Diether Lambrechts
- Vesalius Research Center, VIB, Leuven University, Leuven, Belgium Laboratory for Translational Genetics, Department of Oncology, Leuven University, Leuven, Belgium
| | - Michael Knapp
- Institute for Medical Biometry, Informatics and Epidemiology, University of Bonn, Bonn, Germany
| | - Isabelle Cleynen
- Translational Research Center for Gastrointestinal Disorders, Leuven University, Leuven, Belgium
| | - Peter Whorwell
- Department of Medicine, University of Manchester, Manchester, UK
| | - Lars Agréus
- Centre for Family Medicine, Karolinska Institutet, Stockholm, Sweden
| | - Aldona Dlugosz
- Department of Medicine, Karolinska Institutet, Stockholm, Sweden
| | | | - Jonas Halfvarson
- Department of Internal Medicine, Örebro University Hospital, Örebro, Sweden
| | - Magnus Simrén
- Department of Internal Medicine, Gothenburg University, Gothenburg, Sweden
| | - Bodil Ohlsson
- Department of Clinical Sciences, Skånes University Hospital, Malmoe, Sweden
| | | | - Sander Van Wanrooy
- Translational Research Center for Gastrointestinal Disorders, Leuven University, Leuven, Belgium
| | - Stéphanie Mondelaers
- Translational Research Center for Gastrointestinal Disorders, Leuven University, Leuven, Belgium
| | - Severine Vermeire
- Translational Research Center for Gastrointestinal Disorders, Leuven University, Leuven, Belgium
| | - Greger Lindberg
- Department of Medicine, Karolinska Institutet, Stockholm, Sweden
| | | | - George Dukes
- Academic DPU, GlaxoSmithKline, Research Triangle Par, North Carolina, USA
| | - Mauro D'Amato
- Department of Biosciences and Nutrition, Karolinska Institutet, Stockholm, Sweden
| | - Guy Boeckxstaens
- Translational Research Center for Gastrointestinal Disorders, Leuven University, Leuven, Belgium
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El-Salhy M, Hatlebakk JG, Gilja OH, Hausken T. Irritable bowel syndrome: recent developments in diagnosis, pathophysiology, and treatment. Expert Rev Gastroenterol Hepatol 2014; 8:435-43. [PMID: 24580043 DOI: 10.1586/17474124.2014.888952] [Citation(s) in RCA: 36] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
The diagnosis of irritable bowel syndrome (IBS) remains a diagnosis of exclusion, whereby an extensive investigation is performed to exclude other organic diseases that may explain the symptoms of patients. Attempts to have a positive diagnosis based on symptom assessments failed to achieve widely use in clinical practice. Abnormalities in the gastrointestinal endocrine cells in IBS patients have been reported recently, providing evidence that IBS is an organic disorder, and opening the door to the use of these abnormalities as markers for a positive diagnosis of IBS. New and promising drugs for the treatment of IBS with constipation as the predominant symptom are currently on the market, and the treatment results have been satisfactory thus far.
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Affiliation(s)
- Magdy El-Salhy
- Department of Medicine, Section for Gastroenterology, Stord Hospital, Stord, Norway
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48
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Abstract
Irritable bowel syndrome (IBS) is a functional condition of the bowel that is diagnosed using clinical criteria. This paper discusses the nature of the diagnostic process for IBS and how this impacts epidemiological measurements. Depending on the diagnostic criteria employed, IBS affects around 11% of the population globally. Around 30% of people who experience the symptoms of IBS will consult physicians for their IBS symptoms. These people do not have significantly different abdominal symptoms to those who do not consult, but they do have greater levels of anxiety and lower quality of life. Internationally, there is a female predominance in the prevalence of IBS. There is 25% less IBS diagnosed in those over 50 years and there is no association with socioeconomic status. IBS aggregates within families and the genetic and sociological factors potentially underlying this are reviewed. Patients diagnosed with IBS are highly likely to have other functional disease and have more surgery than the general population. There is no evidence that IBS is associated with an increased mortality risk. The epidemiological evidence surrounding these aspects of the natural history is discussed.
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Affiliation(s)
- Caroline Canavan
- Division of Epidemiology and Public Health, University of Nottingham, Nottingham, UK
| | - Joe West
- Division of Epidemiology and Public Health, University of Nottingham, Nottingham, UK
| | - Timothy Card
- Division of Epidemiology and Public Health, University of Nottingham, Nottingham, UK
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49
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GP consultations for medically unexplained physical symptoms in parents and their children: a systematic review. Br J Gen Pract 2014; 63:e318-25. [PMID: 23643229 PMCID: PMC3635577 DOI: 10.3399/bjgp13x667178] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/31/2022] Open
Abstract
BACKGROUND There is evidence of an association of medically unexplained physical symptoms (MUPS) between parents and children, but it is unclear whether this association is also present for GP consultations. AIM To review the literature investigating the association of GP consultations for MUPS between parents and children. DESIGN OF STUDY Systematic review. METHOD Systematic search of MEDLINE(®), Embase, CINAHL, and PsycINFO databases from their inception to October 2012. Observational studies examining the association of GP consultations for MUPS between parents and children were included. RESULTS Eight studies were included in the review. Three studies found significant associations between GP consultations for multiple MUPS between parents and children. Two studies reported significant associations between irritable bowel syndrome diagnosis in parents and multiple MUPS in children. One study showed no significant associations between multiple MUPS in mothers and functional abdominal pain in children. Two studies investigated the association of non-specific low back pain in parents and children; one study showed a significant association, whereas the other study found no significant association. Formal pooling of the results was not performed owing to a high degree of study heterogeneity. CONCLUSION This review provides evidence of an association between GP consultations for MUPS in parents and children, although the evidence is limited by some potential biases and study heterogeneity. GPs need to be aware of this association, which has implications for management of children presenting with MUPS. More longitudinal research focusing on all common MUPS in children, which relies on more precise sources of data, is needed to further investigate this association.
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50
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El-Salhy M, Gundersen D, Gilja OH, Hatlebakk JG, Hausken T. Is irritable bowel syndrome an organic disorder? World J Gastroenterol 2014; 20:384-400. [PMID: 24574708 PMCID: PMC3923014 DOI: 10.3748/wjg.v20.i2.384] [Citation(s) in RCA: 72] [Impact Index Per Article: 6.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/27/2013] [Revised: 11/05/2013] [Accepted: 11/13/2013] [Indexed: 02/06/2023] Open
Abstract
Irritable bowel syndrome (IBS) is a common gastrointestinal disorder that is generally considered to be functional because there appears to be no associated anatomical defect. Stress and psychological factors are thought to play an important role in IBS. The gut neuroendocrine system (NES), which regulates all functions of the gastrointestinal tract, consists of endocrine cells that are scattered among the epithelial cells of the mucosa, and the enteric nervous system. Although it is capable of operating independently from the central nervous system (CNS), the gut NES is connected to and modulated by the CNS. This review presents evidence for the presence of an anatomical defect in IBS patients, namely in the gastrointestinal endocrine cells. These cells have specialized microvilli that project into the lumen and function as sensors for the luminal content and respond to luminal stimuli by releasing hormones into the lamina propria, which starts a chain reaction that progresses throughout the entire NES. The changes in the gastrointestinal endocrine cells observed in IBS patients are highly consistent with the other abnormalities reported in IBS patients, such as visceral hypersensitivity, dysmotility, and abnormal secretion.
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