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Song Z, Kwon T, Lee J, Won DD, Lee BJ, Choi HS, Liao JC, Park WG, Sonu I, Rogalla S, Rosen MJ, Hu DL, Ziyang JK, Wong SH, Jun BH, Kim S, Park SM. AI-Driven Defecation Analysis by Smart Healthcare Toilet: Exploring Biometric Patterns and Eu-Tenesmus. ADVANCED SCIENCE (WEINHEIM, BADEN-WURTTEMBERG, GERMANY) 2025:e2503247. [PMID: 40349171 DOI: 10.1002/advs.202503247] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 02/20/2025] [Revised: 04/14/2025] [Indexed: 05/14/2025]
Abstract
Defecation, a fundamental physiological process, remains underexplored despite its importance in human health. To address this gap, a smart toilet system is developed that enables real-time monitoring of defecation behaviors. Analyzing 45 defecation events from 11 participants, key defecation parameters are identified, including stool dropping duration, stool thickness, and eu-tenesmus interval. Stool dropping duration follows a log-normal distribution, with longer durations (>5 s) linked to lower Bristol Stool Form Scale (BSFS) scores, suggesting constipation (p = 0.008 for BSFS1/2/3 vs BSFS5/6/7). Stool thickness decreases with increasing BSFS scores (p = 5 × 10⁻⁶ for BSFS1/2/3 vs BSFS5/6/7), validating its role as an objective marker for bowel function. Eu-tenesmus is introduced, defined as the interval between the last stool drop and cleansing, averaging 74.8 s. It shows significant gender differences (p = 0.014) but no correlation with stool consistency, suggesting its potential as an independent biomarker for gut health. Defecation behaviors between humans and animals is also compared in detail. Longitudinal monitoring demonstrates the potential for personalized health tracking and dietary recommendations. Furthermore, the feasibility of biometric identification is established using 11 defecation-related parameters, including stool properties and cleansing behavior. These features enable high participant differentiation, supporting non-invasive identity verification.
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Affiliation(s)
- Zhiquan Song
- School of Chemistry, Chemical Engineering and Biotechnology, Nanyang Technological University, Singapore, Singapore
| | - TaeHyung Kwon
- Department of Civil and Environmental Engineering, Stanford University, Stanford, CA, USA
| | - Jeung Lee
- Department of Civil and Environmental Engineering, Stanford University, Stanford, CA, USA
| | - Daeyoun D Won
- Seokjeong Wellpark Hospital, Jeollabuk-do, Republic of Korea
- Kanaria Health, Seoul, Republic of Korea
| | - Brian J Lee
- School of Mechanical Engineering, Sungkyunkwan University, Suwon, Republic of Korea
| | - Hyuk Soon Choi
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Korea University College of Medicine, Seoul, Republic of Korea
| | - Joseph C Liao
- Department of Urology, Stanford University School of Medicine, Stanford, CA, USA
| | - Walter G Park
- Division of Gastroenterology & Hepatology, Department of Medicine, Stanford University School of Medicine, Stanford, CA, USA
| | - Irene Sonu
- Division of Gastroenterology & Hepatology, Department of Medicine, Stanford University School of Medicine, Stanford, CA, USA
| | - Stephan Rogalla
- Division of Gastroenterology & Hepatology, Department of Medicine, Stanford University School of Medicine, Stanford, CA, USA
| | - Michael J Rosen
- Division of Pediatric Gastroenterology, Hepatology and Nutrition, Department of Pediatrics, Stanford University School of Medicine, Stanford, CA, USA
| | - David L Hu
- George W. Woodruff School of Mechanical Engineering, Georgia Institute of Technology, Atlanta, GA, USA
| | | | - Sunny Hei Wong
- Department of Gastroenterology & Hepatology, Tan Tock Seng Hospital, Singapore
- Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore, Singapore
| | - Bong Hyun Jun
- Department of Bioscience and Biotechnology, Konkuk University, Seoul, Republic of Korea
| | - Soh Kim
- Department of Civil and Environmental Engineering, Stanford University, Stanford, CA, USA
| | - Seung-Min Park
- School of Chemistry, Chemical Engineering and Biotechnology, Nanyang Technological University, Singapore, Singapore
- Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore, Singapore
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Arif TB, Ali SH, Bhojwani KD, Sadiq M, Siddiqui AA, Ur-Rahman A, Khan MZ, Hasan F, Shahzil M. Global prevalence and risk factors of irritable bowel syndrome from 2006 to 2024 using the Rome III and IV criteria: a meta-analysis. Eur J Gastroenterol Hepatol 2025:00042737-990000000-00528. [PMID: 40359286 DOI: 10.1097/meg.0000000000002994] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 05/15/2025]
Abstract
Functional gastrointestinal disorders impact 40% of the global population, with irritable bowel syndrome (IBS) standing out due to its complexity, quality-of-life effects, and economic impact. Our meta-analysis explored the global prevalence of IBS, considering diagnostic criteria, subtypes, sampling methods, geographical variations, and risk factors. The literature search used databases like PubMed and Cochrane Library, focusing on IBS studies from 2006 to June 2024. Eligibility criteria included studies on individuals aged ≥18, based on Rome III/IV criteria, using random or convenience sampling. Data on IBS prevalence, subtypes, and sampling methods were extracted, and statistical analysis was performed using Open MetaAnalyst and the review manager. The study reviewed 96 articles on IBS prevalence using Rome III and IV criteria across 52 countries, revealing a global prevalence of 14.1%. Prevalence varied by subtype: IBS-C (26.1%), IBS-D (26.5%), IBS-M (31.4%), and IBS-U (8.3%). IBS-D was more prevalent under Rome III (26.2%), while IBS-C was more common under Rome IV (34.2%). First-world countries like the UK, China, and Japan had the highest prevalence. Females [odds ratios (OR): 1.49], stress (OR: 2.47), anxiety (OR: 2.93), and depression (OR: 2.24) were significantly more prevalent in IBS patients, while no significant differences were found in smoking, alcohol use, or education levels. This meta-analysis reveals regional and subtype variations in IBS prevalence, with psychological factors significantly impacting its development. The influence of sampling techniques and Rome III/IV criteria on prevalence estimates highlights the need for a multidisciplinary treatment approach, with important implications for IBS management.
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Affiliation(s)
- Taha Bin Arif
- Department of Internal Medicine, Sinai Hospital of Baltimore/The George Washington University Regional Medical Campus, Baltimore, Maryland, USA
| | - Syed Hasham Ali
- Department of Medicine, Dow University of Health Sciences, Karachi, Pakistan
| | - Kapil Dev Bhojwani
- Department of Medicine, Dow University of Health Sciences, Karachi, Pakistan
| | - Mahnoor Sadiq
- Department of Medicine, Dow University of Health Sciences, Karachi, Pakistan
| | - Asad Ali Siddiqui
- Department of Medicine, Dow University of Health Sciences, Karachi, Pakistan
| | - Asad Ur-Rahman
- Department of Gastroenterology and Hepatology, Cleveland Clinic Florida, Weston, Florida, USA
| | - Muhammad Zarrar Khan
- Department of Gastroenterology and Hepatology, Henry Ford Hospital, Royal Oak, Michigan, USA
| | - Fariha Hasan
- Department of Internal Medicine, Cooper University Hospital, Camden, New Jersey, USA and
| | - Muhammad Shahzil
- Department of Internal Medicine, Penn State Milton Hershey Medical Center, Hershey, Pennsylvania, USA
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An Association Between IBS Quality of Life Score and Symptoms of Abdominal Pain, Bloating, and Cramping in IBS-C: A Pooled Phase 3 Trial Correlation Analysis. Gastroenterol Hepatol (N Y) 2024; 20:11-12. [PMID: 39896922 PMCID: PMC11784545] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/04/2025]
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Brick C, Su H, Taylor K, Burgell R. Moving beyond Symptom Criteria to Diagnose and Treat Functional Disorders: Patient-Reported Symptoms of Functional Lower Gastrointestinal Disorders Correlate Poorly with Objective Assessment of Luminal Contents Seen on Intestinal Ultrasound. J Clin Med 2024; 13:4759. [PMID: 39200901 PMCID: PMC11355646 DOI: 10.3390/jcm13164759] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/05/2024] [Revised: 07/22/2024] [Accepted: 07/24/2024] [Indexed: 09/02/2024] Open
Abstract
Background/Objectives: The diagnosis of lower functional gastrointestinal disorders (FGIDs) is currently based on subjective and unreliable patient-reported symptoms, with significant clinical overlap between diagnosed phenotypes. Objective biomarkers are urgently sought. Gastrointestinal ultrasound (GIUS) can objectively and non-invasively assess luminal contents. This study aimed to assess the utility of GIUS in phenotyping patients with lower FGIDs. Methods: Patients with lower FGIDs underwent a GIUS and completed the Rome IV Diagnostic Questionnaire, SAGIS questionnaire, and 100 mm VAS score for overall symptom severity. The faecal loading score (FLS) was obtained using a modified Leech score, where an FLS of >37 was consistent with clinically significant constipation. Results: Eighty-eight patients fulfilled the study requirements. In total, 56 met the Rome IV criteria for irritable bowel syndrome (IBS) subtypes, while 23 met the criteria for functional constipation (FC), 4 for functional diarrhoea (FD), and 5 for other diagnoses. Patients reporting constipation-predominant symptoms had a significantly higher median FLS than those describing diarrhoea-predominant symptoms (FLS = 40 [IQR 20.0-53.3] vs. 13.3 [IQR 6.7-40.0], respectively). However, 27% of patients describing diarrhoea had significant faecal loading on GIUS, and of those who described constipation, 34% did not have significant faecal loading. Sensitivity and specificity for the detection of FLS-indicated constipation by the Rome IV criteria were low at 59% and 66%, respectively. Conclusions: The symptom-based diagnosis of FGID subtypes based on the Rome IV criteria is a poor predictor of faecal loading. These findings should prompt further exploration of the limitations of symptom-based assessment and a shift towards physiological assessment of patients with FGIDs such as gastrointestinal ultrasound to develop more targeted therapy. Future research is underway to determine if targeting objective physiological endpoints results in improved clinical outcomes.
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Affiliation(s)
- Claudia Brick
- Alfred Health, Melbourne, VIC 3004, Australia; (C.B.)
| | - Heidi Su
- Alfred Health, Melbourne, VIC 3004, Australia; (C.B.)
| | - Kirstin Taylor
- Alfred Health, Melbourne, VIC 3004, Australia; (C.B.)
- School of Translational Medicine, Monash University, Melbourne, VIC 3800, Australia
| | - Rebecca Burgell
- Alfred Health, Melbourne, VIC 3004, Australia; (C.B.)
- School of Translational Medicine, Monash University, Melbourne, VIC 3800, Australia
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Jafari S, Atmani A, Gohari S, Seifi E. The Effect of Ondansetron on Improvement of Symptoms in Patients with Irritable Bowel Syndrome with Diarrhea Domination: A Randomized Controlled Trial. Middle East J Dig Dis 2024; 16:178-184. [PMID: 39386337 PMCID: PMC11459287 DOI: 10.34172/mejdd.2024.386] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/10/2023] [Accepted: 03/22/2024] [Indexed: 10/12/2024] Open
Abstract
Background Diarrhea-dominant irritable bowel syndrome (IBS-D) is a deliberating and chronic condition that can impair social activities. Determining proper medication with satisfactory outcomes has been a challenge. The 5-hydroxytryptamine 3 receptor antagonist (5-HT3 RA) drugs have demonstrated favorable outcomes on IBS-D in the last 3 decades. Ondansetron, also a 5-HT3 RA is known as an antiemetic. Our aim was to evaluate the efficacy of ondansetron in IBS-D. Methods In this single-center, double-blind, randomized controlled trial, patients with IBS-D were recruited. Patients were randomized on a 1:1 ratio and assigned into two groups: imipramine 25 mg/daily plus ondansetron 4 mg/3 times per day and imipramine 25 mg/daily plus placebo. The primary endpoint was the frequency of diarrhea per day after 8 weeks of treatment. The secondary endpoints consisted of changes in the frequency of defecation urgency per day, the number of days with gastrointestinal pain and bloating, and the patients' overall satisfaction regarding bowel habits after 8 weeks of the treatment. Results Data from 98 patients were analyzed. Ondansetron, compared to placebo, improved the primary outcome, and the stool consistency was increased significantly (3.29±1.19 vs 4.55±1.17, P<0.001). Moreover, the response rate for the diarrhea frequency was significantly higher in the ondansetron group compared to the placebo (77.5% vs 34.7%, P<0.001). In the ondansetron group, fewer urgencies were experienced, and pain severity and feeling of bloating declined as well (P<0.01). Conclusion Ondansetron can mitigate almost all IBS-D-related symptoms, which may indicate it as a drug of choice; however, further evidence is required to ascertain its safety.
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Affiliation(s)
- Sattar Jafari
- Department of Internal Medicine, Zanjan University of Medical Sciences, Zanjan, Iran
| | - Arezoo Atmani
- Department of Internal Medicine, Vali-e-Asr Hospital, Zanjan University of Medical Sciences, Zanjan, Iran
| | - Sepehr Gohari
- Student Research Center, School of Medicine, Zanjan University of Medical Sciences, Zanjan, Iran
- Department of Family Medicine, Alborz University of Medical Sciences, Alborz, Iran
| | - Ehsan Seifi
- Student Research Center, School of Medicine, Zanjan University of Medical Sciences, Zanjan, Iran
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Lacy BE, Chang L, Rao SSC, Heimanson Z, Sayuk GS. Rifaximin Treatment for Individual and Multiple Symptoms of Irritable Bowel Syndrome With Diarrhea: An Analysis Using New End Points. Clin Ther 2023; 45:198-209. [PMID: 36922331 DOI: 10.1016/j.clinthera.2023.01.010] [Citation(s) in RCA: 9] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/01/2022] [Revised: 01/18/2023] [Accepted: 01/19/2023] [Indexed: 03/15/2023]
Abstract
PURPOSE Rifaximin is indicated for the treatment of irritable bowel syndrome with diarrhea (IBS-D) in adults. The current aim was to evaluate rifaximin efficacy on individual and composite IBS-D symptoms using definitions not previously examined. METHODS Phase III post hoc analyses of two randomized, double-blind, placebo-controlled trials and the open-label phase of a randomized, double-blind, placebo-controlled trial were conducted. Adults with IBS-D received a 2-week course of rifaximin 550 mg TID. Individual and composite responses for abdominal pain (mean weekly improvements from baseline of ≥30%, ≥40%, or ≥50%), bloating (mean weekly improvements from baseline of ≥1 or ≥2 points; or ≥30%, ≥40%, or ≥50%), stool consistency (mean weekly average stool consistency score <3 or <4), and urgency (improvement from baseline of ≥30% or ≥40% in percentage of days with urgency) for ≥2 of the first 4 weeks after treatment, and weekly for 12 weeks, were assessed. FINDINGS Overall, 1258 patients from the double-blind trials (rifaximin [n = 624]; placebo [n = 634]) and 2438 from an open-label trial were analyzed. The percentage of bloating or urgency responders was significantly greater with double-blind rifaximin versus placebo (P ≤ 0.03). A significantly greater percentage of the double-blind group were composite abdominal pain and bloating responders versus placebo for all thresholds analyzed (P < 0.05). A significantly greater percentage of the double-blind group were tri-symptom composite end point responders (abdominal pain, bloating, and fecal urgency) versus placebo (P = 0.001). A significantly greater percentage of patients achieved response (≥30% composite tri-symptom threshold) with double-blind rifaximin versus placebo as early as 1 week posttreatment, with significance maintained through ≥5 weeks after treatment. Open-label results were consistent with those of the double-blind study. IMPLICATIONS Rifaximin significantly improved multiple, concurrent IBS-D symptoms, using clinically relevant definitions of treatment response. Using a novel tri-symptom composite end point (ie, abdominal pain, bloating, fecal urgency), adults with IBS-D treated with a 2-week course of rifaximin were significantly more likely to be composite end point responders than those receiving placebo (≥30% or ≥40% threshold) for the three symptoms. Thus, rifaximin not only met current standard thresholds used for adjudication of responders in clinical trials but also achieved higher thresholds for many of these symptoms, suggesting potential for even more robust clinical improvements. CLINICALTRIALS gov identifiers: NCT00731679, NCT00724126, and NCT01543178. (Clin Ther. 2023;45:XXX-XXX) © 2023 Elsevier HS Journals, Inc.
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Affiliation(s)
- Brian E Lacy
- Division of Gastroenterology and Hepatology, Mayo Clinic, Jacksonville, Florida, USA.
| | - Lin Chang
- Vatche and Tamar Manoukian Division of Digestive Diseases, David Geffen School of Medicine at the University of California, Los Angeles, Los Angeles, California, USA
| | - Satish S C Rao
- Augusta University, Medical College of Georgia, Augusta, Georgia, USA
| | | | - Gregory S Sayuk
- St. Louis Veterans Affairs Medical Center, St. Louis, Missouri, USA
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Howell CA, Kemppinen A, Allgar V, Dodd M, Knowles CH, McLaughlin J, Pandya P, Whorwell P, Markaryan E, Yiannakou Y. Double-blinded randomised placebo controlled trial of enterosgel (polymethylsiloxane polyhydrate) for the treatment of IBS with diarrhoea (IBS-D). Gut 2022; 71:2430-2438. [PMID: 35760493 PMCID: PMC9664110 DOI: 10.1136/gutjnl-2022-327293] [Citation(s) in RCA: 15] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/03/2022] [Accepted: 06/12/2022] [Indexed: 12/08/2022]
Abstract
OBJECTIVE Irritable bowel syndrome with diarrhoea (IBS-D) is a common and challenging condition that significantly reduces quality of life. Enterosgel (polymethylsiloxane polyhydrate) is an intestinal adsorbent which sequesters harmful molecules and is safe and effective in acute infective diarrhoea. This randomised controlled multicentre trial aimed to investigate its safety and efficacy in patients with IBS-D. DESIGN After a 2-week screening phase, participants were randomised into an 8-week double-blind phase, followed by an 8-week open-label and follow-up phase. Participants recorded stool consistency, pain and global symptoms in e-diaries and questionnaires. The primary outcome was the percentage of responders on a composite abdominal pain (≥30% decrease in the weekly score) and stool consistency (50% reduction in days per week with at least one stool of BSFS type 6 or 7) score during at least 4 weeks of the treatment period. RESULTS 440 patients with IBS-D were randomised to the double-blind phase with 393 continuing to the open-label phase. The Primary outcome responder rate by intention-to-treat for enterosgel versus placebo was 37.4% vs 24.3% (OR 1.95, NNT 8, p=0.002). Enterosgel also improved stool consistency (48.5% vs 32.5%, p<0.0001) abdominal pain (53.3% vs 40.2%, p=0.003), stool frequency (treatment effect -0.32 (-0.62 to -0.02)) and urgency (treatment effect -0.59 (-0.85 to -0.33)). 60% of patients reported adequate relief of symptoms after open-label treatment. Adverse event frequency was similar in both groups, with no serious events attributable to enterosgel. CONCLUSION Enterosgel is safe and effective in IBS-D, providing an alternative to the limited current treatment options. TRIAL REGISTRATION NUMBER ISRCTN17149988.
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Affiliation(s)
| | | | | | - Matthew Dodd
- Department of Medical Statistics, School of Hygiene and Tropical Medicin, London, UK
| | - Charles H Knowles
- Queen Mary University Faculty of Medicine and Dentistry, Blizard Institute, London, UK
| | - John McLaughlin
- Division of Diabetes, Endocrinology and Gastroenterology, The University of Manchester, Manchester, UK,Gastroenterology, Northern Care Alliance NHS Foundation Trust, Salford, UK
| | | | - Peter Whorwell
- Neurogastroenterology Unit, Wythenshawe Hospital, Manchester, UK
| | | | - Yan Yiannakou
- Department of Gastroenterology, County Durham and Darlington NHS Foundation Trust, Darlington, UK .,School of Health and Life Sciences, University of Teesside, Middlesbrough, UK
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Sayuk GS, North CS, Pollio DE, Gott BM, Alpers DH. Episodic Memories Among Irritable Bowel Syndrome (IBS) Patients: An Important Aspect of the IBS Symptom Experience. FRONTIERS IN PAIN RESEARCH 2022; 3:892313. [PMID: 35782224 PMCID: PMC9243497 DOI: 10.3389/fpain.2022.892313] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/08/2022] [Accepted: 05/20/2022] [Indexed: 11/21/2022] Open
Abstract
Objective: Some IBS patients possess detailed memories of the events surrounding their bowel symptom onset (“episodic memories”). In this exploratory study we sought to: (1) examine memory relationship with gastrointestinal (GI) symptom severity, extraintestinal symptoms, and mood; (2) qualitatively explore memory valence and content in IBS patients with or without episodic memories. Methods Referral IBS patients n = 29; age 47.0± 2.2 years, 79.3% female) enrolled in this cross-sectional, mixed methods research study. Participants completed validated specific memory instruments [Autobiographical Memory Test (AMT), Sentence Completion for Events from the Past Test (SCEPT)] and relevant questionnaires [IBS symptoms 10-cm visual analog scale); SF-36 Health-related quality of life (HRQOL); Perley-Guze and PHQ-15/12: somatization; Beck Depression/Anxiety Inventories). Qualitative analysis examined the content and valence of general memories. Results 14/29 (48.3%) of IBS subjects endorsed episodic memories of IBS symptom onset, often GI infections/enteritis (35.7%). Recall of the exact year (69%) and month (60%) of symptom onset were common. Episodic memories were associated with greater IBS symptom severity/bother, higher anxiety/depression, and poorer HRQOL. Though AMT and SCEPT memory specificity were not different based on episodic memories, overgeneralization to negatively-valenced cues in the AMT was associated with more severe IBS in those without episodic memory. Qualitative analysis revealed no observable differences in topic focus of IBS patients with and without episodic memories. Conclusions IBS patients often endorse episodic memories associated with symptom onset, and this recall seems to associate with more severe symptoms. Overgeneralization responses to negative stimuli may lead to worse bowel symptoms in those without episodic memories. IBS memory specificity may associate with qualitative differences in processing psychosocial experiences and might be important to IBS pathophysiology.
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Affiliation(s)
- Gregory S. Sayuk
- Division of Gastroenterology, Washington University School of Medicine, St. Louis, MO, United States
- Department of Psychiatry, Washington University School of Medicine, St. Louis, MO, United States
- St. Louis Veterans Affairs Medical Center, St. Louis, MO, United States
- *Correspondence: Gregory S. Sayuk
| | - Carol S. North
- The Altshuler Center for Education & Research, Metrocare Services, Dallas, TX, United States
- Department of Psychiatry, The University of Texas Southwestern Medical Center, Dallas, TX, United States
| | | | - Britt M. Gott
- Department of Psychiatry, Washington University School of Medicine, St. Louis, MO, United States
| | - David H. Alpers
- Division of Gastroenterology, Washington University School of Medicine, St. Louis, MO, United States
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Health-Related Quality of Life in Irritable Bowel Syndrome: A Systematic Review and Meta-analysis. Gastroenterol Nurs 2021; 43:E102-E122. [PMID: 32487960 DOI: 10.1097/sga.0000000000000530] [Citation(s) in RCA: 47] [Impact Index Per Article: 11.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/19/2022] Open
Abstract
Irritable bowel syndrome (IBS) affects up to 20% of the global population and is associated with impaired health-related quality of life (HRQoL). This systematic review and meta-analysis aimed to investigate differences in HRQoL of those with IBS compared with healthy controls and to examine whether HRQoL improves following psychological intervention. Online databases were searched for articles from 2002 to 2017. Studies were screened and data extracted according to predetermined criteria. A total of 4,154 citations were identified from which 36 were eligible for inclusion. Eight studies compared HRQoL of those with IBS (n = 822) with that of healthy individuals (n = 3,809). Those with IBS suffered significant impairment across all HRQoL domains compared with healthy individuals, with the majority of effects (Cohen's d) being moderate to large. Twenty-eight studies investigated HRQoL in IBS following psychological intervention (n = 1,308) relative to controls (n = 1,006). All HRQoL domains improved with large effects following treatment; however, maintenance of these effects was inconsistent. Those with IBS experience poorer HRQoL than the wider community; nevertheless, psychological interventions are associated with improved HRQoL across all domains. High-quality studies are needed to better inform gastroenterological nurses of which interventions are most efficacious in alleviating the burden of IBS, and which IBS subpopulations would benefit.
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Zhang Y, Wang X, Wang S, Yan Z, Li C, Zheng Y, Cui L. Heat Shock Protein 27 Regulates the Inflammatory Response of Intestinal Epithelial Cells by the Nuclear Factor-κB Pathway. Dig Dis Sci 2020; 65:3514-3520. [PMID: 32078087 DOI: 10.1007/s10620-020-06074-z] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/05/2019] [Accepted: 01/12/2020] [Indexed: 12/17/2022]
Abstract
BACKGROUND The specific and accurate pathogenesis of diarrhea-type irritable bowel syndrome is still unclear. AIMS We explored the mechanism of heat shock protein 27 (HSP27) in diarrhea-type irritable bowel syndrome to identify the key targets for the disease. METHODS The human colonic epithelial cell lines Caco-2 and NCM460 were pretreated with KRIBB3 (a phosphorylation inhibitor of HSP27) and then stimulated with lipopolysaccharide for different times. The apoptosis ratios of Caco-2 and NCM460 cells were examined with Annexin V/PI assays. Cell growth was determined using the cell counting kit-8 assay, and the expression levels of IL-1β and IL-6 in the cell supernatant were analyzed by ELISA. In addition, the expression levels of HSP27 and the nuclear factor-κB (NF-κB) signaling pathway were examined by Western blot assay. RESULTS Stimulation with lipopolysaccharide promoted the expression of HSP27 in colonic epithelial cells. HSP27 was phosphorylated at serine 78 and 82 after exposure to LPS. Apoptosis, growth inhibition, and inflammatory factor expression of lipopolysaccharide-induced colonic epithelial cells were greatly exacerbated by KRIBB3 treatment. In addition, KRIBB3 inhibited the phosphorylation of IκB-α and the activation of NF-κB. Gene silencing by small interfering RNA indicated that phosphorylation of HSP27 may regulate the NF-κB pathway. CONCLUSIONS HSP27 plays an important role in the inflammatory response of intestinal human colonic epithelial cells. HSP27 may protect intestinal epithelial cells against damage by regulating the NF-κB pathway.
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Affiliation(s)
- Yajun Zhang
- The Second School of Clinical Medicine, Southern Medical University, Guangzhou, 510280, Guangdong Province, China.,Department of Gastroenterology, The Sixth Medical Center, PLA General Hospital, NO. 6 Fucheng Road, Haidian District, Beijing, 100048, China
| | - Xiaohui Wang
- Department of Gastroenterology, The Sixth Medical Center, PLA General Hospital, NO. 6 Fucheng Road, Haidian District, Beijing, 100048, China
| | - Shaoxin Wang
- Department of Gastroenterology, The Sixth Medical Center, PLA General Hospital, NO. 6 Fucheng Road, Haidian District, Beijing, 100048, China
| | - Zhihui Yan
- Department of Gastroenterology, The Sixth Medical Center, PLA General Hospital, NO. 6 Fucheng Road, Haidian District, Beijing, 100048, China
| | - Chao Li
- Department of Gastroenterology, The Sixth Medical Center, PLA General Hospital, NO. 6 Fucheng Road, Haidian District, Beijing, 100048, China
| | - Yan Zheng
- Department of Gastroenterology, The Sixth Medical Center, PLA General Hospital, NO. 6 Fucheng Road, Haidian District, Beijing, 100048, China
| | - Lihong Cui
- The Second School of Clinical Medicine, Southern Medical University, Guangzhou, 510280, Guangdong Province, China. .,Department of Gastroenterology, The Sixth Medical Center, PLA General Hospital, NO. 6 Fucheng Road, Haidian District, Beijing, 100048, China.
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Zheng Q, Wang J, Zheng H, Lu L, Zhou S, Hao X, Zhang W, Li Y. What types of patients with chronic diarrhea benefit more from acupuncture treatment? A secondary analysis of a randomized controlled trial. Eur J Integr Med 2020. [DOI: 10.1016/j.eujim.2020.101098] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/24/2022]
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12
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Abel JL, Carson RT, Andrae DA. The impact of treatment with eluxadoline on health-related quality of life among adult patients with irritable bowel syndrome with diarrhea. Qual Life Res 2018; 28:369-377. [PMID: 30267294 PMCID: PMC6373309 DOI: 10.1007/s11136-018-2008-z] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 09/17/2018] [Indexed: 12/17/2022]
Abstract
Purpose Irritable bowel syndrome with diarrhea (IBS-D) significantly impacts health-related quality of life (HRQOL). This post hoc analysis of two phase III trials evaluated the effects of eluxadoline treatment on disease-specific HRQOL among patients with IBS-D. Methods Adult patients meeting Rome III criteria for IBS-D were randomized to oral eluxadoline (75 mg or 100 mg) or placebo twice daily in two phase III clinical trials for 52 weeks (IBS-3001) and 26 weeks (IBS-3002). The Irritable Bowel Syndrome Quality of Life (IBS-QOL) questionnaire assessed disease-specific HRQOL throughout the study. Changes from baseline to Week 26 in IBS-QOL total and subscale scores were analyzed using an analysis of covariance model. Percentages of IBS-QOL responders with ≥ 14- and 20-point changes were evaluated for IBS-QOL total and subscale scores. A longitudinal mixed-effects model was fitted to evaluate mean IBS-QOL total scores. A cumulative distribution function for change from baseline to Week 26 in IBS-QOL total score was plotted. Results Mean changes from baseline to Week 26 for the IBS-QOL total and all subscale scores were significantly higher for patients treated with eluxadoline (both doses) compared to placebo. A significantly greater proportion of eluxadoline-treated patients were responders compared to placebo. Mean and mixed-effects model estimated mean IBS-QOL total scores were consistently higher for eluxadoline versus placebo over 52 weeks. Conclusions Compared to placebo, twice-daily eluxadoline treatment significantly improved HRQOL among patients with IBS-D in two phase III trials.
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13
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Disrupted functional connectivity density in irritable bowel syndrome patients. Brain Imaging Behav 2018; 11:1812-1822. [PMID: 27848148 DOI: 10.1007/s11682-016-9653-z] [Citation(s) in RCA: 39] [Impact Index Per Article: 5.6] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/17/2022]
Abstract
Irritable bowel syndrome (IBS) is a common functional gastrointestinal disorder resulting from a dysregulation of the brain-gut axis. However, its exact neural substrate still remains unclear. This study investigated the changes of intrinsic whole brain functional connectivity pattern in IBS using functional connectivity density (FCD). We acquired resting-state functional magnetic resonance imaging (rs-fMRI) data from thirty-two IBS patients and thirty-two healthy controls. Functional connectivity density, a data-driven algorithm, was used to compute the long-range and short-range FCD values for each voxel in the brain of each subject, implying the amount of distant and local functional connections of cortical hubs. The FCD maps were compared between IBS patients and healthy controls. Pearson correlations analysis was also performed between abnormal FCD values and clinical/psychometric scores in patients. Compared to healthy controls, IBS patients showed concurrently decreased long- and short-range FCD in bilateral anterior midcingulate cortices (aMCC) and inferior parietal lobules (IPL), and decreased long-range FCD in right anterior insula, and decreased short-range FCD in bilateral prefrontal cortices, subgenual anterior cingulate cortices and caudates. IBS patients also had concurrently increased long- and short-range FCD mainly in primary sensorimotor cortices, as well as increased long-range FCD in right supplementary motor area and increased short-range FCD in occipital lobe. In addition, some regions with altered FCD showed abnormal functional connectivity in brain regions involved in pain matrix of IBS patients. Furthermore, the abnormal FCD values in right anterior insula and left caudate showed significant correlation with severity of symptoms and disease duration of IBS patients respectively. In conclusion, patients with IBS have widely disrupted FCD, which decreased in brain regions involved in homeostatic afferent network, emotional arouse, and cognitive regulation, while increased in regions associated with sensorimotor modulation. And the observed functional connectivity alterations unveiled complicated working patterns of pain matrix in IBS patients. This study may provide us with new insight into the underlying brain network topology of IBS.
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He X, Cui LH, Wang XH, Yan ZH, Li C, Gong SD, Zheng Y, Luo Z, Wang Y. Modulation of inflammation by toll-like receptor 4/nuclear factor-kappa B in diarrhea-predominant irritable bowel syndrome. Oncotarget 2017; 8:113957-113965. [PMID: 29371960 PMCID: PMC5768377 DOI: 10.18632/oncotarget.23045] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/12/2017] [Accepted: 11/16/2017] [Indexed: 12/12/2022] Open
Abstract
In order to investigate the function of toll-like receptor 4/nuclear factor-kappa B (TLR4/NF-κB) signal pathways in the pathogenesis of diarrhea-predominant irritable bowel syndrome (IBS-D), IBS-D animal models were established in wistar rats challenged with acute and chronic stresses (29 days). Wistar rats without stress-challenged were used as controls. IBS-D models were randomly divided into two groups: one was treated with normal saline, another group was treated with TLR4/NF-κB inhibitor, pyrrolidine dithiocarbamate (PDTC) (50mg/kg/week) for continuous four times. Our results demonstrate that continuous stresses can induce the characteristic symptoms of IBS-D, including high wet stool rate and intestinal flora imbalance. Further examinations of colon tissues show that the protein expression levels of TLR4 and NF-κB in IBS-D groups are higher than that in control group. The secretory levels of interleukin (IL-8), tumor necrosis factor α (TNFα), and myeloid differentiation factor 88 (MyD88) are significantly increased in IBS-D group. Administration with PDTC effectively downregulates levels of these inflammatory factors. In contrast, interleukin-10 (IL-10) is in an opposite alteration with lower levels in IBS-D groups and the PDTC treatment increases it to the levels as in control group. Moreover, inhibition of the TLR4/NF-κB by PDTC improves the microstructure of intestinal mucosa mainly by increasing the height of villi. Our results suggest that TLR4/NF-κB signal pathway plays an important role in the modulation of inflammatory responses in IBS-D, which might be a therapeutic target for the IBS-D. All of these findings also provide the evidence concerning an inherent linkage between the axis of stress/NF-κB/inflammation and IBS-D.
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Affiliation(s)
- Xing He
- Third Military Medical University, Chongqing 400038, China
| | - Li-Hong Cui
- Department of Gastroenterology, Navy General Hospital of PLA, Beijing 100048, China
| | - Xiao-Hui Wang
- Department of Gastroenterology, Navy General Hospital of PLA, Beijing 100048, China
| | - Zhi-Hui Yan
- Department of Gastroenterology, Navy General Hospital of PLA, Beijing 100048, China
| | - Chao Li
- Department of Gastroenterology, Navy General Hospital of PLA, Beijing 100048, China
| | - San-Dong Gong
- Department of Gastroenterology, Navy General Hospital of PLA, Beijing 100048, China
| | - Yan Zheng
- Department of Gastroenterology, Navy General Hospital of PLA, Beijing 100048, China
| | - Zhe Luo
- Department of Gastroenterology, Navy General Hospital of PLA, Beijing 100048, China
| | - Ying Wang
- Department of Gastroenterology, Navy General Hospital of PLA, Beijing 100048, China
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Kawoos Y, Wani ZA, Kadla SA, Shah IA, Hussain A, Dar MM, Margoob MA, Sideeq K. Psychiatric Co-morbidity in Patients With Irritable Bowel Syndrome at a Tertiary Care Center in Northern India. J Neurogastroenterol Motil 2017; 23:555-560. [PMID: 28738451 PMCID: PMC5628988 DOI: 10.5056/jnm16166] [Citation(s) in RCA: 24] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/13/2016] [Revised: 03/21/2017] [Accepted: 04/02/2017] [Indexed: 12/15/2022] Open
Abstract
Background/Aims Irritable bowel syndrome (IBS) is a chronic psycho-physiological disorder. It is considered to be the most common functional gastrointestinal disorder, and about 50–90% of IBS patients have associated psychiatric co-morbidity. We aimed to study psychiatric co-morbidities in patients with IBS visiting a tertiary care center. Methods This was a cross-sectional case-control study conducted over a duration of one and a half years from January 2014 to July 2015. Patients were selected from the out-patient department of gastroenterology. About 160 patients with IBS who fulfilled the inclusion criteria and who gave written informed consent were selected as study cases. The healthy attendants of cases were selected as controls. A total of 200 controls were selected. Rome-III criteria were used to diagnose IBS. For diagnosing psychiatric disorders, we used the Mini International Neuropsychiatric Interview Schedule Plus. Results Mean age of our cases and controls was 39.7 ± 11.4 and 37.7 ± 9.6 years, respectively. Females outnumbered males in our cases as well as their controls by a ratio of 2:1 approximately. Psychiatric disorders were seen in 84.4% of IBS patients as compared to 41.5% in controls. Major psychiatric disorders seen in our patients were generalized anxiety disorders (30.0%) and depression (28.0%). Conclusions The majority of patients with IBS who present to a tertiary care center have co-morbid psychiatric disorders. We need to screen these patients for such co-morbidities and develop a holistic approach for better outcome in such cases.
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Affiliation(s)
- Yuman Kawoos
- Department of Psychiatry, Government Medical College Srinagar, Srinagar, Jammu and Kashimir, India
| | - Zaid A Wani
- Department of Psychiatry, Government Medical College Srinagar, Srinagar, Jammu and Kashimir, India
| | - Showkat A Kadla
- Department of Gastroenterology, Government Medical College Srinagar, Srinagar, Jammu and Kashimir, India
| | - Irfan A Shah
- Department of Neurology, Sheri-Kashmir Institute of Medical Sciences, Srinagar, Jammu and Kashmir, India
| | - Arshad Hussain
- Department of Psychiatry, Government Medical College Srinagar, Srinagar, Jammu and Kashimir, India
| | - M Maqbool Dar
- Department of Psychiatry, Government Medical College Srinagar, Srinagar, Jammu and Kashimir, India
| | - Mushtaq A Margoob
- Department of Psychiatry, Government Medical College Srinagar, Srinagar, Jammu and Kashimir, India
| | - Kouser Sideeq
- Department of Preventive and Social Medicine, Government Medical College Srinagar, Srinagar, Jammu and Kashimir, India
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Harris LA, Baffy N. Modulation of the gut microbiota: a focus on treatments for irritable bowel syndrome. Postgrad Med 2017; 129:872-888. [PMID: 28936910 DOI: 10.1080/00325481.2017.1383819] [Citation(s) in RCA: 53] [Impact Index Per Article: 6.6] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/18/2022]
Abstract
Irritable bowel syndrome (IBS), which is characterized by recurrent abdominal pain and disordered bowel habits, is one of the most common functional bowel disorders. IBS is a substantial burden on both patient health-related quality of life and healthcare costs. Several pathophysiologic mechanisms have been postulated for the occurrence of IBS, including altered gastrointestinal motility, visceral hypersensitivity, changes in gut permeability, immune activation, gut-brain dysregulation, central nervous system dysfunction, and changes in the gut microbiota. Of note, both qualitative and quantitative differences have been observed in the gut microbiota of a population with IBS versus a healthy population. Because of the substantial interest in the gut microbiota and its role as a therapeutic target in IBS, this article provides an overview of specific interventions with the potential to modulate the gut microbiota in IBS, including elimination diets, prebiotics, probiotics, synbiotics, and nonsystemic antibiotics. Although probiotics and synbiotics are generally well tolerated, differences in the composition and concentration of different bacterial species and inclusion or exclusion of prebiotic components varies widely across studies and has prevented strong recommendations on their use in IBS. For nonsystemic antibiotics, rifaximin is indicated in the United States for the treatment of IBS with diarrhea in adults and has been shown to be efficacious and well tolerated in well-designed clinical trials. Overall, more consistent evidence is needed regarding the efficacy and safety of elimination diets, prebiotics, probiotics, and synbiotics for the treatment of patients with IBS. Furthermore, additional well-designed studies are needed that examine alterations in the gut microbiota that occur with these interventions and their potential associations with clinical symptoms of IBS.
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Affiliation(s)
- Lucinda A Harris
- a Division of Gastroenterology & Hepatology , Mayo Clinic , Scottsdale , AZ , USA
| | - Noemi Baffy
- a Division of Gastroenterology & Hepatology , Mayo Clinic , Scottsdale , AZ , USA
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Hubert S, Chadwick A, Wacher V, Coughlin O, Kokai-Kun J, Bristol A. Development of a Modified-Release Formulation of Lovastatin Targeted to Intestinal Methanogens Implicated in Irritable Bowel Syndrome With Constipation. J Pharm Sci 2017; 107:662-671. [PMID: 28989013 DOI: 10.1016/j.xphs.2017.09.028] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/06/2017] [Revised: 09/18/2017] [Accepted: 09/19/2017] [Indexed: 12/19/2022]
Abstract
There is growing evidence that methane production, predominantly by Methanobrevibacter smithii, in the intestines is a cause of constipation, pain, and bloating in irritable bowel syndrome with constipation (IBS-C). M smithii resides primarily in the large intestine but can also colonize the small intestine. In vitro studies found that the prodrug lactone form of lovastatin, found in cholesterol-lowering drugs, inhibited methane production in stool samples from patients with IBS-C. However, the cholesterol-lowering lovastatin β-hydroxyacid was ineffective at inhibiting methane production in this system. A considerable amount of lovastatin is converted to hydroxyacid in the stomach and is absorbed. It was hypothesized that galenic innovations could protect lovastatin from the stomach and allow release in 2 strategic locations, the duodenum and the ileocecal region, to reach M smithii. The desired release profile was achieved by developing an oral dosage form containing lovastatin and coated with 2 different enteric polymers that enabled a pH-dependent "dual pulse" drug release. Combinations of the 2 coated tablets were encapsulated together to deliver the desired amount of lovastatin to the targeted intestinal locations. The capsules have been tested in vitro and in vivo and show promise in treating IBS-C.
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Affiliation(s)
- Steven Hubert
- Synthetic Biologics, Inc., 9605 Medical Center Drive, Suite 270, Rockville, Maryland 20850.
| | - Alan Chadwick
- Aesica Formulation Development, Biocity, Pennyfoot Street, Nottingham NG1 1GF, UK
| | - Vince Wacher
- Synthetic Biologics, Inc., 9605 Medical Center Drive, Suite 270, Rockville, Maryland 20850
| | - Olivia Coughlin
- Synthetic Biologics, Inc., 9605 Medical Center Drive, Suite 270, Rockville, Maryland 20850
| | - John Kokai-Kun
- Synthetic Biologics, Inc., 9605 Medical Center Drive, Suite 270, Rockville, Maryland 20850
| | - Andrew Bristol
- Synthetic Biologics, Inc., 9605 Medical Center Drive, Suite 270, Rockville, Maryland 20850
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Özdener AE, Rivkin A. Eluxadoline in the treatment of diarrhea-predominant irritable bowel syndrome. DRUG DESIGN DEVELOPMENT AND THERAPY 2017; 11:2827-2840. [PMID: 29033544 PMCID: PMC5628681 DOI: 10.2147/dddt.s127405] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
Eluxadoline is a novel drug approved for the management of diarrhea predominant irritable bowel syndrome (IBS-D). It has unique pharmacology and works on three different opioid receptors. Several Phase II and III clinical trials have demonstrated eluxadoline’s efficacy in reducing symptoms related to IBS-D. Clinical trial results and postmarketing reports show a risk of pancreatitis in patients without a gallbladder or those abusing alcohol. This review article will include information on clinical trial results related to IBS-D management as well as eluxadoline’s limitations.
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Affiliation(s)
- Ayşe Elif Özdener
- School of Pharmacy and Health Sciences, Fairleigh Dickinson University, Florham Park, NJ, USA
| | - Anastasia Rivkin
- School of Pharmacy and Health Sciences, Fairleigh Dickinson University, Florham Park, NJ, USA
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Corsetti M, Whorwell P. New therapeutic options for IBS: the role of the first in class mixed µ- opioid receptor agonist and δ-opioid receptor antagonist (mudelta) eluxadoline. Expert Rev Gastroenterol Hepatol 2017; 11:285-292. [PMID: 28276811 DOI: 10.1080/17474124.2017.1298442] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/16/2022]
Abstract
Irritable bowel syndrome (IBS) is a prevalent functional gastrointestinal disorder which represents a major cost to healthcare services. IBS-D patients represent about one-third of the IBS population and are currently treated with antispasmodics, loperamide, bile acid sequestrants and antidepressants. Alosetron and rifaximin are also available in USA, ramosetron in Japan, Korea and Thailand and ondansetron as an off-label treatment. Areas covered: This article focuses on eluxadoline, a novel pharmacological agent that has recently been approved by both the FDA and EMA for treatment of patients with IBS-D. Expert commentary: The efficacy and safety of eluxadoline in treating bowel habit alterations and pain, both in the short and long-term, make the drug a welcome addition to our therapeutic alternatives in IBS-D. Its positioning in any IBS algorithm will depend on the 'real world' prevalence of the small risk of sphincter of Oddi spasm and mild pancreatitis.
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Affiliation(s)
- Maura Corsetti
- a Nottingham Digestive Diseases Biomedical Research Unit , National Institute for Health Research, Nottingham University Hospitals NHS Trust, University of Nottingham , Nottingham , UK
| | - Peter Whorwell
- b Centre for Gastrointestinal Sciences , University of Manchester , Manchester , UK
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Kibune Nagasako C, Garcia Montes C, Silva Lorena SL, Mesquita MA. Irritable bowel syndrome subtypes: Clinical and psychological features, body mass index and comorbidities. REVISTA ESPANOLA DE ENFERMEDADES DIGESTIVAS 2017; 108:59-64. [PMID: 26838486 DOI: 10.17235/reed.2015.3979/2015] [Citation(s) in RCA: 25] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
BACKGROUND Irritable bowel syndrome (IBS) is classified into subtypes according to bowel habit. OBJECTIVE To investigate whether there are differences in clinical features, comorbidities, anxiety, depression and body mass index (BMI) among IBS subtypes. METHODS The study group included 113 consecutive patients (mean age: 48 ± 11 years; females: 94) with the diagnosis of IBS. All of them answered a structured questionnaire for demographic and clinical data and underwent upper endoscopy. Anxiety and depression were assessed by the Hospital Anxiety and Depression scale (HAD). RESULTS The distribution of subtypes was: IBS-diarrhea (IBS-D), 46%; IBS-constipation (IBS-C), 32%, and mixed IBS (IBS-M), 22%. IBS overlap with gastroesophageal reflux disease (GERD), functional dyspepsia, chronic headache and fibromyalgia occurred in 65.5%, 48.7%, 40.7% and 22.1% of patients, respectively. Anxiety and/or depression were found in 81.5%. Comparisons among subgroups showed that bloating was significantly associated with IBS-M compared to IBS-D (odds ratio-OR-5.6). Straining was more likely to be reported by IBS-M (OR 15.3) and IBS-C (OR 12.0) compared to IBS-D patients, while urgency was associated with both IBS-M (OR 19.7) and IBS-D (OR 14.2) compared to IBS-C. In addition, IBS-M patients were more likely to present GERD than IBS-D (OR 6.7) and higher scores for anxiety than IBS-C patients (OR 1.2). BMI values did not differ between IBS-D and IBS-C. CONCLUSION IBS-M is characterized by symptoms frequently reported by both IBS-C (straining) and IBS-D (urgency), higher levels of anxiety, and high prevalence of comorbidities. These features should be considered in the clinical management of this subgroup.
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Lucak S, Chang L, Halpert A, Harris LA. Current and emergent pharmacologic treatments for irritable bowel syndrome with diarrhea: evidence-based treatment in practice. Therap Adv Gastroenterol 2017; 10:253-275. [PMID: 28203283 PMCID: PMC5298476 DOI: 10.1177/1756283x16663396] [Citation(s) in RCA: 34] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/04/2023] Open
Abstract
Irritable bowel syndrome with diarrhea (IBS-D) is a common, chronic functional gastrointestinal disorder with symptoms that can be distressing for patients and often result in substantially impaired quality of life. This review focuses on providing clinicians with information on practical, evidence-based treatment for IBS-D. Current therapies commonly used for the treatment of IBS-D, including pharmacologic and nonpharmacologic interventions, are briefly reviewed, followed by discussion of the emergent pharmacologic treatments (rifaximin and eluxadoline) and medical foods (IBgard® and EnteraGam®). Given the lack of a standard treatment algorithm for IBS-D and the emergence of new pharmacologic therapies, treatment needs to be tailored to the individual patient and take into account the severity of disease. In this context, the latter part of this manuscript examines how treatments for IBS-D can be used in clinical practice by presenting three patient case scenarios with varying degrees of IBS-D severity. For each case, the patient's medical history and clinical presentation are related to the Rome Foundation multidimensional clinical profile (MDCP) and potential treatment options with current and emergent therapies are reviewed. The interplay of gastrointestinal symptoms and their psychosocial impact, as well as the importance of a patient-centered approach to therapy, are discussed. Consideration is given to the potential need for combination therapies and how emergent treatments could fit into the treatment pathway for mild, moderate, and severe cases of IBS-D in clinical practice.
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Affiliation(s)
- Susan Lucak
- Division of Digestive and Liver Diseases, Department of Medicine, Weill Cornell Medicine, 903 Park Avenue, First Floor, New York, NY 10075, USA
| | - Lin Chang
- Division of Digestive Diseases, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA, USA
| | - Albena Halpert
- Section of Gastroenterology & Hepatology, Boston Medical Center, Boston, MA, USA
| | - Lucinda A. Harris
- Division of Gastroenterology and Hepatology, Department of Medicine, Mayo College of Medicine, Scottsdale, AZ, USA
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Safety of Eluxadoline in Patients with Irritable Bowel Syndrome with Diarrhea. Am J Gastroenterol 2017; 112:365-374. [PMID: 27922029 PMCID: PMC5318664 DOI: 10.1038/ajg.2016.542] [Citation(s) in RCA: 64] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/02/2016] [Accepted: 10/01/2016] [Indexed: 02/06/2023]
Abstract
OBJECTIVES Eluxadoline is a mixed μ-opioid receptor (OR) and κ-OR agonist and δ-OR antagonist, approved for the treatment of irritable bowel syndrome with diarrhea (IBS-D). This analysis evaluated the safety and tolerability of eluxadoline 75 and 100 mg twice daily (BID) in one Phase 2 (IBS-2001) and two Phase 3 (IBS-3001 and IBS-3002) studies. METHODS Adults with IBS-D (Rome III criteria) were randomized to placebo or eluxadoline (75 or 100 mg) BID for 12 (IBS-2001), 26 (IBS-3002), or 52 (IBS-3001) weeks. Safety data were pooled. Adverse events (AEs) were assessed, with special focus on opioid-related AEs, including suspected sphincter of Oddi spasm (SOS) events. RESULTS 2,776 patients were included in the enrolled set; the safety set comprised 2,814 patients, based on actual treatments received. The most frequent AEs in the placebo and eluxadoline 75 and 100 mg groups were constipation (2.5, 7.4, and 8.1%, respectively) and nausea (5.0, 8.1, and 7.1%, respectively); discontinuation due to constipation was uncommon (0.3, 1.1, and 1.5%, respectively). Ten SOS events (10/1,839; 0.5%) occurred in eluxadoline-treated patients, manifesting as acute abdominal pain with elevated aminotransferases or lipase, or pancreatitis; all occurred in patients without a gallbladder. Eight of these events occurred with the higher dose of eluxadoline, within 1 week of initiation of therapy, and all resolved with eluxadoline discontinuation. There were five events independently adjudicated as pancreatitis not associated with SOS, three of which were associated with heavy alcohol use. CONCLUSIONS Eluxadoline was well tolerated in Phase 2 and 3 trials, with constipation and nausea the most common AEs. Consistent with the known adverse effects of opioid agonists, clinically apparent SOS events were observed in eluxadoline-treated patients. All occurred in patients without a gallbladder and the majority were observed in patients on the higher dose of eluxadoline, suggesting a possible association.
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Mosaffa-Jahromi M, Lankarani KB, Pasalar M, Afsharypuor S, Tamaddon AM. Efficacy and safety of enteric coated capsules of anise oil to treat irritable bowel syndrome. JOURNAL OF ETHNOPHARMACOLOGY 2016; 194:937-946. [PMID: 27815079 DOI: 10.1016/j.jep.2016.10.083] [Citation(s) in RCA: 37] [Impact Index Per Article: 4.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 05/22/2016] [Revised: 10/07/2016] [Accepted: 10/29/2016] [Indexed: 02/08/2023]
Abstract
ETHNOPHARMACOLOGICAL RELEVANCE Anise is a well-recognized plant in Traditional Persian Medicine (TPM) sources. Anise oil has been suggested for the treatment of bowel disorders in Persian medical textbooks. Based on TPM scholars, this ingredient has a favorable effect on gastrointestinal diseases. We did this trial to determine the efficacy and safety of enteric coated capsules of anise oil for clinical symptoms of irritable bowel syndrome (IBS). METHODS AND MATERIALS This three-armed double-blind clinical trial was carried out from August 2014 to February 2015. 120 patients were divided into three groups by block randomization: AnisEncap, placebo and Colpermin®. Patients in each group received 3 similar capsules per day for 4 weeks. The primary outcome was measured as a visual analogue scale (VAS) score, and the secondary outcome was assessed with an IBS-quality of life questionnaire. Chi-squared tests were used for categorical variables and t-tests to compare continuous variables. RESULTS There were no significant differences in demographic characteristics among the three groups. According to intention-to-treat sample analysis, 75% of patients in the treatment group, 35% in the placebo group and 52.5% in active control group were free from IBS symptoms (P<0.001). The effectiveness of AnisEncap in improving IBS symptoms (abdominal discomfort or pain, bloating, diarrhea, constipation severity, difficulty in defecation, gastroesophageal reflux, headache, tiredness, overall satisfaction and quality of life) was significantly greater than placebo or Colpermin® after the 4-week treatment period and the 2-week follow-up period (P<0.0001). The number needed to treat for enteric coated capsules of anise oil was 4, which indicated significantly superior efficacy compared to the other two groups (P<0.001). CONCLUSION The effectiveness of AnisEncap was superior to that of placebo or Colpermin® in patients with IBS. Further studies are suggested to find the main mechanism of action of anise oil in this regard.
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Affiliation(s)
- Maryam Mosaffa-Jahromi
- Research Center for Traditional Medicine and History of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran
| | | | - Mehdi Pasalar
- Research Center for Traditional Medicine and History of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran.
| | - Suleiman Afsharypuor
- Department of Pharmacognosy, School of Pharmacy, Isfahan University of Medical Sciences, Isfahan, Iran
| | - Ali-Mohammad Tamaddon
- Center for Nanotechnology in Drug Delivery, School of Pharmacy, Shiraz University of Medical Sciences, Shiraz, Iran.
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Corticotropin-releasing hormone receptor 1 (CRH-R1) polymorphisms are associated with irritable bowel syndrome and acoustic startle response. Psychoneuroendocrinology 2016; 73:133-141. [PMID: 27497153 PMCID: PMC5048544 DOI: 10.1016/j.psyneuen.2016.07.204] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/08/2016] [Revised: 06/23/2016] [Accepted: 07/13/2016] [Indexed: 12/19/2022]
Abstract
BACKGROUND Corticotropin-releasing hormone receptor 1 (CRH-R1) in the amygdala and the stria terminalis plays an important role in the activation of central stress circuits. Genetic factors may contribute to the hyperresponsiveness of these circuits in irritable bowel syndrome (IBS). AIMS To determine if CRH-R1 SNPs are associated with: (1) a diagnosis of IBS, (2) gastrointestinal (GI) symptoms, and (3) acoustic startle response (ASR) to threat, which is mediated by the amygdala via CRH. METHODS Three CRH-R1 SNPS (rs110402, rs242924, and rs7209436) were genotyped using salivary DNA from IBS and healthy control subjects (HCs). Eye blink ASR was obtained during safe (no shock), anticipation (abdominal shock may soon occur) and threat (abdominal shock likely) conditions in a subset of subjects. Associations between each SNP with IBS status, clinical traits and ASR were measured. RESULTS 235 IBS patients (mean age 37.5 yrs, 74% F) and 264 HCs (mean age 32.1 yrs, 70% F) were studied. Of these, 57 IBS and 41 HCs underwent the ASR protocol. The presence of IBS was associated with the major allele for all three CRH-R1 SNPs (p=0.009-0.025). Within IBS, the major allele for all three SNPs (p=0.017-0.065) was associated with GI symptom anxiety scores. Within subjects with at least one copy of the major allele for the CRH-R1 SNPs, IBS had significantly lower ASR compared to HCs during threat conditions (p=0.001-0.002). Within IBS, CRH-R1 SNPs were associated with a graded increase in ASR to threat (p=0.007-0.008). CONCLUSION These findings support that CRH-R1 contributes to the dysregulated stress responsiveness in IBS.
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Brown K, Scott-Hoy B, Jennings LW. Response of irritable bowel syndrome with constipation patients administered a combined quebracho/conker tree/ M. balsamea Willd extract. World J Gastrointest Pharmacol Ther 2016; 7:463-468. [PMID: 27602249 PMCID: PMC4986399 DOI: 10.4292/wjgpt.v7.i3.463] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/11/2016] [Revised: 05/08/2016] [Accepted: 06/16/2016] [Indexed: 02/07/2023] Open
Abstract
The aim of this case series was to retrospectively examine the symptom response of irritable bowel syndrome with constipation (IBS-C) patients administered an herbal extract in a real-world setting. Twenty-four IBS-C patients in a community office practice were provided a combination over-the-counter dietary supplement composed of quebracho (150 mg), conker tree (470 mg) and M. balsamea Willd (0.2 mL) extracts (Atrantil™) and chose to take the formulation for a minimum of 2 wk in an attempt to manage their symptoms. Patient responses to the supplement were assessed by visual analogue scale (VAS) for abdominal pain, constipation and bloating at baseline and at 2 wk as part of standard-of-care. Patient scores from VAS assessments recorded in medical chart data were retrospectively compiled and assessed for the effects of the combined extract on symptoms. Sign tests were used to compare changes from baseline to 2 wk of taking the extract. Significance was defined as P < 0.05. Twenty-one of 24 patients (88%) responded to the dietary supplement as measured by individual improvements in VAS scores for abdominal pain, bloating and constipation symptoms comparing scores prior to administration of the extract against those reported after 2 wk. There were also significant improvements in individual as well as mean VAS scores after 2 wk of administration of the combined extract compared to baseline for abdominal pain [8.0 (6.5, 9.0) vs 2.0 (1.0, 3.0), P < 0.001], bloating [8.0 (7.0, 9.0) vs 1.0 (1.0, 2.0), P < 0.001] and constipation [6.0 (3.0, 8.0) vs 2.0 (1.0, 3.0), P < 0.001], respectively. In addition, 21 of 24 patients expressed improved quality of life while taking the formulation. There were no reported side effects to administration of the dietary supplement in this practice population suggesting excellent tolerance of the formulation. This pilot retrospective analysis of symptom scores from patients before and after consuming a quebracho/conker tree/M. balsamea Willd extract may support the formulation’s use in IBS-C.
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Foxx-Orenstein AE. New and emerging therapies for the treatment of irritable bowel syndrome: an update for gastroenterologists. Therap Adv Gastroenterol 2016; 9:354-75. [PMID: 27134665 PMCID: PMC4830102 DOI: 10.1177/1756283x16633050] [Citation(s) in RCA: 31] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/04/2023] Open
Abstract
Irritable bowel syndrome is a functional bowel disorder with gastrointestinal symptoms (e.g. abdominal pain, straining, urgency, incomplete evacuation, nausea, and bloating) that occur alongside bowel function alterations (i.e. constipation, diarrhea, or both). Patients with irritable bowel syndrome may also experience comorbid anxiety and depression. Irritable bowel syndrome is common, with a prevalence estimated between 3% and 28%, affecting patient health and quality of life. Patients with moderate or severe irritable bowel syndrome generally seek medical care, whereas those with milder symptoms may choose self-management. Most patients with irritable bowel syndrome receive outpatient care, but irritable bowel syndrome-related hospitalizations do occur. The pathophysiology of irritable bowel syndrome is multifactorial (i.e. genetics, immune components, changes in the gut microbiota, disturbances in physiologic stress response systems, and psychosocial factors). Management of irritable bowel syndrome can include lifestyle changes, dietary interventions, counseling, psychologic medication, and agents that affect gastrointestinal motility. A number of therapies have emerged in recent years with clinical trial data demonstrating efficacy and safety for patients with irritable bowel syndrome, including agents that target gastrointestinal motility (i.e. linaclotide), gastrointestinal opioid receptors (i.e. asimadoline, eluxadoline), and gut microbiota (i.e. rifaximin). Linaclotide has been shown to significantly improve stool frequency and abdominal pain compared with placebo in constipation-predominant irritable bowel syndrome (number needed to treat, 5.1). Asimadoline shows efficacy in patients with moderate-to-severe irritable bowel syndrome-related pain. Rifaximin provided adequate relief of global irritable bowel syndrome symptoms versus placebo for a significantly greater percentage of patients with diarrhea-predominant irritable bowel syndrome (p < 0.001). Management that encompasses all aspects of irritable bowel syndrome (gastrointestinal symptoms) and comorbid psychologic symptoms (e.g. anxiety or depression) is important for improving overall patient health and well-being.
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Affiliation(s)
- Amy E. Foxx-Orenstein
- Mayo Clinic Division of Gastroenterology and Hepatology, 13400 East Shea Boulevard, Scottsdale, AZ 85259, USA
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Matuchansky C. Irritable Bowel Syndrome: Modern Concepts and Management Options. Am J Med 2016; 129:e39. [PMID: 26777616 DOI: 10.1016/j.amjmed.2015.08.028] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/09/2015] [Accepted: 08/10/2015] [Indexed: 11/25/2022]
Affiliation(s)
- Claude Matuchansky
- Emeritus Professor of Medicine, Lariboisière-St Louis Faculty of Medicine, Paris Diderot University, Paris, France
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Orand A, Gupta A, Shih W, Presson AP, Hammer C, Niesler B, Heendeniya N, Mayer EA, Chang L. Catecholaminergic Gene Polymorphisms Are Associated with GI Symptoms and Morphological Brain Changes in Irritable Bowel Syndrome. PLoS One 2015; 10:e0135910. [PMID: 26288143 PMCID: PMC4546052 DOI: 10.1371/journal.pone.0135910] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/10/2014] [Accepted: 07/28/2015] [Indexed: 01/16/2023] Open
Abstract
BACKGROUND Genetic and environmental factors contribute to the pathophysiology of irritable bowel syndrome (IBS). In particular, early adverse life events (EALs) and the catecholaminergic system have been implicated. AIMS To investigate whether catecholaminergic SNPs with or without interacting with EALs are associated with: 1) a diagnosis of IBS, 2) IBS symptoms and 3) morphological alterations in brain regions associated with somatosensory, viscerosensory, and interoceptive processes. METHODS In 277 IBS and 382 healthy control subjects (HCs), 11 SNPs in genes of the catecholaminergic signaling pathway were genotyped. A subset (121 IBS, 209 HCs) underwent structural brain imaging (magnetic resonance imaging [MRI]). Logistic and linear regressions evaluated each SNP separately and their interactions with EALs in predicting IBS and GI symptom severity, respectively. General linear models determined grey matter (GM) alterations from the SNPs and EALs that were predictive of IBS. RESULTS 1) DIAGNOSIS: There were no statistically significant associations between the SNPs and IBS status with or without the interaction with EAL after adjusting for multiple comparisons. 2) SYMPTOMS: GI symptom severity was associated with ADRA1D rs1556832 (P = 0.010). 3) Brain morphometry: In IBS, the homozygous genotype of the major ADRA1D allele was associated with GM increases in somatosensory regions (FDR q = 0.022), left precentral gyrus (q = 0.045), and right hippocampus (q = 0.009). In individuals with increasing sexual abuse scores, the ADRAβ2 SNP was associated with GM changes in the left posterior insula (q = 0.004) and left putamen volume (q = 0.029). CONCLUSION In IBS, catecholaminergic SNPs are associated with symptom severity and morphological changes in brain regions concerned with sensory processing and modulation and affect regulation. Thus, certain adrenergic receptor genes may facilitate or worsen IBS symptoms.
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Affiliation(s)
- Alexa Orand
- Oppenheimer Center for the Neurobiology of Stress, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, California, United States of America
| | - Arpana Gupta
- Oppenheimer Center for the Neurobiology of Stress, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, California, United States of America
| | - Wendy Shih
- Department of Biostatistics, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, California, United States of America
| | - Angela P. Presson
- Department of Biostatistics, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, California, United States of America
- Division of Epidemiology, Department of Internal Medicine, University of Utah, Salt Lake City, Utah, United States of America
| | - Christian Hammer
- Institute of Human Genetics, Department of Human Molecular Genetics, University of Heidelberg, Heidelberg, Germany
| | - Beate Niesler
- Institute of Human Genetics, Department of Human Molecular Genetics, University of Heidelberg, Heidelberg, Germany
| | - Nuwanthi Heendeniya
- Oppenheimer Center for the Neurobiology of Stress, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, California, United States of America
| | - Emeran A. Mayer
- Oppenheimer Center for the Neurobiology of Stress, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, California, United States of America
| | - Lin Chang
- Oppenheimer Center for the Neurobiology of Stress, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, California, United States of America
- * E-mail:
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Abstract
BACKGROUND Functional bowel disorders are recognized as being common, but remain very difficult to diagnose accurately and to differentiate from one another, despite their significant impact on the quality of life of patients.The aim of this study was to evaluate whether the clinical sign of 'floating stools' is associated with psychological disorders, colonic transit time, or other specific bowel disorders as defined by the Rome III diagnostic criteria. MATERIALS AND METHODS A total of 1252 consecutive patients, referred for and found to have functional gastrointestinal disorders, filled in a standard clinical questionnaire on the basis of the Rome III diagnostic criteria and were asked to provide information on the presence of floating stools. Overall, 344 of these scored positive for functional bowel disorders and underwent psychometric testing and colonic transit time studies. RESULTS Floating stools were reported by 26% of functional bowel disorder patients and 3% of the other functional gastrointestinal disorder patients (P<0.001). The basic demographic characteristics, psychometric evaluation scores, Bristol stool form scales, and total and segmental colonic transit times were not statistically different according to the presence or not of floating stools in these patients. Logistic regression showed that mixed irritable bowel syndrome was the only functional gastrointestinal disorder associated independently with floating stools (P=0.003). CONCLUSION Floating stools are a characteristic of patients with mixed irritable bowel syndrome.
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Hungin APS, Becher A, Cayley B, Heidelbaugh JJ, Muris JWM, Rubin G, Seifert B, Russell A, De Wit NJ. Irritable bowel syndrome: an integrated explanatory model for clinical practice. Neurogastroenterol Motil 2015; 27:750-63. [PMID: 25703486 DOI: 10.1111/nmo.12524] [Citation(s) in RCA: 18] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/30/2014] [Accepted: 01/13/2015] [Indexed: 12/13/2022]
Abstract
BACKGROUND Although irritable bowel syndrome (IBS) is a symptom-based diagnosis, clinicians' management of and communication about the disorder is often hampered by an unclear conceptual understanding of the nature of the problem. We aimed to elucidate an integrated explanatory model (EM) for IBS from the existing literature for pragmatic use in the clinical setting. METHODS Systematic and exploratory literature searches were performed in PubMed to identify publications on IBS and EMs. KEY RESULTS The searches did not identify a single, integrated EM for IBS. However, three main hypotheses were elucidated that could provide components with which to develop an IBS EM: (i) altered peripheral regulation of gut function (including sensory and secretory mechanisms); (ii) altered brain-gut signaling (including visceral hypersensitivity); and (iii) psychological distress. Genetic polymorphisms and epigenetic changes may, to some degree, underlie the etiology and pathophysiology of IBS and could increase the susceptibility to developing the disorder. The three model components also fit into one integrated explanation for abdominal symptoms and changes in stool habit. Additionally, IBS may share a common pathophysiological mechanism with other associated functional syndromes. CONCLUSIONS & INFERENCES It was possible to elucidate an integrated, three-component EM as a basis for clinicians to conceptualize the nature of IBS, with the potential to contribute to better diagnosis and management, and dialog with sufferers.
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Affiliation(s)
- A P S Hungin
- School of Medicine, Pharmacy and Health, Durham University, Stockton-on-Tees, UK
| | - A Becher
- School of Medicine, Pharmacy and Health, Durham University, Stockton-on-Tees, UK.,Research and Evaluation Unit, Oxford PharmaGenesis Ltd, Oxford, UK
| | - B Cayley
- Department of Family Medicine, University of Wisconsin, Madison, WI, USA
| | - J J Heidelbaugh
- Departments of Family Medicine and Urology, Medical School, University of Michigan, Ann Arbor, MI, USA
| | - J W M Muris
- Department of Family Medicine, Care and Public Health Research Institute (CAPHRI), Maastricht University, Maastricht, The Netherlands
| | - G Rubin
- School of Medicine, Pharmacy and Health, Durham University, Stockton-on-Tees, UK
| | - B Seifert
- Institute of General Practice, Charles University, Praha, Czech Republic
| | - A Russell
- Department of Anthropology, Durham University, Durham, UK
| | - N J De Wit
- Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht, The Netherlands
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Chang L, Lembo A, Sultan S. American Gastroenterological Association Institute Technical Review on the pharmacological management of irritable bowel syndrome. Gastroenterology 2014; 147:1149-72.e2. [PMID: 25224525 DOI: 10.1053/j.gastro.2014.09.002] [Citation(s) in RCA: 97] [Impact Index Per Article: 8.8] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Affiliation(s)
- Lin Chang
- Division of Digestive Diseases, David Geffen School of Medicine University of California, Los Angeles, Los Angeles, California
| | - Anthony Lembo
- Harvard Medical School, Beth Israel Deaconess, Boston, Massachusetts
| | - Shahnaz Sultan
- Department of Veterans Affairs Medical Center, Gastroenterology Section, North Florida/South Georgia Veterans Health System, Division of Gastroenterology, Hepatology, and Nutrition, University of Florida, Gainesville, Florida; Minneapolis Veterans Affairs Health System, University of Minnesota, Minneapolis, Minnesota
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Choi YJ, Hwang SW, Kim N, Park JH, Oh JC, Lee DH. Association Between SLC6A4 Serotonin Transporter Gene Lainked Polymorphic Region and ADRA2A -1291C>G and Irritable Bowel Syndrome in Korea. J Neurogastroenterol Motil 2014; 20:388-99. [PMID: 24917480 PMCID: PMC4102162 DOI: 10.5056/jnm14020] [Citation(s) in RCA: 21] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/25/2014] [Revised: 04/26/2014] [Accepted: 04/28/2014] [Indexed: 12/11/2022] Open
Abstract
Background/Aims Despite numerous studies on the relation of genetic polymorphisms with irritable bowel syndrome (IBS), the results still remain inconclusive. The aim of this study was to assess the possible association between SLC6A4 serotonin transporter gene linked polymorphic region (5-HTTLPR), ADRA2A −1291C>G, GNB3 825C>T, CCK1R intron 779T>C and TRPV1 945G>C polymorphisms and IBS based on Rome III criteria in Korea. Methods Study subjects were prospectively recruited from visitors to Seoul National University Bundang Hospital between July 2009 and January 2014. Ninety-nine IBS patients and 171 healthy controls were enrolled. Polymorphisms of above-mentioned 5 genes were genotyped. Serum serotonin from 101 participants was measured by ELISA and compared according to SLC6A4 5-HTTLPR polymorphisms and IBS subtypes. Results Regarding SLC6A4 5-HTTLPR polymorphism, L/L genotype was significantly associated with the total IBS, constipation predominant IBS (IBS-C) and mixture of diarrhea and constipation IBS (IBS-M) (adjusted OR: 4.35, 95% CI: 1.04–16.67; adjusted OR: 11.11, 95% CI: 1.69–50.00 and adjusted OR: 5.56, 95% CI: 1.05–33.33, respectively). Carrying ADRA2A −1291G allele was significantly associated with total IBS and diarrhea predominant IBS (adjusted OR: 3.37, 95% CI: 1.16–9.77 and adjusted OR: 5.64, 95% CI: 1.18–27.01, respectively). IBS-C patients showed reduced level of serum serotonin compared to controls and patients with diarrhea predominant IBS (50.2 ng/mL vs. 69.0 ng/mL and 92.9 ng/mL, P = 0.017 and P = 0.001, respectively). Conclusions Genetic polymorphisms of SLC6A4 5-HTTLPR and ADRA2A −1291C>G could be one of the pathophysiological factors of IBS in Korea. Reduced serum serotonin shown in the IBS-C group suggested a role of serotonin in IBS, but large study is needed for confirming genotypic difference in serum serotonin level.
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Affiliation(s)
- Yoon Jin Choi
- Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, Gyeonggi-do, Korea
| | - Sung Wook Hwang
- Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul, Korea
| | - Nayoung Kim
- Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, Gyeonggi-do, Korea; Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul, Korea
| | - Ji Hyun Park
- Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul, Korea
| | - Jane C Oh
- Yonsei Plus Clinic, Seongnam, Gyeonggi-do, Korea
| | - Dong Ho Lee
- Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, Gyeonggi-do, Korea; Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul, Korea
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Buckley MM, O’Mahony SM, O’Malley D. Convergence of neuro-endocrine-immune pathways in the pathophysiology of irritable bowel syndrome. World J Gastroenterol 2014; 20:8846-8858. [PMID: 25083058 PMCID: PMC4112880 DOI: 10.3748/wjg.v20.i27.8846] [Citation(s) in RCA: 24] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/25/2013] [Revised: 02/13/2014] [Accepted: 05/28/2014] [Indexed: 02/06/2023] Open
Abstract
Disordered signalling between the brain and the gut are generally accepted to underlie the functional bowel disorder, irritable bowel syndrome (IBS). However, partly due to the lack of disease-defining biomarkers, understanding the aetiology of this complex and multifactorial disease remains elusive. This common gastrointestinal disorder is characterised by alterations in bowel habit such as diarrhoea and/or constipation, bloating and abdominal pain, and symptom exacerbation has been linked with periods of stress, both psychosocial and infection-related. Indeed, a high level of comorbidity exists between IBS and stress-related mood disorders such as anxiety and depression. Moreover, studies have observed alterations in autonomic output and neuro-endocrine signalling in IBS patients. Accumulating evidence indicates that a maladaptive stress response, probably mediated by the stress hormone, corticotropin-releasing factor contributes to the initiation, persistence and severity of symptom flares. Other risk factors for developing IBS include a positive family history, childhood trauma, dietary factors and prior gastrointestinal infection. An emerging role has been attributed to the importance of immune factors in the pathophysiology of IBS with evidence of altered cytokine profiles and increased levels of mucosal immune cells. These factors have also been shown to have direct effects on neural signalling. This review discusses how pathological changes in neural, immune and endocrine pathways, and communication between these systems, contribute to symptom flares in IBS.
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Shang JJ, Yuan JY, Xu H, Tang RZ, Dong YB, Xie JQ. Shugan-decoction relieves visceral hyperalgesia and reduces TRPV1 and SP colon expression. World J Gastroenterol 2013; 19:8071-8077. [PMID: 24307802 PMCID: PMC3848156 DOI: 10.3748/wjg.v19.i44.8071] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/05/2013] [Revised: 09/28/2013] [Accepted: 10/22/2013] [Indexed: 02/06/2023] Open
Abstract
AIM: To evaluate the therapeutic effect of Shugan-decoction (SGD) on visceral hyperalgesia and colon gene expressions using a rat model.
METHODS: Ninety-six adult male Wistar rats were randomized into six equal groups for assessment of SGD effects on psychological stress-induced changes using the classic water avoidance stress (WAS) test. Untreated model rats were exposed to chronic (1 h/d for 10 d consecutive) WAS conditions; experimental treatment model rats were administered with intragastric SGD at 1 h before WAS on consecutive days 4-10 (low-dose: 0.1 g/mL; mid-dose: 0.2 g/mL; high-dose: 0.4 g/mL); control treatment model rats were similarly administered with the irritable bowel syndrome drug, dicetel (0.0042 g/mL); untreated normal control rats received no drug and were not subjected to the WAS test. At the end of the 10-d WAS testing period, a semi-quantitative measurement of visceral sensitivity was made by assessing the abdominal withdrawal reflex (AWR) to colorectal balloon-induced distension (at 5 mmHg increments) to determine the pain pressure threshold (PPT, evidenced by pain behavior). Subsequently, the animals were sacrificed and colonic tissues collected for assessment of changes in expressions of proteins related to visceral hypersensitivity (transient receptor potential vanilloid 1, TRPV1) and sustained visceral hyperalgesia (substance P, SP) by immunohistochemistry and real-time polymerase chain reaction. Inter-group differences were assessed by paired t test or repeated measures analysis of variance.
RESULTS: The WAS test successfully induced visceral hypersensitivity, as evidenced by a significantly reduced AWR pressure in the untreated model group as compared to the untreated normal control group (190.4 ± 3.48 mmHg vs 224.0 ± 4.99 mmHg, P < 0.001). SGD treatments at mid-dose and high-dose and the dicetel treatment significantly increased the WAS-reduced PPT (212.5 ± 2.54, 216.5 ± 3.50 and 217.7 ± 2.83 mmHg respectively, all P < 0.001); however, the low-dose SGD treatment produced no significant effect on the WAS-reduced PPT (198.3 ± 1.78 mmHg, P > 0.05). These trends corresponded to the differential expressions observed for both TRPV1 protein (mid-dose: 1.64 ± 0.08 and high-dose: 1.69 ± 0.12 vs untreated model: 3.65 ± 0.32, P < 0.001) and mRNA (0.44 ± 0.16 and 0.15 ± 0.03 vs 1.39 ± 0.15, P < 0.001) and SP protein (0.99 ± 0.20 and 1.03 ± 0.23 vs 2.03 ± 0.12, P < 0.01) and mRNA (1.64 ± 0.19 and 1.32 ± 0.14 vs 2.60 ± 0.33, P < 0.05). These differential expressions of TRPV1 and SP related to mid- and high-dose SGD treatments were statistically similar to the changes induced by dicetel treatment. No signs of overt damage to the rat system were observed for any of the SGD dosages.
CONCLUSION: Shugan-decoction can reduce chronic stress-induced visceral hypersensitivity in rats, and the regulatory mechanism may involve mediating the expressions of TRPV1 and SP in colon tissues.
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Seo AY, Kim N, Oh DH. Abdominal bloating: pathophysiology and treatment. J Neurogastroenterol Motil 2013; 19:433-53. [PMID: 24199004 PMCID: PMC3816178 DOI: 10.5056/jnm.2013.19.4.433] [Citation(s) in RCA: 54] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/03/2013] [Revised: 09/10/2013] [Accepted: 10/16/2013] [Indexed: 12/13/2022] Open
Abstract
Abdominal bloating is a very common and troublesome symptom of all ages, but it has not been fully understood to date. Bloating is usually associated with functional gastrointestinal disorders or organic diseases, but it may also appear alone. The pathophysiology of bloating remains ambiguous, although some evidences support the potential mechanisms, including gut hypersensitivity, impaired gas handling, altered gut microbiota, and abnormal abdominal-phrenic reflexes. Owing to the insufficient understanding of these mechanisms, the available therapeutic options are limited. However, medical treatment with some prokinetics, rifaximin, lubiprostone and linaclotide could be considered in the treatment of bloating. In addition, dietary intervention is important in relieving symptom in patients with bloating.
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Affiliation(s)
- A Young Seo
- Department of Internal Medicine, Seoul National University, Bundang Hospital, Seongnam, Gyeonggi-do, Korea
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