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Katsumata R, Hosokawa T, Manabe N, Mori H, Wani K, Kimura M, Oda S, Ishii K, Tanikawa T, Urata N, Ayaki M, Nishino K, Murao T, Suehiro M, Fujita M, Kawanaka M, Haruma K, Kawamoto H, Takao T, Kamada T. Brain activity during a public-speaking situation in virtual reality in patients with irritable bowel syndrome and functional dyspepsia. J Gastroenterol 2025; 60:561-572. [PMID: 39994039 DOI: 10.1007/s00535-025-02228-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/24/2024] [Accepted: 02/06/2025] [Indexed: 02/26/2025]
Abstract
BACKGROUND Psychosocial stress plays a central role in the pathophysiology of disorders of gut-brain interactions (DGBI), including functional dyspepsia (FD) and irritable bowel syndrome (IBS). Brain activity during psychosocial stress in patients with DGBI has not been adequately investigated. In this prospective study, we aimed to explore brain activity during psychosocial stress in patients with DGBI. METHODS Situations in an unmanned room, public space without attention, and public speaking were simulated in a virtual reality (VR) environment. Subjective stress, emotional state, and gastrointestinal (GI) symptoms were assessed using a visual analog scale, the State-Trait Anxiety Inventory, and the GI Symptom Rating Scale, respectively. Electrocardiograms were recorded to evaluate autonomic function. Activity in the prefrontal cortex (PFC) was examined using functional near-infrared spectroscopy (fNIRS). RESULTS Overall, 15 healthy controls, 15 patients with IBS, and 15 patients with FD were included. In the public-speaking scenario, subjective stress scores significantly decreased (indicating more stress) and sympathetic nervous activity increased equally among the three groups compared with those in an unmanned scene. Patients with IBS had higher activity in the left ventrolateral prefrontal cortex (VLPFC) and lower activity in the dorsolateral PFC (DLPFC) than those with FD and healthy controls. CONCLUSIONS Brain activity increased in the VLPFC and decreased in the DLPFC under stressful psychosocial situations created in the VR space in patients with IBS. Thus, the combination of VR and fNIRS is a viable option for evaluating brain activity under psychosocial stress in natural clinical settings.
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Affiliation(s)
- Ryo Katsumata
- Department of Health Care Medicine, Kawasaki Medical School General Medical Center, 2-6-1 Nakasange Kita-ku, Okayama City, Okayama, Japan.
| | - Takayuki Hosokawa
- Department of Orthoptics, Faculty of Rehabilitation, Kawasaki University of Medical Welfare, Kurashiki, Japan
| | - Noriaki Manabe
- Department of Clinical Pathology and Laboratory Medicine, Kawasaki Medical School General Medical Center, Okayama, Japan
| | - Hitoshi Mori
- Department of Neurology, Kawasaki Medical School General Medical Center, Okayama, Japan
| | - Kenta Wani
- Department of Psychiatry, Kawasaki Medical School General Medical Center, Okayama, Japan
| | - Minako Kimura
- Department of General Internal Medicine 2, Kawasaki Medical School General Medical Center, Okayama, Japan
| | - Shintaro Oda
- Department of General Internal Medicine 2, Kawasaki Medical School General Medical Center, Okayama, Japan
| | - Katsunori Ishii
- Department of General Internal Medicine 2, Kawasaki Medical School General Medical Center, Okayama, Japan
| | - Tomohiro Tanikawa
- Department of General Internal Medicine 2, Kawasaki Medical School General Medical Center, Okayama, Japan
| | - Noriyo Urata
- Department of General Internal Medicine 2, Kawasaki Medical School General Medical Center, Okayama, Japan
| | - Maki Ayaki
- Department of Clinical Pathology and Laboratory Medicine, Kawasaki Medical School General Medical Center, Okayama, Japan
| | - Ken Nishino
- Department of General Internal Medicine 2, Kawasaki Medical School General Medical Center, Okayama, Japan
| | - Takahisa Murao
- Department of Health Care Medicine, Kawasaki Medical School General Medical Center, 2-6-1 Nakasange Kita-ku, Okayama City, Okayama, Japan
| | - Mitsuhiko Suehiro
- Department of General Internal Medicine 2, Kawasaki Medical School General Medical Center, Okayama, Japan
| | - Minoru Fujita
- Department of Clinical Pathology and Laboratory Medicine, Kawasaki Medical School General Medical Center, Okayama, Japan
| | - Miwa Kawanaka
- Department of General Internal Medicine 2, Kawasaki Medical School General Medical Center, Okayama, Japan
| | - Ken Haruma
- Department of General Internal Medicine 2, Kawasaki Medical School General Medical Center, Okayama, Japan
| | - Hirofumi Kawamoto
- Department of General Internal Medicine 2, Kawasaki Medical School General Medical Center, Okayama, Japan
| | - Toshihiro Takao
- Department of Health Care Medicine, Kawasaki Medical School, Kurashiki, Japan
| | - Tomoari Kamada
- Department of Health Care Medicine, Kawasaki Medical School General Medical Center, 2-6-1 Nakasange Kita-ku, Okayama City, Okayama, Japan
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Dong Z, Wang X, Xuan L, Wang J, Zhan T, Chen Y, Xu S, Ji D. The interaction effect between childhood trauma and negative events during adulthood on development and severity of irritable bowel syndrome. BMC Gastroenterol 2025; 25:321. [PMID: 40307690 PMCID: PMC12042304 DOI: 10.1186/s12876-025-03919-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/27/2024] [Accepted: 04/21/2025] [Indexed: 05/02/2025] Open
Abstract
BACKGROUND Childhood trauma and negative events during adulthood were associated with the symptom severity of irritable bowel syndrome (IBS). However, the interaction effect of these negative events on IBS remains poorly understood. METHODS 70 healthy individuals who completed Childhood Trauma Questionnaire (CTQ) and Life Event Scale (LES) and 88 IBS patients, diagnosed based on the Rome IV criteria, who completed CTQ, LES, IBS-Quality of Life (IBS-QOL), and IBS-Severity Scoring System (IBS-SSS) were retrospectively included. Logistic and linear regression analyses were used to investigate the interaction effect between childhood trauma and negative events during adulthood on IBS. RESULTS Female sex, childhood emotional abuse and neglect, and negative events during adulthood were associated with a higher prevalence of IBS. In IBS patients, childhood emotional abuse and neglect, as well as negative events during adulthood, were independently associated with more severe symptoms and worse quality of life. A significant interaction effect between childhood emotional trauma and negative events during adulthood was observed in IBS severity and quality of life, though no interaction effect was found in IBS development. Subsequent analyses revealed that the effect of negative events during adulthood on IBS severity and quality of life increased in IBS patients with childhood emotional trauma (IBS-SSS, β = 5.75, p < 0.001; IBS-QOL, β = 2.1, p < 0.001) compared with those without (IBS-SSS, β = 3.23, p < 0.001; IBS-QOL, β = 0.69, p = 0.011). CONCLUSIONS Childhood emotional trauma and negative events during adulthood were associated with IBS development, higher IBS severity, and worse quality of life. Furthermore, childhood emotional trauma increased the negative effect of negative events during adulthood on IBS severity and quality of life.
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Affiliation(s)
- Zhiyu Dong
- Department of Gastrointestinal Endoscopy, Huadong Hospital, Fudan University, Shanghai, China
- Department of Gastroenterology, Tongji Hospital, Tongji University School of Medicine, Shanghai, China
| | - Xiaomei Wang
- Department of Emergency, Sijing Hospital, Shanghai, China
| | - Liqian Xuan
- Shanghai University of Traditional Chinese Medicine Affiliated Shuguang Hospital, Shanghai, China
| | - Junwen Wang
- Department of Gastroenterology, Tongji Hospital, Tongji University School of Medicine, Shanghai, China
| | - Tingting Zhan
- Department of Gastroenterology, Tongji Hospital, Tongji University School of Medicine, Shanghai, China
| | - Ying Chen
- Department of Gastroenterology, Tongji Hospital, Tongji University School of Medicine, Shanghai, China
| | - Shuchang Xu
- Department of Gastroenterology, Tongji Hospital, Tongji University School of Medicine, Shanghai, China.
| | - Danian Ji
- Department of Gastrointestinal Endoscopy, Huadong Hospital, Fudan University, Shanghai, China.
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Sulaimi F, Ong TSK, Tang ASP, Quek J, Pillay RM, Low DT, Lee CKL, Siah KTH, Ng QX. Risk factors for developing irritable bowel syndrome: systematic umbrella review of reviews. BMC Med 2025; 23:103. [PMID: 39985070 PMCID: PMC11846330 DOI: 10.1186/s12916-025-03930-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/29/2024] [Accepted: 02/06/2025] [Indexed: 02/24/2025] Open
Abstract
BACKGROUND Irritable bowel syndrome (IBS) is a debilitating disorder affecting 4-9% of the global population. It is a multifaceted disorder with complex and varied causes. This review aims to consolidate the evidence regarding IBS risk factors by examining existing systematic reviews and meta-analyses, covering potential genetic, immunological, psychological, and dietary causes. METHODS Systematic literature searches were conducted in MEDLINE, Embase and Cochrane library databases. Study selection and data extraction were conducted independently by four authors, with discrepancies resolved by consensus with a senior author. Systematic reviews examining risk factors of IBS development were eligible for review. Results were narratively synthesized. Quality of reviews were analysed using AMSTAR 2, and evidence were appraised using GRADE methodology. RESULTS A total of 69 systematic reviews were included in this study. Most reviews were of "critically low" quality, while the remaining were "low" quality. Common shortcomings included the absence of a list of excluded studies with justifications for their exclusion and inadequate consideration of the risk of bias in individual studies. Eight major categories of risk factors for IBS identified were as follows: dietary, genetic, environmental, psychological, gut microbiome, socio-economic, physiological, and pathological, albeit overlaps exist. The most frequently reported risk factors for IBS development were female gender and anxiety disorders, with overall GRADE evaluation of "low"; depression and gastroenteritis, with overall GRADE evaluation of "moderate". CONCLUSIONS Clinical practice should prioritize recognition of these risk factors. Future reviews should improve their reporting of results based on the PRISMA guidelines, to enhance the quality of research in this field. PROTOCOL REGISTRATION PROSPERO CRD42023493739.
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Affiliation(s)
- Farisah Sulaimi
- School of Medical Sciences, Wallace Wurth Building, University of New South Wales, Sydney, NSW, Australia
| | - Timothy Sheng Khai Ong
- NUS Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore
| | - Ansel Shao Pin Tang
- NUS Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore
| | - Jingxuan Quek
- NUS Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore
| | - Renish M Pillay
- NUS Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore
| | - Damien Tianle Low
- NUS Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore
| | - Charisse Kai Ling Lee
- NUS Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore
| | - Kewin Tien Ho Siah
- NUS Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore
- Division of Gastroenterology & Hepatology, University Medicine Cluster, National University Hospital, Singapore, Singapore
| | - Qin Xiang Ng
- NUS Saw Swee Hock School of Public Health, National University of Singapore and National University Health System, Singapore, Singapore.
- SingHealth Duke-NUS Global Health Institute, Duke-NUS Medical School, Singapore, Singapore.
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Pop D, Man SC, Farcău D. Anxiety and Depression in Children with Irritable Bowel Syndrome-A Narrative Review. Diagnostics (Basel) 2025; 15:433. [PMID: 40002584 PMCID: PMC11853794 DOI: 10.3390/diagnostics15040433] [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: 12/10/2024] [Revised: 02/03/2025] [Accepted: 02/06/2025] [Indexed: 02/27/2025] Open
Abstract
Irritable bowel syndrome (IBS) is one of the most common functional gastrointestinal disorders diagnosed in children. It has a complex pathophysiology with several potential risk factors, including psychological disorders like anxiety and depression. This paper aimed to find genetic, pathophysiological, and clinical links between psychological factors (mainly anxiety and depression) and IBS in children. Impairment of the gut-brain communication and signalling of serotonin is responsible for both gastrointestinal and psychological disorders. Childhood psychological events seem to be linked to gastrointestinal symptoms not only in childhood but also in adulthood. Evidence of the efficacy of therapies targeting psychological disorders (antidepressant, hypnotherapy, and cognitive behavioural therapy) in children with IBS was evaluated. Further studies that use updated criteria for IBS and uniform questionnaires and outcome measures are needed to draw reliable conclusions regarding the connection between psychological factors and IBS.
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Affiliation(s)
- Daniela Pop
- Third Pediatric Discipline, “Iuliu Hațieganu” University of Medicine and Pharmacy, 400217 Cluj-Napoca, Romania
- Third Pediatric Department, Emergency Hospital for Children, 400217 Cluj-Napoca, Romania
| | - Sorin Claudiu Man
- Third Pediatric Discipline, “Iuliu Hațieganu” University of Medicine and Pharmacy, 400217 Cluj-Napoca, Romania
- Third Pediatric Department, Emergency Hospital for Children, 400217 Cluj-Napoca, Romania
| | - Dorin Farcău
- Third Pediatric Department, Emergency Hospital for Children, 400217 Cluj-Napoca, Romania
- Nursing Discipline, “Iuliu Hațieganu” University of Medicine and Pharmacy, 400217 Cluj-Napoca, Romania
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Asal MGR, El-Sayed AAI, Alsenany SA, Ramzy ZH, Dawood RFA. Self-administered active versus sham acupressure for diarrhea predominant irritable bowel syndrome: a nurse-led randomized clinical trial. BMC Nurs 2025; 24:106. [PMID: 39875940 PMCID: PMC11776273 DOI: 10.1186/s12912-024-02594-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/26/2024] [Accepted: 12/09/2024] [Indexed: 01/30/2025] Open
Abstract
BACKGROUND Diarrhea-predominant irritable bowel syndrome (IBS-D) significantly impacts patients' quality of life, with existing treatments offering limited relief. Self-administered acupressure presents a potential non-invasive, cost-effective treatment option that could alleviate symptoms and enhance health outcomes in these patients. AIM This randomized controlled trial aimed to evaluate the effect of active acupressure compared to sham acupressure on primary and secondary outcomes among IBS-D patients. METHOD The study included 63 patients with IBS-D, recruited from Alexandria Main University Hospital, Egypt. Participants were randomized into either an active acupressure group or a sham acupressure group. Both groups underwent two days of training, followed by four weeks of intervention. The active group applied pressure to specific therapeutic acupoints, while the sham group used non-therapeutic points. Outcomes were assessed at baseline, week 2, and week 4. RESULTS The active acupressure group showed a significant reduction in symptom severity, improved stool consistency, and frequency, and greater adequate symptom relief by week 4 compared to the sham group. Psychological outcomes, including anxiety and depression, also improved significantly in the active group. Additionally, the active group reported reduced use of rescue medications. CONCLUSION Active acupressure is an effective nursing intervention for alleviating symptoms of IBS-D, particularly when applied consistently over time. It improves both physical and psychological outcomes, offering a valuable non-pharmacological treatment option. IMPLICATIONS Nurses can integrate self-administered acupressure into IBS-D care plans, teaching patients this technique to manage symptoms independently, thus enhancing their quality of life (QOL) and reducing reliance on conventional medications. This intervention aligns with holistic nursing care and offers a cost-effective, patient-friendly solution for managing IBS-D. TRIAL REGISTRATION This study was prospectively registered as a randomized controlled trial in https://clinicaltrials.gov/ Registration Date: January 7, 2023, Registration Number: NCT05702255.
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Affiliation(s)
- Maha Gamal Ramadan Asal
- Medical Surgical Nursing Department, Faculty of Nursing, Alexandria University, Alexandria, Egypt
| | | | - Samira Ahmed Alsenany
- Public Health Department, Faculty of Nursing, King Abdulaziz University, Jeddah, Saudi Arabia
| | - Zahraa Hassan Ramzy
- Medical Surgical Nursing Department, Faculty of Nursing, Alexandria University, Alexandria, Egypt
| | - Rasha Fathy Ahmed Dawood
- Medical Surgical Nursing Department, Faculty of Nursing, Alexandria University, Alexandria, Egypt
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Haedrich J, Huber R. Crohn's disease, irritable bowel syndrome, and chronic fatigue: the importance of communication and symptom management-a case report. J Med Case Rep 2025; 19:9. [PMID: 39789666 PMCID: PMC11721286 DOI: 10.1186/s13256-024-05010-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/17/2024] [Accepted: 12/12/2024] [Indexed: 01/12/2025] Open
Abstract
BACKGROUND Crohn's disease and irritable bowel syndrome may both cause abdominal pain and diarrhea. Irritable bowel syndrome not only is an important differential diagnosis for Crohn's disease but also occurs in one out of three patients with Crohn's disease in remission in parallel. If not adequately diagnosed and treated, additional functional symptoms such as fatigue and/or muscle pain may develop, indicating a more severe course. CASE PRESENTATION A 64-year-old Caucasian male with long-standing, widely inactive Crohn's disease presented with persistent diarrhea, bloating, abdominal pain, general fatigue, unexplained hip pain, and frequent shivering with cold extremities, which had worsened following a gastrointestinal infection and psychological stress. A plausible explanation of his symptoms, based on an understanding of mind-body interactions, the autonomic nervous system, and temperature regulation, combined with symptom relief, was associated with rapid and sustainable improvement. After 2.5 years of follow-up, the patient is almost symptom-free. CONCLUSIONS This case report exemplifies the interrelation between organic (Crohn's disease) and functional diseases (irritable bowel syndrome, chronic fatigue syndrome, and somatoform pain). It further demonstrates that these connections may be overlooked in daily practice and that providing a plausible explanation in combination with symptom relief may be important for patients with functional syndromes.
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Affiliation(s)
- Johannes Haedrich
- Center for Complementary Medicine, Department of Internal Medicine II, Faculty of Medicine, Medical Center - University of Freiburg, University of Freiburg, 79106, Freiburg, Germany
| | - Roman Huber
- Center for Complementary Medicine, Department of Internal Medicine II, Faculty of Medicine, Medical Center - University of Freiburg, University of Freiburg, 79106, Freiburg, Germany.
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Tahir AH, Ding Y, Wan J, Shah MK, Janyaro H, Li XJ, Ding MX. Impact of electro-acupuncture on EAAT2 and NMDAR-2B expression in goats with visceral hypersensitivity. Heliyon 2024; 10:e40700. [PMID: 39717594 PMCID: PMC11665384 DOI: 10.1016/j.heliyon.2024.e40700] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/26/2023] [Revised: 11/24/2024] [Accepted: 11/25/2024] [Indexed: 12/25/2024] Open
Abstract
Objective This study evaluates the effect of electro-acupuncture (EA) on visceral hypersensitivity (VH) and the expression of N-methyl-D-aspartate receptor-2B (NMDAR-2B) and glutamate transporter EAAT2 in goats. Methods Twenty-four goats were divided into four groups: saline, 2, 4, 6-Trinitrobenzenesulfonic acid (TNBS), TNBS + EA, and sham EA. EA was administered at Zusanli (ST36) with 60 Hz and 1-3 mA on specified days. Electromyography (EMG) recorded visceromotor response to colorectal distention (CRD). Spinal cords were collected for immunohistochemistry, western blotting, and RT-PCR. The ileum was examined histologically. Results The repeated EA administration significantly attenuated VH (P < 0.05) in TNBS-treated goats without similar effects in the sham group. NMDAR-2B expression increased (P < 0.01), and EAAT2 expression decreased (P < 0.01) in the TNBS group compared to saline. EA increased the EAAT2 and decreased the NMDAR-2B expression (P < 0.01) compared to TNBS, with no change in the sham-EA group. Conclusion EA may alleviate VH by upregulating EAAT2 and downregulating NMDAR-2B in the spinal cord of TNBS-treated goats, indicating its potential for treating chronic visceral pain in gastrointestinal disorders.
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Affiliation(s)
- Adnan Hassan Tahir
- College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, Hubei, China
- Faculty of Veterinary and Animal Sciences, PMAS-Arid Agriculture University, Rawalpindi, Pakistan
| | - Yi Ding
- College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, Hubei, China
| | - Juan Wan
- College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, Hubei, China
- Gannan Innovation and Transformation Medical Research Institute, First Affiliated Hospital, Gannan Medical University, Ganzhou, Jiangxi, China
| | - Manoj Kumar Shah
- College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, Hubei, China
- Department of Pharmacology and Surgery, Institute of Agriculture and Animal Science, Rampur Chitwan, Nepal
| | - Habibullah Janyaro
- College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, Hubei, China
- Shaheed Benazir Bhutto University of Veterinary and Animal Sciences, Sakrand, Pakistan
| | - Xiao-Jing Li
- College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, Hubei, China
- School of Medicine, Shanghai University, Shanghai, China
| | - Ming-Xing Ding
- College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, Hubei, China
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Chapman S, Frostholm L, Chalder T, Graham C, de Thurah A, van Leeuwen T, Pedersen MM, Carstensen T, Weinman J. Preventing medication nonadherence: a framework for interventions to support early engagement with treatment. Health Psychol Rev 2024; 18:884-898. [PMID: 39101263 DOI: 10.1080/17437199.2024.2385525] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/14/2023] [Accepted: 07/23/2024] [Indexed: 08/06/2024]
Abstract
Medication nonadherence is common and results in avoidable morbidity, mortality, and burdens on healthcare systems. This paper proposes a preventative approach to medication nonadherence. We consider existing evidence on the prevalence and determinants of nonadherence early in a patient's medication-taking journey, and map these to potential opportunities for intervention. Many patients stop taking a new medication soon after they are prescribed it, often not collecting the medication. Early patterns of nonadherence are linked to later nonadherence via processes such as habit formation and symptom experiences. Known predictors of nonadherence may be present before someone starts a new treatment, when patients experience disruption to their lives and identity due to illness. Healthcare professionals typically have contact with patients around this time. We argue that it may be possible to prevent medication nonadherence: at the population level; by optimising the prescription process; and through low- and high-intensity interventions for patients with identified early barriers. We give examples of specific interventions and tools that might be needed to operationalise this approach in practice and propose new directions for research to promote early engagement with medication to prevent nonadherence.
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Affiliation(s)
- Sarah Chapman
- Centre for Adherence Research and Education, Institute of Pharmaceutical Science, King's College London, London, United Kingdom
| | - Lisbeth Frostholm
- Research Clinic for Functional Disorders and Psychosomatics, Aarhus University Hospital, Aarhus, Denmark
- Department of Clinical Medicine, Aarhus University, Aarhus, Denmark
| | - Trudie Chalder
- Institute of Psychiatry, Psychology & Neuroscience (IoPPN), Department of Psychological Medicine, School of Academic Psychiatry, King's College London, London, United Kingdom
| | - Christopher Graham
- Department of Psychological Sciences and Health, University of Strathclyde, Strathclyde, United Kingdom
| | - Annette de Thurah
- Department of Clinical Medicine, Aarhus University, Aarhus, Denmark
- Department of Rheumatology, Aarhus University Hospital, Aarhus, Denmark
| | - Tess van Leeuwen
- Centre for Adherence Research and Education, Institute of Pharmaceutical Science, King's College London, London, United Kingdom
- Hogeschool Inholland, Inholland University of Applied Sciences, The Hague, Netherlands
| | - Majbritt Mostrup Pedersen
- Department of Clinical Medicine - Research Clinic for Functional Disorders, Aarhus University Hospital, Aarhus, Denmark
| | - Tina Carstensen
- Research Clinic for Functional Disorders and Psychosomatics, Aarhus University Hospital, Aarhus, Denmark
- Department of Clinical Medicine, Aarhus University, Aarhus, Denmark
| | - John Weinman
- Centre for Adherence Research and Education, Institute of Pharmaceutical Science, King's College London, London, United Kingdom
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Rzeszutek M, Kowalkowska J, Drabarek K, Van Hoy A, Schier K, Lis-Turlejska M, Dragan M, Holas P, Maison D, Litwin E, Wawrzyniak J, Znamirowska W, Szumiał S, Desmond M. Adverse childhood experiences and alexithymia intensity as predictors of temporal dynamics of functioning in individuals with irritable bowel syndrome: A three-wave latent transition analysis. J Psychosom Res 2024; 187:111904. [PMID: 39298867 DOI: 10.1016/j.jpsychores.2024.111904] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/22/2024] [Revised: 08/21/2024] [Accepted: 08/21/2024] [Indexed: 09/22/2024]
Abstract
OBJECTIVE Despite high prevalence of irritable bowel syndrome (IBS) and its significant negative impact on individuals' quality of life, its etiology remains poorly understood. This prospective study explored whether early life factors (adverse childhood experiences; ACEs) and alexithymia intensity, could explain IBS symptom severity and its effects on psychological functioning over time. We also compared the studied variables between an IBS sample and a healthy control group. METHOD Based on the Rome III Diagnostic Criteria for IBS, 245 individuals with a diagnosis of IBS were recruited from a national sample of Poles. The IBS sample completed the following psychometric questionaries in three waves, one month apart: Adverse Childhood Experiences Questionnaire, Toronto Alexithymia Scale, IBS Symptom Severity Score, Short Form Perceived Stress Scale, and Ultra-Brief Patient Health Questionnaire for Anxiety and Depression. Latent transition analysis was used to identify distinct profiles of IBS symptom dynamics. RESULTS The IBS group reported a significantly higher number of ACEs, greater alexithymia severity, and more intense levels of stress, anxiety, and depressive symptoms compared to the healthy controls. Four profiles of IBS individuals with distinct dynamics of IBS symptoms, stress, anxiety, and depressive symptoms were extracted, which correlated with the baseline number of ACEs and alexithymia intensity among participants. CONCLUSION Childhood adversity and associated problems in emotional processing affect IBS symptom severity. ACEs should be included in IBS screening and considered in the design of individualized multidisciplinary treatment approaches for IBS patients.
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Affiliation(s)
| | - Joanna Kowalkowska
- Faculty of Food Science, University of Warmia and Mazury in Olsztyn, Poland
| | | | | | | | - Maja Lis-Turlejska
- Faculty of Psychology, SWPS University of Social Sciences and Humanities, Warsaw, Poland
| | | | - Paweł Holas
- Faculty of Psychology, University of Warsaw, Poland
| | | | | | | | | | | | - Małgorzata Desmond
- Great Ormond Street Institute of Child Health, University College London, United Kingdom
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Yang R, Jiang J, Ouyang J, Zhao Y, Xi B. Efficacy and safety of probiotics in irritable bowel syndrome: A systematic review and meta-analysis. Clin Nutr ESPEN 2024; 60:362-372. [PMID: 38479936 DOI: 10.1016/j.clnesp.2024.02.025] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/15/2023] [Revised: 02/02/2024] [Accepted: 02/20/2024] [Indexed: 04/13/2024]
Abstract
BACKGROUND Irritable bowel syndrome (IBS) is a common gastrointestinal disease characterized by abdominal pain, distension, and altered bowel habits. Probiotics may alleviate IBS symptoms, but clinical trials remain conflicting. AIMS To conduct a systematic review and meta-analysis of clinical trials to evaluate the efficacy and safety of probiotics for IBS patients. METHODS We searched relevant trials in PubMed, Web of Science, Embase, Cochrane Library, and Google Scholar from 2000 to June 2023. Standardized mean difference (SMD) and 95% confidence interval (CI) were calculated for continuous outcomes. A risk ratio (RR) and a 95% CI were calculated for dichotomous outcomes. RESULTS A total of 20 studies involving 3011 patients were obtained. The results demonstrated that probiotics are more effective than placebo in reducing global IBS symptoms improvement rate (RR = 1.401, 95% CI 1.182-1.662, P < 0.001) and quality of life scores (SMD = 0.286, 95% CI = 0.154-0.418, P < 0.001). Subgroup analyses showed that a shorter treatment time (less than eight weeks) could reduce distension scores (SMD = 0.197, 95% CI = 0.038-0.356, P = 0.015). High doses (daily dose of probiotics ≥ 10ˆ10) or multiple strains of probiotics exhibit beneficial effects on abdominal pain (SMD = 0.412, 95% CI = 0.112-0.711, P = 0.007; SMD = 0.590, 95% CI = 0.050-1.129, P = 0.032; respectively). However, there was no significant benefit on global symptom scores (SMD = 0.387, 95% CI 0.122 to 0.653, P = 0.004) with statistically high inter-study heterogeneity (I2 = 91.9%, P < 0.001). Furthermore, there was no significant inter-group difference in terms of adverse events frequency (RR = 0.997, 95% CI 0.845-1.177, P = 0.973). CONCLUSION Probiotics are effective and safe for IBS patients. High doses or multiple probiotic strains seem preferable, but definite conclusions are challenging due to the high heterogeneity. Large-scale, well-designed, and rigorous trials are needed to confirm their effectiveness.
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Affiliation(s)
- Ruwen Yang
- Zhenjiang Hospital of Traditional Chinese Medicine, Affiliated Hospital of Nanjing University of Chinese Medicine, Zhenjiang, China
| | - Jiawei Jiang
- Zhenjiang Hospital of Traditional Chinese Medicine, Affiliated Hospital of Nanjing University of Chinese Medicine, Zhenjiang, China
| | - Jun Ouyang
- Zhenjiang Hospital of Traditional Chinese Medicine, Affiliated Hospital of Nanjing University of Chinese Medicine, Zhenjiang, China
| | - Yuanpei Zhao
- Zhenjiang Hospital of Traditional Chinese Medicine, Affiliated Hospital of Nanjing University of Chinese Medicine, Zhenjiang, China
| | - Biao Xi
- Zhenjiang Hospital of Traditional Chinese Medicine, Affiliated Hospital of Nanjing University of Chinese Medicine, Zhenjiang, China.
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11
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Di Lorenzo C, Nurko S, Hyams JS, Rodriguez-Araujo G, Shakhnovich V, Saps M, Simon M. Safety and efficacy of linaclotide in children aged 7-17 years with irritable bowel syndrome with constipation. J Pediatr Gastroenterol Nutr 2024; 78:539-547. [PMID: 38504394 DOI: 10.1002/jpn3.12103] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/31/2023] [Revised: 11/20/2023] [Accepted: 12/04/2023] [Indexed: 03/21/2024]
Abstract
OBJECTIVES Linaclotide, a guanylate cyclase-C agonist, was recently approved in the United States for the treatment of children 6-17 years old with functional constipation. This study evaluated the safety and efficacy of various linaclotide doses in children 7-17 years old with irritable bowel syndrome with constipation (IBS-C). METHODS In this 4-week, randomized, double-blind, placebo-controlled, parallel-group, Phase 2 study, children with IBS-C were randomized to once-daily placebo or linaclotide (Dose A: 18 or 36 µg, B: 36 or 72 µg, and C: 72 µg or 145 µg, or 290 µg); those aged 7-11 years in a 1:1:1:1 allocation based on weight (18 to <35 kg:18 µg, 36 µg, or 72 µg; or ≥35 kg: 36 µg, 72 µg, or 145 µg), and those aged 12-17 years in a 1:1:1:1:1 allocation (the higher option of Doses A-C or 290 µg). The primary efficacy endpoint was a change from baseline in 4-week overall spontaneous bowel movement (SBM) frequency rate over the treatment period. Adverse events and clinical laboratory measures were also assessed. RESULTS Efficacy, safety, and tolerability were assessed in 101 patients. In the intent-to-treat population, numerical improvement was observed in overall SBM frequency rate with increasing linaclotide doses (A: 1.62, B: 1.52, and C: 2.30, 290 µg: 3.26) compared with placebo. The most reported treatment-emergent adverse events were diarrhea and pain, with most cases being mild and none being severe. CONCLUSIONS Linaclotide was tolerated well in this pediatric population, showing numerical improvement in SBM frequency compared with placebo.
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Affiliation(s)
- Carlo Di Lorenzo
- Department of Gastroenterology & Hepatology & Nutrition, Nationwide Children's Hospital, Columbus, Ohio, USA
| | - Samuel Nurko
- Boston Children's Hospital, Boston, Massachusetts, USA
| | - Jeffrey S Hyams
- Connecticut Children's Medical Center, Hartford, Connecticut, USA
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12
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Lenover MB, Shenk MK. Evolutionary medicine approaches to chronic disease: The case of irritable bowel syndrome. Evol Anthropol 2024; 33:e22010. [PMID: 37909359 DOI: 10.1002/evan.22010] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/22/2022] [Revised: 10/13/2023] [Accepted: 10/16/2023] [Indexed: 11/03/2023]
Abstract
Irritable bowel syndrome (IBS), a gastrointestinal disease, is a global phenomenon correlated with industrialization. We propose that an evolutionary medicine approach is useful to understand this disease from an ultimate perspective and conducted a scoping literature review to synthesize the IBS literature within this framework. Our review suggests five potential evolutionary hypotheses for the cause of IBS, including (a) a dietary mismatch accompanying a nutritional transition, (b) an early hygienic life environment leading to the immune system and microbiotic changes, (c) an outcome of decreased physical activity, (d) a response to changes in environmental light-dark cycles, and (e) an artifact of an evolved fight or flight response. We find key limitations in the available data needed to understand early life, nutritional, and socioeconomic experiences that would allow us to understand evolutionarily relevant risk factors and identify a need for further empirical research to distinguish potential causes and test evolutionary hypotheses.
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Affiliation(s)
- Makenna B Lenover
- Department of Anthropology, The Pennsylvania State University, State College, Pennsylvania, USA
| | - Mary K Shenk
- Department of Anthropology, The Pennsylvania State University, State College, Pennsylvania, USA
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13
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Noemi CN, Bob P, Bókkon I. Long-Term Implicit Epigenetic Stress Information in the Enteric Nervous System and its Contribution to Developing and Perpetuating IBS. Curr Neuropharmacol 2024; 22:2100-2112. [PMID: 38726788 PMCID: PMC11337685 DOI: 10.2174/1570159x22666240507095700] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/23/2024] [Revised: 04/14/2024] [Accepted: 04/24/2024] [Indexed: 08/23/2024] Open
Abstract
Psychiatric and mood disorders may play an important role in the development and persistence of irritable bowel syndrome (IBS). Previously, we hypothesized that stress-induced implicit memories may persist throughout life via epigenetic processes in the enteric nervous system (ENS), independent of the central nervous system (CNS). These epigenetic memories in the ENS may contribute to developing and perpetuating IBS. Here, we further elaborate on our earlier hypothesis. That is, during pregnancy, maternal prenatal stresses perturb the HPA axis and increase circulating cortisol levels, which can affect the maternal gut microbiota. Maternal cortisol can cross the placental barrier and increase cortisol-circulating levels in the fetus. This leads to dysregulation of the HPA axis, affecting the gut microbiota, microbial metabolites, and intestinal permeability in the fetus. Microbial metabolites, such as short-chain fatty acids (which also regulate the development of fetal ENS), can modulate a range of diseases by inducing epigenetic changes. These mentioned processes suggest that stress-related, implicit, long-term epigenetic memories may be programmed into the fetal ENS during pregnancy. Subsequently, this implicit epigenetic stress information from the fetal ENS could be conveyed to the CNS through the bidirectional microbiota-gut-brain axis (MGBA), leading to perturbed functional connectivity among various brain networks and the dysregulation of affective and pain processes.
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Affiliation(s)
- Császár-Nagy Noemi
- National University of Public Services, H-1083 Budapest, Hungary
- Psychosomatic Outpatient Clinics, H-1037 Budapest, Hungary
| | - Petr Bob
- Center for Neuropsychiatric Research of Traumatic Stress, Department of Psychiatry & UHSL, First Faculty of Medicine, and Department of Psychiatry, Faculty of Medicine Pilsen, Charles University, CZ-12108 Prague, Czechia
| | - István Bókkon
- Psychosomatic Outpatient Clinics, H-1037 Budapest, Hungary
- Neuroscience and Consciousness Research Department, Vision Research Institute, Lowell, MA 01854 USA
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14
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Singh SV, Ganguly R, Jaiswal K, Yadav AK, Kumar R, Pandey AK. Molecular signalling during cross talk between gut brain axis regulation and progression of irritable bowel syndrome: A comprehensive review. World J Clin Cases 2023; 11:4458-4476. [PMID: 37469740 PMCID: PMC10353503 DOI: 10.12998/wjcc.v11.i19.4458] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/24/2022] [Revised: 05/09/2023] [Accepted: 06/06/2023] [Indexed: 06/30/2023] Open
Abstract
Irritable bowel syndrome (IBS) is a chronic functional disorder which alters gastrointestinal (GI) functions, thus leading to compromised health status. Pathophysiology of IBS is not fully understood, whereas abnormal gut brain axis (GBA) has been identified as a major etiological factor. Recent studies are suggestive for visceral hyper-sensitivity, altered gut motility and dysfunctional autonomous nervous system as the main clinical abnormalities in IBS patients. Bidirectional signalling interactions among these abnormalities are derived through various exogenous and endogenous factors, such as microbiota population and diversity, microbial metabolites, dietary uptake, and psychological abnormalities. Strategic efforts focused to study these interactions including probiotics, antibiotics and fecal transplantations in normal and germ-free animals are clearly suggestive for the pivotal role of gut microbiota in IBS etiology. Additionally, neurotransmitters act as communication tools between enteric microbiota and brain functions, where serotonin (5-hydroxytryptamine) plays a key role in pathophysiology of IBS. It regulates GI motility, pain sense and inflammatory responses particular to mucosal and brain activity. In the absence of a better understanding of various interconnected crosstalks in GBA, more scientific efforts are required in the search of novel and targeted therapies for the management of IBS. In this review, we have summarized the gut microbial composition, interconnected signalling pathways and their regulators, available therapeutics, and the gaps needed to fill for a better management of IBS.
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Affiliation(s)
- Shiv Vardan Singh
- Department of Biochemistry, University of Allahabad, Allahabad (Prayagraj) 211002, Uttar Pradesh, India
| | - Risha Ganguly
- Department of Biochemistry, University of Allahabad, Allahabad (Prayagraj) 211002, Uttar Pradesh, India
| | - Kritika Jaiswal
- Department of Biochemistry, University of Allahabad, Allahabad (Prayagraj) 211002, Uttar Pradesh, India
| | - Aditya Kumar Yadav
- Department of Biochemistry, University of Allahabad, Allahabad (Prayagraj) 211002, Uttar Pradesh, India
| | - Ramesh Kumar
- Department of Biochemistry, University of Allahabad, Allahabad (Prayagraj) 211002, Uttar Pradesh, India
| | - Abhay K Pandey
- Department of Biochemistry, University of Allahabad, Allahabad (Prayagraj) 211002, Uttar Pradesh, India
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15
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Dothel G, Barbaro MR, Di Vito A, Ravegnini G, Gorini F, Monesmith S, Coschina E, Benuzzi E, Fuschi D, Palombo M, Bonomini F, Morroni F, Hrelia P, Barbara G, Angelini S. New insights into irritable bowel syndrome pathophysiological mechanisms: contribution of epigenetics. J Gastroenterol 2023; 58:605-621. [PMID: 37160449 PMCID: PMC10307698 DOI: 10.1007/s00535-023-01997-6] [Citation(s) in RCA: 13] [Impact Index Per Article: 6.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/12/2022] [Accepted: 04/19/2023] [Indexed: 05/11/2023]
Abstract
Irritable bowel syndrome (IBS) is a complex multifactorial condition including alterations of the gut-brain axis, intestinal permeability, mucosal neuro-immune interactions, and microbiota imbalance. Recent advances proposed epigenetic factors as possible regulators of several mechanisms involved in IBS pathophysiology. These epigenetic factors include biomolecular mechanisms inducing chromosome-related and heritable changes in gene expression regardless of DNA coding sequence. Accordingly, altered gut microbiota may increase the production of metabolites such as sodium butyrate, a prominent inhibitor of histone deacetylases. Patients with IBS showed an increased amount of butyrate-producing microbial phila as well as an altered profile of methylated genes and micro-RNAs (miRNAs). Importantly, gene acetylation as well as specific miRNA profiles are involved in different IBS mechanisms and may be applied for future diagnostic purposes, especially to detect increased gut permeability and visceromotor dysfunctions. In this review, we summarize current knowledge of the role of epigenetics in IBS pathophysiology.
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Affiliation(s)
- Giovanni Dothel
- Department of Pharmacy and Biotechnology, University of Bologna, Bologna, Italy
- Connect By Circular Lab SRL, Madrid, Spain
| | | | - Aldo Di Vito
- Department of Pharmacy and Biotechnology, University of Bologna, Bologna, Italy
| | - Gloria Ravegnini
- Department of Pharmacy and Biotechnology, University of Bologna, Bologna, Italy
| | - Francesca Gorini
- Department of Pharmacy and Biotechnology, University of Bologna, Bologna, Italy
| | - Sarah Monesmith
- Department of Pharmacy and Biotechnology, University of Bologna, Bologna, Italy
| | - Emma Coschina
- Department of Pharmacy and Biotechnology, University of Bologna, Bologna, Italy
| | - Eva Benuzzi
- Department of Pharmacy and Biotechnology, University of Bologna, Bologna, Italy
| | - Daniele Fuschi
- IRCCS Azienda Ospedaliero-Universitaria Di Bologna, Bologna, Italy
| | - Marta Palombo
- Department of Medical and Surgical Sciences, University of Bologna, Bologna, Italy
| | - Francesca Bonomini
- Department of Medical and Surgical Sciences, University of Bologna, Bologna, Italy
| | - Fabiana Morroni
- Department of Pharmacy and Biotechnology, University of Bologna, Bologna, Italy
| | - Patrizia Hrelia
- Department of Pharmacy and Biotechnology, University of Bologna, Bologna, Italy.
| | - Giovanni Barbara
- IRCCS Azienda Ospedaliero-Universitaria Di Bologna, Bologna, Italy
- Department of Medical and Surgical Sciences, University of Bologna, Bologna, Italy
| | - Sabrina Angelini
- Department of Pharmacy and Biotechnology, University of Bologna, Bologna, Italy
- Inter-Departmental Center for Health Sciences & Technologies, CIRI-SDV, University of Bologna, Bologna, Italy
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16
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Steurbaut L, Levy EI, De Geyter C, Buyse S, Vandenplas Y. A narrative review on the diagnosis and management of constipation in infants. Expert Rev Gastroenterol Hepatol 2023; 17:769-783. [PMID: 37501219 DOI: 10.1080/17474124.2023.2242255] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/27/2023] [Accepted: 07/25/2023] [Indexed: 07/29/2023]
Abstract
INTRODUCTION Functional constipation is one of the common disorders of gut-brain interaction in infancy, and decreases the quality of life of infants and parents. AREAS COVERED Relevant articles up to November 2022 were reviewed. We searched in PubMed, Google Scholar, and MEDLINE for guidelines, position papers, reviews, and randomized controlled trials on infant constipation. EXPERT OPINION Randomized controlled trials in this specific age group are mostly limited to trials with infant formula. The prevalence of infant constipation in formula-fed infants is decreasing, and can be associated with adaptations in formula composition. While the supplementation of infant formula with pro-, pre- and/or synbiotics decreases the prevalence of constipation, their efficacy in constipated infants is disappointing. There is limited evidence to support the addition of magnesium to infant formula to treat constipation. The evidence for the efficacy and safety of polyethylene glycol in children < 2 years has expanded over the past years. The administration of lactulose or polyethylene glycol is the preferred medical management, in case nutritional management does result in insufficient improvement.
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Affiliation(s)
- Laurine Steurbaut
- Vrije Universiteit Brussel (VUB), UZ Brussel, KidZ Health Castle, Brussels, Belgium
| | - Elvira Ingrid Levy
- Vrije Universiteit Brussel (VUB), UZ Brussel, KidZ Health Castle, Brussels, Belgium
- Department of Pediatrics, C.H.U. Saint-Pieter, Free University of Brussels, Brussels, Belgium
| | - Charlotte De Geyter
- Vrije Universiteit Brussel (VUB), UZ Brussel, KidZ Health Castle, Brussels, Belgium
| | | | - Yvan Vandenplas
- Vrije Universiteit Brussel (VUB), UZ Brussel, KidZ Health Castle, Brussels, Belgium
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17
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Kumei S, Ishioh M, Nozu T, Okumura T. Prostaglandin I 2 suppresses the development of gut-brain axis disorder in irritable bowel syndrome in rats. Biochim Biophys Acta Gen Subj 2023; 1867:130344. [PMID: 36889449 DOI: 10.1016/j.bbagen.2023.130344] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/10/2022] [Revised: 01/30/2023] [Accepted: 03/02/2023] [Indexed: 03/08/2023]
Abstract
In this study, we attempted to clarify a role of prostaglandin (PG) I2 and its specific receptor, IP in the pathogenesis of irritable bowel syndrome (IBS) using a maternal separation (MS)-induced IBS model. Administration of beraprost (BPS), a specific IP agonist, improved visceral hypersensitivity and depressive state with decreased serum CRF level in the IBS rats. To clarify the mechanism of the effect of BPS, we performed serum metabolome analysis and 1-methylnicotinamide (1-MNA) was identified as a possible candidate for a clue metabolite of pathogenesis of IBS. The serum 1-MNA levels revealed inverse correlation to the level of visceral sensitivity, and positive correlation to a depression marker, immobilizing time. Administration of 1-MNA induced visceral hypersensitivity and depression with increased levels of serum CRF. Since fecal 1-MNA is known for a marker of dysbiosis, we examined the composition of fecal microbiota by T-RFLP analysis. The proportion of clostridium cluster XI, XIVa and XVIII was significantly changed in MS-induced IBS rats treated with BPS. Fecal microbiota transplant of BPS-treated rats improved visceral hypersensitivity and depression in IBS rats. These results suggest for the first time that PGI2-IP signaling plays an important role in IBS phenotypes such as visceral hypersensitivity and depressive state. BPS modified microbiota, thereby inhibition of 1-MNA-CRF pathway, followed by improvement of MS-induced IBS phenotype. These results suggest that the PGI2-IP signaling could be considered to be a therapeutic option for IBS.
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Affiliation(s)
- Shima Kumei
- Department of General Medicine, Asahikawa Medical University, Japan
| | - Masatomo Ishioh
- Department of General Medicine, Asahikawa Medical University, Japan; Division of Metabolism, Biosystemic Science, Gastroenterology and Hematology/Oncology, Department of Medicine, Asahikawa Medical University, Japan
| | - Tsukasa Nozu
- Department of Regional Medicine and Education, Asahikawa Medical University, Japan
| | - Toshikatsu Okumura
- Department of General Medicine, Asahikawa Medical University, Japan; Division of Metabolism, Biosystemic Science, Gastroenterology and Hematology/Oncology, Department of Medicine, Asahikawa Medical University, Japan.
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18
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Namakin K, Moghaddam MH, Sadeghzadeh S, Mehranpour M, Vakili K, Fathi M, Golshan A, Bayat AH, Tajik AH, Eskandari N, Mohammadzadeh I, Benisi SZ, Aliaghaei A, Abdollahifar MA. Elderberry diet improves gut-brain axis dysfunction, neuroinflammation, and cognitive impairment in the rat model of irritable bowel syndrome. Metab Brain Dis 2023; 38:1555-1572. [PMID: 36877342 DOI: 10.1007/s11011-023-01187-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/24/2022] [Accepted: 02/13/2023] [Indexed: 03/07/2023]
Abstract
Irritable bowel syndrome (IBS) is related to a problem in the gut-brain axis. This experimental research aimed to shed light on the potential therapeutic application of elderberry (EB), which can work on the axis and get better the IBS symptoms. There were three groups (36 Sprague-Dawley rats) in this experiment, including control, IBS, and IBS with EB diet (IBS + EB). Making use of intracolonic instillation of 1 ml of 4% acetic acid for 30 s, IBS was induced. 7 days later, the EB extract (2%) was added to the diets of all animals for 8 weeks. Some histological, behavioral, and stereological techniques were used to detect the effects of EB on the gut and brain tissues. The findings showed that the EB diet improved locomotion and decreased anxiety-like behavior in the rat models of IBS. Moreover, the diet dropped the expression of TNF-α and increased mucosal layer thickness and the number of goblet and mast cells in colon tissue samples. In the hippocampal samples, administration of EB prevented astrogliosis and astrocyte reactivity. Although hippocampal and cortical neurons decreased markedly in the IBS group, EB prevented the drop in the number of neurons. Although lots of research is needed to elucidate the effectiveness of EB in IBS and its exact molecular mechanism, the result of this study showed that EB as an antioxidant and immune-modulatory agent could be a promising research target to prevent the impairment in the gut-brain axis, and could ameliorative classic IBS symptoms.
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Affiliation(s)
- Kosar Namakin
- Hearing Disorders Research Center, Loghman-Hakim Hospital, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Meysam Hassani Moghaddam
- Department of Anatomical Sciences, Faculty of Medicine, AJA University of Medical Sciences, Tehran, Iran
| | - Sara Sadeghzadeh
- Hearing Disorders Research Center, Loghman-Hakim Hospital, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Maryam Mehranpour
- Department of Genetics, Faculty of Biological Sciences, North Tehran Branch, Islamic Azad University, Tehran, Iran
| | - Kimia Vakili
- Student Research Committee, Faculty of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Mobina Fathi
- Student Research Committee, Faculty of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Ahmadreza Golshan
- Hearing Disorders Research Center, Loghman-Hakim Hospital, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Amir-Hossein Bayat
- Department of Neuroscience, School of Sciences and Advanced Technology in Medicine, Hamadan University of Medical Sciences, Hamadan, Iran
| | - Amir-Hossein Tajik
- Hearing Disorders Research Center, Loghman-Hakim Hospital, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Neda Eskandari
- Department of Anatomical Sciences, Faculty of Medicine, AJA University of Medical Sciences, Tehran, Iran
| | - Ibrahim Mohammadzadeh
- Hearing Disorders Research Center, Loghman-Hakim Hospital, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Soheila Zamanlui Benisi
- Stem Cell Research Center, Tissue Engineering and Regenerative Medicine Institute, Central Tehran Branch, Islamic Azad University, 1385/768, Tehran, Iran
| | - Abbas Aliaghaei
- Hearing Disorders Research Center, Loghman-Hakim Hospital, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
| | - Mohammad-Amin Abdollahifar
- Hearing Disorders Research Center, Loghman-Hakim Hospital, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
- Department of Biology and Anatomical Sciences, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
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19
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Li YC, Wang Q, Li MG, Hu SF, Xu GY. A paraventricular hypothalamic nucleus input to ventral of lateral septal nucleus controls chronic visceral pain. Pain 2023; 164:625-637. [PMID: 35994589 PMCID: PMC9916060 DOI: 10.1097/j.pain.0000000000002750] [Citation(s) in RCA: 27] [Impact Index Per Article: 13.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/19/2022] [Revised: 07/14/2022] [Accepted: 07/18/2022] [Indexed: 11/25/2022]
Abstract
ABSTRACT Irritable bowel syndrome is a functional gastrointestinal disorder characterized by chronic visceral pain with complex etiology and difficult treatment. Accumulated evidence has confirmed that the sensitization of the central nervous system plays an important role in the development of visceral pain, whereas the exact mechanisms of action of the neural pathways remain largely unknown. In this study, a distinct neural circuit was identified from the paraventricular hypothalamic (PVH) to the ventral of lateral septal (LSV) region. This circuit was responsible for regulating visceral pain. In particular, the data indicated that the PVH CaMKIIα-positive neurons inputs to the LSV CaMKIIα-positive neurons were only activated by colorectal distention rather than somatic stimulations. The PVH-LSV CaMKIIα + projection pathway was further confirmed by experiments containing a viral tracer. Optogenetic inhibition of PVH CaMKIIα + inputs to LSV CaMKIIα-positive neurons suppressed visceral pain, whereas selective activation of the PVH-LSV CaMKIIα + projection evoked visceral pain. These findings suggest the critical role of the PVH-LSV CaMKIIα + circuit in regulating visceral pain.
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Affiliation(s)
- Yong-Chang Li
- Jiangsu Key Laboratory of Neuropsychiatric Diseases and Institute of Neuroscience, Soochow University, Suzhou, Jiangsu, China
| | - Qian Wang
- Department of Anesthesiology, Children's Hospital of Soochow University, Suzhou, China
| | - Meng-Ge Li
- Jiangsu Key Laboratory of Neuropsychiatric Diseases and Institute of Neuroscience, Soochow University, Suzhou, Jiangsu, China
| | - Shu-Fen Hu
- Jiangsu Key Laboratory of Neuropsychiatric Diseases and Institute of Neuroscience, Soochow University, Suzhou, Jiangsu, China
| | - Guang-Yin Xu
- Jiangsu Key Laboratory of Neuropsychiatric Diseases and Institute of Neuroscience, Soochow University, Suzhou, Jiangsu, China
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20
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Ebrahimi A, Forghani M, Bababkhanian M, Ebrahimi M, Adibi Sedeh P. Psychometric properties of Persian version of irritable bowel syndrome- behavioral responses questionnaire (IBS-BRQ). GASTROENTEROLOGY AND HEPATOLOGY FROM BED TO BENCH 2023; 16:326-335. [PMID: 37767317 PMCID: PMC10520395 DOI: 10.22037/ghfbb.v16i2.2440] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 04/22/2023] [Accepted: 03/25/2023] [Indexed: 09/29/2023]
Abstract
Aim This study aimed to determine the psychometric properties of Persian version of Irritable Bowel Syndrome-Behavioral Responses Questionnaire (IBS-BRQ). Background In addition to somatic symptoms and complaints, patients with irritable bowel syndrome have specific dysfunctional behaviors that lead to disease persistence and functional disturbance. Methods Participants included 170 patients with irritable bowel syndrome, who were diagnosed based on ROM-IV criteria and selected from patients referring to the Gastrointestinal Disorders Clinic, as well as 100 persons from the general population in Isfahan in 2020. Both groups completed the 26-item Irritable Bowel Syndrome-Behavioral Responses Questionnaire (IBS-BRQ). Also, questionnaires including the Irritable Bowel Syndrome Symptom Severity Scale (IBS-SSS), Irritable Bowel Syndrome-Quality of Life IBS-QOL, Illness Perception Questionnaire (IPQ-R), Irritable Bowel Syndrome-Patient Satisfaction (IBS-SAT), Hope Scale, Interpersonal Forgiveness Inventory (IFI), and Dysfunctional Attitude Scale- 26-item (DAS-26) were completed to determine the validity of IBS-BRQ. Tests of internal consistency, principal components analyses (PCAs), differentiation analysis, and correlation were used to determine its reliability, along with criterion and construct validity. Results IBS-BRQ was valid and reliable in both groups with a high degree of internal consistency. Cronbach's alpha was obtained in the sample of patients with IBS and the total sample of participants 0.87 and 0.95 respectively. This scale differentiated significantly between IBS patients and non-patients (p<.001). The criterion validity was high as evidenced by a high correlation with DAS-26 (r=0.53, p<0.001), IBS-QOL (r=0.76, p<0.001), IBS-SSS (r=0.44, p<0.001), IPQ-R (r=0.56, p<0.001), and reverse correlation with IFI (r=-0.031, p<0.001), IBS-SAT (r=-0.23, p<0.001), and HOPE (r=-0.49, p<0.001). Conclusion The Persian version of the IBS-BRQ proved to be a well-defined behavioral response measure in IBS patients with high validity and reliability, making it a suitable measure to be used in future IBS clinical research in Iran.
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Affiliation(s)
- Amrollah Ebrahimi
- Department of Health Psychology, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran
| | - Mohammad Forghani
- Faculty of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran
| | - Masoudeh Bababkhanian
- Social Determinants of Health Research Center, Semnan University of Medical Sciences, Semnan, Iran
| | - Mehdi Ebrahimi
- Department of Orthodontics, Faculty of Dentistry, Isfahan University of Medical Sciences, Isfahan, Iran
| | - Peyman Adibi Sedeh
- Integrative Functional Gastroenterology Research Center, Isfahan University of Medical Sciences, Isfahan, Iran
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21
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Császár-Nagy N, Bókkon I. Hypnotherapy and IBS: Implicit, long-term stress memory in the ENS? Heliyon 2022; 9:e12751. [PMID: 36685398 PMCID: PMC9849985 DOI: 10.1016/j.heliyon.2022.e12751] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/12/2022] [Revised: 09/20/2022] [Accepted: 12/27/2022] [Indexed: 01/01/2023] Open
Abstract
The association between irritable bowel syndrome (IBS) and psychiatric and mood disorders may be more fundamental than was previously believed. Prenatal, perinatal, postnatal, and early-age conditions can have a key role in the development of IBS. Subthreshold mental disorders (SMDs) could also be a significant source of countless diverse diseases and may be a cause of IBS development. We hypothesize that stress-induced implicit memories may persist throughout life by epigenetic processes in the enteric nervous system (ENS). These stress-induced implicit memories may play an essential role in the emergence and maintenance of IBS. In recent decades, numerous studies have proven that hypnosis can improve the primary symptoms of IBS and also reduce noncolonic symptoms such as anxiety and depression and improve quality of life and cognitive function. These significant beneficial effects of hypnosis on IBS may be because hypnosis allows access to unconscious brain processes.
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Affiliation(s)
- N. Császár-Nagy
- National University of Public Services, Budapest, Hungary,Psychosomatic Outpatient Clinics, Budapest, Hungary
| | - I. Bókkon
- Psychosomatic Outpatient Clinics, Budapest, Hungary,Vision Research Institute, Neuroscience and Consciousness Research Department, Lowell, MA, USA,Corresponding author. H-1238, Budapest, Láng Endre 68, Hungary.
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22
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Wang X, Shi X, Lv J, Zhang J, Huo Y, Zuo G, Lu G, Liu C, She Y. Acupuncture and related therapies for the anxiety and depression in irritable bowel syndrome with diarrhea (IBS-D): A network meta-analysis of randomized controlled trials. Front Psychiatry 2022; 13:1067329. [PMID: 36620677 PMCID: PMC9816906 DOI: 10.3389/fpsyt.2022.1067329] [Citation(s) in RCA: 11] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/11/2022] [Accepted: 12/07/2022] [Indexed: 12/25/2022] Open
Abstract
Objective A growing number of clinical studies have suggested the value of acupuncture-related therapies for patients with irritable bowel syndrome with diarrhea (IBS-D), and the patient's mental state plays an important role, but there are many types of acupuncture-related therapies involved. This study aimed to evaluate the mental status, efficacy and safety of the different acupuncture-related therapies for IBS-D patients. Methods We searched seven databases to collect randomized controlled trials of acupuncture-related therapies for IBS-D. After independent literature screening and data extraction, the quality of the final included literature was evaluated. Hamilton anxiety rating scale (HAMA), hamilton depression rating scale (HAMD), self-rating anxiety scale (SAS), and self-rating depression scale (SDS) was used as the primary outcome indicator. And the network meta-analysis (NMA) was performed by using Revman 5.4, Stata 15.0 and WinBUGS 1.4.3 software, and the surface under the cumulative ranking curve was conducted to rank the included interventions. Results We analyzed 24 eligible studies with 1,885 patients, involving eight types of acupuncture and related therapies along with comprehensive therapies. The NMA result shows that: for SAS scores, combined therapies were more efficacious than anti-diarrheal or antispasmodic (western medicine, WM) (SMD: -8.92; 95% CI: -15.30, -2.47); for SDS scores, combined therapies were more efficacious than WM (SMD: -8.45; 95% CI: -15.50, -1.41). For HAMA scores, moxibustion (MOX) was more efficacious than placebo (SMD: -8.66; 95% CI: -16.64, -0.38). For HAMD scores, MOX was more efficacious than all other included interventions. For response rate, MOX was more efficacious than the following interventions: acupuncture (ACU) (SMD:0.29; 95% CI:0.08,0.93), Chinese herb medicine (CH) (SMD:0.09; 95% CI:0.02,0.36), combined therapies (SMD:0.23; 95% CI:0.06, 0.85), electroacupuncture (EA) (SMD:0.06; 95% CI:0.01,0.33), warm acupuncture (WA) (SMD:22.16; 95% CI:3.53,148.10), WM (SMD:15.59; 95% CI:4.68,61.21), and placebo (SMD:9.80; 95% CI:2.90,45.51). Combined therapies were more efficacious than the following interventions: CH (SMD:0.39; 95% CI:0.19,0.80), WA (SMD:4.96; 95% CI:1.30,21.62), and WM (SMD:3.62; 95% CI:2.35,5.66). The comprehensive ranking results show that MOX, ACU, combined therapies, and EA had high SUCRA rankings involving different outcome indicators. Conclusion MOX, ACU, combined therapies, and EA better alleviate anxiety and depression among IBS-D patients, and with a higher safety level, may be the optimal therapies. In addition, combining acupuncture-related treatments and other therapies also delivers a higher global benefit level. Systematic review registration [https://www.crd.york.ac.uk/], identifier [CRD42022364560].
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Affiliation(s)
- Xuesong Wang
- School of Acupuncture-Moxibustion and Tuina, Hebei University of Chinese Medicine, Shijiazhuang, Hebei, China
| | - Xuliang Shi
- School of Acupuncture-Moxibustion and Tuina, Hebei University of Chinese Medicine, Shijiazhuang, Hebei, China
- Hebei International Joint Research Center for Dominant Diseases in Chinese Medicine and Acupuncture, Hebei University of Chinese Medicine, Shijiazhuang, Hebei, China
| | - Jing Lv
- School of Acupuncture-Moxibustion and Tuina, Hebei University of Chinese Medicine, Shijiazhuang, Hebei, China
- Hebei International Joint Research Center for Dominant Diseases in Chinese Medicine and Acupuncture, Hebei University of Chinese Medicine, Shijiazhuang, Hebei, China
| | - Juncha Zhang
- School of Acupuncture-Moxibustion and Tuina, Hebei University of Chinese Medicine, Shijiazhuang, Hebei, China
- Hebei International Joint Research Center for Dominant Diseases in Chinese Medicine and Acupuncture, Hebei University of Chinese Medicine, Shijiazhuang, Hebei, China
| | - Yongli Huo
- Department of Spleen and Stomach, Hebei Province Hospital of Chinese Medicine, Shijiazhuang, Hebei, China
| | - Guang Zuo
- School of Acupuncture-Moxibustion and Tuina, Hebei University of Chinese Medicine, Shijiazhuang, Hebei, China
| | - Guangtong Lu
- School of Acupuncture-Moxibustion and Tuina, Hebei University of Chinese Medicine, Shijiazhuang, Hebei, China
| | - Cunzhi Liu
- School of Acupuncture-Moxibustion and Tuina, Beijing University of Chinese Medicine, Beijing, China
| | - Yanfen She
- School of Acupuncture-Moxibustion and Tuina, Hebei University of Chinese Medicine, Shijiazhuang, Hebei, China
- Hebei International Joint Research Center for Dominant Diseases in Chinese Medicine and Acupuncture, Hebei University of Chinese Medicine, Shijiazhuang, Hebei, China
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Nabbijohn AN, Ahola Kohut S. Gastrointestinal Disorders in Adolescents and Young Adults: Preparing for a Smooth Transition to Adult-Centered Care. Gastroenterol Clin North Am 2022; 51:849-865. [PMID: 36376000 DOI: 10.1016/j.gtc.2022.07.008] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/04/2022]
Abstract
Chronic gastrointestinal disorders are prevalent in youth worldwide. The chronicity of these conditions often results in their persistence into adulthood. Challenges typically faced by young people transitioning to adulthood are often exacerbated in those with chronic gastrointestinal disease. Increased awareness of these challenges among health care professionals and appropriate policies and procedures for health care transition are critical. This article summarizes research on the challenges faced by emerging adults with the gastrointestinal disease during the transition to adult care. Barriers to optimal transitional care and current guidelines are discussed and used to offer practical recommendations for health care professionals working with this population.
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Affiliation(s)
- A Natisha Nabbijohn
- Department of Psychology, University of Guelph, 50 Stone Road East, Guelph, Ontario N1G 2W1, Canada
| | - Sara Ahola Kohut
- Department of Gastroenterology, Hepatology, and Nutrition, Hospital for Sick Children, Toronto, Canada; Department of Psychiatry, University of Toronto, Toronto, Canada; Child Health Evaluative Sciences, SickKids Research Institute, Toronto, Canada.
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24
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Karunanayake A, Devanarayana NM, Rajindrajith S. Early life events in functional abdominal pain disorders in children. PLoS One 2022; 17:e0275419. [PMID: 36322579 PMCID: PMC9629606 DOI: 10.1371/journal.pone.0275419] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/30/2020] [Accepted: 09/18/2022] [Indexed: 11/05/2022] Open
Abstract
OBJECTIVES Functional abdominal pain disorders (FAPDs) are common gastrointestinal problems in children, and the pathophysiology is thought to be multifactorial. Adverse early life events (ELE) induce alterations in the central nervous system, perhaps predisposing individuals to develop FAPDs. We aimed to study the potential adverse ELE that are associated with FAPDs. METHODS We steered a school-based survey involving 1000 children from 4 randomly selected schools. FAPDs were assessed using the translated Rome III questionnaire, and ELE were identified using a pre-tested, parental questionnaire. FAPDs were diagnosed using the Rome III criteria. RESULTS Hundred and eighty-two (182) children had FAPDs (62.1% girls, mean age 8.5, SD 2.1). ELE of them were compared with 571 children without FAPDs (51.1% girls, mean age 8.8, SD 1.9). According to the binary logistic regression analysis, family members with abdominal pain, family member with chronic pain other than abdominal pain, prenatal maternal complications and interventional deliveries, were recognized as potential risk factors for the development of FAPDs. Breast feeding over two years has shown to reduce the prevalence of FAPDs.a. CONCLUSIONS Prenatal maternal medical problems are associated a with higher prevalence of FAPDs later in life. Prolonged breastfeeding and normal vaginal delivery could be considered as factors that reduce the vulnerability of developing FAPDs in children. Therefore, minimizing pregnancy-related complications, encouraging vaginal deliveries, and encouraging breastfeeding are potentially valuable measures to prevent FAPDs during childhood.
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25
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Grozić A, Coker K, Dussik CM, Sabir MS, Sabir Z, Bradley A, Zhang L, Park J, Yale S, Kaneko I, Hockley M, Harris LA, Lunsford TN, Sandrin TR, Jurutka PW. Identification of putative transcriptomic biomarkers in irritable bowel syndrome (IBS): Differential gene expression and regulation of TPH1 and SERT by vitamin D. PLoS One 2022; 17:e0275683. [PMID: 36264926 PMCID: PMC9584396 DOI: 10.1371/journal.pone.0275683] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/23/2022] [Accepted: 09/21/2022] [Indexed: 11/06/2022] Open
Abstract
Irritable bowel syndrome (IBS) is one of the most common gastrointestinal disorders and affects approximately 4% of the global population. The diagnosis of IBS can be made based on symptoms using the validated Rome criteria and ruling out commonly occurring organic diseases. Although biomarkers exist for "IBS mimickers" such as celiac disease and inflammatory bowel disease (IBD), no such test exists for IBS. DNA microarrays of colonic tissue have been used to identify disease-associated variants in other gastrointestinal (GI) disorders. In this study, our objective was to identify biomarkers and unique gene expression patterns that may define the pathological state of IBS. Mucosal tissue samples were collected from the sigmoid colon of 29 participants (11 IBS and 18 healthy controls). DNA microarray analysis was used to assess gene expression profiling. Extraction and purification of RNA were then performed and used to synthesize cDNA. Reverse transcriptase quantitative polymerase chain reaction (RT-qPCR) was employed to identify differentially expressed genes in patients diagnosed with IBS compared to healthy, non-IBS patient-derived cDNA. Additional testing probed vitamin D-mediated regulation of select genes associated with serotonergic metabolism. DNA microarray analyses led to the identification of 858 differentially expressed genes that may characterize the IBS pathological state. After screening a series of genes using a combination of gene ontological analysis and RT-qPCR, this spectrum of potential IBS biomarkers was narrowed to 23 genes, some of which are regulated by vitamin D. Seven putative IBS biomarkers, including genes involved in serotonin metabolism, were identified. This work further supports the hypothesis that IBS pathophysiology is evident within the human transcriptome and that vitamin D modulates differential expression of genes in IBS patients. This suggests that IBS pathophysiology may also involve vitamin D deficiency and/or an irregularity in serotonin metabolism.
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Affiliation(s)
- Aleksandra Grozić
- School of Mathematical and Natural Sciences, Arizona State University, Phoenix, AZ, United States of America
| | - Keaton Coker
- School of Mathematical and Natural Sciences, Arizona State University, Phoenix, AZ, United States of America
| | - Christopher M. Dussik
- School of Mathematical and Natural Sciences, Arizona State University, Phoenix, AZ, United States of America
| | - Marya S. Sabir
- School of Mathematical and Natural Sciences, Arizona State University, Phoenix, AZ, United States of America
| | - Zhela Sabir
- School of Mathematical and Natural Sciences, Arizona State University, Phoenix, AZ, United States of America
| | - Arianna Bradley
- School of Mathematical and Natural Sciences, Arizona State University, Phoenix, AZ, United States of America
| | - Lin Zhang
- School of Mathematical and Natural Sciences, Arizona State University, Phoenix, AZ, United States of America
| | - Jin Park
- Biodesign Institute, Arizona State University, Tempe, AZ, United States of America
| | - Steven Yale
- Department of Medicine, University of Central Florida College of Medicine, Orlando, FL, United States of America
| | - Ichiro Kaneko
- School of Mathematical and Natural Sciences, Arizona State University, Phoenix, AZ, United States of America
- Department of Basic Medical Sciences, University of Arizona College of Medicine, Phoenix, AZ, United States of America
| | - Maryam Hockley
- School of Mathematical and Natural Sciences, Arizona State University, Phoenix, AZ, United States of America
| | - Lucinda A. Harris
- Mayo Clinic Division of Gastroenterology & Hepatology, Alix School of Medicine, Mayo Clinic, Scottsdale, AZ, United States of America
| | - Tisha N. Lunsford
- Mayo Clinic Division of Gastroenterology & Hepatology, Alix School of Medicine, Mayo Clinic, Scottsdale, AZ, United States of America
| | - Todd R. Sandrin
- School of Mathematical and Natural Sciences, Arizona State University, Phoenix, AZ, United States of America
- Julie Ann Wrigley Global Futures Laboratory, Arizona State University, Tempe, AZ, United States of America
| | - Peter W. Jurutka
- School of Mathematical and Natural Sciences, Arizona State University, Phoenix, AZ, United States of America
- Department of Basic Medical Sciences, University of Arizona College of Medicine, Phoenix, AZ, United States of America
- * E-mail:
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26
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Zia JK, Lenhart A, Yang PL, Heitkemper MM, Baker J, Keefer L, Saps M, Cuff C, Hungria G, Videlock EJ, Chang L. Risk Factors for Abdominal Pain-Related Disorders of Gut-Brain Interaction in Adults and Children: A Systematic Review. Gastroenterology 2022; 163:995-1023.e3. [PMID: 35716771 PMCID: PMC9509486 DOI: 10.1053/j.gastro.2022.06.028] [Citation(s) in RCA: 58] [Impact Index Per Article: 19.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/26/2022] [Revised: 06/06/2022] [Accepted: 06/08/2022] [Indexed: 12/02/2022]
Abstract
BACKGROUND & AIMS Many studies have assessed risk factors of irritable bowel syndrome (IBS) and other abdominal pain-related disorders of gut-brain interaction (AP-DGBI); however, the role of these factors is unclear due to heterogeneous study designs. The aim of this systematic review was to extensively evaluate the literature and determine clinical risk and protective factors for the presence and persistence of AP-DGBI in children and adults. METHODS A PubMed search identified studies investigating potential risk and protective factors for AP-DGBI in adults and children. Inclusion criteria included fully published studies with a control group; exclusion criteria included poor-quality studies (using a validated scale). For each factor, the proportion of studies that found the factor to be a risk factor, protective factor, or neither was summarized. The number of studies, diagnostic criteria, number of subjects, and average study quality rating provided further context. Whenever possible, a meta-analysis generated pooled odds ratios or mean difference. RESULTS The systematic review included 348 studies. Female sex, gastroenteritis, abuse, stress, psychological disorders, somatic symptoms, and poor sleep were consistent risk factors for developing AP-DGBI in adults and children. In adults, additional risk factors included obesity, smoking, and increased use of medical resources. Protective AP-DGBI factors in adults included social support and optimism; no studies for protective factors were found for children. CONCLUSIONS There are multiple risk factors for AP-DGBI in adults and children. These include female sex, gastroenteritis, abuse, stress, poor sleep, obesity, psychological disorders, and somatic symptoms. Additional studies are needed in children, on protective factors, and on factors associated with persistence of AP-DGBI.
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Affiliation(s)
- Jasmine K. Zia
- Division of Gastroenterology, Department of Medicine, University of Washington, Seattle, Washington
| | - Adrienne Lenhart
- Vatche and Tamar Manoukian Division of Digestive Diseases, Department of Medicine, David Geffen School of Medicine at University of California, Los Angeles, California
| | - Pei-Lin Yang
- School of Nursing, National Defense Medical Center, Taipei, Taiwan
| | - Margaret M. Heitkemper
- Department of Biobehavioral Nursing and Health Informatics, School of Nursing, University of Washington, Seattle, Washington
| | - Jason Baker
- Division of Gastroenterology and Hepatology, Michigan Medicine, Ann Arbor, Michigan
| | - Laurie Keefer
- Division of Gastroenterology, Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, New York
| | - Miguel Saps
- Division of Pediatrics Gastroenterology, Hepatology and Nutrition, Miller School of Medicine, University of Miami, Miami, Florida
| | - Callie Cuff
- Vatche and Tamar Manoukian Division of Digestive Diseases, Department of Medicine, David Geffen School of Medicine at University of California, Los Angeles, California
| | - Gregory Hungria
- Division of Pediatrics Gastroenterology, Hepatology and Nutrition, Miller School of Medicine, University of Miami, Miami, Florida
| | - Elizabeth J. Videlock
- Vatche and Tamar Manoukian Division of Digestive Diseases, Department of Medicine, David Geffen School of Medicine at University of California, Los Angeles, California
| | - Lin Chang
- Vatche and Tamar Manoukian Division of Digestive Diseases, Department of Medicine, David Geffen School of Medicine at University of California, Los Angeles, California.
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27
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Bentele M, Stengel A. [Hypnotherapy for Irritable Bowel Syndrome]. Psychother Psychosom Med Psychol 2022; 72:452-460. [PMID: 36257312 DOI: 10.1055/a-1807-6876] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 06/16/2023]
Abstract
Irritable bowel syndrome (IBS) is a functional disorder of the lower digestive tract. Based on the biopsychosocial model, there is a wide range of therapeutic interventions to deal with the symptoms of IBS and to improve the quality of life of those who are affected. In this context, hypnotherapy and in particular gut-directed hypnosis represents a psychotherapeutic intervention with great empirical evidence for its efficacy.
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Westmore MR, Chakraborty P, Thomas LA, Jenkins L, Ohri F, Baiden P. BMI moderates the association between adverse childhood experiences and COPD. J Psychosom Res 2022; 160:110990. [PMID: 35878540 PMCID: PMC9531576 DOI: 10.1016/j.jpsychores.2022.110990] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/16/2022] [Revised: 07/08/2022] [Accepted: 07/10/2022] [Indexed: 10/17/2022]
Abstract
OBJECTIVES Cigarette smoking and obesity are leading risk factors for chronic obstructive pulmonary disease (COPD). Although studies have established an association between adverse childhood experiences (ACEs) and COPD, few studies have examined whether this association is moderated by cigarette smoking or body mass index (BMI). This cross-sectional study examined the association between ACEs and COPD, and whether cigarette smoking or BMI moderates this association. METHODS Data for this study came from the 2019 Behavioral Risk Factor Surveillance System survey. An analytic sample of 75,700 adults aged 18-79 years (50.7% female) were analyzed using binary logistic regression. The outcome variable investigated was self-reported physician-diagnosed COPD, and the main explanatory variable was ACEs. RESULTS Of the 75,700 respondents examined, 8.1% had COPD. About one in three (33.6%) respondents had no ACEs, 23.1% had one ACE, and about one in five (20.2%) had four or more ACEs. In the multivariable binary logistic regression, we found that the association between ACEs and COPD differs by BMI status. Controlling for the effects of other factors, the association between ACEs and COPD is strongest for respondents who are obese (AOR = 1.41, 95% CI = 1.04-1.91). CONCLUSIONS The findings of this study demonstrate that ACEs are associated with COPD later in adulthood, and BMI moderated this association. The findings of this study add to the number of studies demonstrating the adverse impact of ACEs on chronic health outcomes among adults.
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Affiliation(s)
- Megan R Westmore
- The University of Texas at Arlington, School of Social Work, 211 S. Cooper St., Box 19129, Arlington, TX 76019, United States
| | - Priyanjali Chakraborty
- The University of Texas at Arlington, School of Social Work, 211 S. Cooper St., Box 19129, Arlington, TX 76019, United States
| | - LaTisha A Thomas
- The University of Texas at Arlington, School of Social Work, 211 S. Cooper St., Box 19129, Arlington, TX 76019, United States
| | - Lacey Jenkins
- The University of Texas at Arlington, School of Social Work, 211 S. Cooper St., Box 19129, Arlington, TX 76019, United States
| | - Faheem Ohri
- The University of Texas at Arlington, School of Social Work, 211 S. Cooper St., Box 19129, Arlington, TX 76019, United States
| | - Philip Baiden
- The University of Texas at Arlington, School of Social Work, 211 S. Cooper St., Box 19129, Arlington, TX 76019, United States.
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Prevalence of Gastrointestinal Symptoms and Irritable Bowel Syndrome Among Individuals With Symptomatic Posttraumatic Stress Disorder. J Clin Gastroenterol 2022; 56:592-596. [PMID: 35089910 DOI: 10.1097/mcg.0000000000001670] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/08/2021] [Accepted: 12/16/2021] [Indexed: 12/12/2022]
Abstract
GOALS Our aim was to describe the prevalence of irritable bowel syndrome (IBS) and other gastrointestinal symptoms in a sample of veterans with posttraumatic stress disorder (PTSD) and to examine the relationship between gastrointestinal symptoms, PTSD severity, depression severity, and number of prior traumatic events reported. BACKGROUND IBS and PTSD can co-occur; yet, little research has focused on describing the gastrointestinal symptoms and prevalence of IBS among veterans with PTSD. MATERIALS AND METHODS We examined baseline data from a randomized clinical trial of behavioral interventions for veterans with PTSD. Veterans completed questionnaires assessing gastrointestinal symptoms (Gastrointestinal Patient-Reported Outcome Measures Information Systems; PROMIS) and lifetime traumatic events. Multivariable regression analyses were performed to examine associations between gastrointestinal symptoms and the number of prior traumas reported PTSD severity, and depression symptom severity. RESULTS One hundred eighty-four veterans with a diagnosis of PTSD were included. Twenty-five percent met the Rome III criteria for IBS. Veterans reported gastrointestinal symptoms including abdominal/belly pain (36%), diarrhea (21%), constipation (18%), and bloating/gas (17%). In multivariable analyses, greater PTSD severity was associated with worse constipation ( P =0.008), diarrhea ( P =0.005), and gas/bloating ( P =0.001) when controlling for age and sex. Higher levels of depressive symptoms severity were associated with greater abdominal/belly pain ( P =0.04). CONCLUSIONS Among a sample of veterans with PTSD, rates of IBS and abdominal/belly pain are greater than general US population reference values. Although levels of constipation and bloating/gas are lower than general US population reference values, increased severity of PTSD was associated with increased gastrointestinal symptoms.
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Liang SB, Han M, Cheng HJ, Zhang QY, Zhang NW, Jia BY, Robinson N, Liu JP. Chinese herbal formula Tongxie Yaofang for diarrhea-predominant irritable bowel syndrome: study protocol for a randomized, multiple-blind, placebo-controlled trial. Trials 2022; 23:226. [PMID: 35313933 PMCID: PMC8935852 DOI: 10.1186/s13063-022-06142-x] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/22/2021] [Accepted: 03/03/2022] [Indexed: 12/31/2022] Open
Abstract
Abstract
Introduction
Diarrhea-predominant irritable bowel syndrome (IBS-D) is a bowel disease with a high incidence. It significantly reduces the quality of life of patients and affects the patient's daily activities and mental health. No specific therapeutic medications for IBS-D have been found. Published clinical trials suggest that Chinese herbal formula Tongxie Yaofang (TXYF) for IBS-D may be effective. However, high-quality clinical evidence supporting its use in IBS-D is still lacking. This trial aims to evaluate the therapeutic effects and safety of TXYF for IBS-D in adults.
Methods/design
A randomized, multiple-blind, placebo-controlled trial will be conducted. It will consist of an 8-week intervention followed by a 3-month follow-up period.
The target sample size is 96 IBS-D patients aged 18 to 65 years. The eligible participants will be randomly allocated to either TXYF or placebo group in a ratio of 1:1. Participants in the experimental group will take TXYF granules, while participants in the control group will be given TXYF placebo granules. The primary outcome will be the degree of IBS symptom severity measured using the scale of IBS symptom severity score. The secondary outcomes include: (a) stool frequency, and (b) stool consistency measured using the Bristol stool scale, (c) quality of life measured using the scale of IBS-quality of life, (d) anxiety measured using the self-rating anxiety scale, (e) depression measured by the self-rating depression scale, and (f) the safety of using TXYF and placebo. Safety monitoring and assessment will be undertaken throughout treatment.
Discussion
Chinese herbal formula TXYF consists of four Chinese herbs: Atractylodes macrocephala Koidz., Paeonia lactiflora Pall., Citrus × aurantium L., and Radix saposhnikoviae. It has been used for diarrhea for hundreds of years and may have a potential benefit in treating adults with IBS-D, but due to lack of high-quality evidence, we designed a randomized, multiple-blind, placebo-controlled trial to evaluate its therapeutic effects and safety. This trial will provide important data to guide the clinical practice of TXYF for the treatment of IBS-D in adults.
Trial registration
ISRCTN registry ISRCTN12453166. Registered on 23 March 2021.
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Shen J, Zhang B, Chen J, Cheng J, Wang J, Zheng X, Lan Y, Zhang X. SAHA Alleviates Diarrhea-Predominant Irritable Bowel Syndrome Through Regulation of the p-STAT3/SERT/5-HT Signaling Pathway. J Inflamm Res 2022; 15:1745-1756. [PMID: 35300211 PMCID: PMC8923685 DOI: 10.2147/jir.s331303] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/27/2021] [Accepted: 11/22/2021] [Indexed: 12/12/2022] Open
Abstract
Objective Irritable bowel syndrome (IBS) is characterized by abdominal pain, bloating, and stool irregularity. However, its pathophysiological mechanisms, which trigger intestinal motility disorders and diarrhea leading to diarrhea-predominant IBS (D-IBS), remain largely unknown. Methods In the present study, we established a D-IBS rat model by mother–infant separation combined with restraint stress. Then we exposed the modelled rats to suberoylanilide hydroxamic acid (SAHA) treatment, followed by determination of their visceral sensitivity. Toluidine blue staining served to reveal the effects of SAHA treatment on mast cells of D-IBS model rats. Then we measured the expression of serotonin (5-hydroxytryptamine; 5-HT) and its receptors by ELISA. Results Construction of short hairpin RNA (sh)-serotonin transporter (SERT) lentivirus vectors verified the regulation of the 5-HT signaling pathway by phosphorylated (p)-STAT/SERT. SAHA treatment of D-IBS model rats reduced the fecal water content, electromyography integral change rate, abdominal withdrawal reflex score, and number of mast cells, as well as the expression of 5-HT type 3A (5-HT3AR), 3B receptor (5-HT3BR), and 4 receptor (5-HT4R) receptors. The treatment also elevated the expression of signal transducer and activator for transcription 3 (STAT3) and SERT. Activation of p-STAT3 may reverse the inhibitory effect of SAHA on the elevated visceral sensitivity of D-IBS model rats. Moreover, SAHA promoted the transcription of SERT through repression of the p-STAT3/5-HT signaling, thereby inhibiting the visceral sensitivity of D-IBS model rats. Conclusion This study highlights that SAHA treatment can alleviate D-IBS through regulation of the p-STAT3/SERT/5-HT signaling pathway.
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Affiliation(s)
- Jian Shen
- Department of Pediatrics, Shuguang Hospital Affiliated to Shanghai Traditional Chinese Medical University, Shanghai, 201203, People’s Republic of China
- Correspondence: Jian Shen Department of Pediatrics, Shuguang Hospital Affiliated to Shanghai Traditional Chinese Medical University, Shanghai, 201203, People’s Republic of ChinaTel +86-21-53821650 Email
| | - Bimeng Zhang
- Department of Acupuncture and Moxibustion, Shanghai General Hospital (The First People’s Hospital Affiliated to Shanghai Jiaotong University), Shanghai, 200080, People’s Republic of China
| | - Jianjie Chen
- Department of Internal Medicine, Shuguang Hospital Affiliated to Shanghai Traditional Chinese Medical University, Shanghai, 201203, People’s Republic of China
| | - Jiazheng Cheng
- Department of Pediatrics, Shuguang Hospital Affiliated to Shanghai Traditional Chinese Medical University, Shanghai, 201203, People’s Republic of China
| | - Jiali Wang
- Department of Pediatrics, Shuguang Hospital Affiliated to Shanghai Traditional Chinese Medical University, Shanghai, 201203, People’s Republic of China
| | - Xianhui Zheng
- Department of Pediatrics, Shuguang Hospital Affiliated to Shanghai Traditional Chinese Medical University, Shanghai, 201203, People’s Republic of China
| | - Yu Lan
- Department of Pediatrics, Shuguang Hospital Affiliated to Shanghai Traditional Chinese Medical University, Shanghai, 201203, People’s Republic of China
| | - Xiaowen Zhang
- Department of Pediatrics, Shuguang Hospital Affiliated to Shanghai Traditional Chinese Medical University, Shanghai, 201203, People’s Republic of China
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Quinton S, Doerfler B. Psychological and Nutritional Factors in Pelvic Floor Disorders. Gastroenterol Clin North Am 2022; 51:145-156. [PMID: 35135659 DOI: 10.1016/j.gtc.2021.10.009] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/21/2023]
Abstract
This article discusses the role of psychological and nutritional factors in gastrointestinal pelvic floor disorders such as dyssynergic defection and explores the use of multidisciplinary strategies to enhance treatment.
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Affiliation(s)
| | - Bethany Doerfler
- Division of Gastroenterology and Hepatology, Northwestern University Feinberg School of Medicine, 676 N. Saint Clair Street, Suite 1400, Chicago, IL 60611, USA.
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Tao E, Long G, Yang T, Chen B, Guo R, Ye D, Fang M, Jiang M. Maternal Separation Induced Visceral Hypersensitivity Evaluated via Novel and Small Size Distention Balloon in Post-weaning Mice. Front Neurosci 2022; 15:803957. [PMID: 35153662 PMCID: PMC8831756 DOI: 10.3389/fnins.2021.803957] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/28/2021] [Accepted: 12/20/2021] [Indexed: 11/29/2022] Open
Abstract
Early life stress (ELS) disposes to functional gastrointestinal diseases in adult, such as irritable bowel syndrome (IBS). Maternal separation (MS) is a well-known animal model of IBS and has been shown to induce visceral hypersensitivity in adult rats and mice. However, to the best of our knowledge, it has not been reported whether MS induces visceral hypersensitivity in young mice, such as the post-weaning mice. Moreover, the method for evaluation of visceral sensitivity also has not been described. Accordingly, the present study aims to evaluate the visceral sensitivity caused by MS in post-weaning mice and develop a novel and small size distention balloon for assessment of visceral sensitivity of such mice. Male pups of C57BL/6 mice were randomly divided into two groups, MS (n = 12) and non-separation (NS) (n = 10). MS pups were separated from the dams through postnatal days (PND) 2 to 14, while NS pups were undisturbed. After, all pups stayed with respective dams and were weaned at PND 22. Visceral sensitivity was evaluated by colorectal distention (CRD) with a novel and small size distention balloon at PND 25. The threshold of abdominal withdrawal reflex (AWR) scores were significantly lower in MS than NS. In addition, AWR scores at different pressures of CRD were significantly higher in MS than NS. The results demonstrate that MS induced visceral hypersensitivity in post-weaning mice. The designed small size distention balloon for evaluation of visceral sensitivity is of significance to further study the pathophysiology of IBS from early life to adulthood.
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Affiliation(s)
- Enfu Tao
- Endoscopy Center and Gastrointestinal Laboratory, Children’s Hospital, Zhejiang University School of Medicine, National Clinical Research Center for Child Health, National Children’s Regional Medical Center, Hangzhou, China
- Department of Pediatrics, Wenling Maternal and Child Health Care Hospital, Wenling, China
| | - Gao Long
- Endoscopy Center and Gastrointestinal Laboratory, Children’s Hospital, Zhejiang University School of Medicine, National Clinical Research Center for Child Health, National Children’s Regional Medical Center, Hangzhou, China
| | - Ting Yang
- Endoscopy Center and Gastrointestinal Laboratory, Children’s Hospital, Zhejiang University School of Medicine, National Clinical Research Center for Child Health, National Children’s Regional Medical Center, Hangzhou, China
| | - Bo Chen
- Endoscopy Center and Gastrointestinal Laboratory, Children’s Hospital, Zhejiang University School of Medicine, National Clinical Research Center for Child Health, National Children’s Regional Medical Center, Hangzhou, China
| | - Rui Guo
- Endoscopy Center and Gastrointestinal Laboratory, Children’s Hospital, Zhejiang University School of Medicine, National Clinical Research Center for Child Health, National Children’s Regional Medical Center, Hangzhou, China
| | - Diya Ye
- Endoscopy Center and Gastrointestinal Laboratory, Children’s Hospital, Zhejiang University School of Medicine, National Clinical Research Center for Child Health, National Children’s Regional Medical Center, Hangzhou, China
| | - Marong Fang
- Institute of Neuroscience and Gastrointestinal Laboratory, Children’s Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | - Mizu Jiang
- Endoscopy Center and Gastrointestinal Laboratory, Children’s Hospital, Zhejiang University School of Medicine, National Clinical Research Center for Child Health, National Children’s Regional Medical Center, Hangzhou, China
- *Correspondence: Mizu Jiang,
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Joshee S, Lim L, Wybrecht A, Berriesford R, Riddle M. Meta-analysis and systematic review of the association between adverse childhood events and irritable bowel syndrome. J Investig Med 2022; 70:1342-1351. [PMID: 35086857 DOI: 10.1136/jim-2021-002109] [Citation(s) in RCA: 11] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 01/12/2022] [Indexed: 11/03/2022]
Abstract
Irritable bowel syndrome (IBS) is a disorder of gut-brain interaction characterized by abdominal pain, bowel habits alterations, constipation, and/or diarrhea. Adverse childhood experiences (ACEs) are events such as abuse and mental illness causing childhood trauma. Studies report higher prevalence of ACEs in patients with IBS with varied effect consistency and association strength. A systematic review and meta-analysis were conducted to evaluate current literature, assess heterogeneity and research gaps in this relationship. A search across PubMed, Embase, PsycINFO, and Google Scholar with keywords ('childhood adversity' OR 'childhood trauma' OR 'adverse childhood events') AND ('irritable colon' OR 'irritable bowel syndrome') yielded 106 studies. A restricted maximum likelihood model of 15 chosen studies with 272,686 participants found the association between ACEs and IBS to be uncertain given the considerable heterogeneity (I2=93.58%, p<0.001). Objective reporting methods for ACE and IBS, study size, and study quality explained some heterogeneity. Twelve studies showed publication bias (Egger's test, p<0.001), which further weakened interpretation. Gender-stratified subanalysis of three studies found ACEs associated with IBS in females (pOR=2.20, 95% CI (1.13 to 4.29), I2=66.90%) with substantial heterogeneity, but no association in males (pOR=1.30, 95% CI (0.62 to 2.78)). This meta-analysis explores the current literature to understand the biopsychosocial perspective of IBS and ACEs' role as risk factors. However, the risk of publication and design/study quality biases substantiates the need for further research. If an association is confirmed, further mechanistic research and development of targeted psychological therapies may be warranted.
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Affiliation(s)
- Shreeya Joshee
- University of Nevada Reno School of Medicine, Reno, Nevada, USA
| | - Lauren Lim
- University of Nevada Reno School of Medicine, Reno, Nevada, USA
| | - Alexis Wybrecht
- University of Nevada Reno School of Medicine, Reno, Nevada, USA
| | | | - Mark Riddle
- University of Nevada Reno School of Medicine, Reno, Nevada, USA
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Association of Consuming Tap Water or Purified Water during Infancy with Irritable Bowel Syndrome in Children. CHILDREN 2022; 9:children9020135. [PMID: 35204856 PMCID: PMC8869972 DOI: 10.3390/children9020135] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 10/20/2021] [Revised: 12/30/2021] [Accepted: 01/15/2022] [Indexed: 11/23/2022]
Abstract
Objective: The objective of this study was to analyze the effect of consuming formula powder prepared with tap water or purified water during the first 4 to 6 months of life on the subsequent development of irritable bowel syndrome (IBS). Study design and setting: A total of 917,707 children who were born in Korea between 2007 and 2008 were analyzed. All children were followed up until they lost eligibility for health care services or until 2017. Data on the water used to prepare formula powder were from questionnaires answered by the parents when the child was 4 to 6 months old. IBS was defined as two or more diagnoses of IBS after the age of 4 years. Inverse probability of treatment weighting (IPTW) using the propensity score was used to balance the two groups. The risk of IBS was evaluated using a Cox proportional hazards model. Results: After weighting, there were 73,355 children in the tap water group and 73,351 in the purified water group. The purified water group had a higher risk of IBS (HR: 1.05; 95% CI: 1.01, 1.09). This relationship was also present after the subgroup analyses of males and females and the sensitivity analysis that used different definitions of IBS. Conclusions: Drinking formula powder prepared with purified water rather than tap water during the first 4 to 6 months of age was found to be associated with IBS.
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OUP accepted manuscript. Pathog Dis 2022; 80:6521441. [DOI: 10.1093/femspd/ftac003] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/28/2021] [Revised: 10/30/2021] [Accepted: 02/01/2022] [Indexed: 11/15/2022] Open
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Layer P, Andresen V, Allescher H, Bischoff SC, Claßen M, Elsenbruch S, Freitag M, Frieling T, Gebhard M, Goebel-Stengel M, Häuser W, Holtmann G, Keller J, Kreis ME, Kruis W, Langhorst J, Jansen PL, Madisch A, Mönnikes H, Müller-Lissner S, Niesler B, Pehl C, Pohl D, Raithel M, Röhrig-Herzog G, Schemann M, Schmiedel S, Schwille-Kiuntke J, Storr M, Preiß JC, Andus T, Buderus S, Ehlert U, Engel M, Enninger A, Fischbach W, Gillessen A, Gschossmann J, Gundling F, Haag S, Helwig U, Hollerbach S, Karaus M, Katschinski M, Krammer H, Kuhlbusch-Zicklam R, Matthes H, Menge D, Miehlke S, Posovszky MC, Schaefert R, Schmidt-Choudhury A, Schwandner O, Schweinlin A, Seidl H, Stengel A, Tesarz J, van der Voort I, Voderholzer W, von Boyen G, von Schönfeld J, Wedel T. Update S3-Leitlinie Reizdarmsyndrom: Definition, Pathophysiologie, Diagnostik und Therapie. Gemeinsame Leitlinie der Deutschen Gesellschaft für Gastroenterologie, Verdauungs- und Stoffwechselkrankheiten (DGVS) und der Deutschen Gesellschaft für Neurogastroenterologie und Motilität (DGNM) – Juni 2021 – AWMF-Registriernummer: 021/016. ZEITSCHRIFT FUR GASTROENTEROLOGIE 2021; 59:1323-1415. [PMID: 34891206 DOI: 10.1055/a-1591-4794] [Citation(s) in RCA: 22] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
Affiliation(s)
- P Layer
- Medizinische Klinik, Israelitisches Krankenhaus, Hamburg, Deutschland
| | - V Andresen
- Medizinische Klinik, Israelitisches Krankenhaus, Hamburg, Deutschland
| | - H Allescher
- Zentrum für Innere Medizin, Gastroent., Hepatologie u. Stoffwechsel, Klinikum Garmisch-Partenkirchen, Garmisch-Partenkirchen, Deutschland
| | - S C Bischoff
- Institut für Ernährungsmedizin, Universität Hohenheim, Stuttgart, Deutschland
| | - M Claßen
- Klinik für Kinder- und Jugendmedizin, Klinikum Links der Weser, Bremen, Deutschland
| | - S Elsenbruch
- Klinik für Neurologie, Translational Pain Research Unit, Universitätsklinikum Essen, Essen, Deutschland.,Abteilung für Medizinische Psychologie und Medizinische Soziologie, Ruhr-Universität Bochum, Bochum, Deutschland
| | - M Freitag
- Abteilung Allgemeinmedizin Department für Versorgungsforschung, Universität Oldenburg, Oldenburg, Deutschland
| | - T Frieling
- Medizinische Klinik II, Helios Klinikum Krefeld, Krefeld, Deutschland
| | - M Gebhard
- Gemeinschaftspraxis Pathologie-Hamburg, Hamburg, Deutschland
| | - M Goebel-Stengel
- Innere Medizin II, Helios Klinik Rottweil, Rottweil, und Innere Medizin VI, Psychosomat. Medizin u. Psychotherapie, Universitätsklinikum Tübingen, Tübingen, Deutschland
| | - W Häuser
- Innere Medizin I mit Schwerpunkt Gastroenterologie, Klinikum Saarbrücken, Saarbrücken, Deutschland
| | - G Holtmann
- Faculty of Medicine & Faculty of Health & Behavioural Sciences, Princess Alexandra Hospital, Brisbane, Australien
| | - J Keller
- Medizinische Klinik, Israelitisches Krankenhaus, Hamburg, Deutschland
| | - M E Kreis
- Klinik für Allgemein-, Viszeral- und Gefäßchirurgie, Charité - Universitätsmedizin Berlin, Campus Benjamin Franklin, Berlin, Deutschland
| | | | - J Langhorst
- Klinik für Integrative Medizin und Naturheilkunde, Sozialstiftung Bamberg, Klinikum am Bruderwald, Bamberg, Deutschland
| | - P Lynen Jansen
- Deutsche Gesellschaft für Gastroenterologie, Verdauungs- und Stoffwechselkrankheiten, Berlin, Deutschland
| | - A Madisch
- Klinik für Gastroenterologie, interventionelle Endoskopie und Diabetologie, Klinikum Siloah, Klinikum Region Hannover, Hannover, Deutschland
| | - H Mönnikes
- Klinik für Innere Medizin, Martin-Luther-Krankenhaus, Berlin, Deutschland
| | | | - B Niesler
- Abteilung Molekulare Humangenetik Institut für Humangenetik, Universitätsklinikum Heidelberg, Heidelberg, Deutschland
| | - C Pehl
- Medizinische Klinik, Krankenhaus Vilsbiburg, Vilsbiburg, Deutschland
| | - D Pohl
- Klinik für Gastroenterologie und Hepatologie, Universitätsspital Zürich, Zürich, Schweiz
| | - M Raithel
- Medizinische Klinik II m.S. Gastroenterologie und Onkologie, Waldkrankenhaus St. Marien, Erlangen, Deutschland
| | | | - M Schemann
- Lehrstuhl für Humanbiologie, TU München, Deutschland
| | - S Schmiedel
- I. Medizinische Klinik und Poliklinik Gastroenterologie, Universitätsklinikum Hamburg-Eppendorf, Deutschland
| | - J Schwille-Kiuntke
- Abteilung für Psychosomatische Medizin und Psychotherapie, Medizinische Universitätsklinik Tübingen, Tübingen, Deutschland.,Institut für Arbeitsmedizin, Sozialmedizin und Versorgungsforschung, Universitätsklinikum Tübingen, Tübingen, Deutschland
| | - M Storr
- Zentrum für Endoskopie, Gesundheitszentrum Starnberger See, Starnberg, Deutschland
| | - J C Preiß
- Klinik für Innere Medizin - Gastroenterologie, Diabetologie und Hepatologie, Vivantes Klinikum Neukölln, Berlin, Deutschland
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Shiha MG, Aziz I. Review article: Physical and psychological comorbidities associated with irritable bowel syndrome. Aliment Pharmacol Ther 2021; 54 Suppl 1:S12-S23. [PMID: 34927759 DOI: 10.1111/apt.16589] [Citation(s) in RCA: 21] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/15/2021] [Revised: 08/10/2021] [Accepted: 08/17/2021] [Indexed: 12/11/2022]
Abstract
Irritable bowel syndrome (IBS) is one of the most common gastrointestinal disorders encountered by physicians in primary and secondary care. Patients with IBS commonly present with various extraintestinal complaints, which account for a substantial clinical and economic burden. The common extraintestinal comorbidities associated with IBS include anxiety, depression, somatisation, fibromyalgia, chronic fatigue syndrome, chronic pelvic pain, interstitial cystitis, sexual dysfunction and sleep disturbance. The presence of comorbidity in IBS poses a diagnostic and therapeutic challenge with patients frequently undergoing unnecessary investigations and interventions, including surgery. This review discusses the different physical and psychological comorbidities associated with IBS, the shared pathophysiological mechanisms and potential management strategies.
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Affiliation(s)
- Mohamed G Shiha
- Academic Unit of Gastroenterology, Sheffield Teaching Hospitals, Sheffield, UK
| | - Imran Aziz
- Academic Unit of Gastroenterology, Sheffield Teaching Hospitals, Sheffield, UK.,Department of Infection, Immunity and Cardiovascular Disease, University of Sheffield, Sheffield, UK
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Ye L, Rawls JF. Microbial influences on gut development and gut-brain communication. Development 2021; 148:dev194936. [PMID: 34758081 PMCID: PMC8627602 DOI: 10.1242/dev.194936] [Citation(s) in RCA: 13] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/08/2021] [Accepted: 10/07/2021] [Indexed: 12/15/2022]
Abstract
The developmental programs that build and sustain animal forms also encode the capacity to sense and adapt to the microbial world within which they evolved. This is abundantly apparent in the development of the digestive tract, which typically harbors the densest microbial communities of the body. Here, we review studies in human, mouse, zebrafish and Drosophila that are revealing how the microbiota impacts the development of the gut and its communication with the nervous system, highlighting important implications for human and animal health.
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Baiden P, Panisch LS, Onyeaka HK, LaBrenz CA, Kim Y. Association of childhood physical and sexual abuse with arthritis in adulthood: Findings from a population-based study. Prev Med Rep 2021; 23:101463. [PMID: 34258175 PMCID: PMC8259400 DOI: 10.1016/j.pmedr.2021.101463] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/24/2021] [Revised: 04/26/2021] [Accepted: 06/17/2021] [Indexed: 12/19/2022] Open
Abstract
The objective of this cross-sectional study was to investigate childhood physical and sexual abuse as factors associated with arthritis among adults from selected states in the United States. Data for this study came from the 2019 Behavioral Risk Factor Surveillance System survey. An analytic sample of 75,717 adults 18-75 years old (49.7% female) was analyzed using log-binomial regression. The outcome variable investigated in this study was arthritis, and the main explanatory variables were childhood physical and sexual abuse. Of the 75,717 respondents examined, 20,938 (representing 27.6%) had arthritis. A little over one in four respondents (25.5%) experienced childhood physical abuse and 5.6% experienced childhood sexual abuse by age 18. In the multivariable regression, respondents who experienced childhood physical abuse had 1.36 times the risk of having arthritis when compared to respondents who did not experience childhood physical abuse (ARR = 1.36, p < .001, 95% CI = 1.28-1.46). Respondents who experienced childhood sexual abuse had 1.60 times the risk of having arthritis when compared to respondents who did not experience childhood sexual abuse (ARR = 1.74, p < .001, 95% CI = 1.54-1.97). The findings of this study demonstrate that childhood physical and sexual abuse are associated with arthritis later in adulthood. The associations persisted even after adjusting for demographic, socioeconomic status, body mass index (BMI), current smoking status, and self-perceived physical health. The findings of this study add to the burgeoning number of studies demonstrating the adverse impact of childhood physical and sexual abuse on chronic health outcomes among adults.
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Affiliation(s)
- Philip Baiden
- The University of Texas at Arlington, School of Social Work, 211 S. Cooper St., Box 19129, Arlington, TX 76019, United States
| | - Lisa S. Panisch
- University of Rochester Medical Center, Department of Psychiatry, Center for the Study and Prevention of Suicide, 300 Crittenden Blvd., Rochester, NY 14642, United States
| | - Henry K. Onyeaka
- Harvard Medical School, Department of Psychiatry, Massachusetts General Hospital/McLean Hospital, Boston, MA 02115, United States
| | - Catherine A. LaBrenz
- The University of Texas at Arlington, School of Social Work, 211 S. Cooper St., Box 19129, Arlington, TX 76019, United States
| | - Yeonwoo Kim
- The University of Texas at Arlington, College of Nursing and Health Innovation, Department of Kinesiology, 500 W. Nedderman Dr., Arlington, TX 76019, United States
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Holsting AF, Rask MT, Frostholm L, Rosendal M, Rask CU. Self-help interventions for young people with persistent physical symptoms: A systematic review. J Psychosom Res 2021; 148:110553. [PMID: 34242894 DOI: 10.1016/j.jpsychores.2021.110553] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/13/2021] [Revised: 06/08/2021] [Accepted: 06/16/2021] [Indexed: 12/19/2022]
Abstract
OBJECTIVE Persistent physical symptoms are frequent among young people causing considerable social, psychological, and economic consequences. Easily accessible interventions adapted to non-specialized settings are needed. We aimed to systematically review randomized controlled trials on self-help interventions for young people with persistent physical symptoms compared to active or passive control groups. Our purpose was to 1) describe applied therapeutic approaches and content and 2) examine potential effects on symptom burden and psychosocial outcomes. METHODS We included randomized controlled trials on minimal contact self-help interventions for young people with persistent physical symptoms. Systematic literature searches in PubMed, Cochrane Central, Embase, and PsycINFO were conducted. Study selection, data extraction and quality assessment were performed independently by two reviewers. A narrative synthesis of the effects was performed. RESULTS We identified 11 studies on self-help interventions for young people. The methodological quality of the studies was generally low. Participants suffered from impairing fatigue, headache, abdominal pain, and musculoskeletal or multi-site pain. Applied therapeutic approaches were cognitive behavioral therapy, relaxation training, hypnotherapy, and written self-disclosure. Outcomes were diverse and mainly related to symptom burden, whereas psychosocial outcomes were only sporadically examined. Overall, evidence of effectiveness of self-help interventions in alleviating symptom burden was weak, and potential effects could not be linked to one specific theoretical approach. CONCLUSION Few self-help interventions of diverse content exist for young people with persistent physical symptoms. Rigorously designed studies that include recommended outcome domains assessed by aligned measures are needed to determine and compare the clinical value of such interventions.
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Affiliation(s)
| | - M T Rask
- Research Clinic for Functional Disorders and Psychosomatics, Aarhus University hospital, Denmark.
| | - L Frostholm
- Research Clinic for Functional Disorders and Psychosomatics, Aarhus University hospital, Denmark; Department of Clinical Medicine, Aarhus University, Denmark.
| | - M Rosendal
- Research Clinic for Functional Disorders and Psychosomatics, Aarhus University hospital, Denmark; Research Unit for General Practice, Aarhus University, Denmark.
| | - C U Rask
- Department of Child and Adolescent Psychiatry, Aarhus University Hospital, Denmark; Department of Clinical Medicine, Aarhus University, Denmark.
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Videlock EJ, Chang L. Latest Insights on the Pathogenesis of Irritable Bowel Syndrome. Gastroenterol Clin North Am 2021; 50:505-522. [PMID: 34304785 DOI: 10.1016/j.gtc.2021.04.002] [Citation(s) in RCA: 12] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/18/2022]
Abstract
The pathogenesis of irritable bowel syndrome is multifactorial and complex. Our understanding of its pathophysiology has evolved, but remains incompletely understood. Symptoms result from a dysregulation of brain-gut interactions. Evidence has identified alterations in central and peripheral (gut) mechanisms in irritable bowel syndrome and the bidirectional communication between the brain and the gut. Pertinent mechanisms include disturbed gut motility, visceral hypersensitivity, altered mucosal and immune function, altered gut microbiota, and altered central nervous system processing. This review addresses factors that increase the risk of irritable bowel syndrome and the central and peripheral mechanisms thought to underlie its symptoms.
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Affiliation(s)
- Elizabeth J Videlock
- Vatche and Tamar Manoukian Division of Digestive Diseases, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA
| | - Lin Chang
- Vatche and Tamar Manoukian Division of Digestive Diseases, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA.
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Kim JY, Lim MH. Psychological factors to predict chronic diarrhea and constipation in Korean high school students. Medicine (Baltimore) 2021; 100:e26442. [PMID: 34232176 PMCID: PMC8270581 DOI: 10.1097/md.0000000000026442] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/13/2021] [Revised: 05/19/2021] [Accepted: 06/05/2021] [Indexed: 01/04/2023] Open
Abstract
ABSTRACT Chronic diarrhea and constipation are common in adolescents and are associated with depression and anxiety. However, the association was not reported in adolescents adjusted for other psychological factors (resilience, personality traits, perceived stress, and suicidal ideation). Therefore, we investigated the significant psychological factors predicting chronic diarrhea and constipation in adjusted individuals for co-variables.A total of 819 Korean high school students who completed bowel health and psychological questionnaires were enrolled in this study. Depression and anxiety were assessed using validated questionnaires. We used multivariate analyses, controlling for demographic, dietary, lifestyle, and psychological variables to predict chronic diarrhea and constipation.Chronic diarrhea and constipation were more common in individuals with depression (22.3% and 18.6%, respectively) than in individuals with no depression (7.0% and 10.9%, respectively). In addition, they were more prevalent in individuals with anxiety (24.5% and 18.6%, respectively) than in individuals with no anxiety (9.1% and 12.7%, respectively). Multivariate analyses showed that resilience (adjusted risk ratio [aRR] = 0.98, adjusted 95% confidence interval [CI] = 0.97-0.99), moderate (aRR = 6.77, adjusted 95% CI = 3.55-12.91), and severe depression (aRR = 7.42, adjusted 95% CI = 3.61-15.27) were associated with chronic diarrhea. Only mild depression was associated with chronic constipation (aRR = 2.14, adjusted 95% CI = 1.36-3.38). However, anxiety was not significantly associated with chronic diarrhea or constipation.Among the psychological factors predicting disordered bowel habits, resilience and moderate and severe depression were significant predictors of chronic diarrhea, but not anxiety. Furthermore, only mild depression was an independent predictor of chronic constipation.
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Affiliation(s)
- Ji Young Kim
- Department of Psychology, Graduate School of Dankook University
| | - Myung Ho Lim
- Department of Psychology and Psychotherapy, College of Health Science
- Environmental Health Center, Dankook Medical Hospital, Dankook University, Cheonan, Korea
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Vasant DH, Paine PA, Black CJ, Houghton LA, Everitt HA, Corsetti M, Agrawal A, Aziz I, Farmer AD, Eugenicos MP, Moss-Morris R, Yiannakou Y, Ford AC. British Society of Gastroenterology guidelines on the management of irritable bowel syndrome. Gut 2021; 70:1214-1240. [PMID: 33903147 DOI: 10.1136/gutjnl-2021-324598] [Citation(s) in RCA: 270] [Impact Index Per Article: 67.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/06/2021] [Revised: 03/30/2021] [Accepted: 04/06/2021] [Indexed: 12/11/2022]
Abstract
Irritable bowel syndrome (IBS) remains one of the most common gastrointestinal disorders seen by clinicians in both primary and secondary care. Since publication of the last British Society of Gastroenterology (BSG) guideline in 2007, substantial advances have been made in understanding its complex pathophysiology, resulting in its re-classification as a disorder of gut-brain interaction, rather than a functional gastrointestinal disorder. Moreover, there has been a considerable amount of new evidence published concerning the diagnosis, investigation and management of IBS. The primary aim of this guideline, commissioned by the BSG, is to review and summarise the current evidence to inform and guide clinical practice, by providing a practical framework for evidence-based management of patients. One of the strengths of this guideline is that the recommendations for treatment are based on evidence derived from a comprehensive search of the medical literature, which was used to inform an update of a series of trial-based and network meta-analyses assessing the efficacy of dietary, pharmacological and psychological therapies in treating IBS. Specific recommendations have been made according to the Grading of Recommendations Assessment, Development and Evaluation system, summarising both the strength of the recommendations and the overall quality of evidence. Finally, this guideline identifies novel treatments that are in development, as well as highlighting areas of unmet need for future research.
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Affiliation(s)
- Dipesh H Vasant
- Neurogastroenterology Unit, Gastroenterology, Wythenshawe Hospital, Manchester University NHS Foundation Trust, Manchester, UK.,Division of Diabetes, Endocrinology and Gastroenterology, University of Manchester, Manchester, UK
| | - Peter A Paine
- Division of Diabetes, Endocrinology and Gastroenterology, University of Manchester, Manchester, UK.,Gastroenterology, Salford Royal Foundation Trust, Salford, UK
| | - Christopher J Black
- Leeds Gastroenterology Institute, Leeds Teaching Hospitals NHS Trust, Leeds, UK.,Leeds Institute of Medical Research at St James's, University of Leeds, Leeds, UK
| | - Lesley A Houghton
- Leeds Institute of Medical Research at St James's, University of Leeds, Leeds, UK.,Gastroenterology and Hepatology, Mayo Clinic, Jacksonville, Florida, USA
| | - Hazel A Everitt
- Primary Care and Population Sciences, University of Southampton, Southampton, UK
| | - Maura Corsetti
- Nottingham Digestive Diseases Biomedical Research Unit, University of Nottingham, Nottingham, UK
| | - Anurag Agrawal
- Gastroenterology, Doncaster and Bassetlaw Hospitals NHS Trust, Armthorpe Road, Doncaster, UK
| | - Imran Aziz
- Academic Unit of Gastroenterology, Sheffield Teaching Hospitals NHS Foundation Trust, Sheffield, UK.,Department of Infection, Immunity and Cardiovascular Disease, University of Sheffield, Sheffield, UK
| | - Adam D Farmer
- Department of Gastroenterology, University Hospitals of North Midlands NHS Trust, Stoke-on-Trent, UK.,School of Medicine, Keele University, Keele, UK
| | - Maria P Eugenicos
- Department of Gastroenterology, University of Edinburgh, Western General Hospital, Edinburgh, UK
| | - Rona Moss-Morris
- Department of Psychology, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK
| | - Yan Yiannakou
- Department of Gastroenterology, County Durham and Darlington NHS Foundation Trust, Durham, UK
| | - Alexander C Ford
- Leeds Gastroenterology Institute, Leeds Teaching Hospitals NHS Trust, Leeds, UK .,Leeds Institute of Medical Research at St James's, University of Leeds, Leeds, UK
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Orock A, Yuan T, Greenwood-Van Meerveld B. Importance of Non-pharmacological Approaches for Treating Irritable Bowel Syndrome: Mechanisms and Clinical Relevance. FRONTIERS IN PAIN RESEARCH 2021; 1:609292. [PMID: 35295688 PMCID: PMC8915633 DOI: 10.3389/fpain.2020.609292] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/23/2020] [Accepted: 12/14/2020] [Indexed: 11/16/2022] Open
Abstract
Chronic visceral pain represents a major unmet clinical need with the severity of pain ranging from mild to so severe as to prevent individuals from participating in day-to-day activities and detrimentally affecting their quality of life. Although chronic visceral pain can be multifactorial with many different biological and psychological systems contributing to the onset and severity of symptoms, one of the major triggers for visceral pain is the exposure to emotional and physical stress. Chronic visceral pain that is worsened by stress is a hallmark feature of functional gastrointestinal disorders such as irritable bowel syndrome (IBS). Current pharmacological interventions for patients with chronic visceral pain generally lack efficacy and many are fraught with unwanted side effects. Cognitive behavioral therapy (CBT) has emerged as a psychotherapy that shows efficacy at ameliorating stress-induced chronic visceral pain; however, the molecular mechanisms underlying CBT remain incompletely understood. Preclinical studies in experimental models of stress-induced visceral pain employing environmental enrichment (EE) as an animal model surrogate for CBT are unraveling the mechanism by which environmental signals can lead to long-lasting changes in gene expression and behavior. Evidence suggests that EE signaling interacts with stress and nociceptive signaling. This review will (1) critically evaluate the behavioral and molecular changes that lead to chronic pain in IBS, (2) summarize the pharmacological and non-pharmacological approaches used to treat IBS patients, and (3) provide experimental evidence supporting the potential mechanisms by which CBT ameliorates stress-induced visceral pain.
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Affiliation(s)
- Albert Orock
- Oklahoma Center for Neuroscience, University of Oklahoma Health Sciences Center, Oklahoma City, OK, United States
| | - Tian Yuan
- Oklahoma Center for Neuroscience, University of Oklahoma Health Sciences Center, Oklahoma City, OK, United States
| | - Beverley Greenwood-Van Meerveld
- Oklahoma Center for Neuroscience, University of Oklahoma Health Sciences Center, Oklahoma City, OK, United States
- Oklahoma City VA Health Care System, Oklahoma City, OK, United States
- Department of Physiology, University of Oklahoma Health Sciences Center, Oklahoma City, OK, United States
- *Correspondence: Beverley Greenwood-Van Meerveld
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Hu Z, Li M, Yao L, Wang Y, Wang E, Yuan J, Wang F, Yang K, Bian Z, Zhong LLD. The level and prevalence of depression and anxiety among patients with different subtypes of irritable bowel syndrome: a network meta-analysis. BMC Gastroenterol 2021; 21:23. [PMID: 33413140 PMCID: PMC7791666 DOI: 10.1186/s12876-020-01593-5] [Citation(s) in RCA: 61] [Impact Index Per Article: 15.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/19/2020] [Accepted: 12/21/2020] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Irritable bowel syndrome (IBS) is a very common functional bowel disorder. However, the difference of depression and anxiety comorbidities among different IBS subtypes is still not well evaluated. This study aims to investigate the difference in the level and prevalence of depression and anxiety among healthy controls and patients with different subtypes of IBS. METHODS PubMed, EMBASE and the Cochrane library were searched systematically until August 17, 2020. Studies that investigated depression and/or anxiety levels or prevalence among different IBS-subtype patients measured at baseline or the same point were included. Network meta-analysis was conducted to analyze standardized mean difference (SMD) of anxiety and depression levels, and single arm meta-analysis was performed for prevalence of anxiety and depression among different IBS subtypes. RESULTS Eighteen studies involving 7095 participants were included. Network meta-analyses results showed healthy controls had a lower level of depression than IBS with mixed symptoms of constipation and diarrhea (IBS-M) [SMD = - 1.57; 95% confidence interval (CI) - 2.21, - 0.92], IBS with constipation (IBS-C) (SMD = - 1.53; 95% CI - 2.13, - 0.93) and IBS with diarrhea (IBS-D)(SMD = - 1.41; 95% CI - 1.97, - 0.85), while no significant difference was found between IBS unclassified (IBS-U) and healthy controls (SMD = - 0.58; 95% CI - 2.15, 1.00). There was also no significant difference in the level of depression among different IBS subtypes patients. The results of anxiety were similar to depression. Ranking probability showed that IBS-M was associated with the highest level of depression and anxiety symptoms, followed by IBS-C/IBS-D and IBS-U. Single-arm meta-analysis showed IBS-C had the highest prevalence of depression (38%) and anxiety (40%), followed by IBS-D, IBS-M and IBS-U. CONCLUSION The results indicated that IBS-M was more likely to be associated with a higher level of depression and anxiety, and the prevalence of depression and anxiety in IBS-C was highest. The psychological screening and appropriate psychotherapy are needed for patients with IBS-C, IBS-D and IBS-M instead of IBS-U.
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Affiliation(s)
- Zhichao Hu
- Hong Kong Chinese Medicine Clinical Study Center, School of Chinese Medicine, Hong Kong Baptist University, 7 Baptist University Road, Kowloon, 999077, Hong Kong SAR, China
| | - Meixuan Li
- Evidence-Based Medicine Center, School of Basic Medical Sciences, Lanzhou University, Lanzhou, 730000, China
| | - Liang Yao
- Department of Health Research Methods, Evidence and Impact, McMaster University, Hamilton, ON, L8S 4L8, Canada
| | - Yinshu Wang
- Institute of Digestive Diseases, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, 200032, China
| | - Enkang Wang
- Institute of Digestive Diseases, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, 200032, China
| | - Jianye Yuan
- Institute of Digestive Diseases, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, 200032, China
| | - Fengyun Wang
- Xiyuan Hospital, China Academy of Chinese Medicinal Sciences, Beijing, 100091, China
| | - Kehu Yang
- Evidence-Based Medicine Center, School of Basic Medical Sciences, Lanzhou University, Lanzhou, 730000, China
| | - Zhaoxiang Bian
- Hong Kong Chinese Medicine Clinical Study Center, School of Chinese Medicine, Hong Kong Baptist University, 7 Baptist University Road, Kowloon, 999077, Hong Kong SAR, China.
| | - Linda L D Zhong
- Hong Kong Chinese Medicine Clinical Study Center, School of Chinese Medicine, Hong Kong Baptist University, 7 Baptist University Road, Kowloon, 999077, Hong Kong SAR, China.
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McClain JL, Mazzotta EA, Maradiaga N, Duque-Wilckens N, Grants I, Robison AJ, Christofi FL, Moeser AJ, Gulbransen BD. Histamine-dependent interactions between mast cells, glia, and neurons are altered following early-life adversity in mice and humans. Am J Physiol Gastrointest Liver Physiol 2020; 319:G655-G668. [PMID: 32996781 PMCID: PMC7792668 DOI: 10.1152/ajpgi.00041.2020] [Citation(s) in RCA: 23] [Impact Index Per Article: 4.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/31/2023]
Abstract
Early-life adversity contributes to the development of functional bowel disorders later in life through unresolved mechanisms. Here, we tested the hypothesis that early-life adversity alters anatomical and functional interactions between mast cells and enteric glia. The effects of early-life stress were studied using the neonatal maternal separation (NMS) stress mouse model. Anatomical relationships between mast cells and enteric glia were assessed using immunohistochemistry and mast cell reporter mice (Mcpt5Cre;GCaMP5g-tdT). Immunohistochemistry was used to assess the expression of histamine, histamine 1 (H1) receptors, and glial fibrillary acidic protein. Functional responses of glia to mast cell mediators were assessed in calcium imaging experiments using Sox10CreERT2;GCaMP5g-tdT mice and cultured human enteric glial cells. NMS increases mast cell numbers at the level of the myenteric plexus and their proximity to myenteric ganglia. Myenteric glia respond to mediators released by activated mast cells that are blocked by H1 receptor antagonists in mice and humans and by blocking neuronal activity with tetrodotoxin in mouse tissue. Histamine replicates the effects of mast cell supernatants on enteric glia, and NMS increases histamine production by mast cells. NMS reduces glial responses to mast cell mediators in mouse tissue, while potentiating responses in cultured human enteric glia. NMS increases myenteric glial fibrillary acidic protein expression and reduces glial process length but does not cause neurodegeneration. Histamine receptor expression is not altered by NMS and is localized to neurons in mice, but glia in humans. Early-life stress increases the potential for interactions between enteric glia and mast cells, and histamine is a potential mediator of mast cell-glial interactions through H1 receptors. We propose that glial-mast cell signaling is a mechanism that contributes to enteric neuroplasticity driven by early-life adversity.NEW & NOTEWORTHY Early-life adversity places an individual at risk for developing functional gastrointestinal disorders later in life through unknown mechanisms. Here, we show that interactions between mast cells and glia are disrupted by early-life stress in mice and that histamine is a potential mediator of mast cell-glial interactions.
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Affiliation(s)
- Jonathon L. McClain
- 1Department of Physiology, Michigan State University, East Lansing, Michigan
| | - Elvio A. Mazzotta
- 2Department of Anesthesiology, The Wexner Medical Center, The Ohio State University, Columbus, Ohio
| | - Nidia Maradiaga
- 3Gastrointestinal Stress Biology Laboratory, Department Large Animal Clinical Sciences, Michigan State University, East Lansing, Michigan
| | - Natalia Duque-Wilckens
- 1Department of Physiology, Michigan State University, East Lansing, Michigan,3Gastrointestinal Stress Biology Laboratory, Department Large Animal Clinical Sciences, Michigan State University, East Lansing, Michigan
| | - Iveta Grants
- 2Department of Anesthesiology, The Wexner Medical Center, The Ohio State University, Columbus, Ohio
| | - Alfred J. Robison
- 1Department of Physiology, Michigan State University, East Lansing, Michigan
| | - Fievos L. Christofi
- 2Department of Anesthesiology, The Wexner Medical Center, The Ohio State University, Columbus, Ohio
| | - Adam J. Moeser
- 1Department of Physiology, Michigan State University, East Lansing, Michigan,3Gastrointestinal Stress Biology Laboratory, Department Large Animal Clinical Sciences, Michigan State University, East Lansing, Michigan
| | - Brian D. Gulbransen
- 1Department of Physiology, Michigan State University, East Lansing, Michigan
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Harvey PR, Theron B, Smith SCL, Rastall P, Steves CJ, Harris J, Spector TD, Trudgill NJ. The association between low birth weight, childhood recollections of parental response to illness, and irritable bowel syndrome: a twin study. Neurogastroenterol Motil 2020; 32:e13939. [PMID: 32715594 DOI: 10.1111/nmo.13939] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/11/2019] [Revised: 06/06/2020] [Accepted: 06/16/2020] [Indexed: 12/16/2022]
Abstract
BACKGROUND The aetiology of irritable bowel syndrome (IBS) is multifactorial, including genetic and environmental factors. Previous studies have suggested that low birth weight and family environment during childhood are associated with developing IBS. METHODS A survey was sent to all individuals in a UK twin registry. Questions included IBS diagnosed by the Rome IV criteria and if a doctor had previously diagnosed them with IBS. Subjects were categorized as having IBS by Rome IV criteria, a medical diagnosis of IBS or no IBS. Further questions included subjects' recollections of their parents' responses to illness in both the respondent as a child and in the parents themselves. Information regarding birth weight and gestational age have been collected previously. KEY RESULTS 4258 subjects responded to the questionnaire (51.7%), mean age of 52 (SD 14) years, of whom 98.5% were white and 89.6% female. The mean birth weight was 2.4 (0.6) kg. 5.1% satisfied the Rome IV IBS criteria, the same prevalence as the UK population. However, 14.1% had a previous medical diagnosis of IBS. There was no association found between birth weight and IBS or a medical diagnosis of IBS. On multivariable regression analysis, including parental responses to illness, subjects recalling a parent responding to the parent's bowel symptoms by excusing themselves from household chores were associated with a Rome IV diagnosis of IBS (OR 2.19 (95% CI 1.17-4.10), P = .013). CONCLUSIONS AND INFERENCES There was no association between birth weight and IBS. However, observing their parents excuse themselves from household chores when they had bowel symptoms was associated with IBS in later life.
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Affiliation(s)
- Philip R Harvey
- Department of Gastroenterology, Sandwell & West Birmingham Hospitals NHS Trust, West Bromwich, UK
| | - Byron Theron
- Department of Gastroenterology, Sandwell & West Birmingham Hospitals NHS Trust, West Bromwich, UK
| | - Samuel C L Smith
- Department of Gastroenterology, Sandwell & West Birmingham Hospitals NHS Trust, West Bromwich, UK
| | - Paul Rastall
- Department of Gastroenterology, Sandwell & West Birmingham Hospitals NHS Trust, West Bromwich, UK
| | - Claire J Steves
- Department of Twin Research and Genetic Epidemiology, Kings College London, London, UK
| | - Julliette Harris
- Department of Twin Research and Genetic Epidemiology, Kings College London, London, UK
| | - Timothy D Spector
- Department of Twin Research and Genetic Epidemiology, Kings College London, London, UK
| | - Nigel J Trudgill
- Department of Gastroenterology, Sandwell & West Birmingham Hospitals NHS Trust, West Bromwich, UK
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Low EXS, Mandhari MNKA, Herndon CC, Loo EXL, Tham EH, Siah KTH. Parental, Perinatal, and Childhood Risk Factors for Development of Irritable Bowel Syndrome: A Systematic Review. J Neurogastroenterol Motil 2020; 26:437-446. [PMID: 32989183 PMCID: PMC7547188 DOI: 10.5056/jnm20109] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/12/2020] [Revised: 09/13/2020] [Accepted: 09/20/2020] [Indexed: 12/13/2022] Open
Abstract
Background/Aims Adverse early life experiences are associated with the development of stroke, cancer, diabetes, and chronic respiratory and ischemic heart diseases. These negative experiences may also play a role in the development of irritable bowel syndrome (IBS)--a functional gastrointestinal disease. This review discusses the research to date on the parental, perinatal, and childhood risk and protective factors associated with the development of IBS. Methods A literature search was completed for studies published between 1966 and 2018 that investigated premorbid factors occurring during the perinatal and childhood periods as well as parental factors that were associated with the development of IBS. Results Twenty-seven studies fulfilled the review criteria. Risk factors that appeared in more than one study included: (1) parental IBS, substance abuse, parental punishment, and rejection as parental risk factors; (2) low birth weight as a perinatal risk factor; and (3) crowded living conditions in low-income families, childhood anxiety, depression, or child abuse as childhood risk factors. Protective factors for IBS were emotional warmth from the parents and being born to an older mother. Conclusions More effort is needed to identify what fetal and maternal factors are associated with low birth weight and IBS. A well-executed prospective birth cohort with a collection of bio-samples and functional data will provide a better understanding of how adversity and the interplay between genetics, epigenetics, and numerous risk factors affect the development of IBS.
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Affiliation(s)
- En X S Low
- Department of Medicine, Ng Teng Fong General Hospital, National University Health System, Singapore, Singapore
| | - Maimouna N K Al Mandhari
- Division of Gastroenterology and Hepatology, Department of Medicine, National University Hospital, Singapore, Singapore
| | - Charles C Herndon
- G Oppenheimer Center for Neurobiology of Stress and Resilience (CNSR), David Geffen School of Medicine at UCLA, Los Angeles, CA, USA
| | - Evelyn X L Loo
- Singapore Institute for Clinical Sciences (SICS), Agency for Science, Technology and Research (A*STAR), Singapore, Singapore
- Departments of Pediatrics, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore
| | - Elizabeth H Tham
- Departments of Pediatrics, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore
- Khoo Teck Puat-National University Children’s Medical Institute, National University Health System (NUHS), Singapore, Singapore
| | - Kewin T H Siah
- Division of Gastroenterology and Hepatology, Department of Medicine, National University Hospital, Singapore, Singapore
- Departments of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore
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Vogel SC, Brito NH, Callaghan BL. Early Life Stress and the Development of the Infant Gut Microbiota: Implications for Mental Health and Neurocognitive Development. Curr Psychiatry Rep 2020; 22:61. [PMID: 32918633 DOI: 10.1007/s11920-020-01186-9] [Citation(s) in RCA: 20] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/17/2022]
Abstract
PURPOSE OF REVIEW We review the state of the literature examining associations between early life stress (ELS), gut microbiota, and neurocognitive development and mental health in animals and humans. We identify gaps in current models and areas for future research. RECENT FINDINGS ELS is associated with changes in gut microbiota, which correspond to changes in affective and cognitive functioning in both animals and humans. Some of these ELS-induced psychological changes can be remedied by supplementation with probiotics in early life, suggesting a potential area for intervention for ELS-exposed children. Prenatal stress exposure is rarely studied in humans in relation to gut microbiota, but animal work has suggested important associations between prenatal stress and fetal programming that should be tested in humans. The gut microbiota plays an important role in the association between ELS, neurocognitive development, and mental health. More work is needed to fully understand these associations in humans.
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Affiliation(s)
- Sarah C Vogel
- Department of Applied Psychology, New York University, 246 Greene Street, Kimball Hall, New York, NY, 10003, USA.
| | - Natalie H Brito
- Department of Applied Psychology, New York University, 246 Greene Street, Kimball Hall, New York, NY, 10003, USA
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