|
1
|
Soufan F, Ghosson A, Jaber R, Ghandour A, Uwishema O. The Gut-Brain Axis in Irritable Bowel Syndrome: Implementing the Role of Microbiota and Neuroimmune Interaction in Personalized Prevention-A Narrative Review. Health Sci Rep 2025; 8:e70660. [PMID: 40256131 PMCID: PMC12006843 DOI: 10.1002/hsr2.70660] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/10/2024] [Revised: 01/15/2025] [Accepted: 03/21/2025] [Indexed: 04/22/2025] Open
Abstract
Background and Purpose Irritable bowel syndrome (IBS) is a disorder characterized by microbiota-neuroimmune interaction resulting in disturbance to the gut-brain axis (GBA). The purpose of this review is to garner an overview of the different pathophysiological mechanisms indicated in the development of IBS and the associated sequalae on gut microbiota alongside its role in the GBA. Moreover, we aim to provide an insight into the possibility of utilizing personalized medicine when managing said affected populations. Methods A comprehensive review was performed of the relevant literature pertaining to the current state of GBA alteration implicated in IBS, comprising microbiota-neuroimmune interaction alongside disturbance and activation, respectively. Different search databases were utilized, including PubMed/MEDLINE and ScienceDirect. Results The review demonstrated the most evident etiologies of IBS being the imbalance of microbiota and the alteration to the GBA. Furthermore, the interrelation between microbiota and neuroimmunity was discussed. Promising avenues for IBS prevention and management are offered through emerging research on the pathophysiological mechanisms indicated in IBS-associated GBA alteration. This entails a role for the involved interactions between microbiota modification and neuroimmunity activation. Conclusion Promising prospects for symptom prevention and management are signaled by the possibility of personalized therapy specifically designed to address the GBA dysfunction indicated in IBS. Policymakers and developers should encourage further study and allocate available resources to aid researchers in the implementation and identification of novel preventive therapeutics. Furthermore, physicians should advocate and integrate the use of personalized medical approaches of IBS to help ensure a better quality of life.
Collapse
Affiliation(s)
- Fatima Soufan
- Department of Research and EducationOli Health Magazine OrganizationKigaliRwanda
- Faculty of MedicineBeirut Arab UniversityBeirutLebanon
| | - Abir Ghosson
- Department of Research and EducationOli Health Magazine OrganizationKigaliRwanda
- Faculty of MedicineBeirut Arab UniversityBeirutLebanon
| | - Rayyan Jaber
- Department of Research and EducationOli Health Magazine OrganizationKigaliRwanda
- Faculty of MedicineBeirut Arab UniversityBeirutLebanon
| | - Adel Ghandour
- Department of Research and EducationOli Health Magazine OrganizationKigaliRwanda
- Faculty of MedicineBeirut Arab UniversityBeirutLebanon
| | - Olivier Uwishema
- Department of Research and EducationOli Health Magazine OrganizationKigaliRwanda
| |
Collapse
|
|
2
|
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
|
|
3
|
Mostafa MEA, Alrasheed T. Improvement of irritable bowel syndrome with glucagon like peptide-1 receptor agonists: a systematic review and meta-analysis. Front Endocrinol (Lausanne) 2025; 16:1548346. [PMID: 40134805 PMCID: PMC11932899 DOI: 10.3389/fendo.2025.1548346] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/19/2024] [Accepted: 02/10/2025] [Indexed: 03/27/2025] Open
Abstract
Introduction Irritable bowel syndrome (IBS) is a severe gastrointestinal condition with symptoms like pain, bloating, diarrhea, and constipation. Glucagon-like peptide-1 (GLP-1) receptors, expressed in the central nervous system and peripheral tissues, have been found to affect gut motility. GLP-1 and its analog ROSE-010 have been shown to inhibit the migrating motor complex and decrease gastrointestinal motility in IBS patients. Aim This systematic review and meta-analysis aim to assess the efficacy and safety of GLP-1 receptor agonists in providing pain and symptom relief for individuals with IBS. Methods The study conducted extensive searches across various databases, including Cochrane Library, Web of Science, PubMed, Google Scholar, and Science Direct, to identify studies on IBS and related drugs. A search strategy using keywords and medical subject heading terms (MeSH) was developed to ensure inclusivity. Exclusion criteria included non-English language studies, books, conference papers, case reports, in vitro studies, animal studies, and non-original articles. Results The study found that ROSE-010 (100 µg) significantly lowered pain intensity in IBS patients compared to a placebo, with an overall odds ratio of 2.30, 95% CI: 1.53-3.46. ROSE-010 (300 µg) is more effective than a placebo for all irritable bowel syndrome subtypes, with consistent effects across trials. ROSE-010 is linked to a greater incidence of nausea, vomiting, and headache than placebo. Conclusion ROSE-010, a glucagon-like peptide-1 receptor agonist, has been shown to reduce pain in individuals with IBS. However, its higher frequency of nausea, vomiting, and headache suggests the need for close monitoring and individualized treatment plans. Further investigation is needed to understand its impact on different IBS subtypes and long-term effects. Systematic review registration https://www.crd.york.ac.uk/PROSPERO/, identifier CRD42024613545.
Collapse
Affiliation(s)
- Mohamed E. A. Mostafa
- Department of Anatomy, Faculty of Medicine, University of Tabuk, Tabuk, Saudi Arabia
| | - Tariq Alrasheed
- Department of Internal Medicine, Faculty of Medicine, University of Tabuk, Tabuk, Saudi Arabia
| |
Collapse
|
|
4
|
Pereyra F, Schlottmann F, Casas MA, Steinberg L, Pereyra L. Exploring the gut-brain axis in a large cohort of patients with irritable bowel syndrome: Is there a link between depression and intestinal and extra-intestinal symptoms? GASTROENTEROLOGIA Y HEPATOLOGIA 2025:502370. [PMID: 39909228 DOI: 10.1016/j.gastrohep.2025.502370] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 11/03/2024] [Revised: 01/20/2025] [Accepted: 01/31/2025] [Indexed: 02/07/2025]
Abstract
OBJECTIVE We aimed to determine the prevalence of intestinal and extra-intestinal symptoms according to depression severity in a large cohort of patients with irritable bowel syndrome (IBS). PATIENTS AND METHODS A consecutive series of patients with diagnosis of IBS according to Rome IV criteria undertaking a social-media based program (B15 program) were analyzed. The B15 program provides evidence-based dietary and non-pharmacological recommendations (i.e., mindfulness techniques and exercise) to improve gastrointestinal health. All patients completed the symptom-severity questionnaire (IBS-SSS) to determine severity of disease and the patient health questionnaire (PHQ9) to assess depressive symptoms. Patients' depression severity was stratified according to the PHQ9 score: none (0-4), mild (5-9), moderate (10-14), moderately severe (15-19), and severe (20-27). Demographics, IBS phenotype and prevalence of intestinal and extra-intestinal symptoms were compared among groups. RESULTS A total of 15,675 patients with IBS were included; 895 (12.1%) with none, 5709 (36.4%) with mild, 4279 (27.3%) with moderate, 2457 (15.7%) with moderately severe, and 1335 (8.5%) with severe depression. Mean IBS-SSS score was significantly higher in patients with depressive symptoms (none 256.5 vs. severe 324.1, p<0.0001). IBS-M (mixed bowel habits alternating constipation and diarrhea) was more frequent in those with depression (p<0.0001). The presence of bloating, heartburn, dyspepsia, and belching were significantly more common in patients with higher levels of depression (p<0.0001). The prevalence and number of extra-intestinal symptoms were also associated with the severity of depression (p<0.0001). CONCLUSIONS The presence and severity of depression are strongly associated with the prevalence of intestinal and extra-intestinal symptoms in patients with IBS. Stratifying patients based on both their symptomatic and psychological profile could help targeting therapy.
Collapse
Affiliation(s)
- Facundo Pereyra
- Gastroenterology Department, Cipoletti Hospital, Río Negro, Argentina.
| | | | - María A Casas
- Department of Surgery, Hospital Alemán, Buenos Aires, Argentina
| | - Leandro Steinberg
- Gastroenterology Department, Hospital Carlos Durand, Buenos Aires, Argentina
| | - Lisandro Pereyra
- Gastroenterology Department, Hospital Alemán, Buenos Aires, Argentina
| |
Collapse
|
|
5
|
Prospero L, Riezzo G, D'Attoma B, Ignazzi A, Bianco A, Franco I, Curci R, Campanella A, Bagnato CB, Porcelli P, Giannelli G, Russo F. The impact of locus of control on somatic and psychological profiles of patients with irritable bowel syndrome engaging in aerobic exercise. Sci Rep 2025; 15:3966. [PMID: 39893252 PMCID: PMC11787329 DOI: 10.1038/s41598-025-88466-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/06/2024] [Accepted: 01/28/2025] [Indexed: 02/04/2025] Open
Abstract
Irritable bowel syndrome (IBS) is a chronic and recurrent disorder characterized by gastrointestinal (GI) symptoms and psychological disorders. Individuals with an external locus of control (LoC), a personality trait influencing one's actions and outcomes, are more vulnerable to IBS. Physical activity can deal with GI symptoms, preserving mental and physical health. In this context, our study aimed to investigate differences in symptom and psychological profiles among IBS patients classified by internal or external LoC when patients engaged in an aerobic exercise program (AEP). Each IBS patient was administered the International Physical Activity Questionnaire-Short Form (IPAQ-SF) before treatment, and the Physical Capacity Assessment Tests were applied before and after treatment. Participants filled out a GI symptom questionnaire before and after the intervention and some validated psychological tests to evaluate the changes induced by AEP. The AEP consisted of 180 min of moderate-intensity aerobic walking activity a week. Fifty-four IBS patients completed the 12-week study; 37 belonged to the internal LoC group and 17 to the external one. The internal LoC subgroup had a higher percentage of physically active subjects and a better physical capacity at baseline than those with external LoC. Only patients with an internal LoC achieved a statistically significant increase in physical capacity as the effect of the AEP. However, there was no statistically significant difference when Delta was considered. The somatic and psychological health status of IBS patients in the external LoC group was poorer than that of the internal LoC group at the baseline, particularly abdominal pain, psychosocial functioning, and emotional distress. After AEP, patients showed significant improvement in scores on the IBS-related and psychological scales, regardless of whether they belonged to the external or internal LoC. The present study confirmed the importance of considering both the GI symptoms and the psychological profile when dealing with IBS. AEP organized in walking groups has shown significant improvements for all IBS patients. Since external LoC was associated with poorer health status, individually tailored interventions should be planned to increase patients' self-motivation to treatment.Trial registration: registration number NCT05453084. First Posted Date 12/07/2022.
Collapse
Grants
- RC 2020-2021, Prog. N◦ 16 (DDG no. 700/2020) Ministero della Salute
- RC 2020-2021, Prog. N◦ 16 (DDG no. 700/2020) Ministero della Salute
- RC 2020-2021, Prog. N◦ 16 (DDG no. 700/2020) Ministero della Salute
- RC 2020-2021, Prog. N◦ 16 (DDG no. 700/2020) Ministero della Salute
- RC 2020-2021, Prog. N◦ 16 (DDG no. 700/2020) Ministero della Salute
- RC 2020-2021, Prog. N◦ 16 (DDG no. 700/2020) Ministero della Salute
- RC 2020-2021, Prog. N◦ 16 (DDG no. 700/2020) Ministero della Salute
- RC 2020-2021, Prog. N◦ 16 (DDG no. 700/2020) Ministero della Salute
- RC 2020-2021, Prog. N◦ 16 (DDG no. 700/2020) Ministero della Salute
- RC 2020-2021, Prog. N◦ 16 (DDG no. 700/2020) Ministero della Salute
- RC 2020-2021, Prog. N◦ 16 (DDG no. 700/2020) Ministero della Salute
Collapse
Affiliation(s)
- Laura Prospero
- Functional Gastrointestinal Disorders Research Group, National Institute of Gastroenterology, IRCCS "Saverio de Bellis", Via Turi 27, 70013, Castellana Grotte, BA, Italy
| | - Giuseppe Riezzo
- Functional Gastrointestinal Disorders Research Group, National Institute of Gastroenterology, IRCCS "Saverio de Bellis", Via Turi 27, 70013, Castellana Grotte, BA, Italy
| | - Benedetta D'Attoma
- Functional Gastrointestinal Disorders Research Group, National Institute of Gastroenterology, IRCCS "Saverio de Bellis", Via Turi 27, 70013, Castellana Grotte, BA, Italy
| | - Antonia Ignazzi
- Functional Gastrointestinal Disorders Research Group, National Institute of Gastroenterology, IRCCS "Saverio de Bellis", Via Turi 27, 70013, Castellana Grotte, BA, Italy
| | - Antonella Bianco
- Laboratory of Movement and Wellness, National Institute of Gastroenterology, IRCCS "Saverio de Bellis"", 70013, Castellana Grotte, BA, Italy
| | - Isabella Franco
- Laboratory of Movement and Wellness, National Institute of Gastroenterology, IRCCS "Saverio de Bellis"", 70013, Castellana Grotte, BA, Italy
| | - Ritanna Curci
- Laboratory of Movement and Wellness, National Institute of Gastroenterology, IRCCS "Saverio de Bellis"", 70013, Castellana Grotte, BA, Italy
| | - Angelo Campanella
- Laboratory of Movement and Wellness, National Institute of Gastroenterology, IRCCS "Saverio de Bellis"", 70013, Castellana Grotte, BA, Italy
| | - Claudia Beatrice Bagnato
- Laboratory of Movement and Wellness, National Institute of Gastroenterology, IRCCS "Saverio de Bellis"", 70013, Castellana Grotte, BA, Italy
| | - Piero Porcelli
- Department of Psychology, University of Chieti-Pescara, 66100, Chieti, Italy
| | - Gianluigi Giannelli
- Scientific Direction, National Institute of Gastroenterology, IRCCS "Saverio de Bellis", 70013, Castellana Grotte, BA, Italy
| | - Francesco Russo
- Functional Gastrointestinal Disorders Research Group, National Institute of Gastroenterology, IRCCS "Saverio de Bellis", Via Turi 27, 70013, Castellana Grotte, BA, Italy.
| |
Collapse
|
|
6
|
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
|
|
7
|
Sealschott S, Pickler R, Fortney C, Bailey M, Loman B. Gut Microbiota and Symptom Expression and Severity in Neonatal Abstinence Syndrome. Biol Res Nurs 2024; 26:460-468. [PMID: 38528812 DOI: 10.1177/10998004241242102] [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] [Indexed: 03/27/2024]
Abstract
Problem: Neonatal abstinence syndrome (NAS) affecting neonates with fetal exposure to opioids, is defined by expression and severity of symptoms. The pathophysiology behind symptoms variability is lacking. The study aims were to examine (a) differences in gut microbiota of neonates with and without NAS, (b) the relationships between gut microbiota and symptom expression and NAS severity, and (c) the changes in the neonate gut microbiota diversity during the course of NAS treatment. Methods: A cross-sectional observational design was used to examine differences in microbiota and a longitudinal, repeated measures approach was used to determine relationships between gut microbiota and NAS symptoms. Symptom data were collected using the Finnegan Neonatal Abstinence Scoring Tool and the Neonatal Pain Agitation and Sedation Scale. Stool samples were collected for microbiome analyses with 16S rRNA microbiome sequencing. Results: Differences in alpha and beta diversity between neonates with and without NAS were seen. Relative abundance results revealed 18 taxa were different in neonates with NAS compared to neonates without NAS. No differences were found in alpha or beta diversity in neonates with NAS between enrollment and hospital discharge. There was increased abundance of Escherichia-Shigella and Bacteriodes genera related to higher symptom scores. Discussion: Differences in alpha and beta diversity between neonates with and without NAS may be due to differences in birth mode and type of feeding. The findings of specific increased bacteria related to increased symptoms in the neonates with NAS may also be influenced by birth mode and type of feeding.
Collapse
Affiliation(s)
| | - Rita Pickler
- The Ohio State University College of Nursing, Columbus, OH, USA
| | | | - Michael Bailey
- The Ohio State University College of Nursing, Columbus, OH, USA
- Center for Microbial Pathogenesis, Columbus, The Research Institute at Nationwide Children's Hospital, OH, USA
| | - Brett Loman
- University of Illinois Urbana-Champaign, Urbana, IL, USA
| |
Collapse
|
|
8
|
Khaledi M, Sameni F, Gholipour A, Shahrjerdi S, Golmohammadi R, Gouvarchin Ghaleh HE, Poureslamfar B, Hemmati J, Mobarezpour N, Milasi YE, Rad F, Mehboodi M, Owlia P. Potential role of gut microbiota in major depressive disorder: A review. Heliyon 2024; 10:e33157. [PMID: 39027446 PMCID: PMC11254604 DOI: 10.1016/j.heliyon.2024.e33157] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/04/2023] [Revised: 06/10/2024] [Accepted: 06/14/2024] [Indexed: 07/20/2024] Open
Abstract
Interactions between the gut microbiota and host immunity are sophisticated, dynamic, and host-dependent. Scientists have recently conducted research showing that disturbances in the gut bacterial community can lead to a decrease in some metabolites and, consequently, to behaviors such as depression. Exposure to stressors dropped the relative abundance of bacteria in the genus Bacteroides while soaring the relative abundance of bacteria in the genus Clostridium, Coprococcus, Dialister, and Oscillibacter, which were also reduced in people with depression. Microbiota and innate immunity are in a bilateral relationship. The gut microbiota has been shown to induce the synthesis of antimicrobial proteins such as catalysidins, type C lectins, and defensins. Probiotic bacteria can modulate depressive behavior through GABA signaling. The gut microbiome produces essential metabolites such as neurotransmitters, tryptophan metabolites, and short-chain fatty acids (SCFAs) that can act on the CNS. In the case of dysbiosis, due to mucin changes, the ratio of intestinal-derived molecules may change and contribute to depression. Psychotropics, including Bifidobacterium longum NCC3001, Clostridium butyricum CBM588, and Lactobacillus acidophilus, have mental health benefits, and can have a positive effect on the host-brain relationship, and have antidepressant effects. This article reviews current studies on the association between gut microbiota dysbiosis and depression. Comprehensively, these findings could potentially lead to novel approaches to improving depressive symptoms via gut microbiota alterations, including probiotics, prebiotics, and fecal microbiota transplantation.
Collapse
Affiliation(s)
- Mansoor Khaledi
- Department of Microbiology, Faculty of Medicine, Shahed University, Tehran, Iran
- Cellular and Molecular Research Center, Basic Health Sciences Institute, Shahrekord University of Medical Sciences, Shahrekord, Iran
| | - Fatemeh Sameni
- Department of Microbiology, Faculty of Medicine, Shahed University, Tehran, Iran
| | - Abolfazl Gholipour
- Cellular and Molecular Research Center, Basic Health Sciences Institute, Shahrekord University of Medical Sciences, Shahrekord, Iran
| | - Shahnaz Shahrjerdi
- Department of Physiology and Sports Pathology, Faculty of Sport Sciences, Arak University, Arak, Iran
| | - Reza Golmohammadi
- Baqiyatallah Research Center for Gastroenterology and Liver Diseases (BRCGL), Clinical Sciences Institute, Baqiyatallah University of Medical Sciences, Tehran, Iran
| | | | | | - Jaber Hemmati
- Department of Microbiology, Faculty of Medicine, Hamadan University of Medical Sciences, Hamadan, Iran
| | - Niloofar Mobarezpour
- Reference Laboratory for Bovine Tuberculosis, Razi Vaccine and Serum Research Institute, Karaj, Iran
| | - Yaser Eshaghi Milasi
- Department of Clinical Biochemistry, School of Pharmacy and Pharmaceutical Sciences, Isfahan University of Medical Sciences, Isfahan, Iran
| | - Fatemeh Rad
- Department of Microbiology, Faculty of Medicine, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran
| | - Mahtab Mehboodi
- Department of Microbiology and Virology, Kerman University of Medical Sciences, Kerman, Iran
| | - Parviz Owlia
- Molecular Microbiology Research Center, Faculty of Medicine, Shahed University, Tehran, Iran
| |
Collapse
|
|
9
|
Diao Z, Xu W, Guo D, Zhang J, Zhang R, Liu F, Hu Y, Ma Y. Causal association between psycho-psychological factors, such as stress, anxiety, depression, and irritable bowel syndrome: Mendelian randomization. Medicine (Baltimore) 2023; 102:e34802. [PMID: 37653741 PMCID: PMC10470701 DOI: 10.1097/md.0000000000034802] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/15/2023] [Revised: 07/18/2023] [Accepted: 07/27/2023] [Indexed: 09/02/2023] Open
Abstract
BACKGROUND Pathogenesis, diagnosis, and treatment of irritable bowel syndrome (IBS) have been reported to be challenging hotspots in clinical practice. Previous observational studies have found that stress, anxiety, depression, and other mental and psychological diseases are closely associated with IBS. This study aimed to further explore the causal relationships of these associations through Mendelian randomization (MR). METHODS The data needed for MR were obtained from publicly published genome-wide association databases. We performed a bidirectional, 2-sample MR analysis using instrumental variables (IV) associated with stress, anxiety, and depression, and other mental and psychological factors as exposures and IBS as the outcome. A reverse MR analysis with IBS as exposure and stress, anxiety, depression, and other mental and psychological factors as the outcomes was also performed. The inverse variance weighting (IVW) method was adopted as the main method of MR, and the causal effect between stress, anxiety, depression, and other mental and psychological factors and IBS was evaluated as the main result of the study. In addition, a series of sensitivity analyses was conducted to comprehensively evaluate the causal relationship between them. RESULTS Stress, anxiety, depression, and other mental and psychological factors were the underlying etiologies for IBS (odds ratio [OR] = 1.06, 95% confidence interval [CI]: 1.03-1.08), and they were positively correlated. Univariate analysis further supported the above conclusions (Depression, [OR = 1.31, 95% CI: 1.05-1.63, P = .016], Anxiety, [OR = 1.53, 95% CI: 1.16-2.03, P = .003]). However, in reverse MR analysis, we found that IBS did not affect stress, anxiety, depression, or other mental and psychological factors and that there was no causal relationship between IBS and stress, anxiety, depression, or other mental and psychological factors (P > .05). CONCLUSION This study demonstrates that mental and psychological factors are the underlying etiologies for IBS. These findings may provide important information for physicians regarding the clinical treatment of IBS.
Collapse
Affiliation(s)
- Zhihao Diao
- School of Acupuncture and Tuina, Shandong University of Traditional Chinese Medicine, Jinan, China
| | - Wenchang Xu
- School of Acupuncture and Tuina, Shandong University of Traditional Chinese Medicine, Jinan, China
| | - Danyang Guo
- The First Clinical Medical College, Shandong University of Traditional Chinese Medicine, Jinan, China
| | - Jingzhi Zhang
- School of Acupuncture and Tuina, Shandong University of Traditional Chinese Medicine, Jinan, China
| | - Ruiyu Zhang
- School of Acupuncture and Tuina, Shandong University of Traditional Chinese Medicine, Jinan, China
| | - Fengzhao Liu
- The First Clinical Medical College, Shandong University of Traditional Chinese Medicine, Jinan, China
| | - Yufei Hu
- School of Acupuncture and Tuina, Shandong University of Traditional Chinese Medicine, Jinan, China
| | - Yuxia Ma
- School of Acupuncture and Tuina, Shandong University of Traditional Chinese Medicine, Jinan, China
- Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Jinan, China
| |
Collapse
|
|
10
|
Khayat A, Aldharman SS, Alharbi NN, Alayyaf AS, abdulmuttalib JA, Altalhi ER. Regional and seasonal variations in functional abdominal pain and functional constipation prevalence among Saudi children. SAGE Open Med 2023; 11:20503121231163519. [PMID: 37026105 PMCID: PMC10071212 DOI: 10.1177/20503121231163519] [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: 10/21/2022] [Accepted: 02/24/2023] [Indexed: 04/03/2023] Open
Abstract
OBJECTIVES This study aimed to evaluate functional abdominal pain disorders and functional constipation prevalence in the central region of Saudi Arabia, and compare it to that of the western region. METHODS This was a cross-sectional study using online questionnaires targeting the general population of Riyadh region of Saudi Arabia. Subjects were randomly selected by sharing links on social media groups. Any parent with a 3-18-year-old child was included, and children with chronic medical illnesses or symptoms of organic GI disorders were excluded. RESULTS Three hundred nineteen subjects were included in the final analysis; the prevalence of functional abdominal pain disorders overall was 6.2% and the prevalence of functional constipation was 8.1%. CONCLUSIONS Functional constipation diagnosis seems to be affected by life stressors or a previous viral illness. Seasonal variations had minimal effect on functional abdominal pain disorder and functional constipation symptom frequency and severity.
Collapse
Affiliation(s)
- Ammar Khayat
- Umm Al Qura University, Al Abdeyah,
Makkah, Saudi Arabia
| | - Sarah Salem Aldharman
- College of Medicine, King Saud bin
Abdulaziz University for Health Sciences, Riyadh, Saudi Arabia
| | - Njoud Naif Alharbi
- College of Medicine, Princess Nourah
bint Abdulrahman University, Riyadh, Saudi Arabia
| | | | | | | |
Collapse
|
|
11
|
Almirall M, Casellas F, Dot J, de Torres I, Segurola H, Marsal S. Prevalence of non-coeliac gluten sensitivity and assessment of the response to gluten-free diet in a cohort of patients with fibromyalgia. Rheumatology (Oxford) 2023; 62:1069-1077. [PMID: 35900154 DOI: 10.1093/rheumatology/keac434] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/05/2022] [Revised: 07/22/2022] [Accepted: 07/22/2022] [Indexed: 11/13/2022] Open
Abstract
OBJECTIVES To establish the prevalence of non-coeliac gluten sensitivity (NCGS) in a cohort of fibromyalgia patients and to evaluate their clinical response to a six-week gluten-free diet (GFD), the improvement in their symptoms, the percentage of diet responders who did not fulfil the diagnostic criteria for NCGS and the baseline characteristics that were associated with diet response and diagnostic criteria fulfilment. METHODS Uncontrolled prospective experimental study in a cohort of patients with fibromyalgia from a specialized hospital unit. The percentage of patients that fulfilled the Salerno Experts' Criteria, that responded to GFD, that improved their symptomatology and baseline characteristics associated with GFD response and diagnostic criteria fulfilment was analysed. RESULTS In total, 142 patients were selected and a NCGS prevalence of 5.6% was observed. A total of 21.8% responded to GFD due to their improvement in intestinal symptoms. In total, 74.2% of the responders did not fulfil the Salerno Experts' Criteria. The presence of diarrhoea and intraepithelial lymphocytosis and lower levels of anxiety were predictive factors of GFD response. No predictive factors of NCGS criteria fulfilment were found due to the low number of discriminators between gluten and placebo. CONCLUSIONS A NCGS prevalence similar to that estimated in the general population was found. A GFD cannot be systematically recommended to all patients with fibromyalgia, although it could be evaluated in those with diarrhoea or intraepithelial lymphocytosis to evaluate if there are improvements in their intestinal symptoms.
Collapse
Affiliation(s)
- Miriam Almirall
- Department of Rheumatology, Hospital Universitari Vall d'Hebron.,Rheumatology Research Group, Vall d'Hebron Research Institute
| | | | | | - Inés de Torres
- Department of Pathology, Hospital Universitari Vall d'Hebron.,Department of Morphological Sciences, Autonomous University of Barcelona
| | - Hegoi Segurola
- Nutritional Support Unit, Hospital Universitari Vall d'Hebron, Barcelona, Spain
| | - Sara Marsal
- Department of Rheumatology, Hospital Universitari Vall d'Hebron.,Rheumatology Research Group, Vall d'Hebron Research Institute
| |
Collapse
|
|
12
|
The effect of Benson relaxation technique on the severity of symptoms and quality of life in children with irritable bowel syndrome (IBS): a quasi-experimental study. BMC Gastroenterol 2022; 22:547. [PMID: 36581912 PMCID: PMC9801626 DOI: 10.1186/s12876-022-02631-0] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/26/2022] [Accepted: 12/21/2022] [Indexed: 12/31/2022] Open
Abstract
AIM This study aimed to determine the effect of the Benson relaxation technique on the severity of symptoms and quality of life in children with irritable bowel syndrome (IBS). DESIGN This quasi-experimental study was carried out on children with irritable bowel syndrome in Iran. METHOD Sixty children were randomly divided into control and experimental groups. The Benson relaxation technique was implemented for three weeks for experimental group, while the control group only received the typical medical therapy with no special intervention. The questionnaire of Irritable Bowel Syndrome-quality of life-34 (IBS-QOL-34), and Bowel Symptoms Severity and Frequency Scale (BSS-FS) were used for data gathering before and three weeks after the intervention. Data were analyzed using statistics, appropriate parametric and non-parametric tests. RESULTS According to the results, the experimental group had lower mean scores of qualities of life before the intervention (p < 0.05). The mean score of symptom severity in children with IBS was 13.88 in the experimental group, which changed to 9.83 in the post-test, indicating a significant difference (p < 0.000). The pre-test and post-test mean scores for quality of life in this group were 118.94 and 102.77, respectively, indicating a significant difference (P < 0.001). CONCLUSION The Benson relaxation technique can be a non-pharmacological solution to reduce the severity of symptoms and improve the quality of life of children with IBS. IMPLICATION TO PRACTICE This technique is supposed to contribute as a further intervention in clinical contexts.
Collapse
|
|
13
|
Liu Y, Chen Z, Lin W, Zhou Y, Liu Z, Zhao R, Chen Y, Wu B, Chen A, Lin C. Role of hippocampal circKcnk9 in visceral hypersensitivity and anxiety comorbidity of irritable bowel syndrome. Front Cell Neurosci 2022; 16:1010107. [PMID: 36467610 PMCID: PMC9714028 DOI: 10.3389/fncel.2022.1010107] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/02/2022] [Accepted: 10/17/2022] [Indexed: 02/03/2024] Open
Abstract
Irritable bowel syndrome (IBS) is a common gastrointestinal disorder characterized by recurrent visceral pain and altered bowel habits (diarrhea or constipation). However, the molecular and pathological mechanisms are poorly understood. This study found neonatal colorectal distension to induce visceral hypersensitivity and anxiety. The expression of hippocampal circKcnk9, a novel circRNA, was significantly increased in IBS-like rats. Interestingly, CA1 shcircKcnk9 treatment inhibited long-term potentiation (LTP) and alleviated visceral hypersensitivity and anxiety in IBS-like rats, whereas overexpression of CA1 circKcnk9 induced LTP, visceral hypersensitivity, and anxiety in controls. Several experiments indicated that increased CA1 circKcnk9 acted as a miR-124-3p sponge, which resulted in the inhibitory effect of miR-124-3p on gene silencing. There was a negative correlation between circKcnk9 and miR-124-3p expression. As expected, CA1 administration of agomiR-124-3p decreased CA1 LTP, visceral hypersensitivity, and anxiety in the IBS-like rats. In contrast, CA1 treatment with antagomiR-124-3p induced LTP, visceral hypersensitivity, and anxiety in the controls. Furthermore, bioinformatic analysis and experimental data showed that EZH2 is a circKcnk9/miR-124-3p target gene, and increased EZH2 expression was involved in visceral hypersensitivity and anxiety in IBS-like rats by enhancing hippocampal synaptic plasticity. In conclusion, early life stress induces increased expression of circKcnk9 in the CA1 of IBS-like rats. Increased circKcnk9 expression regulates synaptic transmission and enhances LTP, leading to visceral hypersensitivity and anxiety in IBS-like rats. The underlying circKcnk9 signaling pathway is miR124-3p/EZH2. Increased circKcnk9 reinforces its sponging of miR124-3p and strongly suppresses miR124-3p activity, resulting in increased expression of the target gene EZH2. This study provides a new epigenetic mechanism for visceral hypersensitivity and anxiety in IBS-like rats.
Collapse
Affiliation(s)
- Yuan Liu
- Fujian Provincial Key Laboratory of Brain Aging and Neurodegenerative Diseases, Pain Research Institute, School of Basic Medical Sciences, Fujian Medical University, Fuzhou, China
| | - Zhong Chen
- Fujian Provincial Key Laboratory of Brain Aging and Neurodegenerative Diseases, Pain Research Institute, School of Basic Medical Sciences, Fujian Medical University, Fuzhou, China
| | - Wei Lin
- Department of Pediatrics, The First Affiliated Hospital of Fujian Medical University, Fuzhou, China
| | - Yifei Zhou
- Fujian Provincial Key Laboratory of Brain Aging and Neurodegenerative Diseases, Pain Research Institute, School of Basic Medical Sciences, Fujian Medical University, Fuzhou, China
| | - Zihan Liu
- Fujian Provincial Key Laboratory of Brain Aging and Neurodegenerative Diseases, Pain Research Institute, School of Basic Medical Sciences, Fujian Medical University, Fuzhou, China
| | - Ruixia Zhao
- Fujian Provincial Key Laboratory of Brain Aging and Neurodegenerative Diseases, Pain Research Institute, School of Basic Medical Sciences, Fujian Medical University, Fuzhou, China
| | - Yu Chen
- Fujian Provincial Key Laboratory of Brain Aging and Neurodegenerative Diseases, Pain Research Institute, School of Basic Medical Sciences, Fujian Medical University, Fuzhou, China
| | - Bin Wu
- Department of Pediatrics, The First Affiliated Hospital of Fujian Medical University, Fuzhou, China
| | - Aiqin Chen
- Fujian Provincial Key Laboratory of Brain Aging and Neurodegenerative Diseases, Pain Research Institute, School of Basic Medical Sciences, Fujian Medical University, Fuzhou, China
| | - Chun Lin
- Fujian Provincial Key Laboratory of Brain Aging and Neurodegenerative Diseases, Pain Research Institute, School of Basic Medical Sciences, Fujian Medical University, Fuzhou, China
- Department of Pediatrics, The First Affiliated Hospital of Fujian Medical University, Fuzhou, China
| |
Collapse
|
|
14
|
Xu QY, Zhang HL, Du H, Li YC, Ji FH, Li R, Xu GY. Identification of a Glutamatergic Claustrum-Anterior Cingulate Cortex Circuit for Visceral Pain Processing. J Neurosci 2022; 42:8154-8168. [PMID: 36100399 PMCID: PMC9637003 DOI: 10.1523/jneurosci.0779-22.2022] [Citation(s) in RCA: 14] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/30/2022] [Revised: 08/30/2022] [Accepted: 09/04/2022] [Indexed: 11/21/2022] Open
Abstract
Chronic visceral pain is a major challenge for both patients and health providers. Although the central sensitization of the brain is thought to play an important role in the development of visceral pain, the detailed neural circuits remain largely unknown. Using a well-established chronic visceral hypersensitivity model induced by neonatal maternal deprivation (NMD) in male mice, we identified a distinct pathway whereby the claustrum (CL) glutamatergic neuron projecting to the anterior cingulate cortex (ACC) is critical for visceral pain but not for CFA-evoked inflammatory pain. By a combination of in vivo circuit-dissecting extracellular electrophysiological approaches and visceral pain related electromyographic (EMG) recordings, we demonstrated that optogenetic inhibition of CL glutamatergic activity suppressed the ACC neural activity and visceral hypersensitivity of NMD mice whereas selective activation of CL glutamatergic activity enhanced the ACC neural activity and evoked visceral pain of control mice. Further, optogenetic studies demonstrate a causal link between such neuronal activity and visceral pain behaviors. Chemogenetic activation or inhibition of ACC neural activities reversed the effects of optogenetic manipulation of CL neural activities on visceral pain responses. Importantly, molecular detection showed that NMD significantly enhances the expression of NMDA receptors and activated CaMKIIα in the ACC postsynaptic density (PSD) region. Together, our data establish a functional role for CL→ACC glutamatergic neurons in gating visceral pain, thus providing a potential treatment strategy for visceral pain.SIGNIFICANCE STATEMENT Studies have shown that sensitization of anterior cingulate cortex (ACC) plays an important role in chronic pain. However, it is as yet unknown whether there is a specific brain region and a distinct neural circuit that helps the ACC to distinguish visceral and somatic pain. The present study demonstrates that claustrum (CL) glutamatergic neurons maybe responding to colorectal distention (CRD) rather than somatic stimulation and that a CL glutamatergic projection to ACC glutamatergic neuron regulates visceral pain in mice. Furthermore, excessive NMDA receptors and overactive CaMKIIα in the ACC postsynaptic density (PSD) region were observed in mice with chronic visceral pain. Together, these findings reveal a novel neural circuity underlying the central sensitization of chronic visceral pain.
Collapse
Affiliation(s)
- Qi-Ya Xu
- Jiangsu Key Laboratory of Neuropsychiatric Diseases, Institute of Neuroscience, Soochow University, Suzhou 215123, People's Republic of China
| | - Hai-Long Zhang
- Jiangsu Key Laboratory of Neuropsychiatric Diseases, Institute of Neuroscience, Soochow University, Suzhou 215123, People's Republic of China
| | - Han Du
- Jiangsu Key Laboratory of Neuropsychiatric Diseases, Institute of Neuroscience, Soochow University, Suzhou 215123, People's Republic of China
| | - Yong-Chang Li
- Jiangsu Key Laboratory of Neuropsychiatric Diseases, Institute of Neuroscience, Soochow University, Suzhou 215123, People's Republic of China
| | - Fu-Hai Ji
- Department of Anesthesiology, The First Affiliated Hospital of Soochow University, Suzhou 215006, People's Republic of China
| | - Rui Li
- Department of Gastroenterology, The First Affiliated Hospital of Soochow University, Suzhou 215006, People's Republic of China
| | - Guang-Yin Xu
- Jiangsu Key Laboratory of Neuropsychiatric Diseases, Institute of Neuroscience, Soochow University, Suzhou 215123, People's Republic of China
| |
Collapse
|
|
15
|
Two Gold Kiwifruit Daily for Effective Treatment of Constipation in Adults-A Randomized Clinical Trial. Nutrients 2022; 14:nu14194146. [PMID: 36235798 PMCID: PMC9572406 DOI: 10.3390/nu14194146] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/07/2022] [Revised: 09/23/2022] [Accepted: 10/03/2022] [Indexed: 11/16/2022] Open
Abstract
Chronic constipation is highly prevalent worldwide and may be managed with two green or three gold kiwifruit daily. It is unknown whether a smaller standard serve of gold kiwifruit (two daily) is as effective in constipation management. The study aimed to improve chronic constipation with two gold kiwifruit and psyllium in lieu of a placebo daily over four weeks. Adult participants (18-65 years) with functional constipation (FC, n = 11), constipation-predominant irritable bowel syndrome (IBS-C, n = 13), and healthy controls (n = 32) were block-randomized to the treatment order: gold kiwifruit (2/day) or psyllium (fiber-matched, 7.5 g/day) for four weeks, followed by four weeks washout before crossover. Outcomes included alterations of Gastrointestinal Symptom Rating Scale (GSRS) domains and weekly complete spontaneous bowel movements (CSBM) as part of a larger study. Both interventions reduced GSRS constipation domain scores in all subjects compared to baseline values (p = 0.004). All participants reported significantly more weekly CSBM (p = 0.014). Two gold kiwifruit decreased straining (p = 0.021). Two gold kiwifruit daily are as effective as fiber-matched psyllium in treating constipation in adults and should be considered as a treatment option.
Collapse
|
|
16
|
Cuskelly A, Hoedt EC, Harms L, Talley NJ, Tadros MA, Keely S, Hodgson DM. Neonatal immune challenge influences the microbiota and behaviour in a sexually dimorphic manner. Brain Behav Immun 2022; 103:232-242. [PMID: 35491004 DOI: 10.1016/j.bbi.2022.04.023] [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] [Received: 12/20/2021] [Revised: 03/31/2022] [Accepted: 04/26/2022] [Indexed: 10/18/2022] Open
Abstract
There is comorbidity between anxiety disorders and gastrointestinal disorders, with both linked to adverse early life events. The microbiome gut-brain-axis, a bidirectional communication system, is plastic throughout the neonatal period and is a possible mediator of this relationship. Here, we used a well-established neonatal rodent immune activation model to investigate the long-term effect of neonatal lipopolysaccharide (LPS) exposure on adult behaviour and the relationship to microbiome composition. Wistar rats were injected with LPS (0.05 mg/kg) or saline (equivolume) on postnatal days 3 and 5. In adulthood, behavioural tests were performed to assess anxiety-like behaviour, and microbiota sequencing was performed on stool samples. There were distinctly different behavioural phenotypes for LPS-exposed males and females. LPS-exposed males displayed typical anxiety-like behaviours with significantly decreased social interaction (F(1,22) = 7.576, p = 0.009) and increased defecation relative to saline controls (F(1,23) = 8.623, p = 0.005). LPS-exposed females displayed a different behavioural phenotype with significantly increased social interaction (F(1,22) = 6.094, p = 0.018), and exploration (F(1,24) = 6.359, p = 0.015), compared to saline controls. With respect to microbiota profiling data, Bacteroidota was significantly increased for LPS-exposed females (F(1,14) = 4.931p = 0.035) and Proteobacteria was decreased for LPS-exposed rats of both sexes versus controls (F(1,30) = 4.923p = 0.035). Furthermore, alterations in predicted functional pathways for neurotransmitters in faeces were observed with a decrease in the relative abundance of D-glutamine and D-glutamate metabolism in LPS exposed females compared to control females (p < 0.05). This suggests that neonatal immune activation alters both later life behaviour and adult gut microbiota in sex-specific ways. These findings highlight the importance of sex in determining the impact of neonatal immune activation on social behaviour and the gut microbiota.
Collapse
Affiliation(s)
- A Cuskelly
- School of Psychological Sciences, University of Newcastle, Callaghan, NSW, Australia; Viruses, Infection, Immunity, Vaccine and Asthma (VIVA) Program, Hunter Medical Research Institute (HMRI), Newcastle, NSW, Australia.
| | - E C Hoedt
- Viruses, Infection, Immunity, Vaccine and Asthma (VIVA) Program, Hunter Medical Research Institute (HMRI), Newcastle, NSW, Australia; NHMRC Centre of Research Excellence (CRE) in Digestive Health, HMRI, Newcastle, NSW, Australia; School of Biomedical Sciences and Pharmacy, University of Newcastle, Callaghan, Australia
| | - L Harms
- School of Medicine and Public Health, University of Newcastle, New Lambton, NSW, Australia
| | - N J Talley
- Viruses, Infection, Immunity, Vaccine and Asthma (VIVA) Program, Hunter Medical Research Institute (HMRI), Newcastle, NSW, Australia; NHMRC Centre of Research Excellence (CRE) in Digestive Health, HMRI, Newcastle, NSW, Australia; School of Medicine and Public Health, University of Newcastle, New Lambton, NSW, Australia
| | - M A Tadros
- School of Medicine and Public Health, University of Newcastle, New Lambton, NSW, Australia
| | - S Keely
- Viruses, Infection, Immunity, Vaccine and Asthma (VIVA) Program, Hunter Medical Research Institute (HMRI), Newcastle, NSW, Australia; NHMRC Centre of Research Excellence (CRE) in Digestive Health, HMRI, Newcastle, NSW, Australia; School of Medicine and Public Health, University of Newcastle, New Lambton, NSW, Australia
| | - D M Hodgson
- School of Psychological Sciences, University of Newcastle, Callaghan, NSW, Australia; Viruses, Infection, Immunity, Vaccine and Asthma (VIVA) Program, Hunter Medical Research Institute (HMRI), Newcastle, NSW, Australia
| |
Collapse
|
|
17
|
Zhang Y, Zhang R, Liu P, Wang J, Gao M, Zhang J, Yang J, Yang C, Zhang Y, Sun N. Characteristics and Mediating Effect of Gut Microbiota With Experience of Childhood Maltreatment in Major Depressive Disorder. Front Neurosci 2022; 16:926450. [PMID: 35774560 PMCID: PMC9238290 DOI: 10.3389/fnins.2022.926450] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/22/2022] [Accepted: 05/25/2022] [Indexed: 11/13/2022] Open
Abstract
Gut microbiota and childhood maltreatment are closely related to depressive symptoms. This study aimed to analyze the characteristics of gut microbiota in major depressive disorder (MDD) patients with childhood maltreatment experience and explore the correlation between gut microbiota, childhood maltreatment, and depressive symptoms. A total of 37 healthy controls (HCs) and 53 patients with MDD were enrolled, including 18 MDD patients without childhood maltreatment experience and 35 MDD patients with childhood maltreatment experience. The Hamilton’s Depression Scale (HAMD-24) and Childhood Trauma Questionnaire-Short Form (CTQ-SF) were used to evaluate their depressive symptoms and childhood maltreatment experience, respectively. The composition of gut microbiota was evaluated using 16S rRNA sequencing. Spearman’s correlation analysis was used to evaluate the correlation between different gut microbiota, depressive symptoms and childhood maltreatment. The mediation analysis was used to evaluate the mediating effect of gut microbiota. In the α-diversity analysis, we found that the Simpson index and Pielou’s Evenness index differed significantly between MDD patients without childhood maltreatment experience and HCs. In the β-diversity analysis, principal coordinate analysis (PCoA) showed significant differences between MDD patients without childhood maltreatment experience, MDD patients with childhood maltreatment experience and HCs. Twenty-seven different bacteria were identified through Linear discriminant analysis effect size (LEfSe) analysis at different levels of classification. The analysis of the correlation showed that Blautia, Bifidobacterium, Bacteroides, Roseburia, and Phascolarctobacterium were significantly correlated with HAMD and CTQ-SF scores. The mediation analysis showed that childhood maltreatment had a significant direct effect on the patients’ depressive symptoms, and Blautia, Bifidobacterium, Roseburia had a significant mediating effect. The findings of this study suggested that MDD patients with childhood maltreatment experience had different gut microbiota, which might have a mediating effect on the influence of childhood maltreatment on depressive symptoms.
Collapse
Affiliation(s)
- Yanyan Zhang
- Department of Psychiatry, First Hospital of Shanxi Medical University, Taiyuan, China
- Department of Physiology, Shanxi Medical University, Taiyuan, China
- Key Laboratory of Cellular Physiology, Ministry of Education, Shanxi Medical University, Taiyuan, China
| | - Ruiyu Zhang
- Department of Psychiatry, First Hospital of Shanxi Medical University, Taiyuan, China
- First Clinical Medical College of Shanxi Medical University, Taiyuan, China
| | - Penghong Liu
- Department of Psychiatry, First Hospital of Shanxi Medical University, Taiyuan, China
- First Clinical Medical College of Shanxi Medical University, Taiyuan, China
| | - Jizhi Wang
- Department of Psychiatry, First Hospital of Shanxi Medical University, Taiyuan, China
- First Clinical Medical College of Shanxi Medical University, Taiyuan, China
| | - Mingxue Gao
- Department of Psychiatry, First Hospital of Shanxi Medical University, Taiyuan, China
- First Clinical Medical College of Shanxi Medical University, Taiyuan, China
| | - Jie Zhang
- Department of Psychiatry, First Hospital of Shanxi Medical University, Taiyuan, China
- First Clinical Medical College of Shanxi Medical University, Taiyuan, China
| | - Jun Yang
- Department of Psychiatry, First Hospital of Shanxi Medical University, Taiyuan, China
- First Clinical Medical College of Shanxi Medical University, Taiyuan, China
| | - Chunxia Yang
- Department of Psychiatry, First Hospital of Shanxi Medical University, Taiyuan, China
| | - Yu Zhang
- Department of Physiology, Shanxi Medical University, Taiyuan, China
- Key Laboratory of Cellular Physiology, Ministry of Education, Shanxi Medical University, Taiyuan, China
- *Correspondence: Yu Zhang,
| | - Ning Sun
- Department of Psychiatry, First Hospital of Shanxi Medical University, Taiyuan, China
- First Clinical Medical College of Shanxi Medical University, Taiyuan, China
- Ning Sun,
| |
Collapse
|
|
18
|
Correlation between Intestinal Microflora in Irritable Bowel Syndrome and Severity. DISEASE MARKERS 2022; 2022:1031844. [PMID: 35634439 PMCID: PMC9132690 DOI: 10.1155/2022/1031844] [Citation(s) in RCA: 12] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Received: 04/06/2022] [Revised: 04/21/2022] [Accepted: 04/22/2022] [Indexed: 02/07/2023]
Abstract
Background Irritable bowel syndrome (IBS) is a common chronic functional gastrointestinal disease accompanied by changes in intestinal microecology. This study investigated the relationship between gut microbiota and disease severity in patients with irritable bowel syndrome (IBS). Methods An observational study was performed on 60 IBS patients (study group) and 20 healthy controls admitted to our hospital from January 2013 to December 2014. Fecal samples were taken after admission to measure intestinal flora including Bifidobacterium, Lactobacillus, Enterobacter, and Enterococcus, and patient blood was collected to determine serum D-lactate and diamine oxidase (DAO) levels. The gut microbiota and serum markers of the two groups were analyzed. The correlation of gut microbiota index levels and serum markers with disease severity, as well as the correlation between gut microbiota index levels and serum markers, were analyzed. Results The levels of intestinal Lactobacillus and Bifidobacterium were lower, while the levels of Enterococcus and Enterobacter and serum D-lactate were higher in the study group than those in the control group. The levels of intestinal Lactobacillus and Bifidobacterium were lower, while the levels of Enterococcus and Enterobacter, serum D-lactate, and DAO were higher in patients with moderate IBS than those in patients with mild IBS. The levels of intestinal Lactobacillus and Bifidobacterium were lower in patients with severe IBS than those with moderate IBS, while the levels of Enterococcus and Enterobacter, serum D-lactate, and DAO were higher in patients with severe IBS. There was a significant negative correlation between the levels of Lactobacillus and Bifidobacterium and disease severity and a significant positive correlation between the levels of Enterococcus and Enterobacter, D-lactate, and DAO and disease severity. There was a significant negative correlation between the levels of Lactobacillus and Bifidobacterium and serum D-lactate and DAO, while there was a significant positive correlation between the levels of Enterococcus and Enterobacter and serum D-lactate and DAO (P < 0.05). Conclusion Intestinal flora, D-lactate, and DAO were abnormal in IBS patients, and intestinal flora was closely correlated with disease severity, D-lactate, and DAO levels.
Collapse
|
|
19
|
Lyubashina OA, Sivachenko IB, Panteleev SS. Supraspinal Mechanisms of Intestinal Hypersensitivity. Cell Mol Neurobiol 2022; 42:389-417. [PMID: 33030712 PMCID: PMC11441296 DOI: 10.1007/s10571-020-00967-3] [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] [Subscribe] [Scholar Register] [Received: 06/05/2020] [Accepted: 09/22/2020] [Indexed: 12/13/2022]
Abstract
Gut inflammation or injury causes intestinal hypersensitivity (IHS) and hyperalgesia, which can persist after the initiating pathology resolves, are often referred to somatic regions and exacerbated by psychological stress, anxiety or depression, suggesting the involvement of both the spinal cord and the brain. The supraspinal mechanisms of IHS remain to be fully elucidated, however, over the last decades the series of intestinal pathology-associated neuroplastic changes in the brain has been revealed, being potentially responsible for the phenomenon. This paper reviews current clinical and experimental data, including the authors' own findings, on these functional, structural, and neurochemical/molecular changes within cortical, subcortical and brainstem regions processing and modulating sensory signals from the gut. As concluded in the review, IHS can develop and maintain due to the bowel inflammation/injury-induced persistent hyperexcitability of viscerosensory brainstem and thalamic nuclei and sensitization of hypothalamic, amygdala, hippocampal, anterior insular, and anterior cingulate cortical areas implicated in the neuroendocrine, emotional and cognitive modulation of visceral sensation and pain. An additional contribution may come from the pathology-triggered dysfunction of the brainstem structures inhibiting nociception. The mechanism underlying IHS-associated regional hyperexcitability is enhanced NMDA-, AMPA- and group I metabotropic receptor-mediated glutamatergic neurotransmission in association with altered neuropeptide Y, corticotropin-releasing factor, and cannabinoid 1 receptor signaling. These alterations are at least partially mediated by brain microglia and local production of cytokines, especially tumor necrosis factor α. Studying the IHS-related brain neuroplasticity in greater depth may enable the development of new therapeutic approaches against chronic abdominal pain in inflammatory bowel disease.
Collapse
Affiliation(s)
- Olga A Lyubashina
- Laboratory of Cortico-Visceral Physiology, Pavlov Institute of Physiology, Russian Academy of Sciences, 6 Nab. Makarova, Saint Petersburg, 199034, Russia.
| | - Ivan B Sivachenko
- Laboratory of Cortico-Visceral Physiology, Pavlov Institute of Physiology, Russian Academy of Sciences, 6 Nab. Makarova, Saint Petersburg, 199034, Russia
| | - Sergey S Panteleev
- Laboratory of Cortico-Visceral Physiology, Pavlov Institute of Physiology, Russian Academy of Sciences, 6 Nab. Makarova, Saint Petersburg, 199034, Russia
| |
Collapse
|
|
20
|
van de Wouw M, Wang Y, Workentine ML, Vaghef-Mehrabani E, Dewey D, Reimer RA, Tomfohr-Madsen L, Giesbrecht GF. Associations Between the Gut Microbiota and Internalizing Behaviors in Preschool Children. Psychosom Med 2022; 84:159-169. [PMID: 34654024 DOI: 10.1097/psy.0000000000001026] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
Abstract
OBJECTIVE Emerging evidence points toward a connection between mental health and the gut microbiota and its metabolites (e.g., short-chain fatty acids). It is unknown whether the gut microbiota is associated with the development of mental health problems (e.g., internalizing or externalizing behaviors) in preschool children. The objective of this study was to evaluate associations between the gut microbiota and internalizing and externalizing behaviors in preschool-aged children. METHODS A community sample of 248 typically developing children (3-5 years of age) provided a stool sample for gut microbiota and SCFA analysis. Parents reported child internalizing and externalizing behaviors using the Child Behavior Checklist. Associations between child behaviors and gut microbiota measures were analyzed using Spearman correlations followed by an adjustment for multiple testing, with subanalysis conducted in children clinically "at risk" for behavioral problems compared with those who were not. RESULTS There was a correlation between Shannon alpha diversity with internalizing behaviors (rs = -0.134, p = .035) and its subscale somatic complaints (rs = -0.144, p = .023). In addition, children clinically "at risk" for internalizing problems had decreased alpha diversity (U = 551, p = .017). Internalizing behaviors correlated with valerate and isobutyrate (rs = -0.147, p = .021; rs = -0.140, p = .028, respectively). Furthermore the somatic complaints subscale additionally correlated with acetate and butyrate (rs = -0.219, p = .001; rs = -0.241, p < .001, respectively). These findings were also present in children "at risk" for internalizing problems (U = 569, p = .026; U = 571, p = .028) and somatic complaints (U = 164, p = .004; U = 145, p = .001). CONCLUSIONS These analyses reveal novel associations between internalizing behaviors and the gut microbiota in preschool children. Furthermore, a relationship between somatic complaints and acetate and butyrate was identified, indicating that interventions that increase SCFA production warrant future investigation.
Collapse
Affiliation(s)
- Marcel van de Wouw
- From the Departments of Pediatrics (van de Wouw, Wang, Vaghef-Mehrabani, Dewey, Tomfohr-Madsen, Giesbrecht) and Psychology (Tomfohr-Madsen, Giesbrecht), University of Calgary; Alberta Children's Hospital Research Institute (ACHRI) (Dewey, Reimer, Tomfohr-Madsen, Giesbrecht); and Department of Community Health Sciences (Dewey, Giesbrecht), UCVM Bioinformatics, Faculty of Veterinary Medicine (Workentine), Faculty of Kinesiology (Reimer), and Department of Biochemistry and Molecular Biology, Cumming School of Medicine (Reimer), University of Calgary, Calgary, Alberta, Canada
| | | | | | | | | | | | | | | |
Collapse
|
|
21
|
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
|
|
22
|
Influence of Irritable Bowel Syndrome on Stress and Depressive Symptoms in Nurses: The Korea Nurses' Health Study. INTERNATIONAL JOURNAL OF ENVIRONMENTAL RESEARCH AND PUBLIC HEALTH 2021; 18:ijerph182312324. [PMID: 34886050 PMCID: PMC8657383 DOI: 10.3390/ijerph182312324] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Received: 10/21/2021] [Revised: 11/20/2021] [Accepted: 11/21/2021] [Indexed: 11/23/2022]
Abstract
Despite the high risk of irritable bowel syndrome (IBS) and stress/depressive symptoms in nurses, limited research has examined the relationship between these conditions in female nurses. The purpose of this study was to determine the prevalence of IBS and the influence of IBS on stress and depressive symptoms in female nurses. We analyzed the data from the Korea Nurses’ Health Study. Among 7667 participants from the 7th survey conducted from December 2018 to September 2019, 178 nurses were identified as having IBS based on the Rome IV criteria. Using the propensity score matching, 712 were selected as a comparison group. Multivariate ordinal logistic regression analyses were conducted to examine the influence of IBS on stress and depressive symptoms. The prevalence of IBS was 2.3% and the prevalence of depressive symptoms among nurses with IBS was 13.5%. Female nurses with IBS were 2.214 times more likely to experience increased stress levels. However, when demographics, dietary habits, sleep quality, and depressive symptoms were considered, having IBS was no longer an influential factor for increased stress levels. When all the variables were considered, female nurses with IBS were still 2.205 times more likely to experience depressive symptoms. Adequate support is needed to relieve depressive symptoms in nurses with IBS.
Collapse
|
|
23
|
Yuan PQ, Wu SV, Stengel A, Sato K, Taché Y. Activation of CRF 1 receptors expressed in brainstem autonomic nuclei stimulates colonic enteric neurons and secreto-motor function in male rats. Neurogastroenterol Motil 2021; 33:e14189. [PMID: 34215021 DOI: 10.1111/nmo.14189] [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: 02/02/2021] [Revised: 04/13/2021] [Accepted: 05/04/2021] [Indexed: 02/08/2023]
Abstract
BACKGROUND Hypothalamic corticotropin-releasing factor (CRF) receptor 1 (CRF1 ) plays a role in acute stress-related stimulation of colonic motor function. Less is known on CRF1 signaling in the brainstem. METHODS We investigate CRF1 expression in the brainstem and the colonic response to 4th ventricle (4V) injection of CRF and urocortin (Ucn) 2 (3 µg/rat) in chronically cannulated male rats. KEY RESULTS Transcripts of CRF1 wild-type 1a and splice variants 1c, 1e, 1f, 1o along with three novel variants 1a-2 (desK-110 in exon 5), 1p (-exon 7), and 1q (exon 5 extension) were identified in the pons and medulla. The area postrema, nucleus tractus solitarius, dorsal motor nucleus of the vagus, locus coeruleus, and Barrington's nucleus isolated by laser capture microdissection expressed 1a, 1a-2, and 1p but not 1q. Compared to 4V vehicle, 4V CRF induced fecal pellet output (FPO) and diarrhea that were blocked by the CRF antagonist, astressin-B. CRF2 agonist, Ucn2 had no effect on basal or CRF-induced FPO. CRF actions were correlated with the induction of c-Fos immunoreactivity in myenteric neurons of the proximal and distal colon (pC, dC) and submucosal neurons of dC. c-Fos immunoreactivity occurred in 39% and 37% of myenteric cholinergic and 7% and 58% of nitrergic neurons in the pC and dC, respectively. CONCLUSIONS & INFERENCES CRF1a and its splice variants are expressed in brainstem nuclei, and activation of CRF1 signaling at the level of the brainstem stimulates colonic secretory-motor function through activation of colonic enteric neurons.
Collapse
Affiliation(s)
- Pu-Qing Yuan
- David Geffen School of Medicine, Vatche and Tamar Manoukian Division of Digestive Diseases, University of California at Los Angeles (UCLA), Los Angeles, CA, USA
- VA Greater Los Angeles Healthcare System, Los Angeles, CA, USA
| | - S Vincent Wu
- VA Greater Los Angeles Healthcare System, Los Angeles, CA, USA
| | - Andreas Stengel
- David Geffen School of Medicine, Vatche and Tamar Manoukian Division of Digestive Diseases, University of California at Los Angeles (UCLA), Los Angeles, CA, USA
- Department of Psychosomatic Medicine and Psychotherapy, Medical University Hospital, Tübingen, Germany
- Department for Psychosomatic Medicine, Charité Center for Internal Medicine and Dermatology, Charité-Universitätsmedizin, Berlin, Germany
| | - Ken Sato
- David Geffen School of Medicine, Vatche and Tamar Manoukian Division of Digestive Diseases, University of California at Los Angeles (UCLA), Los Angeles, CA, USA
- Sato Clinic 13-14 Choei Moriyamaku, Nagoya City, Japan
| | - Yvette Taché
- David Geffen School of Medicine, Vatche and Tamar Manoukian Division of Digestive Diseases, University of California at Los Angeles (UCLA), Los Angeles, CA, USA
- VA Greater Los Angeles Healthcare System, Los Angeles, CA, USA
| |
Collapse
|
|
24
|
Brenner D, Shorten GD, O'Mahony SM. Postoperative pain and the gut microbiome. NEUROBIOLOGY OF PAIN 2021; 10:100070. [PMID: 34409198 PMCID: PMC8361255 DOI: 10.1016/j.ynpai.2021.100070] [Citation(s) in RCA: 16] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Received: 01/22/2021] [Revised: 06/24/2021] [Accepted: 07/26/2021] [Indexed: 12/12/2022]
Abstract
Poorly controlled postoperative pain remains a major unresolved challenge globally. The gut microbiome impacts on inflammatory pain and neuropathic pain. Microbiota metabolites can regulate peripheral and central sensitisation. Stress is linked to both postoperative pain and an altered gut microbiome. In excess of 300 million surgical procedures are undertaken worldwide each year. Despite recognition of the prevalence of postoperative pain, and improvements in pain management techniques, poorly controlled postoperative pain remains a major unresolved challenge globally. An estimated 71% and 51% of patients experience moderate to severe pain after surgery in in-patient and outpatient settings, respectively. Inadequately controlled pain after surgery is associated with significant perioperative morbidity including myocardial infarction and pulmonary complications. As many as 20–56% of patients develop chronic pain after commonly performed procedures such as hernia repair, hysterectomy, and thoracotomy. Traditional analgesics and interventions are often ineffective or partially effective in the treatment of postoperative pain, resulting in a chronic pain condition with related socio-economic impacts and reduced quality of life for the patient. Such chronic pain which occurs after surgery is referred to as Persistent Post-Surgical Pain (PPSP). The complex ecosystem that is the gastrointestinal microbiota (including bacteria, fungi, viruses, phage) plays essential roles in the maintenance of the healthy state of the host. A disruption to the balance of this microbiome has been implicated not only in gastrointestinal disease but also neurological disorders including chronic pain. The influence of the gut microbiome is well documented in the context of visceral pain from the gastrointestinal tract while a greater understanding is emerging of the impact on inflammatory pain and neuropathic pain (both of which can occur during the perioperative period). The gut microbiome is an essential source for driving immune maturation and maintaining appropriate immune response. Given that inflammatory processes have been implicated in postoperative pain, aberrant microbiome profiles may play a role in the development of this type of pain. Furthermore, the microorganisms in our gut produce metabolites, neurotransmitters, and neuromodulators which interact with their receptors to regulate peripheral and central sensitisation associated with chronic pain. Microbiota-derived mediators can also regulate neuroinflammation, which is associated with activation of microglia as well as infiltration by immune cells, known to modulate the development and maintenance of central sensitisation. Moreover, risk factors for developing postoperative pain include anxiety, depression, and increased stress response. These central nervous system-related disorders have been associated with an altered gut microbiome and microbiome targeted intervention studies indicate improvements. Females are more likely to suffer from postoperative pain. As gonadal hormones are associated with a differential microbiome and pre-clinical studies show that male microbiome confers protection from inflammatory pain, it is possible that the composition of the microbiome and its by-products contribute to the increased risk for the development of postoperative pain. Very little evidence exists relating the microbiome to somatic pain. Here we discuss the potential role of the gut microbiome in the aetiology and pathophysiology of postoperative pain in the context of other somatic pain syndromes and what is known about microbe-neuron interactions. Investigations are needed to determine the specific role of the gut microbiome in this type of pain which may help inform the development of preventative interventions as well as management strategies to improve patient outcome.
Collapse
Affiliation(s)
- David Brenner
- Department of Anesthesia and Intensive Care Medicine, Cork University Hospital and University College Cork, Ireland
| | - George D Shorten
- Department of Anesthesia and Intensive Care Medicine, Cork University Hospital and University College Cork, Ireland
| | - Siobhain M O'Mahony
- APC Microbiome Ireland, University College Cork, Cork, Ireland.,Department of Anatomy and Neuroscience, University College Cork, Cork, Ireland
| |
Collapse
|
|
25
|
Westfall S, Caracci F, Estill M, Frolinger T, Shen L, Pasinetti GM. Chronic Stress-Induced Depression and Anxiety Priming Modulated by Gut-Brain-Axis Immunity. Front Immunol 2021; 12:670500. [PMID: 34248950 PMCID: PMC8264434 DOI: 10.3389/fimmu.2021.670500] [Citation(s) in RCA: 67] [Impact Index Per Article: 16.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/21/2021] [Accepted: 06/08/2021] [Indexed: 12/18/2022] Open
Abstract
Chronic stress manifests as depressive- and anxiety-like behavior while recurrent stress elicits disproportionate behavioral impairments linked to stress-induced immunological priming. The gut-brain-microbiota-axis is a promising therapeutic target for stress-induced behavioral impairments as it simultaneously modulates peripheral and brain immunological landscapes. In this study, a combination of probiotics and prebiotics, known as a synbiotic, promoted behavioral resilience to chronic and recurrent stress by normalizing gut microbiota populations and promoting regulatory T cell (Treg) expansion through modulation of ileal innate lymphoid cell (ILC)3 activity, an impact reflecting behavioral responses better than limbic brain region neuroinflammation. Supporting this conclusion, a multivariate machine learning model correlatively predicted a cross-tissue immunological signature of stress-induced behavioral impairment where the ileal Treg/T helper17 cell ratio associated to hippocampal chemotactic chemokine and prefrontal cortex IL-1β production in the context of stress-induced behavioral deficits. In conclusion, stress-induced behavioral impairments depend on the gut-brain-microbiota-axis and through ileal immune regulation, synbiotics attenuate the associated depressive- and anxiety-like behavior.
Collapse
Affiliation(s)
- Susan Westfall
- Department of Neurology, Icahn School of Medicine at Mount Sinai, New York, NY, United States
| | - Francesca Caracci
- Department of Neurology, Icahn School of Medicine at Mount Sinai, New York, NY, United States
| | - Molly Estill
- Department of Neuroscience, Icahn School of Medicine at Mount Sinai, New York, NY, United States
| | - Tal Frolinger
- Department of Neurology, Icahn School of Medicine at Mount Sinai, New York, NY, United States
| | - Li Shen
- Department of Neuroscience, Icahn School of Medicine at Mount Sinai, New York, NY, United States
| | - Giulio M. Pasinetti
- Department of Neurology, Icahn School of Medicine at Mount Sinai, New York, NY, United States
- Geriatric Research, Education and Clinical Center, James J. Peters Veterans Affairs Medical Center, Bronx, NY, United States
| |
Collapse
|
|
26
|
Khayat A, Algethami G, Baik S, Alhajori M, Banjar D. The Effect of Using Rome IV Criteria on the Prevalence of Functional Abdominal Pain Disorders and Functional Constipation among Children of the Western Region of Saudi Arabia. Glob Pediatr Health 2021; 8:2333794X211022265. [PMID: 34104704 PMCID: PMC8170292 DOI: 10.1177/2333794x211022265] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/19/2021] [Accepted: 05/10/2021] [Indexed: 12/31/2022] Open
Abstract
Functional gastrointestinal disorders are characterized by absence of anatomical and biochemical alterations, and are diagnosed and classified based on symptomatology. We aim to explore the prevalence of functional abdominal pain disorders and Functional constipation using Rome IV criteria. An online questionnaire was distributed randomly via social media targeting the general population of the western region of Saudi Arabia. Parents who have at least 1 child in the age group 3 to 18 years were included. Children with mental disabilities, or any organic gastrointestinal disorder were excluded. Five hundred thirty-two responded and 215 were excluded. The overall prevalence of functional abdominal pain disorders was 3.1%. The prevalence of functional constipation was 4.7%. Conclusions: Rome IV criteria seems to give a lower functional abdominal pain prevalence than Rome III, online learning did not seem to affect the prevalence of both disorders, but a family stressor seems to increase functional constipation prevalence.
Collapse
Affiliation(s)
- Ammar Khayat
- Department of Pediatrics, Umm Al-Qura
University, Makkah, Saudi Arabia
| | - Ghady Algethami
- Department of Pediatrics, Umm Al-Qura
University, Makkah, Saudi Arabia
| | - Sama Baik
- Department of Pediatrics, Umm Al-Qura
University, Makkah, Saudi Arabia
| | - Mai Alhajori
- Department of Pediatrics, Umm Al-Qura
University, Makkah, Saudi Arabia
| | - Dhayy Banjar
- Department of Pediatrics, Umm Al-Qura
University, Makkah, Saudi Arabia
| |
Collapse
|
|
27
|
Chong KPL, Woo BKP. Emerging wearable technology applications in gastroenterology: A review of the literature. World J Gastroenterol 2021; 27:1149-1160. [PMID: 33828391 PMCID: PMC8006095 DOI: 10.3748/wjg.v27.i12.1149] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/09/2020] [Revised: 02/12/2021] [Accepted: 03/11/2021] [Indexed: 02/06/2023] Open
Abstract
The field of gastroenterology has recently seen a surge in wearable technology to monitor physical activity, sleep quality, pain, and even gut activity. The past decade has seen the emergence of wearable devices including Fitbit, Apple Watch, AbStats, and ingestible sensors. In this review, we discuss current and future devices designed to measure sweat biomarkers, steps taken, sleep efficiency, gastric electrical activity, stomach pH, and intestinal contents. We also summarize several clinical studies to better understand wearable devices so that we may assess their potential benefit in improving healthcare while also weighing the challenges that must be addressed.
Collapse
Affiliation(s)
- Kimberly PL Chong
- College of Osteopathic Medicine, Western University of Health Sciences, Pomona, CA 91766, United States
| | - Benjamin KP Woo
- Department of Psychiatry and Biobehavioral Sciences, Olive View - University of California Los Angeles Medical Center, Sylmar, CA 91342, United States
| |
Collapse
|
|
28
|
Huang ST, Song ZJ, Liu Y, Luo WC, Yin Q, Zhang YM. BNST AV GABA-PVN CRF Circuit Regulates Visceral Hypersensitivity Induced by Maternal Separation in Vgat-Cre Mice. Front Pharmacol 2021; 12:615202. [PMID: 33815103 PMCID: PMC8017215 DOI: 10.3389/fphar.2021.615202] [Citation(s) in RCA: 19] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/08/2020] [Accepted: 02/04/2021] [Indexed: 12/12/2022] Open
Abstract
Visceral hypersensitivity as a common clinical manifestation of irritable bowel syndrome (IBS) may contribute to the development of chronic visceral pain. Our prior studies authenticated that the activation of the corticotropin-releasing factor (CRF) neurons in paraventricular nucleus (PVN) contributed to visceral hypersensitivity in mice, but puzzles still remain with respect to the underlying hyperactivation of corticotropin-releasing factor neurons. Herein, we employed maternal separation (MS) to establish mouse model of visceral hypersensitivity. The neuronal circuits associated with nociceptive hypersensitivity involved paraventricular nucleus CRF neurons by means of techniques such as behavioral test, pharmacology, molecular biology, retrograde neuronal circuit tracers, electrophysiology, chemogenetics and optogenetics. MS could predispose the elevated firing frequency of CRF neurons in PVN in murine adulthood, which could be annulled via the injection of exogenous GABA (0.3mM, 0.2µl) into PVN. The PVN-projecting GABAergic neurons were mainly distributed in the anterior ventral (AV) region in the bed nucleus of stria terminalis (BNST), wherein the excitability of these GABAergic neurons was reduced. Casp3 virus was utilized to induce apoptosis of GABA neurons in BNST-AV region, resulting in the activation of CRF neurons in PVN and visceral hyperalgesia. In parallel, chemogenetic and optogenetic approaches to activate GABAergic BNSTAV-PVN circuit in MS mice abated the spontaneous firing frequency of PVN CRF neurons and prevented the development of visceral hypersensitivity. A priori, PVNCRF-projecting GABAergic neurons in BNST-AV region participated in the occurrence of visceral hypersensitivity induced by MS. Our research may provide a new insight into the neural circuit mechanism of chronic visceral pain.
Collapse
Affiliation(s)
- Si-Ting Huang
- Jiangsu Province Key Laboratory of Anesthesiology, Xuzhou Medical University, Xuzhou, China
| | - Zhi-Jing Song
- Jiangsu Province Key Laboratory of Anesthesiology, Xuzhou Medical University, Xuzhou, China.,Department of Anesthesiology, Xuzhou Municipal Hospital Affiliated with Xuzhou Medical University, Xuzhou, China
| | - Yu Liu
- Jiangsu Province Key Laboratory of Anesthesiology, Xuzhou Medical University, Xuzhou, China
| | - Wen-Chen Luo
- Jiangsu Province Key Laboratory of Anesthesiology, Xuzhou Medical University, Xuzhou, China
| | - Qian Yin
- Jiangsu Province Key Laboratory of Anesthesiology, Xuzhou Medical University, Xuzhou, China
| | - Yong-Mei Zhang
- Jiangsu Province Key Laboratory of Anesthesiology, Xuzhou Medical University, Xuzhou, China
| |
Collapse
|
|
29
|
Ao W, Cheng Y, Chen M, Wei F, Yang G, An Y, Mao F, Zhu X, Mao G. Intrinsic brain abnormalities of irritable bowel syndrome with diarrhea: a preliminary resting-state functional magnetic resonance imaging study. BMC Med Imaging 2021; 21:4. [PMID: 33407222 PMCID: PMC7788841 DOI: 10.1186/s12880-020-00541-9] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/27/2020] [Accepted: 12/22/2020] [Indexed: 02/08/2023] Open
Abstract
Background The aim of the present study was to explore the brain active characteristics of patients with irritable bowel syndrome with diarrhea (IBS-D) using resting-state functional magnetic resonance imaging technology. Methods Thirteen IBS-D patients and fourteen healthy controls (HC) were enrolled. All subjects underwent head MRI examination during resting state. A voxel-based analysis of fractional amplitude of low frequency fluctuation (fALFF) maps between IBS-D and HC was performed using a two-sample t-test. The relationship between the fALFF values in abnormal brain regions and the scores of Symptom Severity Scale (IBS-SSS) were analyzed using Pearson correlation analysis. Results Compared with HC, IBS-D patients had lower fALFF values in the left medial superior frontal gyrus and higher fALFF values in the left hippocampus and right precuneus. There was a positive correlation between the duration scores of IBS-SSS and fALFF values in the right precuneus. Conclusion The altered fALFF values in the medial superior frontal gyri, left hippocampus and right precuneus revealed changes of intrinsic neuronal activity, further revealing the abnormality of gut-brain axis of IBS-D.
Collapse
Affiliation(s)
- Weiqun Ao
- Department of Radiology, Tongde Hospital of Zhejiang Province, Hangzhou, 310012, Zhejiang Province, China
| | - Yougen Cheng
- Department of Radiology, Tongde Hospital of Zhejiang Province, Hangzhou, 310012, Zhejiang Province, China
| | - Mingxian Chen
- Department of Gastroenterology, Tongde Hospital of Zhejiang Province, Hangzhou, 310012, Zhejiang Province, China
| | - Fuquan Wei
- Department of Radiology, Tongde Hospital of Zhejiang Province, Hangzhou, 310012, Zhejiang Province, China
| | - Guangzhao Yang
- Department of Radiology, Tongde Hospital of Zhejiang Province, Hangzhou, 310012, Zhejiang Province, China
| | - Yongyu An
- Department of Radiology, Tongde Hospital of Zhejiang Province, Hangzhou, 310012, Zhejiang Province, China
| | - Fan Mao
- Department of Radiology, Tongde Hospital of Zhejiang Province, Hangzhou, 310012, Zhejiang Province, China
| | - Xiandi Zhu
- Department of Radiology, Tongde Hospital of Zhejiang Province, Hangzhou, 310012, Zhejiang Province, China
| | - Guoqun Mao
- Department of Radiology, Tongde Hospital of Zhejiang Province, Hangzhou, 310012, Zhejiang Province, China.
| |
Collapse
|
|
30
|
Ayuso M, Buyssens L, Stroe M, Valenzuela A, Allegaert K, Smits A, Annaert P, Mulder A, Carpentier S, Van Ginneken C, Van Cruchten S. The Neonatal and Juvenile Pig in Pediatric Drug Discovery and Development. Pharmaceutics 2020; 13:44. [PMID: 33396805 PMCID: PMC7823749 DOI: 10.3390/pharmaceutics13010044] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/16/2020] [Revised: 12/22/2020] [Accepted: 12/22/2020] [Indexed: 02/06/2023] Open
Abstract
Pharmacotherapy in pediatric patients is challenging in view of the maturation of organ systems and processes that affect pharmacokinetics and pharmacodynamics. Especially for the youngest age groups and for pediatric-only indications, neonatal and juvenile animal models can be useful to assess drug safety and to better understand the mechanisms of diseases or conditions. In this respect, the use of neonatal and juvenile pigs in the field of pediatric drug discovery and development is promising, although still limited at this point. This review summarizes the comparative postnatal development of pigs and humans and discusses the advantages of the juvenile pig in view of developmental pharmacology, pediatric diseases, drug discovery and drug safety testing. Furthermore, limitations and unexplored aspects of this large animal model are covered. At this point in time, the potential of the neonatal and juvenile pig as nonclinical safety models for pediatric drug development is underexplored.
Collapse
Affiliation(s)
- Miriam Ayuso
- Comparative Perinatal Development, Department of Veterinary Sciences, University of Antwerp, 2610 Wilrijk, Belgium; (L.B.); (M.S.); (A.V.); (C.V.G.)
| | - Laura Buyssens
- Comparative Perinatal Development, Department of Veterinary Sciences, University of Antwerp, 2610 Wilrijk, Belgium; (L.B.); (M.S.); (A.V.); (C.V.G.)
| | - Marina Stroe
- Comparative Perinatal Development, Department of Veterinary Sciences, University of Antwerp, 2610 Wilrijk, Belgium; (L.B.); (M.S.); (A.V.); (C.V.G.)
| | - Allan Valenzuela
- Comparative Perinatal Development, Department of Veterinary Sciences, University of Antwerp, 2610 Wilrijk, Belgium; (L.B.); (M.S.); (A.V.); (C.V.G.)
| | - Karel Allegaert
- Department of Pharmaceutical and Pharmacological Sciences, KU Leuven, 3000 Leuven, Belgium; (K.A.); (P.A.)
- Department of Development and Regeneration, KU Leuven, 3000 Leuven, Belgium;
- Department of Hospital Pharmacy, Erasmus MC Rotterdam, 3000 CA Rotterdam, The Netherlands
| | - Anne Smits
- Department of Development and Regeneration, KU Leuven, 3000 Leuven, Belgium;
- Neonatal Intensive Care Unit, University Hospitals UZ Leuven, 3000 Leuven, Belgium
| | - Pieter Annaert
- Department of Pharmaceutical and Pharmacological Sciences, KU Leuven, 3000 Leuven, Belgium; (K.A.); (P.A.)
| | - Antonius Mulder
- Department of Neonatology, University Hospital Antwerp, 2650 Edegem, Belgium;
- Laboratory of Experimental Medicine and Pediatrics, University of Antwerp, 2610 Wilrijk, Belgium
| | | | - Chris Van Ginneken
- Comparative Perinatal Development, Department of Veterinary Sciences, University of Antwerp, 2610 Wilrijk, Belgium; (L.B.); (M.S.); (A.V.); (C.V.G.)
| | - Steven Van Cruchten
- Comparative Perinatal Development, Department of Veterinary Sciences, University of Antwerp, 2610 Wilrijk, Belgium; (L.B.); (M.S.); (A.V.); (C.V.G.)
| |
Collapse
|
|
31
|
Xu X, Li YC, Wu YY, Xu YC, Weng RX, Wang CL, Zhang PA, Zhang Y, Xu GY. Upregulation of spinal ASIC1 by miR-485 mediates enterodynia in adult offspring rats with prenatal maternal stress. CNS Neurosci Ther 2020; 27:244-255. [PMID: 33314662 PMCID: PMC7816206 DOI: 10.1111/cns.13542] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/26/2020] [Revised: 10/31/2020] [Accepted: 11/14/2020] [Indexed: 12/28/2022] Open
Abstract
Aims Irritable bowel syndrome (IBS) is a common functional gastrointestinal disease characterized by abdominal pain. Our recent study has shown that the acid‐sensitive ion channel 1 (ASIC1) in dorsal root ganglion (DRG) is involved in stomachache of adult offspring rats subjected with prenatal maternal stress (PMS). MiR‐485 is predicted to target the expression of ASIC1. The aim of the present study was designed to determine whether miR‐485/ASIC1 signaling participates in enterodynia in the spinal dorsal horn of adult offspring rats with PMS. Methods Enterodynia was measured by colorectal distension (CRD). Western blotting, qPCR, and in situ hybridization were performed to detect the expression of ASICs and related miRNAs. Spinal synaptic transmission was also recorded by patch clamping. Results PMS offspring rats showed that spinal ASIC1 protein expression and synaptic transmission were significantly enhanced. Administration of ASICs antagonist amiloride suppressed the synaptic transmission and enterodynia. Besides, PMS induced a significant reduction in the expression of miR‐485. Upregulating the expression markedly attenuated enterodynia, reversed the increase in ASIC1 protein and synaptic transmission. Furthermore, ASIC1 and miR‐485 were co‐expressed in NeuN‐positive spinal dorsal horn neurons. Conclusions Overall, these data suggested that miR‐485 participated in enterodynia in PMS offspring, which is likely mediated by the enhanced ASIC1 activities.
Collapse
Affiliation(s)
- Xue Xu
- The People's Hospital of Suzhou New District, Suzhou, China.,Center for Translational Pain Medicine, Institute of Neuroscience, Soochow University, Suzhou, China
| | - Yong-Chang Li
- Center for Translational Pain Medicine, Institute of Neuroscience, Soochow University, Suzhou, China
| | - Yan-Yan Wu
- Center for Translational Pain Medicine, Institute of Neuroscience, Soochow University, Suzhou, China
| | - Yu-Cheng Xu
- Center for Translational Pain Medicine, Institute of Neuroscience, Soochow University, Suzhou, China
| | - Rui-Xia Weng
- The People's Hospital of Suzhou New District, Suzhou, China.,Center for Translational Pain Medicine, Institute of Neuroscience, Soochow University, Suzhou, China
| | - Cai-Lin Wang
- The People's Hospital of Suzhou New District, Suzhou, China.,Center for Translational Pain Medicine, Institute of Neuroscience, Soochow University, Suzhou, China
| | - Ping-An Zhang
- Center for Translational Pain Medicine, Institute of Neuroscience, Soochow University, Suzhou, China
| | - Ying Zhang
- The People's Hospital of Suzhou New District, Suzhou, China
| | - Guang-Yin Xu
- Center for Translational Pain Medicine, Institute of Neuroscience, Soochow University, Suzhou, China
| |
Collapse
|
|
32
|
Söderquist F, Syk M, Just D, Kurbalija Novicic Z, Rasmusson AJ, Hellström PM, Ramklint M, Cunningham JL. A cross-sectional study of gastrointestinal symptoms, depressive symptoms and trait anxiety in young adults. BMC Psychiatry 2020; 20:535. [PMID: 33176747 PMCID: PMC7661167 DOI: 10.1186/s12888-020-02940-2] [Citation(s) in RCA: 20] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/27/2020] [Accepted: 10/28/2020] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND >Patients with functional gastrointestinal disorders have a high psychiatric co-morbidity. This study aimed to investigate and characterise gastrointestinal symptoms in relation to depressive symptoms and trait anxiety in a well-defined population of young adult psychiatric outpatients and healthy controls. METHODS Gastrointestinal symptoms were assessed with the Gastrointestinal Symptom Rating Scale for Irritable Bowel Syndrome (GSRS-IBS). Depressive symptoms were assessed with the Montgomery-Åsberg Depression Rating Scale- Self assessment (MADRS-S). Trait anxiety was estimated with three of the Swedish universities of Personality (SSP) scales: Somatic trait anxiety, Psychic trait anxiety and Stress susceptibility. Self-ratings were collected from 491 young adult psychiatric outpatients and 85 healthy controls. Gastrointestinal symptom severity was compared between patients with and without current psychotropic medication and controls. Associations between gastrointestinal symptoms, depressive symptoms and trait anxiety were assessed using Spearman's coefficients and generalized linear models adjusting for possible confounders (sex, body mass index, bulimia nervosa). RESULTS Patients, with and without current psychotropic medication, reported significantly more gastrointestinal symptoms than controls. In the generalized linear models, total MADRS-S score (p < 0.001), Somatic trait anxiety (p < 0.001), Psychic trait anxiety (p = 0.002) and Stress susceptibility (p = 0.002) were independent predictors of the total GSRS-IBS score. Further exploratory analysis using unsupervised learning revealed a diverse spectrum of symptoms that clustered into six groups. CONCLUSION Gastrointestinal symptoms are both highly prevalent and diverse in young adult psychiatric outpatients, regardless of current psychotropic medication. Depressive symptom severity and degree of trait anxiety are independently related to the total gastrointestinal symptom burden.
Collapse
Affiliation(s)
- Fanny Söderquist
- Department of Neuroscience, Psychiatry Uppsala University, Uppsala, Sweden
| | - Mikaela Syk
- Department of Neuroscience, Psychiatry Uppsala University, Uppsala, Sweden
| | - David Just
- Department of Neuroscience, Psychiatry Uppsala University, Uppsala, Sweden
| | | | - Annica J Rasmusson
- Department of Neuroscience, Psychiatry Uppsala University, Uppsala, Sweden
| | - Per M Hellström
- Department of Medical Sciences, Gastroenterology/Hepatology, Uppsala University, Uppsala, Sweden
| | - Mia Ramklint
- Department of Neuroscience, Psychiatry Uppsala University, Uppsala, Sweden
| | - Janet L Cunningham
- Department of Neuroscience, Psychiatry Uppsala University, Uppsala, Sweden.
| |
Collapse
|
|
33
|
Yildiz A, Kizil E, Yildiz A. Quality of life and psychometric evaluation of patients diagnosed with irritable bowel syndrome: an observational cohort study. SAO PAULO MED J 2020; 138:282-286. [PMID: 32556060 PMCID: PMC9673838 DOI: 10.1590/1516-3180.2019.0527.r1.16042020] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/05/2020] [Accepted: 04/16/2020] [Indexed: 12/12/2022] Open
Abstract
BACKGROUND Very few data are available for evaluating health-related quality of life among people with irritable bowel syndrome (IBS) and even fewer data are available in relation to anxiety and depression status among these patients. OBJECTIVES To evaluate the quality of life, anxiety and depression status of patients with IBS. DESIGN AND SETTING Observational cohort study conducted in a tertiary-care university hospital. METHODS Patients who had recently been diagnosed with IBS and who had been followed up for IBS-specific treatment for at least three months were included. A quality of life (QoL) survey, the Beck Anxiety Index (BAI) and the Hamilton Depression Index (HAM-D) were applied to the patients. RESULTS In total, 274 patients with IBS were included in the study cohort. These patients presented very high baseline scores for anxiety and depression, and very poor QoL results. CONCLUSION Our study showed that IBS had a very high impact on these patients, regarding their anxiety and depression levels, alongside very poor results relating to quality of life.
Collapse
Affiliation(s)
- Alp Yildiz
- MD. General Surgeon, Department of General Surgery, Yenimahalle Training and Research Hospital, Yildirim Beyazıt University, Ankara, Turkey.
| | - Emre Kizil
- MD. Psychiatrist, Private Emre Kizil Psychiatry Clinic, Cankaya, Ankara, Turkey.
| | - Aybala Yildiz
- MD, PhD. Associate Professor, Department of General Surgery, Yenimahalle Training and Research Hospital, Yildirim Beyazıt University, Ankara, Turkey.
| |
Collapse
|
|
34
|
Chinna Meyyappan A, Milev R. The Safety, Efficacy, and Tolerability of Microbial Ecosystem Therapeutic-2 in People With Major Depression and/or Generalized Anxiety Disorder: Protocol for a Phase 1, Open-Label Study. JMIR Res Protoc 2020; 9:e17223. [PMID: 32495743 PMCID: PMC7303825 DOI: 10.2196/17223] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/27/2019] [Revised: 03/09/2020] [Accepted: 03/30/2020] [Indexed: 12/26/2022] Open
Abstract
BACKGROUND The bidirectional signaling between the gut microbiota and the brain, known as the gut-brain axis, is being heavily explored in current neuropsychiatric research. Analyses of the human gut microbiota have shown considerable individual variability in bacterial content, which is hypothesized to influence brain function, and potentially mood and anxiety symptoms, through gut-brain axis communication. Preclinical and clinical research examining these effects suggests that fecal microbiota transplant (FMT) may aid in improving the severity of depression and anxiety symptoms by recolonizing the gastrointestinal (GI) tract with healthy bacteria. The microbial ecosystem therapeutic (ie, microbial ecosystem therapeutic-2 [MET-2]) used in this study is an alternative treatment to FMT, which comprises 40 different strains of gut bacteria from a healthy donor. OBJECTIVE The primary objective of this study is to assess subjective changes in mood and anxiety symptoms before, during, and after administration of MET-2. The secondary objectives of this study are to assess the changes in metabolic functioning and the level of repopulation of healthy gut bacteria, the safety and tolerability of MET-2, and the effects of early stress on biomarkers of depression/anxiety and the response to treatment. METHODS Adults experiencing depressive or anxiety symptoms will be recruited from the Kingston area. These participants will orally consume an encapsulated MET-2 once daily-containing 40 strains of purified and laboratory-grown bacteria from a single healthy donor-for 8 weeks, followed by a 2-week treatment-free follow-up period. Participants will undergo a series of clinical assessments measuring mood, anxiety, and GI symptoms using validated clinical scales and questionnaires. Molecular data will be collected from blood and fecal samples to assess metabolic changes, neurotransmitter levels, inflammatory markers, and the level of engraftment of the fecal samples that may predict outcomes in depression or anxiety. RESULTS Given the association between the gut bacteria and the risk factors of depression, we expect to observe an improvement in the severity of depressive and anxiety symptoms following treatment, and we expect that this improvement is mediated by the recolonization of the GI tract with healthy bacteria. The recruitment for this study has been completed, and the data obtained are currently being analyzed. CONCLUSIONS This is the first time MET-2 is being tested in psychiatric indications, specifically depression and anxiety. As such, this may be the first study to show the potential effects of microbial therapy in alleviating psychiatric symptoms as well as its safety and tolerability. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID) DERR1-10.2196/17223.
Collapse
Affiliation(s)
- Arthi Chinna Meyyappan
- Centre for Neuroscience Studies, Queen's University, Kingston, ON, Canada.,Providence Care Hospital, Kingston, ON, Canada.,Department of Psychiatry, Queen's University, Kingston, ON, Canada
| | - Roumen Milev
- Centre for Neuroscience Studies, Queen's University, Kingston, ON, Canada.,Providence Care Hospital, Kingston, ON, Canada.,Department of Psychiatry, Queen's University, Kingston, ON, Canada.,Department of Psychology, Queen's University, Kingston, ON, Canada
| |
Collapse
|
|
35
|
Lunde CE, Sieberg CB. Walking the Tightrope: A Proposed Model of Chronic Pain and Stress. Front Neurosci 2020; 14:270. [PMID: 32273840 PMCID: PMC7113396 DOI: 10.3389/fnins.2020.00270] [Citation(s) in RCA: 25] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/20/2019] [Accepted: 03/10/2020] [Indexed: 12/25/2022] Open
Abstract
Pain and stress are both phenomena that challenge an individual’s homeostasis and have significant overlap in conceptual and physiological processes. Allostasis is the ability to adapt to pain and stress and maintain homeostasis; however, if either process becomes chronic, it may result in negative long-term outcomes. The negative effects of stress on health outcomes on physiology and behavior, including pain, have been well documented; however, the specific mechanisms of how stress and what quantity of stress contributes to the maintenance and exacerbation of pain have not been identified, and thus pharmacological interventions are lacking. The objective of this brief review is to: 1. identify the gaps in the literature on the impact of acute and chronic stress on chronic pain, 2. highlight future directions for stress and chronic pain research; and 3. introduce the Pain-Stress Model in the context of the current literature on stress and chronic pain. A better understanding of the connection between stress and chronic pain could provide greater insight into the neurobiology of these processes and contribute to individualized treatment for pain rehabilitation and drug development for these often comorbid conditions.
Collapse
Affiliation(s)
- Claire E Lunde
- Department of Psychiatry, Boston Children's Hospital, Boston, MA, United States.,Biobehavioral Pediatric Pain Lab, Boston Children's Hospital, Boston, MA, United States.,Center for Pain and the Brain (P.A.I.N. Group), Department of Anesthesiology, Critical Care and Pain Medicine, Boston Children's Hospital, Boston, MA, United States.,Nuffield Department of Women's and Reproductive Health, Medical Sciences Division, University of Oxford, Oxford, United Kingdom
| | - Christine B Sieberg
- Department of Psychiatry, Boston Children's Hospital, Boston, MA, United States.,Biobehavioral Pediatric Pain Lab, Boston Children's Hospital, Boston, MA, United States.,Center for Pain and the Brain (P.A.I.N. Group), Department of Anesthesiology, Critical Care and Pain Medicine, Boston Children's Hospital, Boston, MA, United States.,Department of Psychiatry, Harvard Medical School, Boston, MA, United States
| |
Collapse
|
|
36
|
Abstract
The developmental period constitutes a critical window of sensitivity to stress. Indeed, early-life adversity increases the risk to develop psychiatric diseases, but also gastrointestinal disorders such as the irritable bowel syndrome at adulthood. In the past decade, there has been huge interest in the gut-brain axis, especially as regards stress-related emotional behaviours. Animal models of early-life adversity, in particular, maternal separation (MS) in rodents, demonstrate lasting deleterious effects on both the gut and the brain. Here, we review the effects of MS on both systems with a focus on stress-related behaviours. In addition, we discuss more recent findings showing the impact of gut-directed interventions, including nutrition with pre- and probiotics, illustrating the role played by gut microbiota in mediating the long-term effects of MS. Overall, preclinical studies suggest that nutritional approaches with pro- and prebiotics may constitute safe and efficient strategies to attenuate the effects of early-life stress on the gut-brain axis. Further research is required to understand the complex mechanisms underlying gut-brain interaction dysfunctions after early-life stress as well as to determine the beneficial impact of gut-directed strategies in a context of early-life adversity in human subjects.
Collapse
|
|
37
|
Kozlowska K, Chung J, Cruickshank B, McLean L, Scher S, Dale RC, Mohammad SS, Singh-Grewal D, Prabhuswamy MY, Patrick E. Blood CRP levels are elevated in children and adolescents with functional neurological symptom disorder. Eur Child Adolesc Psychiatry 2019; 28:491-504. [PMID: 30143887 DOI: 10.1007/s00787-018-1212-2] [Citation(s) in RCA: 20] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/21/2018] [Accepted: 08/03/2018] [Indexed: 01/09/2023]
Abstract
There is accumulating evidence that patients with functional neurological symptom disorder (FND) show activation of multiple components of the stress system-the hypothalamic-pituitary-adrenal axis, autonomic nervous system, and brain regions involved in arousal- and emotion-processing. This study aims to examine whether the immune-inflammatory component of the stress system is also activated. C-reactive protein (CRP) blood titre levels were measured in 79 children and adolescents with FND. CRP values ≥ 2 mg/L suggest low-grade inflammation. CRP values > 10 mg/L suggest a disease process. Sixty-six percent of subjects (n = 52) had CRP titres ≥ 2 mg/L. The upward shift in the distribution of CRP levels suggested low-grade inflammation (median CRP concentration was 4.60 mg/L, with 75th and 90th percentiles of 6.1 and 10.3 mg/L, respectively). Elevated CRP titres were not explained by sex, pubertal status, BMI, or medical factors. Confounder analyses suggested that history of maltreatment (χ2 = 2.802, df = 1, p = 0.094, φ = 0.190; β = 2.823, p = 0.04) and a diagnosis of anxiety (χ2 = 2.731, df = 1, p = 0.098, φ = 0.187; β = 4.520, p = 0.061) contributed to elevated CRP levels. Future research will need to identify the origins and locations of immune cell activation and the pathways and systems contributing to their activation and modulation. Because functional activity in neurons and glial cells-the brain's innate effector immune cells-is tightly coupled, our finding of elevated CRP titres suggests activation of the immune-inflammatory component of the brain's stress system. A more direct examination of inflammation-related molecules in the brain will help clarify the role of immune-inflammatory processes in FND.
Collapse
Affiliation(s)
- Kasia Kozlowska
- Department Psychological Medicine, The Children's Hospital at Westmead, Locked Bag 4001, Westmead, NSW, 2145, Australia. .,Brain Dynamics Centre, Westmead Institute of Medical Research, Westmead, NSW, Australia. .,Discipline of Psychiatry and Discipline of Child and Adolescent Health, University of Sydney Medical School, Sydney, NSW, Australia.
| | - Jason Chung
- Department of Clinical Biochemistry, The Children's Hospital at Westmead, Locked Bag 4001, Westmead, NSW, 2145, Australia.,Discipline of Child and Adolescent Health, University of Sydney Medical School, Sydney, NSW, Australia
| | - Bronya Cruickshank
- Department Psychological Medicine, The Children's Hospital at Westmead, Locked Bag 4001, Westmead, NSW, 2145, Australia
| | - Loyola McLean
- Westmead Psychotherapy Program for Complex Traumatic Disorders, Western Sydney Local Health District, Building 112, Cumberland Hospital Campus, Parramatta BC, Locked Bag 7118, Parramatta, NSW, 2124, Australia.,Brain and Mind Centre, and Discipline of Psychiatry, University of Sydney Medical School, Sydney, NSW, Australia
| | - Stephen Scher
- Department of Psychiatry, Harvard Medical School, Boston, MA, USA.,McLean Hospital, Belmont, MA, USA.,Discipline of Psychiatry, University of Sydney Medical School, Sydney, NSW, Australia
| | - Russell C Dale
- Discipline of Child and Adolescent Health, University of Sydney Medical School, Sydney, NSW, Australia.,Movement Disorder and Clinical Neuroimmunology Group, Institute for Neuroscience and Muscle Research, The Children's Hospital at Westmead, Locked Bag 4001, Westmead, NSW, 2145, Australia
| | - Shekeeb S Mohammad
- Discipline of Child and Adolescent Health, University of Sydney Medical School, Sydney, NSW, Australia.,Department of Neurology and Neurosurgery, The Children's Hospital at Westmead, Locked Bag 4001, Westmead, NSW, 2145, Australia
| | - Davinder Singh-Grewal
- Discipline of Child and Adolescent Health, University of Sydney Medical School, Sydney, NSW, Australia.,Department of Rheumatology, The Children's Hospital at Westmead, Locked Bag 4001, Westmead, NSW, 2145, Australia.,Discipline of Child and Maternal Health, University of New South Wales, Sydney, NSW, Australia
| | - Mukesh Yajaman Prabhuswamy
- Department Psychological Medicine, The Children's Hospital at Westmead, Locked Bag 4001, Westmead, NSW, 2145, Australia.,Faculty of Medicine, University of New South Wales, Sydney, NSW, Australia.,School of Medicine, Western Sydney University, Campbelltown, NSW, Australia
| | - Ellis Patrick
- School of Mathematics and Statistics, University of Sydney, F07 - Carslaw Building, Sydney, NSW, 2006, Australia.,Westmead Institute for Medical Research, Sydney, NSW, Australia
| |
Collapse
|
|
38
|
Van den Houte K, Carbone F, Pannemans J, Corsetti M, Fischler B, Piessevaux H, Tack J. Prevalence and impact of self-reported irritable bowel symptoms in the general population. United European Gastroenterol J 2019; 7:307-315. [PMID: 31080615 PMCID: PMC6498809 DOI: 10.1177/2050640618821804] [Citation(s) in RCA: 53] [Impact Index Per Article: 8.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/27/2018] [Accepted: 11/20/2018] [Indexed: 12/12/2022] Open
Abstract
Background and aims The symptom-based diagnostic criteria for irritable bowel syndrome (IBS) have recently been revised in the Rome IV consensus. On the other hand, with rising public awareness of IBS, self-diagnosis and self-management is also increasing. We compared the prevalence and impact of Rome IV-based IBS vs self-diagnosed IBS in the general population. Methods An internet panel filled out an online survey on bowel symptoms and their impact on health care utilization and daily activities. Results A representative internet panel of 1012 individuals completed the online survey. Bowel symptoms were present in 68.6% of the population. Of these, 21% consulted a physician for these symptoms in the last year and 42% earlier. Rome IV IBS criteria were fulfilled by 5.5%, and these were younger and more likely to be female. In this subset, 37% had consulted a physician for IBS symptoms in the preceding year and 29% had done so earlier. A colonoscopy had been performed in 22%. Based on a brief description, 17.6% of the population self-identified as suffering from IBS (p < 0.001 compared to Rome IV IBS prevalence), and these were more likely to be female. Concordance with the Rome IV criteria was only 25%, but except for a lower reporting of pain, the symptom pattern, severity, impact on daily life, inability to work and health care utilization were similar to the Rome IV group. A total of 134 days of absence from work were attributed to bowel symptoms in those self-reporting with IBS. Conclusion In the general population, bowel symptoms are highly prevalent, and the self-reported "IBS" is three times more prevalent than according to Rome IV criteria. Self-reported IBS is associated with a similar impact on health care utilization and quality of life but a higher impact on absence from work.
Collapse
Affiliation(s)
- K Van den Houte
- Department of Chronic Diseases, Metabolism and
Ageing, University of Leuven, Translational Research Center for Gastrointestinal
Disorders (TARGID), Leuven, Belgium
| | - F Carbone
- Department of Chronic Diseases, Metabolism and
Ageing, University of Leuven, Translational Research Center for Gastrointestinal
Disorders (TARGID), Leuven, Belgium
| | - J Pannemans
- Department of Chronic Diseases, Metabolism and
Ageing, University of Leuven, Translational Research Center for Gastrointestinal
Disorders (TARGID), Leuven, Belgium
| | - M Corsetti
- Department of Chronic Diseases, Metabolism and
Ageing, University of Leuven, Translational Research Center for Gastrointestinal
Disorders (TARGID), Leuven, Belgium
| | - B Fischler
- Department of Chronic Diseases, Metabolism and
Ageing, University of Leuven, Translational Research Center for Gastrointestinal
Disorders (TARGID), Leuven, Belgium
| | - H Piessevaux
- Department of Chronic Diseases, Metabolism and
Ageing, University of Leuven, Translational Research Center for Gastrointestinal
Disorders (TARGID), Leuven, Belgium
| | - J Tack
- Department of Chronic Diseases, Metabolism and
Ageing, University of Leuven, Translational Research Center for Gastrointestinal
Disorders (TARGID), Leuven, Belgium
| |
Collapse
|
|
39
|
Yang C, Fang X, Zhan G, Huang N, Li S, Bi J, Jiang R, Yang L, Miao L, Zhu B, Luo A, Hashimoto K. Key role of gut microbiota in anhedonia-like phenotype in rodents with neuropathic pain. Transl Psychiatry 2019; 9:57. [PMID: 30705252 PMCID: PMC6355832 DOI: 10.1038/s41398-019-0379-8] [Citation(s) in RCA: 135] [Impact Index Per Article: 22.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/04/2018] [Revised: 12/15/2018] [Accepted: 01/02/2019] [Indexed: 02/07/2023] Open
Abstract
Patients with chronic neuropathic pain frequently suffer from symptoms of anhedonia, which is a core symptom of depression. Accumulating studies suggest that gut microbiota may play a role in depression via gut-microbiota-brain axis. However, it is unknown whether gut microbiota plays a role in neuropathic pain-associated anhedonia. Here, we used a rat model of spared nerve injury (SNI). Hierarchical cluster analysis of sucrose preference test (SPT) results was used to classify the SNI rats with or without anhedonia-like phenotype. The 16S ribosomal RNA sequencing analysis showed abnormal composition of gut microbiota in the anhedonia susceptible compared to sham-operated rats and resilient rats. Furthermore, antibiotics-treated mice showed pain as well as depression-like and anhedonia-like phenotypes, suggesting a role of gut microbiota in these abnormal behaviors. Transplantation of fecal microbiota from anhedonia susceptible rats into antibiotics-treated pseudo-germ-free mice significantly exaggerated pain and depression-like phenotypes, including anhedonia. In contrast, transplantation of fecal microbiota from resilient rats into antibiotics-treated pseudo-germ-free mice significantly improved pain and depression-like phenotypes, including anhedonia. In conclusion, this study suggests that abnormal composition of gut microbiota may contribute to anhedonia susceptibility post SNI surgery, and that gut microbiota also plays a role in the pain as well as depression-like phenotypes. Interestingly, fecal microbiota transplantation from SNI rats with or without anhedonia can alter pain, depression-like and anhedonia-like phenotypes in the pseudo-germ-free mice. Therefore, it is likely that gut microbiota plays a key role in the pain as well as depression-like phenotypes including anhedonia in rodents with neuropathic pain.
Collapse
Affiliation(s)
- Chun Yang
- Department of Anesthesiology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Xi Fang
- Department of Anesthesiology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Gaofeng Zhan
- Department of Anesthesiology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Niannian Huang
- Department of Anesthesiology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Shan Li
- Department of Anesthesiology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Jiangjiang Bi
- Department of Anesthesiology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Riyue Jiang
- Department of Internal Medicine, The Third Affiliated Hospital of Soochow University, Changzhou, China
| | - Ling Yang
- Department of Internal Medicine, The Third Affiliated Hospital of Soochow University, Changzhou, China
| | - Liying Miao
- Department of Internal Medicine, The Third Affiliated Hospital of Soochow University, Changzhou, China
| | - Bin Zhu
- Department of Internal Medicine, The Third Affiliated Hospital of Soochow University, Changzhou, China
| | - Ailin Luo
- Department of Anesthesiology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
| | - Kenji Hashimoto
- Division of Clinical Neuroscience, Chiba University Center for Forensic Mental Health, Chiba, Japan.
| |
Collapse
|
|
40
|
Cojocariu R, Ciobica A, Balmus IM, Guenne S, Trifan A, Stanciu C, Hrițcu L, Lefter R. Antioxidant Capacity and Behavioral Relevance of a Polyphenolic Extract of Chrysanthellum americanum in a Rat Model of Irritable Bowel Syndrome. OXIDATIVE MEDICINE AND CELLULAR LONGEVITY 2019; 2019:3492767. [PMID: 31485290 PMCID: PMC6710773 DOI: 10.1155/2019/3492767] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 02/15/2019] [Revised: 07/12/2019] [Accepted: 07/25/2019] [Indexed: 02/08/2023]
Abstract
Chrysanthellum americanum L. (Vatke) is a medicinal plant from the Compositae family used in west-African traditional medicine, known for its flavonoid and saponin richness and for its strong antioxidant potential. In the present study, we assessed the effects of Chrysanthellum americanum polyphenolic extract in the psychological stress-induced rat model of irritable bowel syndrome (IBS), a chronic functional digestive tract disorder marked by immune and inflammatory-related disturbances of central nervous and peripheral intestinal systems, which is often associated with mood disorders including depression and anxiety. Consequently, memory impairment, anxiety and depression behavioral indicators, and cerebral oxidative stress biomarker dynamics were evaluated in a multifactorial heterotypic stress-exposed IBS rats after 6-day gavage with polyphenolic C. americanum extract (100 mg/kg body weight). Y-maze, elevated plus maze, and forced swimming tests were used for assessing behavioral responses. Administration of the extract exhibited significant anxiolytic and antidepressant-like effects coupled with significantly increased temporal lobe antioxidant enzyme specific activity (superoxide dismutase and glutathione peroxidase) and decreased malondialdehyde levels, a well-known lipid peroxidation marker. Furthermore, linear regression statistical analyses showed significant correlations between the oxidative stress parameters and behavioral tests. In conclusion, our results suggest that the administration of Chrysanthellum americanum polyphenolic extract could ameliorate mood and cognitive disturbances related to stress-induced in an IBS rat model. This could be also related to cerebral oxidative stress status attenuation.
Collapse
Affiliation(s)
- Roxana Cojocariu
- 1Department of Biology, Faculty of Biology, Alexandru Ioan Cuza University, 11th Carol I Avenue, 700506 Iasi, Romania
| | - Alin Ciobica
- 2Department of Research, Faculty of Biology, Alexandru Ioan Cuza University, 11th Carol I Avenue, 700506 Iasi, Romania
| | - Ioana-Miruna Balmus
- 2Department of Research, Faculty of Biology, Alexandru Ioan Cuza University, 11th Carol I Avenue, 700506 Iasi, Romania
| | - Samson Guenne
- 3Laboratory of Applied Biochemistry and Chemistry, University Joseph KI-ZERBO, 03 BP 7021 Ouagadougou 03, Burkina Faso
| | - Anca Trifan
- 4“Grigore T. Popa” University of Medicine and Pharmacy, 16th Universitatii Street, 700115 Iasi, Romania
| | - Carol Stanciu
- 5Center of Biomedical Research, Romanian Academy, 8th Carol I Avenue, 700506 Iasi, Romania
| | - Luminita Hrițcu
- 6Faculty of Veterinary Medicine, University of Agricultural Sciencies and Veterinary Medicine “”Ion Ionescu de la Brad” of Iasi, 3rd Mihail Sadoveanu Alley, Iasi 700490, Romania
| | - Radu Lefter
- 5Center of Biomedical Research, Romanian Academy, 8th Carol I Avenue, 700506 Iasi, Romania
| |
Collapse
|
|
41
|
Dellis AE, Mozaffari S, Nikfar S, Papatsoris AG, Abdollahi M. Is there an appropriate strategy for treating co-morbid irritable bowel syndrome and bladder pain syndrome? Expert Opin Pharmacother 2018; 20:411-414. [PMID: 30589379 DOI: 10.1080/14656566.2018.1559821] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
Abstract
INTRODUCTION Two of the most frequent components of chronic pelvic pain syndrome (CPPS) are irritable bowel syndrome (IBS) and bladder pain syndrome (BPS), characterized by considerable overlapping symptoms and pathophysiology. Currently, its management is challenging meaning there is high the demand for novel efficient therapeutics to aid patient care and to tackle the socioeconomic burden of IBS and BPS. As there are presently no sufficient treatment strategies, identifying the mechanisms that result in their main symptoms is the opportunity for developing appropriate therapies. Areas covered: Herein, the authors explore the potential common treatment strategies for co-morbid IBS and BPS and highlight the absolute need for further research of these deliberating clinical entities. Expert opinion: In the future, the authors summise that the discovery of predictive molecular biomarkers combined with clinical phenotypic categorization will likely allow for more definitive differentiation of patients and thus for better treatment options. Furthermore, it has been suggested that effective IBS treatment strategies would be of great value to co-morbid IBS and BPS therapy.
Collapse
Affiliation(s)
- Athanasios E Dellis
- a Second Department of Surgery, Aretaieion Academic Hospital, School of Medicine , National and Kapodistrian University of Athens , Athens , Greece.,b First Department of Urology, Laikon General Hospital, School of Medicine , National and Kapodistrian University of Athens , Athens , Greece
| | - Shilan Mozaffari
- c Division of Pharmaceutical and Narcotic Affaire, Vice Chancellor for Food and Drug , Kurdistan University of Medical Sciences , Sanandaj , Iran.,d Evidence-based Evaluation of Cost-Effectiveness and Clinical Outcomes Group, The Institute of Pharmaceutical Sciences (TIPS) , Tehran University of Medical Sciences , Tehran , Iran
| | - Shekoufeh Nikfar
- d Evidence-based Evaluation of Cost-Effectiveness and Clinical Outcomes Group, The Institute of Pharmaceutical Sciences (TIPS) , Tehran University of Medical Sciences , Tehran , Iran.,e Department of Pharmacoeconomics and Pharmaceutical Administration, Faculty of Pharmacy and Pharmaceutical Policy Research Center , Tehran University of Medical Sciences , Tehran , Iran
| | - Athanasios G Papatsoris
- f Second Department of Urology, Sismanogleion General Hospital, School of Medicine , National and Kapodistrian University of Athens , Athens , Greece
| | - Mohammad Abdollahi
- g Toxicology and Diseases Group, The Institute of Pharmaceutical Sciences (TIPS) , Tehran University of Medical Sciences , Tehran , Iran.,h Department of Toxicology and Pharmacology, Faculty of Pharmacy , Tehran University of Medical Sciences , Tehran , Iran
| |
Collapse
|
|
42
|
Mudyanadzo TA, Hauzaree C, Yerokhina O, Architha NN, Ashqar HM. Irritable Bowel Syndrome and Depression: A Shared Pathogenesis. Cureus 2018; 10:e3178. [PMID: 30357038 PMCID: PMC6197537 DOI: 10.7759/cureus.3178] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/09/2018] [Accepted: 08/21/2018] [Indexed: 12/13/2022] Open
Abstract
It is common knowledge that dysfunction of the immune and neuroendocrine systems, in addition to neuroplasticity, is among the pathways that underlie irritable bowel syndrome (IBS) and depression. From as early as the 1950s, the association of IBS with psychiatric disease was postulated; however, the exact mechanism remains elusive. There has been considerable research into the association of IBS and depression over the last years; research into the gut-brain axis and alterations in gut microbes have gained momentum to spell out the relationship between depression and IBS. Evidence from these researchers indicate the dysfunction of homeostatic coping mechanisms; corticotropin-releasing factor appears to be at the core of this dysfunction. The multifactorial etiology of both depression and IBS hinders a universal, one-strategy-fits-all treatment approach to patients with comorbid depression and IBS. This review analyzes the pathophysiology that associates these two conditions; it explores the bidirectional communication between the brain and the gastrointestinal tract, and how these influence the endocrine and immune systems. Review articles, clinical trials and randomized controlled trials that analyzed the association of depression and IBS were identified by searching PubMed, Google Scholar, and articles in PMC databases. Full texts written in English and available via these search engines were selected for the synthesis of this review. Alterations to the gut-brain axis, intestinal microbiota, and the neuro-immune system may be the cornerstone to the association of IBS and depression. This literature review opens alternate therapeutic approaches to comorbid IBS and depression and encourages further research into this topic.
Collapse
|
|
43
|
Yeh HW, Chien WC, Chung CH, Hu JM, Tzeng NS. Risk of psychiatric disorders in irritable bowel syndrome-A nationwide, population-based, cohort study. Int J Clin Pract 2018; 72:e13212. [PMID: 29920876 DOI: 10.1111/ijcp.13212] [Citation(s) in RCA: 19] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/09/2018] [Accepted: 04/30/2018] [Indexed: 02/06/2023] Open
Abstract
AIMS This cohort study aimed to investigate the association between irritable bowel syndrome (IBS) and the risk of developing psychiatric disorders. METHODS Utilizing the National Health Insurance Research Database (NHIRD) of Taiwan, IBS patients were identified and compared with age, sex, and index year-matched controls (1:3). RESULTS Of the IBS subjects, 3934 in 22 356 (17.60%, or 1533.68 per 100 000 person-years) developed psychiatric disorders when compared with 6127 in 67 068 (9.14%, or 802 per 100 000 person-years) in the non-IBS control group. Fine and Gray's survival analysis revealed that the study subjects were more likely to develop psychiatric disorders. The crude hazard ratio (HR) is 3.767 (95% CI: 3.614-3.925, P < .001), and the adjusted HR is 3.598 (95% CI: 3.452-3.752, P < .001) in the risk of developing psychiatric disorders after being adjusted for age, sex, comorbidities, geographical area of residence, urbanisation level of residence, and monthly insurance premiums. The cohort study revealed that IBS subjects were associated with an increased risk of anxiety, depression, bipolar, and sleep disorders. CONCLUSIONS This cohort study, using NHIRD, shows evidence support that patients with IBS have a 3.6-fold risk of developing psychiatric disorders. Other large or national datasets should be done to explore to underlying mechanisms.
Collapse
Affiliation(s)
- Hui-Wen Yeh
- Institute of Bioinformatics and System Biology, National Chiao-Tung University, Hsin-Chu, Taiwan
- Department of Nursing, Kang-Ning University (Taipei Campus), Taipei, Taiwan
- Department of Psychiatry, Tri-Service General Hospital, School of Medicine, National Defense Medical Center, Taipei, Taiwan
- Department of Nursing, Tri-Service General Hospital and School of Nursing, National Defense Medical Center, Taipei, Taiwan
| | - Wu-Chien Chien
- Department of Medical Research, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan
- School of Public Health, National Defense Medical Center, Taipei, Taiwan
- Graduate Institute of Life Sciences, National Defense Medical Center, Taipei, Taiwan
| | - Chi-Hsiang Chung
- Department of Medical Research, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan
- School of Public Health, National Defense Medical Center, Taipei, Taiwan
- Taiwanese Injury Prevention and Safety Promotion Association, Taipei, Taiwan
| | - Je-Ming Hu
- Division of Colorectal Surgery, Department of Surgery, Tri-Service General Hospital, School of Medicine, National Defense Medical Center, Taipei, Taiwan
- Department of Emergency Medicine, Tri-Service General Hospital, School of Medicine, National Defense Medical Center, Taipei, Taiwan
- Graduate Institute of Medical Sciences, National Defense Medical Center, Taipei, Taiwan
| | - Nian-Sheng Tzeng
- Department of Psychiatry, Tri-Service General Hospital, School of Medicine, National Defense Medical Center, Taipei, Taiwan
- Student Counseling Center, National Defense Medical Center, Taipei, Taiwan
| |
Collapse
|
|
44
|
de Abreu MS, Giacomini ACVV, Zanandrea R, Dos Santos BE, Genario R, de Oliveira GG, Friend AJ, Amstislavskaya TG, Kalueff AV. Psychoneuroimmunology and immunopsychiatry of zebrafish. Psychoneuroendocrinology 2018; 92:1-12. [PMID: 29609110 DOI: 10.1016/j.psyneuen.2018.03.014] [Citation(s) in RCA: 15] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/23/2018] [Revised: 03/14/2018] [Accepted: 03/21/2018] [Indexed: 12/11/2022]
Abstract
Despite the high prevalence of neural and immune disorders, their etiology and molecular mechanisms remain poorly understood. As the zebrafish (Danio rerio) is increasingly utilized as a powerful model organism in biomedical research, mounting evidence suggests these fish as a useful tool to study neural and immune mechanisms and their interplay. Here, we discuss zebrafish neuro-immune mechanisms and their pharmacological and genetic modulation, the effect of stress on cytokines, as well as relevant models of microbiota-brain interplay. As many human brain diseases are based on complex interplay between the neural and the immune system, here we discuss zebrafish models, as well as recent successes and challenges, in this rapidly expanding field. We particularly emphasize the growing utility of zebrafish models in translational immunopsychiatry research, as they improve our understanding of pathogenetic neuro-immune interactions, thereby fostering future discovery of potential therapeutic agents.
Collapse
Affiliation(s)
- Murilo S de Abreu
- Bioscience Institute, University of Passo Fundo (UPF), Passo Fundo, RS, Brazil; Postgraduate Program in Pharmacology, Federal University of Santa Maria (UFSM), Santa Maria, Brazil; The International Zebrafish Neuroscience Research Consortium (ZNRC), Slidell, LA, USA
| | - Ana C V V Giacomini
- Bioscience Institute, University of Passo Fundo (UPF), Passo Fundo, RS, Brazil; Postgraduate Program in Pharmacology, Federal University of Santa Maria (UFSM), Santa Maria, Brazil; Postgraduate Program in Environmental Sciences, University of Passo Fundo (UPF), Passo Fundo, Brazil
| | - Rodrigo Zanandrea
- Bioscience Institute, University of Passo Fundo (UPF), Passo Fundo, RS, Brazil
| | - Bruna E Dos Santos
- Bioscience Institute, University of Passo Fundo (UPF), Passo Fundo, RS, Brazil
| | - Rafael Genario
- Bioscience Institute, University of Passo Fundo (UPF), Passo Fundo, RS, Brazil
| | | | - Ashton J Friend
- Tulane University School of Science and Engineering, New Orleans, LA, USA
| | - Tamara G Amstislavskaya
- Research Institute of Physiology and Basic Medicine SB RAS, and Department of Neuroscience, Novosibirsk State University, Novosibirsk, Russia
| | - Allan V Kalueff
- School of Pharmacy, Southwest University, Chongqing, China; Ural Federal University, Ekaterinburg, Russia; ZENEREI Research Center, Slidell, LA, USA; Institute of Translational Biomedicine, St. Petersburg State University, St. Petersburg, Russia; Institute of Experimental Medicine, Almazov National Medical Research Center, St. Petersburg, Russia; Russian Research Center for Radiology and Surgical Technologies, Pesochny, Russia; Laboratory of Translational Biopsychiatry, Research Institute of Physiology and Basic Medicine SB RAS, Novosibirsk, Russia.
| |
Collapse
|
|
45
|
Liang S, Wu X, Hu X, Wang T, Jin F. Recognizing Depression from the Microbiota⁻Gut⁻Brain Axis. Int J Mol Sci 2018; 19:ijms19061592. [PMID: 29843470 PMCID: PMC6032096 DOI: 10.3390/ijms19061592] [Citation(s) in RCA: 202] [Impact Index Per Article: 28.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/28/2018] [Revised: 04/19/2018] [Accepted: 05/02/2018] [Indexed: 12/12/2022] Open
Abstract
Major depression is one of the leading causes of disability, morbidity, and mortality worldwide. The brain⁻gut axis functions are disturbed, revealed by a dysfunction of the brain, immune system, endocrine system, and gut. Traditional depression treatments all target the brain, with different drugs and/or psychotherapy. Unfortunately, most of the patients have never received any treatment. Studies indicate that gut microbiota could be a direct cause for the disorder. Abnormal microbiota and the microbiota⁻gut⁻brain dysfunction may cause mental disorders, while correcting these disturbance could alleviate depression. Nowadays, the gut microbiota modulation has become a hot topic in treatment research of mental disorders. Depression is closely related with the health condition of the brain⁻gut axis, and maintaining/restoring the normal condition of gut microbiota helps in the prevention/therapy of mental disorders.
Collapse
Affiliation(s)
- Shan Liang
- Key Laboratory of Mental Health, Institute of Psychology, Chinese Academy of Sciences, Beijing 100101, China.
| | - Xiaoli Wu
- Key Laboratory of Mental Health, Institute of Psychology, Chinese Academy of Sciences, Beijing 100101, China.
- Department of Psychology, University of Chinese Academy of Sciences, Beijing 100049, China.
| | - Xu Hu
- Key Laboratory of Mental Health, Institute of Psychology, Chinese Academy of Sciences, Beijing 100101, China.
| | - Tao Wang
- Key Laboratory of Mental Health, Institute of Psychology, Chinese Academy of Sciences, Beijing 100101, China.
| | - Feng Jin
- Key Laboratory of Mental Health, Institute of Psychology, Chinese Academy of Sciences, Beijing 100101, China.
| |
Collapse
|
|
46
|
Dunphy-Doherty F, O'Mahony SM, Peterson VL, O'Sullivan O, Crispie F, Cotter PD, Wigmore P, King MV, Cryan JF, Fone KCF. Post-weaning social isolation of rats leads to long-term disruption of the gut microbiota-immune-brain axis. Brain Behav Immun 2018; 68:261-273. [PMID: 29104061 DOI: 10.1016/j.bbi.2017.10.024] [Citation(s) in RCA: 84] [Impact Index Per Article: 12.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/22/2017] [Revised: 10/16/2017] [Accepted: 10/28/2017] [Indexed: 12/11/2022] Open
Abstract
Early-life stress is an established risk for the development of psychiatric disorders. Post-weaning isolation rearing of rats produces lasting developmental changes in behavior and brain function that may have translational pathophysiological relevance to alterations seen in schizophrenia, but the underlying mechanisms are unclear. Accumulating evidence supports the premise that gut microbiota influence brain development and function by affecting inflammatory mediators, the hypothalamic-pituitaryadrenal axis and neurotransmission, but there is little knowledge of whether the microbiota-gut-brain axis might contribute to the development of schizophrenia-related behaviors. To this end the effects of social isolation (SI; a well-validated animal model for schizophrenia)-induced changes in rat behavior were correlated with alterations in gut microbiota, hippocampal neurogenesis and brain cytokine levels. Twenty-four male Lister hooded rats were housed in social groups (group-housed, GH, 3 littermates per cage) or alone (SI) from weaning (post-natal day 24) for four weeks before recording open field exploration, locomotor activity/novel object discrimination (NOD), elevated plus maze, conditioned freezing response (CFR) and restraint stress at one week intervals. Post-mortem caecal microbiota composition, cortical and hippocampal cytokines and neurogenesis were correlated to indices of behavioral changes. SI rats were hyperactive in the open field and locomotor activity chambers traveling further than GH controls in the less aversive peripheral zone. While SI rats showed few alterations in plus maze or NOD they froze for significantly less time than GH following conditioning in the CFR paradigm, consistent with impaired associative learning and memory. SI rats had significantly fewer BrdU/NeuN positive cells in the dentate gyrus than GH controls. SI rats had altered microbiota composition with increases in Actinobacteria and decreases in the class Clostridia compared to GH controls. Differences were also noted at genus level. Positive correlations were seen between microbiota, hippocampal IL-6 and IL-10, conditioned freezing and open field exploration. Adverse early-life stress resulting from continuous SI increased several indices of 'anxiety-like' behavior and impaired associative learning and memory accompanied by changes to gut microbiota, reduced hippocampal IL-6, IL-10 and neurogenesis. This study suggests that early-life stress may produce long-lasting changes in gut microbiota contributing to development of abnormal neuronal and endocrine function and behavior which could play a pivotal role in the aetiology of psychiatric illness.
Collapse
Affiliation(s)
- Fionn Dunphy-Doherty
- School of Life Sciences, Medical School, Queen's Medical Centre, The University of Nottingham, Nottingham NG7 2UH, United Kingdom
| | - Siobhain M O'Mahony
- Department of Anatomy and Neuroscience, University College Cork, Ireland; APC Microbiome Institute, University College Cork, Ireland
| | | | - Orla O'Sullivan
- APC Microbiome Institute, University College Cork, Ireland; Teagasc Food Research Centre, Moorepark, Fermoy, Ireland
| | - Fiona Crispie
- Teagasc Food Research Centre, Moorepark, Fermoy, Ireland
| | - Paul D Cotter
- APC Microbiome Institute, University College Cork, Ireland; Teagasc Food Research Centre, Moorepark, Fermoy, Ireland
| | - Peter Wigmore
- School of Life Sciences, Medical School, Queen's Medical Centre, The University of Nottingham, Nottingham NG7 2UH, United Kingdom
| | - Madeleine V King
- School of Life Sciences, Medical School, Queen's Medical Centre, The University of Nottingham, Nottingham NG7 2UH, United Kingdom
| | - John F Cryan
- Department of Anatomy and Neuroscience, University College Cork, Ireland; APC Microbiome Institute, University College Cork, Ireland
| | - Kevin C F Fone
- School of Life Sciences, Medical School, Queen's Medical Centre, The University of Nottingham, Nottingham NG7 2UH, United Kingdom.
| |
Collapse
|