|
1
|
Al-Beltagi M, Saeed NK, Bediwy AS, Elbeltagi R. Breaking the cycle: Psychological and social dimensions of pediatric functional gastrointestinal disorders. World J Clin Pediatr 2025; 14:103323. [DOI: 10.5409/wjcp.v14.i2.103323] [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: 11/14/2024] [Revised: 12/14/2024] [Accepted: 01/02/2025] [Indexed: 03/18/2025] Open
Abstract
BACKGROUND Functional gastrointestinal disorders (FGIDs) in children present with chronic symptoms like abdominal pain, diarrhea, and constipation without identifiable structural abnormalities. These disorders are closely linked to gut-brain axis dysfunction, altered gut microbiota, and psychosocial stress, leading to psychiatric comorbidities such as anxiety, depression, and behavioral issues. Understanding this bidirectional relationship is crucial for developing effective, holistic management strategies that address physical and mental health.
AIM To examine the psychiatric impacts of FGIDs in children, focusing on anxiety and depression and their association with other neurodevelopmental disorders of childhood, such as attention-deficit/hyperactivity disorder, emphasizing the role of the gut-brain axis, emotional dysregulation, and psychosocial stress. Key mechanisms explored include neurotransmitter dysregulation, microbiota imbalance, central sensitization, heightening stress reactivity, emotional dysregulation, and symptom perception. The review also evaluates the role of family dynamics and coping strategies in exacerbating FGID symptoms and contributing to psychiatric conditions.
METHODS A narrative review was conducted using 328 studies sourced from PubMed, Scopus, and Google Scholar, covering research published over the past 20 years. Inclusion criteria focused on studies examining FGID diagnosis, gut-brain mechanisms, psychiatric comorbidities, and psychosocial factors in pediatric populations. FGIDs commonly affecting children, including functional constipation, abdominal pain, irritable bowel syndrome, gastroesophageal reflux, and cyclic vomiting syndrome, were analyzed concerning their psychological impacts.
RESULTS The review highlights a strong connection between FGIDs and psychiatric symptoms, mediated by gut-brain axis dysfunction, dysregulated microbiota, and central sensitization. These physiological disruptions increase children’s vulnerability to anxiety and depression, while psychosocial factors - such as chronic stress, early-life trauma, maladaptive family dynamics, and ineffective coping strategies - intensify the cycle of gastrointestinal and emotional distress.
CONCLUSION Effective management of FGIDs requires a biopsychosocial approach integrating medical, psychological, and dietary interventions. Parental education, early intervention, and multidisciplinary care coordination are critical in mitigating long-term psychological impacts and improving both gastrointestinal and mental health outcomes in children with FGIDs.
Collapse
Affiliation(s)
- Mohammed Al-Beltagi
- Department of Paediatrics, Faculty of Medicine, Tanta University, Tanta 31511, Alghrabia, Egypt
- Department of Pediatric, University Medical Center, King Abdulla Medical City, Arabian Gulf University, Manama 26671, Bahrain
| | - Nermin K Saeed
- Medical Microbiology Section, Department of Pathology, Salmaniya Medical Complex, Governmental Hospitals, Manama 26671, Bahrain
- Medical Microbiology Section, Department of Pathology, The Royal College of Surgeons in Ireland - Bahrain, Busaiteen 15503, Muharraq, Bahrain
| | - Adel S Bediwy
- Department of Pulmonology, Faculty of Medicine, Tanta University, Tanta 31527, Alghrabia, Egypt
- Department of Pulmonology, University Medical Center, King Abdulla Medical City, Arabian Gulf University, Manama 26671, Bahrain
| | - Reem Elbeltagi
- Department of Medicine, Royal College of Surgeons in Ireland - Bahrain, Busaiteen 15503, Muharraq, Bahrain
| |
Collapse
|
|
2
|
Priego-Parra BA, Reyes-Diaz SA, Ordaz-Alvarez HR, Martínez-Pérez GP, Amieva-Balmori M, García-Zermeño KR, Herrera-Sato M, Raña-Garibay RH, Remes-Troche JM. Gastrointestinal Cognition: Pain Catastrophizing in Irritable Bowel Syndrome, a Cross-Sectional Study in Mexico. Neurogastroenterol Motil 2025:e70022. [PMID: 40125778 DOI: 10.1111/nmo.70022] [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: 04/26/2024] [Revised: 01/15/2025] [Accepted: 02/26/2025] [Indexed: 03/25/2025]
Abstract
INTRODUCTION AND AIMS Pain catastrophizing is more common in individuals with irritable bowel syndrome (IBS) than in healthy individuals. Despite this, its prevalence and impact in Latin American populations remain under-researched. OBJECTIVE To assess pain catastrophizing differences between IBS patients and healthy subjects. MATERIALS AND METHODS Cross-sectional study in which subjects with IBS and healthy individuals (HC) were recruited from our tertiary care center. IBS diagnosis was established based on the Rome IV criteria. All participants answered the pain catastrophizing scale (PCS), the hospital anxiety and depression scale (HAD), and the irritable bowel syndrome severity scoring system (IBS-SSS). Group comparisons employed the Student's t-test or Mann-Whitney U test, with Pearson's or Spearman's for correlations and logistic regression to assess IBS predictors. RESULTS A total of 920 participants (66.4% women) with a median age of 23 years (range: 18-60) met the inclusion criteria. IBS individuals had a higher prevalence of clinically significant pain catastrophizing compared to healthy subjects (22.5% vs. 11%, p < 0.0001). When classified by symptom intensity, 52.2% of IBS individuals with severe symptoms exhibited significant catastrophizing, compared to 25.3% with moderate symptoms and 14.7% with mild symptoms (p < 0.0001). Anxiety (OR 2.5, 95% CI 1.9-3.4, p < 0.0001), depression (OR 1.7, 95% CI 1.3-2.3, p < 0.0001), and catastrophizing (OR 2.3, 95% CI 1.6-3.3, p < 0.0001) were significantly associated with IBS. CONCLUSIONS In Mexican individuals with IBS, pain catastrophizing is associated with more severe gastrointestinal symptoms and psychological distress. Comprehensive management of IBS in this population should involve addressing cognitive patterns in conjunction with conventional treatments.
Collapse
Affiliation(s)
- Bryan Adrian Priego-Parra
- Departamento de Fisiología Digestiva y Motilidad Gastrointestinal, Instituto de Investigaciones Médico-Biológicas, Universidad Veracruzana, Veracruz, Mexico
- Centro de Investigaciones Biomédicas, Universidad Veracruzana, Veracruz, Mexico
| | - Sara Alejandra Reyes-Diaz
- Departamento de Fisiología Digestiva y Motilidad Gastrointestinal, Instituto de Investigaciones Médico-Biológicas, Universidad Veracruzana, Veracruz, Mexico
| | - Héctor Ricardo Ordaz-Alvarez
- Departamento de Fisiología Digestiva y Motilidad Gastrointestinal, Instituto de Investigaciones Médico-Biológicas, Universidad Veracruzana, Veracruz, Mexico
| | - Génesis-Patricia Martínez-Pérez
- Departamento de Fisiología Digestiva y Motilidad Gastrointestinal, Instituto de Investigaciones Médico-Biológicas, Universidad Veracruzana, Veracruz, Mexico
| | - Mercedes Amieva-Balmori
- Departamento de Fisiología Digestiva y Motilidad Gastrointestinal, Instituto de Investigaciones Médico-Biológicas, Universidad Veracruzana, Veracruz, Mexico
| | - Karla Rocío García-Zermeño
- Departamento de Fisiología Digestiva y Motilidad Gastrointestinal, Instituto de Investigaciones Médico-Biológicas, Universidad Veracruzana, Veracruz, Mexico
| | - Mitsuko Herrera-Sato
- Departamento de Gastroenterología, Hospital Español de México, Ciudad de Mexico, Mexico
| | | | - José María Remes-Troche
- Departamento de Fisiología Digestiva y Motilidad Gastrointestinal, Instituto de Investigaciones Médico-Biológicas, Universidad Veracruzana, Veracruz, Mexico
| |
Collapse
|
|
3
|
Qiao C, Qin X, Song Y, Guan R, Li B, Zuo Y, Wei W, Han T, Jiang W. Association of childhood emotional neglect, circulating protein biomarkers, with gastrointestinal disorders among UK biobank participants. J Affect Disord 2025; 380:317-330. [PMID: 40120955 DOI: 10.1016/j.jad.2025.03.114] [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: 01/22/2025] [Revised: 03/16/2025] [Accepted: 03/19/2025] [Indexed: 03/25/2025]
Abstract
OBJECTIVE To explore the association between CEN and GIDs, and elucidated the potential role of circulating protein biomarkers. PATIENTS AND METHODS The study utilized UK Biobank data from 156,686 participants, with data collection occurring between March 13, 2006 and October 1, 2010. Participants with GIDs at baseline were excluded from further analysis. CEN data were obtained from the baseline assessments. Differential protein analyses were conducted using OLINK data. GIDs and their subclasses were identified through electronic health records. Cox proportional hazards regression models were employed to assess the association between CEN and the risk of GIDs, along with sensitivity and multidimensional stratification analyses. Additionally, mediation analysis was performed to explore the role of differential protein biomarkers. RESULTS The results indicated that the mild CEN (CENmild) group was associated with a significantly lower risk of various GIDs than the severe CEN (CENsevere) group, including overall GIDs (HR = 0.78,95%CI:0.74-0.81) and peptic ulcers (HR = 0.37,95%CI:0.20-0.68). OLINK differential analysis revealed that APOF expression was significantly higher in the CENmild group compared to the CENsevere group (PAPOF = 7.09E-08,FC = 0.048), whereas other differential protein expression (PBPIFB2 = 8.93E-06,FC = -0.122;PFABP4 = 3.19E-06,FC = -0.101;PGGH = 4.58E-07,FC = -0.054;PLEP = 5.39E-08,FC = -0.195) was significantly lower in the CENsevere group. Cox regression analysis showed that higher APOF expression was associated with a reduced risk of multiple GIDs, while the expression of other differential proteins increased the risk of corresponding GIDs. Mediation analysis indicated that these proteins mediated 0.5 % to 6.7 % of the CEN-GIDs association. CONCLUSION In this cohort study, CEN was significantly associated with a higher risk of GIDs in the adulthood, and circulating protein biomarkers partially mediated the associations.
Collapse
Affiliation(s)
- Conghui Qiao
- Department of Nutrition and Food Hygiene, the National Key Discipline, School of Public Health, Harbin Medical University, Harbin, PR China
| | - Xiaowen Qin
- Department of Nutrition and Food Hygiene, the National Key Discipline, School of Public Health, Harbin Medical University, Harbin, PR China
| | - Yuqing Song
- Department of Nutrition and Food Hygiene, the National Key Discipline, School of Public Health, Harbin Medical University, Harbin, PR China
| | - Ruijie Guan
- Department of Nutrition and Food Hygiene, the National Key Discipline, School of Public Health, Harbin Medical University, Harbin, PR China
| | - Bai Li
- Department of Biology, University of Ottawa, 30 Marie-Curie Private, Gendron Hall, Ottawa, ON K1N 9B4, Canada
| | - Yingdong Zuo
- Department of Nutrition and Food Hygiene, the National Key Discipline, School of Public Health, Harbin Medical University, Harbin, PR China
| | - Wei Wei
- Department of Nutrition and Food Hygiene, the National Key Discipline, School of Public Health, Harbin Medical University, Harbin, PR China.
| | - Tianshu Han
- Department of Nutrition and Food Hygiene, the National Key Discipline, School of Public Health, Harbin Medical University, Harbin, PR China.
| | - Wenbo Jiang
- Department of Nutrition and Food Hygiene, the National Key Discipline, School of Public Health, Harbin Medical University, Harbin, PR China; Department of Biology, University of Ottawa, 30 Marie-Curie Private, Gendron Hall, Ottawa, ON K1N 9B4, Canada.
| |
Collapse
|
|
4
|
Grover M, Vanuytsel T, Chang L. Intestinal Permeability in Disorders of Gut-Brain Interaction: From Bench to Bedside. Gastroenterology 2025; 168:480-495. [PMID: 39236897 DOI: 10.1053/j.gastro.2024.08.033] [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: 02/15/2024] [Revised: 06/27/2024] [Accepted: 08/20/2024] [Indexed: 09/07/2024]
Abstract
Intestinal barrier function lies at a critical interface of a range of peripheral and central processes that influence disorders of gut-brain interactions (DGBI). Although rigorously tested, the role of barrier dysfunction in driving clinical phenotype of DGBI remains to be fully elucidated. In vitro, in vivo, and ex vivo strategies can test various aspects of the broader permeability and barrier mechanisms in the gut. Luminal mediators of host, bacterial, and dietary origin can influence the barrier function and a disrupted barrier can also influence the luminal milieu. Critical to our understanding is how barrier dysfunction is influenced by stress and other comorbidities that associate with DGBI and the crosstalk between barrier and neural, hormonal, and immune responses. Additionally, the microbiome's significant role in the communication between the brain and gut has led to the integrative model of a microbiome gut-brain axis with reciprocal interactions between brain networks and networks composed of multiple cells in the gut, including immune cells, enterochromaffin cells, gut microbiota and the derived luminal mediators. This review highlights the techniques for assessment of barrier function, appraises evidence for barrier dysfunction in DGBI including mechanistic studies in humans, as well as provides an overview of therapeutic strategies that can be used to directly or indirectly restore barrier function in DGBI patients.
Collapse
Affiliation(s)
- Madhusudan Grover
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota
| | - Tim Vanuytsel
- Translational Research Center for Gastrointestinal Disorders (TARGID), Department of Chronic Diseases and Metabolism (ChroMeta), KULeuven, Leuven, Belgium
| | - Lin Chang
- Vatche and Tamar Manoukian Division of Digestive Diseases, Department of Medicine, University of California, Los Angeles, California.
| |
Collapse
|
|
5
|
Zhou Y, Huang C, Lin R, Jiang F, Liu Y, Qin G, Li X, Zhang Y, Yu Y. Association between adverse childhood experiences and gastro-esophageal diseases later in life: A large-population cohort and Mendelian randomization study. J Affect Disord 2025; 372:66-74. [PMID: 39615757 DOI: 10.1016/j.jad.2024.11.074] [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: 08/05/2024] [Revised: 11/24/2024] [Accepted: 11/25/2024] [Indexed: 01/15/2025]
Abstract
BACKGROUND Adverse childhood experiences (ACEs) are widely recognized as associated with stress-associated digestive disorders, yet their comprehensive relationship with gastro-esophageal diseases as well as the potential mechanisms of depression remains underexplored. METHODS The prospective study included 133,638 participants aged 40-69 from UK Biobank with full information on ACEs, depression, and gastro-esophageal diseases. ACEs were retrospectively measured both as individual types (physical, emotional, and sexual abuse, and physical and emotional neglect) and cumulative scores of experienced types. Cox proportional hazards model was utilized to assess the association of ACEs with the overall and type-specific risks of diseases. Two-sample Mendelian randomization (TSMR) was conducted utilizing data from a genome-wide association study of ACEs (N = 185,414) to further examine the causal relationship. Mediation analysis was performed to quantify the role of depression. RESULTS During a median follow-up of 13.3 years, those who had a history of ACEs were observed with a 15 % higher overall risk of gastro-esophageal diseases (HR, 1.15; 95%CI, 1.12-1.19) and 10-25 % increased type-specific risks compared to unexposed participants. Among five individual types of ACEs, the association was more prominent for emotional abuse (1.22, 1.17-1.27) and sexual abuse (1.24, 1.18-1.30). TSMR analysis consistently reported positive associations between ACE and four subtypes of gastro-esophageal diseases. Depression was found to mediate 17.2 % (13.5 %, 24.0 %) of the aforementioned relationship. CONCLUSIONS Our findings highlight the importance of early screening and intervention on ACEs to reduce the long-term risk of gastro-esophageal diseases, and stress the potential of depression as a ponderable indirect intervention target.
Collapse
Affiliation(s)
- Yajing Zhou
- Department of Biostatistics, NHC Key Laboratory for Health Technology Assessment, Key Laboratory of Public Health Safety of Ministry of Education, School of Public Health, Fudan University, Shanghai 200032, China
| | - Chen Huang
- Department of Biostatistics, NHC Key Laboratory for Health Technology Assessment, Key Laboratory of Public Health Safety of Ministry of Education, School of Public Health, Fudan University, Shanghai 200032, China
| | - Ruilang Lin
- Department of Biostatistics, NHC Key Laboratory for Health Technology Assessment, Key Laboratory of Public Health Safety of Ministry of Education, School of Public Health, Fudan University, Shanghai 200032, China
| | - Fangyuan Jiang
- Department of Big Data in Health Science, School of Public Health and The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | - Yahang Liu
- Department of Biostatistics, NHC Key Laboratory for Health Technology Assessment, Key Laboratory of Public Health Safety of Ministry of Education, School of Public Health, Fudan University, Shanghai 200032, China
| | - Guoyou Qin
- Department of Biostatistics, NHC Key Laboratory for Health Technology Assessment, Key Laboratory of Public Health Safety of Ministry of Education, School of Public Health, Fudan University, Shanghai 200032, China; Shanghai Institute of Infectious Disease and Biosecurity, Fudan University, Shanghai, China
| | - Xue Li
- Department of Big Data in Health Science, School of Public Health and The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.
| | - Yiliang Zhang
- Departments of Thoracic Surgery and State Key Laboratory of Genetic Engineering, Fudan University Shanghai Cancer Center, Shanghai, China; Institute of Thoracic Oncology, Fudan University, Shanghai, China; Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China.
| | - Yongfu Yu
- Department of Biostatistics, NHC Key Laboratory for Health Technology Assessment, Key Laboratory of Public Health Safety of Ministry of Education, School of Public Health, Fudan University, Shanghai 200032, China.
| |
Collapse
|
|
6
|
Constantian MB, Zaborek N. Adverse Childhood Experiences (ACEs) in 252 Board-Certified Plastic Surgeons: Prevalences, ACE Clustering, and Effects on Adult Health and Behaviors, Including Self-Defined Depression, Work Addiction, and Burnout. Aesthet Surg J 2025; 45:321-332. [PMID: 39417477 DOI: 10.1093/asj/sjae214] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/09/2024] [Accepted: 10/15/2024] [Indexed: 10/19/2024] Open
Abstract
BACKGROUND The CDC/Kaiser Adverse Childhood Experiences (ACE) study documented that ACEs predict adult health and self-harming behaviors. ACEs have been documented in physicians and are higher in physicians treated for problematic behavior. Plastic surgeons have never been assayed. OBJECTIVES Might ACE prevalences in plastic surgeons predict their adult health and/or behavior? METHODS A total of 252 ABPS-certified plastic surgeons (72% men, 28% women) completed the 10-question CDC/Kaiser ACE survey by deidentified email. Data were collected on adult health and behaviors previously associated with ACEs in the literature. RESULTS In total 42% of plastic surgeons had 1 or more ACEs; 9.9% had 4 or more. Emotional abuse was 2 times higher than the control CDC/Kaiser population, although other ACEs were lower. Gender differences existed: female surgeons suffered more sexual abuse (17% vs 8%), physical neglect (7% vs 1%), violence against their mothers (7% vs 2%), and self-defined burnout (32% vs 17%). ACEs occurred in clusters. Total ACEs predicted autoimmune disorders, chronic pain/fatigue, self-defined depression, irritable bowel, antidepressant/anxiolytic use, alcohol abuse, >3 marriages, >10 sexual partners, sex and work addiction, eating disorders, and self-defined burnout (all P < .020). Emotional abuse predicted alcohol abuse. Sexual abuse predicted sex addiction. Emotional neglect predicted autoimmune disease, antidepressant/anxiolytic use, eating disorder, and work addiction. Physical neglect predicted chronic fatigue/chronic pain, depression, and burnout (all P < .001 or less). CONCLUSIONS Adverse childhood experiences occurred in 42% of our 252-member plastic surgeon cohort and predicted 13 adult illnesses and self-harming behaviors that can impair surgeons' lives and performances. This may facilitate their recognition and treatment.
Collapse
|
|
7
|
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.
Collapse
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
| |
Collapse
|
|
8
|
Mahurkar‐Joshi S, Thompson M, Villarruel E, Lewis JD, Lin LD, Farid M, Nayeb‐Hashemi H, Storage T, Weiss GA, Limketkai BN, Sauk JS, Mayer EA, Chang L. Genome-Wide DNA Methylation Identifies Potential Disease-Specific Biomarkers and Pathophysiologic Mechanisms in Irritable Bowel Syndrome, Inflammatory Bowel Disease, and Celiac Disease. Neurogastroenterol Motil 2025; 37:e14980. [PMID: 39673136 PMCID: PMC11748828 DOI: 10.1111/nmo.14980] [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: 06/02/2024] [Revised: 11/25/2024] [Accepted: 11/26/2024] [Indexed: 12/16/2024]
Abstract
BACKGROUND AND AIMS Irritable bowel syndrome (IBS), inflammatory bowel disease (IBD), and celiac disease (CeD) present with similar gastrointestinal (GI) symptoms. DNA methylation-based biomarkers have not been investigated as diagnostic biomarkers to classify these disorders. We aimed to study DNA methylation profiles of IBS, IBD, CeD, and healthy controls (HC), develop machine learning-based classifiers, and identify associated gene ontology (GO) terms. METHODS Genome-wide DNA methylation of peripheral blood mononuclear cells from 315 patients with IBS, IBD, CeD, and HC was measured using Illumina's 450K or EPIC arrays. A methylation dataset on 304 IBD and HC samples was used for external validation. Differential methylation was measured using general linear models. Classifiers were developed using penalized generalized linear models using double cross-validation controlling for confounders. Functional enrichment was assessed using GO. RESULTS Three hundred and fifteen participants (148 IBS, 47 IBD, 34 CeD, and 86 HC) had DNA methylation data. IBS-IBD and IBD-CeD showed the highest number of differentially methylated CpG sites followed by IBD-HC, CeD-HC, and IBS-HC. IBS-associated genes were enriched in cell adhesion and neuronal pathways, while IBD- and CeD-associated markers were enriched in inflammation and MHC class II pathways, respectively (p < 0.05). Classification performances assessed using area under the receiver operating characteristic curves (AUC) for IBS-IBD, IBS-CeD, and IBD-CeD were 0.80 (95% CI = 0.7-0.87, p = 6.75E-10), 0.78 (95% CI = 0.68-0.86, p = 4.57E-10), and 0.73 (95% CI = 0.62-0.83, p = 0.03), respectively. The performance of IBD-HC was successfully validated using external data (AUC = 0.74 [95% CI = 68-0.80, p < 0.001]). CONCLUSIONS Blood-based DNA methylation biomarkers can potentially distinguish chronic GI disorders that present with similar symptoms. GO suggested functional significance of the classifiers in disease-specific pathology.
Collapse
Affiliation(s)
- Swapna Mahurkar‐Joshi
- G. Oppenheimer Center for the Neurobiology of Stress and ResilienceLos AngelesCaliforniaUSA
- Vatche and Tamar Manoukian Division of Digestive DiseasesLos AngelesCaliforniaUSA
- David Geffen School of Medicine at UCLALos AngelesCaliforniaUSA
| | - Mike Thompson
- Systems BiologyCentre for Genomic RegulationBarcelonaSpain
| | | | - James D. Lewis
- Division of Gastroenterology and HepatologyUniversity of Pennsylvania Perelman School of MedicinePhiladelphiaPennsylvaniaUSA
| | - Lisa D. Lin
- Vatche and Tamar Manoukian Division of Digestive DiseasesLos AngelesCaliforniaUSA
- David Geffen School of Medicine at UCLALos AngelesCaliforniaUSA
| | - Mary Farid
- Vatche and Tamar Manoukian Division of Digestive DiseasesLos AngelesCaliforniaUSA
- David Geffen School of Medicine at UCLALos AngelesCaliforniaUSA
| | - Hamed Nayeb‐Hashemi
- Vatche and Tamar Manoukian Division of Digestive DiseasesLos AngelesCaliforniaUSA
- David Geffen School of Medicine at UCLALos AngelesCaliforniaUSA
| | - Tina Storage
- Vatche and Tamar Manoukian Division of Digestive DiseasesLos AngelesCaliforniaUSA
- David Geffen School of Medicine at UCLALos AngelesCaliforniaUSA
| | - Guy A. Weiss
- Vatche and Tamar Manoukian Division of Digestive DiseasesLos AngelesCaliforniaUSA
- David Geffen School of Medicine at UCLALos AngelesCaliforniaUSA
- UCLA Celiac Disease ProgramLos AngelesCaliforniaUSA
| | - Berkeley N. Limketkai
- Vatche and Tamar Manoukian Division of Digestive DiseasesLos AngelesCaliforniaUSA
- David Geffen School of Medicine at UCLALos AngelesCaliforniaUSA
| | - Jenny S. Sauk
- Vatche and Tamar Manoukian Division of Digestive DiseasesLos AngelesCaliforniaUSA
- David Geffen School of Medicine at UCLALos AngelesCaliforniaUSA
| | - Emeran A. Mayer
- G. Oppenheimer Center for the Neurobiology of Stress and ResilienceLos AngelesCaliforniaUSA
- Vatche and Tamar Manoukian Division of Digestive DiseasesLos AngelesCaliforniaUSA
- David Geffen School of Medicine at UCLALos AngelesCaliforniaUSA
| | - Lin Chang
- G. Oppenheimer Center for the Neurobiology of Stress and ResilienceLos AngelesCaliforniaUSA
- Vatche and Tamar Manoukian Division of Digestive DiseasesLos AngelesCaliforniaUSA
- David Geffen School of Medicine at UCLALos AngelesCaliforniaUSA
| |
Collapse
|
|
9
|
Fritz J, Coffey R, Bloch J, Cutler A, Gabrielson S, DiGiovanni S, Faherty LJ. The relationship between adverse childhood experiences and disorders of the gut-brain interaction. J Pediatr Gastroenterol Nutr 2025; 80:100-107. [PMID: 39584227 DOI: 10.1002/jpn3.12422] [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: 02/16/2024] [Revised: 08/07/2024] [Accepted: 09/11/2024] [Indexed: 11/26/2024]
Abstract
OBJECTIVES Disorders of the gut-brain interaction (DGBI) arise from a complex interplay of psychosocial factors, altered physiology, and early life factors. In adults, adverse childhood experiences (ACEs) have been associated with DGBI. While both ACEs and DGBI are prevalent among children, the relationship between ACEs and DGBI in childhood is not well understood. METHODS Retrospective review of patients aged 3-18 years with ACE scores documented between October 1, 2019 and April 30, 2022 who were divided into three comparison groups: (1) not referred to pediatric gastroenterology (GI); (2) referred to GI and diagnosed with a DGBI; and (3) referred to GI and not diagnosed with a DGBI. RESULTS Of 29,490 patients with ACE scores documented during the study period, 897 completed a GI consultation. Four hundred and one (44.7%) were diagnosed with a DGBI. With each additional adverse experience, patients were 1.09 times more likely to have a DGBI diagnosis (95% confidence interval [CI] = 1.056-1.163; p ≤ 0.001). An anxiety diagnosis mediated 73% of this relationship (p = 0.012). CONCLUSIONS Among patients receiving pediatric GI specialty care, higher ACE scores were associated with a higher likelihood of a DGBI diagnosis. Anxiety largely mediates this relationship, suggesting potential avenues for targeted, multidisciplinary interventions in both primary and specialty care settings.
Collapse
Affiliation(s)
- Julia Fritz
- Maine Medical Partners Pediatric Gastroenterology, Portland, Maine, USA
- Department of Pediatrics, Maine Medical Center, Portland, Maine, USA
- Tufts University School of Medicine, Boston, Massachusetts, USA
| | - Rachel Coffey
- Department of Pediatrics, Maine Medical Center, Portland, Maine, USA
| | - Jackson Bloch
- Maine Medical Partners Pediatric Gastroenterology, Portland, Maine, USA
| | - Anya Cutler
- MaineHealth Institute for Research Center for Interdisciplinary Population and Health Research, Portland, Maine, USA
| | - Sarah Gabrielson
- The Barbara Bush Children's Hospital at Maine Medical Center, Portland, Maine, USA
| | - Stephen DiGiovanni
- Department of Pediatrics, Maine Medical Center, Portland, Maine, USA
- Tufts University School of Medicine, Boston, Massachusetts, USA
| | - Laura J Faherty
- Department of Pediatrics, Maine Medical Center, Portland, Maine, USA
- Tufts University School of Medicine, Boston, Massachusetts, USA
- RAND Corporation, Boston, Massachusetts, USA
| |
Collapse
|
|
10
|
Lenover Moyer MB, Jasani K, Waldman AB, Chinchilli VM, Shenk MK. The Developmental Origins of Irritable Bowel Syndrome: A Systematic Review and Meta-Analysis. Am J Hum Biol 2025; 37:e24209. [PMID: 39760236 DOI: 10.1002/ajhb.24209] [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: 09/20/2024] [Revised: 12/06/2024] [Accepted: 12/26/2024] [Indexed: 01/07/2025] Open
Abstract
OBJECTIVES The Developmental Origins of Health and Disease (DOHaD) framework contends that chronic diseases are attributable to behavioral and environmental risks encountered during vital periods of fetal and childhood development. Clinical research investigating irritable bowel syndrome (IBS) largely focuses on adult risk factors, with emerging evidence of epigenetic contributions. Limited work considers potential childhood exposures. This paper applies a life course approach to the study of IBS, exploring the available evidence to ascertain the potential developmental origins of IBS. METHODS A systematic literature review was conducted adhering to MOOSE and PRISMA protocols, identifying papers from 1970 through April 2024 examining all IBS risk factors during the prenatal, postnatal, childhood, and adolescent periods. Data were extracted from screened papers and analyzed via meta-analysis using a random effects model. RESULTS A total of 27 case-control, cohort, and cross-sectional studies were identified for analysis. The meta-analysis revealed significant childhood risk factors for adult IBS, including family history (pooled OR 2.17, 95% CI 1.89-2.49, p < 0.0001, n = 11) and the occurrence of any childhood trauma event (pooled OR 1.61, 95% CI 1.29-2.01, p < 0.0001, n = 6). Physical and sexual trauma were the strongest trauma predictors. Factors including breastfeeding and Cesarean section were not significant. CONCLUSIONS This study found IBS is strongly predicted by traumatic childhood experiences, as well as having an immediate family member with IBS. These demonstrated environmental and genetic components indicate a potential gene-environment interaction during childhood, suggesting a need for primary research to better understand the developmental origins of IBS.
Collapse
Affiliation(s)
- Makenna B Lenover Moyer
- Department of Anthropology, The Pennsylvania State University, University Park, Pennsylvania, USA
| | - Krishangi Jasani
- Department of Anthropology, The Pennsylvania State University, University Park, Pennsylvania, USA
| | - Alexandra B Waldman
- Department of Biobehavioral Health, The Pennsylvania State University, University Park, Pennsylvania, USA
| | - Vernon M Chinchilli
- Department of Public Health Sciences, Penn State College of Medicine, Hershey, Pennsylvania, USA
| | - Mary K Shenk
- Department of Anthropology, The Pennsylvania State University, University Park, Pennsylvania, USA
| |
Collapse
|
|
11
|
Lee AH, Mahurkar-Joshi S, Naliboff B, Gupta A, Labus J, Tillisch K, Mayer E, Chang L. Role of Sex, Anxiety, and Resilience in the Association Between Adverse Childhood Experiences and Irritable Bowel Syndrome. Clin Gastroenterol Hepatol 2025; 23:154-162.e2. [PMID: 38878847 PMCID: PMC11648812 DOI: 10.1016/j.cgh.2024.05.041] [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: 03/12/2024] [Revised: 05/14/2024] [Accepted: 05/28/2024] [Indexed: 07/10/2024]
Abstract
BACKGROUND & AIMS Adverse childhood experiences (ACE) are associated with increased risk of irritable bowel syndrome (IBS), a female-predominant chronic abdominal disorder. Factors contributing to this association have not been well-studied. We compared sex differences in ACE for adults with and without IBS and evaluated the impact of anxiety and resilience on the relationship between ACE and IBS. METHODS Sex and disease differences in total score and ACE subtypes from the ACE Questionnaire in subjects with IBS and control subjects were assessed. Cross-sectional mediation analysis determined if anxiety (Hospital Anxiety and Depression Scale) and resilience (Connor-Davidson Resilience Scale or Brief Resilience Scale) mediated the relationship between ACE and IBS. RESULTS Of 798 participants studied, 368 met IBS diagnostic criteria (265 women, 103 men) and 430 were healthy control subjects (277 women, 153 men). Prevalence and number of ACE were higher in IBS versus control subjects (P < .001) but similar between IBS women and men. Household mental illness increased odds of having IBS in women (odds ratio [OR], 1.95; 95% confidence interval [CI], 1.35-2.85; false discovery rate [FDR], 0.002) and men (OR, 2.32; 95% CI, 1.26-4.33; FDR, 0.014). Emotional abuse increased odds of having IBS in women (OR, 1.94; 95% CI, 1.23-3.09; FDR, 0.019) and sexual abuse increased odds of IBS in men (OR, 3.54; 95% CI, 1.35-10.38; FDR, 0.027). Anxiety mediated 54% (P < .001) of ACE's effect on IBS risk and resilience mediated 12%-14% (Connor-Davidson Resilience Scale, P = .008; Brief Resilience Scale, P = .018). CONCLUSIONS Both men and women with a history of ACE are twice as likely to have IBS than those without an ACE. Anxiety mediated the relationship between ACE and IBS in men and women and resilience mediated this relationship only in women.
Collapse
Affiliation(s)
- Anna H Lee
- G. Oppenheimer Center for Neurobiology of Stress and Resilience, Vatche & Tamar Manoukian Division of Digestive Diseases, Department of Medicine, David Geffen School of Medicine, University of California, Los Angeles, California
| | - Swapna Mahurkar-Joshi
- G. Oppenheimer Center for Neurobiology of Stress and Resilience, Vatche & Tamar Manoukian Division of Digestive Diseases, Department of Medicine, David Geffen School of Medicine, University of California, Los Angeles, California
| | - Bruce Naliboff
- G. Oppenheimer Center for Neurobiology of Stress and Resilience, Vatche & Tamar Manoukian Division of Digestive Diseases, Department of Medicine, David Geffen School of Medicine, University of California, Los Angeles, California
| | - Arpana Gupta
- G. Oppenheimer Center for Neurobiology of Stress and Resilience, Vatche & Tamar Manoukian Division of Digestive Diseases, Department of Medicine, David Geffen School of Medicine, University of California, Los Angeles, California
| | - Jennifer Labus
- G. Oppenheimer Center for Neurobiology of Stress and Resilience, Vatche & Tamar Manoukian Division of Digestive Diseases, Department of Medicine, David Geffen School of Medicine, University of California, Los Angeles, California
| | - Kirsten Tillisch
- G. Oppenheimer Center for Neurobiology of Stress and Resilience, Vatche & Tamar Manoukian Division of Digestive Diseases, Department of Medicine, David Geffen School of Medicine, University of California, Los Angeles, California
| | - Emeran Mayer
- G. Oppenheimer Center for Neurobiology of Stress and Resilience, Vatche & Tamar Manoukian Division of Digestive Diseases, Department of Medicine, David Geffen School of Medicine, University of California, Los Angeles, California
| | - Lin Chang
- G. Oppenheimer Center for Neurobiology of Stress and Resilience, Vatche & Tamar Manoukian Division of Digestive Diseases, Department of Medicine, David Geffen School of Medicine, University of California, Los Angeles, California.
| |
Collapse
|
|
12
|
Szkodny LE, Bardach SH, Hacker K, Tormey LK, Gohres K, Siegel CA, Salwen-Deremer JK. Implementation of a Trauma-Informed Care Approach in a Gastroenterology Setting. Dig Dis Sci 2025; 70:119-127. [PMID: 39614025 PMCID: PMC11762216 DOI: 10.1007/s10620-024-08766-2] [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: 03/18/2024] [Accepted: 11/18/2024] [Indexed: 12/01/2024]
Abstract
BACKGROUND Most individuals who come under the care of large healthcare systems will have experienced at least one traumatic incident in their lifetime that may continue to influence their mental and physical health, disease management, and engagement with treatment and medical professionals. Histories of trauma are especially common in patients with gastrointestinal (GI) illness. Trauma reactions can arise in GI settings, but healthcare providers may not recognize these reactions or know how to respond effectively. AIMS We aimed to increase awareness and understanding of the relationship between trauma and GI symptoms, trauma reactions in a healthcare setting, strategies for responding to patients in emotional distress, and opportunities to reduce risk of retraumatization in a GI setting. METHODS Within a larger initiative to enhance behavioral healthcare access and engagement in a GI setting, patient and stakeholder interviews were conducted, and a needs assessment survey was administered. Interview and survey findings informed development of innovative solutions to the identified need for improved trauma services and resources using an iterative, team-based approach. RESULTS Programs and resources were developed and implemented to increase recognition of the impact of trauma, improve responses to trauma reactions during encounters with patients (e.g., clinical and procedure visits, telephone calls), and provide support to patients receiving GI care. CONCLUSIONS Trauma-focused programming specific to the needs of patients with GI conditions is desired by patients, providers, and staff. Education, intervention, and support initiatives have potential to increase awareness of the effects of trauma and enhance experience of healthcare.
Collapse
Affiliation(s)
- Lauren E Szkodny
- Department of Psychiatry, Dartmouth-Hitchcock Medical Center, One Medical Center Drive, Lebanon, NH, USA.
| | - Shoshana H Bardach
- The Dartmouth Institute for Health Policy and Clinical Practice, Hanover, NH, USA
- Geisel School of Medicine at Dartmouth, Hanover, NH, USA
| | - Katrina Hacker
- Department of Psychiatry, Dartmouth-Hitchcock Medical Center, One Medical Center Drive, Lebanon, NH, USA
- Center for Digestive Health, Section of Gastroenterology & Hepatology, Dartmouth-Hitchcock Medical Center, Lebanon, NH, USA
| | - Lauren K Tormey
- Center for Digestive Health, Section of Gastroenterology & Hepatology, Dartmouth-Hitchcock Medical Center, Lebanon, NH, USA
| | | | - Corey A Siegel
- Center for Digestive Health, Section of Gastroenterology & Hepatology, Dartmouth-Hitchcock Medical Center, Lebanon, NH, USA
| | - Jessica K Salwen-Deremer
- Department of Psychiatry, Dartmouth-Hitchcock Medical Center, One Medical Center Drive, Lebanon, NH, USA
- Center for Digestive Health, Section of Gastroenterology & Hepatology, Dartmouth-Hitchcock Medical Center, Lebanon, NH, USA
| |
Collapse
|
|
13
|
Dai Q, Li M, Wang Z, Xu Q, Zhang X, Tao L. The Mediating Effects of Chronic Diseases in the Relationship Between Adverse Childhood Experiences and Trajectories of Depressive Symptoms in Later Life: A Nationwide Longitudinal Study. Healthcare (Basel) 2024; 12:2539. [PMID: 39765965 PMCID: PMC11675985 DOI: 10.3390/healthcare12242539] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/14/2024] [Revised: 12/02/2024] [Accepted: 12/12/2024] [Indexed: 01/11/2025] Open
Abstract
Background: Numerous studies have established a link between adverse childhood experiences (ACEs) and the development of depression in later life. However, the interactive relationships between ACEs, depression, and chronic diseases are still not well understood. In this study, the aim was to investigate the impact of ACEs on depressive trajectories among middle-aged and elderly individuals in China, as well as to examine the mediating roles of chronic diseases in this association. Methods: Data were drawn from 6921 participants aged 45 and older, using the China Health and Retirement Longitudinal Study (CHARLS) data from 2011, 2013, 2015, and 2018, combined with the 2014 life history survey. Depressive symptom scores were assessed using the widely recognized CES-D-10 scale. The trajectories of depressive symptoms were identified via group-based trajectory modeling (GBTM). The association between ACEs and depressive trajectories was analyzed using multinomial logistic regression, and the KHB method was employed to test the mediating effects of different chronic diseases. Results: The age of the 6921 participants was 57.2 ± 8.0 years, with females comprising 53.9% and males 46.1%. We found that approximately 70% of Chinese middle-aged and older adults had experienced at least one ACE, and 4.8% had experienced four or more ACEs. The following four distinct trajectories of depressive symptoms were identified: continuing-low (N = 1897, 27.4%), continuing-low-to-middle (N = 2937, 42.4%), continuing-middle-to-high (N = 1649, 23.8%), and continuing-high (N = 438, 6.3%). Compared to individuals without ACEs, those with four or more ACEs had a significantly higher likelihood of following the continuing-low-to-middle trajectory (OR = 2.407, 95%CI: 1.633-3.550), the continuing-middle-to-high trajectory (OR = 7.458, 95%CI: 4.999-11.127), and the continuing-high trajectory (OR = 20.219, 95%CI: 12.115-33.744), rather than the continuing-low trajectory. Exposure to a greater number of ACEs was associated with an increased risk of following an adverse trajectory of depressive symptoms. Multiple chronic diseases significantly mediated the relationship between ACEs and depressive trajectories, with arthritis or rheumatism exerting the largest mediating effect, followed by digestive and respiratory diseases. Conclusions: These findings indicated that ACEs were associated with a higher risk of worse depressive symptom trajectories, with different chronic diseases mediating this relationship. Therefore, developing public measures to prevent ACEs can reduce the risk of chronic diseases and depression in middle-aged and elderly people. Additionally, strengthening the prevention and management of chronic diseases in individuals exposed to ACEs may further reduce their subsequent risk of depression.
Collapse
Affiliation(s)
- Qianqian Dai
- Research Center of Clinical Epidemiology, Peking University Third Hospital, Beijing 100191, China; (Q.D.); (Z.W.)
| | - Ming Li
- School of Social Sciences, Tsinghua University, Beijing 100084, China;
| | - Zhaoyu Wang
- Research Center of Clinical Epidemiology, Peking University Third Hospital, Beijing 100191, China; (Q.D.); (Z.W.)
| | - Qianqian Xu
- Institute of Basic Theory for Chinese Medicine, China Academy of Chinese Medical Sciences, Beijing 100700, China;
| | - Xinyi Zhang
- Dongzhimen Hospital, Beijing University of Chinese Medicine, Beijing 100700, China;
| | - Liyuan Tao
- Research Center of Clinical Epidemiology, Peking University Third Hospital, Beijing 100191, China; (Q.D.); (Z.W.)
| |
Collapse
|
|
14
|
Yuan X, Chai J, Xu W, Zhao Y. Exploring the Potential of Probiotics and Prebiotics in Major Depression: From Molecular Function to Clinical Therapy. Probiotics Antimicrob Proteins 2024; 16:2181-2217. [PMID: 39078446 DOI: 10.1007/s12602-024-10326-z] [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] [Accepted: 07/10/2024] [Indexed: 07/31/2024]
Abstract
Major depressive disorder (MDD) represents a complex and challenging mental health condition with multifaceted etiology. Recent research exploring the gut-brain axis has shed light on the potential influence of gut microbiota on mental health, offering novel avenues for therapeutic intervention. This paper reviews current evidence on the role of prebiotics and probiotics in the context of MDD treatment. Clinical studies assessing the effects of prebiotic and probiotic interventions have demonstrated promising results, showcasing improvements in depression symptoms and metabolic parameters in certain populations. Notably, prebiotics and probiotics have shown the capacity to modulate inflammatory markers, cortisol levels, and neurotransmitter pathways linked to MDD. However, existing research presents varied outcomes, underscoring the need for further investigation into specific microbial strains, dosage optimization, and long-term effects. Future research should aim at refining personalized interventions, elucidating mechanisms of action, and establishing standardized protocols to integrate these interventions into clinical practice. While prebiotics and probiotics offer potential adjunctive therapies for MDD, continued interdisciplinary efforts are vital to harnessing their full therapeutic potential and reshaping the landscape of depression treatment paradigms.
Collapse
Affiliation(s)
- Xin Yuan
- Graduate School of Heilongjiang University of Chinese Medicine, Harbin, 150040, China
- The First Affiliated Hospital of Heilongjiang University of Chinese Medicine, Harbin, 150040, China
- The Second Affiliated Hospital of Heilongjiang University of Chinese Medicine, Harbin, 150040, China
| | - Jianbo Chai
- Heilongjiang Mental Hospital, Harbin, 150036, China
| | - Wenqiang Xu
- Harbin Jiarun Hospital, Harbin, 150040, China
| | - Yonghou Zhao
- Heilongjiang Mental Hospital, Harbin, 150036, China.
| |
Collapse
|
|
15
|
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.
Collapse
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
| |
Collapse
|
|
16
|
Schubach A, Quigley BM, Lackner JM, Gudleski GD. Somatization Mediates the Relationship Between Childhood Trauma and Pain Ratings in Patients with Irritable Bowel Syndrome. J Clin Gastroenterol 2024; 58:1034-1042. [PMID: 38266076 DOI: 10.1097/mcg.0000000000001974] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/11/2023] [Accepted: 12/27/2023] [Indexed: 01/26/2024]
Abstract
GOALS To identify potential mechanisms by which childhood trauma may lead to the adult development of abdominal symptoms in patients with irritable bowel syndrome (IBS). BACKGROUND Patients with IBS frequently report a history of childhood trauma. The pathophysiology by which abdominal pain arises in patients with IBS is multidimensional, consisting of both peripheral factors, such as altered motility, inflammation, and bacterial overgrowth, as well as central factors, such as psychological distress and neuro-hormonal dysregulation. STUDY Adult psychological factors (anxiety, depression, and somatization) were examined to determine if they mediate the relationship between retrospective reports of childhood trauma and current adult IBS abdominal symptoms in a study of 436 patients (M age=41.6, 79% F) meeting Rome III diagnosis criteria. Childhood trauma was measured using retrospective questions assessing physical and sexual abuse. Psychological factors in adulthood were measured with the subscales of the Brief Symptom Inventory-18. Outcome variables included adult IBS symptoms of abdominal pain, bloating, and satisfaction with bowel habits from the IBS Symptoms Severity Scale. RESULTS Results indicated that somatization mediated the relationship between childhood abuse and abdominal pain and bloating but not bowel satisfaction. CONCLUSIONS This study provides insight into the multifactorial nature of IBS-associated abdominal pain in patients with a history of childhood trauma, elucidating the need for a trauma-informed treatment approach for patients with histories of abuse.
Collapse
Affiliation(s)
- Abigail Schubach
- Department of Medicine, Division of Behavioral Medicine, Jacobs School of Medicine and Biomedical Sciences, University of Buffalo, Buffalo, NY
| | | | | | | |
Collapse
|
|
17
|
Shin A. Editorial: Disordered eating and irritable bowel syndrome-Do maladaptive eating and weight control behaviours increase risk of a maladaptive gut? Aliment Pharmacol Ther 2024; 60:969-970. [PMID: 39205374 DOI: 10.1111/apt.18232] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 09/04/2024]
Abstract
LINKED CONTENTThis article is linked to Yang et al paper. To view this article, visit https://doi.org/10.1111/apt.18197
Collapse
Affiliation(s)
- Andrea Shin
- Vatche and Tamar Manoukian Division of Digestive Diseases, University of California Los Angeles, Los Angeles, California, USA
| |
Collapse
|
|
18
|
Labus JS, Delgadillo DR, Cole S, Wang C, Naliboff B, Chang L, Ellingson BM, Mayer EA. IBS stress reactivity phenotype is associated with blood transcriptome profiles and microstructural and functional brain changes. MEDRXIV : THE PREPRINT SERVER FOR HEALTH SCIENCES 2024:2024.08.07.24311369. [PMID: 39211876 PMCID: PMC11361226 DOI: 10.1101/2024.08.07.24311369] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 09/04/2024]
Abstract
Background & Aims Clinical evidence suggests significant interindividual differences in stress reactivity (SR), but biological mechanisms and therapeutic implications of these differences are poorly understood. We aimed to identify the biological basis of increased SR by investigating associations between a psychometric-based phenotype with blood transcriptomics profiles of increased sympathetic nervous system (SNS) activation and brain imaging phenotypes in irritable bowel syndrome (IBS) participants and healthy controls (HCs). Methods A cross-sectional observational study design, transcriptomics profiling, multimodal brain imaging, and psychosocial assessments were obtained in 291 female and male IBS participants and HCs. Prior to analyses, unsupervised clustering was applied to derive high and low SR subgroups across participants based on two measures of SR. General linear models tested for SR group differences in clinical and biological parameters. Exploratory analyses examined associations between SR group-specific brain alterations and gene expression. Results The high, compared to low SR group showed greater cyclic AMP response element-binding protein (CREB) gene expression consistent with tonic SNS activity and proinflammatory changes in whole blood. Brain imaging showed neuroplastic changes in the high SR group consistent with an upregulation of ascending arousal systems and sensory processing and integration regions, and functional connectivity changes in the central autonomic network. SR moderated the sex difference in extraintestinal symptoms. Conclusions The findings support a model of tonically increased SNS activity as a plausible risk factor for increased autonomic reactivity to psychosocial stressors and low grade immune activation in both IBS and HCs, with a greater prevalence in IBS. These findings may have important implications for personalized treatment interventions in IBS.
Collapse
|
|
19
|
Sakuma T, Muratsubaki T, Kano M, Kanazawa M, Fukudo S. Association between disturbance of self-organization and irritable bowel syndrome in Japanese population using the international trauma questionnaire. Sci Rep 2024; 14:18412. [PMID: 39117720 PMCID: PMC11310398 DOI: 10.1038/s41598-024-68196-y] [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: 12/06/2023] [Accepted: 07/22/2024] [Indexed: 08/10/2024] Open
Abstract
Disturbance of self-organization (DSO) is defined by affective dysregulation, negative self-concept, and disturbances in relationships. Along with post-traumatic stress disorder (PTSD), DSO is a part of complex post-traumatic stress disorder (CPTSD), which often results from childhood trauma and has life-long consequences. We investigated the association between CPTSD, PTSD, DSO, childhood adversity, and irritable bowel syndrome (IBS). Individuals with IBS exhibited markedly higher prevalences of DSO, CPTSD, and PTSD symptoms and higher trauma scores compared with healthy individuals. The odds of having IBS were 3.718 and 1.924 times greater for those with DSO symptoms (p < .001) and CPTSD symptoms (p = .005), respectively. IBS severity was highest in the DSO group, followed by the CPTSD, PTSD, and non-DSO/CPTSD/PTSD groups. DSO symptoms mediate the impact of childhood adversity on IBS symptoms, explaining half of this effect, whereas PTSD symptoms do not. These findings suggest a significant role of DSO in the development of IBS.
Collapse
Affiliation(s)
- Tomoko Sakuma
- Department of Behavioral Medicine, Tohoku University Graduate School of Medicine, 2-1 Seiryo-Machi, Aoba-Ku, Sendai, Miyagi, 980-8575, Japan
| | - Tomohiko Muratsubaki
- Department of Behavioral Medicine, Tohoku University Graduate School of Medicine, 2-1 Seiryo-Machi, Aoba-Ku, Sendai, Miyagi, 980-8575, Japan
| | - Michiko Kano
- Department of Behavioral Medicine, Tohoku University Graduate School of Medicine, 2-1 Seiryo-Machi, Aoba-Ku, Sendai, Miyagi, 980-8575, Japan
| | - Motoyori Kanazawa
- Department of Behavioral Medicine, Tohoku University Graduate School of Medicine, 2-1 Seiryo-Machi, Aoba-Ku, Sendai, Miyagi, 980-8575, Japan
| | - Shin Fukudo
- Department of Behavioral Medicine, Tohoku University Graduate School of Medicine, 2-1 Seiryo-Machi, Aoba-Ku, Sendai, Miyagi, 980-8575, Japan.
- Department of Psychosomatic Medicine, Tohoku University Hospital, Sendai, Japan.
- Research Center for Accelerator and Radioisotope Science, Tohoku University, Sendai, Japan.
- Department of Psychosomatic Medicine, Japanese Red Cross Ishinomaki Hospital, Ishinomaki, Japan.
| |
Collapse
|
|
20
|
Rameshkumar S, Arizmendi BJ, Salwen-Deremer JK. The role of arousal in maintaining the relationship between insomnia and gastrointestinal conditions. Transl Gastroenterol Hepatol 2024; 9:41. [PMID: 39091658 PMCID: PMC11292074 DOI: 10.21037/tgh-23-126] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/23/2023] [Accepted: 04/30/2024] [Indexed: 08/04/2024] Open
Abstract
The relationship between gastrointestinal (GI) conditions and sleep disturbance has been well established. With a higher-than-average prevalence of sleep disturbance in individuals with GI conditions, it is imperative to better understand the maintaining factors driving this comorbidity. Although there are separate, ongoing investigations into both the biological mechanisms and interventions for the sleep and GI relationship, there is a considerable need to further specify common and mutually influential pathways. In our review, we highlight arousal as both a unifying feature of insomnia and various GI conditions as well as a possible mechanism for action for the bidirectional relationship. This review aims to summarize the relationship between arousal, insomnia, and GI conditions, specifically examining sources of arousal across four broad domains: psychosocial factors, physical health factors, daily living factors, and sociocultural factors. Online databases, including PubMed, PsychInfo, and Google Scholar, were searched for full-text English language articles focused on patients with insomnia and/or GI conditions and involving mental health, physical comorbidities, and social factors. Understanding the nature of this bidirectional relationship between sleep and GI through the lens of arousal as a common mechanism will lend itself to using a multidisciplinary approach to treatment and care.
Collapse
Affiliation(s)
| | - Brian J. Arizmendi
- Department of Psychiatry and Psychology, Mayo Clinic Arizona, Scottsdale, AZ, USA
| | - Jessica K. Salwen-Deremer
- Department of Psychiatry & Center for Digestive Health, Dartmouth-Hitchcock Medical Center, Lebanon, NH, USA
| |
Collapse
|
|
21
|
Gonzales J, Dharshika C, Mazhar K, Morales-Soto W, McClain JL, Moeser AJ, Nault R, Price TJ, Gulbransen BD. Early life adversity promotes gastrointestinal dysfunction through a sex-dependent phenotypic switch in enteric glia. BIORXIV : THE PREPRINT SERVER FOR BIOLOGY 2024:2024.05.31.596805. [PMID: 38895433 PMCID: PMC11185517 DOI: 10.1101/2024.05.31.596805] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/21/2024]
Abstract
Irritable bowel syndrome and related disorders of gut-brain interaction (DGBI) are common and exhibit a complex, poorly understood etiology that manifests as abnormal gut motility and pain. Risk factors such as biological sex, stressors during critical periods, and inflammation are thought to influence DGBI vulnerability by reprogramming gut-brain circuits, but the specific cells affected are unclear. Here, we used a model of early life stress to understand cellular mechanisms in the gut that produce DGBIs. Our findings identify enteric glia as a key cellular substrate in which stress and biological sex converge to dictate DGBI susceptibility. Enteric glia exhibit sexual dimorphism in genes and functions related to cellular communication, inflammation, and disease susceptibility. Experiencing early life stress has sex-specific effects on enteric glia that cause a phenotypic switch in male glia toward a phenotype normally observed in females. This phenotypic transformation is followed by physiological changes in the gut, mirroring those observed in DGBI in humans. These effects are mediated, in part, by alterations to glial prostaglandin and endocannabinoid signaling. Together, these data identify enteric glia as a cellular integration site through which DGBI risk factors produce changes in gut physiology and suggest that manipulating glial signaling may represent an attractive target for sex-specific therapeutic strategies in DGBIs.
Collapse
|
|
22
|
Hou W, Ma H, Huang C, Li Y, Li L, Zhang L, Qu Y, Xun Y, Yang Q, He Z, Tai F. Effects of paternal deprivation on empathetic behavior and the involvement of oxytocin receptors in the anterior cingulate cortex. Horm Behav 2024; 162:105536. [PMID: 38522143 DOI: 10.1016/j.yhbeh.2024.105536] [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: 09/23/2023] [Revised: 03/04/2024] [Accepted: 03/18/2024] [Indexed: 03/26/2024]
Abstract
Paternal deprivation (PD) impairs social cognition and sociality and increases levels of anxiety-like behavior. However, whether PD affects the levels of empathy in offspring and its underlying mechanisms remain unknown. The present study found that PD increased anxiety-like behavior in mandarin voles (Microtus mandarinus), impaired sociality, reduced the ability of emotional contagion, and the level of consolation behavior. Meanwhile, PD reduced OT neurons in the paraventricular nucleus (PVN) in both male and female mandarin voles. PD decreased the level of OT receptor (OTR) mRNA in the anterior cingulate cortex (ACC) of male and female mandarin voles. Besides, OTR overexpression in the ACC reversed the PD-induced changes in anxiety-like behavior, social preference, emotional contagion, and consolation behavior. Interference of OTR expression in the ACC increased levels of anxiety-like behaviors, while it reduced levels of sociality, emotional contagion, and consolation. These results revealed that the OTR in the ACC is involved in the effects of PD on empathetic behaviors, and provide mechanistic insight into how social experiences affect empathetic behaviors.
Collapse
Affiliation(s)
- Wenjuan Hou
- Institute of Brain and Behavioral Sciences, College of Life Sciences, Shaanxi Normal University, Xi'an 710062, China; School of Environmental and Material Engineering, Yantai University, 264005, China
| | - Huan Ma
- Institute of Brain and Behavioral Sciences, College of Life Sciences, Shaanxi Normal University, Xi'an 710062, China
| | - Caihong Huang
- Institute of Brain and Behavioral Sciences, College of Life Sciences, Shaanxi Normal University, Xi'an 710062, China
| | - Yin Li
- Institute of Brain and Behavioral Sciences, College of Life Sciences, Shaanxi Normal University, Xi'an 710062, China
| | - Lu Li
- Institute of Brain and Behavioral Sciences, College of Life Sciences, Shaanxi Normal University, Xi'an 710062, China
| | - Lizi Zhang
- Institute of Brain and Behavioral Sciences, College of Life Sciences, Shaanxi Normal University, Xi'an 710062, China
| | - Yishan Qu
- Institute of Brain and Behavioral Sciences, College of Life Sciences, Shaanxi Normal University, Xi'an 710062, China
| | - Yufeng Xun
- Institute of Brain and Behavioral Sciences, College of Life Sciences, Shaanxi Normal University, Xi'an 710062, China
| | - Qixuan Yang
- Institute of Brain and Behavioral Sciences, College of Life Sciences, Shaanxi Normal University, Xi'an 710062, China
| | - Zhixiong He
- Institute of Brain and Behavioral Sciences, College of Life Sciences, Shaanxi Normal University, Xi'an 710062, China.
| | - Fadao Tai
- Institute of Brain and Behavioral Sciences, College of Life Sciences, Shaanxi Normal University, Xi'an 710062, China.
| |
Collapse
|
|
23
|
Camilleri M, Jencks K. Pharmacogenetics in IBS: update and impact of GWAS studies in drug targets and metabolism. Expert Opin Drug Metab Toxicol 2024; 20:319-332. [PMID: 38785066 PMCID: PMC11139426 DOI: 10.1080/17425255.2024.2349716] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/28/2023] [Accepted: 04/26/2024] [Indexed: 05/25/2024]
Abstract
INTRODUCTION Medications are frequently prescribed for patients with irritable bowel syndrome (IBS) or disorders of gut brain interaction. The level of drug metabolism and modifications in drug targets determine medication efficacy to modify motor or sensory function as well as patient response outcomes. AREAS COVERED The literature search included PubMed searches with the terms: pharmacokinetics, pharmacogenomics, epigenetics, clinical trials, irritable bowel syndrome, disorders of gut brain interaction, and genome-wide association studies. The main topics covered in relation to irritable bowel syndrome were precision medicine, pharmacogenomics related to drug metabolism, pharmacogenomics related to mechanistic targets, and epigenetics. EXPERT OPINION Pharmacogenomics impacting drug metabolism [CYP 2D6 (cytochrome P450 2D6) or 2C19 (cytochrome P450 2C19)] is the most practical approach to precision medicine in the treatment of IBS. Although there are proof of concept studies that have documented the importance of genetic modification of transmitters or receptors in altering responses to medications in IBS, these principles have rarely been applied in patient response outcomes. Genome-wide association (GWAS) studies have now documented the association of symptoms with genetic variation but not the evaluation of treatment responses. Considerably more research, particularly focused on patient response outcomes and epigenetics, is essential to impact this field in clinical medicine.
Collapse
Affiliation(s)
- Michael Camilleri
- Clinical Enteric Neuroscience Translational and Epidemiological Research (CENTER), Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN, USA
| | - Kara Jencks
- Clinical Enteric Neuroscience Translational and Epidemiological Research (CENTER), Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN, USA
| |
Collapse
|
|
24
|
Gaus OV, Livzan MA, Gavrilenko DA. Risk factors for irritable bowel syndrome: A review. TERAPEVT ARKH 2024; 96:159-167. [DOI: 10.26442/00403660.2024.02.202597] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 09/17/2024]
Abstract
Irritable bowel syndrome (IBS) is one of the most common diseases of the digestive tract from the group of disorders of interaction in the gut-brain axis. IBS has a negative impact of on patients' quality of life and the significant social and economic burden of the disease due to the low effectiveness of available treatment strategies, which are only symptomatic, without impacting factors and mechanisms of intestinal dysfunction. From this perspective, it is critical to study the factors contributing to the onset and persistence of IBS symptoms to improve the early diagnosis of the disease and implement targeted prevention technology in at-risk groups. The objective of this paper is to systematize data on the main risk factors for IBS, including hereditary predisposition, stress and psycho-emotional state, diet and eating habits, and acute intestinal infections.
Collapse
|
|
25
|
Priego-Parra BA, Triana-Romero A, Lajud-Barquín FA, de Fátima Higuera-DelaTijera M, Martínez-Vázquez SE, Salgado-Álvarez GA, García-Mora U, Cruz-Márquez MÁ, Cano-Contreras AD, Cid HV, Remes-Troche JM. Association of adverse childhood experiences with irritable bowel syndrome in Mexican adults: A cross-sectional study. Neurogastroenterol Motil 2024; 36:e14743. [PMID: 38243398 DOI: 10.1111/nmo.14743] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/12/2023] [Revised: 11/21/2023] [Accepted: 01/11/2024] [Indexed: 01/21/2024]
Abstract
BACKGROUND Adverse childhood experiences (ACEs) are linked to the development of gastrointestinal disorders during adulthood, but there is limited research on the prevalence of ACEs in Latin American populations. This study aimed to assess the prevalence and impact of ACEs on Mexican adults with irritable bowel syndrome (IBS). METHODS In this cross-sectional study, we recruited 290 Mexican adults (aged 18-65), including 90 individuals with IBS and 200 healthy controls. All participants completed four self-reported questionnaires: The Adverse Childhood Experiences Questionnaire (ACEs), Visceral Sensitivity Index, Irritable Bowel Syndrome Symptom Severity Scale, and Hospital Anxiety and Depression Scale. Statistical analyses included mean differences using either the Student's t-test or the Wilcoxon test, correlations assessed with Spearman's correlation coefficient, and logistic regression models. Statistical significance was defined as a p-value less than 0.05. KEY RESULTS Among IBS subjects, the prevalence of ACEs was 80%, significantly higher than the 59% prevalence observed in controls (p < 0.0001). Individuals with ACEs exhibited elevated levels of anxiety and depression. Seventy-five percent of IBS subjects with severe symptoms reported four or more ACEs. The presence of four or more ACEs was found to be associated with an increased risk of IBS. CONCLUSIONS AND INFERENCES ACEs are notably prevalent among Mexican individuals with IBS and are positively correlated with the severity of gastrointestinal pain. These findings underscore the critical significance of evaluating and addressing ACEs in the comprehensive management of IBS within Latin American populations.
Collapse
Affiliation(s)
- Bryan Adrian Priego-Parra
- Departamento de Fisiología y Motilidad Digestiva, Instituto de Investigaciones Médico-Biológicas, Universidad Veracruzana, Veracruz, Mexico
- Centro de Investigaciones Biomédicas, Universidad Veracruzana, Veracruz, Mexico
| | - Arturo Triana-Romero
- Departamento de Fisiología y Motilidad Digestiva, Instituto de Investigaciones Médico-Biológicas, Universidad Veracruzana, Veracruz, Mexico
| | | | | | | | - Giovanni Alejandro Salgado-Álvarez
- Departamento de Fisiología y Motilidad Digestiva, Instituto de Investigaciones Médico-Biológicas, Universidad Veracruzana, Veracruz, Mexico
| | - Uriel García-Mora
- Departamento de Fisiología y Motilidad Digestiva, Instituto de Investigaciones Médico-Biológicas, Universidad Veracruzana, Veracruz, Mexico
| | - Miguel Ángel Cruz-Márquez
- Departamento de Fisiología y Motilidad Digestiva, Instituto de Investigaciones Médico-Biológicas, Universidad Veracruzana, Veracruz, Mexico
| | - Ana Delfina Cano-Contreras
- Departamento de Fisiología y Motilidad Digestiva, Instituto de Investigaciones Médico-Biológicas, Universidad Veracruzana, Veracruz, Mexico
| | - Héctor-Vivanco Cid
- Departamento de Fisiología y Motilidad Digestiva, Instituto de Investigaciones Médico-Biológicas, Universidad Veracruzana, Veracruz, Mexico
| | - José María Remes-Troche
- Departamento de Fisiología y Motilidad Digestiva, Instituto de Investigaciones Médico-Biológicas, Universidad Veracruzana, Veracruz, Mexico
| |
Collapse
|
|
26
|
Ahuja NK. Hypermobility, Trauma, and the Roads That Lead to Rome. Dig Dis Sci 2024; 69:653-654. [PMID: 38112836 DOI: 10.1007/s10620-023-08203-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/07/2023] [Accepted: 11/19/2023] [Indexed: 12/21/2023]
Affiliation(s)
- Nitin K Ahuja
- University of Pennsylvania Perelman School of Medicine, Philadelphia, USA.
| |
Collapse
|
|
27
|
Jha P, Dangi N, Sharma S. Probiotics Show Promise as a Novel Natural Treatment for Neurological Disorders. Curr Pharm Biotechnol 2024; 25:799-806. [PMID: 37877144 DOI: 10.2174/0113892010261604230919170143] [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: 05/26/2023] [Revised: 08/17/2023] [Accepted: 08/21/2023] [Indexed: 10/26/2023]
Abstract
Probiotics are beneficial microorganisms shown to improve human health when consumed regularly and in sufficient quantities. Numerous health benefits can be attained by possessing important metabolites with nutritional and medicinal qualities. It has been shown through scientific research that these living microbial consortiums can influence a variety of mental health outcomes, including but not limited to anxiety, depression, cognitive processes, stress responses, and behavioral patterns. Selected strains of bacteria and yeasts control how the central nervous system (CNS) communicates with the gut-brain axis (GBA) through neuronal, humoral, and metabolic pathways to ease mood. Psychobiotics are substances that can affect the digestive system as well as mood and anxiety. There is scant evidence to validate the beneficial effects of psychiatric drugs in treating neurological diseases or disorders. The therapeutic method of research into psychobiotics opens exciting prospects for the future of the field of development. This review compiles the current evidence available in the scientific literature on the use of probiotics to influence neurological disorders.
Collapse
Affiliation(s)
- Preeti Jha
- Department of Biotechnology, Amity Institute of Biotechnology, Amity University, Jaipur, 303002, Rajasthan, India
| | - Neha Dangi
- Department of Pharmaceutical Sciences, Alwar Pharmacy College, M.I.A., Alwar, 301030, Rajasthan, India
| | - Shikha Sharma
- Department of Pharmaceutical Science, Lords University, Alwar, 301028, Rajasthan, India
| |
Collapse
|
|
28
|
Bussières A, Hancock MJ, Elklit A, Ferreira ML, Ferreira PH, Stone LS, Wideman TH, Boruff JT, Al Zoubi F, Chaudhry F, Tolentino R, Hartvigsen J. Adverse childhood experience is associated with an increased risk of reporting chronic pain in adulthood: a stystematic review and meta-analysis. Eur J Psychotraumatol 2023; 14:2284025. [PMID: 38111090 PMCID: PMC10993817 DOI: 10.1080/20008066.2023.2284025] [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: 05/11/2023] [Accepted: 08/22/2023] [Indexed: 12/20/2023] Open
Abstract
Background: Adverse childhood experiences (ACEs) have been shown to negatively affect health in adulthood. Estimates of associations between ACEs and chronic painful conditions are lacking.Objectives: This systematic review and meta-analysis aimed to evaluate associations between exposure to ACEs and chronic pain and pain-related disability in adults.Methods: We searched 10 electronic databases from inception to February 2023. We included observational studies assessing associations between direct ACEs (childhood sexual, physical, emotional abuse, or neglect) alone or in combination with indirect ACEs (witnessing domestic violence, household mental illness), and adult chronic pain (≥3 months duration) and pain-related disability (daily activities limited by chronic pain). Pairs of reviewers independently extracted data and assessed study risks of bias. Random-effect models were used to calculate pooled adjusted odds ratios [aOR]. Tau square [T2], 95% prediction intervals [95%PI] and I2 expressed the amount of heterogeneity, and meta-regressions and subgroup meta-analyses investigated sources of heterogeneity (PROSPERO: CRD42020150230).Results: We identified 85 studies including 826,452 adults of which 57 studies were included in meta-analyses. Study quality was generally good or fair (n = 70). The odds of reporting chronic pain in adulthood were significantly higher among individuals exposed to a direct ACE (aOR, 1.45, 95%CI, 1.38-1.53). Individuals reporting childhood physical abuse were significantly more likely to report both chronic pain (aOR, 1.50, 95CI, 1.39-1.64) and pain-related disability (1.46, 95CI, 1.03-2.08) during adulthood. Exposure to any ACEs alone or combined with indirect ACEs significantly increase the odds of adult chronic painful conditions (aOR, 1.53, 95%CI, 1.42-1.65) and pain-related disability (aOR, 1.29; 95%CI, 1.01-1.66). The risk of chronic pain in adulthood significantly increased from one ACE (aOR, 1.29, 95%CI, 1.22-1.37) to four or more ACEs (1.95, 95%CI, 1.73-2.19).Conclusions: Single and cumulative ACEs are significantly associated with reporting of chronic pain and pain-related disability as an adult.
Collapse
Affiliation(s)
- André Bussières
- School of Physical and Occupational Therapy, Faculty of Medicine and Health Sciences, McGill University, Montreal, Canada
- Département Chiropratique, Université du Québec à Trois-Rivières, Trois-Rivières, Canada
| | - Mark J. Hancock
- Faculty of Medicine, Health and Human Sciences, Macquarie University, Sydney, Australia
| | - Ask Elklit
- National Centre for Psychotraumatology, Department of Psychology, University of Southern DenmarkOdense, Denmark
| | - Manuela L. Ferreira
- Sydney Musculoskeletal Health, The Kolling Institute, School of Health Sciences, Faculty of Medicine and Health, The University of Sydney, Sydney, Australia
| | - Paulo H. Ferreira
- Musculoskeletal Health, Faculty of Health Sciences, Charles Perkins Centre, The University of Sydney, Sydney, Australia
| | - Laura S. Stone
- Faculty of Dentistry, McGill University, Montreal, Canada
- Alan Edwards Centre for Research on Pain, McGill University, Montreal, Canada
- Department of Anesthesiology, Faculty of Medicine, University of Minnesota, Minneapolis, MN, USA
| | - Timothy H. Wideman
- School of Physical and Occupational Therapy, Faculty of Medicine and Health Sciences, McGill University, Montreal, Canada
- Alan Edwards Centre for Research on Pain, McGill University, Montreal, Canada
| | - Jill T. Boruff
- Schulich Library of Physical Sciences, Life Sciences, and Engineering, McGill University, Montreal, Canada
| | - Fadi Al Zoubi
- Department of Rehabilitation Sciences, The Hong Kong Polytechnic University, Hung Hom, Hong Kong
| | - Fauzia Chaudhry
- School of Physical and Occupational Therapy, Faculty of Medicine and Health Sciences, McGill University, Montreal, Canada
| | - Raymond Tolentino
- Department of Family Medicine, Faculty of Medicine and Health Sciences, McGill University, Montreal
| | - Jan Hartvigsen
- Center for Muscle and Joint Health, Department of Sports Science and Clinical Biomechanics, University of Southern Denmark, Odense, Denmark
- Chiropractic Knowledge Hub, Odense, Denmark
| |
Collapse
|
|
29
|
Minjoz S, Sinniger V, Hot P, Bonaz B, Pellissier S. The burden of early life stress in chronic inflammatory bowel diseases. J Health Psychol 2023; 28:1204-1216. [PMID: 37203800 DOI: 10.1177/13591053231173918] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 05/20/2023] Open
Abstract
The aim of this study was to evaluate the prevalence of early life stress (ELS) in a population with inflammatory bowel diseases (IBD) and to estimate its burden on mental, physical, and digestive health. Ninety-three participants with IBD were asked to anonymously complete questionnaires (Childhood Trauma Questionnaire-Short Form, Early Life Event Scale, Perceived Stress Scale, Hospital Anxiety and Depression Scale, Ways of Coping Checklist, Gastro-Intestinal Quality of Life Index questionnaire, and ad hoc questions about symptoms). The prevalence of patients with IBD who were exposed to at least one childhood abuse was 53%. Mental health and quality of life were significantly poorer in patients with IBD who were exposed to early abuse than in those who were not. Patients exposed to ELS had also more digestive perturbations and fatigue. These results suggest that early abuse should be considered a component of IBD care.
Collapse
Affiliation(s)
- Séphora Minjoz
- Université Savoie Mont Blanc, Université Grenoble Alpes, LIP/PC2S, France
- Université Savoie Mont Blanc, Université Grenoble Alpes, LPNC, France
| | - Valérie Sinniger
- Université Grenoble Alpes, Inserm, U1216, CHU Grenoble Alpes, France
| | - Pascal Hot
- Université Savoie Mont Blanc, Université Grenoble Alpes, LPNC, France
- Institut Universitaire de France, France
| | - Bruno Bonaz
- Université Grenoble Alpes, Inserm, U1216, CHU Grenoble Alpes, France
| | - Sonia Pellissier
- Université Savoie Mont Blanc, Université Grenoble Alpes, LIP/PC2S, France
| |
Collapse
|
|
30
|
Tao E, Wu Y, Hu C, Zhu Z, Ye D, Long G, Chen B, Guo R, Shu X, Zheng W, Zhang T, Jia X, Du X, Fang M, Jiang M. Early life stress induces irritable bowel syndrome from childhood to adulthood in mice. Front Microbiol 2023; 14:1255525. [PMID: 37849921 PMCID: PMC10577190 DOI: 10.3389/fmicb.2023.1255525] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/10/2023] [Accepted: 09/15/2023] [Indexed: 10/19/2023] Open
Abstract
Background Irritable bowel syndrome (IBS) is one of the most common functional gastrointestinal disorder. Traditionally, early life stress (ELS) is predisposed to IBS in adult. However, whether ELS induces IBS in early life remains unclear. Methods Separated cohort studies were conducted in neonatal male pups of C57BL/6 mice by maternal separation (MS) model. MS and non-separation mice were scheduled to be evaluated for prime IBS-phenotypes, including visceral hypersensitivity, intestinal motility, intestinal permeability, and anxiety-like behavior. Ileal contents and fecal samples were collected and analyzed by 16S rRNA gene sequencing and bacterial community analyses. Subcellular structures of intestinal epithelial, such as epithelial tight junctions and mitochondria, were observed under transmission electron microscopy. Results MS induced visceral hypersensitivity and decreased total intestinal transit time from childhood to adulthood. In addition, MS induced intestinal hyperpermeability and anxiety-like behavior from adolescence to adulthood. Besides, MS affected intestinal microbial composition from childhood to adulthood. Moreover, MS disrupted intestinal mitochondrial structure from childhood to adulthood. Conclusion The study showed for the first time that MS induced IBS from early life to adulthood in mice. The disrupted intestinal mitochondrial structure and the significant dysbiosis of intestinal microbiota in early life may contribute to the initiation and progress of IBS from early life to adulthood.
Collapse
Affiliation(s)
- Enfu Tao
- Pediatric 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 Neonatology and NICU, Wenling Maternal and Child Health Care Hospital, Wenling, China
| | - Yuhao Wu
- Pediatric 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
| | - Chenmin Hu
- Pediatric 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
| | - Zhenya Zhu
- Pediatric 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
- Pediatric 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
| | - Gao Long
- Pediatric 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
- Pediatric 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
- Pediatric 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
| | - Xiaoli Shu
- Pediatric 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
| | - Wei Zheng
- Pediatric 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 Gastroenterology, Children's Hospital, Zhejiang University School of Medicine, National Clinical Research Center for Child Health, National Children's Regional Medical Center, Hangzhou, China
| | - Ting Zhang
- Pediatric 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
| | - Xinyi Jia
- Pediatric 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 Gastroenterology, Children's Hospital, Zhejiang University School of Medicine, National Clinical Research Center for Child Health, National Children's Regional Medical Center, Hangzhou, China
| | - Xiao Du
- Pediatric 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 Gastroenterology, 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
- Pediatric 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 Gastroenterology, Children's Hospital, Zhejiang University School of Medicine, National Clinical Research Center for Child Health, National Children's Regional Medical Center, Hangzhou, China
| |
Collapse
|
|
31
|
Zhou GQ, Huang MJ, Yu X, Zhang NN, Tao S, Zhang M. Early life adverse exposures in irritable bowel syndrome: new insights and opportunities. Front Pediatr 2023; 11:1241801. [PMID: 37732013 PMCID: PMC10507713 DOI: 10.3389/fped.2023.1241801] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/17/2023] [Accepted: 08/22/2023] [Indexed: 09/22/2023] Open
Abstract
Irritable bowel syndrome (IBS) is a prevalent functional gastrointestinal disorder worldwide. Extensive research has identified multiple factors contributing to its development, including genetic predisposition, chronic infection, gut dysbiosis, aberrant serotonin metabolism, and brain dysfunction. Recent studies have emphasized the critical role of the early life stage as a susceptibility window for IBS. Current evidence suggests that diet can heighten the risk of IBS in offspring by influencing the microbiota composition, intestinal epithelium structure, gene expression, and brain-gut axis. The use of antibiotics during pregnancy and the neonatal period disrupts the normal gut microbiota structure, aligning it with the characteristics observed in IBS patients. Additionally, early life stress impacts susceptibility to IBS by modulating TLR4, NK1, and the hypothalamic-pituitary-adrenal (HPA) axis while compromising the offspring's immune system. Formula feeding facilitates the colonization of pathogenic bacteria in the intestines, concurrently reducing the presence of probiotics. This disruption of the Th1 and Th2 cell balance in the immune system weakens the intestinal epithelial barrier. Furthermore, studies suggest that delivery mode influences the occurrence of IBS by altering the composition of gut microbes. This review aims to provide a comprehensive summary of the existing evidence regarding the impact of adverse early life exposures on IBS during pregnancy, intrapartum, and neonatal period. By consolidating this knowledge, the review enhances our understanding of the direct and indirect mechanisms underlying early life-related IBS and offers new insights and research directions from childhood to adulthood.
Collapse
Affiliation(s)
| | | | | | | | | | - Ming Zhang
- Department of General Practice, Honghui Hospital, Xi'an Jiaotong University, Xi’an, China
| |
Collapse
|
|
32
|
Ortega MA, Álvarez-Mon MA, García-Montero C, Fraile-Martínez Ó, Monserrat J, Martinez-Rozas L, Rodríguez-Jiménez R, Álvarez-Mon M, Lahera G. Microbiota-gut-brain axis mechanisms in the complex network of bipolar disorders: potential clinical implications and translational opportunities. Mol Psychiatry 2023; 28:2645-2673. [PMID: 36707651 PMCID: PMC10615769 DOI: 10.1038/s41380-023-01964-w] [Citation(s) in RCA: 37] [Impact Index Per Article: 18.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/27/2022] [Revised: 01/02/2023] [Accepted: 01/13/2023] [Indexed: 01/28/2023]
Abstract
Bipolar disorders (BD) represent a severe leading disabling mental condition worldwide characterized by episodic and often progressive mood fluctuations with manic and depressive stages. The biological mechanisms underlying the pathophysiology of BD remain incompletely understood, but it seems that there is a complex picture of genetic and environmental factors implicated. Nowadays, gut microbiota is in the spotlight of new research related to this kind of psychiatric disorder, as it can be consistently related to several pathophysiological events observed in BD. In the context of the so-called microbiota-gut-brain (MGB) axis, it is shown to have a strong influence on host neuromodulation and endocrine functions (i.e., controlling the synthesis of neurotransmitters like serotonin or mediating the activation of the hypothalamic-pituitary-adrenal axis), as well as in modulation of host immune responses, critically regulating intestinal, systemic and brain inflammation (neuroinflammation). The present review aims to elucidate pathophysiological mechanisms derived from the MGB axis disruption and possible therapeutic approaches mainly focusing on gut microbiota in the complex network of BD. Understanding the mechanisms of gut microbiota and its bidirectional communication with the immune and other systems can shed light on the discovery of new therapies for improving the clinical management of these patients. Besides, the effect of psychiatric drugs on gut microbiota currently used in BD patients, together with new therapeutical approaches targeting this ecosystem (dietary patterns, probiotics, prebiotics, and other novelties) will also be contemplated.
Collapse
Affiliation(s)
- Miguel A Ortega
- Department of Medicine and Medical Specialities, University of Alcala, Alcalá de Henares, Spain.
- Ramón y Cajal Institute of Sanitary Research (IRYCIS), Madrid, Spain.
| | - Miguel Angel Álvarez-Mon
- Department of Medicine and Medical Specialities, University of Alcala, Alcalá de Henares, Spain
- Ramón y Cajal Institute of Sanitary Research (IRYCIS), Madrid, Spain
- Department of Psychiatry and Mental Health, Hospital Universitario Infanta Leonor, Madrid, Spain
| | - Cielo García-Montero
- Department of Medicine and Medical Specialities, University of Alcala, Alcalá de Henares, Spain
- Ramón y Cajal Institute of Sanitary Research (IRYCIS), Madrid, Spain
| | - Óscar Fraile-Martínez
- Department of Medicine and Medical Specialities, University of Alcala, Alcalá de Henares, Spain
- Ramón y Cajal Institute of Sanitary Research (IRYCIS), Madrid, Spain
| | - Jorge Monserrat
- Department of Medicine and Medical Specialities, University of Alcala, Alcalá de Henares, Spain
- Ramón y Cajal Institute of Sanitary Research (IRYCIS), Madrid, Spain
| | - Lucia Martinez-Rozas
- Department of Medicine and Medical Specialities, University of Alcala, Alcalá de Henares, Spain
- Ramón y Cajal Institute of Sanitary Research (IRYCIS), Madrid, Spain
| | - Roberto Rodríguez-Jiménez
- Department of Legal Medicine and Psychiatry, Complutense University, Madrid, Spain
- Institute for Health Research 12 de Octubre Hospital, (Imas 12)/CIBERSAM (Biomedical Research Networking Centre in Mental Health), Madrid, Spain
| | - Melchor Álvarez-Mon
- Department of Medicine and Medical Specialities, University of Alcala, Alcalá de Henares, Spain
- Ramón y Cajal Institute of Sanitary Research (IRYCIS), Madrid, Spain
- Immune System Diseases-Rheumatology, Oncology Service an Internal Medicine, University Hospital Príncipe de Asturias (CIBEREHD), Alcalá de Henares, Spain
- Psychiatry Service, Center for Biomedical Research in the Mental Health Network, University Hospital Príncipe de Asturias, Alcalá de Henares, Spain
| | - Guillermo Lahera
- Department of Medicine and Medical Specialities, University of Alcala, Alcalá de Henares, Spain
- Ramón y Cajal Institute of Sanitary Research (IRYCIS), Madrid, Spain
- Psychiatry Service, Center for Biomedical Research in the Mental Health Network, University Hospital Príncipe de Asturias, Alcalá de Henares, Spain
| |
Collapse
|
|
33
|
Rohr JC, Bourassa KA, Thompson DS, Fowler JC, Frueh BC, Weinstein BL, Petrosino J, Madan A. History of childhood physical abuse is associated with gut microbiota diversity among adult psychiatric inpatients. J Affect Disord 2023; 331:50-56. [PMID: 36933668 DOI: 10.1016/j.jad.2023.03.023] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/05/2022] [Revised: 03/03/2023] [Accepted: 03/11/2023] [Indexed: 03/20/2023]
Abstract
BACKGROUND Traumatic life events are associated with the development of psychiatric and chronic medical illnesses. This exploratory study examined the relationship between traumatic life events and the gut microbiota among adult psychiatric inpatients. METHODS 105 adult psychiatric inpatients provided clinical data and a single fecal sample shortly after admission. A modified version of the Stressful Life Events Screening Questionnaire was used to quantify history of traumatic life events. 16S rRNA gene sequencing was used to analyze the gut microbial community. RESULTS Gut microbiota diversity was not associated with overall trauma score or any of the three trauma factor scores. Upon item-level analysis, history of childhood physical abuse was uniquely associated with beta diversity. Linear Discriminant Analysis Effect Size (LefSe) analyses revealed that childhood physical abuse was associated with abundance of distinct bacterial taxa associated with inflammation. LIMITATIONS This study did not account for dietary differences, though diet was highly restricted as all participants were psychiatric inpatients. Absolute variance accounted for by the taxa was small though practically meaningful. The study was not powered for full subgroup analysis based on race and ethnicity. CONCLUSIONS This study is among the first to demonstrate a relationship between childhood physical abuse and gut microbiota composition among adult psychiatric patients. These findings suggest that early childhood adverse events may have long-conferred systemic consequences. Future efforts may target the gut microbiota for the prevention and/or treatment of psychiatric and medical risk associated with traumatic life events.
Collapse
Affiliation(s)
- Jessica C Rohr
- Department of Psychiatry & Behavioral Health, Houston Methodist, Houston, TX, USA.
| | - Katelynn A Bourassa
- Department of Psychiatry & Behavioral Health, Houston Methodist, Houston, TX, USA
| | - Dominique S Thompson
- Department of Psychiatry & Behavioral Health, Houston Methodist, Houston, TX, USA; Department of Molecular Virology & Microbiology, Alkek Center for Metagenomics and Microbiome Research, Baylor College of Medicine, Houston, TX, USA
| | - J Christopher Fowler
- Department of Psychiatry & Behavioral Health, Houston Methodist, Houston, TX, USA; Houston Methodist Academic Institute, Houston, TX, USA; Department of Psychiatry, Weill Cornell Medical College, New York, NY, USA
| | | | - Benjamin L Weinstein
- Department of Psychiatry & Behavioral Health, Houston Methodist, Houston, TX, USA
| | - Joseph Petrosino
- Department of Molecular Virology & Microbiology, Alkek Center for Metagenomics and Microbiome Research, Baylor College of Medicine, Houston, TX, USA
| | - Alok Madan
- Department of Psychiatry & Behavioral Health, Houston Methodist, Houston, TX, USA; Houston Methodist Academic Institute, Houston, TX, USA; Department of Psychiatry, Weill Cornell Medical College, New York, NY, USA
| |
Collapse
|
|
34
|
Wang S, Cui J, Jiang S, Zheng C, Zhao J, Zhang H, Zhai Q. Early life gut microbiota: Consequences for health and opportunities for prevention. Crit Rev Food Sci Nutr 2022; 64:5793-5817. [PMID: 36537331 DOI: 10.1080/10408398.2022.2158451] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/24/2022]
Abstract
The gut microbiota influences many aspects of the host, including immune system maturation, nutrient absorption and metabolism, and protection from pathogens. Increasing evidences from cohort and animal studies indicate that changes in the gut microbiota early in life increases the risk of developing specific diseases early and later in life. Therefore, it is becoming increasingly important to identify specific disease prevention or therapeutic solutions targeting the gut microbiota, especially during infancy, which is the window of the human gut microbiota establishment process. In this review, we provide an overview of current knowledge concerning the relationship between disturbances in the gut microbiota early in life and health consequences later in life (e.g., necrotizing enterocolitis, celiac disease, asthma, allergies, autism spectrum disorders, overweight/obesity, diabetes and growth retardation), with a focus on changes in the gut microbiota prior to disease onset. In addition, we summarize and discuss potential microbiota-based interventions early in life (e.g., diet adjustments, probiotics, prebiotics, fecal microbiota transplantation, environmental changes) to promote health or prevent the development of specific diseases. This knowledge should aid the understanding of early life microbiology and inform the development of prediction and prevention measures for short- and long-term health disorders based on the gut microbiota.
Collapse
Affiliation(s)
- Shumin Wang
- State Key Laboratory of Food Science and Technology, Jiangnan University, Wuxi, Jiangsu, China
- School of Food Science and Technology, Jiangnan University, Wuxi, Jiangsu, China
| | - Jingjing Cui
- Wuxi School of Medicine, Jiangnan University, Wuxi, China
| | - Shilong Jiang
- Nutrition and Metabolism Research Division, Innovation Center, Heilongjiang Feihe Dairy Co., Ltd, Beijing, China
- PKUHSC-China Feihe Joint Research Institute of Nutrition and Healthy Lifespan Development, Beijing, China
| | - Chengdong Zheng
- Nutrition and Metabolism Research Division, Innovation Center, Heilongjiang Feihe Dairy Co., Ltd, Beijing, China
- PKUHSC-China Feihe Joint Research Institute of Nutrition and Healthy Lifespan Development, Beijing, China
| | - Jianxin Zhao
- State Key Laboratory of Food Science and Technology, Jiangnan University, Wuxi, Jiangsu, China
- School of Food Science and Technology, Jiangnan University, Wuxi, Jiangsu, China
| | - Heng Zhang
- Wuxi School of Medicine, Jiangnan University, Wuxi, China
- Department of Child Health Care, Wuxi Maternity and Child Health Care Hospital, Wuxi, Jiangsu, China
| | - Qixiao Zhai
- State Key Laboratory of Food Science and Technology, Jiangnan University, Wuxi, Jiangsu, China
- School of Food Science and Technology, Jiangnan University, Wuxi, Jiangsu, China
| |
Collapse
|
|
35
|
Bauer EE, Reed CH, Lyte M, Clark PJ. An evaluation of the rat intestinal monoamine biogeography days following exposure to acute stress. Front Physiol 2022; 13:1021985. [PMID: 36582358 PMCID: PMC9792511 DOI: 10.3389/fphys.2022.1021985] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/18/2022] [Accepted: 11/16/2022] [Indexed: 12/15/2022] Open
Abstract
Stress-induced abnormalities in gut monoamine levels (e.g., serotonin, dopamine, norepinephrine) have been linked to gastrointestinal (GI) dysfunction, as well as the worsening of symptoms in GI disorders. However, the influence of stress on changes across the entire intestinal monoamine biogeography has not been well-characterized, especially in the days following stress exposure. Therefore, the aim of this study was to comprehensively assess changes to monoamine neurochemical signatures across the entire rat intestinal tract days after exposure to an acute stressor. To the end, adult male F344 rats were subjected to an episode of unpredictable tail shocks (acute stress) or left undisturbed. Forty-eight hours later rats were euthanized either following a 12 h period of fasting or 30 min of food access to evaluate neurochemical profiles during the peri- and early postprandial periods. Monoamine-related neurochemicals were measured via UHPLC in regions of the small intestine (duodenum, jejunum, ileum), large intestine (cecum, proximal colon, distal colon), cecal contents, fecal contents, and liver. The results suggest a relatively wide-spread increase in measures of serotonin activity across intestinal regions can be observed 48 h after exposure to acute stress, however some evidence was found supporting localized differences in serotonin metabolization. Moreover, acute stress exposure reduced catecholamine-related neurochemical concentrations most notably in the ileum, and to a lesser extent in the cecal contents. Next, stress-related fecal serotonin concentrations were consistent with intestinal profiles. However, fecal dopamine was elevated in association with stress, which did not parallel findings in any other intestinal area. Finally, stress exposure and the food access period together only had minor effects on intestinal monoamine profiles. Taken together, these data suggest nuanced differences in monoaminergic profiles exist across intestinal regions the days following exposure to an acute stressor, highlighting the importance of assessments that consider the entire intestinal tract biogeography when investigating stress-related biological outcomes that may be relevant to GI pathophysiology.
Collapse
Affiliation(s)
- Ella E. Bauer
- Department of Food Science and Human Nutrition, Iowa State University, Ames, IA, United States
| | - Carter H. Reed
- Department of Food Science and Human Nutrition, Iowa State University, Ames, IA, United States
- Department of Kinesiology, Iowa State University, Ames, IA, United States
| | - Mark Lyte
- Department of Veterinary Microbiology and Preventive Medicine, Iowa State University, Ames, IA, United States
| | - Peter J. Clark
- Department of Food Science and Human Nutrition, Iowa State University, Ames, IA, United States
| |
Collapse
|
|
36
|
Salwen-Deremer JK, Sun M. Management of Sleep and Fatigue in Gastrointestinal Patients. Gastroenterol Clin North Am 2022; 51:829-847. [PMID: 36375999 DOI: 10.1016/j.gtc.2022.07.007] [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: 11/04/2022]
Abstract
Sleep is an essential physiologic process, and unfortunately, people with gastrointestinal (GI) conditions are more likely than people in the general population to experience poor sleep quality, sleep disorders, and fatigue. Herein, we present information on common sleep disorders, fatigue, and data on these problems in various GI populations. We also discuss several treatments for sleep concerns and emerging research on the use of these treatments in GI populations. Cases that illustrate the GI/sleep relationship are presented, in addition to guidance for your own practice and cultural considerations.
Collapse
Affiliation(s)
- Jessica K Salwen-Deremer
- Departments of Psychiatry and Medicine, Section of Gastroenterology & Hepatology, The Geisel School of Medicine at Dartmouth, Dartmouth-Hitchcock Medical Center, One Medical Center Drive, Lebanon, NH 03756, USA.
| | - Michael Sun
- Department of Psychological and Brain Sciences, Dartmouth College, 3 Maynard Street, Hanover, NH 03755, USA
| |
Collapse
|
|
37
|
Cénat JM. Complex Racial Trauma: Evidence, Theory, Assessment, and Treatment. PERSPECTIVES ON PSYCHOLOGICAL SCIENCE 2022; 18:675-687. [PMID: 36288462 DOI: 10.1177/17456916221120428] [Citation(s) in RCA: 40] [Impact Index Per Article: 13.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/15/2022]
Abstract
Racial trauma refers to experiences related to threats, prejudices, harm, shame, humiliation, and guilt associated with various types of racial discrimination, either for direct victims or witnesses. In North American, European, and colonial zeitgeist societies, Black, Indigenous, and people of color (BIPOC) experience racial microaggressions and interpersonal, institutional, and systemic racism on a repetitive, constant, inevitable, and cumulative basis. Although complex trauma differs from racial trauma in its origin, the consistency of racist victimization beyond childhood, and the internalized racism associated with it, strong similarities exist. Similar to complex trauma, racial trauma surrounds the victims’ life course and engenders consequences on their physical and mental health, behavior, cognition, relationships with others, self-concept, and social and economic life. There is no way to identify racial trauma other than through a life-course approach that captures the complex nature of individual, collective, historical, and intergenerational experiences of racism experienced by BIPOC communities in Western society. This article presents evidence for complex racial trauma (CoRT), a theoretical framework of CoRT, and guidelines for its assessment and treatment. Avenues for future research, intervention, and training are also presented.
Collapse
Affiliation(s)
- Jude Mary Cénat
- School of Psychology, University of Ottawa
- Interdisciplinary Centre for Black Health, University of Ottawa
- University of Ottawa Research on Black Health, University of Ottawa
| |
Collapse
|
|
38
|
Salwen-Deremer JK, Ballou S. Painful GI Conditions and Their Bidirectional Relationships with Sleep Disturbances. CURRENT SLEEP MEDICINE REPORTS 2022. [DOI: 10.1007/s40675-022-00230-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/14/2022]
|
|
39
|
Mallaret G, Lashermes A, Meleine M, Boudieu L, Barbier J, Aissouni Y, Gelot A, Chassaing B, Gewirtz AT, Ardid D, Carvalho FA. Involvement of toll-like receptor 5 in mouse model of colonic hypersensitivity induced by neonatal maternal separation. World J Gastroenterol 2022; 28:3903-3916. [PMID: 36157543 PMCID: PMC9367235 DOI: 10.3748/wjg.v28.i29.3903] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/15/2022] [Revised: 06/09/2022] [Accepted: 07/06/2022] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Chronic abdominal pain is the most common cause for gastroenterology consultation and is frequently associated with functional gastrointestinal disorders including irritable bowel syndrome and inflammatory bowel disease. These disorders present similar brain/gut/microbiota trialogue alterations, associated with abnormal intestinal permeability, intestinal dysbiosis and colonic hypersensitivity (CHS). Intestinal dysbiosis can alter colon homeostasis leading to abnormal activation of the innate immunity that promotes CHS, perhaps involving the toll-like receptors (TLRs), which play a central role in innate immunity.
AIM To understand the mechanisms between early life event paradigm on intestinal permeability, fecal microbiota composition and CHS development in mice with TLRs expression in colonocytes.
METHODS Maternal separation model (NMS) CHS model, which mimics deleterious events in childhood that can induce a wide range of chronic disorders during adulthood were used. Colonic sensitivity of NMS mice was evaluated by colorectal distension (CRD) coupled with intracolonic pressure variation (IPV) measurement. Fecal microbiota composition was analyzed by 16S rRNA sequencing from weaning to CRD periods. TLR mRNA expression was evaluated in colonocytes. Additionally, the effect of acute intrarectal instillation of the TLR5 agonist flagellin (FliC) on CHS in adult naive wildtype mice was analyzed.
RESULTS Around 50% of NMS mice exhibited increased intestinal permeability and CHS associated with intestinal dysbiosis, characterized by a significant decrease of species richness, an alteration of the core fecal microbiota and a specific increased relative abundance of flagellated bacteria. Only TLR5 mRNA expression was increased in colonocytes of NMS mice with CHS. Acute intrarectal instillation of FliC induced transient increase of IPV, reflecting transient CHS appearance.
CONCLUSION Altogether, these data suggest a pathophysiological continuum between intestinal dysbiosis and CHS, with a role for TLR5.
Collapse
Affiliation(s)
- Geoffroy Mallaret
- Department of Pharmacology, UMR 1107 NeuroDol, University of Clermont Auvergne, Clermont-Ferrand 63000, France
| | - Amandine Lashermes
- Department of Microbiology, Université Paris-Saclay, National Research Institute for Agriculture, Food and the Environment, AgroParisTech, Micalis Institute, Jouy-en-Josas 78350, France
| | - Mathieu Meleine
- Department of Pharmacology, UMR 1107 NeuroDol, University of Clermont Auvergne, Clermont-Ferrand 63000, France
| | - Ludivine Boudieu
- Department of Pharmacology, UMR 1107 NeuroDol, University of Clermont Auvergne, Clermont-Ferrand 63000, France
| | - Julie Barbier
- Department of Pharmacology, UMR 1107 NeuroDol, University of Clermont Auvergne, Clermont-Ferrand 63000, France
| | - Youssef Aissouni
- Department of Pharmacology, UMR 1107 NeuroDol, University of Clermont Auvergne, Clermont-Ferrand 63000, France
| | - Agathe Gelot
- Department of Pharmacology, UMR 1107 NeuroDol, University of Clermont Auvergne, Clermont-Ferrand 63000, France
| | - Benoit Chassaing
- Team “Mucosal Microbiota in Chronic Inflammatory Diseases”, INSERM U1016, CNRS UMR 8104, Université Paris Cité, Paris 75014, France
| | - Andrew T Gewirtz
- Center for Inflammation, Institute for Biomedical Sciences, Georgia State University, Atlanta, GA30033, United States
| | - Denis Ardid
- Department of Pharmacology, UMR 1107 NeuroDol, University of Clermont Auvergne, Clermont-Ferrand 63000, France
| | - Frederic Antonio Carvalho
- Department of Pharmacology, INSERM 1107 NeuroDOL/University of Clermont Auvergne, Clermont-Ferrand 63000, France
| |
Collapse
|
|
40
|
Wang J, Duan G, Zhan T, Dong Z, Zhang Y, Chen Y, Sun H, Xu S. Upregulation of Netrin-1 in the hippocampus mediates the formation of visceral hypersensitivity induced by maternal separation. Front Mol Neurosci 2022; 15:908911. [PMID: 35966013 PMCID: PMC9366914 DOI: 10.3389/fnmol.2022.908911] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/31/2022] [Accepted: 06/24/2022] [Indexed: 11/13/2022] Open
Abstract
Early adverse life events (EALs), such as maternal separation (MS), can cause visceral hypersensitivity, which is thought to be a key pathophysiological mechanism of irritable bowel syndrome (IBS). Previous studies mainly focused on EALs-induced visceral hypersensitivity in adulthood but did not consider that it may have occurred in the preadult period. We previously found that rats who experienced MS suffered from visceral hypersensitivity starting from the post-weaning period. Moreover, the hippocampus is considered to be critical in regulating the formation of visceral hypersensitivity induced by MS. But the underlying mechanisms throughout different life periods are unclear. In this study, behavioral tests, RNA-seq, lentiviral interference, and molecular biology techniques were applied to investigate the molecular mechanism in the hippocampus underlying MS-induced long-lasting visceral hypersensitivity. It was found that both visceral sensitivity and anxiety-like behaviors were significantly increased in MS rats in post-weaning, prepubertal, and adult periods, especially in the prepubertal period. Subsequently, RNA-seq targeting the hippocampus identified that the expression level of Netrin-1 was significantly increased in all periods, which was further confirmed by quantitative real-time PCR and Western blot. Knocking-down hippocampal Netrin-1 in the post-weaning period by lentivirus interference alleviated visceral hypersensitivity and anxiety-like behaviors of MS rats in the later phase of life. In addition, deleted in colorectal cancer (DCC), instead of neogenin-1(Neo-1) or uncoordinated (UNC5), was proved to be the specific functional receptor of Netrin-1 in regulating visceral hypersensitivity, whose upregulation may result in the most severe symptoms in the prepubertal period. Furthermore, the activation of the Netrin-1/DCC pathway could enhance long-term potentiation (LTP) in the hippocampus, probably via recruitment of the AMPA receptor subunit GluA1, which finally resulted in the formation of visceral hypersensitivity. These novel findings suggest that long-lasting over-expression of Netrin-1 can mediate visceral hypersensitivity and anxiety disorder from the post-weaning period to adulthood by activating DCC/GluA1 pathway in the hippocampus. Moreover, early intervention of Netrin-1 in the post-weaning period could lead to significant symptom relief afterward, which provides evidence that the Netrin-1/DCC/GluA1 signaling pathway may be a potential therapeutic target for the treatment of visceral hypersensitivity in clinics.
Collapse
|
|
41
|
Alsubaie MA, Alkhalifah HA, Ali AH, Bahabri MA, Alharbi BA, Alfakeh SA. Adverse Childhood Experiences and Their Effect on Irritable Bowel Syndrome Among Saudi Arabian Adults. Cureus 2022; 14:e25791. [PMID: 35812574 PMCID: PMC9270910 DOI: 10.7759/cureus.25791] [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] [Accepted: 06/09/2022] [Indexed: 12/04/2022] Open
Abstract
Background Adverse childhood experiences (ACEs) are traumatic events that occur before 18 years of age. ACEs have been associated with many negative health problems, including the development of chronic diseases, such as irritable bowel syndrome (IBS), a functional gastrointestinal disorder characterized by abdominal pain. We investigated the prevalence of ACEs among patients with IBS, identified the types of ACEs commonly related to patients with IBS, and further assessed the impact of ACEs on IBS severity. Methodology A cross-sectional study was performed. The study targeted patients with IBS aged ≥ 18 years who were recruited from gastroenterology outpatient clinics at King Abdulaziz University Hospital. Adults were contacted and invited to take part in the study by completing a survey. Data were collected using two validated questionnaires, the ACE questionnaire for adults and the IBS symptom severity scoring system. Results The study included 109 patients with IBS (59.6% females). The prevalence of ACEs (patients with IBS exposed to at least one ACE) was 63.3%. The most prevalent type was emotional abuse (34.9%), followed by both physical abuse and emotional neglect (28.4%). Females reported significantly more ACEs (p = 0.035) than males. The overall IBS symptoms (r = 0.195, p = 0.043) and abdominal pain (r = 0.240, p = 0.012) severity were significantly correlated with total ACEs score. Conclusions Our findings point to a probable association between ACEs exposure and IBS, demonstrating their long-term impacts on symptoms severity. Further studies are needed to acquire a better understanding of the potential impact of ACEs on IBS.
Collapse
|
|
42
|
Kutschke J, Harris JR, Bengtson MB. The relationships between IBS and perceptions of physical and mental health-a Norwegian twin study. BMC Gastroenterol 2022; 22:266. [PMID: 35643443 PMCID: PMC9145077 DOI: 10.1186/s12876-022-02340-8] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/07/2022] [Accepted: 05/18/2022] [Indexed: 11/10/2022] Open
Abstract
BACKGROUND AND AIMS Poor quality of life is a main complaint among individuals with irritable bowel syndrome (IBS). Self-rated health (SRH) is a powerful predictor of clinical outcomes, and also reflects psychological and social aspects of life and an overall sense of well-being. This population-based twin study evaluates how IBS affects ratings of physical and mental health, and influences perceptions of hindrance of daily activity by physical or mental health. Further, we examine how IBS is related to these SRH measures. METHODS The sample included 5288 Norwegian twins aged 40-80, of whom 575 (10.9%) suffer from IBS. Hierarchical regressions were used to estimate the impact of IBS on perceptions of health, before and after accounting for other chronic physical and mental health conditions. Two dimensions of SRH, physical and mental, and two aspects of functional limitations, the extent to which physical or mental health interferes with daily activities, were included as outcomes in separate models. Co-twin control analyses were used to explore whether the relationships between IBS and the four measures of SRH are causal, or due to shared genetic or shared environment effects. RESULTS IBS was an independent predictor of poor self-rated physical health (OR = 1.82 [1.41; 2.33]), the size of this effect was comparable to that predicted by chronic somatic conditions. However, in contrast to somatic diseases, IBS was associated with the perception that poorer ratings of mental health (OR = 1.45 [1.02; 2.06]), but not physical health (OR = 1.23 [0.96; 1.58]), interfered with daily activity. The co-twin control analyses suggest that causal mechanisms best explain the relationships between IBS with self-rated physical health and with hindrance of daily activities. In contrast, the relationship between IBS and self-rated mental health was consistent with shared genetic effects. CONCLUSION IBS is predictive of poor self-rated physical health. The relationship between IBS and self-rated mental health is best explained by shared genetic effects which might partially explain why mental health interferes with daily activity to a larger degree among those with IBS.
Collapse
Affiliation(s)
| | - Jennifer R Harris
- Centre for Fertility and Health, The Norwegian Institute of Public Health, Oslo, Norway
| | | |
Collapse
|
|
43
|
Kindt S, Louis H, De Schepper H, Arts J, Caenepeel P, De Looze D, Gerkens A, Holvoet T, Latour P, Mahler T, Mokaddem F, Nullens S, Piessevaux H, Poortmans P, Rasschaert G, Surmont M, Vafa H, Van Malderen K, Vanuytsel T, Wuestenberghs F, Tack J. Belgian consensus on irritable bowel syndrome. Acta Gastroenterol Belg 2022; 85:360-382. [PMID: 35709780 DOI: 10.51821/85.2.10100] [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] [Indexed: 11/11/2022]
Abstract
BACKGROUND Irritable bowel syndrome (IBS) is characterised by recurrent abdominal pain related to defaecation or associated with altered stool frequency or consistency. Despite its prevalence, major uncertainties in the diagnostic and therapeutic management persist in clinical practice. METHODS A Delphi consensus was conducted by 20 experts from Belgium, and consisted of literature review and voting process on 78 statements. Grading of recommendations, assessment, development and evaluation criteria were applied to evaluate the quality of evidence. Consensus was defined as > 80 % agreement. RESULTS Consensus was reached for 50 statements. The Belgian consensus agreed as to the multifactorial aetiology of IBS. According to the consensus abdominal discomfort also represents a cardinal symptom, while bloating and abdominal distension often coexist. IBS needs subtyping based on stool pattern. The importance of a positive diagnosis, relying on history and clinical examination is underlined, while additional testing should remain limited, except when alarm features are present. Explanation of IBS represents a crucial part of patient management. Lifestyle modification, spasmolytics and water-solube fibres are considered first-line agents. The low FODMAP diet, selected probiotics, cognitive behavioural therapy and specific treatments targeting diarrhoea and constipation are considered appropriate. There is a consensus to restrict faecal microbiota transplantation and gluten-free diet, while other treatments are strongly discouraged. CONCLUSIONS A panel of Belgian gastroenterologists summarised the current evidence on the aetiology, symptoms, diagnosis and treatment of IBS with attention for the specificities of the Belgian healthcare system.
Collapse
Affiliation(s)
- S Kindt
- Department of gastroenterology and Hepatology, Universitair Ziekenhuis Brussel, Vrije Universiteit Brussel, Brussel, Belgium
| | - H Louis
- Department of Gastroenterology, Hepatopancreatology and Digestive Oncology, Erasme University Hospital, Université Libre de Bruxelles, Route de Lennik 808, 1070 Brussels, Belgium
| | - H De Schepper
- Department of Gastroenterology and Hepatology, University Hospital Antwerp, Antwerp, Belgium
| | - J Arts
- Department of Gastroenterology and Hepatology, University Hospitals Leuven, Leuven, Belgium
- Department of Gastroenterology, AZ Sint-Lucas, Brugge, Belgium
| | - P Caenepeel
- Department of Gastroenterology and Hepatology, University Hospitals Leuven, Leuven, Belgium
- Department of Gastroenterology, Ziekenhuis Oost-Limburg, Campus Sint-Jan, Genk, Belgium
- UHasselt, Hasselt, Belgium
| | - D De Looze
- Department of Gastroenterology and Hepatology, University Hospital Ghent, Gent, Belgium
| | - A Gerkens
- Boitsfort Medical Center, Brussels, Belgium
| | - T Holvoet
- Department of Gastroenterology and Hepatology, University Hospital Ghent, Gent, Belgium
- Department of Gastroenterology, AZ Nikolaas, Sint Niklaas, Belgium
| | - P Latour
- Department of Gastroenterology, Hepatology and Digestive Oncology, Centre Hospitalier Universitaire de Liège, Liège, Belgium
| | - T Mahler
- Department of Pediatrics, Universitair Ziekenuis Brussel, Brussel, Belgium
| | - F Mokaddem
- Department of Gastroenterology and Hepatology, Vivalia-Centre Sud Luxembourg, Arlon, Belgium
| | - S Nullens
- Department of Gastroenterology and Hepatology, University Hospital Antwerp, Antwerp, Belgium
| | - H Piessevaux
- Department of Hepato-gastroenterology, Cliniques universitaires St-Luc, Université catholique de Louvain, Brussels, Belgium
| | - P Poortmans
- Department of gastroenterology and Hepatology, Universitair Ziekenhuis Brussel, Vrije Universiteit Brussel, Brussel, Belgium
| | - G Rasschaert
- Department of gastroenterology and Hepatology, Universitair Ziekenhuis Brussel, Vrije Universiteit Brussel, Brussel, Belgium
| | - M Surmont
- Department of gastroenterology and Hepatology, Universitair Ziekenhuis Brussel, Vrije Universiteit Brussel, Brussel, Belgium
| | - H Vafa
- Department of Gastroenterology and Hepatology, Chirec-Site Delta, Brussels, Belgium
| | - K Van Malderen
- Department of Gastroenterology and Hepatology, University Hospital Antwerp, Antwerp, Belgium
| | - T Vanuytsel
- Department of Gastroenterology and Hepatology, University Hospitals Leuven, Leuven, Belgium
| | - F Wuestenberghs
- Department of Gastroenterology and Hepatology, CHU UCL Namur, Université catholique de Louvain, Yvoir, Belgium
| | - J Tack
- Department of Gastroenterology and Hepatology, University Hospitals Leuven, Leuven, Belgium
| |
Collapse
|
|
44
|
Tao E, Zhu Z, Hu C, Long G, Chen B, Guo R, Fang M, Jiang M. Potential Roles of Enterochromaffin Cells in Early Life Stress-Induced Irritable Bowel Syndrome. Front Cell Neurosci 2022; 16:837166. [PMID: 35370559 PMCID: PMC8964523 DOI: 10.3389/fncel.2022.837166] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/16/2021] [Accepted: 02/09/2022] [Indexed: 12/04/2022] Open
Abstract
Irritable bowel syndrome (IBS) is one of the most common functional gastrointestinal disorders, also known as disorders of the gut–brain interaction; however, the pathophysiology of IBS remains unclear. Early life stress (ELS) is one of the most common risk factors for IBS development. However, the molecular mechanisms by which ELS induces IBS remain unclear. Enterochromaffin cells (ECs), as a prime source of peripheral serotonin (5-HT), play a pivotal role in intestinal motility, secretion, proinflammatory and anti-inflammatory effects, and visceral sensation. ECs can sense various stimuli and microbiota metabolites such as short-chain fatty acids (SCFAs) and secondary bile acids. ECs can sense the luminal environment and transmit signals to the brain via exogenous vagal and spinal nerve afferents. Increasing evidence suggests that an ECs-5-HT signaling imbalance plays a crucial role in the pathogenesis of ELS-induced IBS. A recent study using a maternal separation (MS) animal model mimicking ELS showed that MS induced expansion of intestinal stem cells and their differentiation toward secretory lineages, including ECs, leading to ECs hyperplasia, increased 5-HT production, and visceral hyperalgesia. This suggests that ELS-induced IBS may be associated with increased ECs-5-HT signaling. Furthermore, ECs are closely related to corticotropin-releasing hormone, mast cells, neuron growth factor, bile acids, and SCFAs, all of which contribute to the pathogenesis of IBS. Collectively, ECs may play a role in the pathogenesis of ELS-induced IBS. Therefore, this review summarizes the physiological function of ECs and focuses on their potential role in the pathogenesis of IBS based on clinical and pre-clinical evidence.
Collapse
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
- Wenling Maternal and Child Health Care Hospital, Wenling, China
| | - Zhenya Zhu
- 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
| | - Chenmin Hu
- 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
| | - 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
| | - 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
| | - Marong Fang
- Institute of Neuroscience and Gastrointestinal Laboratory, Children’s Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | - Mizu Jiang
- Department of Gastroenterology, 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,
| |
Collapse
|
|
45
|
Calderon G, Patel C, Camilleri M, James-Stevenson T, Bohm M, Siwiec R, Rogers N, Wo J, Lockett C, Gupta A, Xu H, Shin A. Associations of Habitual Dietary Intake With Fecal Short-Chain Fatty Acids and Bowel Functions in Irritable Bowel Syndrome. J Clin Gastroenterol 2022; 56:234-242. [PMID: 33780215 PMCID: PMC8435047 DOI: 10.1097/mcg.0000000000001521] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/15/2020] [Accepted: 01/29/2021] [Indexed: 12/10/2022]
Abstract
BACKGROUND GOALS Diet may contribute to symptoms of irritable bowel syndrome (IBS) and luminal production of putative IBS biomarkers including short-chain fatty acids (SCFAs). Study aims were to to assess relationships of habitual fiber or starch intake with fecal SCFAs in patients with IBS and healthy volunteers (HVs). STUDY In 18 HVs and 30 patients with IBS (13 constipation-predominant [IBS-C] and 17 diarrhea-predominant [IBS-D]), habitual diet using a food frequency questionnaire; bowel functions using a validated bowel diary; and fecal SCFAs by HPLC-mass spectrometry were assessed. Associations of fiber and starch with SCFAs were analyzed using Spearman (rs) and Pearson (R) correlations. Relationships between other dietary endpoints, SCFAs, and bowel functions were explored. RESULTS Habitual fiber or starch intakes were not significantly correlated with SCFAs or bowel functions in all participants or HVs nor with SCFAs in IBS. Starch was negatively correlated (R=-0.53; P=0.04) with complete evacuation in IBS-D. Fiber (rs=0.65; P=0.02) and starch (rs=0.56; P=0.05) were correlated with ease of passage in IBS-C. Stool form, frequency, and ease of passage were positively correlated with total SCFAs (all P<0.05), acetate (all P<0.01), propionate (all P<0.05), and butyrate (form P=0.01; ease of passage P=0.05) among all participants, but not in IBS. Complete evacuation was negatively correlated with propionate (R=-0.34; P=0.04) in all participants. Total (P=0.04) and individual SCFAs (all P<0.05) were positively correlated with stool form in HVs. CONCLUSIONS Habitual fiber and starch intake does not influence fecal SCFAs but may influence bowel functions in IBS. Fecal SCFAs correlate with bowel functions among all participants including HVs.
Collapse
Affiliation(s)
- Gerardo Calderon
- Division of Gastroenterology and Hepatology, Department of Medicine, Indiana University School of Medicine
| | - Chirag Patel
- Division of Gastroenterology and Hepatology, Department of Medicine, Indiana University School of Medicine
| | - Michael Camilleri
- Clinical Enteric Neuroscience Translational and Epidemiological Research (C.E.N.T.E.R.), Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN
| | - Toyia James-Stevenson
- Division of Gastroenterology and Hepatology, Department of Medicine, Indiana University School of Medicine
| | - Matthew Bohm
- Division of Gastroenterology and Hepatology, Department of Medicine, Indiana University School of Medicine
| | - Robert Siwiec
- Division of Gastroenterology and Hepatology, Department of Medicine, Indiana University School of Medicine
| | - Nicholas Rogers
- Division of Gastroenterology and Hepatology, Department of Medicine, Indiana University School of Medicine
| | - John Wo
- Division of Gastroenterology and Hepatology, Department of Medicine, Indiana University School of Medicine
| | - Carolyn Lockett
- Division of Gastroenterology and Hepatology, Department of Medicine, Indiana University School of Medicine
| | - Anita Gupta
- Division of Gastroenterology and Hepatology, Department of Medicine, Indiana University School of Medicine
| | - Huiping Xu
- Department of Biostatistics; Indiana University School of Medicine, Indianapolis, IN
| | - Andrea Shin
- Division of Gastroenterology and Hepatology, Department of Medicine, Indiana University School of Medicine
| |
Collapse
|
|
46
|
Li Y, Thelen KM, Fernández KM, Nelli R, Fardisi M, Rajput M, Trottier NL, Contreras GA, Moeser AJ. Developmental alterations of intestinal SGLT1 and GLUT2 induced by early weaning coincides with persistent low-grade metabolic inflammation in female pigs. Am J Physiol Gastrointest Liver Physiol 2022; 322:G346-G359. [PMID: 34984921 PMCID: PMC9076411 DOI: 10.1152/ajpgi.00207.2021] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [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 (ELA) is linked with the increased risk for inflammatory and metabolic diseases in later life, but the mechanisms remain poorly understood. Intestinal epithelial glucose transporters sodium-glucose-linked transporter 1 (SGLT1) and glucose transporter 2 (GLUT2) are the major route for intestinal glucose uptake but have also received increased attention as modulators of inflammatory and metabolic diseases. Here, we tested the hypothesis that early weaning (EW) in pigs, an established model of ELA, alters the development of epithelial glucose transporters and coincides with elevated markers of metabolic inflammation. The jejunum and ileum of 90-day-old pigs previously exposed to EW (16 days wean age), exhibited reduced SGLT1 activity (by ∼ 30%, P < 0.05) than late weaned (LW, 28 days wean age) controls. In contrast, GLUT2-mediated glucose transport was increased (P = 0.003) in EW pigs than in LW pigs. Reciprocal changes in SGLT1- and GLUT2-mediated transport coincided with transporter protein expression in the intestinal brush-border membranes (BBMs) that were observed at 90 days and 150 days of age. Ileal SGLT1-mediated glucose transport and BBM expression were inhibited by the β-adrenergic receptor (βAR) blocker propranolol in EW and LW pigs. In contrast, propranolol enhanced ileal GLUT2-mediated glucose transport (P = 0.015) and brush-border membrane vesicle (BBMV) abundance (P = 0.035) in LW pigs, but not in EW pigs. Early-weaned pigs exhibited chronically elevated blood glucose and C-reactive protein (CRP) levels, and adipocyte hypertrophy and upregulated adipogenesis-related gene expression in visceral adipose tissue. Altered development of intestinal glucose transporters by EW could underlie the increased risk for later life inflammatory and metabolic diseases.NEW & NOTEWORTHY These studies reveal that early-life adversity in the form of early weaning in pigs causes a developmental shift in intestinal glucose transport from SGLT1 toward GLUT2-mediated transport. Early weaning also induced markers of metabolic inflammation including persistent elevations in blood glucose and the inflammatory marker CRP, along with increased visceral adiposity. Altered intestinal glucose transport might contribute to increased risk for inflammatory and metabolic diseases associated with early-life adversity.
Collapse
Affiliation(s)
- Yihang Li
- 1Department of Large Animal Clinical Sciences, College of Veterinary Medicine, Michigan State University, East Lansing, Michigan
| | - Kyan M. Thelen
- 1Department of Large Animal Clinical Sciences, College of Veterinary Medicine, Michigan State University, East Lansing, Michigan
| | - Karina Matos Fernández
- 1Department of Large Animal Clinical Sciences, College of Veterinary Medicine, Michigan State University, East Lansing, Michigan
| | - Rahul Nelli
- 1Department of Large Animal Clinical Sciences, College of Veterinary Medicine, Michigan State University, East Lansing, Michigan
| | - Mahsa Fardisi
- 1Department of Large Animal Clinical Sciences, College of Veterinary Medicine, Michigan State University, East Lansing, Michigan
| | - Mrigendra Rajput
- 1Department of Large Animal Clinical Sciences, College of Veterinary Medicine, Michigan State University, East Lansing, Michigan
| | - Nathalie L. Trottier
- 3Department of Animal Science, Michigan State University, East Lansing, Michigan
| | - Genaro A. Contreras
- 1Department of Large Animal Clinical Sciences, College of Veterinary Medicine, Michigan State University, East Lansing, Michigan
| | - Adam J. Moeser
- 1Department of Large Animal Clinical Sciences, College of Veterinary Medicine, Michigan State University, East Lansing, Michigan,2Department of Physiology, Michigan State University, East Lansing, Michigan
| |
Collapse
|
|
47
|
Hendrix J, Ranginani D, Montero AM, Lockett C, Xu H, James-Stevenson T, Shin A. Early adverse life events and post-traumatic stress disorder in patients with constipation and suspected disordered defecation. Neurogastroenterol Motil 2022; 34:e14195. [PMID: 34121276 PMCID: PMC8715864 DOI: 10.1111/nmo.14195] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/02/2021] [Revised: 04/15/2021] [Accepted: 05/18/2021] [Indexed: 02/05/2023]
Abstract
BACKGROUND Early adverse life events (EALs) and post-traumatic stress disorder (PTSD) are associated with irritable bowel syndrome (IBS). Disordered defecation (DD) presents with symptoms of IBS or functional constipation (FC) and is associated with psychological distress. However, the role of trauma and stress in chronic constipation is poorly defined. We aimed to examine EALS, PTSD, and psychological symptoms in patients with constipation and suspected DD. METHODS We conducted a survey study among adults with constipation who completed anorectal manometry (ARM) and balloon expulsion testing (BET). Data were collected on socio-demographics, EALs, PTSD, bowel symptoms, quality of life, and anxiety and depression. We performed comparisons between individuals with normal versus abnormal ARM or BET, subgroup analysis by detailed ARM and BET findings, and latent class analysis using individual EAL domains. KEY RESULTS Among 712 eligible patients, 69 completed the study. EALs and provisional PTSD were present in 75.4% and 27.5%, respectively; rates did not differ between those with normal versus abnormal ARM or BET. Normal testing was associated with higher rates of specific EAL domains (emotional abuse and mental illness), higher depression scores, and poorer mental component scores in both primary and subgroup comparisons (all p < 0.05). Normal testing was associated with a lower likelihood of high-EAL latent class (p = 0.01) membership. Presence of IBS or FC did not influence associations. CONCLUSIONS & INFERENCES Early adverse life events and PTSD are prevalent in patients with constipation and suspected DD. Those with normal ARM and BET have higher rates of prior emotional abuse and poorer mental health.
Collapse
Affiliation(s)
- Justin Hendrix
- Division of Gastroenterology and Hepatology, Department of Medicine, Indiana University School of Medicine, Indianapolis, Indiana
| | - Dheeksha Ranginani
- Division of Gastroenterology and Hepatology, Department of Medicine, Indiana University School of Medicine, Indianapolis, Indiana
| | - Anne Mary Montero
- Division of Gastroenterology and Hepatology, Department of Medicine, Indiana University School of Medicine, Indianapolis, Indiana
| | - Carolyn Lockett
- Division of Gastroenterology and Hepatology, Department of Medicine, Indiana University School of Medicine, Indianapolis, Indiana
| | - Huiping Xu
- Department of Biostatistics and Health Data Science, Indiana University School of Medicine, Indianapolis, Indiana
| | - Toyia James-Stevenson
- Division of Gastroenterology and Hepatology, Department of Medicine, Indiana University School of Medicine, Indianapolis, Indiana
| | - Andrea Shin
- Division of Gastroenterology and Hepatology, Department of Medicine, Indiana University School of Medicine, Indianapolis, Indiana
| |
Collapse
|
|
48
|
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: 3] [Impact Index Per Article: 1.0] [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.
Collapse
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
| |
Collapse
|
|
49
|
Keefer L, Ballou SK, Drossman DA, Ringstrom G, Elsenbruch S, Ljótsson B. A Rome Working Team Report on Brain-Gut Behavior Therapies for Disorders of Gut-Brain Interaction. Gastroenterology 2022; 162:300-315. [PMID: 34529986 DOI: 10.1053/j.gastro.2021.09.015] [Citation(s) in RCA: 92] [Impact Index Per Article: 30.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/07/2021] [Revised: 09/04/2021] [Accepted: 09/10/2021] [Indexed: 12/14/2022]
Abstract
BACKGROUND AND AIMS This Rome Foundation Working Team Report reflects the consensus of an international interdisciplinary team of experts regarding the use of behavioral interventions, specifically brain-gut behavior therapies (BGBTs), in patients with disorders of gut-brain interaction (DGBIs). METHODS The committee members reviewed the extant scientific literature and, when possible, addressed gaps in this literature through the lens of their clinical and scientific expertise. The Delphi method was used to create consensus on the goals, structure, and framework before writing the report. The report is broken into 5 parts: 1) definition and evidence for BGBT, 2) the gut-brain axis as the mechanistic basis for BGBT, 3) targets of BGBTs, 4) common and unique therapeutic techniques seen in BGBT, and 5) who and how to refer for BGBT. RESULTS We chose to not only review for the reader the 5 existing classes of BGBT and their evidence, but to connect DGBI-specific behavioral targets and techniques as they relate directly, or in some cases indirectly, to the gut-brain axis. In doing so, we expect to increase gastrointestinal providers' confidence in identifying and referring appropriate candidates for BGBT and to support clinical decision making for mental health professionals providing BGBT. CONCLUSIONS Both gastrointestinal medical providers and behavioral health providers have an opportunity to optimize care for DGBIs through a collaborative integrated approach that begins with an effective patient-provider relationship, thoughtful communication about the brain-gut axis and, when appropriate, a well communicated referral to BGBT.
Collapse
Affiliation(s)
- Laurie Keefer
- Icahn School of Medicine at Mount Sinai, New York, New York.
| | - Sarah K Ballou
- Beth Israel Deaconess Medical Center, Boston, Massachusetts
| | - Douglas A Drossman
- Center for Education and Practice of Biopsychosocial Care and Drossman Gastroenterology, University of North Carolina School of Medicine, Chapel Hill, North Carolina
| | - Gisela Ringstrom
- Department of Internal Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden
| | - Sigrid Elsenbruch
- Department of Medical Psychology and Medical Sociology, Faculty of Medicine, Ruhr University Bochum, Bochum, Germany; Department of Neurology, University Hospital Essen, University of Duisburg-Essen, Essen, Germany
| | - Brjánn Ljótsson
- Division of Psychology, Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden
| |
Collapse
|
|
50
|
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
| | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | |
Collapse
|