|
1
|
Sternes PR, Shah A, Ayala Pintos C, Fairlie T, Koloski N, Kang S, Tousignant KD, McIlroy SJ, Morrison M, Tyson GW, Holtmann GJ. The biogeography of the mucosa-associated microbiome in health and disease. Front Microbiol 2024; 15:1454910. [PMID: 39469457 PMCID: PMC11513579 DOI: 10.3389/fmicb.2024.1454910] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/25/2024] [Accepted: 09/26/2024] [Indexed: 10/30/2024] Open
Abstract
Introduction Little is known about the biogeography of the mucosa associated microbiome (MAM) in patients with inflammatory bowel disease (IBD) versus controls in different segments of the gastrointestinal tract, as well as the links between the MAM, gastrointestinal symptoms, and use of proton pump inhibitors (PPI). Methods We recruited 59 controls (without structural abnormalities and gastrointestinal symptoms), 44 patients with ulcerative colitis (UC) and 31 with Crohn's disease (CD). Biopsies from various segments of the upper and lower gastrointestinal tract were collected. Microbial composition was assessed via 16S rRNA gene amplicon analysis and the bacterial load of the mucosal biopsies were assessed via qPCR. The MAM was examined in the context of disease status, PPI usage, the severity of gastrointestinal symptoms, and the symptom response to a standardised nutrient challenge (SNC). Results Microbial communities of the MAM in the upper and lower gastrointestinal tract differed. IBD patients were characterised by relative and absolute depletion of numerous genera known to produce butyrate and/or propionate, with the largest differentiation being the depletion of Faecalibacterium in the lower gastrointestinal tract of CD patients. Notably, PPI users exhibited an enrichment of Faecalibacterium in the lower gastrointestinal tract. The severity of gastrointestinal symptoms, as well as the symptom response to the SNC, were significantly associated with MAM composition in the gastrointestinal tract. Conclusion The absolute and relative composition of the MAM is variable across different segments of the gastrointestinal tract. These quantitative changes indicates that MAM can be targeted in specific segments of the GI tract to improve patient outcomes.
Collapse
Affiliation(s)
- Peter R. Sternes
- Centre for Microbiome Research, School of Biomedical Sciences, Queensland University of Technology (QUT), Translational Research Institute, Woolloongabba, QLD, Australia
| | - Ayesha Shah
- Department of Gastroenterology and Hepatology, Princess Alexandra Hospital, Brisbane, QLD, Australia
- Faculty of Medicine, University of Queensland, Brisbane, QLD, Australia
| | - Camila Ayala Pintos
- Centre for Microbiome Research, School of Biomedical Sciences, Queensland University of Technology (QUT), Translational Research Institute, Woolloongabba, QLD, Australia
| | - Thomas Fairlie
- Department of Gastroenterology and Hepatology, Princess Alexandra Hospital, Brisbane, QLD, Australia
- Faculty of Medicine, University of Queensland, Brisbane, QLD, Australia
| | - Natasha Koloski
- Department of Gastroenterology and Hepatology, Princess Alexandra Hospital, Brisbane, QLD, Australia
- Faculty of Health and Behavioural Sciences, University of Queensland, Brisbane, QLD, Australia
| | - Seungha Kang
- Frazer Institute, Faculty of Medicine, University of Queensland, Woolloongabba, QLD, Australia
| | - Kaylyn D. Tousignant
- Centre for Microbiome Research, School of Biomedical Sciences, Queensland University of Technology (QUT), Translational Research Institute, Woolloongabba, QLD, Australia
| | - Simon J. McIlroy
- Centre for Microbiome Research, School of Biomedical Sciences, Queensland University of Technology (QUT), Translational Research Institute, Woolloongabba, QLD, Australia
| | - Mark Morrison
- Department of Gastroenterology and Hepatology, Princess Alexandra Hospital, Brisbane, QLD, Australia
- Faculty of Medicine, University of Queensland, Brisbane, QLD, Australia
- Frazer Institute, Faculty of Medicine, University of Queensland, Woolloongabba, QLD, Australia
| | - Gene W. Tyson
- Centre for Microbiome Research, School of Biomedical Sciences, Queensland University of Technology (QUT), Translational Research Institute, Woolloongabba, QLD, Australia
| | - Gerald J. Holtmann
- Department of Gastroenterology and Hepatology, Princess Alexandra Hospital, Brisbane, QLD, Australia
- Faculty of Medicine, University of Queensland, Brisbane, QLD, Australia
| |
Collapse
|
|
2
|
Chen SH, Wu HS, Jiang XF, Zhou C, Bian XR, He X, Li B, Dong YJ, Wang KG, Shen SH, Lv GY, Zhi YH. Bioinformatics and LC-QTOF-MS based discovery of pharmacodynamic and Q-markers of Pitongshu against functional dyspepsia. JOURNAL OF ETHNOPHARMACOLOGY 2024; 329:118096. [PMID: 38537841 DOI: 10.1016/j.jep.2024.118096] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 01/25/2024] [Revised: 03/08/2024] [Accepted: 03/21/2024] [Indexed: 04/13/2024]
Abstract
ETHNOPHARMACOLOGICAL RELEVANCE Pitongshu (PTS) is a clinically effective empirical formula for the treatment of FD. The efficacy and safety of PTS have been demonstrated in randomized, controlled, double-blind trials, but there is a lack of understanding of the systematic evaluation of the efficacy of PTS and its material basis. OBJECTIVE To investigate the efficacy of PTS in Functional dyspepsia (FD) mice and possible Q-markers. METHOD In this study, we used "irregular feeding + chronic unpredictable chronic stimulation" to establish a mice model of FD with hepatogastric disharmony. The efficacy of PTS was assessed from hair condition, behavioral, pain, gastrointestinal function, and serum 5-HT, GAS, MTL levels in mice by instillation of different doses of PTS. In addition, the composition of drugs in blood was analyzed by LC-QTOF-MS and potential Q-markers were selected by combining network pharmacology, molecular docking and actual content. RESULT Our study showed that different doses of PTS increased pain threshold and writhing latency, decreased the number of writhings, increased gastric emptying rate and small intestinal propulsion rate, decreased total acidity of gastric contents and gastric acid secretion, and increased serum levels of 5-HT, GAS, and MTL in mice to different degrees. Enrichment analysis showed that PTS may be anti-FD through multiple pathways such as Serotonergic synapse, thyroid hormone signaling pathway, cholinergic synapse, and dopaminergic synapse. In addition, potential active ingredient substances were explored by LC-QTOF-MS combined with bioinformatics. Combined with the actual contentselected six constituents, hesperidin, neohesperidin, naringin, paeoniflorin, magnolol and honokiol, possible as Q-markers. CONCLUSION PTS may exert its anti-FD effects through multi-component, multi-target and multi-pathway". Constituents, hesperidin, neohesperidin, naringin, paeoniflorin, magnolol and honokiol may be the Q-markers of its anti-FD effects.
Collapse
Affiliation(s)
- Su-Hong Chen
- Collaborative Innovation Center of Yangtze River Delta Region Green Pharmaceuticals, Zhejiang University of Technology, No. 18, Chaowang Road, Xiacheng District, Hangzhou, Zhejiang, 310014, China; College of Pharmaceutical Science, Zhejiang Chinese Medical University, No. 548, Binwen Road, Binjiang District, Hangzhou, Zhejiang, 310014, China; Zhejiang Provincial Key Laboratory of TCM for Innovative R & D and Digital Intelligent Manufacturing of TCM Great Health Products, Huzhou, zhejiang 313200, China
| | - Han-Song Wu
- Collaborative Innovation Center of Yangtze River Delta Region Green Pharmaceuticals, Zhejiang University of Technology, No. 18, Chaowang Road, Xiacheng District, Hangzhou, Zhejiang, 310014, China; Zhejiang Provincial Key Laboratory of TCM for Innovative R & D and Digital Intelligent Manufacturing of TCM Great Health Products, Huzhou, zhejiang 313200, China
| | - Xiao-Feng Jiang
- Collaborative Innovation Center of Yangtze River Delta Region Green Pharmaceuticals, Zhejiang University of Technology, No. 18, Chaowang Road, Xiacheng District, Hangzhou, Zhejiang, 310014, China; Zhejiang Provincial Key Laboratory of TCM for Innovative R & D and Digital Intelligent Manufacturing of TCM Great Health Products, Huzhou, zhejiang 313200, China
| | - Cong Zhou
- Collaborative Innovation Center of Yangtze River Delta Region Green Pharmaceuticals, Zhejiang University of Technology, No. 18, Chaowang Road, Xiacheng District, Hangzhou, Zhejiang, 310014, China; Zhejiang Provincial Key Laboratory of TCM for Innovative R & D and Digital Intelligent Manufacturing of TCM Great Health Products, Huzhou, zhejiang 313200, China
| | - Xue-Ren Bian
- Collaborative Innovation Center of Yangtze River Delta Region Green Pharmaceuticals, Zhejiang University of Technology, No. 18, Chaowang Road, Xiacheng District, Hangzhou, Zhejiang, 310014, China; Zhejiang Provincial Key Laboratory of TCM for Innovative R & D and Digital Intelligent Manufacturing of TCM Great Health Products, Huzhou, zhejiang 313200, China
| | - Xinglishang He
- Collaborative Innovation Center of Yangtze River Delta Region Green Pharmaceuticals, Zhejiang University of Technology, No. 18, Chaowang Road, Xiacheng District, Hangzhou, Zhejiang, 310014, China; Zhejiang Provincial Key Laboratory of TCM for Innovative R & D and Digital Intelligent Manufacturing of TCM Great Health Products, Huzhou, zhejiang 313200, China
| | - Bo Li
- Collaborative Innovation Center of Yangtze River Delta Region Green Pharmaceuticals, Zhejiang University of Technology, No. 18, Chaowang Road, Xiacheng District, Hangzhou, Zhejiang, 310014, China; Zhejiang Provincial Key Laboratory of TCM for Innovative R & D and Digital Intelligent Manufacturing of TCM Great Health Products, Huzhou, zhejiang 313200, China
| | - Ying-Jie Dong
- Collaborative Innovation Center of Yangtze River Delta Region Green Pharmaceuticals, Zhejiang University of Technology, No. 18, Chaowang Road, Xiacheng District, Hangzhou, Zhejiang, 310014, China; College of Pharmaceutical Science, Zhejiang Chinese Medical University, No. 548, Binwen Road, Binjiang District, Hangzhou, Zhejiang, 310014, China; Zhejiang Provincial Key Laboratory of TCM for Innovative R & D and Digital Intelligent Manufacturing of TCM Great Health Products, Huzhou, zhejiang 313200, China
| | - Kun-Gen Wang
- The First Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou, Zhejiang, 310006, China; Kun-Gen Wang National Famous Chinese Medicine Doctor Studio, Hangzhou, Zhejiang, 310006, China.
| | - Shu-Hua Shen
- The First Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou, Zhejiang, 310006, China; Kun-Gen Wang National Famous Chinese Medicine Doctor Studio, Hangzhou, Zhejiang, 310006, China.
| | - Gui-Yuan Lv
- College of Pharmaceutical Science, Zhejiang Chinese Medical University, No. 548, Binwen Road, Binjiang District, Hangzhou, Zhejiang, 310014, China.
| | - Yi-Hui Zhi
- The First Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou, Zhejiang, 310006, China; Kun-Gen Wang National Famous Chinese Medicine Doctor Studio, Hangzhou, Zhejiang, 310006, China.
| |
Collapse
|
|
3
|
Aregawi LG, Shokrolahi M, Gebremeskel TG, Zoltan C. The Effect of Ginger Supplementation on the Improvement of Dyspeptic Symptoms in Patients With Functional Dyspepsia. Cureus 2023; 15:e46061. [PMID: 37771933 PMCID: PMC10525921 DOI: 10.7759/cureus.46061] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 09/27/2023] [Indexed: 09/30/2023] Open
Abstract
Background Functional dyspepsia (FD) is a common gastrointestinal disorder with a higher occurrence in the Western world. Conventional medications are not effective for FD with patients turning to alternative herbal medicines such as ginger. This study aimed to evaluate the effect of ginger supplementation on the improvement of FD symptoms. Methodology A before-and-after clinical study was conducted at the University of Debrecen, Internal Medicine outpatient department over a period of four weeks. Two Swanson ginger supplements each at a dose of 540 mg/day before lunch and dinner were given to 51 FD patients. Wilcoxon signed-rank test was used to estimate the differences in FD symptoms after ginger supplementation and at the baseline. The p-value was determined to test the association between variables, with p-values <0.05 considered the cutoff for statistically significant association. Results In this study, after four weeks of ginger supplementation, we observed a significant change in most dyspepsia symptoms as follows: postprandial fullness (p = 0.033, 95% CI = 0.01-0.26), early satiety (p = 0.001, 95% CI = 0.10-0.37), epigastric pain (p = 0.000, 95% CI = 0.16-0.42), epigastric burning (p = 0.003, 95% CI = 0.10-0.45), and heartburn (p = 0.209, 95% CI = -0.04-0.20). Conclusions Based on our findings ginger can be considered as a promising alternative supplementary medicine for FD.
Collapse
Affiliation(s)
- Lemlem Gebremariam Aregawi
- Institute of Nutrition, Faculty of Medical Sciences, University of Debrecen, Debrecen, HUN
- Public Health, College of Medicine and Health Sciences, Adigrat University, Adigrat, ETH
| | | | - Teferi Gebru Gebremeskel
- Flinders Health and Medical Research Institute (FHMRI), College of Medicine and Public Health, Flinders University, Adelaide, AUS
| | - Csiki Zoltan
- Internal Medicine, University of Debrecen, Debrecen, HUN
| |
Collapse
|
|
4
|
Shah A, Kang S, Talley NJ, Do A, Walker MM, Shanahan ER, Koloski NA, Jones MP, Keely S, Morrison M, Holtmann GJ. The duodenal mucosa associated microbiome, visceral sensory function, immune activation and psychological comorbidities in functional gastrointestinal disorders with and without self-reported non-celiac wheat sensitivity. Gut Microbes 2022; 14:2132078. [PMID: 36303431 PMCID: PMC9621048 DOI: 10.1080/19490976.2022.2132078] [Citation(s) in RCA: 11] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/04/2023] Open
Abstract
Frequently, patients with functional gastrointestinal disorders (FGIDs) report intolerance of wheat products. We compared gastrointestinal symptoms, sensory function, psychiatric comorbidities, gut-homing immune cells, and duodenal mucosa-associated microbiome (d-MAM) in FGID patients and controls with and without self-reported wheat sensitivity (SR-NCWS). We recruited 40 FGID patients and 20 controls referred by GPs for treatment. Gastrointestinal/extraintestinal symptoms, visceral sensory function, psychological comorbidities, and SR-NCWS were assessed in a standardized approach. Peripheral gut homing T-cells (CD4+α4+β7+CCR9+/CD8+α4+β7+CCR9+) were quantified, and the d-MAM was assessed by DNA sequencing for 46 subjects. Factors of bacterial genera were extracted utilizing factor analysis with varimax rotation and factors univariately associated with FGID or SR-NCWS included in a subsequent multivariate analysis of variance to identify statistically independent discriminators. Anxiety scores (p < .05) and increased symptom responses to a nutrient challenge (p < .05) were univariately associated with FGID. Gut homing T-cells were increased in FGID patients with SR-NCWS compared to other groups (p all <0.05). MANOVA revealed that anxiety (p = .03), visceral sensory function (p = 0.007), and a d-MAM factor comprise members of the Alloprevotella, Prevotella, Peptostreptococcus, Leptotrichia, and Veillonella lineages were significantly (p = .001) associated with FGID, while gut homing CD4+α4+ β7+CCR9+ T-cells were associated (p = .002) with SR-NCWS. Compared to controls, patients with and without SR-NCWS show that there are shifts in the amplicon sequence variants within specific bacterial genera between the FGID subgroups (particularly Prevotella and Streptococcus) as well as distinct bacterial taxa discriminatory for the two different FGID subtypes. Compared to controls, both FGID patients with and without SR-NCWS have an increased symptom response to a standardized nutrient challenge and increased anxiety scores. The FGID patients with SR-NCWS - as compared to FGID without SR-NCWS (and controls without SR-NCWS) - have increased gut homing T-cells. The d-MAM profiles suggest species and strain-based variations between the two FGID subtypes and in comparison to controls.
Collapse
Affiliation(s)
- Ayesha Shah
- Department of Gastroenterology and Hepatology, Princess Alexandra Hospital, Brisbane, Australia,Translational Research Institute Queensland, Australia,Faculty of Medicine, University of Queensland, Brisbane, Australia
| | - Seungha Kang
- Faculty of Medicine, University of Queensland, Brisbane, Australia,University of Queensland Diamantina Institute, Woolloongabba, Australia
| | - Nicholas J Talley
- College of Health, Medicine and Wellbeing, University of Newcastle, Callaghan, and Hunter Medical Research Institute, New Lambton Heights, Australia
| | - Anh Do
- Department of Gastroenterology and Hepatology, Princess Alexandra Hospital, Brisbane, Australia,Faculty of Medicine, University of Queensland, Brisbane, Australia
| | - Marjorie M Walker
- College of Health, Medicine and Wellbeing, University of Newcastle, Callaghan, and Hunter Medical Research Institute, New Lambton Heights, Australia
| | - Erin R Shanahan
- Department of Gastroenterology and Hepatology, Princess Alexandra Hospital, Brisbane, Australia,Translational Research Institute Queensland, Australia
| | - Natasha A Koloski
- Department of Gastroenterology and Hepatology, Princess Alexandra Hospital, Brisbane, Australia,Translational Research Institute Queensland, Australia,Faculty of Medicine, University of Queensland, Brisbane, Australia,College of Health, Medicine and Wellbeing, University of Newcastle, Callaghan, and Hunter Medical Research Institute, New Lambton Heights, Australia
| | - Michael P Jones
- College of Health, Medicine and Wellbeing, University of Newcastle, Callaghan, and Hunter Medical Research Institute, New Lambton Heights, Australia
| | - Simon Keely
- School of Biomedical Sciences and Pharmacy, University of Newcastle, Callaghan, and Hunter Medical Research Institute, New Lambton Heights, Australia
| | - Mark Morrison
- Department of Gastroenterology and Hepatology, Princess Alexandra Hospital, Brisbane, Australia,Faculty of Medicine, University of Queensland, Brisbane, Australia,University of Queensland Diamantina Institute, Woolloongabba, Australia,CONTACT Mark Morrison
| | - Gerald J Holtmann
- Department of Gastroenterology and Hepatology, Princess Alexandra Hospital, Brisbane, Australia,Translational Research Institute Queensland, Australia,Faculty of Medicine, University of Queensland, Brisbane, Australia,Gerald J Holtmann Princess Alexandra Hospital, Brisbane Department of Gastroenterology and Hepatology & University of Queensland 199 Ipswich Road, Woolloongabba, Queensland, Australia
| |
Collapse
|
|
5
|
Karpe AV, Liu JW, Shah A, Koloski N, Holtmann G, Beale DJ. Utilising lipid and, arginine and proline metabolism in blood plasma to differentiate the biochemical expression in functional dyspepsia (FD) and irritable bowel syndrome (IBS). Metabolomics 2022; 18:38. [PMID: 35687195 DOI: 10.1007/s11306-022-01900-z] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/18/2021] [Accepted: 05/25/2022] [Indexed: 02/07/2023]
Abstract
Functional gastrointestinal disorders (FGID) such as functional dyspepsia (FD) and irritable bowel syndrome (IBS) are highly prevalent and debilitating attributed to altered gut function and gut-brain interactions. FGID can be reliably diagnosed based upon the symptom pattern; but in the clinical setting FD or IBS a frequent diagnoses of exclusion after relevant structural causes of symptoms have been ruled out by appropriate testing. Thus far, there is no established biomarker for FGIDs. To address this limitation, we utilised multi-omics and chemometrics integration to characterise the blood plasma biochemistry in patients with IBS, FD, an overlap of FD/IBS, and controls using liquid chromatography-mass spectrometry (LC-MS) techniques.Cholesterol metabolism products Cholest-5,24-dien-3β-ol, 3-O-β-D-glucopyranoside, energy pathway metabolites, immunoglobulin-γ2 and immunoglobulin-κ, and carbonic anhydrase-1 proteins were particularly elevated in IBS. Furthermore, arginine and proline metabolisms, thyroid hormone synthesis, ferroptosis and, complementary and coagulation cascades were particularly upregulated in patients with IBS. Cer(d18:1/26:1(17Z)) and PI(14:0/22:1(11Z)) lipids were elevated in FD and FD-IBS but were depleted in IBS. Markers of central carbon metabolism and lipidome profiles allowed better discrimination and model predictability than metaproteome profile in healthy and FGID conditions.Overall, the multi-omics integration allowed the discrimination of healthy controls and FGID patients. It also effectively differentiated the biochemistry of FGID subtypes including FD, IBS and FD-IBS co-occurrence. This study points towards the possibility of multi-omics integration for rapid and high throughput analysis of plasma samples to support clinicians screen and diagnose patients with suspected FGIDs.
Collapse
Affiliation(s)
- Avinash V Karpe
- CSIRO Land and Water, P. O. Box 2583, 4001, Dutton Park, QLD, Australia
- Department of Chemistry & Biotechnology, School of Science, Computing & Engineering Technologies (SoSCET), Swinburne University of Technology, 3122, Hawthorn, VIC, Australia
| | - Jian-Wei Liu
- CSIRO Land and Water, Black Mountain, Clunies Ross Street, 2601, Acton, ACT, Australia
| | - Ayesha Shah
- Department of Gastroenterology & Hepatology, Princess Alexandra Hospital, 4103, Woolloongabba, QLD, Australia
| | - Natasha Koloski
- Faculty of Health and Medicine, University of Newcastle, 2308, Callaghan, NSW, Australia
- School of Medicine, The University of Queensland, 4072, St. Lucia, QLD, Australia
| | - Gerald Holtmann
- Department of Gastroenterology & Hepatology, Princess Alexandra Hospital, 4103, Woolloongabba, QLD, Australia
- School of Medicine, The University of Queensland, 4072, St. Lucia, QLD, Australia
| | - David J Beale
- CSIRO Land and Water, P. O. Box 2583, 4001, Dutton Park, QLD, Australia.
| |
Collapse
|
|
6
|
Concomitant Irritable Bowel Syndrome Does Not Influence the Response to Antimicrobial Therapy in Patients with Functional Dyspepsia. Dig Dis Sci 2022; 67:2299-2309. [PMID: 34392491 DOI: 10.1007/s10620-021-07149-1] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/03/2021] [Accepted: 05/03/2021] [Indexed: 12/12/2022]
Abstract
BACKGROUND AND AIMS Antimicrobial therapy improves symptoms in patients with irritable bowel syndrome (IBS), but the efficacy in functional dyspepsia (FD) is largely unknown. While FD and IBS frequently overlap, it is unknown if concomitant IBS in FD alters the response to antimicrobial therapy in FD. Thus, we aimed to assess and compare the effect of antimicrobial therapy on visceral sensory function and symptom improvement in FD patients with and without IBS. METHODS Adult patients with FD with or without IBS received rifaximin 550 mg BD for 10 days, followed by a 6-week follow-up period. The total gastrointestinal symptom score as measured by the SAGIS (Structured Assessment of Gastrointestinal Symptoms) questionnaire and subscores (dyspepsia, diarrhea, and constipation), symptom response to a standardized nutrient challenge and normalization of the glucose breath tests were measured. RESULTS Twenty-one consecutive adult patients with FD and 14/21 with concomitant IBS were recruited. Treatment with rifaximin resulted in a significant (p = 0.017) improvement in the total SAGIS score from 34.7 (± 15.4) at baseline to 26.0 (± 16.8) at 2 weeks and 25.6 (± 17.8) at 6 weeks post-treatment. Similarly, compared to baseline there was a statistically significant improvement in SAGIS subscores for dyspepsia and diarrhea (all p < 0.05) and effects persisted for 6 weeks post-treatment. Similarly, the symptom score (and subscores) following a standardized nutrient challenge improved significantly (p < 0.001) 2 weeks post-treatment. The presence of concomitant IBS did not significantly influence the improvement of symptoms after antibiotic therapy (all p > 0.5). CONCLUSIONS In FD patients, the response to antimicrobial therapy with rifaximin is not influenced by concomitant IBS symptoms.
Collapse
|
|
7
|
Wauters L, Dickman R, Drug V, Mulak A, Serra J, Enck P, Tack J, Accarino A, Barbara G, Bor S, Coffin B, Corsetti M, De Schepper H, Dumitrascu D, Farmer A, Gourcerol G, Hauser G, Hausken T, Karamanolis G, Keszthelyi D, Malagelada C, Milosavljevic T, Muris J, O'Morain C, Papathanasopoulos A, Pohl D, Rumyantseva D, Sarnelli G, Savarino E, Schol J, Sheptulin A, Smet A, Stengel A, Storonova O, Storr M, Törnblom H, Vanuytsel T, Velosa M, Waluga M, Zarate N, Zerbib F. United European Gastroenterology (UEG) and European Society for Neurogastroenterology and Motility (ESNM) consensus on functional dyspepsia. Neurogastroenterol Motil 2021; 33:e14238. [PMID: 34586707 DOI: 10.1111/nmo.14238] [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: 11/01/2020] [Revised: 12/15/2020] [Accepted: 12/22/2020] [Indexed: 02/05/2023]
Abstract
BACKGROUND Functional dyspepsia (FD) is one of the most common conditions in clinical practice. In spite of its prevalence, FD is associated with major uncertainties in terms of its definition, underlying pathophysiology, diagnosis, treatment, and prognosis. METHODS A Delphi consensus was initiated with 41 experts from 22 European countries who conducted a literature summary and voting process on 87 statements. Quality of evidence was evaluated using the grading of recommendations, assessment, development, and evaluation (GRADE) criteria. Consensus (defined as >80% agreement) was reached for 36 statements. RESULTS The panel agreed with the definition in terms of its cardinal symptoms (early satiation, postprandial fullness, epigastric pain, and epigastric burning), its subdivision into epigastric pain syndrome and postprandial distress syndrome, and the presence of accessory symptoms (upper abdominal bloating, nausea, belching), and overlapping conditions. Also, well accepted are the female predominance of FD, its impact on quality of life and health costs, and acute gastrointestinal infections, and anxiety as risk factors. In terms of pathophysiological mechanisms, the consensus supports a role for impaired gastric accommodation, delayed gastric emptying, hypersensitivity to gastric distention, Helicobacter pylori infection, and altered central processing of signals from the gastroduodenal region. There is consensus that endoscopy is mandatory for establishing a firm diagnosis of FD, but that in primary care, patients without alarm symptoms or risk factors can be managed without endoscopy. There is consensus that H. pylori status should be determined in every patient with dyspeptic symptoms and H. pylori positive patients should receive eradication therapy. Also, proton pump inhibitor therapy is considered an effective therapy for FD, but no other treatment approach reached a consensus. The long-term prognosis and life expectancy are favorable. CONCLUSIONS AND INFERENCES A multinational group of European experts summarized the current state of consensus on the definition, diagnosis and management of FD.
Collapse
Affiliation(s)
- Lucas Wauters
- Department of Gastroenterology and Hepatology, University Hospitals Leuven, Leuven, Belgium
| | - Ram Dickman
- Division of Gastroenterology, Rabin Medical Center, Beilinson Hospital, Petach Tikwa, Israel
| | - Vasile Drug
- University of Medicine and Pharmacy Gr T Popa Iasi and University Hospital St Spiridon, Iasi, Romania
| | - Agata Mulak
- Department of Gastroenterology and Hepatology, Wroclaw Medical University, Wroclaw, Poland
| | - Jordi Serra
- University Hospital Germans Trias I Pujol and Centro de Investigación Biomédica en Red de enfermedades Hepáticas y Digestivas (CIBERehd), Badalona, Spain
| | - Paul Enck
- Department of Internal Medicine VI: Psychosomatic Medicine and Psychotherapy, University Hospital Tübingen, Tübingen, Germany
| | - Jan Tack
- Department of Gastroenterology and Hepatology, University Hospitals Leuven, Leuven, Belgium
| | | | - Anna Accarino
- CIBERehd and Departament de Medicina, Digestive System Research Unit, University Hospital Vall D'Hebron, Barcelona, Spain
| | - Giovanni Barbara
- Department of Medical and Surgical Sciences, University of Bologna, Bologna, Italy
| | - Serhat Bor
- Division of Gastroenterology, School of Medicine, Ege University, Izmir, Turkey
| | - Benoit Coffin
- Université de Paris and AP-HP Hôpital Louis Mourier, Paris, France
| | - Maura Corsetti
- NIHR Nottingham Biomedical Research Centre (BRC), Hospitals NHS Trust and the University of Nottingham, Nottingham, UK
| | - Heiko De Schepper
- Department of Gastroenterology and Hepatology, University Hospital Antwerp, Antwerp, Belgium
| | - Dan Dumitrascu
- 2nd Department of Internal Medicine, Iuliu Hatieganu University of Medicine and Pharmacy, Cluj-Napoca, Romania
| | - Adam Farmer
- Wingate Institute of Neurogastroenterology, Barts and London School of Medicine and Dentistry, Queen Mary University of London, London, UK
| | | | - Goran Hauser
- Medical Faculty Rijeka, University of Rijeka and Clinical Hospital Centre Rijeka, Rijeka, Croatia
| | - Trygve Hausken
- Department of Gastroenterology, Haukeland University Hospital, Bergen, Norway
| | - George Karamanolis
- Gastroentrology Unit, Aretaieio Hospital, National and Kapodistrian University of Athens, Athens, Greece
| | - Daniel Keszthelyi
- Division of Gastroenterology-Hepatology, Maastricht University Medical Center, Maastricht, The Netherlands
| | - Carolin Malagelada
- CIBERehd and Departament de Medicina, Digestive System Research Unit, University Hospital Vall D'Hebron, Barcelona, Spain
| | | | - Jean Muris
- Department of General Practice, Caphri Institute, Maastricht University, Maastricht, The Netherlands
| | - Colm O'Morain
- Department of Medicine, Trinity College Dublin and National Clinical Lead for Gastroenterology and Hepatology, Royal College Physicians Ireland, Dublin, Ireland
| | | | - Daniel Pohl
- Division of Gastroenterology and Hepatology, University Hospital Zurich, Zurich, Switzerland
| | - Diana Rumyantseva
- I.M. Sechenov First Moscow State Medical University, Ministry of Health of the Russian Federation (Sechenov University), Moscow, Russia
| | - Giovanni Sarnelli
- Department of Clinical Medicine and Surgery, University of Naples Federico II, Naples, Italy
| | - Edoardo Savarino
- Gastroenterology Unit, Departmento of Surgery, Oncology and Gastroenterology, University of Padua, Padua, Italy
| | - Jolien Schol
- Department of Gastroenterology and Hepatology, University Hospitals Leuven, Leuven, Belgium
| | - Arkady Sheptulin
- I.M. Sechenov First Moscow State Medical University, Ministry of Health of the Russian Federation (Sechenov University), Moscow, Russia
| | - Annemieke Smet
- Laboratory of Experimental Medicine and Pediatrics and InflA-Med Centre of Excellence, University of Antwerp, Antwerp, Belgium
| | - Andreas Stengel
- Department of Psychosomatic Medicine and Psychotherapy, Internal Medicine VI, University Hospital Tübingen, and Charité Center for Internal Medicine and Dermatology, Tübingen, Germany
- Department for Psychosomatic Medicine, Charité-Universitätsmedizin, Freie Universität Berlin, Humboldt-Universität zu Berlin and Berlin Institute of Health, Berlin, Germany
- Center of Endoscopy, Starnberg, Germany
- Ludwig-Maximilians-University, Munich, Germany
| | - Olga Storonova
- I.M. Sechenov First Moscow State Medical University, Ministry of Health of the Russian Federation (Sechenov University), Moscow, Russia
| | - Martin Storr
- Department for Psychosomatic Medicine, Charité-Universitätsmedizin, Freie Universität Berlin, Humboldt-Universität zu Berlin and Berlin Institute of Health, Berlin, Germany
| | - Hans Törnblom
- Department of Internal Medicine, Sahlgrenska University Hospital, Gothenburg, Sweden
| | - Tim Vanuytsel
- Department of Gastroenterology and Hepatology, University Hospitals Leuven, Leuven, Belgium
| | | | - Marek Waluga
- Department of Gastroenterology and Hepatology, Medical University of Silesia, Katowice, Poland
| | - Natalia Zarate
- Gastrointestinal Physiology Unit, University College London Hospital, London, UK
| | - Frank Zerbib
- CHU de Bordeaux, Centre Medico-chirurgical Magellan, Hôpital Haut-Lévêque and Gastroenterology Department, Université de Bordeaux, INSERM CIC, Bordeaux, France
| |
Collapse
|
|
8
|
Talley NJ, Walker MM, Jones M, Keely S, Koloski N, Cameron R, Fairlie T, Burns G, Shah A, Hansen T, Harris G, Holtmann G. Letter: budesonide for functional dyspepsia with duodenal eosinophilia-randomised, double-blind, placebo-controlled parallel-group trial. Aliment Pharmacol Ther 2021; 53:1332-1333. [PMID: 34029411 DOI: 10.1111/apt.16396] [Citation(s) in RCA: 12] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/21/2022]
Affiliation(s)
- N J Talley
- University of Newcastle, Newcastle, NSW, Australia.,NHMRC Centre of Research Excellence in Digestive Health, New Lambton Heights, NSW, Australia
| | - M M Walker
- University of Newcastle, Newcastle, NSW, Australia.,NHMRC Centre of Research Excellence in Digestive Health, New Lambton Heights, NSW, Australia
| | - M Jones
- NHMRC Centre of Research Excellence in Digestive Health, New Lambton Heights, NSW, Australia.,Department of Psychology, Macquarie University, Ryde, NSW, Australia
| | - S Keely
- University of Newcastle, Newcastle, NSW, Australia.,NHMRC Centre of Research Excellence in Digestive Health, New Lambton Heights, NSW, Australia
| | - N Koloski
- University of Newcastle, Newcastle, NSW, Australia.,NHMRC Centre of Research Excellence in Digestive Health, New Lambton Heights, NSW, Australia.,Department of Psychology, Macquarie University, Ryde, NSW, Australia.,Department of Gastroenterology, Princess Alexander Hospital, Woolloongabba, Qld, Australia
| | - R Cameron
- University of Newcastle, Newcastle, NSW, Australia.,NHMRC Centre of Research Excellence in Digestive Health, New Lambton Heights, NSW, Australia
| | - T Fairlie
- Department of Gastroenterology, Princess Alexander Hospital, Woolloongabba, Qld, Australia
| | - G Burns
- University of Newcastle, Newcastle, NSW, Australia.,NHMRC Centre of Research Excellence in Digestive Health, New Lambton Heights, NSW, Australia
| | - A Shah
- NHMRC Centre of Research Excellence in Digestive Health, New Lambton Heights, NSW, Australia.,Department of Gastroenterology, Princess Alexander Hospital, Woolloongabba, Qld, Australia.,School of Medicine, University of Queensland, St Lucia, Qld, Australia
| | - T Hansen
- Department of Psychology, Macquarie University, Ryde, NSW, Australia
| | - G Harris
- University of Newcastle, Newcastle, NSW, Australia.,NHMRC Centre of Research Excellence in Digestive Health, New Lambton Heights, NSW, Australia
| | - G Holtmann
- NHMRC Centre of Research Excellence in Digestive Health, New Lambton Heights, NSW, Australia.,Department of Gastroenterology, Princess Alexander Hospital, Woolloongabba, Qld, Australia.,School of Medicine, University of Queensland, St Lucia, Qld, Australia
| |
Collapse
|
|
9
|
Wauters L, Dickman R, Drug V, Mulak A, Serra J, Enck P, Tack J, Accarino A, Barbara G, Bor S, Coffin B, Corsetti M, De Schepper H, Dumitrascu D, Farmer A, Gourcerol G, Hauser G, Hausken T, Karamanolis G, Keszthelyi D, Malagelada C, Milosavljevic T, Muris J, O'Morain C, Papathanasopoulos A, Pohl D, Rumyantseva D, Sarnelli G, Savarino E, Schol J, Sheptulin A, Smet A, Stengel A, Storonova O, Storr M, Törnblom H, Vanuytsel T, Velosa M, Waluga M, Zarate N, Zerbib F. United European Gastroenterology (UEG) and European Society for Neurogastroenterology and Motility (ESNM) consensus on functional dyspepsia. United European Gastroenterol J 2021; 9:307-331. [PMID: 33939891 PMCID: PMC8259261 DOI: 10.1002/ueg2.12061] [Citation(s) in RCA: 51] [Impact Index Per Article: 12.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/01/2020] [Revised: 12/15/2020] [Accepted: 12/22/2020] [Indexed: 12/15/2022] Open
Abstract
Background Functional dyspepsia (FD) is one of the most common conditions in clinical practice. In spite of its prevalence, FD is associated with major uncertainties in terms of its definition, underlying pathophysiology, diagnosis, treatment, and prognosis. Methods A Delphi consensus was initiated with 41 experts from 22 European countries who conducted a literature summary and voting process on 87 statements. Quality of evidence was evaluated using the grading of recommendations, assessment, development, and evaluation (GRADE) criteria. Consensus (defined as >80% agreement) was reached for 36 statements. Results The panel agreed with the definition in terms of its cardinal symptoms (early satiation, postprandial fullness, epigastric pain, and epigastric burning), its subdivision into epigastric pain syndrome and postprandial distress syndrome, and the presence of accessory symptoms (upper abdominal bloating, nausea, belching), and overlapping conditions. Also, well accepted are the female predominance of FD, its impact on quality of life and health costs, and acute gastrointestinal infections, and anxiety as risk factors. In terms of pathophysiological mechanisms, the consensus supports a role for impaired gastric accommodation, delayed gastric emptying, hypersensitivity to gastric distention, Helicobacter pylori infection, and altered central processing of signals from the gastroduodenal region. There is consensus that endoscopy is mandatory for establishing a firm diagnosis of FD, but that in primary care, patients without alarm symptoms or risk factors can be managed without endoscopy. There is consensus that H. pylori status should be determined in every patient with dyspeptic symptoms and H. pylori positive patients should receive eradication therapy. Also, proton pump inhibitor therapy is considered an effective therapy for FD, but no other treatment approach reached a consensus. The long‐term prognosis and life expectancy are favorable. Conclusions and Inferences A multinational group of European experts summarized the current state of consensus on the definition, diagnosis and management of FD.
Current knowledge
Functional dyspepsia is one of the most common conditions encountered in clinical practice. There is a lack of guidance for clinicians in guiding diagnosis and treatment of this prevalent condition. No treatments are currently approved for the treatment of functional dyspepsia in Europe.
What is new here
A Delphi panel consisting of 41 experts from 22 European countries established the level of consensus on 87 statements regarding functional dyspepsia. The statements reaching consensus serve to guide clinicians in recognizing, diagnosing and treating FD in clinical practice. Endoscopy is mandatory for establishing a firm diagnosis of functional dyspepsia D, but in primary care patients without alarm symptoms or risk factors can be managed without endoscopy. Helicobacter pylori status should be determined in every patient with dyspeptic symptoms and H. Pylori positive patients should receive eradication therapy. Proton pump inhibitor‐therapy is considered an effective therapy for FD, but no other treatment approach reached consensus support.
Collapse
Affiliation(s)
- Lucas Wauters
- Department of Gastroenterology and Hepatology, University Hospitals Leuven, Leuven, Belgium
| | - Ram Dickman
- Division of Gastroenterology, Rabin Medical Center, Beilinson Hospital, Petach Tikwa, Israel
| | - Vasile Drug
- University of Medicine and Pharmacy Gr T Popa Iasi and University Hospital St Spiridon, Iasi, Romania
| | - Agata Mulak
- Department of Gastroenterology and Hepatology, Wroclaw Medical University, Wroclaw, Poland
| | - Jordi Serra
- University Hospital Germans Trias I Pujol and Centro de Investigación Biomédica en Red de enfermedades Hepáticas y Digestivas (CIBERehd), Badalona, Spain
| | - Paul Enck
- Department of Internal Medicine VI: Psychosomatic Medicine and Psychotherapy, University Hospital Tübingen, Tübingen, Germany
| | - Jan Tack
- Department of Gastroenterology and Hepatology, University Hospitals Leuven, Leuven, Belgium
| | | | - Anna Accarino
- CIBERehd and Departament de Medicina, Digestive System Research Unit, University Hospital Vall D'Hebron, Barcelona, Spain
| | - Giovanni Barbara
- Department of Medical and Surgical Sciences, University of Bologna, Bologna, Italy
| | - Serhat Bor
- Division of Gastroenterology, School of Medicine, Ege University, Izmir, Turkey
| | - Benoit Coffin
- Université de Paris and AP-HP Hôpital Louis Mourier, Paris, France
| | - Maura Corsetti
- NIHR Nottingham Biomedical Research Centre (BRC), Hospitals NHS Trust and the University of Nottingham, Nottingham, UK
| | - Heiko De Schepper
- Department of Gastroenterology and Hepatology, University Hospital Antwerp, Antwerp, Belgium
| | - Dan Dumitrascu
- 2nd Department of Internal Medicine, Iuliu Hatieganu University of Medicine and Pharmacy, Cluj-Napoca, Romania
| | - Adam Farmer
- Wingate Institute of Neurogastroenterology, Barts and London School of Medicine and Dentistry, Queen Mary University of London, London, UK
| | | | - Goran Hauser
- Medical Faculty Rijeka, University of Rijeka and Clinical Hospital Centre Rijeka, Rijeka, Croatia
| | - Trygve Hausken
- Department of Gastroenterology, Haukeland University Hospital, Bergen, Norway
| | - George Karamanolis
- Gastroentrology Unit, Aretaieio Hospital, National and Kapodistrian University of Athens, Athens, Greece
| | - Daniel Keszthelyi
- Division of Gastroenterology-Hepatology, Maastricht University Medical Center, Maastricht, The Netherlands
| | - Carolin Malagelada
- CIBERehd and Departament de Medicina, Digestive System Research Unit, University Hospital Vall D'Hebron, Barcelona, Spain
| | | | - Jean Muris
- Department of General Practice, Caphri Institute, Maastricht University, Maastricht, The Netherlands
| | - Colm O'Morain
- Department of Medicine, Trinity College Dublin and National Clinical Lead for Gastroenterology and Hepatology, Royal College Physicians Ireland, Dublin, Ireland
| | | | - Daniel Pohl
- Division of Gastroenterology and Hepatology, University Hospital Zurich, Zurich, Switzerland
| | - Diana Rumyantseva
- I.M. Sechenov First Moscow State Medical University, Ministry of Health of the Russian Federation (Sechenov University), Moscow, Russia
| | - Giovanni Sarnelli
- Department of Clinical Medicine and Surgery, University of Naples Federico II, Naples, Italy
| | - Edoardo Savarino
- Gastroenterology Unit, Departmento of Surgery, Oncology and Gastroenterology, University of Padua, Padua, Italy
| | - Jolien Schol
- Department of Gastroenterology and Hepatology, University Hospitals Leuven, Leuven, Belgium
| | - Arkady Sheptulin
- I.M. Sechenov First Moscow State Medical University, Ministry of Health of the Russian Federation (Sechenov University), Moscow, Russia
| | - Annemieke Smet
- Laboratory of Experimental Medicine and Pediatrics and InflA-Med Centre of Excellence, University of Antwerp, Antwerp, Belgium
| | - Andreas Stengel
- Department of Psychosomatic Medicine and Psychotherapy, Internal Medicine VI, University Hospital Tübingen, and Charité Center for Internal Medicine and Dermatology, Tübingen, Germany.,Department for Psychosomatic Medicine, Charité-Universitätsmedizin, Freie Universität Berlin, Humboldt-Universität zu Berlin and Berlin Institute of Health, Berlin, Germany.,Center of Endoscopy, Starnberg, Germany.,Ludwig-Maximilians-University, Munich, Germany
| | - Olga Storonova
- I.M. Sechenov First Moscow State Medical University, Ministry of Health of the Russian Federation (Sechenov University), Moscow, Russia
| | - Martin Storr
- Department for Psychosomatic Medicine, Charité-Universitätsmedizin, Freie Universität Berlin, Humboldt-Universität zu Berlin and Berlin Institute of Health, Berlin, Germany
| | - Hans Törnblom
- Department of Internal Medicine, Sahlgrenska University Hospital, Gothenburg, Sweden
| | - Tim Vanuytsel
- Department of Gastroenterology and Hepatology, University Hospitals Leuven, Leuven, Belgium
| | | | - Marek Waluga
- Department of Gastroenterology and Hepatology, Medical University of Silesia, Katowice, Poland
| | - Natalia Zarate
- Gastrointestinal Physiology Unit, University College London Hospital, London, UK
| | - Frank Zerbib
- CHU de Bordeaux, Centre Medico-chirurgical Magellan, Hôpital Haut-Lévêque and Gastroenterology Department, Université de Bordeaux, INSERM CIC, Bordeaux, France
| |
Collapse
|
|
10
|
Induction of Meal-related Symptoms as a Novel Mechanism of Action of the Duodenal-Jejunal Bypass Sleeve. J Clin Gastroenterol 2020; 54:528-535. [PMID: 32301829 DOI: 10.1097/mcg.0000000000001353] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Abstract
BACKGROUND Treatment with a duodenal-jejunal bypass sleeve (DJBS) induces clinically significant weight loss, but little is known about the mechanisms of action of this device. AIM The aim of this study was to characterize the mechanisms of action of the DJBS and determine the durability of weight loss and metabolic improvements. MATERIALS AND METHODS We studied a cohort of 19 subjects with severe obesity and type 2 diabetes (baseline body mass index: 43.7±5.3 kg/m). Anthropometry, body composition, blood pressure, biochemical measures, and dietary intake were monitored for 48 weeks after DJBS implantation, and then for 1 year after device removal. Gastric emptying and triglyceride absorption were measured at baseline, 8 weeks after implant, and within 3 weeks of device explant. Visceral sensory function was assessed at baseline, 4 weeks after implant, and within 3 weeks after explant. RESULTS Significant weight loss (P<0.01) occurred following DJBS placement, with a mean weight reduction of 17.0±6.5% at 48 weeks. The symptom burden following a standardized nutrient challenge was increased after DJBS implantation (P<0.05), returning to baseline after DJBS removal. Neither gastric emptying nor triglyceride absorption changed with the device in situ. A significant reduction in energy intake was observed [baseline: 7703±2978 kJ (1841±712 kcal), 24 weeks: 4824±2259 kJ (1153±540 kcal), and 48 weeks: 4474±1468 kJ (1069±351 kcal)]. After 1 year, anthropometry remained significantly improved, but there was no durable impact on metabolic outcomes. CONCLUSIONS DJBS treatment resulted in substantial weight loss. Weight loss is related to reduced caloric intake, which seems linked to an augmented upper gastrointestinal symptom response, but not altered fat absorption.
Collapse
|
|
11
|
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.
Collapse
|
|
12
|
Ji E, Wang T, Guo F, Zhang Y, Tang C, Tang D, Wei J, Yang H, Xian M. Xiaoerfupi alleviates the symptoms of functional dyspepsia by regulating the HTR3A and c-FOS. Biomed Pharmacother 2019; 120:109442. [DOI: 10.1016/j.biopha.2019.109442] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/17/2019] [Revised: 08/20/2019] [Accepted: 09/06/2019] [Indexed: 01/23/2023] Open
|
|
13
|
Estremera-Arevalo F, Barcelo M, Serrano B, Rey E. Nutrient drink test: A promising new tool for irritable bowel syndrome diagnosis. World J Gastroenterol 2019; 25:837-847. [PMID: 30809083 PMCID: PMC6385016 DOI: 10.3748/wjg.v25.i7.837] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/10/2018] [Revised: 01/11/2019] [Accepted: 01/26/2019] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Irritable bowel syndrome (IBS) is a highly prevalent condition. It is diagnosed on the basis of chronic symptoms after the clinical and/or investigative exclusion of organic diseases that can cause similar symptoms. There is no reproducible non-invasive test for the diagnosis of IBS, and this raises diagnostic uncertainty among physicians and hinders acceptance of the diagnosis by patients. Functional gastrointestinal (GI) syndromes often present with overlapping upper and lower GI tract symptoms, now believed to be generated by visceral hypersensitivity. This study examines the possibility that, in IBS, a nutrient drink test (NDT) provokes GI symptoms that allow a positive differentiation of these patients from healthy subjects.
AIM To evaluate the NDT for the diagnosis of IBS.
METHODS This prospective case-control study compared the effect of two different nutrient drinks on GI symptoms in 10 IBS patients (patients) and 10 healthy controls (controls). The 500 kcal high nutrient drink and the low nutrient 250 kcal drink were given in randomized order on separate days. Symptoms were assessed just before and at several time points after drink ingestion. Global dyspepsia and abdominal scores were derived from individual symptom data recorded by two questionnaires designed by our group, the upper and the general GI symptom questionnaires, respectively. Psycho-social morbidity and quality of life were also formally assessed. The scores of patients and controls were compared using single factor analysis of variance test.
RESULTS At baseline, IBS patients compared to controls had significantly higher levels of GI symptoms such as gastro-esophageal reflux (P = 0.05), abdominal pain (P = 0.001), dyspepsia (P = 0.001), diarrhea (P = 0.001), and constipation (P = 0.001) as well as higher psycho-social morbidity and lower quality of life. The very low incidence of GI symptoms reported by control subjects did not differ significantly for the two test drinks. Compared with the low nutrient drink, IBS patients with the high nutrient drink had significantly more dyspeptic symptoms at 30 (P = 0.014), 45 (P = 0.002), 60 (P = 0.001), and 120 min (P = 0.011). Dyspeptic symptoms triggered by the high nutrient drink during the first 120 min gave the best differentiation between healthy controls and patients (area under receiver operating curve of 0.915 at 45 min for the dyspepsia score). Continued symptom monitoring for 24 h did not enhance separation of patients from controls.
CONCLUSION A high NDT merits further evaluation as a diagnostic tool for IBS.
Collapse
Affiliation(s)
| | - Marta Barcelo
- Department of Gastroenterolgy, Hospital Infanta Leonor, Madrid 28031, Spain
| | - Blanca Serrano
- Department of Digestive Diseases, Hospital Clinico San Carlos, Madrid 28040, Spain
| | - Enrique Rey
- Department of Digestive Diseases, Hospital Clinico San Carlos and Complutense University, Madrid 28040, Spain
| |
Collapse
|
|
14
|
Holtmann GJ, Talley NJ. Inconsistent symptom clusters for functional gastrointestinal disorders in Asia: is Rome burning? Gut 2018; 67:1911-1915. [PMID: 29921653 DOI: 10.1136/gutjnl-2017-314775] [Citation(s) in RCA: 19] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/30/2017] [Revised: 04/06/2018] [Accepted: 05/12/2018] [Indexed: 12/11/2022]
Affiliation(s)
- Gerald J Holtmann
- Department of Gastroenterology and Hepatology, Princess Alexandra Hospital, Brisbane, Faculties of Medicine and Health and Behavioural Sciences, University of Queensland and Translational Research Institute (TRI), Brisbane, Queensland, Australia
| | - Nicholas J Talley
- Faculty of Health and Medicine, University of Newcastle, Newcastle, New South Wales, Australia
| |
Collapse
|
|
15
|
Hammer V, Hammer K, Memaran N, Huber WD, Hammer K, Hammer J. Relationship Between Abdominal Symptoms and Fructose Ingestion in Children with Chronic Abdominal Pain. Dig Dis Sci 2018; 63:1270-1279. [PMID: 29511898 PMCID: PMC5895692 DOI: 10.1007/s10620-018-4997-4] [Citation(s) in RCA: 19] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/11/2017] [Accepted: 02/22/2018] [Indexed: 12/25/2022]
Abstract
BACKGROUND Limited valid data are available regarding the association of fructose-induced symptoms, fructose malabsorption, and clinical symptoms. AIM To develop a questionnaire for valid symptom assessment before and during a carbohydrate breath test and to correlate symptoms with fructose breath test results in children/adolescents with functional abdominal pain. METHODS A Likert-type questionnaire assessing symptoms considered relevant for hydrogen breath test in children was developed and underwent initial validation. Fructose malabsorption was determined by increased breath hydrogen in 82 pediatric patients with functional abdominal pain disorders; fructose-induced symptoms were quantified by symptom score ≥2 and relevant symptom increase over baseline. The results were correlated with clinical symptoms. The time course of symptoms during the breath test was assessed. RESULTS The questionnaire exhibited good psychometric properties in a standardized assessment of the severity of carbohydrate-related symptoms. A total of 40 % (n = 33) had malabsorption; symptoms were induced in 38 % (n = 31), but only 46 % (n = 15) with malabsorption were symptomatic. There was no significant correlation between fructose malabsorption and fructose-induced symptoms. Clinical symptoms correlated with symptoms evoked during the breath test (p < 0.001, r2 = 0.21) but not with malabsorption (NS). Malabsorbers did not differ from non-malabsorbers in terms of symptoms during breath test. Symptomatic patients had significantly higher pain and flatulence scores over the 9-h observation period (p < 0.01) than did nonsymptomatic patients; the meteorism score was higher after 90 min. CONCLUSIONS Fructose-induced symptoms but not fructose malabsorption are related to increased abdominal symptoms and have distinct timing patterns.
Collapse
Affiliation(s)
- Veronika Hammer
- Abteilung für Gastroenterologie und Hepatologie, Universitätsklinik für Innere Medizin 3, Medical University of Vienna, Währinger Gürtel 18 - 20, 1090, Vienna, Austria
| | - Katharina Hammer
- Abteilung für Gastroenterologie und Hepatologie, Universitätsklinik für Innere Medizin 3, Medical University of Vienna, Währinger Gürtel 18 - 20, 1090, Vienna, Austria
| | - Nima Memaran
- Klinische Abteilung für Pädiatrische Nephrologie und Gastroenterologie, Universitätsklinik für Kinder- und Jugendheilkunde, Medical University of Vienna, Vienna, Austria
- Department of Pediatric Kidney, Liver and Metabolic Diseases, Children's Hospital, Hannover Medical School, Hanover, Germany
| | - Wolf-Dietrich Huber
- Klinische Abteilung für Pädiatrische Nephrologie und Gastroenterologie, Universitätsklinik für Kinder- und Jugendheilkunde, Medical University of Vienna, Vienna, Austria
| | - Karin Hammer
- St. Anna Kinderspital, Medical University of Vienna, Vienna, Austria
| | - Johann Hammer
- Abteilung für Gastroenterologie und Hepatologie, Universitätsklinik für Innere Medizin 3, Medical University of Vienna, Währinger Gürtel 18 - 20, 1090, Vienna, Austria.
| |
Collapse
|
|
16
|
Gray MA, Chao CY, Staudacher HM, Kolosky NA, Talley NJ, Holtmann G. Anti-TNFα therapy in IBD alters brain activity reflecting visceral sensory function and cognitive-affective biases. PLoS One 2018. [PMID: 29518097 PMCID: PMC5843226 DOI: 10.1371/journal.pone.0193542] [Citation(s) in RCA: 38] [Impact Index Per Article: 5.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/25/2022] Open
Abstract
Background In inflammatory bowel disease (IBD), immune activation with increased circulating TNF-α is linked to the intensity of gastrointestinal symptoms and depression or anxiety. A central feature of depression is cognitive biases linked to negative attributions about self, the world and the future. We aimed to assess the effects of anti-TNFα therapy on the central processing of self-attribution biases and visceral afferent information in patients with Crohn’s disease. Methods We examined 9 patients with Crohn’s disease (age 26.1±10.6. yrs, 5 female, 5 ileocolonic, 2 colonic and 2 ileal disease) during chronic anti-TNFα therapy (5 adalimumab, 4 infliximab). Patients were studied twice in randomized order before and after anti-TNFα administration. On each occasion patients underwent functional magnetic resonance imaging (fMRI) of the brain during a test of implicit attribution biases regarding sickness/health and undertook a standardized nutrient challenge. Results Following anti-TNFα treatment, ratings of ‘fullness’ following nutrient challenge reduced compared to pre-treatment ratings (p<0.05). Reaction times revealed improved processing of self-related and positive health words, consistent with improved implicit sense of wellbeing that correlated with improvements in sensory function after treatment (r = 0.67, p<0.05). Treatment-associated improvements in implicit processing were mirrored by alterations of prefrontal, amygdala, posterior cingulate and visual regions. Between patients, the degree of functional amygdala change was additionally explained by individual differences in attention regulation and body awareness rankings. Conclusion In patients with Crohn’s disease, anti-TNFα administration reduces visceral sensitivity and improves implicit cognitive-affective biases linked to alterations in limbic (amygdala) function.
Collapse
Affiliation(s)
- Marcus A. Gray
- Department of Gastroenterology & Hepatology, Princess Alexandra Hospital Brisbane, Queensland, Australia
- Translational Research Institute, Brisbane, Queensland, Australia
- Faculty of Health and Behavioral Science, University of Queensland, St. Lucia, Brisbane, Queensland, Australia
- * E-mail:
| | - Che-yung Chao
- Department of Gastroenterology & Hepatology, Princess Alexandra Hospital Brisbane, Queensland, Australia
| | - Heidi M. Staudacher
- Department of Gastroenterology & Hepatology, Princess Alexandra Hospital Brisbane, Queensland, Australia
- Translational Research Institute, Brisbane, Queensland, Australia
| | - Natasha A. Kolosky
- Department of Gastroenterology & Hepatology, Princess Alexandra Hospital Brisbane, Queensland, Australia
- Translational Research Institute, Brisbane, Queensland, Australia
- Faculty of Medicine, University of Queensland, St. Lucia, Brisbane, Queensland, Australia
- 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
| | - Gerald Holtmann
- Department of Gastroenterology & Hepatology, Princess Alexandra Hospital Brisbane, Queensland, Australia
- Translational Research Institute, Brisbane, Queensland, Australia
- Faculty of Health and Behavioral Science, University of Queensland, St. Lucia, Brisbane, Queensland, Australia
| |
Collapse
|
|
17
|
Talley NJ. Functional Dyspepsia: Advances in Diagnosis and Therapy. Gut Liver 2018; 11:349-357. [PMID: 28452210 PMCID: PMC5417776 DOI: 10.5009/gnl16055] [Citation(s) in RCA: 72] [Impact Index Per Article: 10.3] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/28/2016] [Accepted: 05/19/2016] [Indexed: 12/13/2022] Open
Abstract
Functional dyspepsia (FD) is a common but under-recognized syndrome comprising bothersome recurrent postprandial fullness, early satiety, or epigastric pain/burning. Epidemiologically, there are two clinically distinct FD syndromes (although these often overlap clinically): postprandial distress syndrome (PDS; comprising early satiety or meal-related fullness) and epigastric pain syndrome. Symptoms of gastroesophageal reflux disease overlap with FD more than expected by chance; a subset has pathological acid reflux. The pre-test probability of FD in a patient who presents with classical FD symptoms and no alarm features is high, approximately 0.7. Coexistent heartburn should not lead to the exclusion of FD as a diagnosis. One of the most exciting observations in FD has been the consistent finding of increased duodenal eosinophilia, notably in PDS. Small bowel homing T cells, signaling intestinal inflammation, and increased cytokines have been detected in the circulation, and elevated tumor necrosis factor-α levels have been significantly correlated with increased anxiety. Postinfectious gastroenteritis is a risk factor for FD. Therapeutic options remain limited and provide only symptomatic benefit in most cases. Only one therapy is known to change the natural history of FD–Helicobacter pylori eradication. Treatment of duodenal eosinophilia is under investigation.
Collapse
Affiliation(s)
- Nicholas J Talley
- Faculty of Health and Medicine, University of Newcastle and Hunter Medical Research Institute, Newcastle, NSW, Australia
| |
Collapse
|
|
18
|
Nitazoxanide and Doxycycline Sensitivity Among Metronidazole Resistant Helicobacter pylori Isolates from Patients with Gastritis. ARCHIVES OF CLINICAL INFECTIOUS DISEASES 2018. [DOI: 10.5812/archcid.66693] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
|
|
19
|
Fan K, Talley NJ. Functional dyspepsia and duodenal eosinophilia: A new model. J Dig Dis 2017; 18:667-677. [PMID: 29083538 DOI: 10.1111/1751-2980.12556] [Citation(s) in RCA: 18] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/29/2017] [Revised: 10/20/2017] [Accepted: 10/26/2017] [Indexed: 12/11/2022]
Abstract
Functional dyspepsia (FD) is a highly prevalent disorder that affects more than 10% of the population. In the past decade, the theoretical underpinning of the concept of FD has begun to change, in light of new data on the underlying pathophysiological mechanisms of this disorder, with a focus on the duodenum. The Rome IV criteria, published in 2016, note that gastroesophageal reflux disease and irritable bowel syndrome overlap with FD more than expected by chance, suggesting that they may be part of the same disease spectrum. Infection by Helicobacter pylori (H. pylori) may explain a minority of cases of FD and in the Rome IV criteria H. pylori-associated dyspepsia (defined as symptom relief after eradication therapy) is considered a separate entity. Duodenal inflammation characterized by increased eosinophils and in some cases mast cells, may impair the intestinal barrier. Post-infectious gastroenteritis is now an established risk factor for FD. Other risk factors may include atopy, owning herbivore pets and exposure to antibiotics, together with gastroduodenal microbiome disturbances. Small bowel homing T cells and increased cytokines in the circulation occur in FD, correlating with slow gastric emptying, and a possible association with autoimmune rheumatological disease supports background immune system activation. A genetic predisposition is possible. FD has been linked to psychological disorders, but in some cases psychological distress may be driven by gut mechanisms. Therapeutic options are limited and, aside from responders to H. pylori eradication, provide only modest and temporary relief. Advances in understanding FD may alter clinical practice, and the treatment of duodenal inflammation or microbiome alterations may lead to a cure for a subset of these patients in the future.
Collapse
Affiliation(s)
- Kening Fan
- School of Medicine and Public Health, University of Newcastle and Hunter Medical Research Institute, Newcastle, New South Wales, Australia
| | - Nicholas J Talley
- School of Medicine and Public Health, University of Newcastle and Hunter Medical Research Institute, Newcastle, New South Wales, Australia
| |
Collapse
|
|
20
|
Choi YJ, Kim N, Yoon H, Shin CM, Park YS, Kim JW, Kim YS, Lee DH, Jung HC. Overlap between irritable bowel syndrome and functional dyspepsia including subtype analyses. J Gastroenterol Hepatol 2017; 32:1553-1561. [PMID: 28160607 DOI: 10.1111/jgh.13756] [Citation(s) in RCA: 37] [Impact Index Per Article: 4.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/02/2016] [Revised: 12/16/2016] [Accepted: 01/23/2017] [Indexed: 12/18/2022]
Abstract
BACKGROUND AND AIM Coexistent gastrointestinal symptom profiles and prevalence or associated factors for the overlap between each functional dyspepsia (FD) and irritable bowel syndrome (IBS) group remain unclear. Thus, the aim of the present study was to evaluate the clinicodemographic features of FD, IBS, and IBS-FD overlap and assess the risk factors thereof, including subtype and genetic polymorphisms for IBS-FD. METHODS Consecutive patients were enrolled from the outpatient Gastroenterology clinics of Bundang Seoul National University Hospitals in Korea. All gastrointestinal symptoms occurring at least once per week in the previous 3 months were recorded. Diagnostic criteria of functional gastrointestinal disorders were based on the Rome III criteria. Risk factors including genetic polymorphisms of 5-HTTLPR and ADRA2A 1291 G alleles and CCK-1R intron 779T>C were assessed using a multivariate logistic regression model. RESULTS A total of 632 subjects (278 control subjects, 308 FD, 156 IBS, and 110 who met the criteria for both FD and IBS) were included in this study. Patients with IBS-FD overlap had more severe symptoms (such as bloating, nausea, vomiting, hard or lumpy stools, defecation straining, and a feeling of incomplete bowel movement) and higher depression scores compared with non-overlap patients. Single/divorced or widowed marital status, nausea, bloating, and a feeling of incomplete emptying after bowel movements were independent risk factors for IBS-FD overlap among IBS patients. In contrast, young age, depression, bloating, and postprandial distress syndrome were positively associated with IBS-FD overlap among FD patients. 5-HTTLPR L/L was a risk factor for the co-occurrence of IBS-C among FD patients (OR: 12.47; 95% CI: 2.00-77.75; P = 0.007). CONCLUSIONS Bloating was a risk factor for IBS-FD overlap. Patients with postprandial distress syndrome have a higher risk of coexisting IBS, particularly constipation-dominant IBS.
Collapse
Affiliation(s)
- Yoon Jin Choi
- Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, Gyeonggi-do, South Korea
| | - Nayoung Kim
- Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, Gyeonggi-do, South Korea.,Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul, South Korea
| | - Hyuk Yoon
- Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, Gyeonggi-do, South Korea
| | - Cheol Min Shin
- Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, Gyeonggi-do, South Korea
| | - Young Soo Park
- Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, Gyeonggi-do, South Korea.,Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul, South Korea
| | - Jin-Wook Kim
- Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, Gyeonggi-do, South Korea.,Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul, South Korea
| | - Yong Sung Kim
- Department of Gastroenterology, Wonkwang Digestive Disease Research Institute, Wonkwang University Sanbon Hospital, Gunpo, South Korea
| | - Dong Ho Lee
- Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, Gyeonggi-do, South Korea.,Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul, South Korea
| | - Hyun Chae Jung
- Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul, South Korea
| |
Collapse
|
|
21
|
Yamawaki H, Futagami S, Wakabayashi M, Sakasegawa N, Agawa S, Higuchi K, Kodaka Y, Iwakiri K. Management of functional dyspepsia: state of the art and emerging therapies. Ther Adv Chronic Dis 2017; 9:23-32. [PMID: 29344328 DOI: 10.1177/2040622317725479] [Citation(s) in RCA: 33] [Impact Index Per Article: 4.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/16/2017] [Accepted: 05/31/2017] [Indexed: 12/14/2022] Open
Abstract
Patients with functional dyspepsia, defined in the 2016 Rome IV criteria as bothersome clinical dyspepsia symptoms, experience markedly reduced quality of life. Several etiologies have been associated with the disorder. In the Rome IV criteria, the brain-gut axis was acknowledged as an important factor in the etiology of functional gastrointestinal (GI) disorders. The distinct subgroups of functional dyspepsia, epigastric pain syndrome (EPS) and postprandial distress syndrome (PDS), are treated differently: acid secretion inhibitors are recommended with patients with EPS, whereas prokinetic drugs as mosapride and acotiamide are recommended for patients with PDS. A previous study has reported that proton pump inhibitors (PPIs) and H2-blockers were equally effective in functional dyspepsia. A new drug, acotiamide, a muscarinic antagonist and cholinesterase inhibitor, has been shown to improve gastric motility in rodents and dogs, and to reduce PDS symptoms in patients in double-blind multicenter studies. The pharmacological mechanisms of acotiamide remain unknown; whether acotiamide alters gastric emptying and gastric accommodation in patients with functional dyspepsia remains an open question. Other emerging treatment options include Rikkunshito, a herbal medicine that improves gastric emptying through 5-hydroxytryptamine (5-HT)2B-mediated pharmacological action, and tricyclic antidepressants (TCAs). Different drugs are needed to accommodate the clinical symptoms and etiology in individual patients.
Collapse
Affiliation(s)
- Hiroshi Yamawaki
- Department of Internal Medicine, Division of Gastroenterology, Nihon Ika Daigaku, Bunkyo-ku, Tokyo, Japan
| | - Seiji Futagami
- Department of Internal Medicine, Division of Gastroenterology, Nippon Medical School, 1-1-5 Sendagi, Bunkyo-ku, Tokyo, 113-8602, Japan
| | - Mako Wakabayashi
- Department of Internal Medicine, Division of Gastroenterology, Nihon Ika Daigaku, Bunkyo-ku, Tokyo, Japan
| | - Noriko Sakasegawa
- Department of Internal Medicine, Division of Gastroenterology, Nihon Ika Daigaku, Bunkyo-ku, Tokyo, Japan
| | - Shuhei Agawa
- Department of Internal Medicine, Division of Gastroenterology, Nihon Ika Daigaku, Bunkyo-ku, Tokyo, Japan
| | - Kazutoshi Higuchi
- Department of Internal Medicine, Division of Gastroenterology, Nihon Ika Daigaku, Bunkyo-ku, Tokyo, Japan
| | - Yasuhiro Kodaka
- Department of Internal Medicine, Division of Gastroenterology, Nihon Ika Daigaku, Bunkyo-ku, Tokyo, Japan
| | - Katsuhiko Iwakiri
- Department of Internal Medicine, Division of Gastroenterology, Nihon Ika Daigaku, Bunkyo-ku, Tokyo, Japan
| |
Collapse
|
|
22
|
Talley NJ. Editorial: Moving Away From Focussing on Gastric Pathophysiology in Functional Dyspepsia: New Insights and Therapeutic Implications. Am J Gastroenterol 2017; 112:141-144. [PMID: 28050031 DOI: 10.1038/ajg.2016.519] [Citation(s) in RCA: 18] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/21/2016] [Accepted: 10/10/2016] [Indexed: 12/11/2022]
Abstract
Functional dyspepsia (FD) is a prevalent syndrome that affects up to one in six Americans, although misdiagnosis as gastroesophageal reflux disease may be common. Early satiety, postprandial fullness, and epigastric pain or burning are the cardinal symptoms. Traditionally, FD has been blamed on gastric dysfunction and much research effort has focussed on unlocking the gastric pathophysiology. New research suggests gastric dysfunction has only a minor role in the pathogenesis in many cases, and the focus has begun to shift to evaluation of duodenal feedback and subtle inflammation including duodenal eosinophilia. These new data and the management implications are reviewed.
Collapse
Affiliation(s)
- Nicholas J Talley
- The University of Newcastle, University Drive, Callaghan, New South Wales, Australia
| |
Collapse
|
|
23
|
Baradaran Moghaddam A, Mansouri S, Alebouyeh M, Farzi N, Bayati S, Amirmozafari N. Sensitivity to nitazoxanide among metronidazole resistant Helicobacter pylori strains in patients with gastritis. Med J Islam Repub Iran 2016; 30:405. [PMID: 27683646 PMCID: PMC5038992] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/24/2016] [Accepted: 07/04/2016] [Indexed: 11/25/2022] Open
Abstract
BACKGROUND In this study, the efficacy of nitazoxanide in the treatment of Helicobacter pylori isolates, which were resistant to metronidazole, was examined. METHODS One hundred twenty two patients who underwent endoscopy examinations at Kasra and Laleh hospitals in Tehran from November 2014 to July 2015 were enrolled. Helicobacter pylori strains were isolated from the patients' endoscopy biopsies by bacteriological culture. Those bacterial isolates resistant to metronidazole were examined for susceptibility to nitazoxanide. Serial agar dilution method was utilized to determine the minimum inhibitory concentrations for the antibiotics. RESULTS From 122 gastric biopsy specimens, 55 H. pylori isolates were recovered (45%); of which, 40 (72.7%) were resistant to metronidazole. Comparing the MIC values of nitazoxanide with metronidazole revealed significant differences (p<0.05). The MIC50 and MIC90 values for nitazoxanide and metronidazole were 8 and ≥8μg/ml, and 32 and 64μg/ml, respectively. CONCLUSION The high levels of metronidazole resistance suggest that this medication may not be beneficial for first-line therapy in Iran. However, considering the relative effectiveness of nitazoxanide, it may be considered a suitable alternative for patients in Iran.
Collapse
Affiliation(s)
- Ali Baradaran Moghaddam
- 1 MSc, Department of Microbiology, School of Medicine, Kerman University of Medical Sciences, Kerman, Iran.
| | - Shahla Mansouri
- 2 Professor of Microbiology, Department of Microbiology, School of Medicine, Kerman University of Medical Sciences, Kerman, Iran.
| | - Masoud Alebouyeh
- 3 Assistant Professor, Foodborne and Waterborne Diseases Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
| | - Nastaran Farzi
- 4 MSc, Research Institute for Gastroenterology and Liver Disease, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
| | - Saeed Bayati
- 5 MSc, Department of Microbiology, School of Medicine, Iran University of Medical Sciences, Tehran, Iran.
| | - Nour Amirmozafari
- 5 Professor, Department of Microbiology, School of Medicine, Iran University of Medical Sciences, Tehran, Iran. ,(Corresponding author) Professor, Department of Microbiology, School of Medicine, Iran University of Medical Sciences, Tehran, Iran.
| |
Collapse
|
|
24
|
Eslick GD, Howell SC, Talley NJ. Dysmotility Symptoms Are Independently Associated With Weight Change: A Population-based Study of Australian Adults. J Neurogastroenterol Motil 2015; 21:603-11. [PMID: 26424045 PMCID: PMC4622143 DOI: 10.5056/jnm14124] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/16/2014] [Revised: 04/16/2015] [Accepted: 07/16/2015] [Indexed: 01/12/2023] Open
Abstract
Background/Aims Weight loss is a recognized alarm symptom for organic gastrointestinal (GI) disease, yet the association between weight change (loss or gain) and specific GI symptoms remains poorly described. We assess the associations between GI symptoms and weight change in a population-based sample of Australian adults. Methods The prevalence of 26 GI symptoms was determined by a postal survey to 5000 residents in western Sydney, Australia (60% response rate). These were classified a priori into 5 symptom groups–abdominal pain, esophageal symptoms, dysmotility symptoms, diarrhea and constipation. Weight change was measured by two items which assessed weight loss and weight gain. Clinically relevant weight change was defined as a loss or gain of 3 or more kilograms in the past 3 months. Results Prevalence estimates for clinically relevant weight loss and gain in the past 3 months were 10.3% and 8.1%, respectively. When the 5 symptom groups were evaluated simultaneously, the dysmotility symptoms of fullness after meals emerged as a predictor of both weight loss (OR, 1.57; 95% CI, 1.32–1.88; P < 0.001) and weight gain (OR, 0.85; 95% CI, 0.72–0.99; P = 0.040), which also included bloating (OR, 1.64; 95% CI 1.46–1.84; P < 0.001). The associations remained significant following adjustment for socio-economic status, body mass index, and eating behaviors. Conclusions Specific dysmotility symptoms are independently predictive of both weight loss and weight gain. Different pathogenic mechanisms may be involved.
Collapse
Affiliation(s)
- Guy D Eslick
- School of Public Health, The University of Sydney, Sydney, New South Wales, Australia.,Department of Medicine, The University of Sydney, Nepean Hospital, Penrith, New South Wales, Australia
| | - Stuart C Howell
- School of Public Health, The University of Sydney, Sydney, New South Wales, Australia.,Department of Medicine, The University of Sydney, Nepean Hospital, Penrith, New South Wales, Australia
| | - Nicholas J Talley
- Department of Medicine, The University of Sydney, Nepean Hospital, Penrith, New South Wales, Australia.,Faculty of Health, The University of Newcastle, Callaghan, New South Wales, Australia
| |
Collapse
|
|
25
|
Ling W, Li Y, Jiang W, Sui Y, Zhao HL. Common Mechanism of Pathogenesis in Gastrointestinal Diseases Implied by Consistent Efficacy of Single Chinese Medicine Formula: A PRISMA-Compliant Systematic Review and Meta-Analysis. Medicine (Baltimore) 2015; 94:e1111. [PMID: 26166106 PMCID: PMC4504579 DOI: 10.1097/md.0000000000001111] [Citation(s) in RCA: 23] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/12/2022] Open
Abstract
Gastrointestinal (GI) disorders often manifest similar symptoms with overlapping clinical diagnosis and unmet medical needs. Traditional Chinese medicine (TCM) has history-proven benefits for GI diseases; albeit language barrier prevents Western readers from accessing the original reports in Chinese. The TCM formula Si-Ni-San (SNS) consists of 4 herbs targeting on homeostatic disturbances characterized by "reflux" and "irritable" problems. Here we used SNS as a therapeutic tool to explore the common mechanisms of pathogenesis in non-neoplastic GI diseases.Data sources from PUBMED, Chinese National Knowledge Infrastructure, and Wanfang databases were searched for clinical trials. Comparisons were SNS as intervention and Western conventional medicine as control, which treat patients with upper GI disorders (gastroesophageal reflux disease, peptic ulcer, chronic gastritis, duodenogastric reflux), lower GI diseases (irritable bowel syndrome, ulcerative colitis), and functional dyspepsia. Participants and studies in accordance with the Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) Statement were eligible. We used the Jadad scale to assess methodological qualities, the fixed or random-effect model to evaluate therapeutic efficacy, and the funnel plots to explore publication bias. Outcome was clinical efficacy defined by symptom relief with normal GI endoscopy, radiology, and pathology.We included 83 studies involving 7762 participants: 1708 versus 1397 of the upper GI disorders in 34 studies, 901 versus 768 of the lower GI diseases in 19 studies, 1641 versus 1348 of functional dyspepsia in 30 studies, and 328 versus 287 of relapse rate in 8 studies. Six studies had a Jadad score >2 points and the rest were <2 points. Pooled data showed significant efficacy of SNS for the upper GI disorders (odds ratio [OR] = 3.9, 95% confidence interval [CI] = 3.09-4.92), lower GI diseases (OR = 4.91, 95% CI = 3.71-6.51), and functional dyspepsia (N = 2989; OR = 3.94, 95% CI = 3.17-4.90). The relapse rate was 12.9% for SNS, significantly <46.5% for conventional therapies (OR = 0.16, 95% CI = 0.11-0.25).The consistent efficacy of the single TCM formula implicates common mechanisms of pathogenesis in GI disorders.
Collapse
Affiliation(s)
- Wei Ling
- From the Center for Systems Medicine, Guilin Medical University, Guilin (WL, YL, WJ, YS, H-LZ); Department of Gastroenterology, The Affiliated Hospital of Inner Mongolia Medical University, Hohhot (YL); Department of Traditional Chinese Medicine, The Affiliated Hospital of Guilin Medical University, Guilin (WJ); and Guangdong Hospital of Traditional Chinese Medicine, Guangzhou University of Chinese Medicine, Guangzhou, China (YS)
| | | | | | | | | |
Collapse
|
|
26
|
Giacosa A, Guido D, Grassi M, Riva A, Morazzoni P, Bombardelli E, Perna S, Faliva MA, Rondanelli M. The Effect of Ginger (Zingiber officinalis) and Artichoke (Cynara cardunculus) Extract Supplementation on Functional Dyspepsia: A Randomised, Double-Blind, and Placebo-Controlled Clinical Trial. EVIDENCE-BASED COMPLEMENTARY AND ALTERNATIVE MEDICINE : ECAM 2015; 2015:915087. [PMID: 25954317 PMCID: PMC4411465 DOI: 10.1155/2015/915087] [Citation(s) in RCA: 31] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 12/09/2014] [Accepted: 03/23/2015] [Indexed: 02/06/2023]
Abstract
Objective. Functional dyspepsia (FD) is a frequent clinical finding in western world. The aim of this study is to compare the efficacy of a ginger and artichoke supplementation versus placebo in the treatment of FD. Methods. A prospective multicentre, double blind, randomized, placebo controlled, parallel-group comparison of the supplement and placebo over a period of 4 weeks was performed. Two capsules/day were supplied (before lunch and dinner) to 126 FD patients (supplementation/placebo: 65/61). Results. After 14 days of treatment, only supplementation group (SG) showed a significant amelioration (SG: α S = +1.195 MCA score units (u), P = 0.017; placebo: α P = +0.347 u, P = 0.513). The intercept (α) resulted to be significantly higher in SG than in placebo (α S - α P = +0.848 u, P < 0.001). At the end of the study, the advantage of SG versus placebo persists without variation (β S - β P = +0.077 u, P = 0.542). In SG, a significant advantage is observed for nausea (β S - β P = -0.398 u, P < 0.001), epigastric fullness (β S - β P = -0.241, P < 0.001), epigastric pain (β S - β P = -0.173 u, P = 0.002), and bloating (β S - β P = -0.167 u, P = 0.017). Conclusions. The association between ginger and artichoke leaf extracts appears safe and efficacious in the treatment of FD and could represent a promising treatment for this disease.
Collapse
Affiliation(s)
- Attilio Giacosa
- Department of Gastroenterology, Policlinico di Monza, 20900 Milan, Italy
| | - Davide Guido
- Section of Biostatistics, Neurophysiology and Psychiatry, Department of Brain and Behavioral Sciences, University of Pavia, 27100 Pavia, Italy
| | - Mario Grassi
- Section of Biostatistics, Neurophysiology and Psychiatry, Department of Brain and Behavioral Sciences, University of Pavia, 27100 Pavia, Italy
| | - Antonella Riva
- Research and Development Unit, Indena, 20139 Milan, Italy
| | | | | | - Simone Perna
- Section of Human Nutrition, Department of Public Health, Experimental and Forensic Medicine, University of Pavia, Azienda di Servizi alla Persona, 27100 Pavia, Italy
| | - Milena A. Faliva
- Section of Human Nutrition, Department of Public Health, Experimental and Forensic Medicine, University of Pavia, Azienda di Servizi alla Persona, 27100 Pavia, Italy
| | - Mariangela Rondanelli
- Section of Human Nutrition, Department of Public Health, Experimental and Forensic Medicine, University of Pavia, Azienda di Servizi alla Persona, 27100 Pavia, Italy
| |
Collapse
|
|
27
|
Gururatsakul M, Holloway RH, Bellon M, Bartholomeusz D, Talley NJ, Holtmann GJ. Complicated and uncomplicated peptic ulcer disease: altered symptom response to a nutrient challenge linked to gastric motor dysfunction. Digestion 2015; 89:239-46. [PMID: 24903331 DOI: 10.1159/000360635] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/17/2013] [Accepted: 02/16/2014] [Indexed: 02/04/2023]
Abstract
BACKGROUND Bleeding peptic ulcer (BPU) frequently occurs in the absence of preceding dyspeptic symptoms. We have observed that patients with BPU had a diminished symptom response to nutrient challenge test compared to uncomplicated peptic ulcer disease (uPUD). We postulated that more symptoms are manifest in patients with uPUD than BPU because there are greater derangements in gastric motor function. AIM To assess gastric emptying in patients with BPU, uPUD and healthy controls (HC). METHODS We studied 17 patients with BPU, 10 with uPUD, and 15 HC. After an 8-hour fast, subjects ingested 200 ml of an enteral feeding solution, containing 5 MBq (99m)Tc-rhenium sulphide colloid, every 5 min up to a cumulative volume of 800 ml. Gastric emptying was measured by scintigraphy for the total, proximal and distal stomach. RESULTS Patients with uPUD had significantly higher gastric retention in the proximal and total stomach at 100 min than HC and BPU, while BPU had similar percent retention to HC. Patients with uPUD had significantly higher cumulative symptom response to the nutrient challenge than did HC and BPU, while BPU had similar symptom responses to HC. CONCLUSIONS Patients with uPUD have significantly delayed gastric emptying compared to HC and BPU. Data suggest that in addition to alterations of visceral sensory function, altered gastric motor function occurs during a nutrient challenge in uPUD but not BPU. Gastric motor function may contribute to the manifestation of dyspeptic symptoms in PUD.
Collapse
Affiliation(s)
- Montri Gururatsakul
- Department of Gastroenterology and Hepatology, Royal Adelaide Hospital, Adelaide, S.A., Australia
| | | | | | | | | | | |
Collapse
|
|
28
|
Tseng PH, Wu YW, Lee YC, Cheng MF, Tzen KY, Wang HP, Lin JT, Hsieh ST, Yang WS, Wu MS. Normal values and symptom correlation of a simplified oatmeal-based gastric emptying study in the Chinese population. J Gastroenterol Hepatol 2014; 29:1873-82. [PMID: 24909819 DOI: 10.1111/jgh.12640] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 04/10/2014] [Indexed: 12/09/2022]
Abstract
BACKGROUND AND AIM Instant oatmeal has been proposed as a good alternative to the standardized low-fat egg white test meal for gastric emptying studies. We aim to establish normal values of oatmeal-based gastric emptying scintigraphy and test its correlation with gastroparesis symptoms in the Chinese population. METHODS This study prospectively enrolled 60 healthy volunteers, 30 functional dyspepsia and 30 diabetes patients with gastroparesis symptoms. All participants were evaluated using the Gastroparesis Cardinal Symptom Index. Each participant ingested instant oatmeal mixed with 1 mCi of (99m) Tc diethylenetriaminepentacetic acid, and serial imaging was immediately acquired for 3 h in the supine position using a left anterior oblique projection. Time-activity curves were generated and quantitative parameters were determined. Normal values were established from healthy volunteers and further applied in the symptomatic patients. RESULTS All participants finished the test meal and tolerated the procedure well. All gastric emptying parameters were not significantly affected by age or gender. Values above the 95th percentile of T1/2 , gastric retention at 1, 2, and 3 h (85 min, 65%, 28%, and 8%, respectively) were indicative of delayed gastric emptying. Values below the 5th percentile of gastric retention at 0.5 and 1 h (40% and 15%, respectively) were indicative of rapid gastric emptying. The lower gastric retention limit at 0.5 and 1 h were 40% and 15%, respectively. Four (13.3%) diabetes and four (13.3%) functional dyspepsia patients had delayed emptying while three diabetes patients (10%) had rapid emptying. Gastric emptying parameters correlated best with vomiting (r = 0.621) and nausea (r = 0.566) in diabetes patients. CONCLUSIONS We established normal values of oatmeal-based gastric emptying scintigraphy and observed good correlation with cardinal gastroparesis symptoms in the Chinese population.
Collapse
Affiliation(s)
- Ping-Huei Tseng
- Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan; Graduate Institute of Clinical Medicine, College of Medicine, National Taiwan University, Taipei, Taiwan
| | | | | | | | | | | | | | | | | | | |
Collapse
|
|
29
|
Pleyer C, Bittner H, Locke GR, Choung RS, Zinsmeister AR, Schleck CD, Herrick LM, Talley NJ. Overdiagnosis of gastro-esophageal reflux disease and underdiagnosis of functional dyspepsia in a USA community. Neurogastroenterol Motil 2014; 26:1163-71. [PMID: 24916517 DOI: 10.1111/nmo.12377] [Citation(s) in RCA: 44] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/20/2014] [Accepted: 05/08/2014] [Indexed: 12/15/2022]
Abstract
BACKGROUND There is symptom overlap between gastro-esophageal reflux disease (GERD) and functional dyspepsia (FD). We aimed to test the hypothesis that FD cases are now more likely mislabeled as GERD. METHODS In subjects from Olmsted County, MN seen at Mayo Clinic: (i) Investigation of GERD and FD diagnosis rates between 1985 and 2009. (ii) Assessment of survey-based upper gastrointestinal symptoms between 1988 and 2009. (iii) Analysis of patients reporting GERD and/or FD symptoms and subsequently receiving a consistent diagnosis of GERD and/or FD during a medical encounter. (iv) Assess the association between PPI use and GERD and/or FD symptoms and between actual diagnoses received. KEY RESULTS (i) Yearly GERD diagnosis rates rose between 1985 and 2009 (325-1866 per 100 000). FD diagnosis rates rose from 45 in 1985, to 964 in 1999 but decreased to 452 per 100 000 in 2009. (ii) Reported GERD symptoms did not significantly change between three survey waves in the years 1988-2009 (p = 0.052), whereas FD symptoms slightly increased (p = 0.01). (iii) 62.9% of subjects reporting GERD symptoms received a GERD diagnosis, however only 12.5% of subjects reporting FD symptoms received a FD diagnosis. (iv) PPI use was associated with documented GERD diagnosis (p < 0.001), however there was no significant association between GERD symptoms and PPI use (p = 0.078). CONCLUSIONS & INFERENCES We have found evidence supporting a systematic bias away from diagnosing FD, favoring a GERD diagnosis.
Collapse
Affiliation(s)
- C Pleyer
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN, USA
| | | | | | | | | | | | | | | |
Collapse
|
|
30
|
Prevalence of irritable bowel syndrome and functional dyspepsia, overlapping symptoms, and associated factors in a general population of Bangladesh. Indian J Gastroenterol 2014; 33:265-73. [PMID: 24664445 DOI: 10.1007/s12664-014-0447-1] [Citation(s) in RCA: 30] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/31/2013] [Accepted: 02/12/2014] [Indexed: 02/04/2023]
Abstract
BACKGROUND This community-based survey aimed to find out the prevalence of irritable bowel syndrome (IBS), functional dyspepsia (FD), overlapping symptoms, and associated factors for overlap. METHOD By cluster sampling method, 3,000 (1,523 male) randomly selected adult subjects in the Sylhet district of Bangladesh were interviewed by a questionnaire based on ROME III criteria. Multivariate logistic regression analyses were done to find out the factors for overlap with significance level set at ≤0.05. RESULTS The mean age of the study population was 33.9 ± 16.4 years. Prevalence of IBS and FD and IBS-FD were 12.9 % (n = 387), 8.3 % (n = 249), and 3.5 % (n = 105), respectively. Approximately 27.1 % of IBS patients and 42.1 % of FD patients had overlapping IBS-FD. The odds ratio for IBS-FD overlap was 6.3 (95 % CI, 4.8-8.4). Mean age (p = 0.011) and epigastric pain (p = 0.002) were more in overlap patients than FD alone, whereas epigastric pain syndrome subtype (p < 0.009) was more prevalent in lone FD subjects. In the multivariate logistic analysis, early satiety (OR, 3.0; 95 % CI, 1.2-7.5; p = 0.018) and epigastric pain (OR, 14.5; 95 % CI, 5.0-42.1; p = 0.000) in FD patients appeared as independent risk factors for overlap. Bloating (p = 0.026), <3 stools per week (p = 0.050), abdominal pain reduced by defecation (p = 0.002), abdominal pain severity score (p = 0.004), and overall symptom frequency score (p = 0.000) were more in overlap patients than IBS-alone patients. In IBS patients, bloating (OR, 3.6; CI, 2.0-6.5; p = 0.000) was found as potential symptom associated with IBS-FD overlap. CONCLUSION FD was a less prevalent disorder than IBS in our community, and significant overlap existed between the two disorders. Early satiety, epigastric pain, and bloating were important factors associated with overlap.
Collapse
|
|
31
|
Devanarayana NM, Rajindrajith S, Bandara C, Shashiprabha G, Benninga MA. Ultrasonographic assessment of liquid gastric emptying and antral motility according to the subtypes of irritable bowel syndrome in children. J Pediatr Gastroenterol Nutr 2013; 56:443-448. [PMID: 23201712 DOI: 10.1097/mpg.0b013e31827f7a3d] [Citation(s) in RCA: 29] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
OBJECTIVES Gastric motor abnormalities have been reported in adults with irritable bowel syndrome (IBS), commonly in constipation-predominant IBS (IBS-C); however, such studies are uncommon in children. Furthermore, differences of gastric motility have not been studied in children with different IBS subtypes. METHODS Seventy-six children (33 [43%] boys, age 4-14 years, mean 7.9 years, SD 3.0 years) fulfilling Rome III criteria for IBS and 20 healthy controls (8 [40%] boys, age 4-14 years, mean 8.4 years, SD 3.0 years) were recruited (diarrhea-predominant IBS=21, IBS-C=31, mixed IBS=19, and unsubtyped IBS=5). Liquid gastric emptying rate (GER) and antral motility were assessed using an ultrasound method. RESULTS Average GER (43.8% vs 66.2% in controls), amplitude of antral contractions (56.4% vs 89%), and antral motility index (5.1 vs 8.3) were lower and fasting antral area (1.6 vs 0.6) was higher in patients with IBS (P<0.0001). Frequency of antral contractions F (8.9 vs 9.3) did not show a significant difference. Patients exposed to stressful events had a significantly lower GER, compared to those not exposed to such events (P=0.03). Gastric motility parameters had no correlation with severity of symptoms. GER (42.6%, 46.3%, 39.6%), fasting antral area (1.4 cm², 1.8 cm², 1.8 cm²), amplitude of antral contractions (53%, 58.9%, 51.8%), frequency of antral contractions (8.7, 8.9, 9.2), and antral motility index (4.7, 5.3, 4.8) were not different among diarrhea-predominant IBS, IBS-C, and mixed IBS (P>0.05). CONCLUSIONS GER and antral motility parameters were significantly impaired in children with IBS compared with controls. GER and antral motility parameters were not different between IBS subtypes.
Collapse
Affiliation(s)
- Niranga M Devanarayana
- Department of Physiology, Faculty of Medicine, University of Kelaniya, Thalagolla Road, Ragama, Sri Lanka.
| | | | | | | | | |
Collapse
|
|
32
|
Gururatsakul M, Holloway RH, Talley NJ, Holtmann GJ. Association between clinical manifestations of complicated and uncomplicated peptic ulcer and visceral sensory dysfunction. J Gastroenterol Hepatol 2010; 25:1162-9. [PMID: 20594234 DOI: 10.1111/j.1440-1746.2010.06269.x] [Citation(s) in RCA: 11] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/07/2023]
Abstract
BACKGROUND AND AIMS Peptic ulcer disease (PUD) usually manifests as either dyspepsia or less commonly with complications such as bleeding. Patients with bleeding ulcers are often asymptomatic until the bleeding occurs. A lack of dyspeptic symptoms might be explained by impaired visceral sensory function. The aim of this study was to assess symptom profiles and compare visceral sensory thresholds in patients with bleeding peptic ulcer (BPU) and uncomplicated PUD. METHODS A total of 30 patients with BPU, 25 with uncomplicated PUD and 32 healthy controls (HC) without dyspeptic symptoms were recruited. In ulcer patients after at least 8 weeks of ulcer treatment and an 8-hr fast, visceral sensitivity was tested using a standardized nutrient challenge with an enteral feeding solution. Five key symptoms (fullness, abdominal pain, retrosternal/abdominal burning, nausea, and regurgitation) were assessed using visual analog scales (0-100). RESULTS Twenty-five of the 30 (83%, 95% confidence interval 65-94%) patients with BPU had no dyspeptic symptoms compared with none of the 25 uncomplicated PUD patients. Patients with BPU and HC had significantly lower symptom responses (BPU 127.6 +/- 24.6, HC 89.8 +/- 13.9) to the nutrient challenge than uncomplicated PUD patients (338.4 +/- 56.2, P < 0.0001). Patients with dyspeptic symptoms (30/55) had significantly higher symptom responses (327.3 +/- 47.8) than the 25/55 patients without symptoms (98.9 +/- 23.4, P < 0.0001). CONCLUSION Most patients with BPU present without dyspeptic symptoms. Even after healing of the ulcer, patients with uncomplicated PUD have a significantly augmented symptom response to a standardized nutrient challenge compared to patients with complicated ulcers and HC. Differences in the processing of upper gastrointestinal visceral afferents may play a major role in the clinical presentation (complicated vs uncomplicated) of PUD.
Collapse
Affiliation(s)
- Montri Gururatsakul
- Department of Gastroenterology and Hepatology, Royal Adelaide Hospital, Adelaide, SA, Australia.
| | | | | | | |
Collapse
|
|
33
|
Abstract
Dyspepsia is a common term used for a heterogeneous group of abdominal symptoms. Functional dyspepsia (FD) is the focus of this review. The 2006 Rome III criteria defined FD and its subgroups, postprandial distress syndrome (PDS) and epigastric pain syndrome (EPS). FD is a very common condition with a high prevalence throughout the world, adversely affecting the quality of life of patients. The pathophysiology of FD has been under investigation during the past two decades. Multiple mechanisms such as abnormal gastric emptying, visceral hypersensitivity, impaired gastric accommodation, and central nervous system factors are likely involved. Several tests are available for the assessment of various physiologic functions possibly involved in the pathogenesis of FD, and some of these could be used in clinical practice, helping to understand the abnormalities underlining patients' complaints. Currently, the possibilities of pharmacological therapy for FD are still limited, however, experience of using prokinetics, tricyclic antidepressants, selective serotonin-reuptake inhibitors (SSRIs), proton-pump inhibitors (PPIs), and several alternative techniques has been accumulated. The different combinations of alterations in physiologic gastrointestinal and central nervous system functions result in the very heterogeneous nature of FD so combined approaches to these patients could be beneficial in challenging cases.
Collapse
|
|
34
|
Gururatsakul M, Holloway RH, Adam B, Liebregts T, Talley NJ, Holtmann GJ. The ageing gut: diminished symptom response to a standardized nutrient stimulus. Neurogastroenterol Motil 2010; 22:246-e77. [PMID: 19814772 DOI: 10.1111/j.1365-2982.2009.01413.x] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
Abstract
BACKGROUND The prevalence of dyspepsia and the severity of reflux symptoms decreases with advancing age. We postulate that advancing age influences sensory function and this will be associated with a diminished symptom response to a standardized meal stimulus.Our aim was to assess the influence of age on visceral sensory function. METHODS Baseline gastrointestinal symptoms and anxiety and depression were assessed in 53 healthy volunteers using validated questionnaires. After an 8-h fast, subjects received 200 mL of a standardized enteral feeding solution every 5 min up to a cumulative volume of 800 mL. After each 200 mL drink, five key symptoms were assessed (fullness, abdominal pain, retrosternal/abdominal burning, nausea and regurgitation) using a standardized instrument on visual analogue scales (0-100). The cumulative symptom score across all symptoms was calculated. KEY RESULTS Fullness was the most prominent symptom reported (79.8 +/- 9.5) followed by nausea (14.9 +/- 4.9) and pain (9.8 +/- 4.5); these three items accounted for more than 90% of the overall symptom load. The cumulative pain and nausea scores during a standardized nutrient challenge were significantly and inversely correlated with age (r = -0.43, P = 0.002 and r = -0.28, P = 0.045). Subjects >60 years of age reported significantly lower pain and nausea scores (0.9 +/- 0.9, 4.5 +/- 3.9) than did subjects <40 years (22 +/- 11.9, P = 0.002; 29.3 +/- 12, P = 0.043). CONCLUSIONS & INFERENCES Symptom responses to a standardized nutrient challenge, in particular pain and nausea, are inversely correlated with age.
Collapse
Affiliation(s)
- M Gururatsakul
- Department of Gastroenterology and Hepatology, Royal Adelaide Hospital; and University of Adelaide, Adelaide, SA, Australia.
| | | | | | | | | | | |
Collapse
|
|
35
|
Haag S, Senf W, Tagay S, Heuft G, Gerken G, Talley NJ, Holtmann G. Is there any association between disturbed gastrointestinal visceromotor and sensory function and impaired quality of life in functional dyspepsia? Neurogastroenterol Motil 2010; 22:262-e79. [PMID: 19814775 DOI: 10.1111/j.1365-2982.2009.01415.x] [Citation(s) in RCA: 38] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
Abstract
BACKGROUND Functional dyspepsia (FD) is now categorized into the epigastric pain syndrome (EPS) and the postprandial distress syndrome (PDS). However, the role of disturbed gastric emptying and sensory function for the reduction of health-related quality of life (HRQOL) has not yet been studied in EPS and PDS. METHODS A total of 300 refractory FD patients and 450 healthy blood donors (BD) were studied. BD were stratified in subjects with (BD+) and without (BD-) concomitant FD symptoms. Gastric motor and sensory function, generic and disease-specific HRQOL [physical (PCS) and mental component summary (MCS)] and affective disorders were assessed. Twenty randomly selected BD-, 50 BD+ (36 PDS, 72%), and 110 FD (95 PDS, 86.4%) patients had additional function testing. KEY RESULTS Health-related quality of life was significantly reduced in FD patients (PCS = 40.7 +/- 8.8, MCS = 39.7 +/- 11.3, both P < 0.0001) compared to BD+ (PCS = 52.0 +/- 7.6, MCS = 49.0 +/- 9.4) and BD- (PCS = 56.0 +/- 4.3, MCS = 52.8 +/- 7.2). GET (t((1/2)), min) was significantly (both P < 0.0001) longer in FD patients (143.0 +/- 7.3) compared to BD+ (101.1 +/- 6.3) and BD- (73.8 +/- 7.6). FD patients scored significantly higher for 'pain' (P < 0.0001) and 'nausea' (P = 0.023), there was no difference for 'fullness' compared to BD. Impairment of GET was not associated with HRQOL. In FD patients, an augmented symptom response to the test meal (fullness, nausea) was associated with MCS, there was no difference between FD patients with EPS or PDS. CONCLUSIONS & INFERENCES In EPS and PDS, delayed gastric empting and altered sensory function are disease markers but not directly linked to the severity of HRQOL impairment or clinical presentation of FD.
Collapse
Affiliation(s)
- S Haag
- Department of Gastroenterology and Hepatology, University of Essen, Essen, Germany
| | | | | | | | | | | | | |
Collapse
|
|
36
|
Dumping syndrome: establishing criteria for diagnosis and identifying new etiologies. Dig Dis Sci 2010; 55:117-23. [PMID: 19714467 DOI: 10.1007/s10620-009-0939-5] [Citation(s) in RCA: 45] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/24/2009] [Accepted: 08/03/2009] [Indexed: 12/15/2022]
Abstract
AIMS To investigate the current incidence and identify the current etiologies of rapid gastric emptying (dumping syndrome) in patients with a spectrum of gastrointestinal symptoms, including nausea, vomiting, abdominal pain, or diarrhea. METHODS The results for a 4-h radionuclide gastric emptying test (GET) using a standardized scintigraphic technique were reviewed in 545 patients to see which patients met criteria for rapid gastric emptying, defined as >50% emptying of isotope-labeled solid meal at 1 h. RESULTS Forty-eight of 545 (8.8%) patients (28 females, mean age 46 +/- 2 years, range 32-58 years) had rapid GET. Seventeen of 59 (35%) met Rome III diagnostic criteria for cyclic vomiting syndrome (CVS). Twelve of these 59 (25%) patients were regarded as non-ulcer dyspepsia and six (13%) had dyspepsia in the setting of diabetes mellitus. Five (10.5%) were post-fundoplication surgery, where an accidental vagotomy was confirmed by sham meal challenge; previous gastric bypass surgery for obesity had been performed in three (6%) patients. Five (10.5%) patients with unexplained abdominal pain and diarrhea had the working diagnosis of irritable bowel syndrome. CONCLUSIONS Rapid gastric emptying can be identified in a sizeable subset (9%) of patients with unexplained nausea, vomiting, abdominal pain, and diarrhea when criteria are applied to the standardized scintigraphic gastric emptying meal.
Collapse
|
|
37
|
Kamiya T, Adachi H, Hirako M, Shikano M, Matsuhisa E, Wada T, Ogasawara N, Nojiri S, Kataoka H, Sasaki M, Ohara H, Joh T. Impaired gastric motility and its relationship to reflux symptoms in patients with nonerosive gastroesophageal reflux disease. J Gastroenterol 2009; 44:183-9. [PMID: 19214661 DOI: 10.1007/s00535-008-2289-z] [Citation(s) in RCA: 36] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/06/2008] [Accepted: 08/22/2008] [Indexed: 02/04/2023]
Abstract
BACKGROUND More than half of patients with refluxrelated symptoms have no endoscopic evidence of mucosal breaks. These patients are considered to have nonerosive gastroesophageal reflux disease (NERD). The pathogenesis of NERD may be multifactorial, but the role played by gastric motility in symptom generation in patients with NERD has not been examined. In this study, we elucidate gastric motility in patients with NERD and the efficacy of a prokinetic agent in the treatment of NERD. METHODS Gastric motility was evaluated with electrogastrography (EGG) and by measurement of gastric emptying using the acetaminophen method in 26 patients with NERD and in 11 matched healthy controls. NERD patients were treated with a prokinetic agent (mosapride 15 mg, orally three times daily) for a period of 4 weeks, after which gastric motility was measured again. RESULTS Compared with the healthy controls, the NERD patients showed a significantly lower percentage of normogastria, a lower power ratio in EGG, and delayed gastric emptying. Ten patients had normal gastric motor function (group A), and 16 showed abnormalities of either gastric myoelectrical activity or gastric emptying (group B). After treatment with mosapride, gastric motility improved significantly in both groups of patients compared with pretreatment values. The subjective assessment by the patient after the treatment was improved in 20.0% of group A versus 62.5% of group B patients (P < 0.05). CONCLUSIONS Gastric hypomotility appears to be an important factor in reflux symptom generation in some NERD patients.
Collapse
Affiliation(s)
- Takeshi Kamiya
- Department of Gastroenterology and Metabolism, Nagoya City University Graduate School of Medical Sciences, 1 Kawasumi, Mizuho, Mizuho-ku, Nagoya, 467-8601, Japan
| | | | | | | | | | | | | | | | | | | | | | | |
Collapse
|
|
38
|
Lim D, Park WP, Lee YH, Lee QJ, Kim HS. Development and clinical testing of an ultrasonic diagnostic system for functional gastrointestinal disorders. ULTRASOUND IN MEDICINE & BIOLOGY 2008; 34:874-884. [PMID: 18255221 DOI: 10.1016/j.ultrasmedbio.2007.11.023] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 06/11/2007] [Revised: 10/03/2007] [Accepted: 11/29/2007] [Indexed: 05/25/2023]
Abstract
Functional gastrointestinal disorders (FGIDs) affect millions of people without regard for age, race or sex, but little information related to FGIDs and few methods are available for diagnosing FGIDs. Therefore, the aims of this study were to investigate any alterations to the gastrointestinal tracts induced by FGIDs and to develop and test an ultrasonic diagnostic system capable of detecting the alteration in the gastrointestinal tract. Palpation/percussion examinations were performed on 40 participants with or without FGIDs to identify any mechanical alterations to the gastrointestinal tract induced by FGIDs. An ultrasonic diagnostic system for FGIDs was developed and clinical trials were performed on same participants used in the palpation/percussion examinations to test the system under actual clinical conditions. The results obtained from the palpation/percussion examinations showed that a gastrointestinal tract with a FGID became more rigid than a healthy tract (p < 0.05). Clinical trials also showed that gastrointestinal tracts in the patient group with FGIDs were in fact more rigid than those in the control group without FGIDs (p < 0.05). These findings indicated that our newly designed ultrasonic diagnostic system may be useful in clinics to accurately diagnose FGIDs through detecting mechanical alterations to the rigidity of the gastrointestinal tract induced by FGIDs. The current study may be valuable by identifying for the first time mechanical alterations of the gastrointestinal tract induced by FGIDs and may prove valuable as the first step in the development of a diagnostic system for FGIDs.
Collapse
Affiliation(s)
- Dohyung Lim
- Department of Biomedical Engineering, and Research Institute for Medical Instruments and Rehabilitation Engineering, Yonsei University, Wonju, Gangwon, Republic of Korea
| | | | | | | | | |
Collapse
|
|
39
|
Abstract
The author summarizes the historical development of our knowledge about functional dyspepsia and overviews the so-called "road to Rome" process. Between 1988 and 2006, expert committees developed using the Delphi method subsequent classifications of functional gastrointestinal disorders (Rome I-III). The Rome III classification reassessed the diagnostic criteria for functional dyspepsia and distinguished new subgroups as the postprandial distress and epigastric pain syndrome. The rationale for the proposed new classification was based on the inadequacy of prior approaches such as the predominant symptom, the results of factor analyses in tertiary care and in the general population, clinical experience and new observations in the peer-reviewed literature. Epidemiologic data suggest that dyspeptic symptoms date back to the 1730s and their prevalence increased markedly subsequently, remaining the commonest diagnosis even in the endoscopic era. The current worldwide prevalence of functional dyspepsia is 7-45%, with large geographic variations. The role of Helicobacter pylori and Salmonella infection as etiologic factors is discussed. Amongst the pathophysiological features, the recent data on the role of phenotypic changes of acid secretion, alterations of fundic accommodation and antro-duodenal motility and gastric emptying, gastric hypersensitivity and hormonal disturbances are presented, but all these abnormalities are present only in a small part of the patients. The possible role of the polymorphism of alpha-adrenoceptor gene was also raised. The treatment of functional dyspepsia led to equivocal results and the high rate of placebo response makes difficult any interpretation. According to the recent meta-analyses, proton pump inhibitors and H 2 -histamine receptor blockers are superior to placebo. In spite of good results, cisapride was withdrawn in 2004. Eradication of Helicobacter pylori can induce sustained remission in a small but significant minority of patients. However, it might prevent further development of peptic ulcer and gastric carcinoma and from public health view, eradication of the infection must be performed by using a test-and-treat or test-and-scope strategy and the benefits and risks of this approach must be discussed with the patient. Each of the above treatments achieves transient symptomatic improvement only and follow-up of dyspeptic patients for 5-7 years showed the benign, but recurrent nature of the disease in 50% of the cases. The aim of the Rome III classification is the identification of pathophysiological changes associated with the new subgroups of functional dyspepsia which will permit their targeted pharmacologic treatment leading to better and cost-efficient results.
Collapse
Affiliation(s)
- György Miklós Buzás
- Ferencvárosi Egészségügyi Szolgálat Gasztroenterológia Budapest Mester u. 45. 1095.
| |
Collapse
|
|
40
|
Zuo XL, Li YQ, Li WJ, Guo YT, Lu XF, Li JM, Desmond PV. Alterations of food antigen-specific serum immunoglobulins G and E antibodies in patients with irritable bowel syndrome and functional dyspepsia. Clin Exp Allergy 2007; 37:823-30. [PMID: 17517095 DOI: 10.1111/j.1365-2222.2007.02727.x] [Citation(s) in RCA: 80] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
BACKGROUND Post-prandial worsening of symptoms as well as adverse reactions to one or more foods are common in the patients with functional gastrointestinal diseases, such as irritable bowel syndrome (IBS) and functional dyspepsia (FD). However, the role played by true food allergy in the pathogenesis of these diseases is still controversial and there are no well-established tests to identify food allergy in this condition. OBJECTIVE To investigate serum food antigen-specific IgG, IgE antibody and total IgE antibody titres in controls and patients with IBS and FD, and to correlate symptoms with the food antigen-specific IgG titres in IBS and FD patients. METHODS Thirty-seven IBS patients, 28 FD patients and 20 healthy controls participated in this study. Serum IgG and IgE antibody titres to 14 common foods including beef, chicken, codfish, corn, crab, eggs, mushroom, milk, pork, rice, shrimp, soybean, tomatoes and wheat were analysed by ELISA. Serum total IgE titres were also measured. Last, symptomatology was assessed in the study. Results IBS patients had significantly higher titres of IgG antibody to crab (P=0.000), egg (P=0.000), shrimp (P=0.000), soybean (P=0.017) and wheat (P=0.004) than controls. FD patients had significantly higher titres of IgG antibody to egg (P=0.000) and soybean (P=0.017) than controls. The percentage of individuals with detectable positive food antigen-specific IgE antibodies of the three groups did not show any significant differences (P=0.971). There were no significant differences between IBS patients, FD patients and controls in the serum total IgE antibody titres (P=0.978). Lastly, no significant correlation was seen between symptom severity and serum food antigen-specific IgG antibody titres both in IBS and FD patients. CONCLUSION Serum IgG antibody titres to some common foods increased in IBS and FD patients compared to controls. But there is no significant correlation between symptom severity and elevated serum food antigen-specific IgG antibodies in these patients.
Collapse
Affiliation(s)
- X L Zuo
- Department of Gastroenterology, Qilu Hospital, Shandong University, Jinan, China
| | | | | | | | | | | | | |
Collapse
|
|
41
|
von Arnim U, Peitz U, Vinson B, Gundermann KJ, Malfertheiner P. STW 5, a phytopharmacon for patients with functional dyspepsia: results of a multicenter, placebo-controlled double-blind study. Am J Gastroenterol 2007; 102:1268-75. [PMID: 17531013 DOI: 10.1111/j.1572-0241.2006.01183.x] [Citation(s) in RCA: 94] [Impact Index Per Article: 5.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
BACKGROUND Functional dyspepsia (FD) constitutes a complex picture with a variety of epigastric symptoms. No standard therapy is currently available for FD. OBJECTIVE This multicenter, placebo-controlled, double-blind study evaluated the efficacy and tolerability of the herbal drug STW 5, mainly comprising a fresh plant extract from Iberis amara. METHODS Patients with FD were included. Gastrointestinal endoscopy, H. pylori-status, and a 7-day run-in phase were required. A total of 315 patients were treated with 3 x 20 drops/day of either STW 5 or placebo. Symptom assessment: day 0, 2, 4, and 8 wk of treatment. The principal outcome criterion was the change in a validated Gastrointestinal Symptom Score (GIS). Symptom severity was rated using the Likert scale. RESULTS A total of 315 patients remained in the safety population. Of them, 158 were treated with STW 5 and 157 with placebo. The intention-to-treat population comprised 308 patients. Dropout number was similar in both groups. GIS showed improvement during the treatment period. The STW 5 group improved 6.9+/-4.8 points up to day 56, placebo group by 5.9+/-4.3 (P<0.05). H. pylori did not influence the results. Drug tolerability and safety were similar in both groups. CONCLUSION This placebo-controlled study with an 8-wk treatment period documents the efficacy of STW 5 in FD.
Collapse
Affiliation(s)
- Ulrike von Arnim
- Otto-von-Guericke-Universität Magdeburg, Zentrum für Innere Medizin, 39120 Magdeburg, Germany
| | | | | | | | | |
Collapse
|
|
42
|
Haag S, Senf W, Tagay S, Langkafel M, Braun-Lang U, Pietsch A, Heuft G, Talley NJ, Holtmann G. Is there a benefit from intensified medical and psychological interventions in patients with functional dyspepsia not responding to conventional therapy? Aliment Pharmacol Ther 2007; 25:973-86. [PMID: 17403002 DOI: 10.1111/j.1365-2036.2007.03277.x] [Citation(s) in RCA: 59] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Abstract
AIM In a prospective randomized, controlled trial, to compare the long-term outcome of intensive medical therapy (with or without cognitive-behavioural or muscle relaxation therapy) vs. standard medical therapy in patients with refractory functional dyspepsia (FD), referred to a tertiary referral medical center. METHODS A total of 100 consecutive FD patients were allocated to a standardized symptom-oriented 4 month therapy (SMT, n = 24), intensive medical therapy (IMT, medical therapy with testing-for and targeting-of abnormalities of motor-and-sensory function, n = 28) or IMT plus psychological interventions (either progressive-muscle relaxation (IMT-MR, n = 20) or cognitive-behavioural therapy (IMT-CBT, n = 28). The symptom intensity (SI) and health-related quality-of-life (HRQoL) after 12 months were prespecified primary outcome parameters. RESULTS After 12 months, significantly greater improvement of SI occurred in patients with IMT-all (with or without psychological interventions) compared with SMT (P < 0.025 vs. IMT-all). IMT, IMT-MR and IMT-CBT alone also resulted in significantly better improvement of the primary outcome parameters (P all < 0.025 vs. SMT). HRQoL significantly improved in all groups with intensive medical therapy but not standard medical therapy. Differences between intensive medical therapy-all and standard medical therapy were not significant. Concomitant anxiety and depression was improved significantly by IMT-CBT (vs. SMT) but not other treatments. CONCLUSIONS In FD patients with refractory symptoms, intensified medical management involving function testing and psychological intervention yields superior long-term-outcomes. Additional CBT may be effective for the control of concomitant anxiety and depression.
Collapse
Affiliation(s)
- S Haag
- Department of Gastroenterology and Hepatology, and Clinic for Psychosomatic Medicine and Psychotherapy, University Hospital Essen, Essen, Germany
| | | | | | | | | | | | | | | | | |
Collapse
|
|
43
|
Mizuta Y, Shikuwa S, Isomoto H, Mishima R, Akazawa Y, Masuda JI, Omagari K, Takeshima F, Kohno S. Recent insights into digestive motility in functional dyspepsia. J Gastroenterol 2006; 41:1025-40. [PMID: 17160514 DOI: 10.1007/s00535-006-1966-z] [Citation(s) in RCA: 48] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/06/2006] [Accepted: 10/02/2006] [Indexed: 02/04/2023]
Abstract
Functional gastrointestinal disorders, such as functional dyspepsia (FD) and irritable bowel syndrome, are common pathologies of the gut. FD is a clinical syndrome defined as chronic or recurrent pain or discomfort of unknown origin in the upper abdomen. The pathophysiological mechanisms responsible for FD have not been fully elucidated, but new ideas regarding its pathophysiology and the significance of the pathophysiology with respect to the symptom pattern of FD have emerged. In particular, there is growing interest in alterations in gastric motility, such as accommodation to a meal or gastric emptying, and visceral sensation in FD. The mechanisms underlying impaired gastroduodenal motor function are unclear, but possible factors include abnormal neurohormonal function, autonomic dysfunction, visceral hypersensitivity to acid or mechanical distention, Helicobacter pylori infection, acute gastrointestinal infection, psychosocial comorbidity, and stress. Although the optimum treatment for FD is not yet clearly established, acid-suppressive drugs, prokinetic agents, eradication of H. pylori, and antidepressants have been widely used in the management of patients with FD. The therapeutic efficacy of prokinetics such as itopride hydrochloride and mosapride citrate in the treatment of FD is supported by the results of relatively large and well-controlled studies. In addition, recent research has yielded new therapeutic agents and modalities for dysmotility in FD, including agonists/antagonists of various sensorimotor receptors, activation of the nitrergic pathway, kampo medicine, acupuncture, and gastric electric stimulation. This review discusses recent research on the pathophysiology of and treatment options for FD, with special attention given to digestive dysmotility.
Collapse
Affiliation(s)
- Yohei Mizuta
- Second Department of Internal Medicine, Nagasaki University School of Medicine, 1-7-1 Sakamoto, Nagasaki 852-8501, Japan
| | | | | | | | | | | | | | | | | |
Collapse
|
|
44
|
Talley NJ, Locke GR, Tack J. Does delayed gastric emptying really cause symptoms in functional dyspepsia? We still doubt it! Gut 2006; 55:1674; author reply 1674. [PMID: 17047125 PMCID: PMC1860081 DOI: 10.1136/gut.2005.105601] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/08/2022]
|
|
45
|
Kasicka-Jonderko A, Kamińska M, Jonderko K, Setera O, Błońska-Fajfrowska B. Short- and medium-term reproducibility of gastric emptying of a solid meal determined by a low dose of 13C-octanoic acid and nondispersive isotope-selective infrared spectrometry. World J Gastroenterol 2006; 12:1243-8. [PMID: 16534878 PMCID: PMC4124436 DOI: 10.3748/wjg.v12.i8.1243] [Citation(s) in RCA: 11] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
AIM: To evaluate the reproducibility of a modified 13C breath test-based measurement of solid phase gastric emptying (GE) within the frames of a simple-repeated measure study protocol.
METHODS: Twelve healthy subjects (6 females and 6 males, mean age 24.9 ± 0.7 years) were recruited to undergo three identical GE examinations. In six subjects the first two examinations were performed 2 d apart, and the third session was carried out at a median interval of 19.5 d (range 18 - 20 d) from the second one. In another six subjects the first two measurements were taken 20 d apart (median, range: 17-23 d), whereas the third session took place 2 d after the second one. Probes of expiratory air collected before and during six hours after intake of a solid meal (378 kcal) labelled with 75 μL (68 mg) 13C-octanoic acid, were measured for 13CO2 enrichment with the nondispersive isotope-selective infrared spectrometry NDIRS apparatus.
RESULTS: Taking coefficients of variation for paired examinations into account, the short-term reproducibility of the GE measurement was slightly but not significantly better than the medium-term one: 7.7% and 11.2% for the lag phase (T-Lag), 7.3% and 10.9% for the gastric half emptying time (T½). The least differences in GE parameters detectable at P = 0.05 level in the 12 paired examinations were 9.6 and 15.6 min for T-Lag, 11.6 and 19.7 min for T½ by a two-day or two to three-week time gap, respectively.
CONCLUSION: The low-cost modification of the breath test involving a lower dose of 13C-octanoic acid and NDIRS, renders good short- and medium-term reproducibility, as well as sensitivity of the measurement of gastric emptying of solids.
Collapse
Affiliation(s)
- Anna Kasicka-Jonderko
- Department of Basic Biomedical Science, School of Pharmacy, Medical University of Silesia, 3 Kasztanowa street, PL-41-205 Sosnowiec, Poland.
| | | | | | | | | |
Collapse
|
|
46
|
Frissora CL, Koch KL. Symptom overlap and comorbidity of irritable bowel syndrome with other conditions. Curr Gastroenterol Rep 2005; 7:264-71. [PMID: 16042909 DOI: 10.1007/s11894-005-0018-9] [Citation(s) in RCA: 76] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
Irritable bowel syndrome (IBS) is one of several highly prevalent, multi-symptom gastrointestinal motility disorders that have a wide clinical spectrum and are associated with symptoms of gastrointestinal dysmotility and visceral hypersensitivity. Symptom overlap and comorbidity between IBS and other gastrointestinal motility disorders (eg, chronic constipation, functional dyspepsia, gastroesophageal reflux disease), with gastrointestinal disorders that are not related to motility (eg, celiac disease, lactose intolerance), and with somatic conditions (eg, fibromyalgia, chronic fatigue syndrome), are frequent. The clinical associations and pathophysiologic links between IBS and these disorders continue to be explored. This review discusses overlapping symptoms and comorbidity of IBS with select gastrointestinal and non-gastrointestinal disorders and attempts to identify commonalities among these conditions.
Collapse
Affiliation(s)
- Christine L Frissora
- Department of Medicine, The Weill Medical College of Cornell University, 520 E. 70th Street, Suite J-314, New York, NY 10021, USA.
| | | |
Collapse
|
|
47
|
Abstract
Functional dyspepsia (FD) is one of the most common gastrointestinal disorders. This review summarizes recent progress in our understanding of the pathogenesis and therapy for FD. Although distinction among FD, irritable bowel syndrome, and reflux disease is difficult in population-based studies, separate entities can be recognized in patients who seek medical attention. The pathogenesis of FD remains unclear, but recent studies have demonstrated a role for acute gastrointestinal infection in triggering FD and in genetic polymorphisms of G-proteins in predisposing to FD. The role of abnormalities in gastric motor function, visceral hypersensitivity, and psychosocial factors in the pathophysiology of dyspeptic symptoms has been the topic of multiple studies. Treatment options for FD remain limited. Recent studies have focused on acid-suppressive drugs and on novel prokinetics. Progress in our understanding of the pathogenesis and pathophysiology of FD may lead to new or improved treatment modalities. Areas of major advances are the role of infection and genetic predisposition and studies on the role of abnormalities in gastric motility and sensitivity.
Collapse
Affiliation(s)
- Jan Tack
- Department of Internal Medicine, Division of Gastroenterology, University Hospital Gasthuisberg, University of Leuven, Herestraat 49, B-3000 Leuven, Belgium.
| | | |
Collapse
|
|
48
|
Abstract
PURPOSE OF REVIEW Abnormalities of gastric sensory and motor function are considered key players in the pathogenesis of upper gastrointestinal symptoms in functional dyspepsia and in gastroparesis. This review summarizes recent progress in our understanding of normal and pathologic gastric sensory and motor function. RECENT FINDINGS Several novel tests have been developed to study gastric sensitivity and meal-induced accommodation, including scintigraphic analysis of meal distribution within the stomach, single photon emission computed tomography of gastric volumes, and nutrient or water challenge tests. Several studies have reported on the occurrence of delayed gastric emptying in functional dyspepsia and in gastroparesis, but the correlation with symptoms was generally poor. The pathways and neurotransmitter involved in gastric hypersensitivity are progressively being unraveled. Several studies have confirmed and focused on increased symptom occurrence after nutrient challenge in functional dyspepsia. The role of the proximal stomach in the control of food intake and the stomach as a target in the treatment of obesity are areas of intense research. Studies have reported on pharmacologic approaches as well as electric stimulation in the treatment of gastric sensorimotor dysfunction. SUMMARY Progress in our understanding of normal and abnormal gastric sensory and motor function may lead to new or improved treatment modalities. Areas of major advances are the study of meal-induced symptoms in functional dyspepsia, unraveling of the role of the stomach in the control of food intake, and the use of gastric electric stimulation in gastroparesis and in obesity.
Collapse
Affiliation(s)
- Jan Tack
- University Hospital Gasthuisberg, University of Leuven, Belgium.
| |
Collapse
|
|
49
|
Abstract
PURPOSE OF REVIEW Since its introduction just over 10 years ago, there have been a number of studies that have used the octanoate breath test to assess gastric emptying. Although use of the method is on the increase (the number of gastric emptying studies published on PubMed using the octanoate breath test has doubled between the periods 1997-2000 and 2001-2004 compared with a drop of approximately 20% in the use of scintigraphy over the same periods), the methodology has not achieved universal acceptance, primarily because it can provide results comparable to established techniques only indirectly. RECENT FINDINGS Recent methods for overcoming this difficulty are reviewed, including modified methods for breath test interpretation and the application of the related saliva test. The latter promises to be useful as a non-invasive proxy for established techniques, such as scintigraphy, for further validation of the breath test. Recent applications of octanoate-based methods are briefly considered. SUMMARY A novel approach detailed in this review for breath test interpretation, where the bicarbonate pool is modelled as a single compartment, could prove useful for obtaining breath test gastric emptying parameters that are directly comparable with those obtained from the gold standard, gamma scintigraphy. In combination with the saliva test, this could add credence to use of the octanoate breath test as a clinically accepted diagnostic tool, in addition to its potential in research.
Collapse
Affiliation(s)
- Sarah J Jackson
- MRC-Human Nutrition Research, Elsie Widdowson Laboratory, Cambridge, UK.
| | | |
Collapse
|
|
50
|
Tougas G, Earnest DL, Chen Y, Vanderkoy C, Rojavin M. Omeprazole delays gastric emptying in healthy volunteers: an effect prevented by tegaserod. Aliment Pharmacol Ther 2005; 22:59-65. [PMID: 15963081 DOI: 10.1111/j.1365-2036.2005.02528.x] [Citation(s) in RCA: 31] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/19/2022]
Abstract
BACKGROUND Proton-pump inhibitors effectively suppress stomach acidity. They are widely used for treating gastro-oesophageal reflux disease and related conditions. While generally safe, omeprazole and other proton-pump inhibitors can delay gastric emptying. AIM To test the hypothesis that tegaserod can normalize or prevent omeprazole-induced delay in gastric emptying. METHODS This was a randomized, double-blind, placebo-controlled, parallel group study in 40 healthy male volunteers. After informed consent and screening, qualified volunteers were treated with unblinded omeprazole 20 mg b.d. and either blinded tegaserod 6 mg t.d.s. (active treatment group) or placebo-matching tegaserod t.d.s. (control group) for 14 days. Gastric emptying was assessed before and after treatment, using a scintigraphy method. RESULTS Omeprazole monotherapy significantly delayed gastric emptying expressed by duration of lag-phase (P < 0.007), time to gastric half-emptying (P < 0.003), and gastric retention of the meal at 60 (P < 0.002) and 120 min (P < 0.04) after its ingestion. Tegaserod taken together with omeprazole effectively prevented development of the above effects. Combined treatment was safe and well tolerated. CONCLUSION Concomitant administration of tegaserod 6 mg t.d.s. prevented development of the delayed gastric emptying induced by omeprazole monotherapy.
Collapse
Affiliation(s)
- G Tougas
- McMaster University, Hamilton, ON, Canada
| | | | | | | | | |
Collapse
|