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Fakhri Bafghi MS, Khoshnam Rad N, Roostaei G, Nikfar S, Abdollahi M. The reality of modeling irritable bowel syndrome: progress and challenges. Expert Opin Drug Discov 2025; 20:433-445. [PMID: 40162721 DOI: 10.1080/17460441.2025.2481264] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/03/2024] [Accepted: 03/14/2025] [Indexed: 04/02/2025]
Abstract
INTRODUCTION Irritable bowel syndrome (IBS) is a common gastrointestinal disorder that is often therapeutically challenging. While research has advanced our understanding of IBS pathophysiology, developing precise models to predict drug response and treatment outcomes remains a significant hurdle. AREAS COVERED This perspective provides an overview of the use of animal models alongside cutting-edge technologies used to bring drugs from bench to bedside.Furthermore, the authors examine the progress and limitations of IBS modeling. The authors further discuss the challenges of traditional animal models and gives a spotlight to the potential of innovative technologies, such as organ-on-chip systems, computational models, and artificial intelligence (AI). These approaches intend to enhance both the understanding and treatment of IBS. EXPERT OPINION Although animal models have been central to understanding IBS research, they have limitations. The future of IBS research resides in integrating organ-on-chip systems and utilizing modern technological developments, such as AI. These tools will enable the design of more effective treatment strategies and improve patients' overall well-being. To achieve this, collaboration between experts from various disciplines is essential to improve these models and guarantee their clinical application and reliability.
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Affiliation(s)
- Maryam S Fakhri Bafghi
- Department of Internal Medicine, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran
| | - Niloofar Khoshnam Rad
- Thoracic Research Center, Imam Khomeini Hospital Complex, Tehran, Iran
- Department of Toxicology and Pharmacology, Faculty of Pharmacy and Pharmaceutical Sciences Research Center (PSRC), Tehran University of Medical Sciences, Tehran, Iran
| | - Ghazal Roostaei
- Thoracic Research Center, Imam Khomeini Hospital Complex, Tehran, Iran
- Rasoul Akram Hospital Clinical Research Development Center, School of Medicine, Rasool Akram Medical Complex, Iran University of Medical Sciences, Tehran, Iran
| | - Shekoufeh Nikfar
- Department of Toxicology and Pharmacology, Faculty of Pharmacy and Pharmaceutical Sciences Research Center (PSRC), Tehran University of Medical Sciences, Tehran, Iran
- Personalized Medicine Research Center, Endocrinology and Metabolism Research Institute, Tehran University of Medical Sciences (TUMS), Tehran, Iran
| | - Mohammad Abdollahi
- Department of Toxicology and Pharmacology, Faculty of Pharmacy and Pharmaceutical Sciences Research Center (PSRC), Tehran University of Medical Sciences, Tehran, Iran
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2
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Aljameeli AM, Alsuwayt B, Bharati D, Gohri V, Mohite P, Singh S, Chidrawar V. Chloride channels and mast cell function: pioneering new frontiers in IBD therapy. Mol Cell Biochem 2025:10.1007/s11010-025-05243-w. [PMID: 40038149 DOI: 10.1007/s11010-025-05243-w] [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: 08/30/2024] [Accepted: 02/22/2025] [Indexed: 03/06/2025]
Abstract
Emerging evidence indicates that chloride channels (ClCs) significantly affect the pathogenesis of inflammatory bowel disease (IBD) through their regulatory roles in mast cell function and epithelial integrity. IBD, encompassing conditions such as Crohn's disease and ulcerative colitis, involves chronic inflammation of the gastrointestinal tract, where channels influence immune responses, fluid balance, and cellular signalling pathways essential for maintaining mucosal homeostasis. This review examines the specific roles of ClC in mast cells, focussing on the regulation of mast cell activation, degranulation, cytokine release, and immune cell recruitment in inflamed tissues. Key channels, including Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) and ClC-2, are discussed in detail because of their involvement in maintaining intestinal epithelial barrier function, a critical factor disrupted in IBD. For example, CFTR facilitates chloride ion transport across epithelial cells, which is essential for mucosal hydration and maintenance of the intestinal barrier. Reduced CFTR function can compromise this barrier, permitting microbial antigens to penetrate the underlying tissues and triggering excessive immune responses. ClC-2, another chloride channel expressed in mast cells and epithelial cells, supports tight junction integrity, contributes to barrier function, and reduces intestinal permeability. Dysregulation of these channels is linked to altered mast cell activity and excessive release of pro-inflammatory mediators, exacerbating IBD symptoms, such as diarrhoea, abdominal pain, and tissue damage. Here, we review recent pharmacological strategies targeting ClC, including CFTR potentiators and ClC-2 activators, which show the potential to mitigate inflammatory responses. Additionally, experimental approaches for selective modulation of chloride channels in mast cells have been explored. Although targeting ClC offers promising therapeutic avenues, challenges remain in achieving specificity and minimizing side effects. This review highlights the therapeutic potential of Cl channel modulation in mast cells as a novel approach for IBD treatment, aiming to reduce inflammation and restore intestinal homeostasis in affected patients.
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Affiliation(s)
- Ahmed M Aljameeli
- Department of Pharmacy Practice, College of Pharmacy, University of Hafr Al-Batin, Hafr Albatin, Saudi Arabia
| | - Bader Alsuwayt
- Department of Pharmacy Practice, College of Pharmacy, University of Hafr Al-Batin, Hafr Albatin, Saudi Arabia
| | - Deepak Bharati
- AETs St. John Institute of Pharmacy and Research, Palghar, Maharashtra, 401 404, India
| | - Vaishnavi Gohri
- AETs St. John Institute of Pharmacy and Research, Palghar, Maharashtra, 401 404, India
| | - Popat Mohite
- AETs St. John Institute of Pharmacy and Research, Palghar, Maharashtra, 401 404, India.
| | - Sudarshan Singh
- Office of Research Administration, Chiang Mai University, Chiang Mai, 50200, Thailand
- Faculty of Pharmacy, Chiang Mai University, Chiang Mai, 50200, Thailand
| | - Vijay Chidrawar
- School of Pharmacy and Technology Management, SVKM's Narsee Monjee Institute of Management Studies (NMIMS), Deemed-to-University, Green Industrial Park, TSIIC, Polepally, Jadcherla, Hyderabad, Telangana, 509301, India.
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Molfetta R, Carnevale A, Marangio C, Putro E, Paolini R. Beyond the "Master" Role in Allergy: Insights into Intestinal Mast Cell Plasticity and Gastrointestinal Diseases. Biomedicines 2025; 13:320. [PMID: 40002733 PMCID: PMC11853218 DOI: 10.3390/biomedicines13020320] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/20/2024] [Revised: 01/10/2025] [Accepted: 01/27/2025] [Indexed: 02/27/2025] Open
Abstract
Mast cells (MCs) are essential components of the immune system that enter the circulation as immature bone marrow progenitors and differentiate in peripheral organs under the influence of microenvironment factors. As tissue-resident secretory immune cells, MCs rapidly detect the presence of bacteria and parasites because they harbor many surface receptors, which enable their activation via a multitude of stimuli. MC activation has been traditionally linked to IgE-mediated allergic reactions, but MCs play a pivotal role in different physiological and pathological processes. In gut, MCs are essential for the maintenance of gastrointestinal (GI) barrier function, and their interactions with neurons, immune cells, and epithelial cells have been related to various GI disorders. This review recapitulates intestinal MC roles in diseases with a main focus on inflammatory bowel disease (IBD) and irritable bowel syndrome (IBS). Emerging therapies targeting MCs and their mediators in clinical practices will also be discussed.
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Affiliation(s)
| | | | | | | | - Rossella Paolini
- Department of Molecular Medicine, Laboratory Affiliated to Istituto Pasteur Italia-Fondazione Cenci Bolognetti, Sapienza University of Rome, 00161 Rome, Italy; (R.M.); (A.C.); (C.M.); (E.P.)
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Gomathinayagam S, Srinivasan R, Gomathi A, Jayaraj R, Vasconcelos V, Sudhakaran R, Easwaran N, Meivelu Moovendhan, Kodiveri Muthukaliannan G. Oral Administration of Carotenoid-Rich Dunaliella salina Powder Inhibits Colon Carcinogenesis via Modulation of Wnt/β-catenin Signaling Cascades in a Rat Model. Appl Biochem Biotechnol 2025; 197:159-178. [PMID: 39106028 DOI: 10.1007/s12010-024-05024-z] [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] [Accepted: 07/23/2024] [Indexed: 08/07/2024]
Abstract
The present study aims to investigate the oral therapeutic and molecular role of carotenoid-rich Dunaliella salina powder (DSP) against 1,2-dimethylhydrazine (DMH)-triggered colon carcinogenesis. In this study, thirty six male Wistar rats were categorized into six distinct groups (G1-G6): G1 group with no intervention, G2 group received only DSP (1000 mg/kg), G3 group received only DMH carcinogen (20 mg/kg), and G4-G6 group received both DMH and DSP at various phases (pre-initiation, post-initiation and entire phases) for 32 weeks. Body weight, tumor incidence, tumor volume, histopathological examination, antioxidants, and detoxification enzymes activities were analyzed in the experimental rats. In addition, the protein expression profile of components involved in the Wnt/β-catenin signaling pathway was determined by western blot analysis. Matrix metalloproteinases (MMP-7 and MMP-9), proliferation marker (PCNA), and pro-apoptotic (Bcl-2 and Bax) proteins were analyzed using immunohistochemistry. Colorimetric assay was used to determine the levels of anti-inflammatory (iNOS and COX-2) and apoptotic proteins (Caspase-3 and Caspase-9). Results showed that concomitant administration of DSP with DMH significantly reduced tumor progression and prevented colon carcinogenesis in rats. However, treatment with DSP before or after DMH exposure did not significantly prevent colon carcinogenesis. DMH and DSP treatment group showed increased activities of antioxidant enzymes with significant reduction in the oxidative stress. Additionally, the detoxification enzymes and colonic histopathology of those rats were restored to that of control rats. The administration of DSP to rats exposed to DMH exhibited antitumor effects via inhibition of the Wnt/β-catenin signaling pathway with induced apoptosis through the Bcl-2/Bax/caspases signaling cascades. Moreover, the same group also showed significant anti-inflammatory activity via regulating iNOS and COX-2 biomarkers. Our findings revealed molecular chemopreventive activity of carotenoid-rich DSP through regulating Wnt/beta-catenin and intrinsic apoptotic pathways. Thus, DSP is propound to function as a potent antioxidant, anti-proliferative, and anti-inflammatory therapeutic agent against colon carcinogenesis.
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Affiliation(s)
| | - Ramachandran Srinivasan
- Centre for Ocean Research (DST-FIST Sponsored Centre), MoES - Earth Science & Technology Cell, Sathyabama Research Park, Sathyabama Institute of Science and Technology, Chennai, 600119, Tamil Nadu, India
| | - Ajitha Gomathi
- School of Bio-Sciences and Technology, Vellore Institute of Technology, Vellore, 632014, Tamil Nadu, India
| | - Rama Jayaraj
- Jindal Institute of Behavioral Sciences, Jindal Global Institution of Eminence Deemed to Be University, Sonipat, 131001, India
- Director of Clinical Sciences, Northern Territory Institute of Research and Training, Darwin, NT, 0909, Australia
| | - Vitor Vasconcelos
- CIIMAR/CIMAR-Interdisciplinary Centre of Marine and Environmental Research, University of Porto, Terminal de Cruzeiros do Porto de Leixões, 4450-208, Matosinhos, Portugal
- Department of Biology, Faculty of Sciences, University of Porto, 4069-007, Porto, Portugal
| | - Raja Sudhakaran
- School of Bio-Sciences and Technology, Vellore Institute of Technology, Vellore, 632014, Tamil Nadu, India
| | - Nalini Easwaran
- School of Bio-Sciences and Technology, Vellore Institute of Technology, Vellore, 632014, Tamil Nadu, India
| | - Meivelu Moovendhan
- Center for Global Health Research, Saveetha Medical College and Hospital, Saveetha Institute of Medical and Technical Sciences (SIMATS), Saveetha University, Thandalam, Chennai, Tamil Nadu, 602105, India
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García Mansilla MJ, Rodríguez Sojo MJ, Lista AR, Ayala Mosqueda CV, Ruiz Malagón AJ, Gálvez J, Rodríguez Nogales A, Rodríguez Sánchez MJ. Exploring Gut Microbiota Imbalance in Irritable Bowel Syndrome: Potential Therapeutic Effects of Probiotics and Their Metabolites. Nutrients 2024; 17:155. [PMID: 39796588 PMCID: PMC11723002 DOI: 10.3390/nu17010155] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/04/2024] [Revised: 12/24/2024] [Accepted: 12/26/2024] [Indexed: 01/13/2025] Open
Abstract
Irritable bowel syndrome is a common functional gastrointestinal disorder characterized by recurrent abdominal discomfort, bloating, cramping, flatulence, and changes in bowel movements. The pathophysiology of IBS involves a complex interaction between motor, sensory, microbiological, immunological, and psychological factors. Diversity, stability, and metabolic activity of the gut microbiota are frequently altered in IBS, thus leading to a situation of gut dysbiosis. Therefore, the use of probiotics and probiotic-derived metabolites may be helpful in balancing the gut microbiota and alleviating irritable bowel syndrome symptoms. This review aimed to report and consolidate recent progress in understanding the role of gut dysbiosis in the pathophysiology of IBS, as well as the current studies that have focused on the use of probiotics and their metabolites, providing a foundation for their potential beneficial effects as a complementary and alternative therapeutic strategy for this condition due to the current absence of effective and safe treatments.
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Affiliation(s)
- María José García Mansilla
- Department of Pharmacology, Centro de investigación Biomédica (CIBM), University of Granada, 18071 Granada, Spain; (M.J.G.M.); (M.J.R.S.); (J.G.); (A.R.N.); (M.J.R.S.)
| | - María Jesús Rodríguez Sojo
- Department of Pharmacology, Centro de investigación Biomédica (CIBM), University of Granada, 18071 Granada, Spain; (M.J.G.M.); (M.J.R.S.); (J.G.); (A.R.N.); (M.J.R.S.)
- Instituto de Investigación Biosanitaria de Granada (ibs.GRANADA), 18012 Granada, Spain; (A.R.L.); (C.V.A.M.)
| | - Andrea Roxana Lista
- Instituto de Investigación Biosanitaria de Granada (ibs.GRANADA), 18012 Granada, Spain; (A.R.L.); (C.V.A.M.)
| | | | - Antonio Jesús Ruiz Malagón
- Instituto de Investigación Biomédica de Málaga y Plataforma en Nanomedicina-IBIMA Plataforma BIONAND, 29590 Málaga, Spain
| | - Julio Gálvez
- Department of Pharmacology, Centro de investigación Biomédica (CIBM), University of Granada, 18071 Granada, Spain; (M.J.G.M.); (M.J.R.S.); (J.G.); (A.R.N.); (M.J.R.S.)
- Instituto de Investigación Biosanitaria de Granada (ibs.GRANADA), 18012 Granada, Spain; (A.R.L.); (C.V.A.M.)
- CIBER de Enfermedades Hepáticas y Digestivas (CIBER-EHD), Instituto de Salud Carlos III, 28029 Madrid, Spain
| | - Alba Rodríguez Nogales
- Department of Pharmacology, Centro de investigación Biomédica (CIBM), University of Granada, 18071 Granada, Spain; (M.J.G.M.); (M.J.R.S.); (J.G.); (A.R.N.); (M.J.R.S.)
- Instituto de Investigación Biosanitaria de Granada (ibs.GRANADA), 18012 Granada, Spain; (A.R.L.); (C.V.A.M.)
| | - María José Rodríguez Sánchez
- Department of Pharmacology, Centro de investigación Biomédica (CIBM), University of Granada, 18071 Granada, Spain; (M.J.G.M.); (M.J.R.S.); (J.G.); (A.R.N.); (M.J.R.S.)
- Instituto de Investigación Biosanitaria de Granada (ibs.GRANADA), 18012 Granada, Spain; (A.R.L.); (C.V.A.M.)
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6
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Aggeletopoulou I, Triantos C. Microbiome Shifts and Their Impact on Gut Physiology in Irritable Bowel Syndrome. Int J Mol Sci 2024; 25:12395. [PMID: 39596460 PMCID: PMC11594715 DOI: 10.3390/ijms252212395] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/01/2024] [Revised: 11/17/2024] [Accepted: 11/18/2024] [Indexed: 11/28/2024] Open
Abstract
Irritable bowel syndrome (IBS) is one of the most prevalent functional gastrointestinal disorders characterized by recurrent abdominal pain and altered bowel habits. The exact pathophysiological mechanisms for IBS development are not completely understood. Several factors, including genetic predisposition, environmental and psychological influences, low-grade inflammation, alterations in gastrointestinal motility, and dietary habits, have been implicated in the pathophysiology of the disorder. Additionally, emerging evidence highlights the role of gut microbiota in the pathophysiology of IBS. This review aims to thoroughly investigate how alterations in the gut microbiota impact physiological functions such as the brain-gut axis, immune system activation, mucosal inflammation, gut permeability, and intestinal motility. Our research focuses on the dynamic "microbiome shifts", emphasizing the enrichment or depletion of specific bacterial taxa in IBS and their profound impact on disease progression and pathology. The data indicated that specific bacterial populations are implicated in IBS, including reductions in beneficial species such as Lactobacillus and Bifidobacterium, along with increases in potentially harmful bacteria like Firmicutes and Proteobacteria. Emphasis is placed on the imperative need for further research to delineate the role of specific microbiome alterations and their potential as therapeutic targets, providing new insights into personalized treatments for IBS.
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Affiliation(s)
| | - Christos Triantos
- Division of Gastroenterology, Department of Internal Medicine, University Hospital of Patras, 26504 Patras, Greece;
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7
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Harris CI, Nasar B, Finnerty CC. Nutritional Implications of Mast Cell Diseases. J Acad Nutr Diet 2024; 124:1387-1396. [PMID: 38754765 DOI: 10.1016/j.jand.2024.05.008] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/18/2023] [Revised: 05/05/2024] [Accepted: 05/09/2024] [Indexed: 05/18/2024]
Affiliation(s)
| | | | - Celeste C Finnerty
- Division of Surgical Sciences, Department of Surgery, University of Texas Medical Branch, Galveston, Texas; The Mast Cell Disease Society, Inc., Sterling, Massachusetts
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8
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Gupta P, Dev K, Kaur G. Phytoconstituents as modulator of inflammatory pathways for COVID-19: A comprehensive review and recommendations. Phytother Res 2024; 38:5389-5416. [PMID: 39246209 DOI: 10.1002/ptr.8302] [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: 01/18/2024] [Revised: 07/04/2024] [Accepted: 07/12/2024] [Indexed: 09/10/2024]
Abstract
SARS-CoV-2 infection causes disruptions in inflammatory pathways, which fundamentally contribute to COVID-19 pathophysiology. The present review critically evaluates the gaps in scientific literature and presents the current status regarding the inflammatory signaling pathways in COVID-19. We propose that phytoconstituents can be used to treat COVID-19 associated inflammation, several already formulated in traditional medications. For this purpose, extensive literature analysis was conducted in the PubMed database to collect relevant in vitro, in vivo, and human patient studies where inflammation pathways were shown to be upregulated in COVID-19. Parallelly, scientific literature was screened for phytoconstituents with known cellular mechanisms implicated for inflammation or COVID-19 associated inflammation. Studies with insufficient evidence on cellular pathways for autophagy and mitophagy were considered out of scope and excluded from the study. The final analysis was visualized in figures and evaluated for accuracy. Our findings demonstrate the frequent participation of NF-κB, a transcription factor, in inflammatory signaling pathways linked to COVID-19. Moreover, the MAPK signaling pathway is also implicated in producing inflammatory molecules. Furthermore, it was also analyzed that the phytoconstituents with flavonoid and phenolic backbones could inhibit either the TLR4 receptor or its consecutive signaling molecules, thereby, decreasing NF-κB activity and suppressing cytokine production. Although, allopathy has treated the early phase of COVID-19, anti-inflammatory phytoconstituents and existing ayurvedic formulations may act on the COVID-19 associated inflammatory pathways and provide an additional treatment strategy. Therefore, we recommend the usage of flavonoids and phenolic phytoconstituents for the treatment of inflammation associated with COVID-19 infection and similar viral ailments.
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Affiliation(s)
- Pragati Gupta
- School of Biotechnology, Shoolini University, Solan, Himachal Pradesh, India
| | - Kamal Dev
- School of Biotechnology, Shoolini University, Solan, Himachal Pradesh, India
- Department of Pharmacology & Toxicology, Wright State University, Dayton, Ohio, USA
| | - Gurjot Kaur
- School of Pharmaceutical Sciences, Shoolini University, Solan, Himachal Pradesh, India
- National Center cum Department of Human Genome Research Center and Studies, Panjab University, Chandigarh, Punjab, India
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Maisto M, Piccolo V, Marzocchi A, Maresca DC, Romano B, Summa V, Tenore GC, Ercolano G, Ianaro A. Nutraceutical formulation based on a synergic combination of melatonin and palmitoylethanolamide for the management of allergic events. Front Nutr 2024; 11:1417747. [PMID: 39257610 PMCID: PMC11385308 DOI: 10.3389/fnut.2024.1417747] [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: 04/15/2024] [Accepted: 08/12/2024] [Indexed: 09/12/2024] Open
Abstract
The management of allergic events is a growing global health issue, especially in industrialized countries. This disease is an immune-mediated process, regulated by the interaction of IgE with an allergen, resulting in mast cell activation, which concerns the release of several immune-inflammatory modulators, i.e., histamine, β-hexosaminidase, COX-2, IL-6, and TNF-α, responsible for the main allergic-reaction associated symptoms. The aim of the present study was the efficacy evaluation of an alternative remedy, an innovative nutraceutical formulation (NF) based on the synergic combination of melatonin (MEL) and palmitoylethanolamide (PEA) for the prevention and treatment of immune disease. At first, the intestinal bioaccessibility of PEA and MEL in NF was assessed at 1.6 and 36%, respectively. Then the MEL and PEA ability to modulate the release of immune-inflammatory modulators in the human mast cell line (HMC-1.2) at their bioaccessible concentration was investigated. Our results underline that NF treatment was able to reduce COX-2 mRNA transcription levels (-30% vs. STIM, p < 0.0001) in stimulated HMC-1.2 and to contract COX-2 enzymatic activity directly (IC50: 152 μg/mL). Additionally, NF showed valuable ability in reducing histamine and β-hexosaminidase release in stimulated HMC-1.2, as well as in decreasing TNF-α and IL-6 mRNA transcription levels and protein production.
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Affiliation(s)
- Maria Maisto
- ChimNutra Labs, Department of Pharmacy, University of Naples Federico II, Naples, Italy
| | - Vincenzo Piccolo
- Department of Pharmacy, University of Naples Federico II, Naples, Italy
| | - Adua Marzocchi
- ChimNutra Labs, Department of Pharmacy, University of Naples Federico II, Naples, Italy
| | | | - Benedetta Romano
- Department of Pharmacy, University of Naples Federico II, Naples, Italy
| | - Vincenzo Summa
- Department of Pharmacy, University of Naples Federico II, Naples, Italy
| | - Gian Carlo Tenore
- Department of Pharmacy, University of Naples Federico II, Naples, Italy
| | - Giuseppe Ercolano
- Department of Pharmacy, University of Naples Federico II, Naples, Italy
| | - Angela Ianaro
- Department of Pharmacy, University of Naples Federico II, Naples, Italy
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Nair B, Kamath AJ, Tergaonkar V, Sethi G, Nath LR. Mast cells and the gut-liver Axis: Implications for liver disease progression and therapy. Life Sci 2024; 351:122818. [PMID: 38866220 DOI: 10.1016/j.lfs.2024.122818] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/22/2024] [Revised: 05/24/2024] [Accepted: 06/07/2024] [Indexed: 06/14/2024]
Abstract
The role of mast cells, traditionally recognized for their involvement in immediate hypersensitivity reactions, has garnered significant attention in liver diseases. Studies have indicated a notable increase in mast cell counts following hepatic injury, underscoring their potential contribution to liver disorder pathogenesis. Predominantly situated in connective tissue that envelops the hepatic veins, bile ducts, and arteries, mast cells are central to both initiating and perpetuating liver disorders. Additionally, they are crucial for maintaining gastrointestinal barrier function. The gut-liver axis emphasizes the complex, two-way communication between the gut microbiome and the liver. Past research has implicated gut microbiota and their metabolites in the progression of hepatic disorders. This review sheds light on how mast cells are activated in various liver conditions such as alcoholic liver disease (ALD), non-alcoholic fatty liver disease (NAFLD), viral hepatitis, hepatic fibrogenesis, and hepatocellular carcinoma. It also briefly explores the connection between the gut microbiome and mast cell activation in these hepatic conditions.
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Affiliation(s)
- Bhagyalakshmi Nair
- Department of Pharmacognosy, Amrita School of Pharmacy, Amrita Vishwa Vidyapeetham, AIMS Health Science Campus, Ponekkara, P.O., Kochi, Kerala 682041, India; Department of Pharmacology, Amrita School of Pharmacy, Amrita Vishwa Vidyapeetham, AIMS Health Science Campus, Ponekkara, P.O., Kochi, Kerala 682041, India
| | - Adithya Jayaprakash Kamath
- Department of Pharmacognosy, Amrita School of Pharmacy, Amrita Vishwa Vidyapeetham, AIMS Health Science Campus, Ponekkara, P.O., Kochi, Kerala 682041, India; Department of Pharmaceutics, Amrita School of Pharmacy, Amrita Vishwa Vidyapeetham, AIMS Health Science Campus, Ponekkara, P.O., Kochi, Kerala 682041, India
| | - Vinay Tergaonkar
- Laboratory of NFκB Signalling, Institute of Molecular and Cell Biology (IMCB), Agency for Science, Technology and Research (A*STAR), 61 Biopolis Drive, Proteos, 138673, Singapore
| | - Gautam Sethi
- Department of Pharmacology, Yong Loo Lin School of Medicine, National University of Singapore, 117600, Singapore.
| | - Lekshmi R Nath
- Department of Pharmacognosy, Amrita School of Pharmacy, Amrita Vishwa Vidyapeetham, AIMS Health Science Campus, Ponekkara, P.O., Kochi, Kerala 682041, India.
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11
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Özdemir Ö, Kasımoğlu G, Bak A, Sütlüoğlu H, Savaşan S. Mast cell activation syndrome: An up-to-date review of literature. World J Clin Pediatr 2024; 13:92813. [PMID: 38948000 PMCID: PMC11212760 DOI: 10.5409/wjcp.v13.i2.92813] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/06/2024] [Revised: 05/03/2024] [Accepted: 05/28/2024] [Indexed: 06/07/2024] Open
Abstract
Mast cells are a subtype of white blood cells and are involved in the immune system. These cells contain many chemical substances called mediators, which are involved in the allergic response. The fact that mast cells play a role in many events that require urgent intervention, especially anaphylaxis, has led to a more detailed study of these cells. The diseases also caused by dysfunctions of mast cells have been examined in many circumstances. For instance, mast cell activation syndrome is known as an augmented number of cells due to decreased cell death, resulting in clinical symptoms affecting many systems. The main common symptoms include flushing, hypotension, urticaria, angioedema, headache, vomiting and diarrhea. Although the underlying mechanism is not yet clearly known, we aim to review the literature in a broad perspective and bring together the existing knowledge in the light of the literature due to the diversity of its involvement in the body and the fact that it is a little known syndrome.
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Affiliation(s)
- Öner Özdemir
- Department of Pediatric Allergy and Immunology, Sakarya University, Sakarya, Adapazarı 54100, Türkiye
| | - Gökçe Kasımoğlu
- Department of Pediatrics, Sakarya University, Sakarya, Adapazarı 54100, Türkiye
| | - Ayşegül Bak
- Department of Pediatrics, Sakarya University, Sakarya, Adapazarı 54100, Türkiye
| | - Hüseyin Sütlüoğlu
- Department of Pediatrics, Kocaeli City Hospital, Kocaeli 50123, Türkiye
| | - Süreyya Savaşan
- Department of Pediatrics, Children’s Hospital of Michigan, Hematology/Oncology, Central Michigan University College of Medicine, Mount Pleasant, MI 48859, United States
- Barbara Ann Karmanos Cancer Institute, Wayne State University, Detroit, MI 12345, United States
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12
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Liang YF, Chen XQ, Zhang MT, Tang HY, Shen GM. Research Progress of Central and Peripheral Corticotropin-Releasing Hormone in Irritable Bowel Syndrome with Comorbid Dysthymic Disorders. Gut Liver 2024; 18:391-403. [PMID: 37551453 PMCID: PMC11096901 DOI: 10.5009/gnl220346] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/05/2022] [Revised: 04/26/2023] [Accepted: 05/22/2023] [Indexed: 08/09/2023] Open
Abstract
Irritable bowel syndrome (IBS) is considered a stress disorder characterized by psychological and gastrointestinal dysfunction. IBS patients not only suffer from intestinal symptoms such as abdominal pain, diarrhea, or constipation but also, experience dysthymic disorders such as anxiety and depression. Studies have found that corticotropin-releasing hormone plays a key role in IBS with comorbid dysthymic disorders. Next, we will summarize the effects of corticotropin-releasing hormone from the central nervous system and periphery on IBS with comorbid dysthymic disorders and relevant treatments based on published literatures in recent years.
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Affiliation(s)
- Yi Feng Liang
- College of Acupuncture and Massage, Anhui University of Chinese Medicine, Hefei, China
| | - Xiao Qi Chen
- College of Acupuncture and Massage, Anhui University of Chinese Medicine, Hefei, China
| | - Meng Ting Zhang
- College of Integrated Chinese and Western Medicine, Anhui University of Chinese Medicine, Hefei, China
| | - He Yong Tang
- College of Integrated Chinese and Western Medicine, Anhui University of Chinese Medicine, Hefei, China
| | - Guo Ming Shen
- College of Integrated Chinese and Western Medicine, Anhui University of Chinese Medicine, Hefei, China
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13
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Amin S, Massoumi H, Tewari D, Roy A, Chaudhuri M, Jazayerli C, Krishan A, Singh M, Soleimani M, Karaca EE, Mirzaei A, Guaiquil VH, Rosenblatt MI, Djalilian AR, Jalilian E. Cell Type-Specific Extracellular Vesicles and Their Impact on Health and Disease. Int J Mol Sci 2024; 25:2730. [PMID: 38473976 PMCID: PMC10931654 DOI: 10.3390/ijms25052730] [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: 01/31/2024] [Revised: 02/22/2024] [Accepted: 02/25/2024] [Indexed: 03/14/2024] Open
Abstract
Extracellular vesicles (EVs), a diverse group of cell-derived exocytosed particles, are pivotal in mediating intercellular communication due to their ability to selectively transfer biomolecules to specific cell types. EVs, composed of proteins, nucleic acids, and lipids, are taken up by cells to affect a variety of signaling cascades. Research in the field has primarily focused on stem cell-derived EVs, with a particular focus on mesenchymal stem cells, for their potential therapeutic benefits. Recently, tissue-specific EVs or cell type-specific extracellular vesicles (CTS-EVs), have garnered attention for their unique biogenesis and molecular composition because they enable highly targeted cell-specific communication. Various studies have outlined the roles that CTS-EVs play in the signaling for physiological function and the maintenance of homeostasis, including immune modulation, tissue regeneration, and organ development. These properties are also exploited for disease propagation, such as in cancer, neurological disorders, infectious diseases, autoimmune conditions, and more. The insights gained from analyzing CTS-EVs in different biological roles not only enhance our understanding of intercellular signaling and disease pathogenesis but also open new avenues for innovative diagnostic biomarkers and therapeutic targets for a wide spectrum of medical conditions. This review comprehensively outlines the current understanding of CTS-EV origins, function within normal physiology, and implications in diseased states.
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Affiliation(s)
- Sohil Amin
- Department of Ophthalmology and Visual Sciences, Illinois Eye and Ear Infirmary, University of Illinois at Chicago, Chicago, IL 60612, USA; (S.A.); (H.M.); (D.T.); (A.R.); (M.C.); (C.J.); (A.K.); (M.S.); (M.S.); (E.E.K.); (V.H.G.); (M.I.R.); (E.J.)
| | - Hamed Massoumi
- Department of Ophthalmology and Visual Sciences, Illinois Eye and Ear Infirmary, University of Illinois at Chicago, Chicago, IL 60612, USA; (S.A.); (H.M.); (D.T.); (A.R.); (M.C.); (C.J.); (A.K.); (M.S.); (M.S.); (E.E.K.); (V.H.G.); (M.I.R.); (E.J.)
- Richard and Loan Hill Department of Bioengineering, University of Illinois at Chicago, Chicago, IL 60607, USA
| | - Deepshikha Tewari
- Department of Ophthalmology and Visual Sciences, Illinois Eye and Ear Infirmary, University of Illinois at Chicago, Chicago, IL 60612, USA; (S.A.); (H.M.); (D.T.); (A.R.); (M.C.); (C.J.); (A.K.); (M.S.); (M.S.); (E.E.K.); (V.H.G.); (M.I.R.); (E.J.)
| | - Arnab Roy
- Department of Ophthalmology and Visual Sciences, Illinois Eye and Ear Infirmary, University of Illinois at Chicago, Chicago, IL 60612, USA; (S.A.); (H.M.); (D.T.); (A.R.); (M.C.); (C.J.); (A.K.); (M.S.); (M.S.); (E.E.K.); (V.H.G.); (M.I.R.); (E.J.)
| | - Madhurima Chaudhuri
- Department of Ophthalmology and Visual Sciences, Illinois Eye and Ear Infirmary, University of Illinois at Chicago, Chicago, IL 60612, USA; (S.A.); (H.M.); (D.T.); (A.R.); (M.C.); (C.J.); (A.K.); (M.S.); (M.S.); (E.E.K.); (V.H.G.); (M.I.R.); (E.J.)
| | - Cedra Jazayerli
- Department of Ophthalmology and Visual Sciences, Illinois Eye and Ear Infirmary, University of Illinois at Chicago, Chicago, IL 60612, USA; (S.A.); (H.M.); (D.T.); (A.R.); (M.C.); (C.J.); (A.K.); (M.S.); (M.S.); (E.E.K.); (V.H.G.); (M.I.R.); (E.J.)
| | - Abhi Krishan
- Department of Ophthalmology and Visual Sciences, Illinois Eye and Ear Infirmary, University of Illinois at Chicago, Chicago, IL 60612, USA; (S.A.); (H.M.); (D.T.); (A.R.); (M.C.); (C.J.); (A.K.); (M.S.); (M.S.); (E.E.K.); (V.H.G.); (M.I.R.); (E.J.)
| | - Mannat Singh
- Department of Ophthalmology and Visual Sciences, Illinois Eye and Ear Infirmary, University of Illinois at Chicago, Chicago, IL 60612, USA; (S.A.); (H.M.); (D.T.); (A.R.); (M.C.); (C.J.); (A.K.); (M.S.); (M.S.); (E.E.K.); (V.H.G.); (M.I.R.); (E.J.)
| | - Mohammad Soleimani
- Department of Ophthalmology and Visual Sciences, Illinois Eye and Ear Infirmary, University of Illinois at Chicago, Chicago, IL 60612, USA; (S.A.); (H.M.); (D.T.); (A.R.); (M.C.); (C.J.); (A.K.); (M.S.); (M.S.); (E.E.K.); (V.H.G.); (M.I.R.); (E.J.)
| | - Emine E. Karaca
- Department of Ophthalmology and Visual Sciences, Illinois Eye and Ear Infirmary, University of Illinois at Chicago, Chicago, IL 60612, USA; (S.A.); (H.M.); (D.T.); (A.R.); (M.C.); (C.J.); (A.K.); (M.S.); (M.S.); (E.E.K.); (V.H.G.); (M.I.R.); (E.J.)
- Department of Ophthalmology, University of Health Sciences, Ankara Bilkent City Hospital, Ankara 06800, Turkey
| | - Arash Mirzaei
- Department of Ophthalmology, University of Medical Sciences, Farabi Eye Hospital, Tehran 13366 16351, Iran;
| | - Victor H. Guaiquil
- Department of Ophthalmology and Visual Sciences, Illinois Eye and Ear Infirmary, University of Illinois at Chicago, Chicago, IL 60612, USA; (S.A.); (H.M.); (D.T.); (A.R.); (M.C.); (C.J.); (A.K.); (M.S.); (M.S.); (E.E.K.); (V.H.G.); (M.I.R.); (E.J.)
| | - Mark I. Rosenblatt
- Department of Ophthalmology and Visual Sciences, Illinois Eye and Ear Infirmary, University of Illinois at Chicago, Chicago, IL 60612, USA; (S.A.); (H.M.); (D.T.); (A.R.); (M.C.); (C.J.); (A.K.); (M.S.); (M.S.); (E.E.K.); (V.H.G.); (M.I.R.); (E.J.)
| | - Ali R. Djalilian
- Department of Ophthalmology and Visual Sciences, Illinois Eye and Ear Infirmary, University of Illinois at Chicago, Chicago, IL 60612, USA; (S.A.); (H.M.); (D.T.); (A.R.); (M.C.); (C.J.); (A.K.); (M.S.); (M.S.); (E.E.K.); (V.H.G.); (M.I.R.); (E.J.)
| | - Elmira Jalilian
- Department of Ophthalmology and Visual Sciences, Illinois Eye and Ear Infirmary, University of Illinois at Chicago, Chicago, IL 60612, USA; (S.A.); (H.M.); (D.T.); (A.R.); (M.C.); (C.J.); (A.K.); (M.S.); (M.S.); (E.E.K.); (V.H.G.); (M.I.R.); (E.J.)
- Richard and Loan Hill Department of Bioengineering, University of Illinois at Chicago, Chicago, IL 60607, USA
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14
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Zhou Y, Pang M, Ma Y, Lu L, Zhang J, Wang P, Li Q, Yang F. Cellular and Molecular Roles of Immune Cells in the Gut-Brain Axis in Migraine. Mol Neurobiol 2024; 61:1202-1220. [PMID: 37695471 DOI: 10.1007/s12035-023-03623-1] [Citation(s) in RCA: 4] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/24/2023] [Accepted: 08/29/2023] [Indexed: 09/12/2023]
Abstract
Migraine is a complex and multi-system dysfunction. The realization of its pathophysiology and diagnosis is developing rapidly. Migraine has been linked to gastrointestinal disorders such as irritable bowel syndrome and celiac disease. There is also direct and indirect evidence for a relationship between migraine and the gut-brain axis, but the exact mechanism is not yet explained. Studies have shown that this interaction appears to be influenced by a variety of factors, such as inflammatory mediators, gut microbiota, neuropeptides, and serotonin pathways. Recent studies suggest that immune cells can be the potential tertiary structure between migraine and gut-brain axis. As the hot interdisciplinary subject, the relationship between immunology and gastrointestinal tract is now gradually clear. Inflammatory signals are involved in cellular and molecular responses that link central and peripheral systems. The gastrointestinal symptoms associated with migraine and experiments associated with antibiotics have shown that the intestinal microbiota is abnormal during the attacks. In this review, we focus on the mechanism of migraine and gut-brain axis, and summarize the tertiary structure between immune cells, neural network, and gastrointestinal tract.
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Affiliation(s)
- Yichen Zhou
- School of Basic Medical Sciences, Capital Medical University, Beijing, China
| | - Miaoyi Pang
- School of Basic Medical Sciences, Capital Medical University, Beijing, China
| | - Yiran Ma
- School of Basic Medical Sciences, Capital Medical University, Beijing, China
| | - Lingling Lu
- Department of Neurobiology, School of Basic Medical Sciences, Capital Medical University, Beijing, China
| | - Jiannan Zhang
- Department of Neurobiology, School of Basic Medical Sciences, Capital Medical University, Beijing, China
| | - Peipei Wang
- Department of Neurobiology, School of Basic Medical Sciences, Capital Medical University, Beijing, China
| | - Qian Li
- Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Capital Medical University, Beijing, China
| | - Fei Yang
- Department of Neurobiology, School of Basic Medical Sciences, Capital Medical University, Beijing, China.
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15
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Xia Y, Peng S, Lin M, Duan H, Yuan F, Shao M, Tan W, Luo H. Apigenin attenuates visceral hypersensitivity in water avoidance stress rats by modulating the microbiota-gut-brain axis and inhibiting mast cell activation. Biomed Pharmacother 2023; 167:115562. [PMID: 37801900 DOI: 10.1016/j.biopha.2023.115562] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/22/2023] [Revised: 09/08/2023] [Accepted: 09/19/2023] [Indexed: 10/08/2023] Open
Abstract
Visceral hypersensitivity (VH) and gut microbiota dysbiosis significantly contribute to the occurrence and development of irritable bowel syndrome (IBS), exacerbated by stress. Apigenin, a natural flavonoid derived from plants, possesses a range of beneficial properties. However, additional research is necessary to investigate its potential in alleviating symptoms of IBS and elucidating its underlying mechanisms of action. Our study confirms that apigenin effectively reverses mast cell and microglial activation, regulates the composition and abundance of the gut microbiota, improves intestinal barrier function in rats induced with water-avoidance stress, and mitigates VH and colonic hypermotility. Furthermore, in vitro studies suggest a potential role of dysbiotic gut microbiota in activating mast cells at the cellular level. Notably, apigenin inhibits mast cell degranulation through the toll-like receptor 4 (TLR4) / myeloid differentiation primary response gene 88 (MyD88) / nuclear factor-kappa B (NF-κB) pathway. In conclusion, this study discusses the potential therapeutic effects of apigenin in alleviating VH and modulating the gut-brain axis in water-avoidance stress rats, providing a novel or alternative treatment approach for IBS.
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Affiliation(s)
- Yuan Xia
- Department of Gastroenterology, Renmin Hospital of Wuhan University, Wuhan, Hubei Province, China; Key Laboratory of Hubei Province for Digestive System Diseases, Renmin Hospital of Wuhan University, Wuhan, Hubei Province, China
| | - Shuai Peng
- Department of Gastroenterology, Renmin Hospital of Wuhan University, Wuhan, Hubei Province, China; Key Laboratory of Hubei Province for Digestive System Diseases, Renmin Hospital of Wuhan University, Wuhan, Hubei Province, China
| | - Mengjuan Lin
- Department of Gastroenterology, Renmin Hospital of Wuhan University, Wuhan, Hubei Province, China; Key Laboratory of Hubei Province for Digestive System Diseases, Renmin Hospital of Wuhan University, Wuhan, Hubei Province, China
| | - Houyu Duan
- Department of Gastroenterology, Renmin Hospital of Wuhan University, Wuhan, Hubei Province, China; Key Laboratory of Hubei Province for Digestive System Diseases, Renmin Hospital of Wuhan University, Wuhan, Hubei Province, China
| | - Fangting Yuan
- Department of Gastroenterology, Renmin Hospital of Wuhan University, Wuhan, Hubei Province, China; Key Laboratory of Hubei Province for Digestive System Diseases, Renmin Hospital of Wuhan University, Wuhan, Hubei Province, China
| | - Ming Shao
- Department of Gastroenterology, Renmin Hospital of Wuhan University, Wuhan, Hubei Province, China; Key Laboratory of Hubei Province for Digestive System Diseases, Renmin Hospital of Wuhan University, Wuhan, Hubei Province, China
| | - Wei Tan
- Department of Gastroenterology, Renmin Hospital of Wuhan University, Wuhan, Hubei Province, China; Key Laboratory of Hubei Province for Digestive System Diseases, Renmin Hospital of Wuhan University, Wuhan, Hubei Province, China.
| | - Hesheng Luo
- Department of Gastroenterology, Renmin Hospital of Wuhan University, Wuhan, Hubei Province, China; Key Laboratory of Hubei Province for Digestive System Diseases, Renmin Hospital of Wuhan University, Wuhan, Hubei Province, China.
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16
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Wang J, Yang M, Xu K, Wan X, Xie J, Yu H, Fang J, Wang Z, Xu P. The causal associations between growth factors and constipation: a two-sample Mendelian randomization study. Front Physiol 2023; 14:1204146. [PMID: 37501926 PMCID: PMC10369006 DOI: 10.3389/fphys.2023.1204146] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/12/2023] [Accepted: 06/28/2023] [Indexed: 07/29/2023] Open
Abstract
Introduction: Certain growth factors (GFs) are associated with constipation, but few studies has analyzed the causal associations between the two. Therefore, this study used two-sample Mendelian randomization (MR) to systematically analyze the causal associations between GF levels and constipation based on data from genome-wide association studies (GWAS). Methods: Both GF and constipation data were obtained from European populations. GFs, as an exposure variable, were obtained from a genetic map of the human plasma proteome containing 3,301 samples, another GWAS dataset on 90 circulating proteins containing 30,931 samples, and a GWAS dataset containing 3,788 samples. Constipation, as an outcome variable, was obtained from the FinnGen project containing 26,919 cases and 282,235 controls and another UK Biobank dataset containing 3,328 cases and 459,682 controls. Single-nucleotide polymorphisms strongly associated with GFs were regarded as instrumental variables. Inverse-variance weighting, MR-Egger regression, weight median, simple mode, and weight mode methods were used to determine genetic associations. Cochran's Q test, Egger intercept, and Mendelian Randomization Pleiotropy RESidual Sum and Outlier tests were used to analyze sensitivity. Results: The IVW analysis based on FinnGen showed that NGFI-A-binding protein 2 and vascular endothelial growth factor receptor 2 were inversely associated with constipation, and that fibroblast growth factor 7 and transforming growth factor beta receptor II levels were positively associated with constipation. The IVW analysis based on UK Biobank showed that proheparin-binding epidermal growth factor, platelet-derived growth factor AA, and vascular endothelial growth factor121 were inversely associated with constipation. Conclusion: This study showed that some GFs are genetically associated with the risk of constipation.
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Affiliation(s)
- Jiachen Wang
- Department of Joint Surgery, HongHui Hospital, Xi’an Jiaotong University, Xi’an, Shaanxi, China
| | - Mingyi Yang
- Department of Joint Surgery, HongHui Hospital, Xi’an Jiaotong University, Xi’an, Shaanxi, China
| | - Ke Xu
- Department of Joint Surgery, HongHui Hospital, Xi’an Jiaotong University, Xi’an, Shaanxi, China
| | - Xianjie Wan
- Department of Joint Surgery, HongHui Hospital, Xi’an Jiaotong University, Xi’an, Shaanxi, China
| | - Jiale Xie
- Department of Joint Surgery, HongHui Hospital, Xi’an Jiaotong University, Xi’an, Shaanxi, China
| | - Hui Yu
- Department of Joint Surgery, HongHui Hospital, Xi’an Jiaotong University, Xi’an, Shaanxi, China
| | - Jiaxin Fang
- Department of Clinical Medicine, Xi’an Jiaotong University, Xi’an, Shaanxi, China
| | - Zehua Wang
- Department of Clinical Medicine, Xi’an Jiaotong University, Xi’an, Shaanxi, China
| | - Peng Xu
- Department of Joint Surgery, HongHui Hospital, Xi’an Jiaotong University, Xi’an, Shaanxi, China
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17
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Sun Z, Wang X, Feng S, Xie C, Xing Y, Guo L, Zhao J, Ji C. A review of neuroendocrine immune system abnormalities in IBS based on the brain–gut axis and research progress of acupuncture intervention. Front Neurosci 2023; 17:934341. [PMID: 36968497 PMCID: PMC10034060 DOI: 10.3389/fnins.2023.934341] [Citation(s) in RCA: 7] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/02/2022] [Accepted: 02/07/2023] [Indexed: 03/11/2023] Open
Abstract
Irritable bowel syndrome (IBS) is a common digestive disorder observed in clinics. Current studies suggest that the pathogenesis of the disease is closely related to abnormal brain–gut interactions, hypokinesia, visceral sensory hypersensitivity in the gastrointestinal tract, and alterations in the intestinal microenvironment. However, it is difficult for a single factor to explain the heterogeneity of symptoms. The Rome IV criteria emphasized the holistic biologic-psycho-social model of IBS, suggesting that symptoms of the disease are closely related to neurogastroenterology and various abnormalities in brain–gut interaction. This study comprehensively reviewed the relationship between the brain–gut axis and IBS, the structure of the brain–gut axis, and the relationship between the brain–gut axis and intestinal microenvironment, and discussed the relationship between the abnormal regulation of the nervous system, endocrine system, and immune system and the incidence of IBS on the basis of brain–gut axis. In terms of treatment, acupuncture therapy can regulate the neuroendocrine-immune system of the body and improve the intestinal microenvironment, and it has the advantages of safety, economy, and effectiveness. We study the pathogenesis of IBS from local to global and micro to macro, and review the use of acupuncture to treat the disease as a whole so as to provide new ideas for the treatment of the disease.
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Affiliation(s)
- Zhangyin Sun
- College of Acupuncture and Moxibustion, Shaanxi University of Traditional Chinese Medicine, Xianyang, China
- Department of Acupuncture and Moxibustion, Shaanxi Hospital of Traditional Chinese Medicine, Xi'an, China
| | - Xuejiao Wang
- College of Acupuncture and Moxibustion, Shaanxi University of Traditional Chinese Medicine, Xianyang, China
- Department of Acupuncture and Moxibustion, Shaanxi Hospital of Traditional Chinese Medicine, Xi'an, China
| | - Shangsheng Feng
- MOE Key Laboratory of Biomedical Information Engineering, Xi'an Jiaotong University, Xi'an, China
| | - Chaoju Xie
- College of Acupuncture and Moxibustion, Shaanxi University of Traditional Chinese Medicine, Xianyang, China
- Department of Acupuncture and Moxibustion, Shaanxi Hospital of Traditional Chinese Medicine, Xi'an, China
| | - Yu Xing
- College of Acupuncture and Moxibustion, Shaanxi University of Traditional Chinese Medicine, Xianyang, China
- Department of Acupuncture and Moxibustion, Shaanxi Hospital of Traditional Chinese Medicine, Xi'an, China
| | - Liang Guo
- College of Acupuncture and Moxibustion, Shaanxi University of Traditional Chinese Medicine, Xianyang, China
- Department of Acupuncture and Moxibustion, Shaanxi Hospital of Traditional Chinese Medicine, Xi'an, China
| | - Jingyu Zhao
- Department of Acupuncture and Moxibustion, Xi'an Hospital of Traditional Chinese Medicine, Xi'an, China
- *Correspondence: Jingyu Zhao
| | - Changchun Ji
- Department of Acupuncture and Moxibustion, Shaanxi Hospital of Traditional Chinese Medicine, Xi'an, China
- Department of Acupuncture and Moxibustion, Shaanxi Provincial Institute of Traditional Chinese Medicine, Xi'an, China
- Changchun Ji
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18
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Namakin K, Moghaddam MH, Sadeghzadeh S, Mehranpour M, Vakili K, Fathi M, Golshan A, Bayat AH, Tajik AH, Eskandari N, Mohammadzadeh I, Benisi SZ, Aliaghaei A, Abdollahifar MA. Elderberry diet improves gut-brain axis dysfunction, neuroinflammation, and cognitive impairment in the rat model of irritable bowel syndrome. Metab Brain Dis 2023; 38:1555-1572. [PMID: 36877342 DOI: 10.1007/s11011-023-01187-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/24/2022] [Accepted: 02/13/2023] [Indexed: 03/07/2023]
Abstract
Irritable bowel syndrome (IBS) is related to a problem in the gut-brain axis. This experimental research aimed to shed light on the potential therapeutic application of elderberry (EB), which can work on the axis and get better the IBS symptoms. There were three groups (36 Sprague-Dawley rats) in this experiment, including control, IBS, and IBS with EB diet (IBS + EB). Making use of intracolonic instillation of 1 ml of 4% acetic acid for 30 s, IBS was induced. 7 days later, the EB extract (2%) was added to the diets of all animals for 8 weeks. Some histological, behavioral, and stereological techniques were used to detect the effects of EB on the gut and brain tissues. The findings showed that the EB diet improved locomotion and decreased anxiety-like behavior in the rat models of IBS. Moreover, the diet dropped the expression of TNF-α and increased mucosal layer thickness and the number of goblet and mast cells in colon tissue samples. In the hippocampal samples, administration of EB prevented astrogliosis and astrocyte reactivity. Although hippocampal and cortical neurons decreased markedly in the IBS group, EB prevented the drop in the number of neurons. Although lots of research is needed to elucidate the effectiveness of EB in IBS and its exact molecular mechanism, the result of this study showed that EB as an antioxidant and immune-modulatory agent could be a promising research target to prevent the impairment in the gut-brain axis, and could ameliorative classic IBS symptoms.
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Affiliation(s)
- Kosar Namakin
- Hearing Disorders Research Center, Loghman-Hakim Hospital, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Meysam Hassani Moghaddam
- Department of Anatomical Sciences, Faculty of Medicine, AJA University of Medical Sciences, Tehran, Iran
| | - Sara Sadeghzadeh
- Hearing Disorders Research Center, Loghman-Hakim Hospital, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Maryam Mehranpour
- Department of Genetics, Faculty of Biological Sciences, North Tehran Branch, Islamic Azad University, Tehran, Iran
| | - Kimia Vakili
- Student Research Committee, Faculty of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Mobina Fathi
- Student Research Committee, Faculty of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Ahmadreza Golshan
- Hearing Disorders Research Center, Loghman-Hakim Hospital, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Amir-Hossein Bayat
- Department of Neuroscience, School of Sciences and Advanced Technology in Medicine, Hamadan University of Medical Sciences, Hamadan, Iran
| | - Amir-Hossein Tajik
- Hearing Disorders Research Center, Loghman-Hakim Hospital, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Neda Eskandari
- Department of Anatomical Sciences, Faculty of Medicine, AJA University of Medical Sciences, Tehran, Iran
| | - Ibrahim Mohammadzadeh
- Hearing Disorders Research Center, Loghman-Hakim Hospital, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Soheila Zamanlui Benisi
- Stem Cell Research Center, Tissue Engineering and Regenerative Medicine Institute, Central Tehran Branch, Islamic Azad University, 1385/768, Tehran, Iran
| | - Abbas Aliaghaei
- Hearing Disorders Research Center, Loghman-Hakim Hospital, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
| | - Mohammad-Amin Abdollahifar
- Hearing Disorders Research Center, Loghman-Hakim Hospital, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
- Department of Biology and Anatomical Sciences, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
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19
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Ertaş R, Türk M, Yücel MB, Muñoz M, Ertaş ŞK, Atasoy M, Maurer M. Eating Increases and Exercise Decreases Disease Activity in Patients With Symptomatic Dermographism. THE JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY. IN PRACTICE 2023; 11:932-940. [PMID: 36535522 DOI: 10.1016/j.jaip.2022.11.041] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 05/09/2022] [Revised: 11/13/2022] [Accepted: 11/25/2022] [Indexed: 12/23/2022]
Abstract
BACKGROUND Eating can increase disease activity in patients with symptomatic dermographism , the most common subtype of chronic inducible urticaria, but it is unclear how common this is. The effects of exercising on symptomatic dermographism disease activity have also not yet been determined. OBJECTIVE To assess the impact of exercise and nonspecific carbohydrate-rich food intake on the severity and intensity of symptomatic dermographism after exercise and nonspecific carbohydrate-rich food intake. METHODS We assessed disease activity by FricTest provocation testing in 75 symptomatic dermographism patients before and after eating, exercising, or both. We determined the rates of food-dependent (FD) symptomatic dermographism and food-exacerbated (FE) symptomatic dermographism. By comparing post- and pre-exercise FricTest scores, we identified complete responders: that is, patients with a negative FricTest response after exercising and partial responders. Finally, we evaluated whether exercise protects patients with FD-symptomatic dermographism or FE-symptomatic dermographism from eating-induced worsening of symptomatic dermographism. RESULTS Of 64 symptomatic dermographism patients, eight had FD-symptomatic dermographism (13%), 42 had FE-symptomatic dermographism (66%), and 14 patients showed no negative impact of eating on disease activity (21%). Physical exercise reduced FricTest skin provocation test responses in 83% of 58 patients. Exercising protected patients with FD/FE-symptomatic dermographism from worsening of symptomatic dermographism owing to eating in half of cases, with higher rates for exercise after eating (67%) compared with exercise before eating (35%). CONCLUSIONS Our study shows that eating often worsen symptomatic dermographism symptoms, and exercise often improves it. Our findings might aid patients in controlling symptoms better.
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Affiliation(s)
- Ragıp Ertaş
- Urticaria Center of Reference and Excellence, Chronic Skin Diseases Unit, Department of Dermatology, University of Health Sciences, Kayseri City Education and Research Hospital, Kayseri, Turkey.
| | - Murat Türk
- Clinic of Allergy and Immunology, University of Health Sciences, Kayseri City Education and Research Hospital, Kayseri, Turkey
| | - Muhammed Burak Yücel
- Urticaria Center of Reference and Excellence, Chronic Skin Diseases Unit, Department of Dermatology, University of Health Sciences, Kayseri City Education and Research Hospital, Kayseri, Turkey
| | - Melba Muñoz
- Urticaria Center of Reference and Excellence, Institute of Allergology, Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany; Fraunhofer Institute for Translational Medicine and Pharmacology ITMP, Allergology and Immunology, Berlin, Germany
| | - Şule Ketenci Ertaş
- Department of Internal Medicine, Division of Rheumatology, Kayseri Acıbadem Hospital, Kayseri, Turkey
| | - Mustafa Atasoy
- Department of Dermatology, Biruni University, İstanbul, Turkey
| | - Marcus Maurer
- Urticaria Center of Reference and Excellence, Institute of Allergology, Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany; Fraunhofer Institute for Translational Medicine and Pharmacology ITMP, Allergology and Immunology, Berlin, Germany.
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20
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Wang J, Zhao D, Lei Z, Ge P, Lu Z, Chai Q, Zhang Y, Qiang L, Yu Y, Zhang X, Li B, Zhu S, Zhang L, Liu CH. TRIM27 maintains gut homeostasis by promoting intestinal stem cell self-renewal. Cell Mol Immunol 2023; 20:158-174. [PMID: 36596873 PMCID: PMC9887071 DOI: 10.1038/s41423-022-00963-1] [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: 08/06/2022] [Accepted: 11/20/2022] [Indexed: 01/05/2023] Open
Abstract
Dysregulation of gut homeostasis is associated with irritable bowel syndrome (IBS), a chronic functional gastrointestinal disorder affecting approximately 11.2% of the global population. The poorly understood pathogenesis of IBS has impeded its treatment. Here, we report that the E3 ubiquitin ligase tripartite motif-containing 27 (TRIM27) is weakly expressed in IBS but highly expressed in inflammatory bowel disease (IBD), a frequent chronic organic gastrointestinal disorder. Accordingly, knockout of Trim27 in mice causes spontaneously occurring IBS-like symptoms, including increased visceral hyperalgesia and abnormal stool features, as observed in IBS patients. Mechanistically, TRIM27 stabilizes β-catenin and thus activates Wnt/β-catenin signaling to promote intestinal stem cell (ISC) self-renewal. Consistent with these findings, Trim27 deficiency disrupts organoid formation, which is rescued by reintroducing TRIM27 or β-catenin. Furthermore, Wnt/β-catenin signaling activator treatment ameliorates IBS symptoms by promoting ISC self-renewal. Taken together, these data indicate that TRIM27 is critical for maintaining gut homeostasis, suggesting that targeting the TRIM27/Wnt/β-catenin axis could be a potential treatment strategy for IBS. Our study also indicates that TRIM27 might serve as a potential biomarker for differentiating IBS from IBD.
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Affiliation(s)
- Jing Wang
- CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing, 100101, China
| | - Dongdong Zhao
- CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing, 100101, China
- Savaid Medical School, University of Chinese Academy of Sciences, Beijing, 101408, China
| | - Zehui Lei
- CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing, 100101, China
- Savaid Medical School, University of Chinese Academy of Sciences, Beijing, 101408, China
| | - Pupu Ge
- CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing, 100101, China
| | - Zhe Lu
- CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing, 100101, China
- Savaid Medical School, University of Chinese Academy of Sciences, Beijing, 101408, China
| | - Qiyao Chai
- CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing, 100101, China
| | - Yong Zhang
- CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing, 100101, China
- State Key Laboratory of Proteomics, National Center for Protein Sciences, Beijing Institute of Lifeomics, Beijing, 100850, China
| | - Lihua Qiang
- CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing, 100101, China
- Savaid Medical School, University of Chinese Academy of Sciences, Beijing, 101408, China
| | - Yang Yu
- CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing, 100101, China
- Savaid Medical School, University of Chinese Academy of Sciences, Beijing, 101408, China
| | - Xinwen Zhang
- CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing, 100101, China
| | - Bingxi Li
- CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing, 100101, China
| | - Shu Zhu
- Institute of Immunology, Chinese Academy of Sciences Key Laboratory of Innate Immunity and Chronic Disease, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, 230027, China
| | - Lingqiang Zhang
- State Key Laboratory of Proteomics, National Center for Protein Sciences, Beijing Institute of Lifeomics, Beijing, 100850, China.
| | - Cui Hua Liu
- CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing, 100101, China.
- Savaid Medical School, University of Chinese Academy of Sciences, Beijing, 101408, China.
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21
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Senchukova MA. Microbiota of the gastrointestinal tract: Friend or foe? World J Gastroenterol 2023; 29:19-42. [PMID: 36683718 PMCID: PMC9850957 DOI: 10.3748/wjg.v29.i1.19] [Citation(s) in RCA: 18] [Impact Index Per Article: 9.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/21/2022] [Revised: 11/05/2022] [Accepted: 12/16/2022] [Indexed: 01/04/2023] Open
Abstract
The gut microbiota is currently considered an external organ of the human body that provides important mechanisms of metabolic regulation and protection. The gut microbiota encodes over 3 million genes, which is approximately 150 times more than the total number of genes present in the human genome. Changes in the qualitative and quantitative composition of the microbiome lead to disruption in the synthesis of key bacterial metabolites, changes in intestinal barrier function, and inflammation and can cause the development of a wide variety of diseases, such as diabetes, obesity, gastrointestinal disorders, cardiovascular issues, neurological disorders and oncological concerns. In this review, I consider issues related to the role of the microbiome in the regulation of intestinal barrier function, its influence on physiological and pathological processes occurring in the body, and potential new therapeutic strategies aimed at restoring the gut microbiome. Herewith, it is important to understand that the gut microbiota and human body should be considered as a single biological system, where change of one element will inevitably affect its other components. Thus, the study of the impact of the intestinal microbiota on health should be considered only taking into account numerous factors, the role of which has not yet been fully elucidated.
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Affiliation(s)
- Marina A Senchukova
- Department of Oncology, Orenburg State Medical University, Orenburg 460000, Russia
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22
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Zhang X, Liu Y, Ou Y, Yang M, Yuan J, He Q, Li Y, Mi N, Xie P, Li W, Wu S, Qin X, Qi J, Xia B. Gender-specific association between the regular use of statins and the risk of irritable bowel syndrome: A population-based prospective cohort study. Front Pharmacol 2023; 13:1044542. [PMID: 36686671 PMCID: PMC9853052 DOI: 10.3389/fphar.2022.1044542] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/14/2022] [Accepted: 12/15/2022] [Indexed: 01/09/2023] Open
Abstract
Introduction: In addition to lipid-lowering effects, statins might modulate the gut microbiome and alleviate systematic inflammation, which in turn, may have a protective effect against irritable bowel syndrome (IBS). The aim of our study was to evaluate the gender-specific association between statin exposure and the risk of IBS. Method: We undertook a prospective analysis based on the United Kingdom Biobank, a large ongoing cohort including 477,293 participants aged 37-73 years. We included participants based on information on their personal statin use and also those free of IBS and cancer at the baseline. We evaluated the gender-specific hazard ratio (HR) and 95% confidence interval (CI) with Cox proportional hazards regression, adjusting for demographic factors, lifestyle factors, comorbidities, and statin indications. Result: A total of 438,805 participants (206,499 males and 232,306 females) were included in the analysis. Among male participants, the regular use of statins was associated with a decreased risk of IBS (HR: 0.77; 95% CI: 0.61-0.97). This association persists across multiple sensitivity and subgroup analyses and did not show clear evidence of variance among the major types of statins. We did not find sufficient evidence of the association between the statin use and IBS risk in females (HR: 0.98; 95% CI: 0.82-1.16). Conclusion: Our study found that the regular use of statins was associated with a decreased risk of IBS in male participants. Further studies are required to confirm the beneficial effect of statins.
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Affiliation(s)
- Xiaoying Zhang
- Health Management Center, The Seventh Affiliated Hospital, Sun Yat-sen University, Shenzhen, China
| | - Yuyao Liu
- School of Medicine, Sun Yat-sen University, Shenzhen, China
| | - Yanghui Ou
- Center for Digestive Disease, The Seventh Affiliated Hospital, Sun Yat-sen University, Shenzhen, China
| | - Man Yang
- Center for Digestive Disease, The Seventh Affiliated Hospital, Sun Yat-sen University, Shenzhen, China
| | - Jinqiu Yuan
- Center for Digestive Disease, The Seventh Affiliated Hospital, Sun Yat-sen University, Shenzhen, China
- Clinical Research Center, The Seventh Affiliated Hospital, Sun Yat-sen University, Shenzhen, , China
- Big Data Center, The Seventh Affiliated Hospital, Sun Yat-sen University, Shenzhen, China
- Chinese Health Risk Management Collaboration (CHRIMAC), Shenzhen, China
| | - Qiangsheng He
- Clinical Research Center, The Seventh Affiliated Hospital, Sun Yat-sen University, Shenzhen, , China
- Big Data Center, The Seventh Affiliated Hospital, Sun Yat-sen University, Shenzhen, China
- Chinese Health Risk Management Collaboration (CHRIMAC), Shenzhen, China
| | - Yanfei Li
- Chinese Health Risk Management Collaboration (CHRIMAC), Shenzhen, China
| | - Ningning Mi
- Evidence Based Medicine Center, School of Basic Medical Sciences, Lanzhou University, Lanzhou, China
| | - Peng Xie
- Center for Digestive Disease, The Seventh Affiliated Hospital, Sun Yat-sen University, Shenzhen, China
| | - Wenjing Li
- Clinical Research Center, The Seventh Affiliated Hospital, Sun Yat-sen University, Shenzhen, , China
| | - Siqin Wu
- School of Medicine, Sun Yat-sen University, Shenzhen, China
| | - Xiwen Qin
- Special Minimally Invasive Surgery Department, The First Hospital of Lanzhou University, Lanzhou, China
- Department of Pharmacology and Pharmacy, LKS Faculty of Medicine, The University of Hong Kong, Hong Kong, Hong Kong SAR, China
- Laboratory of Data Discovery for Health (D24H), The University of Hong Kong, Hong Kong, Hong Kong SAR, China
| | - Jian Qi
- Center for Digestive Disease, The Seventh Affiliated Hospital, Sun Yat-sen University, Shenzhen, China
| | - Bin Xia
- Clinical Research Center, The Seventh Affiliated Hospital, Sun Yat-sen University, Shenzhen, , China
- Big Data Center, The Seventh Affiliated Hospital, Sun Yat-sen University, Shenzhen, China
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23
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Brierley SM, Greenwood-Van Meerveld B, Sarnelli G, Sharkey KA, Storr M, Tack J. Targeting the endocannabinoid system for the treatment of abdominal pain in irritable bowel syndrome. Nat Rev Gastroenterol Hepatol 2023; 20:5-25. [PMID: 36168049 DOI: 10.1038/s41575-022-00682-y] [Citation(s) in RCA: 18] [Impact Index Per Article: 9.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 08/16/2022] [Indexed: 12/27/2022]
Abstract
The management of visceral pain in patients with disorders of gut-brain interaction, notably irritable bowel syndrome, presents a considerable clinical challenge, with few available treatment options. Patients are increasingly using cannabis and cannabinoids to control abdominal pain. Cannabis acts on receptors of the endocannabinoid system, an endogenous system of lipid mediators that regulates gastrointestinal function and pain processing pathways in health and disease. The endocannabinoid system represents a logical molecular therapeutic target for the treatment of pain in irritable bowel syndrome. Here, we review the physiological and pathophysiological functions of the endocannabinoid system with a focus on the peripheral and central regulation of gastrointestinal function and visceral nociception. We address the use of cannabinoids in pain management, comparing them to other treatment modalities, including opioids and neuromodulators. Finally, we discuss emerging therapeutic candidates targeting the endocannabinoid system for the treatment of pain in irritable bowel syndrome.
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Affiliation(s)
- Stuart M Brierley
- Visceral Pain Research Group, College of Medicine and Public Health, Flinders Health and Medical Research Institute, Flinders University, Bedford Park, South Australia, Australia
- Hopwood Centre for Neurobiology, Lifelong Health, South Australian Health and Medical Research Institute, North Terrace, Adelaide, South Australia, Australia
| | | | - Giovanni Sarnelli
- Department of Clinical Medicine and Surgery, University of Naples "Federico II", Naples, Italy
| | - Keith A Sharkey
- Hotchkiss Brain Institute, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada.
- Snyder Institute for Chronic Diseases, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada.
- Department of Physiology and Pharmacology, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada.
| | - Martin Storr
- Department of Medicine, Ludwig-Maximilians University, Munich, Germany
- Zentrum für Endoskopie, Starnberg, Germany
| | - Jan Tack
- Translational Research Center for Gastrointestinal Disorders, University of Leuven, Leuven, Belgium
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24
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Császár-Nagy N, Bókkon I. Hypnotherapy and IBS: Implicit, long-term stress memory in the ENS? Heliyon 2022; 9:e12751. [PMID: 36685398 PMCID: PMC9849985 DOI: 10.1016/j.heliyon.2022.e12751] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/12/2022] [Revised: 09/20/2022] [Accepted: 12/27/2022] [Indexed: 01/01/2023] Open
Abstract
The association between irritable bowel syndrome (IBS) and psychiatric and mood disorders may be more fundamental than was previously believed. Prenatal, perinatal, postnatal, and early-age conditions can have a key role in the development of IBS. Subthreshold mental disorders (SMDs) could also be a significant source of countless diverse diseases and may be a cause of IBS development. We hypothesize that stress-induced implicit memories may persist throughout life by epigenetic processes in the enteric nervous system (ENS). These stress-induced implicit memories may play an essential role in the emergence and maintenance of IBS. In recent decades, numerous studies have proven that hypnosis can improve the primary symptoms of IBS and also reduce noncolonic symptoms such as anxiety and depression and improve quality of life and cognitive function. These significant beneficial effects of hypnosis on IBS may be because hypnosis allows access to unconscious brain processes.
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Affiliation(s)
- N. Császár-Nagy
- National University of Public Services, Budapest, Hungary,Psychosomatic Outpatient Clinics, Budapest, Hungary
| | - I. Bókkon
- Psychosomatic Outpatient Clinics, Budapest, Hungary,Vision Research Institute, Neuroscience and Consciousness Research Department, Lowell, MA, USA,Corresponding author. H-1238, Budapest, Láng Endre 68, Hungary.
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25
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Beneficial Effects of Limosilactobacillus fermentum in the DCA Experimental Model of Irritable Bowel Syndrome in Rats. Nutrients 2022; 15:nu15010024. [PMID: 36615683 PMCID: PMC9824399 DOI: 10.3390/nu15010024] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/08/2022] [Revised: 12/15/2022] [Accepted: 12/16/2022] [Indexed: 12/24/2022] Open
Abstract
Limosilactobacillus fermentum CECT5716, a probiotic strain isolated from human milk, has reported beneficial effects on different gastrointestinal disorders. Moreover, it has shown its ability to restore altered immune responses, in association with microbiome modulation in different pathological conditions. Therefore, our aim was to assess the effects of a Limosilacbacillus fermentum CECT5716 in a rat experimental model of irritable bowel syndrome (IBS) that resembles human IBS. The experimental IBS was induced by deoxycholic acid (DCA) in rats and then, Limosilactobacillus fermentum CECT5716 (109 CFU/day/rat) was administered. Behavioral studies, hyperalgesia and intestinal hypersensitivity determinations were performed and the impact of the probiotic on the inflammatory and intestinal barrier integrity was evaluated. Additionally, the gut microbiota composition was analyzed. Limosilactobacillus fermentum CECT5716 attenuated the anxiety-like behavior as well as the visceral hypersensitivity and referred pain. Moreover, this probiotic ameliorated the gut inflammatory status, re-establishing the altered intestinal permeability, reducing the mast cell degranulation and re-establishing the gut dysbiosis in experimental IBS. Therefore, our results suggest a potential use of Limosilactobacillus fermentum CECT5716 in clinical practice for the management of IBS patients.
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26
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Xu YXY, Zhang XZ, Weng MM, Cheng YK, Liu RD, Long SR, Wang ZQ, Cui J. Oral immunization of mice with recombinant Lactobacillus plantarum expressing a Trichinella spiralis galectin induces an immune protection against larval challenge. Parasit Vectors 2022; 15:475. [PMID: 36539832 PMCID: PMC9764493 DOI: 10.1186/s13071-022-05597-w] [Citation(s) in RCA: 11] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/30/2022] [Accepted: 11/23/2022] [Indexed: 12/24/2022] Open
Abstract
BACKGROUND Trichinella spiralis is an important foodborne parasite that presents a severe threat to food safety. The development of an anti-Trichinella vaccine is an important step towards controlling Trichinella infection in food animals and thus ensure meat safety. Trichinella spiralis galectin (Tsgal) is a novel protein that has been identified on the surface of this nematode. Recombinant Tsgal (rTsgal) was found to participate in larval invasion of intestinal epithelium cells (IECs), whereas anti-rTsgal antibodies impeded the invasion. METHODS The rTsgal/pSIP409- pgsA' plasmid was constructed and transferred into Lactobacillus plantarum strain NC8, following which the in vitro biological properties of rTsgal/NC8 were determined. Five groups of mice were orally immunized three times, with a 2-week interval between immunizations, with recombinant NC8-Tsgal, recombinant NC8-Tsgal + α-lactose, empty NC8, α-lactose only or phosphate-buffered saline (PBS), respectively. The vaccinated mice were infected orally with T. spiralis larvae 2 weeks following the last vaccination. Systemic and intestinal local mucosal immune responses and protection were also assessed, as were pathological changes in murine intestine and skeletal muscle. RESULTS rTsgal was expressed on the surface of NC8-Tsgal. Oral immunization of mice with rTsgal vaccine induced specific forms of serum immunoglobulin G (IgG), namely IgG1/IgG2a, as well as IgA and gut mucosal secretion IgA (sIgA). The levels of interferon gamma and interleukin-4 secreted by cells of the spleen, mesenteric lymph nodes, Peyer's patches and intestinal lamina propria were significantly elevated at 2-6 weeks after immunization, and continued to rise following challenge. Immunization of mice with the oral rTsgal vaccine produced a significant immune protection against T. spiralis challenge, as demonstrated by a 57.28% reduction in the intestinal adult worm burden and a 53.30% reduction in muscle larval burden, compared to the PBS control group. Immunization with oral rTsgal vaccine also ameliorated intestinal inflammation, as demonstrated by a distinct reduction in the number of gut epithelial goblet cells and mucin 2 expression level in T. spiralis-infected mice. Oral administration of lactose alone also reduced adult worm and larval burdens and relieved partially inflammation of intestine and muscles. CONCLUSIONS Immunization with oral rTsgal vaccine triggered an obvious gut local mucosal sIgA response and specific systemic Th1/Th2 immune response, as well as an evident protective immunity against T. spiralis challenge. Oral rTsgal vaccine provided a prospective approach for control of T. spiralis infection.
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Affiliation(s)
- Yang Xiu Yue Xu
- grid.207374.50000 0001 2189 3846Department of Parasitology, Medical College, Zhengzhou University, Zhengzhou, 450052 China
| | - Xin Zhuo Zhang
- grid.207374.50000 0001 2189 3846Department of Parasitology, Medical College, Zhengzhou University, Zhengzhou, 450052 China
| | - Min Min Weng
- grid.207374.50000 0001 2189 3846Department of Parasitology, Medical College, Zhengzhou University, Zhengzhou, 450052 China
| | - Yong Kang Cheng
- grid.207374.50000 0001 2189 3846Department of Parasitology, Medical College, Zhengzhou University, Zhengzhou, 450052 China
| | - Ruo Dan Liu
- grid.207374.50000 0001 2189 3846Department of Parasitology, Medical College, Zhengzhou University, Zhengzhou, 450052 China
| | - Shao Rong Long
- grid.207374.50000 0001 2189 3846Department of Parasitology, Medical College, Zhengzhou University, Zhengzhou, 450052 China
| | - Zhong Quan Wang
- grid.207374.50000 0001 2189 3846Department of Parasitology, Medical College, Zhengzhou University, Zhengzhou, 450052 China
| | - Jing Cui
- grid.207374.50000 0001 2189 3846Department of Parasitology, Medical College, Zhengzhou University, Zhengzhou, 450052 China
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27
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Bai SJ, Han LL, Liu RD, Long SR, Zhang X, Cui J, Wang ZQ. Oral vaccination of mice with attenuated Salmonella encoding Trichinella spiralis calreticulin and serine protease 1.1 confers protective immunity in BALB/c mice. PLoS Negl Trop Dis 2022; 16:e0010929. [PMID: 36445875 PMCID: PMC9707759 DOI: 10.1371/journal.pntd.0010929] [Citation(s) in RCA: 11] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/18/2022] [Accepted: 11/02/2022] [Indexed: 12/03/2022] Open
Abstract
BACKGROUND Trichinella spiralis is a foodborne parasitic nematode which is a serious risk to meat safety. Development of anti-Trichinella vaccine is needed to control Trichinella infection in food animals. In this study, two novel T. spiralis genes (calreticulin and serine protease 1.1) in combination were used to construct oral DNA vaccines, and their induced protective immunity was evaluated in a murine model. METHODOLOGY/PRINCIPAL FINDINGS TsCRT+TsSP1.1, TsCRT and TsSP1.1 DNA were transformed into attenuated Salmonella typhimurium ΔcyaSL1344. Oral vaccination of mice with TsCRT+TsSP1.1, TsCRT and TsSP1.1 DNA vaccines elicited a gut local mucosal sIgA response and systemic Th1/Th2 mixed response. Oral vaccination with TsCRT+TsSP1.1 induced obviously higher level of serum specific antibodies, mucosal sIgA and cellular immune response than either of single TsCRT or TsSP1.1 DNA vaccination. Oral vaccination of mice with TsCRT+TsSP1.1 exhibited a 53.4% reduction of enteral adult worms and a 46.05% reduction of muscle larvae, conferred a higher immune protection than either of individual TsCRT (44.28 and 42.46%) or TsSP1.1 DNA vaccine (35.43 and 29.29%) alone. Oral vaccination with TsCRT+TsSP1.1, TsCRT and TsSP1.1 also obviously ameliorated inflammation of intestinal mucosa and skeletal muscles of vaccinated mice after challenge. CONCLUSIONS TsCRT and TsSP1.1 might be regarded the novel potential targets for anti-Trichinella vaccines. Attenuated Salmonella-delivered DNA vaccine provided a prospective approach to control T. spiralis infection in food animals.
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Affiliation(s)
- Sheng Jie Bai
- Department of Parasitology, Medical College, Zhengzhou University, Zhengzhou, People’s Repuplic of China
| | - Lu Lu Han
- Department of Parasitology, Medical College, Zhengzhou University, Zhengzhou, People’s Repuplic of China
| | - Ruo Dan Liu
- Department of Parasitology, Medical College, Zhengzhou University, Zhengzhou, People’s Repuplic of China
| | - Shao Rong Long
- Department of Parasitology, Medical College, Zhengzhou University, Zhengzhou, People’s Repuplic of China
| | - Xi Zhang
- Department of Parasitology, Medical College, Zhengzhou University, Zhengzhou, People’s Repuplic of China
| | - Jing Cui
- Department of Parasitology, Medical College, Zhengzhou University, Zhengzhou, People’s Repuplic of China
| | - Zhong Quan Wang
- Department of Parasitology, Medical College, Zhengzhou University, Zhengzhou, People’s Repuplic of China
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Ruiz-Malagón AJ, Rodríguez-Sanchez MJ, Rodríguez-Sojo MJ, Vezza T, Pischel I, Algieri F, Rodríguez-Cabezas ME, Rodríguez-Nogales A, Gálvez J. Intestinal anti-inflammatory and visceral analgesic effects of a Serpylli herba extract in an experimental model of irritable bowel syndrome in rats. Front Pharmacol 2022; 13:967644. [PMID: 36120292 PMCID: PMC9479127 DOI: 10.3389/fphar.2022.967644] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/14/2022] [Accepted: 08/11/2022] [Indexed: 11/13/2022] Open
Abstract
Ethnopharmacological relevance:Serpylli herba extract (SHE), composed of the aerial parts of wild thyme (Thymus serpyllum L.) (Lamiaceae family), is traditionally used in Europe and North Africa to treat diarrhea, gastric ulcers, intestinal parasites and upper respiratory tract infections. Recently, SHE has generated a great interest for irritable bowel syndrome (IBS) management, probably due to its intestinal anti-inflammatory properties shown in experimental colitis and the fact that its active components could preserve the intestinal barrier integrity, which is altered in patients with IBS.Aim of study: We aimed to test the effects of a SHE in a rat experimental model resembling human IBS.Materials and methods: IBS was provoked by deoxycholic acid (DCA). Rats were then treated with SHE (100 mg/kg) or gabapentin (70 mg/kg) and different inflammatory and gut barrier integrity markers were evaluated. Moreover, several gut hypersensitivity and hyperalgesia determinations were performed.Results: SHE improved referred pain and visceral hypersensitivity. Additionally, SHE enhanced immune status by downregulating of the expression of the pro-inflammatory mediators Il-1β, Il-6, Ifn-γ, Tlr-4, and the inducible enzyme Cox-2, thus inducing visceral analgesia, and promoting the restore of the gut barrier function by upregulating the mucins Muc-2 and Muc-3. These anti-inflammatory effects could be related to its action on mast cells since it significantly inhibited the β-Hexosaminidase production in RBL-2H3 cells. Lastly, SHE also seems to modulate the serotonin pathway by restoring the altered expression of the 5-HT receptors Htr-3 and Htr-4.Conclusion: SHE could be considered a potential new treatment for IBS, since it ameliorates hypersensitivity, visceral hyperalgesia, and inflammation. These beneficial effects may be due to the inhibition of mast cells degranulation and serotonin pathway.
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Affiliation(s)
- Antonio Jesús Ruiz-Malagón
- Center for Biomedical Research (CIBM), Department of Pharmacology, University of Granada, Granada, Spain
- Instituto de Investigación Biosanitaria de Granada (ibs.GRANADA), Granada, Spain
| | - María José Rodríguez-Sanchez
- Center for Biomedical Research (CIBM), Department of Pharmacology, University of Granada, Granada, Spain
- Instituto de Investigación Biosanitaria de Granada (ibs.GRANADA), Granada, Spain
- Servicio de Digestivo, Hospital Universitario Virgen de las Nieves, Granada, Spain
| | - María Jesús Rodríguez-Sojo
- Center for Biomedical Research (CIBM), Department of Pharmacology, University of Granada, Granada, Spain
- Instituto de Investigación Biosanitaria de Granada (ibs.GRANADA), Granada, Spain
| | - Teresa Vezza
- Center for Biomedical Research (CIBM), Department of Pharmacology, University of Granada, Granada, Spain
- Instituto de Investigación Biosanitaria de Granada (ibs.GRANADA), Granada, Spain
| | - Ivo Pischel
- Centre for Pharmacognosy and Phytotherapy, UCL School of Pharmacy, University of London, London, United Kingdom
| | - Francesca Algieri
- Center for Biomedical Research (CIBM), Department of Pharmacology, University of Granada, Granada, Spain
- *Correspondence: Francesca Algieri, ; María Elena Rodríguez-Cabezas,
| | - María Elena Rodríguez-Cabezas
- Center for Biomedical Research (CIBM), Department of Pharmacology, University of Granada, Granada, Spain
- Instituto de Investigación Biosanitaria de Granada (ibs.GRANADA), Granada, Spain
- *Correspondence: Francesca Algieri, ; María Elena Rodríguez-Cabezas,
| | - Alba Rodríguez-Nogales
- Center for Biomedical Research (CIBM), Department of Pharmacology, University of Granada, Granada, Spain
- Instituto de Investigación Biosanitaria de Granada (ibs.GRANADA), Granada, Spain
- Servicio de Digestivo, Hospital Universitario Virgen de las Nieves, Granada, Spain
| | - Julio Gálvez
- Center for Biomedical Research (CIBM), Department of Pharmacology, University of Granada, Granada, Spain
- Instituto de Investigación Biosanitaria de Granada (ibs.GRANADA), Granada, Spain
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Madrid, Spain
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López-Gómez L, Antón J, López-Tofiño Y, Pomana B, Uranga JA, Abalo R. Effects of Commercial Probiotics on Colonic Sensitivity after Acute Mucosal Irritation. INTERNATIONAL JOURNAL OF ENVIRONMENTAL RESEARCH AND PUBLIC HEALTH 2022; 19:ijerph19116485. [PMID: 35682075 PMCID: PMC9180892 DOI: 10.3390/ijerph19116485] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 03/15/2022] [Revised: 05/23/2022] [Accepted: 05/24/2022] [Indexed: 12/10/2022]
Abstract
Gastrointestinal pathologies associated with abdominal pain, such as irritable bowel syndrome or inflammatory bowel disease, lack sufficiently effective treatments. In our study we have used a rat model of visceral pain (72 animals; n = 8–13 per experimental group) to analyze the consequences of intracolonic administration of the irritant acetic acid on visceral sensitivity, histology of the colonic wall, and inflammatory response. Moreover, we have studied the possible beneficial effects of a pretreatment with a commercial probiotic (Actimel®). Contrary to expectations, acetic acid application (7 cm proximal to the anus) decreased the nociceptive response to intracolonic mechanical stimulation, with a slight increase in the histological damage of colonic mucosa. The intensity of these changes depended on the concentration (4% or 0.6%) and the time of application (30 or 60 min). Pretreatment with probiotics (by daily gavage, for 1 week) normalized the values obtained in the visceral sensitivity test but revealed an increase in the number of macrophages. These results suggest a possible activation of inhibitory mechanisms early after colonic irritation, not previously described (which need further experimental confirmation), and the ability of probiotics to normalize the effects of acetic acid. In addition, pretreatment with probiotics has a direct effect on immune functions, stimulating macrophagic activity.
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Affiliation(s)
- Laura López-Gómez
- Department of Basic Health Sciences, University Rey Juan Carlos (URJC), 28922 Alcorcón, Spain; (L.L.-G.); (J.A.); (Y.L.-T.); (B.P.)
- High Performance Research Group in Physiopathology and Pharmacology of the Digestive System (NeuGut-URJC), University Rey Juan Carlos, 28922 Alcorcón, Spain
| | - Jaime Antón
- Department of Basic Health Sciences, University Rey Juan Carlos (URJC), 28922 Alcorcón, Spain; (L.L.-G.); (J.A.); (Y.L.-T.); (B.P.)
| | - Yolanda López-Tofiño
- Department of Basic Health Sciences, University Rey Juan Carlos (URJC), 28922 Alcorcón, Spain; (L.L.-G.); (J.A.); (Y.L.-T.); (B.P.)
- High Performance Research Group in Physiopathology and Pharmacology of the Digestive System (NeuGut-URJC), University Rey Juan Carlos, 28922 Alcorcón, Spain
| | - Bianca Pomana
- Department of Basic Health Sciences, University Rey Juan Carlos (URJC), 28922 Alcorcón, Spain; (L.L.-G.); (J.A.); (Y.L.-T.); (B.P.)
| | - José A. Uranga
- Department of Basic Health Sciences, University Rey Juan Carlos (URJC), 28922 Alcorcón, Spain; (L.L.-G.); (J.A.); (Y.L.-T.); (B.P.)
- High Performance Research Group in Physiopathology and Pharmacology of the Digestive System (NeuGut-URJC), University Rey Juan Carlos, 28922 Alcorcón, Spain
- Correspondence: (J.A.U.); (R.A.)
| | - Raquel Abalo
- Department of Basic Health Sciences, University Rey Juan Carlos (URJC), 28922 Alcorcón, Spain; (L.L.-G.); (J.A.); (Y.L.-T.); (B.P.)
- High Performance Research Group in Physiopathology and Pharmacology of the Digestive System (NeuGut-URJC), University Rey Juan Carlos, 28922 Alcorcón, Spain
- Associated I+D+i Unit to the Institute of Medicinal Chemistry (IQM), Scientific Research Superior Council (CSIC), 28006 Madrid, Spain
- Working Group of Basic Sciences in Pain and Analgesia of the Spanish Society of Pain, 28046 Madrid, Spain
- Correspondence: (J.A.U.); (R.A.)
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30
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Li J, Tang H, Tu W. Mechanism of dexmedetomidine preconditioning on spinal cord analgesia in rats with functional chronic visceral pain. Acta Cir Bras 2022; 37:e370203. [PMID: 35507967 PMCID: PMC9064187 DOI: 10.1590/acb370203] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/06/2021] [Accepted: 01/03/2022] [Indexed: 11/22/2022] Open
Abstract
Purpose: To analyze the effect and mechanism of dexmedetomidine (DEX) analgesia pretreatment on functional chronic visceral pain in rats. Methods: Rats were divided into six groups: W1, W2, W3, W4, W5, and W6. The behavioral changes and electrophysiological indexes of rats in each group before and after DEX treatment were detected. Results: The levels of abdominal withdrawal reflex (AWR) in W5 and W6 groups were significantly lower than those in group W3, while the levels of thermal withdrawal latency (TWL) and mechanical withdrawal threshold (MWT) were significantly higher than those in group W3 (p < 0.05). The electromyographic signals of W1, W5, and W6 groups showed little fluctuation, while those of groups W2, W3, and W4 showed obvious fluctuation. TLR4 mRNA expression, IRF3, P65, and phosphorylation levels in W4, W5, and W6 groups were significantly lower than those in group W2 (p < 0.05). Conclusions: Dexmedetomidine epidural anesthesia pretreatment could significantly inhibit visceral pain response in rats with functional chronic visceral pain, and its mechanism was related to the activation of TLR4 in spinal dorsal horn tissue of rats and the activation inhibition of IRF3 and P65 in the downstream key signals.
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Affiliation(s)
- Jun Li
- Southern Medical University, China
| | - Huizhong Tang
- People’s Hospital of Guangxi Zhuang Autonomous Region, China
| | - Weifeng Tu
- General Hospital of Southern Theatre Command, China
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31
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Inczefi O, Bacsur P, Resál T, Keresztes C, Molnár T. The Influence of Nutrition on Intestinal Permeability and the Microbiome in Health and Disease. Front Nutr 2022; 9:718710. [PMID: 35548572 PMCID: PMC9082752 DOI: 10.3389/fnut.2022.718710] [Citation(s) in RCA: 30] [Impact Index Per Article: 10.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/01/2021] [Accepted: 02/22/2022] [Indexed: 01/09/2023] Open
Abstract
The leakage of the intestinal barrier and the disruption of the gut microbiome are increasingly recognized as key factors in different pathophysiological conditions, such as irritable bowel syndrome (IBS), inflammatory bowel disease (IBD), chronic liver diseases, obesity, diabetes mellitus, types of cancer, and neuropsychiatric disorders. In this study, the mechanisms leading to dysbiosis and "leaky gut" are reviewed, and a short summary of the current knowledge regarding different diseases is provided. The simplest way to restore intestinal permeability and the microbiota could be ideal nutrition. Further therapeutic options are also available, such as the administration of probiotics or postbiotics or fecal microbiota transplantation.
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Affiliation(s)
- Orsolya Inczefi
- Department of Gastroenterology, Albert Szent-Györgyi Medical School, University of Szeged, Szeged, Hungary
| | - Péter Bacsur
- Department of Gastroenterology, Albert Szent-Györgyi Medical School, University of Szeged, Szeged, Hungary
| | - Tamás Resál
- Department of Gastroenterology, Albert Szent-Györgyi Medical School, University of Szeged, Szeged, Hungary
| | - Csilla Keresztes
- Department for Medical Communication and Translation Studies, Albert Szent-Györgyi Medical School, University of Szeged, Szeged, Hungary
| | - Tamás Molnár
- Department of Gastroenterology, Albert Szent-Györgyi Medical School, University of Szeged, Szeged, Hungary,*Correspondence: Tamás Molnár,
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32
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Yang W, Yang X, Cai X, Zhou Z, Yao H, Song X, Zhao T, Xiong P. The Prevalence of Irritable Bowel Syndrome Among Chinese University Students: A Systematic Review and Meta-Analysis. Front Public Health 2022; 10:864721. [PMID: 35493361 PMCID: PMC9051230 DOI: 10.3389/fpubh.2022.864721] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/28/2022] [Accepted: 03/14/2022] [Indexed: 11/26/2022] Open
Abstract
Background Irritable bowel syndrome (IBS) has become a common public health issue among university students, impairing their physical and mental health. This meta-analysis aimed to examine the pooled prevalence of IBS and its associated factors among Chinese university students. Methods Databases of PubMed, EMBASE, MEDLINE (via EBSCO), CINAHL (via EBSCO), Wan Fang, CNKI and Weipu (via VIP) were systematically searched from inception date to May 31, 2021. Meta-analysis was performed using random-effects models. Meta-regression and subgroup analysis were used to detect the potential source of heterogeneity. Key Results A total of 22 cross-sectional studies (14 were in Chinese and 8 were in English) with 33,166 Chinese university students were included. The pooled prevalence of IBS was estimated as 11.89% (95% CI = 8.06%, 16.35%). The prevalence was 10.50% (95% CI = 6.80%, 15.87%) in Rome II criteria, 12.00% (95% CI = 8.23%, 17.17%) in Rome III criteria, and 3.66% (95% CI = 2.01%, 6.60%) in Rome IV criteria. The highest prevalence of IBS was 17.66% (95% CI = 7.37%, 36.64%) in North China, and the lowest was 3.18% (95% CI = 1.28%, 7.68%) in South China. Subgroup analyses indicated that gender, major, anxiety and depression symptoms, drinking and smoking behaviors were significantly associated with the prevalence of IBS. Meta-regression analyses suggested that region influenced prevalence estimates for IBS. Conclusions and Inferences This meta-analysis illustrated that IBS is very common in Chinese university students. Regular screening, effective prevention, and appropriate treatments should be implemented to reduce the risk of IBS in this population. More future studies should be conducted in Northeastern and Southwestern parts of China.
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Affiliation(s)
- Weixin Yang
- Department of Public Health and Preventive Medicine, School of Medicine, Jinan University, Guangzhou, China
| | - Xiao Yang
- Department of Public Health and Preventive Medicine, School of Medicine, Jinan University, Guangzhou, China
| | - Xianghao Cai
- Department of Public Health and Preventive Medicine, School of Medicine, Jinan University, Guangzhou, China
| | - Zhuoren Zhou
- Department of Public Health and Preventive Medicine, School of Medicine, Jinan University, Guangzhou, China
| | - Huan Yao
- Department of Public Health and Preventive Medicine, School of Medicine, Jinan University, Guangzhou, China
| | - Xingrong Song
- Department of Anesthesiology, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou, China
| | - Tianyun Zhao
- Department of Anesthesiology, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou, China
| | - Peng Xiong
- Department of Public Health and Preventive Medicine, School of Medicine, Jinan University, Guangzhou, China
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33
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Curci F, Corbo F, Clodoveo ML, Salvagno L, Rosato A, Corazza I, Budriesi R, Micucci M, Mattioli LB. Polyphenols from Olive-Mill Wastewater and Biological Activity: Focus on Irritable Bowel Syndrome. Nutrients 2022; 14:nu14061264. [PMID: 35334922 PMCID: PMC8952826 DOI: 10.3390/nu14061264] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/31/2022] [Revised: 03/09/2022] [Accepted: 03/11/2022] [Indexed: 02/04/2023] Open
Abstract
Waste represents a cost for companies, in particular for agro-food companies, which can become a resource as a secondary material. In this work, we examine three products of olive-oil waste water, named MOMAST® (Plus30, PW25, and HY100). Based on the chemical composition, obtained with different methods, we hypothesized a possible application as food supplements in irritable bowel syndrome (IBS). We therefore studied MOMASTs on some targets linked to this pathology: antioxidant action and spontaneous and induced intestinal contractility of the ileum and colon. Plus30, which showed a more promising biological of activity also for its oleuropein content, was characterized by an interesting action against some microorganisms. The results highlighted the ability of Plus30 to modulate spontaneous and induced contractility, to exert a good antioxidant action, and to significantly act on various microorganisms. These effects are synergistic in the presence of antibiotics. In conclusion, we can confirm that Plus30 could be a great candidate as a food supplement in patients with IBS.
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Affiliation(s)
- Francesca Curci
- Department of Pharmacy-Drug Sciences, University of Bari “Aldo Moro”, 70125 Bari, Italy; (F.C.); (F.C.); (L.S.); (A.R.)
| | - Filomena Corbo
- Department of Pharmacy-Drug Sciences, University of Bari “Aldo Moro”, 70125 Bari, Italy; (F.C.); (F.C.); (L.S.); (A.R.)
| | - Maria Lisa Clodoveo
- Interdisciplinary Department of Medicine, School of Medicine, University of Bari “Aldo Moro”, 70124 Bari, Italy;
| | - Lara Salvagno
- Department of Pharmacy-Drug Sciences, University of Bari “Aldo Moro”, 70125 Bari, Italy; (F.C.); (F.C.); (L.S.); (A.R.)
| | - Antonio Rosato
- Department of Pharmacy-Drug Sciences, University of Bari “Aldo Moro”, 70125 Bari, Italy; (F.C.); (F.C.); (L.S.); (A.R.)
| | - Ivan Corazza
- Department of Experimental Diagnostic and Specialty Medicine (DIMES), Alma Mater Studiorum University of Bologna, 40138 Bologna, Italy;
| | - Roberta Budriesi
- Department of Pharmacy and Biotechnology, Food Chemistry and Nutraceutical Lab, Alma Mater Studiorum-University of Bologna, 40126 Bologna, Italy;
- Correspondence: ; Tel.: +39-051-209-9721
| | - Matteo Micucci
- Department of Biomolecular Sciences, University of Urbino “Carlo Bo”, 61029 Urbino, Italy;
- UniCamillus-Saint Camillus International University of Health Sciences, Via di Sant’Alessandro, 800131 Rome, Italy
| | - Laura Beatrice Mattioli
- Department of Pharmacy and Biotechnology, Food Chemistry and Nutraceutical Lab, Alma Mater Studiorum-University of Bologna, 40126 Bologna, Italy;
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Tao E, Zhu Z, Hu C, Long G, Chen B, Guo R, Fang M, Jiang M. Potential Roles of Enterochromaffin Cells in Early Life Stress-Induced Irritable Bowel Syndrome. Front Cell Neurosci 2022; 16:837166. [PMID: 35370559 PMCID: PMC8964523 DOI: 10.3389/fncel.2022.837166] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/16/2021] [Accepted: 02/09/2022] [Indexed: 12/04/2022] Open
Abstract
Irritable bowel syndrome (IBS) is one of the most common functional gastrointestinal disorders, also known as disorders of the gut–brain interaction; however, the pathophysiology of IBS remains unclear. Early life stress (ELS) is one of the most common risk factors for IBS development. However, the molecular mechanisms by which ELS induces IBS remain unclear. Enterochromaffin cells (ECs), as a prime source of peripheral serotonin (5-HT), play a pivotal role in intestinal motility, secretion, proinflammatory and anti-inflammatory effects, and visceral sensation. ECs can sense various stimuli and microbiota metabolites such as short-chain fatty acids (SCFAs) and secondary bile acids. ECs can sense the luminal environment and transmit signals to the brain via exogenous vagal and spinal nerve afferents. Increasing evidence suggests that an ECs-5-HT signaling imbalance plays a crucial role in the pathogenesis of ELS-induced IBS. A recent study using a maternal separation (MS) animal model mimicking ELS showed that MS induced expansion of intestinal stem cells and their differentiation toward secretory lineages, including ECs, leading to ECs hyperplasia, increased 5-HT production, and visceral hyperalgesia. This suggests that ELS-induced IBS may be associated with increased ECs-5-HT signaling. Furthermore, ECs are closely related to corticotropin-releasing hormone, mast cells, neuron growth factor, bile acids, and SCFAs, all of which contribute to the pathogenesis of IBS. Collectively, ECs may play a role in the pathogenesis of ELS-induced IBS. Therefore, this review summarizes the physiological function of ECs and focuses on their potential role in the pathogenesis of IBS based on clinical and pre-clinical evidence.
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Affiliation(s)
- Enfu Tao
- Endoscopy Center and Gastrointestinal Laboratory, Children’s Hospital, Zhejiang University School of Medicine, National Clinical Research Center for Child Health, National Children’s Regional Medical Center, Hangzhou, China
- Wenling Maternal and Child Health Care Hospital, Wenling, China
| | - Zhenya Zhu
- Endoscopy Center and Gastrointestinal Laboratory, Children’s Hospital, Zhejiang University School of Medicine, National Clinical Research Center for Child Health, National Children’s Regional Medical Center, Hangzhou, China
| | - Chenmin Hu
- Endoscopy Center and Gastrointestinal Laboratory, Children’s Hospital, Zhejiang University School of Medicine, National Clinical Research Center for Child Health, National Children’s Regional Medical Center, Hangzhou, China
| | - Gao Long
- Endoscopy Center and Gastrointestinal Laboratory, Children’s Hospital, Zhejiang University School of Medicine, National Clinical Research Center for Child Health, National Children’s Regional Medical Center, Hangzhou, China
| | - Bo Chen
- Endoscopy Center and Gastrointestinal Laboratory, Children’s Hospital, Zhejiang University School of Medicine, National Clinical Research Center for Child Health, National Children’s Regional Medical Center, Hangzhou, China
| | - Rui Guo
- Endoscopy Center and Gastrointestinal Laboratory, Children’s Hospital, Zhejiang University School of Medicine, National Clinical Research Center for Child Health, National Children’s Regional Medical Center, Hangzhou, China
| | - Marong Fang
- Institute of Neuroscience and Gastrointestinal Laboratory, Children’s Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | - Mizu Jiang
- Department of Gastroenterology, Children’s Hospital, Zhejiang University School of Medicine, National Clinical Research Center for Child Health, National Children’s Regional Medical Center, Hangzhou, China
- *Correspondence: Mizu Jiang,
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Alesci A, Pergolizzi S, Fumia A, Calabrò C, Lo Cascio P, Lauriano ER. Mast cells in goldfish (
Carassius auratus
) gut: Immunohistochemical characterization. ACTA ZOOL-STOCKHOLM 2022. [DOI: 10.1111/azo.12417] [Citation(s) in RCA: 16] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Affiliation(s)
- Alessio Alesci
- Department of Chemical, Biological, Pharmaceutical and Environmental Sciences University of Messina Messina Italy
| | - Simona Pergolizzi
- Department of Chemical, Biological, Pharmaceutical and Environmental Sciences University of Messina Messina Italy
| | - Angelo Fumia
- Department of Clinical and Experimental Medicine University of Messina Messina Italy
| | - Concetta Calabrò
- Department of Chemical, Biological, Pharmaceutical and Environmental Sciences University of Messina Messina Italy
| | - Patrizia Lo Cascio
- Department of Chemical, Biological, Pharmaceutical and Environmental Sciences University of Messina Messina Italy
| | - Eugenia Rita Lauriano
- Department of Chemical, Biological, Pharmaceutical and Environmental Sciences University of Messina Messina Italy
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36
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Li R, Chen S, Gu X, An S, Wang Z. Role of the nuclear receptor subfamily 4a in mast cells in the development of irritable bowel syndrome. Comput Struct Biotechnol J 2022; 20:1198-1207. [PMID: 35317226 PMCID: PMC8907967 DOI: 10.1016/j.csbj.2022.02.017] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/19/2021] [Revised: 02/17/2022] [Accepted: 02/19/2022] [Indexed: 11/15/2022] Open
Abstract
The activation of mast cells (MCs) and mediator release are closely related to the pathophysiology of irritable bowel syndrome (IBS). However, the exact underlying mechanisms are still not completely understood. The nuclear receptor subfamily 4a (Nr4a) is a family of orphan nuclear receptors implicated in regulating MC activation, degranulation, cytokine/chemokine synthesis and release. Acute and chronic stress trigger hypothalamic–pituitaryadrenal axis (HPA) activation to induce the release of corticotropin-releasing hormone (CRH), resulting in MC activation and induction of the Nr4a family. Our newest data showed that Nr4a members were specially over-expressed in colonic MCs of the chronic water-avoidance stress (WAS)-induced visceral hyperalgesia mice, suggesting that Nr4a members might be involved in the pathophysiology of visceral hypersensitivity. In this review, we highlight the present knowledge on roles of Nr4a members in the activation of MCs and the pathophysiology of IBS, and discuss signaling pathways that modulate the activation of Nr4a family members. We propose that a better understanding of Nr4a members and their modulators may facilitate the development of more selective and effective therapies to treat IBS patients.
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Affiliation(s)
| | | | | | - Shuhong An
- Corresponding authors at: Department of Human Anatomy, Shandong First Medical University & Shandong Academy of Medical Sciences, 2 Ying Sheng Dong Lu, Taian 271000, China.
| | - Zhaojin Wang
- Corresponding authors at: Department of Human Anatomy, Shandong First Medical University & Shandong Academy of Medical Sciences, 2 Ying Sheng Dong Lu, Taian 271000, China.
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37
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Maioli TU, Trindade LM, Souza A, Torres L, Andrade MER, Cardoso VN, Generoso SV. Non-pharmacologic strategies for the management of intestinal inflammation. Biomed Pharmacother 2021; 145:112414. [PMID: 34808552 DOI: 10.1016/j.biopha.2021.112414] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/29/2021] [Revised: 10/28/2021] [Accepted: 11/05/2021] [Indexed: 02/06/2023] Open
Abstract
Inflammatory bowel diseases, irritable bowel syndrome, and mucositis are characterized by intestinal inflammation, but vary according to their pathological mechanisms, severity, location, and etiology. Significant intestinal inflammation that occurs in these diseases induces weight loss, nutritional depletion, and gastrointestinal tract dysfunction. Nutritional support is important in alleviating symptoms and improving patients' quality of life. In this review, we summarize some nutritional components used to manage intestinal disorders. These include fatty acids, probiotics, parabiotics, postbiotics, prebiotics, synbiotics, and low FODMAP (LFD) diets. These components and LFD diets have been studied and clinical trials have been designed to develop new strategies to alleviate intestinal inflammation and improve the quality of life. Clinical trials on their use in intestinal inflammation do not allow firm conclusions to be drawn mainly because of the heterogeneity of the dose used and the study design or their inconclusive results. However, in the majority of cases, the use of omega-3, probiotics, parabiotics, postbiotics, prebiotics, synbiotics, and LFD improve the health.
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Affiliation(s)
- Tatiani Uceli Maioli
- Programa de Pós-Graduação em Nutrição e Saúde, Departamento de Nutrição, Universidade Federal de Minas Gerais, Brazil
| | - Luísa Martins Trindade
- Programa de Pós-Graduação em Ciência de Alimentos, Faculdade de Farmácia, Universidade Federal de Minas Gerais, Brazil
| | - Aline Souza
- Programa de Pós-Graduação em Nutrição e Saúde, Departamento de Nutrição, Universidade Federal de Minas Gerais, Brazil
| | - Lícia Torres
- Programa de Pós-Graduação em Bioquímica e Imunologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Brazil
| | | | | | - Simone Vasconcelos Generoso
- Programa de Pós-Graduação em Nutrição e Saúde, Departamento de Nutrição, Universidade Federal de Minas Gerais, Brazil.
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Retornaz F, Grino M, Vanhaudenhuyse A, Chiche L, Stavris C, Bennani M, Faymonville ME, Alitta A. Hypnotherapy in Treatment of Mastocytosis: A Prospective Study. Int J Clin Exp Hypn 2021; 69:468-482. [PMID: 34474650 DOI: 10.1080/00207144.2021.1965484] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/12/2022]
Abstract
Mastocytosis is an orphan disease associated with many systemic symptoms, chronic handicap, and potentially marked social consequences despite improved therapies. In this study, the authors aimed to measure the effect of 2 hypnosis sessions on mastocytosis symptoms in a clinical setting. Questionnaires (pain, flushes, energy, digestive symptoms, quality of life, perceived symptom severity, and global impression of change) were completed pre- and posthypnosis intervention. Data from 20 patients were analyzed (mean age: 53.3 years, 75% female). Compared to baseline assessment, patients exhibited a significant improvement immediately after the first and second hypnosis sessions with regard to the number of days with abdominal pain, abdominal pain intensity and fatigue (p = .03 and p = .005; p = .05 and p = .02; p = .034, and p = .039, respectively). Perceived severity of symptoms was significantly improved throughout the study (p = .0075). Long-term improvement in global impression of change was observed in half the responders (8/16). Patients with mastocytosis had an improvement in disabling symptoms with the impact of hypnotic intervention persisting at 1 month. Several patients experienced long-term improvement.
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Affiliation(s)
- Frédérique Retornaz
- Unité de Soins et de Recherche en Médecine Interne et Maladies Infectieuses, Hôpital Européen, Marseille, France
| | - Michel Grino
- Département de Recherche Clinique, Centre Gérontologique Départemental, Marseille, France.,C2VN, Aix Marseille Univ., INSERM, INRAE, France
| | - Audrey Vanhaudenhuyse
- Département d'Algologie, CHU De Liège-B35, and Sensation and Perception Research Group, GIGA Consciousness, University of Liège, Domaine Universitaire du Sart Tilman, Belgium
| | - Laurent Chiche
- Unité de Soins et de Recherche en Médecine Interne et Maladies Infectieuses, Hôpital Européen, Marseille, France
| | - Chloé Stavris
- Unité de Soins et de Recherche en Médecine Interne et Maladies Infectieuses, Hôpital Européen, Marseille, France
| | - Myriam Bennani
- Unité de Soins et de Recherche en Médecine Interne et Maladies Infectieuses, Hôpital Européen, Marseille, France
| | - Marie Elisabeth Faymonville
- Département d'Algologie, CHU De Liège-B35, and Sensation and Perception Research Group, GIGA Consciousness, University of Liège, Domaine Universitaire du Sart Tilman, Belgium
| | - Anouk Alitta
- Unité de Soins et de Recherche en Médecine Interne et Maladies Infectieuses, Hôpital Européen, Marseille, France
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Nutraceuticals in Immune Function. Molecules 2021; 26:molecules26175310. [PMID: 34500743 PMCID: PMC8433708 DOI: 10.3390/molecules26175310] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/03/2021] [Accepted: 08/24/2021] [Indexed: 01/01/2023] Open
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Friesen C, Colombo J, Schurman J. Update on the Role of Allergy in Pediatric Functional Abdominal Pain Disorders: A Clinical Perspective. Nutrients 2021; 13:2056. [PMID: 34208479 PMCID: PMC8235503 DOI: 10.3390/nu13062056] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/13/2021] [Revised: 06/07/2021] [Accepted: 06/12/2021] [Indexed: 11/16/2022] Open
Abstract
Both functional abdominal pain disorders (FAPDs) and food allergies are relatively common in children and adolescents, and most studies report an association between FAPDs and allergic conditions. FAPDs share pathophysiologic processes with allergies, including both immune and psychological processes interacting with the microbiome. No conclusive data are implicating IgE-mediated reactions to foods in FAPDs; however, there may be patients who have IgE reactions localized to the gastrointestinal mucosa without systemic symptoms that are not identified by common tests. In FAPDs, the data appears stronger for aeroallergens than for foods. It also remains possible that food antigens initiate an IgG reaction that promotes mast cell activation. If a food allergen is identified, the management involves eliminating the specific food from the diet. In the absence of systemic allergic symptoms or oral allergy syndrome, it appears unlikely that allergic triggers for FAPDs can be reliably identified by standard testing. Medications used to blunt allergic reactions or symptomatically treat allergic reactions may be useful in FAPDs. The purpose of the current manuscript is to review the current literature regarding the role of allergy in FAPDs from a clinical perspective, including how allergy may fit in the current model of FAPDs.
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Affiliation(s)
- Craig Friesen
- Division of Gastroenterology, Hepatology and Nutrition, Children’s Mercy Kansas City, School of Medicine, University of Missouri-Kansas City, Kansas City, MO 64108, USA; (J.C.); (J.S.)
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Rohrhofer J, Zwirzitz B, Selberherr E, Untersmayr E. The Impact of Dietary Sphingolipids on Intestinal Microbiota and Gastrointestinal Immune Homeostasis. Front Immunol 2021; 12:635704. [PMID: 34054805 PMCID: PMC8160510 DOI: 10.3389/fimmu.2021.635704] [Citation(s) in RCA: 34] [Impact Index Per Article: 8.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/30/2020] [Accepted: 04/23/2021] [Indexed: 12/12/2022] Open
Abstract
The large surfaces of gastrointestinal (GI) organs are well adapted to their diverse tasks of selective nutritional uptake and defense against the external environment. To maintain a functional balance, a vast number of immune cells is located within the mucosa. A strictly regulated immune response is required to impede constant inflammation and to maintain barrier function. An increasing prevalence of GI diseases has been reported in Western societies over the past decades. This surge in GI disorders has been linked to dietary changes followed by an imbalance of the gut microbiome, leading to a chronic, low grade inflammation of the gut epithelium. To counteract the increasing health care costs associated with diseases, it is paramount to understand the mechanisms driving immuno-nutrition, the associations between nutritional compounds, the commensal gut microbiota, and the host immune response. Dietary compounds such as lipids, play a central role in GI barrier function. Bioactive sphingolipids (SLs), e.g. sphingomyelin (SM), sphingosine (Sph), ceramide (Cer), sphingosine-1- phosphate (S1P) and ceramide-1-phosphate (C1P) may derive from dietary SLs ingested through the diet. They are not only integral components of cell membranes, they additionally modulate cell trafficking and are precursors for mediators and second messenger molecules. By regulating intracellular calcium levels, cell motility, cell proliferation and apoptosis, SL metabolites have been described to influence GI immune homeostasis positively and detrimentally. Furthermore, dietary SLs are suggested to induce a shift in the gut microbiota. Modes of action range from competing with the commensal bacteria for intestinal cell attachment to prevention from pathogen invasion by regulating innate and immediate defense mechanisms. SL metabolites can also be produced by gut microorganisms, directly impacting host metabolic pathways. This review aims to summarize recent findings on SL signaling and functional variations of dietary SLs. We highlight novel insights in SL homeostasis and SL impact on GI barrier function, which is directly linked to changes of the intestinal microbiota. Knowledge gaps in current literature will be discussed to address questions relevant for understanding the pivotal role of dietary SLs on chronic, low grade inflammation and to define a balanced and healthy diet for disease prevention and treatment.
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Affiliation(s)
- Johanna Rohrhofer
- Gastrointestinal Immunology Group, Institute of Pathophysiology and Allergy Research, Center for Pathophysiology, Infectiology and Immunology, Medical University of Vienna, Vienna, Austria
| | - Benjamin Zwirzitz
- Unit of Food Microbiology, Institute of Food Safety, Food Technology and Veterinary Public Health, University of Veterinary Medicine, Vienna, Austria
| | - Evelyne Selberherr
- Unit of Food Microbiology, Institute of Food Safety, Food Technology and Veterinary Public Health, University of Veterinary Medicine, Vienna, Austria
| | - Eva Untersmayr
- Gastrointestinal Immunology Group, Institute of Pathophysiology and Allergy Research, Center for Pathophysiology, Infectiology and Immunology, Medical University of Vienna, Vienna, Austria
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Ma J, Wang FY, Xu L, Wang YF, Tang XD. Mechanism of mast cell-mediated COX2-PGE2-Eps signaling pathway in visceral hypersensitivity in irritable bowel syndrome. Shijie Huaren Xiaohua Zazhi 2021; 29:306-311. [DOI: 10.11569/wcjd.v29.i6.306] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
Irritable bowel syndrome (IBS) is a functional gastrointestinal disorder (FGID) whose pathophysiological mechanism is complex, involving genetic factors, psychosocial factors, low-grade mucosal inflammation, changes in the intestinal barrier, bacterial flora disorder, neuroimmune abnormalities, and high visceral sensitivity. In recent years, the mechanism of visceral hypersensitivity in IBS has become a hot research topic. Mast cells (MCs) are a group of immune cells that are distributed in the central nervous system and digestive system. The COX2-PGE2-Eps signaling pathway plays a major role in the visceral hypersensitivity in IBS, from peripheral sensitization to central sensitization, which provides a new idea for further clarifying the pathological mechanism of IBS.
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Affiliation(s)
- Jing Ma
- Graduate School of China Academy of Chinese Medical Sciences, Beijing 100000, China
| | - Feng-Yun Wang
- Department of Spleen and Stomach, Xiyuan Hospital of China Academy of Chinese Medical Sciences, Beijing 100091, China
| | - Lin Xu
- Graduate School of China Academy of Chinese Medical Sciences, Beijing 100000, China
| | - Yi-Fan Wang
- Peking University Traditional Chinese Medicine Clinical Medical School, Beijing 100091, China
| | - Xu-Dong Tang
- China Academy of Chinese Medical Sciences, Beijing 100091, China
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Effects of Coffee and Its Components on the Gastrointestinal Tract and the Brain-Gut Axis. Nutrients 2020; 13:nu13010088. [PMID: 33383958 PMCID: PMC7824117 DOI: 10.3390/nu13010088] [Citation(s) in RCA: 59] [Impact Index Per Article: 11.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/09/2020] [Revised: 12/23/2020] [Accepted: 12/25/2020] [Indexed: 02/06/2023] Open
Abstract
Coffee is one of the most popular beverages consumed worldwide. Roasted coffee is a complex mixture of thousands of bioactive compounds, and some of them have numerous potential health-promoting properties that have been extensively studied in the cardiovascular and central nervous systems, with relatively much less attention given to other body systems, such as the gastrointestinal tract and its particular connection with the brain, known as the brain–gut axis. This narrative review provides an overview of the effect of coffee brew; its by-products; and its components on the gastrointestinal mucosa (mainly involved in permeability, secretion, and proliferation), the neural and non-neural components of the gut wall responsible for its motor function, and the brain–gut axis. Despite in vitro, in vivo, and epidemiological studies having shown that coffee may exert multiple effects on the digestive tract, including antioxidant, anti-inflammatory, and antiproliferative effects on the mucosa, and pro-motility effects on the external muscle layers, much is still surprisingly unknown. Further studies are needed to understand the mechanisms of action of certain health-promoting properties of coffee on the gastrointestinal tract and to transfer this knowledge to the industry to develop functional foods to improve the gastrointestinal and brain–gut axis health.
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