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Cuende-Estévez M, Hussein H, Pia F, Backaert W, Van Gerven L, Aguilera-Lizarraga J, Boeckxstaens GE. Increased Allergic Rhinitis Prevalence and Symptom Severity in Patients With Irritable Bowel Syndrome. Neurogastroenterol Motil 2025:e70108. [PMID: 40516111 DOI: 10.1111/nmo.70108] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/03/2025] [Revised: 05/30/2025] [Accepted: 06/04/2025] [Indexed: 06/16/2025]
Abstract
BACKGROUND Patients with irritable bowel syndrome (IBS) have an increased risk of developing both airway and allergic diseases. However, the relationship between allergic rhinitis (AR), one of the most common chronic upper airway inflammatory diseases, and IBS remains poorly understood. The aim of this study is to provide a better understanding of airway complications in patients with IBS and to evaluate the presence of potential airborne and dietary antigen cross-reactivity in concomitant IBS and AR. METHODS A total of 287 participants, 54 healthy volunteers without gastrointestinal complaints and 232 patients with I fulfilling Rome IV criteria, were invited to complete self-administered questionnaires assessing the severity of upper airway symptoms and the prevalence of allergic rhinitis. RESULTS Overall, patients with IBS had a threefold higher risk of questionnaire-based allergic rhinitis than control subjects (95% CI, 1.49-6.12). Furthermore, patients with IBS + AR showed reduced sleep quality, mood, and personal satisfaction associated with their upper airway complaints, compared to IBS patients without AR. Forty-seven (18/38) percent of IBS + AR patients reported IBS symptoms in response to ingestion of food items with molecular mimicry of the aeroallergen to which the patient is sensitized. CONCLUSION Our study shows that patients with IBS have an increased frequency of concomitant allergic rhinitis, which contributes to a further reduction in quality of life. We also provide evidence of potential cross-reactive reactions between aeroallergens and dietary antigens in patients with concomitant IBS and AR.
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Affiliation(s)
- María Cuende-Estévez
- Department of Chronic Diseases and Metabolism (CHROMETA), Center for Intestinal Neuroimmune Interactions, Translational Research Center for Gastrointestinal Disorders (TARGID), KU Leuven, Leuven, Belgium
| | - Hind Hussein
- Department of Chronic Diseases and Metabolism (CHROMETA), Center for Intestinal Neuroimmune Interactions, Translational Research Center for Gastrointestinal Disorders (TARGID), KU Leuven, Leuven, Belgium
| | - Fedrica Pia
- Department of Chronic Diseases and Metabolism (CHROMETA), Center for Intestinal Neuroimmune Interactions, Translational Research Center for Gastrointestinal Disorders (TARGID), KU Leuven, Leuven, Belgium
| | - Wout Backaert
- Department of Microbiology, Immunology and Transplantation, Allergy and Clinical Immunology Research Group, KU Leuven, Leuven, Belgium
- Department of Otorhinolaryngology, Head and Neck Surgery, University Hospitals Leuven, Leuven, Belgium
| | - Laura Van Gerven
- Department of Microbiology, Immunology and Transplantation, Allergy and Clinical Immunology Research Group, KU Leuven, Leuven, Belgium
- Department of Otorhinolaryngology, Head and Neck Surgery, University Hospitals Leuven, Leuven, Belgium
- Department of Neurosciences, Experimental Otorhinolaryngology, KU Leuven, Leuven, Belgium
| | - Javier Aguilera-Lizarraga
- Department of Chronic Diseases and Metabolism (CHROMETA), Center for Intestinal Neuroimmune Interactions, Translational Research Center for Gastrointestinal Disorders (TARGID), KU Leuven, Leuven, Belgium
| | - Guy E Boeckxstaens
- Department of Chronic Diseases and Metabolism (CHROMETA), Center for Intestinal Neuroimmune Interactions, Translational Research Center for Gastrointestinal Disorders (TARGID), KU Leuven, Leuven, Belgium
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Huang Y, Cai L, Liu J, Yang R, Wei L, Gui X, Luo H. Is there a bidirectional relationship between allergic rhinitis and irritable bowel syndrome? A meta-analysis. J Glob Health 2025; 15:04155. [PMID: 40511506 PMCID: PMC12163863 DOI: 10.7189/jogh.15.04155] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 06/16/2025] Open
Abstract
Background Some studies suggest a link between allergic rhinitis (AR) and irritable bowel syndrome (IBS), but evidence is insufficient. This meta-analysis aimed to explore the relationship between AR and IBS. Methods We searched the relevant literature in six electronic databases. We included a total of nine articles, seven of which took AR as the research object, two of which took IBS as the research object. We performed a meta-analysis using random effects and estimated the resultant odds ratio (OR). Results A total of 10 627 patients with AR were included in seven studies, including 956 patients diagnosed with AR in the IBS population and 9671 patients diagnosed with AR in the non-IBS population. By heterogeneity test, X2 = 10.12, F-statistic (F) = 6, P = 0.12, I2 = 41%, OR = 2.88, and Z-score (Z) = 21.97 (P < 0.00001), the results were statistically significant. Patients with AR have an increased risk of developing IBS compared to patients without AR. A total of 1099 patients with IBS were included in two studies, including 384 patients with IBS in AR patients and 715 patients with IBS in the healthy population. After the heterogeneity test, X2 = 0.11, F = 1, P = 0.74, I2 = 0%, OR = 2.15, and Z = 11.81 (P < 0.00001), the results were statistically significant. Patients with IBS have an increased risk of developing AR compared to patients without IBS. Conclusions The bidirectional association between AR and IBS provides a basis for exploring potential new mechanisms between the two. Registration No. INPLASY202440057.
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Affiliation(s)
- Yifen Huang
- Department of Internal Medicine, The First Affiliated Hospital of Guangxi University of Chinese Medicine, Guangxi University of Chinese Medicine, Nanning, China
| | - Lun Cai
- Department of Internal Medicine, The First Affiliated Hospital of Guangxi University of Chinese Medicine, Guangxi University of Chinese Medicine, Nanning, China
| | - Jie Liu
- Department of Internal Medicine, The First Affiliated Hospital of Guangxi University of Chinese Medicine, Guangxi University of Chinese Medicine, Nanning, China
| | - RongRong Yang
- Department of Internal Medicine, The First Affiliated Hospital of Guangxi University of Chinese Medicine, Guangxi University of Chinese Medicine, Nanning, China
| | - Liping Wei
- Department of Rehabilitation, The First Affiliated Hospital of Guangxi University of Chinese Medicine, Guangxi University of Chinese Medicine, Nanning, China
| | - Xiongbin Gui
- Department of Otorhinolaryngology, The First Affiliated Hospital of Guangxi University of Chinese Medicine, Guangxi University of Chinese Medicine, Nanning, China
| | - Huazheng Luo
- Department of Internal Medicine, The First Affiliated Hospital of Guangxi University of Chinese Medicine, Guangxi University of Chinese Medicine, Nanning, China
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Cameron R, Jones M, Eslick G, Talley N. Colonic Diverticulosis and Uncomplicated Diverticulitis Are Associated With a Lower Not Higher Risk of Mortality When Confounding Factors Are Held Constant. J Gastroenterol Hepatol 2025; 40:1221-1229. [PMID: 40091500 PMCID: PMC12062918 DOI: 10.1111/jgh.16928] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/03/2024] [Revised: 02/06/2025] [Accepted: 02/23/2025] [Indexed: 03/19/2025]
Abstract
BACKGROUND AND AIM The association between colonic diverticulosis, diverticulitis, and mortality is controversial. This study evaluated the association between diverticular disease and mortality over a prolonged period in a GP cohort. METHODS GP records were sourced from the United Kingdom medical database (THIN). Diverticulosis and diverticulitis were identified via Read codes. The overall patient cohort (n = 1 274 260) included patients with colonic diverticula (n = 39 521 [3.1%], mean age 54) and no diverticula (control group) (n = 1 234 739 [96.9%], mean age 38). Poisson regression estimated relative rates, and durational time at risk and survival probability were calculated. RESULTS Colonic diverticula are associated with an increased mortality risk when compared with nondiverticular patients (OR = 1.89, 95% CI 1.84-1.94; p < 0.001). However, controlling for age, sex, and potential confounding variables yielded a decreased mortality risk overall for colonic diverticula patients (HR = 0.66, 95% 0.64-0.6; p < 0.001). When the diverticulitis cohort is separated into uncomplicated and complicated, increased mortality is observed in both uncomplicated diverticulitis (HR = 0.64, 95% CI 0.61-0.66; p < 0.001) and complicated diverticulitis (HR = 1.14, 95% CI 1.02-1.28; p = 0.024), but on controlling for confounding, there is a decreased risk of mortality for uncomplicated diverticulitis (HR = 0.65, 95% CI 0.63-0.66; p < 0.001) but almost two times increased mortality risk for complicated diverticulitis (HR = 1.18, 95% CI 1.05-1.32; p = 0.006). CONCLUSIONS In this large UK GP sample, controlling for age, sex, and comorbidities, patients with uncomplicated diverticula are associated with a lower mortality risk. However, complicated diverticulitis still carries two times the risk of mortality than those with no or uncomplicated colonic diverticula.
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Affiliation(s)
- Raquel A. Cameron
- College of Health, Medicine and WellbeingUniversity of NewcastleNewcastleAustralia
- NHMRC Centre for Research Excellence in Digestive HealthNewcastleAustralia
- Hunter Medical Research InstituteNewcastleAustralia
| | - Michael P. Jones
- NHMRC Centre for Research Excellence in Digestive HealthNewcastleAustralia
- School of Psychological SciencesMacquarie UniversityNorth RydeAustralia
| | - Guy D. Eslick
- NHMRC Centre for Research Excellence in Digestive HealthNewcastleAustralia
- Hunter Medical Research InstituteNewcastleAustralia
| | - Nicholas J. Talley
- College of Health, Medicine and WellbeingUniversity of NewcastleNewcastleAustralia
- NHMRC Centre for Research Excellence in Digestive HealthNewcastleAustralia
- Hunter Medical Research InstituteNewcastleAustralia
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Qi C, Li A, Su F, Wang Y, Zhou L, Tang C, Feng R, Mao R, Chen M, Chen L, Koppelman GH, Bourgonje AR, Zhou H, Hu S. An atlas of the shared genetic architecture between atopic and gastrointestinal diseases. Commun Biol 2024; 7:1696. [PMID: 39719505 DOI: 10.1038/s42003-024-07416-7] [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: 05/19/2024] [Accepted: 12/18/2024] [Indexed: 12/26/2024] Open
Abstract
Comorbidity among atopic diseases (ADs) and gastrointestinal diseases (GIDs) has been repeatedly demonstrated by epidemiological studies, whereas the shared genetic liability remains largely unknown. Here we establish an atlas of the shared genetic architecture between 10 ADs or related traits and 11 GIDs, comprehensively investigating the comorbidity-associated genomic regions, cell types, genes and genetically predicted causality. Although distinct genetic correlations between AD-GID are observed, including 14 genome-wide and 28 regional correlations, genetic factors of Crohn's disease (CD), ulcerative colitis (UC), celiac disease and asthma subtypes are converged on CD4+ T cells consistently across relevant tissues. Fourteen genes are associated with comorbidities, with three genes are known treatment targets, showing probabilities for drug repurposing. Lower expressions of WDR18 and GPX4 in PBMC CD4+ T cells predict decreased risk of CD and asthma, which could be novel drug targets. MR unveils certain ADs led to higher risk of GIDs or vice versa. Taken together, here we show distinct genetic correlations between AD-GID pairs, but the correlated genomic loci converge on the dysregulation of CD4+ T cells. Inhibiting WDR18 and GPX4 expressions might be candidate therapeutic strategies for CD and asthma. Estimated causality indicates potential guidance for preventing comorbidity.
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Affiliation(s)
- Cancan Qi
- Microbiome Medicine Center, Division of Laboratory Medicine, Zhujiang Hospital, Southern Medical University, Guangzhou, Guangdong, China
| | - An Li
- Department of Periodontology, Stomatological Hospital, Southern Medical University, Guangzhou, China
| | - Fengyuan Su
- Department of Gastroenterology, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, Guangdong, China
- Institute of Precision Medicine, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, Guangdong, China
| | - Yu Wang
- Department of Gastroenterology, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, Guangdong, China
| | - Longyuan Zhou
- Department of Gastroenterology, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, Guangdong, China
| | - Ce Tang
- Department of Gastroenterology, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, Guangdong, China
- Institute of Precision Medicine, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, Guangdong, China
| | - Rui Feng
- Department of Gastroenterology, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, Guangdong, China
- Department of Gastroenterology, Guangxi Hospital Division of The First Affiliated Hospital, Sun Yat-Sen University, Nanning, Guangxi, China
| | - Ren Mao
- Department of Gastroenterology, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, Guangdong, China
| | - Minhu Chen
- Department of Gastroenterology, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, Guangdong, China
| | - Lianmin Chen
- Department of Cardiology, The First Affiliated Hospital of Nanjing Medical University, Nanjing Medical University, Nanjing, Jiangsu, China
- Cardiovascular Research Center, The Affiliated Suzhou Hospital of Nanjing Medical University, Suzhou Municipal Hospital, Gusu School, Nanjing Medical University, Suzhou, Jiangsu, China
| | - Gerard H Koppelman
- University of Groningen University Medical Centre Groningen, Groningen Research Institute for Asthma and COPD, Groningen, the Netherlands
- University of Groningen University Medical Centre Groningen, Beatrix Children's Hospital, Department of Paediatric Pulmonology and Paediatric Allergology, Groningen, the Netherlands
| | - Arno R Bourgonje
- Department of Gastroenterology and Hepatology, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands.
- The Henry D. Janowitz Division of Gastroenterology, Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
| | - Hongwei Zhou
- Microbiome Medicine Center, Division of Laboratory Medicine, Zhujiang Hospital, Southern Medical University, Guangzhou, Guangdong, China.
| | - Shixian Hu
- Department of Gastroenterology, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, Guangdong, China.
- Institute of Precision Medicine, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, Guangdong, China.
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Trukhmanov AS, Rumyantseva DE. Functional Dyspepsia and Gastroesophageal Reflux Disease: From Pathogenesis to Current Treatment Strategies. RUSSIAN JOURNAL OF GASTROENTEROLOGY, HEPATOLOGY, COLOPROCTOLOGY 2024; 34:83-92. [DOI: 10.22416/1382-4376-2024-34-5-83-92] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/02/2025]
Abstract
Aim: to present a modern view on the combination of functional dyspepsia (FD) and gastroesophageal reflux disease (GERD) and to evaluate the effectiveness of acotiamide in patients with FD and GERD.Key points. The high frequency of the combination of FD and GERD is caused by common pathogenetic mechanisms and presents an urgent problem in clinical practice. The concurrent occurrence of these diseases alters the clinical picture, complicates differential diagnostics, and leads to inadequate prescription of drugs. Medical treatment for patients with FD and GERD includes the use of proton pump inhibitors (PPIs) and prokinetics. Currently, acotiamide is recognized as an effective drug that affects the motility of the upper gastrointestinal tract. Acotiamide is an antagonist of muscarinic M1 and M2 receptors and a reversible inhibitor of acetylcholinesterase. The clinical efficacy of this drug has been demonstrated not only in patients with FD but also in those with a combination of FD and GERD.Conclusion. Administration of acotiamide is pathogenetically justified in patients with the combination of GERD and FD.
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Affiliation(s)
- A. S. Trukhmanov
- I.M. Sechenov First Moscow State Medical University (Sechenov University)
| | - D. E. Rumyantseva
- I.M. Sechenov First Moscow State Medical University (Sechenov University)
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Khan A, Menon R, Corning B, Cohn S, Kumfa C, Raji M. Mirtazapine for gastrointestinal and neuropsychological symptoms in older adults with irritable bowel syndrome. Therap Adv Gastroenterol 2024; 18:17562848241278125. [PMID: 39493642 PMCID: PMC11526313 DOI: 10.1177/17562848241278125] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/13/2024] [Accepted: 08/08/2024] [Indexed: 11/05/2024] Open
Abstract
Irritable bowel syndrome (IBS) is a common and potentially modifiable contributor to excess disability, morbidity, and poor quality of life. Clinical trials of medications for IBS have largely been in younger adults. Yet, a growing number of adults aged 65 and older are living with IBS. No data exist to guide clinicians in the safe and effective use of medications (e.g., anticholinergics, anti-spasmodics, and tricyclic antidepressants (TCA)) for IBS in the geriatric population. These medications-especially anticholinergics and TCAs-carry a high risk of adverse effects (ADE) in older adults because of age-associated decline in drug metabolism and the high prevalence of multiple chronic conditions. Five or more medications (polypharmacy) are frequently used to treat common psychiatric and medical comorbidities of IBS: anxiety, depression, insomnia, migraine headache, diarrhea, nausea, poor appetite, pruritus/skin atopy, and fibromyalgia. These neurological and psychiatric comorbidities reflect shared pathogenic mechanisms and bidirectional crosstalk of high inflammation, alteration of gut microbiota, and dysregulation of multiple gastrointestinal and central nervous system-active neurotransmitters (e.g., serotonin, neuropeptides). Currently, these IBS-associated conditions are treated with multiple medications-which increase the risk of adverse drug-drug interactions. One way to reduce the number of medications used for IBS-associated conditions is the use of one medication that treats many or all of these conditions-Mirtazapine. In this perspective article, we present evidence from basic science, case series, observational and epidemiological studies, clinical studies, and clinical trials supporting mirtazapine, a noradrenergic and specific serotonergic receptor antagonist-with 5-hydroxytryptamine-2 and 3 antagonism, as a potential pharmacotherapeutic intervention for the myriad symptoms and conditions associated with IBS. Specifically, we found evidence of mirtazapine's role in treating diarrhea, insomnia, migraine headache, nausea, and poor appetite. We propose a large randomized controlled trial to study mirtazapine as a potential one-stop treatment for multiple IBS symptoms, with the potential to reduce polypharmacy and ADEs, especially in the geriatric population.
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Affiliation(s)
- Ayesha Khan
- Department of Internal Medicine, University of Texas at Medical Branch, 301 University Blvd, 5.138 RS, Galveston, TX 77555-5302, USA
| | - Raakhi Menon
- Department of Internal Medicine, University of Texas at Medical Branch, Galveston, TX, USA
| | - Brooke Corning
- Department of Gastroenterology and Hepatology, University of Texas at Medical Branch, Galveston, TX, USA
| | - Steven Cohn
- Department of Gastroenterology and Hepatology, University of Texas at Medical Branch, Galveston, TX, USA
| | - Cecil Kumfa
- Division of Geriatrics and Palliative Medicine, University of Texas at Medical Branch, Galveston, TX, USA
| | - Mukaila Raji
- Division of Geriatrics and Palliative Medicine, University of Texas at Medical Branch, Galveston, TX, USA
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Jones MP, Koloski NA, Walker MM, Holtmann GJ, Shah A, Eslick GD, Talley NJ. A Minority of Childhood Disorders of Gut-Brain Interaction Persist Into Adulthood: A Risk-Factor Analysis. Am J Gastroenterol 2024; 119:1894-1900. [PMID: 38483301 DOI: 10.14309/ajg.0000000000002751] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/05/2023] [Accepted: 03/06/2024] [Indexed: 04/24/2024]
Abstract
INTRODUCTION Disorders of gut-brain interaction (DGBIs) may originate in childhood. There are currently limited data on persistence of DGBI into adulthood and risk factors for persistence. Furthermore, there are no data on this question from general practice, where the majority of DGBIs are diagnosed and managed. This study documents the proportion of childhood-diagnosed DGBIs that persisted into adulthood and what factors were associated with persistence. METHODS General practice records were obtained for more than 60,000 patients whose medical record spanned both childhood and adulthood years. Patients with diagnosed organic gastrointestinal disorder were excluded. Medical records were also interrogated for potential risk factors. RESULTS Eleven percent of patients with irritable bowel syndrome (IBS) and 20% of patients with functional dyspepsia (FD) diagnosed in childhood had repeat diagnoses of the same condition in adulthood. Female sex (odds ratio [OR] 2.02) was associated with persistence for IBS, while a childhood diagnosis of gastritis (OR 0.46) was risk-protective. Childhood non-steroidal anti-inflammatory drug use (OR 1.31, 95% confidence interval [CI] 1.09-1.56) was a risk factor for persistence in IBS. For FD, a childhood diagnosis of asthma (OR 1.30, 95% CI 1.00-1.70) was a risk factor, as was anxiety for both IBS (OR 1.24, 95% CI 1.00-1.54) and FD (OR 1.48 95% CI 1.11-1.97) with a similar finding for depression for IBS (OR 1.34, 95% CI 1.11-1.62) and FD (OR 1.88 95% CI 1.47-2.42). DISCUSSION Childhood DGBIs persist into adulthood in 10%-20% of patients, suggesting that management monitoring should continue into adulthood. Those diagnosed with anxiety or mood disorders in childhood should receive particular attention, and prescription of non-steroidal anti-inflammatory drugs in children should be made judiciously.
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Affiliation(s)
- Michael P Jones
- School of Psychological Sciences, Macquarie University, North Ryde, New South Wales, Australia
| | - Natasha A Koloski
- Faculty of Health and Medicine, University of Newcastle, Newcastle, New South Wales, Australia
- Department of Gastroenterology and Hepatology, Princess Alexandra Hospital and Translational Research Institute (TRI), Woolloongabba, Queensland, Australia
| | - Marjorie M Walker
- Faculty of Health and Medicine, University of Newcastle, Newcastle, New South Wales, Australia
| | - Gerald J Holtmann
- Department of Gastroenterology and Hepatology, Princess Alexandra Hospital and Translational Research Institute (TRI), Woolloongabba, Queensland, Australia
| | - Ayesha Shah
- Department of Gastroenterology and Hepatology, Princess Alexandra Hospital and Translational Research Institute (TRI), Woolloongabba, Queensland, Australia
| | - Guy D Eslick
- Faculty of Health and Medicine, University of Newcastle, Newcastle, New South Wales, Australia
| | - Nicholas J Talley
- Faculty of Health and Medicine, University of Newcastle, Newcastle, New South Wales, Australia
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Ford AC, Staudacher HM, Talley NJ. Postprandial symptoms in disorders of gut-brain interaction and their potential as a treatment target. Gut 2024; 73:1199-1211. [PMID: 38697774 DOI: 10.1136/gutjnl-2023-331833] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/05/2024] [Accepted: 04/23/2024] [Indexed: 05/05/2024]
Abstract
Postprandial, or meal-related, symptoms, such as abdominal pain, early satiation, fullness or bloating, are often reported by patients with disorders of gut-brain interaction, including functional dyspepsia (FD) or irritable bowel syndrome (IBS). We propose that postprandial symptoms arise via a distinct pathophysiological process. A physiological or psychological insult, for example, acute enteric infection, leads to loss of tolerance to a previously tolerated oral food antigen. This enables interaction of both the microbiota and the food antigen itself with the immune system, causing a localised immunological response, with activation of eosinophils and mast cells, and release of inflammatory mediators, including histamine and cytokines. These have more widespread systemic effects, including triggering nociceptive nerves and altering mood. Dietary interventions, including a diet low in fermentable oligosaccharides, disaccharides, monosaccharides and polyols, elimination of potential food antigens or gluten, IgG food sensitivity diets or salicylate restriction may benefit some patients with IBS or FD. This could be because the restriction of these foods or dietary components modulates this pathophysiological process. Similarly, drugs including proton pump inhibitors, histamine-receptor antagonists, mast cell stabilisers or even tricyclic or tetracyclic antidepressants, which have anti-histaminergic actions, all of which are potential treatments for FD and IBS, act on one or more of these mechanisms. It seems unlikely that food antigens driving intestinal immune activation are the entire explanation for postprandial symptoms in FD and IBS. In others, fermentation of intestinal carbohydrates, with gas release altering reflex responses, adverse reactions to food chemicals, central mechanisms or nocebo effects may dominate. However, if the concept that postprandial symptoms arise from food antigens driving an immune response in the gastrointestinal tract in a subset of patients is correct, it is paradigm-shifting, because if the choice of treatment were based on one or more of these therapeutic targets, patient outcomes may be improved.
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Affiliation(s)
- Alexander C Ford
- Leeds Gastroenterology Institute, St James's University Hospital, Leeds, UK
| | - Heidi M Staudacher
- Deakin University-Geelong Waterfront Campus, Geelong, Victoria, Australia
| | - Nicholas J Talley
- Health, University of Newcastle, Callaghan, New South Wales, Australia
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Hasosah M, Al Sarkhy A, AlQuiar K, AlMuslami I, AlAhmadi N, Almehaidib A, AlShahrani A, Alanazi A, Khan M, Aljohani A, Alanazi S, Alhassan T, AlNaqeeb A, Hameedaldeen M, Albalawi S, Abdulmenem S, Almehaidib I, Qurashi M. Prevalence of functional gastrointestinal disorders in Saudi infants and toddlers: A cross-sectional multicenter study. Saudi J Gastroenterol 2024; 30:145-153. [PMID: 38059377 PMCID: PMC11198919 DOI: 10.4103/sjg.sjg_259_23] [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: 07/14/2023] [Revised: 11/07/2023] [Accepted: 11/08/2023] [Indexed: 12/08/2023] Open
Abstract
BACKGROUND Functional gastrointestinal disorders (FGIDs) are common pediatric problems, but their prevalence in Saudi Arabia is unknown. We aimed to assess the prevalence of FGIDs and risk factors among children in six regions of Saudi Arabia. METHODS This was a cross-sectional multicenter study enrolling children aged 0-48 months, attending pediatric clinics. Questionnaires evaluated the clinical history, symptoms, and sociodemographic information. FGIDs were defined according to Rome IV criteria. RESULTS The study involved 1011 infants and toddlers (mean [standard deviation (SD)] aged, 21.7 [19.4] months; FGIDs and mean [SD] age 17.4 [16.4] months; controls). FGIDs were diagnosed in 483 (47.7%) of all infants and toddlers. The prevalence of FGIDs was significantly higher in children aged 0-12 months than in those aged 13-48 months ( P < 0.001). The most common disorders were functional regurgitation (13.8%) in infants and functional constipation (9.6%) in toddlers. Univariate regression analysis confirmed that the rate of FGIDs was higher in term gestational age infants (odds ratio (OR) 2.7; 95% confidence interval (CI), 1.76-4.17, P < 0.001), in partial breastfeeding (OR 0.58; 95% CI, 0.40-0.84, P = 0.003), in formula feeding (OR 2.25; 95% CI, 1.51-3.35, P < 0.001), and in subjects with no history of food allergy (OR 2.40; 95% CI, 1.58-3.64, P < 0.001). CONCLUSIONS FGIDs are common in Saudi infants and toddlers (47.7%). Regurgitation is most prevalent in infants, and functional constipation is most common in toddlers. Term gestational age infant, partial breastfeeding, formula feeding, and subjects with no history of food allergy are associated with the prevalence of FGIDs.
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Affiliation(s)
- Mohammed Hasosah
- Pediatric Gastroenterology Department, King Saud bin Abdulaziz University for Health Sciences, King Abdullah International Medical Research Center (KAIMRC), National Guard Hospital, Jeddah, KSA
| | - Ahmed Al Sarkhy
- Pediatric Gastroenterology Unit, King Saud University Medical City, King Saud University, Riyadh, KSA
| | - Khalid AlQuiar
- Pediatric Gastroenterology, King Salman Armed Forces Hospital, Tabouk, KSA
| | | | - Najat AlAhmadi
- Pediatric Gastroenterology, Maternal Children Hospital, Almadinah Almonawarah, KSA
| | - Ali Almehaidib
- Pediatric Gastroenterology, King Faisal Specialist Hospital and Research Center, Riyadh, KSA
| | - Adel AlShahrani
- Pediatric Gastroenterology, Maternal Children Hospital, Khamis Mushait, KSA
| | - Aziz Alanazi
- Pediatric Gastroenterology, King Abdullah International Medical Research Center (KAIMRC), National Guard Hospital, Riyadh, KSA
| | - Muhammad Khan
- Pediatric Gastroenterology Department, King Saud bin Abdulaziz University for Health Sciences, King Abdullah International Medical Research Center (KAIMRC), National Guard Hospital, Jeddah, KSA
| | - Abrar Aljohani
- Pediatric Gastroenterology Department, King Saud bin Abdulaziz University for Health Sciences, King Abdullah International Medical Research Center (KAIMRC), National Guard Hospital, Jeddah, KSA
| | - Saqqar Alanazi
- Pediatric Gastroenterology, King Salman Armed Forces Hospital, Tabouk, KSA
| | - Tariq Alhassan
- Pediatric Gastroenterology Unit, King Saud University Medical City, King Saud University, Riyadh, KSA
| | - Ahlam AlNaqeeb
- Pediatric Gastroenterology Unit, King Saud University Medical City, King Saud University, Riyadh, KSA
| | - Marwah Hameedaldeen
- Pediatric Gastroenterology Department, King Saud bin Abdulaziz University for Health Sciences, King Abdullah International Medical Research Center (KAIMRC), National Guard Hospital, Jeddah, KSA
| | - Sanabil Albalawi
- Pediatric Gastroenterology, King Salman Armed Forces Hospital, Tabouk, KSA
| | - Safa Abdulmenem
- Pediatric Gastroenterology, Maternal Children Hospital, Dammam, KSA
| | - Ibrahim Almehaidib
- Department of Internal Medicine, Imam Mohammed Ibn Saud Islamic University, Riyadh, KSA
| | - Mansour Qurashi
- Neonatology Department, King Saud bin Abdulaziz University for Health Sciences, King Abdullah International Medical Research Center (KAIMRC), National Guard Hospital, Jeddah, KSA
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10
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Sachar M, Mautner Wizentier M, Risner E, Asmail H, Omara M, Chablaney S, Khan A, Knotts R. Risk factors associated with functional esophageal disorders (FED) versus gastroesophageal reflux disease (GERD). Surg Endosc 2024; 38:2842-2849. [PMID: 38528263 DOI: 10.1007/s00464-024-10714-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/04/2023] [Accepted: 01/28/2024] [Indexed: 03/27/2024]
Abstract
INTRODUCTION Despite the high prevalence of typical symptoms of gastroesophageal reflux disease (GERD), approximately 30% of patients have functional esophageal disorders (FED) on ambulatory reflux monitoring, which may include reflux hypersensitivity (RH; defined as physiologic acid exposure but temporally correlated symptoms of reflux), or functional heartburn (FH; defined as physiologic acid exposure and negative symptom correlation). There are limited epidemiological data characterizing these conditions. We investigated demographic and socioeconomic factors as well as medical comorbidities which may predispose to FED versus pathologic GERD. METHODS Adult patients with reflux symptoms for at least 3 months were studied with 24-h pH-impedance testing from 11/2019 to 3/2021. Participants were categorized into pathologic GERD, FH, or RH using pH-impedance data and reported symptom correlation. Demographic data, including age, gender, race/ethnicity, zip code, insurance status, and medical comorbidity data were retrospectively retrieved from the electronic medical record on all participants. RESULTS 229 patients were included. Non-Hispanic Asian ethnicity (OR 5.65; p = 0.01), underweight BMI (OR 7.33; p = 0.06), chronic pain (OR 2.33; p < 0.01), insomnia (OR 2.83; p = 0.06), and allergic rhinitis (OR 3.90; p < 0.01) were associated with a greater risk for FED. Overweight BMI (OR 0.48; p = 0.03) and alcohol use (OR 0.57; p = 0.06) were associated with a decreased risk for FED. DISCUSSION This is the first report of a greater risk of FED in patients with underweight BMI, insomnia, chronic pain, allergic rhinitis, or of Asian or Hispanic ethnicities. The weak associations between female gender and anxiety are corroborated in other studies. Our findings enable clinicians to better screen patients with reflux for this disorder.
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Affiliation(s)
- Moniyka Sachar
- Department of Medicine, New York University Langone Health, 247 E 28th Street, New York, NY, 10016, USA.
| | | | - Emma Risner
- Department of Biostatistics, New York University School of Public Health, New York, USA
| | - Hannah Asmail
- Department of Biostatistics, New York University School of Public Health, New York, USA
| | - Mathew Omara
- Division of Gastroenterology & Hepatology, Department of Medicine, Center for Esophageal Health, NYU Grossman School of Medicine, NYU Langone Health, New York, NY, USA
| | - Shreya Chablaney
- Division of Gastroenterology & Hepatology, Department of Medicine, Center for Esophageal Health, NYU Grossman School of Medicine, NYU Langone Health, New York, NY, USA
| | - Abraham Khan
- Division of Gastroenterology & Hepatology, Department of Medicine, Center for Esophageal Health, NYU Grossman School of Medicine, NYU Langone Health, New York, NY, USA
| | - Rita Knotts
- Division of Gastroenterology & Hepatology, Department of Medicine, Center for Esophageal Health, NYU Grossman School of Medicine, NYU Langone Health, New York, NY, USA
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11
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Yamamoto Y, Furukawa S, Miyake T, Watanabe J, Nakamura Y, Taguchi Y, Yamamoto T, Kato A, Kusumoto K, Yoshida O, Takeshita E, Ikeda Y, Yamamoto N, Saeki Y, Yamaguchi O, Hiasa Y. Multimorbidity of Allergic Diseases Is Associated With Functional Gastrointestinal Disorders in a Young Japanese Population. J Neurogastroenterol Motil 2024; 30:229-235. [PMID: 38576372 PMCID: PMC10999849 DOI: 10.5056/jnm23015] [Citation(s) in RCA: 2] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/31/2023] [Revised: 03/20/2023] [Accepted: 04/10/2023] [Indexed: 04/06/2024] Open
Abstract
Background/Aims Although certain allergic diseases have been reported to be associated with the prevalence of functional dyspepsia (FD) and irritable bowel syndrome (IBS), it is unclear whether the presence of multiple allergic diseases further increases the prevalence of FD and IBS. The aim of this study is to determine this issue in young people. Methods A cohort of 8923 Japanese university students was enrolled and diagnoses of FD and IBS were confirmed using Rome III criteria. Allergic disorders diagnosed at medical institutions were obtained by means of a self-administered questionnaire. Results The prevalence of FD, IBS, and their overlap was found to be 1.9%, 6.5%, and 1.1%, respectively. Pollen allergy was independently positively correlated with FD, IBS, and overlap of FD and IBS. Allergic rhinitis was positively linked to IBS. Drug allergy was positively associated with FD. The presence of multiple allergic diseases was positively correlated with FD and IBS (FD: adjusted OR for 2 allergic diseases: 1.95 [95% CI, 1.24-2.98], P for trend = 0.003; and IBS: adjusted OR for 1 allergic disease: 1.40 [95% CI, 1.15-1.69], 2 allergic diseases 1.47 [95% CI, 1.12-1.91], and 3 or more allergic diseases: 2.22 [95% CI, 1.45-3.28], P for trend = 0.001). Additionally, the concomitant existence of multiple allergic diseases was also demonstrated to have a trend that correlated with the overlap of FD and IBS (P for trend = 0.018). Conclusion Allergic disease multimorbidity is positively correlated with the prevalence of FD and IBS in a young population.
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Affiliation(s)
| | - Shinya Furukawa
- Health Services Center, Ehime University, Matsuyama, Ehime, Japan
| | - Teruki Miyake
- Department of Gastroenterology and Metabology, Ehime University Graduate School of Medicine, Shitsukawa, Toon, Ehime, Japan
| | - Junichi Watanabe
- Department of Physical Therapy, Faculty of Health Sciences, Yamagata Prefectural University of Health Sciences, Yamagata, Japan
| | - Yukihiro Nakamura
- Department of Cardiology, Pulmonary, Hypertension and Nephropathy, Ehime University Graduate School of Medicine, Ehime, Japan
| | - Yoshihiro Taguchi
- Department of Cardiology, Pulmonary, Hypertension and Nephropathy, Ehime University Graduate School of Medicine, Ehime, Japan
| | - Tetsuya Yamamoto
- Department of Cardiology, Pulmonary, Hypertension and Nephropathy, Ehime University Graduate School of Medicine, Ehime, Japan
| | - Aki Kato
- Health Services Center, Ehime University, Matsuyama, Ehime, Japan
| | | | - Osamu Yoshida
- Department of Gastroenterology and Metabology, Ehime University Graduate School of Medicine, Shitsukawa, Toon, Ehime, Japan
| | - Eiji Takeshita
- Department of Inflammatory Bowel Diseases and Therapeutics, Ehime University Graduate School of Medicine, Ehime, Japan
| | - Yoshio Ikeda
- Endoscopy Center, Ehime University Hospital, Toon, Ehime, Japan
| | - Naofumi Yamamoto
- Faculty of Collaborative Regional Innovation, Ehime University, Matsuyama, Ehime, Japan
| | - Yuka Saeki
- Health Services Center, Ehime University, Matsuyama, Ehime, Japan
- Community Health Systems for Nursing, Ehime University Graduate School of Medicine, Toon, Ehime, Japan
| | - Osamu Yamaguchi
- Department of Cardiology, Pulmonary, Hypertension and Nephropathy, Ehime University Graduate School of Medicine, Ehime, Japan
| | - Yoichi Hiasa
- Department of Gastroenterology and Metabology, Ehime University Graduate School of Medicine, Shitsukawa, Toon, Ehime, Japan
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12
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Karthik KP, Dileep A, Rajagopala S, Arun Kumar M, Dharmarajan P, Vellela J. Ayurvedic clinical decision-making methods to predict, prevent and manage childhood allergic disorders. J Ayurveda Integr Med 2024; 15:100857. [PMID: 38237455 PMCID: PMC10828817 DOI: 10.1016/j.jaim.2023.100857] [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: 11/24/2021] [Revised: 08/14/2023] [Accepted: 11/24/2023] [Indexed: 02/03/2024] Open
Abstract
Allergy is a conundrum lacking satisfactory answers despite its global prevalence. Traditional systems of medicine may contain sustainable and effective solutions for the same. For mainstreaming them, an evaluation based on the system's own methods is inevitable rather than symptom-based correlations. Atopy is a novel entity in Ayurveda, but the methods of tripartite delineation (disease pattern, disease targets and influencing factors) of novel diseases and multifactorial approach to diagnosis and management in Ayurveda can bring about comprehensiveness in collection and categorization of data regarding the entity. This in turn can make the prediction, prevention and management of the same more precise, effective and sustainable. The article provides a template for the application of Ayurvedic biological framework in the diagnosis and management of novel diseases, with special reference to childhood allergic disorders.
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Affiliation(s)
| | | | - S Rajagopala
- Department of Kaumarabhritya, All Institute of Ayurveda, India
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13
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Fairlie T, Shah A, Talley NJ, Chey WD, Koloski N, Yeh Lee Y, Gwee KA, Jones MP, Holtmann G. Overlap of disorders of gut-brain interaction: a systematic review and meta-analysis. Lancet Gastroenterol Hepatol 2023; 8:646-659. [PMID: 37211024 DOI: 10.1016/s2468-1253(23)00102-4] [Citation(s) in RCA: 13] [Impact Index Per Article: 6.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/10/2023] [Revised: 03/29/2023] [Accepted: 03/29/2023] [Indexed: 05/23/2023]
Abstract
BACKGROUND Rome criteria differentiate distinct types of disorders of gut-brain interaction (DGBI); also known as functional gastrointestinal disorders. Overlap of symptom categories frequently occurs. This systematic review and meta-analysis aimed to define the prevalence of DGBI overlap and compare overlap in population-based, primary care or tertiary care health settings. Furthermore, we aimed to compare symptom severity of psychological comorbidities in DGBI with and without overlap. METHODS For this systematic review and meta-analysis we searched MEDLINE (PubMed) and Embase electronic databases from inception until March 1, 2022, for original articles and conference abstracts of observational cross-sectional, case-controlled, or cohort design studies that reported the prevalence of DGBI overlap in adult participants (aged ≥18 years). We included only those studies where the diagnosis of DGBI was based on clinical assessment, questionnaire data, or specific symptom-based criteria. Studies were excluded if reporting on mixed populations of DGBI and organic diseases. Aggregate patient data were extracted from eligible published studies. The prevalence of DGBI overlap in all studies was pooled using the DerSimonian and Laird random effects model, and further analysis stratified by subgroups (care setting, diagnostic criteria, geographic region, and gross domestic product per capita). We also assessed the relationship between DGBI overlap with anxiety, depression, and quality of life symptom scores. This study was registered with PROSPERO (CRD42022311101). FINDINGS 46 of 1268 screened studies, reporting on 75 682 adult DGBI participants, were eligible for inclusion in this systematic review and meta-analysis. Overall, 24 424 (pooled prevalence 36·5% [95% CI 30·7 to 42·6]) participants had a DGBI overlap, with considerable between-study heterogeneity (I2=99·51, p=0·0001). In the tertiary health-care setting, overlap among participants with DGBI was more prevalent (8373 of 22 617, pooled prevalence 47·3% [95% CI 33·2 to 61·7]) compared with population-based cohorts (11 332 of 39 749, pooled prevalence 26·5% [95% CI 20·5 to 33·4]; odds ratio 2·50 [95% CI 1·28 to 4·87]; p=0·0084). Quality of life physical component scores were significantly lower in participants with DGBI overlap compared with participants without overlap (standardised mean difference -0·47 [95% CI -0·80 to -0·14]; p=0·025). Participants with DGBI overlap had both increased symptom scores for anxiety (0·39 [95% CI 0·24 to 0·54]; p=0·0001) and depression (0·41 [0·30 to 0·51]; p=0·0001). INTERPRETATION Overlap of DGBI subtypes is frequent, and is more prevalent in tertiary care settings and associated with more severe symptom manifestations or psychological comorbidities. Despite the large sample size, the comparative analyses revealed substantial heterogeneity, and the results should be interpreted with caution. FUNDING National Health and Medical Research Council and Centre for Research Excellence.
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Affiliation(s)
- Thomas Fairlie
- Faculty of Medicine and Faculty of Health and Behavioural Sciences, University of Queensland, Brisbane, QLD, Australia; Department of Gastroenterology and Hepatology, Princess Alexandra Hospital, Brisbane, QLD, Australia
| | - Ayesha Shah
- Faculty of Medicine and Faculty of Health and Behavioural Sciences, University of Queensland, Brisbane, QLD, Australia; Department of Gastroenterology and Hepatology, Princess Alexandra Hospital, Brisbane, QLD, Australia
| | - Nicholas J Talley
- School of Medicine and Public Health, and Hunter Medical Research Institute, University of Newcastle, Newcastle, NSW, Australia
| | - William D Chey
- Division of Gastroenterology, Michigan Medicine, University of Michigan, Ann Arbor, MI, USA
| | - Natasha Koloski
- Faculty of Medicine and Faculty of Health and Behavioural Sciences, University of Queensland, Brisbane, QLD, Australia; Department of Gastroenterology and Hepatology, Princess Alexandra Hospital, Brisbane, QLD, Australia; School of Medicine and Public Health, and Hunter Medical Research Institute, University of Newcastle, Newcastle, NSW, Australia
| | - Yeong Yeh Lee
- School of Medical Sciences, Universiti Sains Malaysia, Kota Bharu, Malaysia
| | - Kok-Ann Gwee
- Yong Loo Lin School of Medicine, National University of Singapore, Singapore
| | - Michael P Jones
- School of Psychological Sciences, Macquarie University, Sydney, NSW, Australia
| | - Gerald Holtmann
- Faculty of Medicine and Faculty of Health and Behavioural Sciences, University of Queensland, Brisbane, QLD, Australia; Department of Gastroenterology and Hepatology, Princess Alexandra Hospital, Brisbane, QLD, Australia.
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14
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Wiklendt L, Mohd Rosli R, Kumar R, Paskaranandavadivel N, Bampton PA, Maslen L, Costa M, Brookes SJ, O'Grady G, Dinning PG. Inhibited postprandial retrograde cyclic motor pattern in the distal colon of patients with diarrhea-predominant irritable bowel syndrome. Am J Physiol Gastrointest Liver Physiol 2023; 325:G62-G79. [PMID: 37162180 DOI: 10.1152/ajpgi.00114.2022] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/02/2022] [Revised: 05/08/2023] [Accepted: 05/08/2023] [Indexed: 05/11/2023]
Abstract
Patients with irritable bowel syndrome (IBS) have recurrent lower abdominal pain, associated with altered bowel habit (diarrhea and/or constipation). As bowel habit is altered, abnormalities in colonic motility are likely to contribute; however, characterization of colonic motor patterns in patients with IBS remains poor. Utilizing fiber-optic manometry, we aimed to characterize distal colonic postprandial colon motility in diarrhea-predominant IBS. After an overnight fast, a 72-sensor (spaced at 1-cm intervals) manometry catheter was colonoscopically placed to the proximal colon, in 13 patients with IBS-D and 12 healthy adults. Recordings were taken for 2 h pre and post a 700 kcal meal. Data were analyzed with our two developed automated techniques. In both healthy adults and patients with IBS-D, the dominant frequencies of pressure waves throughout the colon are between 2 and 4 cycles per minute (cpm) and the power of these frequencies increased significantly after a meal. Although these pressure waves formed propagating contractions in both groups, the postprandial propagating contraction increase was significantly smaller in patients compared with healthy adults. In healthy adults during the meal period, retrograde propagation between 2 and 8 cpm was significantly greater than antegrade propagation at the same frequencies. This difference was not observed in IBS-D. Patients with IBS-D show reduced prevalence of the retrograde cyclic motor pattern postprandially compared with the marked prevalence in healthy adults. We hypothesize that this reduction may allow premature rectal filling, leading to postprandial urgency and diarrhea.NEW & NOTEWORTHY Compared with healthy adults this study has shown a significant reduction in the prevalence of the postprandial retrograde cyclic motor pattern in the distal colon of patients with diarrhea-predominant irritable bowel syndrome. We hypothesize that this altered motility may allow for premature rectal filling which contributes to the postprandial urgency and diarrhea experienced by these patients.
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Affiliation(s)
- Lukasz Wiklendt
- College of Medicine and Public Health, Flinders University, Adelaide, South Australia, Australia
| | - Reizal Mohd Rosli
- College of Medicine and Public Health, Flinders University, Adelaide, South Australia, Australia
| | - Raghu Kumar
- Department of Gastroenterology and Surgery, Flinders Medical Centre, Adelaide, South Australia, Australia
| | | | - Peter A Bampton
- Department of Gastroenterology and Surgery, Flinders Medical Centre, Adelaide, South Australia, Australia
| | - Lyn Maslen
- Department of Gastroenterology and Surgery, Flinders Medical Centre, Adelaide, South Australia, Australia
| | - Marcello Costa
- College of Medicine and Public Health, Flinders University, Adelaide, South Australia, Australia
| | - Simon J Brookes
- College of Medicine and Public Health, Flinders University, Adelaide, South Australia, Australia
| | - Greg O'Grady
- Auckland Bioengineering Institute, University of Auckland, Auckland, New Zealand
- Department of Surgery, University of Auckland, Auckland, New Zealand
| | - Phil G Dinning
- College of Medicine and Public Health, Flinders University, Adelaide, South Australia, Australia
- Department of Gastroenterology and Surgery, Flinders Medical Centre, Adelaide, South Australia, Australia
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15
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Vernon-Roberts A, Alexander I, Day AS. Prevalence of Functional Gastrointestinal Disorders (Rome IV Criteria) among a Cohort of New Zealand Children. GASTROINTESTINAL DISORDERS 2023; 5:261-272. [DOI: 10.3390/gidisord5020021] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 10/10/2023] Open
Abstract
Functional gastrointestinal disorders (FGIDs) are characterised by recurring gastrointestinal symptoms that are not secondary to organic disease. FGIDs may cause reduced quality of life, with approximately 22% of children experiencing at least one FGID. This study aimed to assess FGID prevalence among children attending a tertiary care hospital in New Zealand (NZ). Methods: Children aged ≥ four years were prospectively recruited from Christchurch Hospital, NZ. Data were collected on demographics, medical history, gastrointestinal symptoms (Rome IV), and quality of life (EQ-5D-Y). An analysis was carried out using analysis of variance and the chi-squared test of independence. Results: The cohort included 156 children, with a mean age of 9.5 years (SD 3.3), 56% male. According to the Rome IV criteria, 29% experienced at least one FGID, most commonly functional constipation and functional dyspepsia. FGID symptoms were associated with Māori ethnicity (p = 0.012) and parental FGID (p < 0.001). Quality of life was lower in the FGID group in the domain ‘Feeling worried, sad, or unhappy’ (p = 0.002). Conclusion: the association of FGIDs with worse quality of life, in particular relating to worry and sadness, should highlight the importance of providing support to school age children experiencing FGID symptoms.
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Affiliation(s)
- Angharad Vernon-Roberts
- Department of Paediatrics, University of Otago, Christchurch, Christchurch 8011, New Zealand
| | - India Alexander
- Department of Paediatrics, University of Otago, Christchurch, Christchurch 8011, New Zealand
| | - Andrew S. Day
- Department of Paediatrics, University of Otago, Christchurch, Christchurch 8011, New Zealand
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16
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Burns GL, Bruce JK, Minahan K, Mathe A, Fairlie T, Cameron R, Naudin C, Nair PM, Potter MDE, Irani MZ, Bollipo S, Foster R, Gan LT, Shah A, Koloski NA, Foster PS, Horvat JC, Veysey M, Holtmann G, Powell N, Walker MM, Talley NJ, Keely S. Type 2 and type 17 effector cells are increased in the duodenal mucosa but not peripheral blood of patients with functional dyspepsia. Front Immunol 2023; 13:1051632. [PMID: 36685573 PMCID: PMC9852875 DOI: 10.3389/fimmu.2022.1051632] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/11/2022] [Accepted: 12/15/2022] [Indexed: 01/07/2023] Open
Abstract
Background Functional dyspepsia is characterised by chronic symptoms of post-prandial distress or epigastric pain not associated with defined structural pathology. Increased peripheral gut-homing T cells have been previously identified in patients. To date, it is unknown if these T cells were antigen-experienced, or if a specific phenotype was associated with FD. Objective This study aimed to characterise T cell populations in the blood and duodenal mucosa of FD patients that may be implicated in disease pathophysiology. Methods We identified duodenal T cell populations from 23 controls and 49 Rome III FD patients by flow cytometry using a surface marker antibody panel. We also analysed T cell populations in peripheral blood from 37 controls and 61 patients. Where available, we examined the number of duodenal eosinophils in patients and controls. Results There was a shift in the duodenal T helper cell balance in FD patients compared to controls. For example, patients had increased duodenal mucosal Th2 populations in the effector (13.03 ± 16.11, 19.84 ± 15.51, p=0.038), central memory (23.75 ± 18.97, 37.52 ± 17.51, p=0.007) and effector memory (9.80±10.50 vs 20.53±14.15, p=0.001) populations. Th17 populations were also increased in the effector (31.74±24.73 vs 45.57±23.75, p=0.03) and effector memory (11.95±8.42 vs 18.44±15.63, p=0.027) subsets. Peripheral T cell populations were unchanged between FD and control. Conclusion Our findings identify an association between lymphocyte populations and FD, specifically a Th2 and Th17 signature in the duodenal mucosa. The presence of effector and memory cells suggest that the microinflammation in FD is antigen driven.
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Affiliation(s)
- Grace L. Burns
- College of Health, Medicine and Wellbeing, The University of Newcastle, Callaghan, NSW, Australia,Immune Health Research Program, Hunter Medical Research Institute, New Lambton Heights, NSW, Australia,National Health & Medical Research Council (NHMRC) Centre of Research Excellence in Digestive Health, University of Newcastle, Newcastle, NSW, Australia
| | - Jessica K. Bruce
- College of Health, Medicine and Wellbeing, The University of Newcastle, Callaghan, NSW, Australia,Immune Health Research Program, Hunter Medical Research Institute, New Lambton Heights, NSW, Australia,National Health & Medical Research Council (NHMRC) Centre of Research Excellence in Digestive Health, University of Newcastle, Newcastle, NSW, Australia
| | - Kyra Minahan
- College of Health, Medicine and Wellbeing, The University of Newcastle, Callaghan, NSW, Australia,Immune Health Research Program, Hunter Medical Research Institute, New Lambton Heights, NSW, Australia,National Health & Medical Research Council (NHMRC) Centre of Research Excellence in Digestive Health, University of Newcastle, Newcastle, NSW, Australia
| | - Andrea Mathe
- College of Health, Medicine and Wellbeing, The University of Newcastle, Callaghan, NSW, Australia,Immune Health Research Program, Hunter Medical Research Institute, New Lambton Heights, NSW, Australia
| | - Thomas Fairlie
- National Health & Medical Research Council (NHMRC) Centre of Research Excellence in Digestive Health, University of Newcastle, Newcastle, NSW, Australia,Translational Research Institute, Brisbane, QLD, Australia,Department of Gastroenterology and Hepatology, Princess Alexandra Hospital, Brisbane, QLD, Australia
| | - Raquel Cameron
- College of Health, Medicine and Wellbeing, The University of Newcastle, Callaghan, NSW, Australia,Immune Health Research Program, Hunter Medical Research Institute, New Lambton Heights, NSW, Australia,National Health & Medical Research Council (NHMRC) Centre of Research Excellence in Digestive Health, University of Newcastle, Newcastle, NSW, Australia
| | - Crystal Naudin
- College of Health, Medicine and Wellbeing, The University of Newcastle, Callaghan, NSW, Australia,Immune Health Research Program, Hunter Medical Research Institute, New Lambton Heights, NSW, Australia
| | - Prema M. Nair
- College of Health, Medicine and Wellbeing, The University of Newcastle, Callaghan, NSW, Australia,Immune Health Research Program, Hunter Medical Research Institute, New Lambton Heights, NSW, Australia,National Health & Medical Research Council (NHMRC) Centre of Research Excellence in Digestive Health, University of Newcastle, Newcastle, NSW, Australia
| | - Michael D. E. Potter
- College of Health, Medicine and Wellbeing, The University of Newcastle, Callaghan, NSW, Australia,Immune Health Research Program, Hunter Medical Research Institute, New Lambton Heights, NSW, Australia,National Health & Medical Research Council (NHMRC) Centre of Research Excellence in Digestive Health, University of Newcastle, Newcastle, NSW, Australia
| | - Mudar Zand Irani
- College of Health, Medicine and Wellbeing, The University of Newcastle, Callaghan, NSW, Australia,Immune Health Research Program, Hunter Medical Research Institute, New Lambton Heights, NSW, Australia,National Health & Medical Research Council (NHMRC) Centre of Research Excellence in Digestive Health, University of Newcastle, Newcastle, NSW, Australia
| | - Steven Bollipo
- College of Health, Medicine and Wellbeing, The University of Newcastle, Callaghan, NSW, Australia,Department of Gastroenterology, John Hunter Hospital, Newcastle, NSW, Australia
| | - Robert Foster
- Department of Gastroenterology, John Hunter Hospital, Newcastle, NSW, Australia
| | - Lay T. Gan
- Department of Gastroenterology, John Hunter Hospital, Newcastle, NSW, Australia
| | - Ayesha Shah
- National Health & Medical Research Council (NHMRC) Centre of Research Excellence in Digestive Health, University of Newcastle, Newcastle, NSW, Australia,Translational Research Institute, Brisbane, QLD, Australia,Department of Gastroenterology and Hepatology, Princess Alexandra Hospital, Brisbane, QLD, Australia
| | - Natasha A. Koloski
- National Health & Medical Research Council (NHMRC) Centre of Research Excellence in Digestive Health, University of Newcastle, Newcastle, NSW, Australia,Translational Research Institute, Brisbane, QLD, Australia,Department of Gastroenterology and Hepatology, Princess Alexandra Hospital, Brisbane, QLD, Australia
| | - Paul S. Foster
- College of Health, Medicine and Wellbeing, The University of Newcastle, Callaghan, NSW, Australia,Immune Health Research Program, Hunter Medical Research Institute, New Lambton Heights, NSW, Australia
| | - Jay C. Horvat
- College of Health, Medicine and Wellbeing, The University of Newcastle, Callaghan, NSW, Australia,Immune Health Research Program, Hunter Medical Research Institute, New Lambton Heights, NSW, Australia
| | - Martin Veysey
- College of Health, Medicine and Wellbeing, The University of Newcastle, Callaghan, NSW, Australia,Hull-York Medical School, University of Hull, Hull, United Kingdom
| | - Gerald Holtmann
- National Health & Medical Research Council (NHMRC) Centre of Research Excellence in Digestive Health, University of Newcastle, Newcastle, NSW, Australia,Translational Research Institute, Brisbane, QLD, Australia,Department of Gastroenterology and Hepatology, Princess Alexandra Hospital, Brisbane, QLD, Australia
| | - Nick Powell
- Faculty of Medicine, Imperial College London, London, United Kingdom
| | - Marjorie M. Walker
- College of Health, Medicine and Wellbeing, The University of Newcastle, Callaghan, NSW, Australia,Immune Health Research Program, Hunter Medical Research Institute, New Lambton Heights, NSW, Australia,National Health & Medical Research Council (NHMRC) Centre of Research Excellence in Digestive Health, University of Newcastle, Newcastle, NSW, Australia
| | - Nicholas J. Talley
- College of Health, Medicine and Wellbeing, The University of Newcastle, Callaghan, NSW, Australia,Immune Health Research Program, Hunter Medical Research Institute, New Lambton Heights, NSW, Australia,National Health & Medical Research Council (NHMRC) Centre of Research Excellence in Digestive Health, University of Newcastle, Newcastle, NSW, Australia
| | - Simon Keely
- College of Health, Medicine and Wellbeing, The University of Newcastle, Callaghan, NSW, Australia,Immune Health Research Program, Hunter Medical Research Institute, New Lambton Heights, NSW, Australia,National Health & Medical Research Council (NHMRC) Centre of Research Excellence in Digestive Health, University of Newcastle, Newcastle, NSW, Australia,*Correspondence: Simon Keely,
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17
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Schinnerling K, Penny HA, Soto JA, Melo-Gonzalez F. Immune Responses at Host Barriers and Their Importance in Systemic Autoimmune Diseases. ADVANCES IN EXPERIMENTAL MEDICINE AND BIOLOGY 2023; 1408:3-24. [PMID: 37093419 DOI: 10.1007/978-3-031-26163-3_1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 04/25/2023]
Abstract
Host barriers such as the skin, the lung mucosa, the intestinal mucosa and the oral cavity are crucial at preventing contact with potential threats and are populated by a diverse population of innate and adaptive immune cells. Alterations in antigen recognition driven by genetic and environmental factors can lead to autoimmune systemic diseases such rheumatoid arthritis, systemic lupus erythematosus and food allergy. Here we review how different immune cells residing at epithelial barriers, host-derived signals and environmental signals are involved in the initiation and progression of autoimmune responses in these diseases. We discuss how regulation of innate responses at these barriers and the influence of environmental factors such as the microbiota can affect the susceptibility to develop local and systemic autoimmune responses particularly in the cases of food allergy, systemic lupus erythematosus and rheumatoid arthritis. Induction of pathogenic autoreactive immune responses at host barriers in these diseases can contribute to the initiation and progression of their pathogenesis.
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Affiliation(s)
| | - Hugo A Penny
- Academic Unit of Gastroenterology, Royal Hallamshire Hospital, Sheffield, S10 2JF, UK
- Department of Infection, Immunity and Cardiovascular Diseases, University of Sheffield, Sheffield, UK
| | - Jorge A Soto
- Facultad de Ciencias de la Vida, Universidad Andrés Bello, Santiago, Chile.
- Millennium Institute on Immunology and Immunotherapy, Santiago, Chile.
| | - Felipe Melo-Gonzalez
- Facultad de Ciencias de la Vida, Universidad Andrés Bello, Santiago, Chile.
- Millennium Institute on Immunology and Immunotherapy, Santiago, Chile.
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18
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Brown G, Hoedt EC, Keely S, Shah A, Walker MM, Holtmann G, Talley NJ. Role of the duodenal microbiota in functional dyspepsia. Neurogastroenterol Motil 2022; 34:e14372. [PMID: 35403776 PMCID: PMC9786680 DOI: 10.1111/nmo.14372] [Citation(s) in RCA: 19] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/20/2021] [Revised: 02/04/2022] [Accepted: 03/14/2022] [Indexed: 12/30/2022]
Abstract
BACKGROUND Functional dyspepsia (FD) is a common and debilitating gastrointestinal disorder attributed to altered gut-brain interactions. While the etiology of FD remains unknown, emerging research suggests the mechanisms are likely multifactorial and heterogenous among patient subgroups. Small bowel motor disturbances, visceral hypersensitivity, chronic microinflammation, and increased intestinal tract permeability have all been linked to the pathogenesis of FD. Recently, alterations to the gut microbiome have also been implicated to play an important role in the disease. Changes to the duodenal microbiota may either trigger or be a consequence of immune and neuronal disturbances observed in the disease, but the mechanisms of influence of small intestinal flora on gastrointestinal function and symptomatology are unknown. PURPOSE This review summarizes and synthesizes the literature on the link between the microbiota, low-grade inflammatory changes in the duodenum and FD. This review is not intended to provide a complete overview of FD or the small intestinal microbiota, but instead outline some of the key conceptual advances in understanding the interactions between altered gastrointestinal bacterial communities; dietary factors; host immune activation; and stimulation of the gut-brain axes in patients with FD versus controls. Current and emerging treatment approaches such as dietary interventions and antibiotic or probiotic use that have demonstrated symptom benefits for patients are reviewed, and their role in modulating the host-microbiota is discussed. Finally, suggested opportunities for diagnostic and therapeutic improvements for patients with this condition are presented.
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Affiliation(s)
- Georgia Brown
- School of Medicine and Public HealthUniversity of NewcastleNewcastleNew South WalesAustralia,AGIRA (Australian Gastrointestinal Research Alliance)NewcastleNew South WalesAustralia,NHMRC Centre of Research Excellence in Digestive HealthNewcastleNew South WalesAustralia
| | - Emily C. Hoedt
- AGIRA (Australian Gastrointestinal Research Alliance)NewcastleNew South WalesAustralia,NHMRC Centre of Research Excellence in Digestive HealthNewcastleNew South WalesAustralia,School of Biomedical Sciences and PharmacyUniversity of NewcastleNewcastleNew South WalesAustralia,Hunter Medical Research InstituteNew Lambton HeightsNewcastleNew South WalesAustralia
| | - Simon Keely
- AGIRA (Australian Gastrointestinal Research Alliance)NewcastleNew South WalesAustralia,NHMRC Centre of Research Excellence in Digestive HealthNewcastleNew South WalesAustralia,School of Biomedical Sciences and PharmacyUniversity of NewcastleNewcastleNew South WalesAustralia,Hunter Medical Research InstituteNew Lambton HeightsNewcastleNew South WalesAustralia
| | - Ayesha Shah
- AGIRA (Australian Gastrointestinal Research Alliance)NewcastleNew South WalesAustralia,NHMRC Centre of Research Excellence in Digestive HealthNewcastleNew South WalesAustralia,Faculty of Medicine and Faculty of Health and Behavioural SciencesThe University of QueenslandSt. LuciaQueenslandAustralia
| | - Marjorie M. Walker
- School of Medicine and Public HealthUniversity of NewcastleNewcastleNew South WalesAustralia,AGIRA (Australian Gastrointestinal Research Alliance)NewcastleNew South WalesAustralia,NHMRC Centre of Research Excellence in Digestive HealthNewcastleNew South WalesAustralia
| | - Gerald Holtmann
- AGIRA (Australian Gastrointestinal Research Alliance)NewcastleNew South WalesAustralia,NHMRC Centre of Research Excellence in Digestive HealthNewcastleNew South WalesAustralia,Faculty of Medicine and Faculty of Health and Behavioural SciencesThe University of QueenslandSt. LuciaQueenslandAustralia,Department of Gastroenterology & HepatologyPrincess Alexandra HospitalWoolloongabbaQueenslandAustralia
| | - Nicholas J. Talley
- School of Medicine and Public HealthUniversity of NewcastleNewcastleNew South WalesAustralia,AGIRA (Australian Gastrointestinal Research Alliance)NewcastleNew South WalesAustralia,NHMRC Centre of Research Excellence in Digestive HealthNewcastleNew South WalesAustralia,Hunter Medical Research InstituteNew Lambton HeightsNewcastleNew South WalesAustralia
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19
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Hussein H, Boeckxstaens GE. Immune-mediated food reactions in irritable bowel syndrome. Curr Opin Pharmacol 2022; 66:102285. [PMID: 36063569 DOI: 10.1016/j.coph.2022.102285] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/31/2022] [Revised: 05/23/2022] [Accepted: 08/03/2022] [Indexed: 11/03/2022]
Abstract
Irritable bowel syndrome (IBS) is a chronic functional gastrointestinal disorder characterized by recurrent abdominal pain and an altered defecation pattern. Depending on the criteria used, it affects between 5 and 10% of the general population and has a serious impact on quality of life. Most patients with IBS show an induction or exacerbation of their symptoms, particularly abdominal pain, after eating certain foods. This raises the question of the role played by food in IBS pathophysiology. In this review, we describe the multiple risk factors of IBS, and we give an overview of the role of food as a trigger of IBS, distinguishing between immune and non-immune reactions to food. We finally highlight recent findings identifying an immune-mediated mechanism underlying food-induced abdominal pain in IBS.
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Affiliation(s)
- Hind Hussein
- KU Leuven Department of Chronic Diseases, Metabolism and Ageing, Leuven, Belgium; Translational Research Centre for Gastrointestinal Disorders, Center for Intestinal Neuroimmune Interaction, Leuven, Belgium
| | - Guy E Boeckxstaens
- KU Leuven Department of Chronic Diseases, Metabolism and Ageing, Leuven, Belgium; Translational Research Centre for Gastrointestinal Disorders, Center for Intestinal Neuroimmune Interaction, Leuven, Belgium.
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20
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Jones MP, Shah A, Walker MM, Koloski NA, Holtmann G, Talley NJ. Overlap of heartburn, functional dyspepsia, and irritable bowel syndrome in a population sample: Prevalence, temporal stability, and associated comorbidities. Neurogastroenterol Motil 2022; 34:e14349. [PMID: 35293084 DOI: 10.1111/nmo.14349] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/23/2021] [Revised: 02/02/2022] [Accepted: 02/22/2022] [Indexed: 02/08/2023]
Abstract
BACKGROUND Co-occurring (overlapping) irritable bowel syndrome (IBS), functional dyspepsia (FD), and heartburn has been observed. However, whether it is a distinct entity has not been established, nor what clinical, demographic, lifestyle, and psychological traits are associated with it. This study sought to estimate the prevalence and temporal stability of this overlap and to identify features specific to it in order to gain some insights into the potential etiopathogenesis. METHODS Two waves of a survey to a population-representative sample were conducted 3 years apart, recruiting 1312 individuals for this study. The chance-expected probability of complete overlap (CO) was calculated and compared with the observed CO. A range of demographic, lifestyle factors, medical diagnoses, sleep quality, and psychological distress were tested to identify predictors of overlap using logistic regression. KEY RESULTS CO was observed in 2.1% (95% confidence interval 1.9, 3.7) of the sample and was closely replicated in wave 2 at 2.0%. The observed CO was greater than expected by chance (0.2%) to a statistically significant extent (p < 0.001). Overlap between IBS subtypes, FD subtypes, and heartburn was also elevated above chance expectation. Individuals with CO were separately differentiated from others with respect to elevated rates of self-reported medically diagnosed asthma, elevated psychological distress score, and elevated impact on sleep quality. The discrimination provided by these factors was further independent of age and sex. CONCLUSIONS AND INFERENCES Overlap between IBS, FD, and heartburn (GERD) appears to be a distinct entity that has a profile including psychological morbidity, sleep disturbance, and elevated rates of atopy.
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Affiliation(s)
- Michael P Jones
- School of Psychological Sciences, Macquarie University, North Ryde, New South Wales, Australia
| | - Ayesha Shah
- Department of Gastroenterology and Hepatology, Princess Alexandra Hospital and Translational Research Institute (TRI), Woolloongabba, Queensland, Australia.,Faculty of Medicine, University of Queensland, Brisbane, Queensland, Australia
| | - Marjorie M Walker
- College of Health, Medicine and Well Being, University of Newcastle, Newcastle, New South Wales, Australia
| | - Natasha A Koloski
- Department of Gastroenterology and Hepatology, Princess Alexandra Hospital and Translational Research Institute (TRI), Woolloongabba, Queensland, Australia.,Faculty of Medicine, University of Queensland, Brisbane, Queensland, Australia.,College of Health, Medicine and Well Being, University of Newcastle, Newcastle, New South Wales, Australia
| | - Gerald Holtmann
- Department of Gastroenterology and Hepatology, Princess Alexandra Hospital and Translational Research Institute (TRI), Woolloongabba, Queensland, Australia.,Faculty of Medicine, University of Queensland, Brisbane, Queensland, Australia
| | - Nicholas J Talley
- College of Health, Medicine and Well Being, University of Newcastle, Newcastle, New South Wales, Australia
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21
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Ito K, Kanemitsu Y, Kamiya T, Fukumitsu K, Takeda N, Tajiri T, Kurokawa R, Nishiyama H, Yap J, Fukuda S, Uemura T, Ohkubo H, Maeno K, Ito Y, Oguri T, Takemura M, Niimi A. Functional gastrointestinal disorders are associated with capsaicin cough sensitivity in severe asthma. Allergol Int 2022; 72:271-278. [PMID: 36192325 DOI: 10.1016/j.alit.2022.08.009] [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: 06/09/2022] [Revised: 08/06/2022] [Accepted: 08/30/2022] [Indexed: 11/17/2022] Open
Abstract
BACKGROUND Although sensory nerve dysfunction is related to the pathology of severe uncontrolled asthma and functional gastrointestinal disorders (FGIDs), the impact of comorbid FGIDs on the pathophysiology of severe uncontrolled asthma remains poorly understood. The aim was to clarify the physiological relationships between severe uncontrolled asthma and FGIDs. METHODS Fifty-two patients with severe uncontrolled asthma who visited our hospital between September 2016 and August 2019 were retrospectively analyzed. Clinical characteristics, other comorbidities including gastroesophageal reflux disease (GERD), and biomarkers such as fractional nitric oxide (FeNO) and capsaicin cough sensitivity (C-CS) before the beginning of biologics or bronchial thermoplasty, were compared between patients with and without comorbid FGIDs. C-CS was evaluated by C5 (concentration of inhaled capsaicin that induced five or more coughs), and C5 ≤2.44 μM was defined as heightened C-CS. RESULTS Seventeen patients had comorbid FGIDs. These patients had a lower FeNO level (21.9 ± 1.7 ppb vs. 33.9 ± 2.8 ppb, P = 0.04), a lower C5 threshold (2.24 ± 2.88 μM vs. 8.91 ± 5.5 μM, P < 0.001), a higher prevalence of comorbid GERD (64.7% vs. 31.7%, P = 0.03), and a higher prevalence of heightened C-CS (70.6% vs. 28.6%, P = 0.007) than those without FGIDs. Analysis of covariance showed a significant effect of FGIDs on C-CS in severe uncontrolled asthma without being affected by GERD. CONCLUSIONS Comorbid FGIDs are associated with heightened C-CS in patients with severe uncontrolled asthma, and they may be an important extra-respiratory manifestation of the airway neuronal dysfunction phenotype of severe uncontrolled asthma.
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Affiliation(s)
- Keima Ito
- Department of Respiratory Medicine, Allergy and Clinical Immunology, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan
| | - Yoshihiro Kanemitsu
- Department of Respiratory Medicine, Allergy and Clinical Immunology, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan.
| | - Takeshi Kamiya
- Department of Medical Innovation, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan
| | - Kensuke Fukumitsu
- Department of Respiratory Medicine, Allergy and Clinical Immunology, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan
| | - Norihisa Takeda
- Department of Respiratory Medicine, Allergy and Clinical Immunology, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan
| | - Tomoko Tajiri
- Department of Respiratory Medicine, Allergy and Clinical Immunology, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan
| | - Ryota Kurokawa
- Department of Respiratory Medicine, Allergy and Clinical Immunology, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan
| | - Hirono Nishiyama
- Department of Respiratory Medicine, Allergy and Clinical Immunology, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan
| | - Jennifer Yap
- Department of Respiratory Medicine, Allergy and Clinical Immunology, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan
| | - Satoshi Fukuda
- Department of Respiratory Medicine, Allergy and Clinical Immunology, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan
| | - Takehiro Uemura
- Department of Respiratory Medicine, Allergy and Clinical Immunology, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan
| | - Hirotsugu Ohkubo
- Department of Respiratory Medicine, Allergy and Clinical Immunology, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan
| | - Ken Maeno
- Department of Respiratory Medicine, Allergy and Clinical Immunology, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan
| | - Yutaka Ito
- Department of Respiratory Medicine, Allergy and Clinical Immunology, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan
| | - Tetsuya Oguri
- Department of Respiratory Medicine, Allergy and Clinical Immunology, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan; Department of Education and Research Center for Community Medicine, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan
| | - Masaya Takemura
- Department of Respiratory Medicine, Allergy and Clinical Immunology, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan; Department of Education and Research Center for Community Medicine, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan
| | - Akio Niimi
- Department of Respiratory Medicine, Allergy and Clinical Immunology, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan
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22
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Exploring the Differences in the Gut Microbiome in Atopic Dermatitis According to the Presence of Gastrointestinal Symptoms. J Clin Med 2022; 11:jcm11133690. [PMID: 35806975 PMCID: PMC9267706 DOI: 10.3390/jcm11133690] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/02/2022] [Revised: 06/24/2022] [Accepted: 06/24/2022] [Indexed: 02/04/2023] Open
Abstract
(1) Background: Atopic dermatitis (AD) is a multifactorial chronic allergic skin disease. Gastrointestinal (GI) functions have been suggested to be associated with its incidence or severity. As modulators of the gut–skin axis, gut microbes might affect the pathophysiology of AD. (2) Methods: We divided a cohort of patients with AD according to their GI symptoms as follows: AD with epigastric fullness (ADwEF), AD with epigastric rigidity (ADwER), and AD without GI symptoms (ADw/oGI). The gut microbial profiles were analyzed using 16S rRNA amplicon sequencing. (3) Results: The microbiota of the ADwER group showed low diversity indices in richness and evenness and formed a separate cluster to the other groups. In the ADwER group, the proportion of Bacteroides increased, while that of Prevotella decreased; functional pathways related to phosphotransferase systems were not abundant relative to those in the ADw/oGI group. Taken together, patients with AD with GI symptoms have a different microbiome from patients with simple AD. (4) Conclusions: In an exploratory study aimed at evaluating the relationship between AD and GI symptoms, the gut microbiome in patients with AD with GI symptoms differed from that in patients with simple AD, and this result could serve as a basis for further gut–skin axis studies.
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23
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Ceulemans M, Jacobs I, Wauters L, Vanuytsel T. Immune Activation in Functional Dyspepsia: Bystander Becoming the Suspect. Front Neurosci 2022; 16:831761. [PMID: 35557605 PMCID: PMC9087267 DOI: 10.3389/fnins.2022.831761] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/08/2021] [Accepted: 03/25/2022] [Indexed: 11/13/2022] Open
Abstract
Disorders of gut-brain interaction (DGBI), formerly termed functional gastrointestinal disorders (FGID), are highly prevalent although exact pathophysiological mechanisms remain unclear. Intestinal immune activation has been recognized, but increasing evidence supports a pivotal role for an active inflammatory state in these disorders. In functional dyspepsia (FD), marked eosinophil and mast cell infiltration has been repeatedly demonstrated and associations with symptoms emphasize the relevance of an eosinophil-mast cell axis in FD pathophysiology. In this Review, we highlight the importance of immune activation in DGBI with a focus on FD. We summarize eosinophil biology in both homeostasis and inflammatory processes. The evidence for immune activation in FD is outlined with attention to alterations on both cellular and molecular level, and how these may contribute to FD symptomatology. As DGBI are complex and multifactorial conditions, we shed light on factors associated to, and potentially influencing immune activation, including bidirectional gut-brain interaction, allergy and the microbiota. Crucial studies reveal a therapeutic benefit of treatments targeting immune activation, suggesting that specific anti-inflammatory therapies could offer renewed hope for at least a subset of DGBI patients. Lastly, we explore the future directions for DGBI research that could advance the field. Taken together, emerging evidence supports the recognition of FD as an immune-mediated organic-based disorder, challenging the paradigm of a strictly functional nature.
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Affiliation(s)
- Matthias Ceulemans
- Department of Chronic Diseases and Metabolism, Translational Research Center for Gastrointestinal Disorders (TARGID), Katholieke Universiteit Leuven, Leuven, Belgium
| | - Inge Jacobs
- Allergy and Clinical Immunology Research Group, Department of Microbiology, Immunology and Transplantation, Katholieke Universiteit Leuven, Leuven, Belgium
| | - Lucas Wauters
- Department of Chronic Diseases and Metabolism, Translational Research Center for Gastrointestinal Disorders (TARGID), Katholieke Universiteit Leuven, Leuven, Belgium
- Department of Gastroenterology and Hepatology, University Hospitals Leuven, Leuven, Belgium
| | - Tim Vanuytsel
- Department of Chronic Diseases and Metabolism, Translational Research Center for Gastrointestinal Disorders (TARGID), Katholieke Universiteit Leuven, Leuven, Belgium
- Department of Gastroenterology and Hepatology, University Hospitals Leuven, Leuven, Belgium
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24
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Aguilera-Lizarraga J, Hussein H, Boeckxstaens GE. Immune activation in irritable bowel syndrome: what is the evidence? Nat Rev Immunol 2022; 22:674-686. [PMID: 35296814 DOI: 10.1038/s41577-022-00700-9] [Citation(s) in RCA: 50] [Impact Index Per Article: 16.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 02/18/2022] [Indexed: 12/15/2022]
Abstract
Irritable bowel syndrome (IBS) is a chronic functional gastrointestinal disorder that is characterized by abdominal pain and an altered defecation pattern. It affects between 5 and 20% of the general population and can seriously impact quality of life. The pathophysiology of IBS is rather complex and multifactorial including, for example, altered signalling by the gut-brain axis, dysbiosis, abnormal visceral pain signalling and intestinal immune activation. The latter has gained particular interest in recent years, with growing insight into the bidirectional communication between the nervous system and the immune system. In this Review, we detail the current evidence suggesting that immune activation contributes to the pathology seen in patients with IBS and discuss the potential mechanisms involved. Moreover, we describe how immune mediators, particularly those released by mast cells, can directly activate or sensitize pain-transmitting nerves, leading to increased pain signalling and abdominal pain. Finally, we discuss the potential of interventions targeting immune activation as a new therapeutic strategy for patients suffering from IBS.
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Affiliation(s)
- Javier Aguilera-Lizarraga
- Laboratory for Intestinal Neuroimmune Interactions, Translational Research Centre for Gastrointestinal Disorders, Department of Chronic Diseases, Metabolism and Ageing, KU Leuven, Leuven, Belgium
| | - Hind Hussein
- Laboratory for Intestinal Neuroimmune Interactions, Translational Research Centre for Gastrointestinal Disorders, Department of Chronic Diseases, Metabolism and Ageing, KU Leuven, Leuven, Belgium
| | - Guy E Boeckxstaens
- Laboratory for Intestinal Neuroimmune Interactions, Translational Research Centre for Gastrointestinal Disorders, Department of Chronic Diseases, Metabolism and Ageing, KU Leuven, Leuven, Belgium.
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25
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Velosa M, Sifrim D. Editorial: rumination-more frequent than previously thought. Aliment Pharmacol Ther 2022; 55:112-113. [PMID: 34907563 DOI: 10.1111/apt.16660] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/19/2022]
Affiliation(s)
- Monica Velosa
- Wingate Institute of Neurogastroenterology, Barts and the London School of Medicine and Dentistry, Queen Mary University of London, London, UK
| | - Daniel Sifrim
- Wingate Institute of Neurogastroenterology, Barts and the London School of Medicine and Dentistry, Queen Mary University of London, London, UK
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26
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Zand Irani M, Talley NJ. Editorial: rumination-more frequent than previously thought. Authors' reply. Aliment Pharmacol Ther 2022; 55:114-115. [PMID: 34907562 DOI: 10.1111/apt.16682] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/09/2022]
Affiliation(s)
- Mudar Zand Irani
- NHMRC Centre of Research Excellence in Digestive Health, University of Newcastle and Hunter Medical Research Institute, Newcastle, Australia
| | - Nicholas J Talley
- NHMRC Centre of Research Excellence in Digestive Health, University of Newcastle and Hunter Medical Research Institute, Newcastle, Australia
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27
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Kim S, Keum B, Byun J, Kim B, Lee K, Yeon J, Lee J, Choi H, Kim E, Jeen Y, Lee H, Chun H, Kim T. Colonic Mucosal Immune Activation in Mice with Ovalbumin-Induced Allergic Airway Disease: Association between Allergic Airway Disease and Irritable Bowel Syndrome. Int J Mol Sci 2021; 23:ijms23010181. [PMID: 35008607 PMCID: PMC8745416 DOI: 10.3390/ijms23010181] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/12/2021] [Revised: 12/12/2021] [Accepted: 12/20/2021] [Indexed: 11/16/2022] Open
Abstract
Recent studies on the pathophysiology of irritable bowel syndrome (IBS) have focused on the role of mast cells (MCs) in intestinal mucosal immunity. A link between allergic airway diseases (AADs) and IBS has been suggested because both diseases have similar pathophysiology. We aimed to investigate whether the induction of AAD in mice could lead to inflammation of the colonic mucosa, similar to IBS. We also evaluated whether this inflammatory response could be suppressed by administering a therapeutic agent. Mice were divided into three groups: control, AAD-induced, and salbutamol-treated. An AAD mouse model was established by intraperitoneal injection and nasal challenge with ovalbumin. Mice with AAD were intranasally administered salbutamol. Analyses of cytokine levels, MC count, and tryptase levels in the intestinal mucosa were performed to compare the changes in inflammatory responses among the three groups. Inflammation was observed in the intestinal mucosa of mice in the AAD group. This inflammation in AAD mice was suppressed after salbutamol treatment. Our study demonstrates that AAD induces an inflammatory response similar to that in IBS, suggesting a possible association between IBS and AADs. In patients with IBS with such allergic components, salbutamol may have the potential to alleviate the inflammatory response.
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Affiliation(s)
- Sanghyun Kim
- Department of Internal Medicine, College of Medicine, Korea University, Seoul 02841, Korea; (S.K.); (B.K.); (J.L.); (H.C.); (E.K.); (Y.J.); (H.L.)
| | - Bora Keum
- Department of Internal Medicine, College of Medicine, Korea University, Seoul 02841, Korea; (S.K.); (B.K.); (J.L.); (H.C.); (E.K.); (Y.J.); (H.L.)
| | - Junhyoung Byun
- Department of Otorhinolaryngology-Head & Neck Surgery, College of Medicine, Korea University, Seoul 02841, Korea; (J.B.); (B.K.); (K.L.); (J.Y.)
| | - Byoungjae Kim
- Department of Otorhinolaryngology-Head & Neck Surgery, College of Medicine, Korea University, Seoul 02841, Korea; (J.B.); (B.K.); (K.L.); (J.Y.)
| | - Kijeong Lee
- Department of Otorhinolaryngology-Head & Neck Surgery, College of Medicine, Korea University, Seoul 02841, Korea; (J.B.); (B.K.); (K.L.); (J.Y.)
| | - Jiwoo Yeon
- Department of Otorhinolaryngology-Head & Neck Surgery, College of Medicine, Korea University, Seoul 02841, Korea; (J.B.); (B.K.); (K.L.); (J.Y.)
| | - Jaemin Lee
- Department of Internal Medicine, College of Medicine, Korea University, Seoul 02841, Korea; (S.K.); (B.K.); (J.L.); (H.C.); (E.K.); (Y.J.); (H.L.)
| | - Hyuksoon Choi
- Department of Internal Medicine, College of Medicine, Korea University, Seoul 02841, Korea; (S.K.); (B.K.); (J.L.); (H.C.); (E.K.); (Y.J.); (H.L.)
| | - Eunsun Kim
- Department of Internal Medicine, College of Medicine, Korea University, Seoul 02841, Korea; (S.K.); (B.K.); (J.L.); (H.C.); (E.K.); (Y.J.); (H.L.)
| | - Yoontae Jeen
- Department of Internal Medicine, College of Medicine, Korea University, Seoul 02841, Korea; (S.K.); (B.K.); (J.L.); (H.C.); (E.K.); (Y.J.); (H.L.)
| | - Hongsik Lee
- Department of Internal Medicine, College of Medicine, Korea University, Seoul 02841, Korea; (S.K.); (B.K.); (J.L.); (H.C.); (E.K.); (Y.J.); (H.L.)
| | - Hoonjai Chun
- Department of Internal Medicine, College of Medicine, Korea University, Seoul 02841, Korea; (S.K.); (B.K.); (J.L.); (H.C.); (E.K.); (Y.J.); (H.L.)
- Correspondence: (H.C.); (T.K.)
| | - Taehoon Kim
- Department of Otorhinolaryngology-Head & Neck Surgery, College of Medicine, Korea University, Seoul 02841, Korea; (J.B.); (B.K.); (K.L.); (J.Y.)
- Correspondence: (H.C.); (T.K.)
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28
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Irani MZ, Jones MP, Halland M, Herrick L, Choung RS, Loftus YAS, Walker MM, Murray JA, Talley NJ. Prevalence, symptoms and risk factor profile of rumination syndrome and functional dyspepsia: a population-based study. Aliment Pharmacol Ther 2021; 54:1416-1431. [PMID: 34626489 PMCID: PMC10835603 DOI: 10.1111/apt.16630] [Citation(s) in RCA: 20] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/13/2021] [Revised: 08/26/2021] [Accepted: 09/21/2021] [Indexed: 12/11/2022]
Abstract
BACKGROUND Rumination syndrome is a functional gastroduodenal disorder characterised by effortless regurgitation of recently ingested food. Emerging evidence reports duodenal eosinophilic inflammation in a subset, suggesting a shared pathophysiology with functional dyspepsia (FD). AIM To assess the clinical features of rumination syndrome and FD in a community-based study. METHODS We mailed a survey assessing gastrointestinal symptoms, diet and psychological symptoms to 9835 residents of Olmsted County, MN, USA in 2017-2018; diagnostic codes were obtained from linked clinical records. The two disorders were assessed as mutually exclusive in 'pure' forms with a separate overlap group, all compared to a control group not meeting criteria for either. Prevalence of associations, and univariate and independent associations with predictors were assessed by logistic regression. RESULTS Prevalence of rumination syndrome and FD were 5.8% and 7.1%, respectively; the overlap was 3.83-times more likely than expected by chance. Independent predictors for rumination (odds ratio (OR), 95% confidence interval (CI)) were female gender (1.79, 1.21-2.63), smoking (1.89, 1.28-2.78), gluten-free diet (1.58, 1.14-2.19), allergic rhinitis (1.45, 1.01-2.08) and depression (1.10, 1.05-1.16). FD was independently associated with female gender, depression, non-coeliac wheat sensitivity, migraine, irritable bowel syndrome and somatic symptoms. A similar reported efficacy (≥54%) of low fat or dairy-free diets was found with both disorders (P = 0.53 and P = 1.00, respectively). The strongest independent associations with overlapping FD and rumination syndrome were a history of rheumatoid arthritis (3.93, 1.28-12.06) and asthma (3.02, 1.44-6.34). CONCLUSION Rumination syndrome overlaps with FD with a shared risk factor profile, suggesting a common pathophysiology.
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Affiliation(s)
- Mudar Zand Irani
- Faculty of Health and Medicine, University of Newcastle, Newcastle, Australia
- NHMRC Centre of Research Excellence in Digestive Health
- Hunter Medical Research Institute, New Lambton Heights, Australia
| | - Michael P. Jones
- NHMRC Centre of Research Excellence in Digestive Health
- School of Psychological Sciences, Macquarie University, North Ryde, Australia
| | - Magnus Halland
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota
| | - Linda Herrick
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota
| | - Rok Seon Choung
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota
| | | | - Marjorie M. Walker
- Faculty of Health and Medicine, University of Newcastle, Newcastle, Australia
- NHMRC Centre of Research Excellence in Digestive Health
| | - Joseph A. Murray
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota
| | - Nicholas J. Talley
- Faculty of Health and Medicine, University of Newcastle, Newcastle, Australia
- NHMRC Centre of Research Excellence in Digestive Health
- Hunter Medical Research Institute, New Lambton Heights, Australia
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Jones MP, Shah A, Walker MM, Koloski NA, Holtmann G, Talley NJ. Antibiotic use but not gastrointestinal infection frequently precedes first diagnosis of functional gastrointestinal disorders. United European Gastroenterol J 2021; 9:1074-1080. [PMID: 34653313 PMCID: PMC8598965 DOI: 10.1002/ueg2.12164] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/10/2021] [Accepted: 07/27/2021] [Indexed: 12/17/2022] Open
Abstract
INTRODUCTION While the etiopathogenesis of functional gastrointestinal disorders (FGIDs) is not completely understood, alterations of the intestinal microbiome have been observed. Antibiotics can induce dysbiosis, but whether antibiotics are a risk factor for the onset of FGIDs is uncertain. Antibiotics have been reported as both a risk factor for new onset FGID but also as a therapy for existing FGID. This study aimed to estimate the fraction of cases where antibiotics provoked the onset of FGID. METHOD Electronic medical records were obtained from general practices (primary care) in the United Kingdom. Dates of antibiotic prescription (AP) were compared with first date of FGID diagnosis and contrasted across three prevalent FGIDs and controls without gastrointestinal disorders. RESULTS There were 10,926 GI healthy controls, 4326 IBS alone, 3477 FD alone, 340 chronic constipation and 4402 with overlap of multiple conditions. Both the prevalence of AP and rate were higher in FGID patients and increased with diagnosis of multiple FGIDs. 7%-14% of FGID patients were prescribed their first recorded antibiotic in the 12 months prior to their first FGID diagnosis and 20%-33% were prescribed an antibiotic in the same period. Differences between FGID groups were not accounted for by social deprivation and only rate of AP was moderated by social deprivation. In contrast, only 5%-10% of patients ever had a gastrointestinal infection recorded and only 1.5%-3.5% prior to their first FGID diagnosis. CONCLUSION These data indicate that antibiotics are prescribed prior to FGID diagnosis in a significant minority of care-seeking FGID patients, opening the potential for this medication to contribute to the pathophysiology. APs appears to mostly be for non-gastrointestinal conditions.
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Affiliation(s)
- Michael P. Jones
- School of Psychological SciencesMacquarie UniversityNorth RydeNew South WalesAustralia
| | - Ayesha Shah
- Department of Gastroenterology and HepatologyPrincess Alexandra Hospital and Translational Research Institute (TRI)WoolloongabbaQueenslandAustralia
- Faculty of MedicineUniversity of QueenslandBrisbaneQueenslandAustralia
| | - Marjorie M. Walker
- College of Health, Medicine and Well BeingUniversity of NewcastleNewcastleNew South WalesAustralia
| | - Natasha A. Koloski
- Department of Gastroenterology and HepatologyPrincess Alexandra Hospital and Translational Research Institute (TRI)WoolloongabbaQueenslandAustralia
- Faculty of MedicineUniversity of QueenslandBrisbaneQueenslandAustralia
- College of Health, Medicine and Well BeingUniversity of NewcastleNewcastleNew South WalesAustralia
| | - Gerald Holtmann
- Department of Gastroenterology and HepatologyPrincess Alexandra Hospital and Translational Research Institute (TRI)WoolloongabbaQueenslandAustralia
- Faculty of MedicineUniversity of QueenslandBrisbaneQueenslandAustralia
| | - Nicholas J. Talley
- College of Health, Medicine and Well BeingUniversity of NewcastleNewcastleNew South WalesAustralia
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Melchior C, Fremaux S, Jouët P, Macaigne G, Raynaud JJ, Facon S, Iglicki F, Taes Y, Sabate JM. Perceived Gastrointestinal Symptoms and Association With Meals in a French Cohort of Patients With Irritable Bowel Syndrome. J Neurogastroenterol Motil 2021; 27:574-580. [PMID: 34642277 PMCID: PMC8521472 DOI: 10.5056/jnm20201] [Citation(s) in RCA: 2] [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] [Received: 09/08/2020] [Revised: 11/13/2020] [Accepted: 12/02/2020] [Indexed: 12/13/2022] Open
Abstract
Background/Aims The aim of our study is to evaluate the association between meals and perceived gastrointestinal symptoms in real life in a French cohort of irritable bowel syndrome (IBS) patients. Methods This prospective cross-sectional observational study included patients from the French association (association des patients souffrant du syndrome de l’intestin irritable [APSSII]) of IBS. Data were collected on demographics, IBS subtype, dietary food, and meal-induced gastrointestinal symptoms from patient filled self-questionnaires or questionnaires. Results Eighty-four patients with IBS were included; 82.3% female with a mean age of 46.9 ± 15.7 years. Each transit pattern subtype represented one-third of the population. Forty-five percent of patients had severe IBS according to IBS-Severity Scoring System; mean IBS Quality of Life score was 53.9 ± 18.3. Patients believed that food could trigger or exacerbate gastrointestinal symptoms in 73.3% and 93.4%, respectively. Eighty-nine percent had already tried diets, mostly lactose free diet and low fermentable, oligosaccharides, disaccharides, monosaccharides, and polyols diet in 61.3% and 53.6% of cases. Thirty-nine percent of meals induced gastrointestinal symptoms. Meal-induced gastrointestinal symptoms were associated with severity and subtype but not with quality of life. Conclusions This study has confirmed the important link between gastrointestinal symptoms and food. Gastrointestinal symptoms induced by meals are frequent and associated with severity and IBS-diarrhea subtype. Our study also underlines patients’ interest in food and diet. More knowledge is needed on food that triggers IBS symptoms but also on diet conditions in order to improve this condition.
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Affiliation(s)
- Chloé Melchior
- INSERM UMR 1073, Institute for Research and Innovation in Biomedicine, Normandy University, Rouen, France.,Department of Gastroenterology and INSERM CIC-CRB 1404, Rouen University Hospital, Rouen, France.,Department of Molecular and Clinical Medicine, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden
| | - Simon Fremaux
- Service de Gastroentérologie, Hôpital Avicenne AP-HP, INSERM U-987, Bobigny, France
| | - Pauline Jouët
- Service de Gastroentérologie, Hôpital Avicenne AP-HP, INSERM U-987, Bobigny, France
| | - Gilles Macaigne
- Department of Hepatogastroenterology, Marne-la-Vallee Hospital, Jossigny, France
| | - Jean-Jacques Raynaud
- Service de Gastroentérologie, Hôpital Avicenne AP-HP, INSERM U-987, Bobigny, France
| | - Suzelle Facon
- The French Association of IBS Patients (APSSII), Paris France
| | - Franck Iglicki
- Gastroenterology Unit, AP-HP, Louis Mourier Hospital and Denis Diderot University Paris 7, Paris, France
| | | | - Jean-Marc Sabate
- Service de Gastroentérologie, Hôpital Avicenne AP-HP, INSERM U-987, Bobigny, France
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Ronkainen J, Aro P, Jones M, Walker MM, Agréus L, Andreasson A, Talley NJ. Duodenal eosinophilia and the link to anxiety: A population-based endoscopic study. Neurogastroenterol Motil 2021; 33:e14109. [PMID: 33687126 DOI: 10.1111/nmo.14109] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/27/2020] [Revised: 01/27/2021] [Accepted: 02/05/2021] [Indexed: 02/06/2023]
Abstract
INTRODUCTION The concept of gut-to-brain communication via microbial or inflammatory pathways is gaining increased attention but genuine pathology directly linking gut perturbation to anxiety is lacking. We hypothesized that duodenal eosinophilia, as known to occur in functional dyspepsia (FD), may be an underlying cause of anxiety and may help explain the striking association between FD and anxiety. METHODS Randomly selected subjects from the national population register of Sweden completed the validated Abdominal Symptom Questionnaire; 1000 completed esophagogastroduodenoscopy and the Hospital Anxiety and Depression Scale questionnaire. Duodenal biopsies were obtained from 1st (D1) and 2nd portion (D2). Eligible subjects who underwent endoscopy (n = 887) were invited to participate in a 10-year follow-up study with the same questionnaires. Among endoscopy normal subjects, FD was identified by Rome criteria, and controls were symptom free. Duodenal eosinophilia was based on pre-defined cut-offs. Finding are reported as odds ratios (ORs) with 95% confidence interval and p-value. RESULTS The study population comprised 89 cases with FD and 124 healthy controls (mean age 62 years, SD 12, 34% male). Clinical anxiety at follow-up was elevated in those with D1 eosinophilia at baseline considering either new-onset anxiety (OR = 4.5, 95% CI 0.8, 23.8; p = 0.08) or follow-up anxiety adjusting for baseline anxiety (OR = 4.51 (95% CI 1.03, 19.81; p = 0.046). CONCLUSION Duodenal eosinophilia may potentially be a mechanism linked to anxiety independent of FD.
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Affiliation(s)
- Jukka Ronkainen
- Center for Life Course Health Research, University of Oulu, Oulu, Finland.,Primary Health Care Center, Tornio, Finland
| | | | - Mike Jones
- Macquarie University, North Ryde, NSW, Australia
| | - Marjorie M Walker
- Priority Research Centre for Digestive Health and Neurogastroenterology, Faculty of Health and Medicine, University of Newcastle, Newcastle, Australia.,Hunter Medical Research Institute, Lot 1, Kookaburra Circuit, New Lambton Heights, NSW, Australia
| | - Lars Agréus
- Division of Family Medicine and Primary Care, Division of Neurobiology, Care Sciences and Society, Karolinska Institutet, Stockholm, Sweden
| | - Anna Andreasson
- Macquarie University, North Ryde, NSW, Australia.,Stress Research Institute, Stockholm University, Stockholm, Sweden.,Department of Medicine Solna, Karolinska Institutet, Stockholm, Sweden
| | - Nicholas J Talley
- Priority Research Centre for Digestive Health and Neurogastroenterology, Faculty of Health and Medicine, University of Newcastle, Newcastle, Australia.,Hunter Medical Research Institute, Lot 1, Kookaburra Circuit, New Lambton Heights, NSW, Australia
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Sjölund J, Kull I, Bergström A, Järås J, Ludvigsson JF, Törnblom H, Simrén M, Olén O. Allergy-related diseases in childhood and risk for abdominal pain-related functional gastrointestinal disorders at 16 years-a birth cohort study. BMC Med 2021; 19:214. [PMID: 34526042 PMCID: PMC8444367 DOI: 10.1186/s12916-021-02069-3] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/14/2021] [Accepted: 07/21/2021] [Indexed: 12/31/2022] Open
Abstract
BACKGROUND Studies on allergy-related diseases in relation to abdominal pain-related functional gastrointestinal disorders (AP-FGIDs) in children are few and results are contradictory. We examined the associations between childhood allergy-related diseases and adolescent AP-FGIDs in general and irritable bowel syndrome (IBS) in particular. METHOD Prospective population-based birth cohort study of 4089 children born in Sweden 1994-1996. We analysed data from 2949 children with complete follow-up at 16 years (y) and no diagnosis of inflammatory bowel disease or coeliac disease at 12y or 16y. Asthma, rhinitis, eczema, and food hypersensitivity (FH) were assessed through questionnaires at 1-2y, 4y, 8y, 12y, and 16y. AP-FGIDs and IBS were assessed through questionnaires at 16y and defined according to the Rome III criteria. Associations between childhood allergy-related diseases and any AP-FGID and IBS and 16y respectively were examined using binomial generalized linear models with a log link function and described as relative risk with 95% confidence intervals. RESULTS The prevalence of any AP-FGID and IBS at 16y were 12.0% and 6.0% respectively. Eczema at 1-2y, 4y, and 8y, and FH at 12y and 16y were associated with an increased risk for any AP-FGID at 16y. Asthma and FH at 12y and 16y were associated with an increased risk for IBS at 16y. The relative risk for IBS at 16y increased with increasing number of concurrent allergy-related diseases at 16y, but linear trend for relative risk was only borderline statistically significant (P for trend = 0.05). CONCLUSIONS This prospective population-based study demonstrated positive associations between childhood allergy-related diseases and adolescent AP-FGIDs, including IBS, implicating shared pathophysiology among these disorders.
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Affiliation(s)
- Jessica Sjölund
- Department of Molecular and Clinical Medicine, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Box 428, 405 30, Gothenburg, Sweden.
| | - Inger Kull
- Department of Clinical Science and Education, Södersjukhuset, Karolinska Institutet, Stockholm, Sweden.,Sachs' Children's Hospital, Stockholm, Sweden
| | - Anna Bergström
- Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden.,Centre for Occupational and Environmental Medicine, Stockholm County Council, Stockholm, Sweden
| | - Jacob Järås
- Division of Clinical Epidemiology, Department of Medicine Solna, Karolinska Institutet, Stockholm, Sweden
| | - Jonas F Ludvigsson
- Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.,Department of Paediatrics, Örebro University Hospital, Örebro, Sweden.,Division of Epidemiology and Public Health, School of Medicine, University of Nottingham, Nottingham, UK.,Department of Medicine, Columbia University College of Physicians and Surgeons, New York, NY, USA
| | - Hans Törnblom
- Department of Molecular and Clinical Medicine, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Box 428, 405 30, Gothenburg, Sweden
| | - Magnus Simrén
- Department of Molecular and Clinical Medicine, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Box 428, 405 30, Gothenburg, Sweden.,Centre for Functional GI and Motility Disorders, University of North Carolina, Chapel Hill, NC, USA
| | - Ola Olén
- Sachs' Children's Hospital, Stockholm, Sweden.,Division of Clinical Epidemiology, Department of Medicine Solna, Karolinska Institutet, Stockholm, Sweden
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Beser OF, Cullu Cokugras F, Dogan G, Akgun O, Elevli M, Yilmazbas P, Ocal M, Bayrak NA, Sezer Yamanel RG, Bozaykut A, Celtik C, Polat E, Gerenli N, Bozlak S, Ayyildiz Civan H, Ozkul Saglam N, Hatipoglu SS, Özgürhan G, Sunnetci Silistre E, Solmaz B, Kutluk G, Genc HS, Onal H, Usta AM, Urganci N, Sahin A, Cam S, Yildirim S, Yildirim A, Vandenplas Y. The frequency of and factors affecting functional gastrointestinal disorders in infants that presented to tertiary care hospitals. Eur J Pediatr 2021; 180:2443-2452. [PMID: 33811535 DOI: 10.1007/s00431-021-04059-2] [Citation(s) in RCA: 14] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/22/2021] [Revised: 03/21/2021] [Accepted: 03/29/2021] [Indexed: 12/17/2022]
Abstract
This study aimed to determine the prevalence of infantile functional gastrointestinal disorders (FGIDs) based on Rome IV diagnostic criteria, and to determine the associated patient demographic and nutritional characteristics. A total of 2383 infants aged 1-12 months which were evaluated by 28 general pediatricians and pediatric gastroenterologists on the same day at nine tertiary care hospitals around Istanbul, Turkey, between November 2017 and March 2018, were included in the study. Patients included consulted the pediatric outpatient clinics because of any complaints, but not for vaccines and/or routine well child follow-ups as this is not part of the activities in the tertiary care hospitals. The patients were diagnosed with FGIDs based on Rome IV diagnostic criteria. The patients were divided into a FGID group and non-FGID group, and anthropometric measurements, physical examination findings, nutritional status, risk factors, and symptoms related to FGIDs were evaluated using questionnaires. Among the 2383 infants included, 837 (35.1%) had ≥1 FGIDs, of which 260 (31%) had already presented to hospital with symptoms of FGIDs and 577 (69%) presented to hospital with other symptoms, but were diagnosed with FGIDs by a pediatrician. Infant colic (19.2%), infant regurgitation (13.4%), and infant dyschezia (9.8%) were the most common FGIDs. One FGID was present in 76%, and ≥2 FGIDs were diagnosed in 24%. The frequency of early supplementary feeding was higher in the infants in the FGID group aged ≤6 months than in the non-FGID group (P = 0.039).Conclusion: FGIDs occur quite common in infants. Since early diversification was associated with the presence of FGIDs, nutritional guidance and intervention should be part of the first-line treatment. Only 31% of the infants diagnosed with a FGID were presented because of symptoms indicating a FGID. What is Known: • The functional gastrointestinal disorders (FGIDs) are a very common disorder and affect almost half of all infants. • In infants, the frequency of FGIDs increases with mistakes made in feeding. When FGIDs are diagnosed in infants, nutritional support should be the first-line treatment. What is New: • This study shows that only a third of children presented to hospital because of the symptoms of FGIDs, but pediatricians were able to make the diagnosis in suspected infants after appropriate evaluation. • The early starting of complementary feeding (<6 months) is a risk factor for the development of FGIDs.
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Affiliation(s)
- Omer Faruk Beser
- Cerrahpasa Medical Faculty, Paediatric Gastroenterology, Hepatology and Nutrition, Istanbul University-Cerrahpasa, Istanbul, Turkey.
| | - Fugen Cullu Cokugras
- Cerrahpasa Medical Faculty, Paediatric Gastroenterology, Hepatology and Nutrition, Istanbul University-Cerrahpasa, Istanbul, Turkey
| | - Guzide Dogan
- Haseki Education and Training Hospital, Department of Paediatric, University of Health Sciences, Istanbul, Turkey
| | - Ozlem Akgun
- Haseki Education and Training Hospital, Department of Paediatric, University of Health Sciences, Istanbul, Turkey
| | - Murat Elevli
- Haseki Education and Training Hospital, Department of Paediatric, University of Health Sciences, Istanbul, Turkey
| | - Pinar Yilmazbas
- Okmeydani Education and Training Hospital, Department of Paediatric, University of Health Sciences, Istanbul, Turkey
| | - Meric Ocal
- Okmeydani Education and Training Hospital, Department of Paediatric, University of Health Sciences, Istanbul, Turkey
| | - Nevzat Aykut Bayrak
- Zeynep Kamil Education and Training Hospital, Department of Paediatric, University of Health Sciences, Istanbul, Turkey
| | - Rabia Gonul Sezer Yamanel
- Zeynep Kamil Education and Training Hospital, Department of Paediatric, University of Health Sciences, Istanbul, Turkey
| | - Abdulkadir Bozaykut
- Zeynep Kamil Education and Training Hospital, Department of Paediatric, University of Health Sciences, Istanbul, Turkey
| | - Coşkun Celtik
- Umraniye Education and Training Hospital, Paediatric Gastroenterology, Hepatology and Nutrition, University of Health Sciences, Istanbul, Turkey
| | - Esra Polat
- Umraniye Education and Training Hospital, Paediatric Gastroenterology, Hepatology and Nutrition, University of Health Sciences, Istanbul, Turkey
| | - Nelgin Gerenli
- Umraniye Education and Training Hospital, Paediatric Gastroenterology, Hepatology and Nutrition, University of Health Sciences, Istanbul, Turkey
| | - Serdar Bozlak
- Umraniye Education and Training Hospital, Department of Paediatric, University of Health Sciences, Istanbul, Turkey
| | - Hasret Ayyildiz Civan
- Bakirkoy Dr. Sadi Konuk Education and Training Hospital, Department of Paediatric, University of Health Sciences, Istanbul, Turkey
| | - Neslihan Ozkul Saglam
- Bakirkoy Dr. Sadi Konuk Education and Training Hospital, Department of Paediatric, University of Health Sciences, Istanbul, Turkey
| | - Sadik Sami Hatipoglu
- Bakirkoy Dr. Sadi Konuk Education and Training Hospital, Department of Paediatric, University of Health Sciences, Istanbul, Turkey
| | - Gamze Özgürhan
- Istanbul Education and Training Hospital, Department of Paediatric, University of Health Sciences, Istanbul, Turkey
| | - Eda Sunnetci Silistre
- Istanbul Education and Training Hospital, Department of Paediatric, University of Health Sciences, Istanbul, Turkey
| | - Burcu Solmaz
- Istanbul Education and Training Hospital, Department of Paediatric, University of Health Sciences, Istanbul, Turkey
| | - Gunsel Kutluk
- Kanuni Sultan Suleyman Education and Training Hospital, Paediatric Gastroenterology, Hepatology and Nutrition, University of Health Sciences, Istanbul, Turkey
| | - Hamide Sevinc Genc
- Kanuni Sultan Suleyman Education and Training Hospital, Department of Paediatric, University of Health Sciences, Istanbul, Turkey
| | - Hasan Onal
- Kanuni Sultan Suleyman Education and Training Hospital, Pediatric Metabolic Disease, University of Health Sciences, Istanbul, Turkey
| | - Ayse Merve Usta
- Sisli Hamidiye Etfal Education and Training Hospital, Paediatric Gastroenterology, Hepatology and Nutrition, University of Health Sciences, Istanbul, Turkey
| | - Nafiye Urganci
- Sisli Hamidiye Etfal Education and Training Hospital, Paediatric Gastroenterology, Hepatology and Nutrition, University of Health Sciences, Istanbul, Turkey
| | - Ayse Sahin
- Sisli Hamidiye Etfal Education and Training Hospital, Department of Paediatric, University of Health Sciences, Istanbul, Turkey
| | - Sebahat Cam
- Goztepe Education and Training Hospital, Paediatric Gastroenterology, Hepatology and Nutrition, Medeniyet University, Istanbul, Turkey
| | - Sema Yildirim
- Goztepe Education and Training Hospital, Department of Paediatric, Medeniyet University, Istanbul, Turkey
| | - Asilay Yildirim
- Goztepe Education and Training Hospital, Department of Paediatric, Medeniyet University, Istanbul, Turkey
| | - Yvan Vandenplas
- Kidz Health Castle, Paediatric Gastroenterology, Hepatology and Nutrition, Universitair Ziekenhuis Brussel, Brussel, Belgium
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Friesen C, Colombo J, Schurman J. Update on the Role of Allergy in Pediatric Functional Abdominal Pain Disorders: A Clinical Perspective. Nutrients 2021; 13:2056. [PMID: 34208479 PMCID: PMC8235503 DOI: 10.3390/nu13062056] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/13/2021] [Revised: 06/07/2021] [Accepted: 06/12/2021] [Indexed: 11/16/2022] Open
Abstract
Both functional abdominal pain disorders (FAPDs) and food allergies are relatively common in children and adolescents, and most studies report an association between FAPDs and allergic conditions. FAPDs share pathophysiologic processes with allergies, including both immune and psychological processes interacting with the microbiome. No conclusive data are implicating IgE-mediated reactions to foods in FAPDs; however, there may be patients who have IgE reactions localized to the gastrointestinal mucosa without systemic symptoms that are not identified by common tests. In FAPDs, the data appears stronger for aeroallergens than for foods. It also remains possible that food antigens initiate an IgG reaction that promotes mast cell activation. If a food allergen is identified, the management involves eliminating the specific food from the diet. In the absence of systemic allergic symptoms or oral allergy syndrome, it appears unlikely that allergic triggers for FAPDs can be reliably identified by standard testing. Medications used to blunt allergic reactions or symptomatically treat allergic reactions may be useful in FAPDs. The purpose of the current manuscript is to review the current literature regarding the role of allergy in FAPDs from a clinical perspective, including how allergy may fit in the current model of FAPDs.
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Affiliation(s)
- Craig Friesen
- Division of Gastroenterology, Hepatology and Nutrition, Children’s Mercy Kansas City, School of Medicine, University of Missouri-Kansas City, Kansas City, MO 64108, USA; (J.C.); (J.S.)
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Huang YC, Wu MC, Wang YH, Wei JCC. Influence of constipation on atopic dermatitis: A nationwide population-based cohort study in Taiwan. Int J Clin Pract 2021; 75:e13691. [PMID: 32852877 DOI: 10.1111/ijcp.13691] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/24/2020] [Accepted: 08/21/2020] [Indexed: 12/19/2022] Open
Abstract
BACKGROUND Atopic dermatitis (AD) is the chronic inflammatory disorder that affects both in childhood and adulthood. Mounting evidence indicates that gut dysbiosis contributes to AD via the gut-skin axis. Constipation can result in alteration of the gut microflora. The clinical impact of constipation on AD has not been researched. Therefore, we aim to assess the risk of AD in constipated patients by the population-based cohort study. METHODS We collected 85 554 constipated people and 85 554 people without constipation between 1999 and 2013 from the Taiwanese National Health Insurance Research Database. Propensity score analysis was administrated to match age, gender, comorbidities and medications at a ratio of 1:1. Multiple Cox regression analysis was utilised to evaluate the adjusted hazard ratio of AD. In addition, sensitivity tests and a stratified analysis were conducted. RESULTS The incidence of AD was 4.9 per 1000 person-years in the constipation group, which was higher than the rate of 2.1 per 1000 person-years observed in the non-constipation group. After adjustment for age, gender, comorbidities, corticosteroids, antihistamine and antibiotics, constipated people had a 2.31-fold greater risk of AD compared with those without constipation (adjusted hazard ratio [aHR]: 2.31 (95% CI 2.17-2.46). Moreover, constipated people had a higher likelihood of AD, regardless of gender, comorbidities, as well as the usage of corticosteroids, antihistamines and antibiotics. CONCLUSION Constipation is associated with a significantly risk factor of AD. Clinicians should be careful of the possibility of AD in constipated people. Further study is warranted to investigate the possible pathological mechanisms of this relationship.
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Affiliation(s)
- Yen-Chu Huang
- Division of Pediatric Gastroenterology, Children's Medical Center, Taichung Veterans General Hospital, Taichung City, Taiwan
| | - Meng-Che Wu
- Division of Pediatric Gastroenterology, Children's Medical Center, Taichung Veterans General Hospital, Taichung City, Taiwan
| | - Yu-Hsun Wang
- Department of Medical Research, Chung Shan Medical University Hospital, Taichung City, Taiwan
| | - James Cheng-Chung Wei
- Department of Rheumatology, BenQ Medical Center, The Affiliated BenQ Hospital of Nanjing Medical University, Nanjing, China
- Beijing Tsinghua Changgung Hospital, School of Clinical Medicine, Tsinghua University, Beijing, China
- Division of Allergy, Immunology and Rheumatology, Chung Shan Medical University Hospital, Taichung City, Taiwan
- Institute of Medicine, College of Medicine, Chung Shan Medical University, Taichung City, Taiwan
- Graduate Institute of Integrated Medicine, China Medical University, Taichung City, Taiwan
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Spiller R. Impact of Diet on Symptoms of the Irritable Bowel Syndrome. Nutrients 2021; 13:nu13020575. [PMID: 33572262 PMCID: PMC7915127 DOI: 10.3390/nu13020575] [Citation(s) in RCA: 44] [Impact Index Per Article: 11.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/20/2021] [Revised: 02/02/2021] [Accepted: 02/04/2021] [Indexed: 02/08/2023] Open
Abstract
Irritable bowel syndrome (IBS), with its key features of abdominal pain and disturbed bowel habit, is thought by both patients and clinicians to be strongly influenced by diet. However, the complexities of diet have made identifying specific food intolerances difficult. Eating disorders can masquerade as IBS and may need specialist treatment. While typical food allergy is readily distinguished from IBS, the mechanisms of gut-specific adverse reactions to food are only just being defined. These may include gut-specific mast cell activation as well as non-specific activation by stressors and certain foods. Visceral hypersensitivity, in some cases mediated by mast cell activation, plays a key part in making otherwise innocuous gut stimuli painful. Rapidly fermented poorly absorbed carbohydrates produce gaseous distension as well as short-chain fatty acids and lowering of colonic pH which may cause symptoms in IBS patients. Limiting intake of these in low FODMAP and related diets has proven popular and apparently successful in many patients. Existing diet, colonic microbiota and their metabolic products may be helpful in predicting who will respond. Wheat intolerance may reflect the fact that wheat is often a major source of dietary FODMAPs. It may also be either a forme fruste of coeliac disease or non-specific immune activation. Wheat exclusion can be successful in some of these patients. More research is needed to fully understand the mechanisms of food intolerances and how to best ameliorate them in a personalised medicine approach to diet in IBS.
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Affiliation(s)
- Robin Spiller
- NIHR Nottingham Biomedical Research Centre, Nottingham NG7 2UH, UK
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37
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Aguilera-Lizarraga J, Florens MV, Viola MF, Jain P, Decraecker L, Appeltans I, Cuende-Estevez M, Fabre N, Van Beek K, Perna E, Balemans D, Stakenborg N, Theofanous S, Bosmans G, Mondelaers SU, Matteoli G, Ibiza Martínez S, Lopez-Lopez C, Jaramillo-Polanco J, Talavera K, Alpizar YA, Feyerabend TB, Rodewald HR, Farre R, Redegeld FA, Si J, Raes J, Breynaert C, Schrijvers R, Bosteels C, Lambrecht BN, Boyd SD, Hoh RA, Cabooter D, Nelis M, Augustijns P, Hendrix S, Strid J, Bisschops R, Reed DE, Vanner SJ, Denadai-Souza A, Wouters MM, Boeckxstaens GE. Local immune response to food antigens drives meal-induced abdominal pain. Nature 2021; 590:151-156. [PMID: 33442055 DOI: 10.1038/s41586-020-03118-2] [Citation(s) in RCA: 191] [Impact Index Per Article: 47.8] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/18/2020] [Accepted: 11/27/2020] [Indexed: 12/19/2022]
Abstract
Up to 20% of people worldwide develop gastrointestinal symptoms following a meal1, leading to decreased quality of life, substantial morbidity and high medical costs. Although the interest of both the scientific and lay communities in this issue has increased markedly in recent years, with the worldwide introduction of gluten-free and other diets, the underlying mechanisms of food-induced abdominal complaints remain largely unknown. Here we show that a bacterial infection and bacterial toxins can trigger an immune response that leads to the production of dietary-antigen-specific IgE antibodies in mice, which are limited to the intestine. Following subsequent oral ingestion of the respective dietary antigen, an IgE- and mast-cell-dependent mechanism induced increased visceral pain. This aberrant pain signalling resulted from histamine receptor H1-mediated sensitization of visceral afferents. Moreover, injection of food antigens (gluten, wheat, soy and milk) into the rectosigmoid mucosa of patients with irritable bowel syndrome induced local oedema and mast cell activation. Our results identify and characterize a peripheral mechanism that underlies food-induced abdominal pain, thereby creating new possibilities for the treatment of irritable bowel syndrome and related abdominal pain disorders.
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Affiliation(s)
- Javier Aguilera-Lizarraga
- Laboratory for Intestinal Neuroimmune Interactions, Translational Research Center for Gastrointestinal Disorders, KU Leuven Department of Chronic Diseases, Metabolism and Ageing, Leuven, Belgium
| | - Morgane V Florens
- Laboratory for Intestinal Neuroimmune Interactions, Translational Research Center for Gastrointestinal Disorders, KU Leuven Department of Chronic Diseases, Metabolism and Ageing, Leuven, Belgium
| | - Maria Francesca Viola
- Laboratory for Intestinal Neuroimmune Interactions, Translational Research Center for Gastrointestinal Disorders, KU Leuven Department of Chronic Diseases, Metabolism and Ageing, Leuven, Belgium
| | - Piyush Jain
- Laboratory for Intestinal Neuroimmune Interactions, Translational Research Center for Gastrointestinal Disorders, KU Leuven Department of Chronic Diseases, Metabolism and Ageing, Leuven, Belgium
| | - Lisse Decraecker
- Laboratory for Intestinal Neuroimmune Interactions, Translational Research Center for Gastrointestinal Disorders, KU Leuven Department of Chronic Diseases, Metabolism and Ageing, Leuven, Belgium
| | - Iris Appeltans
- Laboratory for Intestinal Neuroimmune Interactions, Translational Research Center for Gastrointestinal Disorders, KU Leuven Department of Chronic Diseases, Metabolism and Ageing, Leuven, Belgium
| | - Maria Cuende-Estevez
- Laboratory for Intestinal Neuroimmune Interactions, Translational Research Center for Gastrointestinal Disorders, KU Leuven Department of Chronic Diseases, Metabolism and Ageing, Leuven, Belgium
| | - Naomi Fabre
- Laboratory for Intestinal Neuroimmune Interactions, Translational Research Center for Gastrointestinal Disorders, KU Leuven Department of Chronic Diseases, Metabolism and Ageing, Leuven, Belgium
| | - Kim Van Beek
- Laboratory for Intestinal Neuroimmune Interactions, Translational Research Center for Gastrointestinal Disorders, KU Leuven Department of Chronic Diseases, Metabolism and Ageing, Leuven, Belgium
| | - Eluisa Perna
- Laboratory for Intestinal Neuroimmune Interactions, Translational Research Center for Gastrointestinal Disorders, KU Leuven Department of Chronic Diseases, Metabolism and Ageing, Leuven, Belgium
| | - Dafne Balemans
- Laboratory for Intestinal Neuroimmune Interactions, Translational Research Center for Gastrointestinal Disorders, KU Leuven Department of Chronic Diseases, Metabolism and Ageing, Leuven, Belgium
| | - Nathalie Stakenborg
- Laboratory for Intestinal Neuroimmune Interactions, Translational Research Center for Gastrointestinal Disorders, KU Leuven Department of Chronic Diseases, Metabolism and Ageing, Leuven, Belgium
| | - Stavroula Theofanous
- Laboratory for Intestinal Neuroimmune Interactions, Translational Research Center for Gastrointestinal Disorders, KU Leuven Department of Chronic Diseases, Metabolism and Ageing, Leuven, Belgium
| | - Goele Bosmans
- Laboratory for Intestinal Neuroimmune Interactions, Translational Research Center for Gastrointestinal Disorders, KU Leuven Department of Chronic Diseases, Metabolism and Ageing, Leuven, Belgium
| | - Stéphanie U Mondelaers
- Laboratory for Intestinal Neuroimmune Interactions, Translational Research Center for Gastrointestinal Disorders, KU Leuven Department of Chronic Diseases, Metabolism and Ageing, Leuven, Belgium
| | - Gianluca Matteoli
- Laboratory for Mucosal Immunology, Translational Research Center for Gastrointestinal Disorders, KU Leuven Department of Chronic Diseases, Metabolism and Ageing, Leuven, Belgium
| | - Sales Ibiza Martínez
- Laboratory for Mucosal Immunology, Translational Research Center for Gastrointestinal Disorders, KU Leuven Department of Chronic Diseases, Metabolism and Ageing, Leuven, Belgium.,Laboratory of Cell Biology and Histology, Department of Veterinary Sciences, University of Antwerp, Wilrijk, Belgium
| | - Cintya Lopez-Lopez
- Gastrointestinal Diseases Research Unit, Queen's University, Kingston, Ontario, Canada
| | | | - Karel Talavera
- Laboratory for Ion Channel Research, VIB Center for Brain and Disease Research, KU Leuven Department of Cellular and Molecular Medicine, Leuven, Belgium
| | - Yeranddy A Alpizar
- Neuroscience Research group, BIOMED, Hasselt University, Hasselt, Belgium
| | | | - Hans-Reimer Rodewald
- Division of Cellular Immunology, German Cancer Research Center, Heidelberg, Germany
| | - Ricard Farre
- Mucosal Permeability Lab, Translational Research Center for Gastrointestinal Disorders, KU Leuven Department of Chronic Diseases, Metabolism and Ageing, Leuven, Belgium
| | - Frank A Redegeld
- Division of Pharmacology, Utrecht Institute for Pharmaceutical Sciences, Faculty of Science, Utrecht University, Utrecht, the Netherlands
| | - Jiyeon Si
- KU Leuven Laboratory of Molecular Bacteriology, Department of Microbiology and Immunology, Rega Institute, Leuven, Belgium.,VIB KU Leuven Center for Microbiology, Leuven, Belgium
| | - Jeroen Raes
- KU Leuven Laboratory of Molecular Bacteriology, Department of Microbiology and Immunology, Rega Institute, Leuven, Belgium.,VIB KU Leuven Center for Microbiology, Leuven, Belgium
| | - Christine Breynaert
- Allergy and Clinical Immunology Research Group, KU Leuven Department of Microbiology, Immunology and Transplantation, Leuven, Belgium
| | - Rik Schrijvers
- Allergy and Clinical Immunology Research Group, KU Leuven Department of Microbiology, Immunology and Transplantation, Leuven, Belgium
| | - Cédric Bosteels
- Laboratory of Immunoregulation, VIB Center for Inflammation Research, Ghent, Belgium.,Department of Internal Medicine and Pediatrics, Ghent University, Ghent, Belgium
| | - Bart N Lambrecht
- Laboratory of Immunoregulation, VIB Center for Inflammation Research, Ghent, Belgium.,Department of Internal Medicine and Pediatrics, Ghent University, Ghent, Belgium.,Department of Pulmonary Medicine, Erasmus University Medical Center Rotterdam, Rotterdam, The Netherlands
| | - Scott D Boyd
- Department of Pathology, Stanford University School of Medicine, Stanford, CA, USA.,Sean N. Parker Center for Allergy and Asthma Research, Stanford University School of Medicine, Stanford, CA, USA
| | - Ramona A Hoh
- Department of Pathology, Stanford University School of Medicine, Stanford, CA, USA
| | - Deirdre Cabooter
- KU Leuven Department of Pharmaceutical and Pharmacological Sciences, Leuven, Belgium
| | - Maxim Nelis
- KU Leuven Department of Pharmaceutical and Pharmacological Sciences, Leuven, Belgium
| | - Patrick Augustijns
- KU Leuven Department of Pharmaceutical and Pharmacological Sciences, Leuven, Belgium
| | - Sven Hendrix
- Department of Morphology, Biomedical Research Institute, Hasselt University, Hasselt, Belgium.,Medical School Hamburg, Hamburg, Germany
| | - Jessica Strid
- Department of Immunology and Inflammation, Imperial College London, London, UK
| | - Raf Bisschops
- Laboratory for Intestinal Neuroimmune Interactions, Translational Research Center for Gastrointestinal Disorders, KU Leuven Department of Chronic Diseases, Metabolism and Ageing, Leuven, Belgium
| | - David E Reed
- Gastrointestinal Diseases Research Unit, Queen's University, Kingston, Ontario, Canada
| | - Stephen J Vanner
- Gastrointestinal Diseases Research Unit, Queen's University, Kingston, Ontario, Canada
| | - Alexandre Denadai-Souza
- Laboratory for Intestinal Neuroimmune Interactions, Translational Research Center for Gastrointestinal Disorders, KU Leuven Department of Chronic Diseases, Metabolism and Ageing, Leuven, Belgium
| | - Mira M Wouters
- Laboratory for Intestinal Neuroimmune Interactions, Translational Research Center for Gastrointestinal Disorders, KU Leuven Department of Chronic Diseases, Metabolism and Ageing, Leuven, Belgium
| | - Guy E Boeckxstaens
- Laboratory for Intestinal Neuroimmune Interactions, Translational Research Center for Gastrointestinal Disorders, KU Leuven Department of Chronic Diseases, Metabolism and Ageing, Leuven, Belgium.
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Kumari MV, Amarasiri L, Rajindrajith S, Devanarayana NM. Functional abdominal pain disorders and asthma: two disorders, but similar pathophysiology? Expert Rev Gastroenterol Hepatol 2021; 15:9-24. [PMID: 32909837 DOI: 10.1080/17474124.2020.1821652] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/19/2020] [Accepted: 09/07/2020] [Indexed: 02/08/2023]
Abstract
INTRODUCTION Functional abdominal pain disorders (FAPDs) and asthma are common ailments affecting both children and adults worldwide. Multiple studies have demonstrated an association between these two disorders. However, the exact reason for this observed association is not apparent. AREAS COVERED The current review has explored available literature and outlined multiple underlying pathophysiological mechanisms, common to both asthma and FAPDs, as possible reasons for this association. EXPERT OPINION Smooth muscle dysfunction, hypersensitivity and hyper-responsiveness, mucosal inflammation, and barrier dysfunction involving gastrointestinal and respiratory tracts are the main underlying pathophysiological mechanisms described for the generation of symptoms in FAPDs and asthma. In addition, alterations in neuroendocrine regulatory functions, immunological dysfunction, and microbial dysbiosis have been described in both disorders. We believe that the pathophysiological processes that were explored in this article would be able to expand the mechanisms of the association. The in-depth knowledge is needed to be converted to therapeutic and preventive strategies to improve the quality of care of children suffering from FAPDs and asthma.
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Affiliation(s)
- Manori Vijaya Kumari
- Department of Physiology, Faculty of Medicine & Allied Sciences, Rajarata University of Sri Lanka , Anuradhapura, Sri Lanka
| | - Lakmali Amarasiri
- Department of Physiology, Faculty of Medicine, University of Colombo , Colombo, Sri Lanka
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Wu MC, Jan MS, Chiou JY, Wang YH, Wei JCC. Constipation might be associated with risk of allergic rhinitis: A nationwide population-based cohort study. PLoS One 2020; 15:e0239723. [PMID: 33006996 PMCID: PMC7531808 DOI: 10.1371/journal.pone.0239723] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/01/2020] [Accepted: 09/11/2020] [Indexed: 12/12/2022] Open
Abstract
Background Allergic rhinitis (AR) is a burdensome respiratory disorder whose etiology and pathophysiology remain controversial and most likely multifactorial. Accumulated evidence indicates that gut dysbiosis contributes to AR via the gut-airway axis. Constipation could result in alteration of the intestinal microflora. The clinical impact of constipation on AR has not been studied. We aimed to evaluate the risk of AR in constipated patients using a nationwide longitudinal population-based cohort. Methods We identified 57786 patients with constipation and 57786 matched controls between 1999 and 2013 from the Longitudinal Health Insurance Database, which is a subset of Taiwanese National Health Insurance Research Database. Propensity score analysis was used for matching age, sex, comorbidities, and medications at a ratio of 1:1. Multiple Cox regression and subgroup analyses were used to estimate the adjusted hazard ratio of AR. Results The incidence of AR was 32.2 per 1,000 person-years in constipated patients, which was twice that of non-constipated patients. After adjustment for patients’ age, gender, comorbidities, and medications, patients with constipation had a 2.3-fold risk of AR compared to those without constipation (adjusted hazard ratio [aHR]: 2.30; 95% CI, 2.23–2.37). In subgroup analyses, patients aged 20–39 years had a 2.24-fold higher risk of AR in the constipation cohort (aHR; 95% CI, 2.12–2.36). Patients aged <20, 40–64, and ≥65 years had a 2.09, 2.05, and 2.07-fold risk of AR in the constipation cohort, respectively (aHR; 95% CI, 1.98–2.20, 1.94–2.18, and 1.92–2.23). Also, patients with constipation had a higher likelihood of AR, regardless of sex, and with or without comorbidities including hyperlipidemia, hypertension, chronic kidney disease, chronic liver disease, diabetes, chronic obstructive pulmonary disease, rheumatoid arthritis, dyspepsia, irritable bowel syndrome, and anxiety. Conclusion Constipation might be associated with an increased risk of incidental AR. It seems that physicians should keep a higher index of suspicion for AR in people with constipation. The patency issue of gut could not be ignored in patients with AR.
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Affiliation(s)
- Meng-Che Wu
- Institute of Medicine, Chung Shan Medical University, Taichung, Taiwan
- Division of Gastroenterology, Children’s Medical Center, Taichung Veterans General Hospital, Taichung, Taiwan
| | - Ming-Shiou Jan
- Institute of Biochemistry, Microbiology and Immunology, Chung Shan Medical University, Taichung, Taiwan
- Immunology Research Center, Chung Shan Medical University, Taichung, Taiwan
- Division of Allergy, Immunology and Rheumatology, Chung Shan Medical University Hospital, Taichung, Taiwan
| | - Jeng-Yuan Chiou
- School of Health Policy and Management, Chung Shan Medical University, Taichung, Taiwan
| | - Yu-Hsun Wang
- Department of Medical Research, Chung Shan Medical University Hospital, Taichung, Taiwan
| | - James Cheng-Chung Wei
- Institute of Medicine, Chung Shan Medical University, Taichung, Taiwan
- Division of Allergy, Immunology and Rheumatology, Chung Shan Medical University Hospital, Taichung, Taiwan
- Graduate Institute of Integrated Medicine, China Medical University, Taichung, Taiwan
- * E-mail:
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40
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Acid inhibitors and allergy: comorbidity, causation and confusion. Nat Commun 2020; 11:3950. [PMID: 32769978 PMCID: PMC7414203 DOI: 10.1038/s41467-020-17831-z] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/19/2019] [Accepted: 07/17/2020] [Indexed: 12/27/2022] Open
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Black CJ, Yiannakou Y, Houghton LA, Shuweihdi F, West R, Guthrie E, Ford AC. Anxiety-related factors associated with symptom severity in irritable bowel syndrome. Neurogastroenterol Motil 2020; 32:e13872. [PMID: 32396247 DOI: 10.1111/nmo.13872] [Citation(s) in RCA: 29] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/10/2020] [Revised: 03/10/2020] [Accepted: 04/14/2020] [Indexed: 02/08/2023]
Abstract
BACKGROUND Gastrointestinal symptom-specific anxiety and somatization have both been associated with higher symptom severity in patients with irritable bowel syndrome (IBS); however, this relationship has not been explored fully. Moreover, the performance of the visceral sensitivity index (VSI) for measuring gastrointestinal symptom-specific anxiety has not been examined in a UK population. We conducted a cross-sectional survey to examine these issues. METHODS Gastrointestinal symptom-specific anxiety was measured using the VSI, and somatization was measured via the patient health questionnaire-12 (PHQ-12) in adults from the UK community with Rome IV-defined IBS. Exploratory factor analysis was performed on the VSI, prior to subsequent analyses, to establish its factor structure. Multiple regression analysis was used to determine the relationship between demographic features, different factors of the VSI, somatization, and IBS symptom severity. KEY RESULTS A total of 811 individuals with IBS provided complete data. Factor analysis of the VSI revealed a three-factor structure, accounting for 47% of the variance. The first of these VSI factors and the PHQ-12 were both strongly and independently associated with IBS symptom severity, for the group as a whole and for all four IBS subtypes. Most VSI items concerned with overt gastrointestinal symptom-specific anxiety loaded onto the other two VSI factors that were not associated with symptom severity. CONCLUSIONS AND INFERENCES The factor structure of the VSI requires further investigation. Our findings cast doubt on the central role of gastrointestinal symptom-specific anxiety as a driver for symptom severity in IBS. Awareness of both gastrointestinal and extra-intestinal symptoms, however, is strongly associated with symptom severity.
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Affiliation(s)
- Christopher J Black
- Leeds Gastroenterology Institute, St. James's University Hospital, Leeds, UK.,Leeds Institute of Medical Research at St. James's, University of Leeds, Leeds, UK
| | - Yan Yiannakou
- County Durham and Darlington NHS Foundation Trust, Durham, UK
| | - Lesley A Houghton
- Leeds Institute of Medical Research at St. James's, University of Leeds, Leeds, UK
| | - Farag Shuweihdi
- Leeds Institute of Health Sciences, University of Leeds, Leeds, UK
| | - Robert West
- Leeds Institute of Health Sciences, University of Leeds, Leeds, UK
| | - Elspeth Guthrie
- Leeds Institute of Health Sciences, University of Leeds, Leeds, UK
| | - Alexander C Ford
- Leeds Gastroenterology Institute, St. James's University Hospital, Leeds, UK.,Leeds Institute of Medical Research at St. James's, University of Leeds, Leeds, UK
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Nakane S, Mukaino A, Ihara E, Ogawa Y. Autoimmune gastrointestinal dysmotility: the interface between clinical immunology and neurogastroenterology. Immunol Med 2020; 44:74-85. [DOI: 10.1080/25785826.2020.1797319] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/16/2022] Open
Affiliation(s)
- Shunya Nakane
- Department of Molecular Neurology and Therapeutics, Kumamoto University Hospital, Kumamoto, Japan
| | - Akihiro Mukaino
- Department of Molecular Neurology and Therapeutics, Kumamoto University Hospital, Kumamoto, Japan
| | - Eikichi Ihara
- Department of Gastroenterology and Metabolism, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
- Department of Medicine and Bioregulatory Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
| | - Yoshihiro Ogawa
- Department of Medicine and Bioregulatory Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
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Siah KTH, Santosa A, Cheung CKY, Soh AYS, Bigliardi PL. Atopic Patients Who Fulfilled Rome III Criteria for Irritable Bowel Syndrome Had Higher Animal Danders Sensitization. J Neurogastroenterol Motil 2020; 26:267-273. [PMID: 32235034 PMCID: PMC7176502 DOI: 10.5056/jnm19181] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/18/2019] [Revised: 11/06/2019] [Accepted: 11/25/2019] [Indexed: 12/12/2022] Open
Abstract
Background/Aims The relationship between animal exposure and irritable bowel syndrome (IBS) is debated. Epidemiological studies have shown that atopy is more prevalent in IBS patients and vice versa. We set out to examine the association between animal danders sensitization and IBS-like symptoms in atopic patients. Methods We recruited 69 consecutive atopic patients from the allergy clinic of a tertiary hospital. Subjects completed validated bowel questionnaires, underwent skin prick test, blood was collected for serum total immunoglobulin E, and ImmunoCAP immune solid-phase allergen chip (ISAC) IgE multiplex assay. Results Twenty-eight (41.0%) atopic patients fulfilled the Rome III IBS criteria (atopy-IBS). There were no differences in gender, age, pet ownership, total serum IgE, or food allergen sensitization between atopy-IBS group and atopy-non-IBS group. We found that atopy-IBS group had significantly higher number of positive skin prick test for cat dander (64.3% vs 24.4%, P < 0.001), dog dander (64.3% vs 41.5%, P = 0.015) and weed pollens (32.1% vs 14.6%, P = 0.050) compared to atopy-non-IBS group. Out of 112 components from 51 allergen sources (both aeroallergen and food allergens), only Fel d1 (a major cat dander antigen) IgE is significantly higher in atopy-IBS group than atopy-non-IBS group (21.4% vs 2.4%, P = 0.029). Majority of atopy-IBS patients had mixed-type IBS. Conclusions We demonstrated an association between animal danders sensitization, in particular cat dander sensitization, and IBS-like symptoms in atopic patients. Future studies are needed to explore the relationship between aeroallergen and functional gastrointestinal disorders. Sensitization may be related to the pathophysiology of IBS or it could be that we are missing aeroallergen-induced gut allergy.
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Affiliation(s)
- Kewin T H Siah
- Division of Gastroenterology and Hepatology, University Medicine Cluster, National University Health System, Singapore.,Yong Loo Lin School of Medicine, National University of Singapore, Singapore
| | - Amelia Santosa
- Yong Loo Lin School of Medicine, National University of Singapore, Singapore.,Division of Rheumatology, University Medicine Cluster, National University Health System, Singapore
| | | | - Alex Y S Soh
- Division of Gastroenterology and Hepatology, University Medicine Cluster, National University Health System, Singapore.,Yong Loo Lin School of Medicine, National University of Singapore, Singapore
| | - Paul L Bigliardi
- Department of Dermatology, Division of Dermato-Allergy, University of Minnesota, Minneapolis, MN, USA
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Wauters L, Burns G, Ceulemans M, Walker MM, Vanuytsel T, Keely S, Talley NJ. Duodenal inflammation: an emerging target for functional dyspepsia? Expert Opin Ther Targets 2020; 24:511-523. [PMID: 32249629 DOI: 10.1080/14728222.2020.1752181] [Citation(s) in RCA: 34] [Impact Index Per Article: 6.8] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
Introduction: Functional dyspepsia (FD) is one of the most common functional gastrointestinal disorders and is classified into postprandial distress and epigastric pain syndrome. Despite the recognition of duodenal inflammation as a potential trigger of symptoms, only limited anti-inflammatory therapies exist.Areas covered: This narrative review summarizes the recent advances in the pathophysiology and treatment of FD; it identifies potential therapeutic targets and gaps in the field. An electronic literature search was conducted in Pubmed up to 31st of December 2019.Expert opinion: There is compelling evidence for the role of duodenal inflammation and the eosinophil-mast cell axis in the pathogenesis of dyspeptic symptoms. Traditional prokinetic drugs and neuromodulators target gastric dysmotility and visceral hypersensitivity but are hampered by limited efficacy and side effects. Independent of acid suppression, the anti-inflammatory action of proton pump inhibitors, which remain the first-line therapy in FD, may also explain their therapeutic effect. Other existing and newly established anti-inflammatory drugs should be investigated while trials including probiotics and selective antibiotics should examine the host microbiome and immune activation. Targeted treatments for potential causes of duodenal pathology, such as impaired permeability and dysbiosis, are likely to emerge in the future.
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Affiliation(s)
- Lucas Wauters
- Translational Research in Gastrointestinal Diseases (TARGID), KU Leuven, Leuven, Belgium.,Department of Gastroenterology and Hepatology, University Hospitals Leuven, Leuven, Belgium
| | - Grace Burns
- Faculty of Health and Medicine, University of Newcastle and Hunter Medical Research Institute, Callaghan, Australia
| | - Matthias Ceulemans
- Translational Research in Gastrointestinal Diseases (TARGID), KU Leuven, Leuven, Belgium
| | - Marjorie M Walker
- Faculty of Health and Medicine, University of Newcastle and Hunter Medical Research Institute, Callaghan, Australia
| | - Tim Vanuytsel
- Translational Research in Gastrointestinal Diseases (TARGID), KU Leuven, Leuven, Belgium.,Department of Gastroenterology and Hepatology, University Hospitals Leuven, Leuven, Belgium
| | - Simon Keely
- Faculty of Health and Medicine, University of Newcastle and Hunter Medical Research Institute, Callaghan, Australia.,Vaccine and Asthma (VIVA) Program, Hunter Medical Research Institute, Callaghan, Australia
| | - Nicholas J Talley
- Faculty of Health and Medicine, University of Newcastle and Hunter Medical Research Institute, Callaghan, Australia
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Wauters L, Talley NJ, Walker MM, Tack J, Vanuytsel T. Novel concepts in the pathophysiology and treatment of functional dyspepsia. Gut 2020; 69:591-600. [PMID: 31784469 DOI: 10.1136/gutjnl-2019-318536] [Citation(s) in RCA: 149] [Impact Index Per Article: 29.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/29/2019] [Revised: 11/18/2019] [Accepted: 11/19/2019] [Indexed: 02/07/2023]
Abstract
Emerging data increasingly point towards the duodenum as a key region underlying the pathophysiology of functional dyspepsia (FD), one of the most prevalent functional GI disorders. The duodenum plays a major role in the control and coordination of gastroduodenal function. Impaired duodenal mucosal integrity and low-grade inflammation have been associated with altered neuronal signalling and systemic immune activation, and these alterations may ultimately lead to dyspeptic symptoms. Likely luminal candidates inducing the duodenal barrier defect include acid, bile, the microbiota and food antigens although no causal association with symptoms has been convincingly demonstrated. Recognition of duodenal pathology in FD will hopefully lead to the discovery of new biomarkers and therapeutic targets, allowing biologically targeted rather than symptom-based therapy. In this review, we summarise the recent advances in the diagnosis and treatment of FD with a focus on the duodenum.
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Affiliation(s)
- Lucas Wauters
- Gastroenterology and Hepatology, University Hospitals Leuven, Leuven, Belgium.,Translational Research in Gastrointestinal Disorders, KU Leuven, Leuven, Belgium
| | - Nicholas J Talley
- Faculty of Health and Medicine, University of Newcastle, Newcastle, New South Wales, Australia .,School of medicine and public Health, Hunter Medical Research Institute, New Lambton Heights, New South Wales, Australia
| | - Marjorie M Walker
- Anatomical Pathology, University of Newcastle, Newcastle, New South Wales, Australia
| | - Jan Tack
- Gastroenterology and Hepatology, University Hospitals Leuven, Leuven, Belgium.,Translational Research in Gastrointestinal Disorders, KU Leuven, Leuven, Belgium
| | - Tim Vanuytsel
- Gastroenterology and Hepatology, University Hospitals Leuven, Leuven, Belgium.,Translational Research in Gastrointestinal Disorders, KU Leuven, Leuven, Belgium
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Jones MP, Faresjö Å, Beath A, Faresjö T, Ludvigsson J. Abdominal Pain in Children Develops With Age and Increases With Psychosocial Factors. Clin Gastroenterol Hepatol 2020; 18:360-367.e1. [PMID: 31009796 DOI: 10.1016/j.cgh.2019.04.036] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/18/2018] [Revised: 04/08/2019] [Accepted: 04/13/2019] [Indexed: 02/07/2023]
Abstract
BACKGROUND & AIMS Functional gastrointestinal disorders are highly prevalent, cause significant suffering, and are costly to society. Pain is a central feature of 2 of the most common functional gastrointestinal disorders: irritable bowel syndrome and functional dyspepsia. Although these disorders have been well studied in adults, their etiology is poorly understood. We sought to identify early life factors associated with the development of abdominal pain in children (age, 2-12 y). METHODS We collected data from the All Babies in Southeast Sweden study of 1781 children, born from October 1, 1997, through October 31, 1999, whose families answered questions about abdominal pain and risk factors at birth, 1 year, 2.5 years, 5 years, 8 years, and 10 to 12 years. We used latent growth curve models to evaluate risk factors for development of abdominal pain. The primary outcomes were prevalence of abdominal pain and associated factors. RESULTS The prevalence of abdominal pain increased linearly with age in the study cohort, increasing by approximately 6% per year. Psychosocial variables associated with slope of the growth curve included lower emotional control at age 2 years (P = .005), parental concern for the child at age 2 years (P = .02), and measures of parental stress (P = .004). Nonvaginal birth was associated with a reduced slope of the growth curve (P = .03). CONCLUSIONS In a study of children in Sweden, we found early psychosocial environment and mode of delivery at birth was associated with development of childhood abdominal pain. Factors associated with development of the early immune system, identified in previous recall-based research, were not supported by data from this study. These findings have important implications for the prevention of abdominal pain in children and later in life.
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Affiliation(s)
- Michael P Jones
- Psychology Department, Macquarie University, North Ryde, New South Wales, Australia.
| | - Åshild Faresjö
- Division of Community Medicine, Department of Medical Health and Science, Linköping University, Linköping, Sweden
| | - Alissa Beath
- Psychology Department, Macquarie University, North Ryde, New South Wales, Australia
| | - Tomas Faresjö
- Division of Community Medicine, Department of Medical Health and Science, Linköping University, Linköping, Sweden
| | - Johnny Ludvigsson
- Division of Pediatrics, Department of Clinical and Experimental Medicine, Linköping University, Linköping, Sweden; Division of Pediatrics, Crown Princess Victoria Children's Hospital, Region Östergötland, Linköping, Sweden
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Ho SW, Lin CP, Ku MS. The impact of allergic rhinitis on gastrointestinal disorders among young adults. J Eval Clin Pract 2020; 26:242-247. [PMID: 30773746 DOI: 10.1111/jep.13108] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/13/2018] [Revised: 01/13/2019] [Accepted: 01/14/2019] [Indexed: 12/20/2022]
Abstract
BACKGROUND An association between allergic rhinitis (AR) and digestive diseases (DDs) has been reported; however, studies have only focused on the prevalence of DDs in populations of patients with AR. In individuals with specific DDs, the impact of AR on the frequency of clinical visits for each DD has not been studied. Moreover, the association between topical steroid usage for AR and DDs has not been investigated. METHODS Data from 16 526 men and 18 438 women, aged 21 to 30 years, were collected from a national database. Individuals were separated into the AR and non-AR groups. Eight common DDs were studied: (1) gastroesophageal reflux disease (GERD), (2) gastritis and duodenitis, (3) peptic ulcers, (4) irritable bowel syndrome, (5) gastric functional disease, (6) intestinal functional disease, (7) gastroenteritis and colitis, and (8) constipation. The rate of each DD was compared between groups. In individuals with specific DDs, the frequency of clinical visits for each DD was also compared between groups. Between users and nonusers of topical steroids in the AR group, the rate of DDs was compared. RESULTS Significant associations were observed between all eight DDs and AR in both sexes. In comparison to the non-AR group, women with AR visited clinics more frequently for gastritis/duodenitis, gastric and intestinal functional disease, gastroenteritis/colitis, and constipation, while men with AR visited clinics more frequently for gastritis/duodenitis, gastric functional disease, gastroenteritis/colitis, and constipation. Female topical-steroid users with AR had higher rates of GERD, irritable bowel syndrome, gastric or intestinal functional disease, and gastritis/colitis. Male topical-steroid users with AR had higher rates of GERD and peptic ulcers. CONCLUSION AR was associated with DDs in both sexes. However, the influence of AR on clinical visit frequency varied among specific DD groups. Topical steroid usage for AR was associated with some DDs, but the association requires future evaluation.
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Affiliation(s)
- Sai-Wai Ho
- School of Medicine, Chung Shan Medical University, Taichung, Taiwan.,Department of Emergency Medicine, Chung Shan Medical University Hospital, Taichung, Taiwan
| | - Ching-Pin Lin
- Institute of Biochemistry, Microbiology and Immunology, Chung Shan Medical University, Taichung, Taiwan.,Division of Gastroenterology, Department of Internal Medicine, Chung Shan Medical University Hospital, Taichung, Taiwan
| | - Min-Sho Ku
- School of Medicine, Chung Shan Medical University, Taichung, Taiwan.,Division of Allergy, Asthma and Rheumatology, Department of Pediatrics, Chung Shan Medical University Hospital, Taichung, Taiwan
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Abstract
Chronic unexplained gastrointestinal symptoms impact more than 1 in 5 Americans and their families; these disorders include the irritable bowel syndrome (IBS) and functional dyspepsia (FD), currently classified by Rome IV as functional gastrointestinal disorders. By definition, IBS and FD have no established pathology, but emerging evidence suggests this paradigm may need revision. Immune activation and, in subsets, subtle intestinal pathology have been identified in FD (most notably, postprandial distress syndrome) and IBS-diarrhea. A disease model is proposed that accounts for all of the intestinal and extraintestinal symptoms, relationship to food and infection, and the overlap with gastroesophageal reflux disease. It is speculated that antigen presentation to the mucosa (e.g., microbial antigens or food proteins after acute gastroenteritis) induces, in a genetically primed host, immune activation of the intestine with low-grade intestinal inflammation and subsequently neuronal structural and functional alterations, producing regional intestinal hypersensitivity and motor dysfunction. Immune activation may explain the female predominance and fluctuations in immune activity for symptom variability over time. In the future, as further evidence accumulates, the management paradigm may potentially shift to objective pathology-based subtyping based on serological, microbiological, and clinical assessments to identify when targeted therapies should be deployed in subsets. Potential targeted interventions may include therapies to dampen down immune activation or block release of key mediators such as histamine, specific microbial targeted treatments that may reverse disease, and dietary advice to eliminate relevant food antigens after objective in vivo testing. Only by identifying causation can we eventually anticipate cure, and as the true pathology unravels in subsets, this may become a reality.
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Jung HK, Tae CH, Moon CM, Kim SE, Shim KN, Jung SA. Chronic unexplained nausea in adults: Prevalence, impact on quality of life, and underlying organic diseases in a cohort of 5096 subjects comprehensively investigated. PLoS One 2019; 14:e0225364. [PMID: 31856259 PMCID: PMC6922349 DOI: 10.1371/journal.pone.0225364] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/18/2018] [Accepted: 11/03/2019] [Indexed: 12/31/2022] Open
Abstract
We evaluated to define the clinically significant chronic nausea in general population and to assess the prevalence of chronic unexplained nausea after exclusion of organic causes through the meticulous medical examination. Two phase studies were conducted. In phase 1, telephone survey was conducted to define the clinically significant nausea in 5000 representative subjects for a general population. Clinically significant nausea was identified by lowered quality of life if the frequency was 'more than one day per week'. Its prevalence was 1.6% (1.4-1.8%) and about 90% of nausea was not accompanied with vomiting. In phase 2, 5096 participants in a comprehensive health-screening cohort were enrolled. We investigated demographics, gastrointestinal symptoms, somatization symptoms and health related quality of life using validated questionnaire. All participants underwent meticulous medical examinations including endoscopy, abdominal ultrasound, thyroid function test, and blood testing. Among a total of 5096 subjects (men 51.8%, mean age 47.5 ± 10.0 years), organic diseases associated with chronic nausea were reflux esophagitis, duodenal ulcer and hyperthyroidism. The prevalence of chronic unexplained nausea was 0.6% (95% CI 0.4-0.8%) and there were significant overlap with functional dyspepsia and irritable bowel syndrome. HRQoL is significantly lower in people with nausea occurring 'more than one day per week' in a general population. Most chronic nausea was not accompanied with vomiting. Chronic unexplained nausea is uncommon affecting only 0.6% of the population but are more likely to report functional dyspepsia and irritable bowel syndrome.
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Affiliation(s)
- Hye-Kyung Jung
- Department of Internal Medicine, College of Medicine, Ewha Womans University, Seoul, Korea
- * E-mail:
| | - Chung Hyun Tae
- Department of Internal Medicine, College of Medicine, Ewha Womans University, Seoul, Korea
| | - Chang Mo Moon
- Department of Internal Medicine, College of Medicine, Ewha Womans University, Seoul, Korea
| | - Seong-Eun Kim
- Department of Internal Medicine, College of Medicine, Ewha Womans University, Seoul, Korea
| | - Ki-Nam Shim
- Department of Internal Medicine, College of Medicine, Ewha Womans University, Seoul, Korea
| | - Sung-Ae Jung
- Department of Internal Medicine, College of Medicine, Ewha Womans University, Seoul, Korea
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Abstract
PURPOSE OF REVIEW Functional dyspepsia is a common condition, and the condition is defined by symptoms using Rome IV criteria. This review addresses the issue of functional dyspepsia in elderly patients, epidemiology, investigation, and treatment. RECENT FINDINGS Recent studies show that while the prevalence of dyspepsia declines in the elderly, it is still prevalant investigations to confirm the diagnosis (including mandatory upper gastrointestinal endoscopy) must exclude organic disease. These include ulcers (particularly associated with nonsteroidal antiinflammatory drugs), Helicobacter pylori pathologies, cancer, coeliac disease, and autoimmune gastritis. Recent research is unraveling pathophysiology beyond symptom-only definitions, focusing on the duodenum with innate immune disturbance (duodenal eosinophilia) and microbial disruption as possible cause. Management of functional dyspepsia includes making a secure diagnosis, treatment with first-line proton pump inhibitors (PPI), then tricyclic antidepressants, and careful choice of prokinetics. Herbal treatments (peppermint oil) and STW-5 have in this age group limited efficacy. Further studies are needed to define the prevalence of functional dyspepsia in the elderly and of prime importance, to exclude organic disease as a cause for symptoms of dyspepsia.
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Affiliation(s)
- Marjorie M Walker
- Faculty of Health & Medicine, University of Newcastle, Callaghan, 2305, NSW, Australia.,Australian Gastrointestinal Research Alliance (AGIRA), Callaghan, 2305, NSW, Australia
| | - Nicholas J Talley
- Faculty of Health & Medicine, University of Newcastle, Callaghan, 2305, NSW, Australia. .,Australian Gastrointestinal Research Alliance (AGIRA), Callaghan, 2305, NSW, Australia.
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