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Rivera-Arce LA, Cruz ML, Rodriguez-Cintron U, Torres-Pirela JP, Appleyard CB. Implication of the enteric glia in the IBS-like colonic inflammation associated with endometriosis. BMC Womens Health 2024; 24:647. [PMID: 39707348 PMCID: PMC11662455 DOI: 10.1186/s12905-024-03480-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/09/2024] [Accepted: 11/25/2024] [Indexed: 12/23/2024] Open
Abstract
BACKGROUND Endometriosis is a complex gynecological disorder characterized by the ectopic growth of endometrial tissue. Symptoms of endometriosis are known to impair the quality of life of patients, and among these are found dysmenorrhea, chronic pelvic pain, and gastrointestinal (GI) issues. GI issues such as painful bowel movements, bloating and constipation or diarrhea, are one of the common reasons for misdiagnosis with irritable bowel syndrome (IBS). Enteric glial cells (EGC) are known to play a role in pain associated with IBS, and reactive gliosis has been reported in patients with IBS, but the role of EGC in endometriosis has yet to be elucidated. We hypothesized that endometriosis will induce reactive gliosis, with increased expression of the glial fibrillary acidic protein (GFAP) and S100B, in the myenteric plexus of colonic sections in an animal model of endometriosis. METHODS In the present study animal experiments were employed to explore the impact of endometriosis on the gastrointestinal tract. Using a surgically induced endometriosis rat model, we collected ileal and colonic segments for analysis. We used H&E to assess microscopic damage in colon and ileum, immunofluorescence to measure GFAP and S100B expression in the colon, and toluidine blue staining to measure mast cell infiltration in colon and ileum. Immunofluorescence images were captured using confocal microscope and analyzed using ImageJ software. RESULTS All endometriosis animals developed vesicles. These animals had a significant increase in the colonic macroscopic damage compared to Sham and Naïve controls. Colonic and ileal sections didn't show statistical differences in microscopic damage between groups, yet endometriosis ileum had significantly increased mast cell infiltration compared to Naïve. GFAP immunostaining showed significantly increased integrated density in endometriosis when compared to Sham or Naïve, while no statistical difference was found in S100B integrated density between groups. CONCLUSIONS We conclude that endometriosis can alter GI homeostasis by inducing colon inflammation, reactive gliosis, and ileal mast cell infiltration. Taken together this suggests endometriosis can mimic IBS histopathology beyond the symptomatology, reinforcing this disease's complexity and the need to treat it beyond the gynecological setting.
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Affiliation(s)
- Luis A Rivera-Arce
- Department of Basic Sciences - Physiology Division, Ponce Health Sciences University, Ponce Research Institute, PO Box 7004, Ponce, 00732-7004, PR, Puerto Rico
| | - Myrella L Cruz
- Department of Basic Sciences - Physiology Division, Ponce Health Sciences University, Ponce Research Institute, PO Box 7004, Ponce, 00732-7004, PR, Puerto Rico
| | - Ulises Rodriguez-Cintron
- Department of Basic Sciences - Physiology Division, Ponce Health Sciences University, Ponce Research Institute, PO Box 7004, Ponce, 00732-7004, PR, Puerto Rico
| | - James P Torres-Pirela
- Department of Basic Sciences - Physiology Division, Ponce Health Sciences University, Ponce Research Institute, PO Box 7004, Ponce, 00732-7004, PR, Puerto Rico
| | - Caroline B Appleyard
- Department of Basic Sciences - Physiology Division, Ponce Health Sciences University, Ponce Research Institute, PO Box 7004, Ponce, 00732-7004, PR, Puerto Rico.
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Barbaro MR, Cremon C, Marasco G, Savarino E, Guglielmetti S, Bonomini F, Palombo M, Fuschi D, Rotondo L, Mantegazza G, Duncan R, di Sabatino A, Valente S, Pasquinelli G, Vergnolle N, Stanghellini V, Collins SM, Barbara G. Molecular Mechanisms Underlying Loss of Vascular and Epithelial Integrity in Irritable Bowel Syndrome. Gastroenterology 2024; 167:1152-1166. [PMID: 39004156 DOI: 10.1053/j.gastro.2024.07.004] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/22/2023] [Revised: 06/28/2024] [Accepted: 07/01/2024] [Indexed: 07/16/2024]
Abstract
BACKGROUND & AIMS The pathophysiology of irritable bowel syndrome (IBS) is multifactorial and includes epithelial barrier dysfunction, a key element at the interface between the gut lumen and the deeper intestinal layers. Beneath the epithelial barrier there is the vascular one representing the last barrier to avoid luminal antigen dissemination The aims of this study were to correlate morpho-functional aspects of epithelial and vascular barriers with symptom perception in IBS. METHODS Seventy-eight healthy subjects (controls) and 223 patients with IBS were enrolled in the study and phenotyped according to validated questionnaires. Sugar test was used to evaluate in vivo permeability. Immunohistochemistry, western blot, and electron microscopy were used to characterize the vascular barrier. Vascular permeability was evaluated by assessing the mucosal expression of plasmalemma vesicle-associated protein-1 and vascular endothelial cadherin. Caco-2 or human umbilical vein endothelial cell monolayers were incubated with soluble mediators released by mucosal biopsies to highlight the mechanisms involved in permeability alteration. Correlation analyses have been performed among experimental and clinical data. RESULTS The intestinal epithelial barrier was compromised in patients with IBS throughout the gastrointestinal tract. IBS-soluble mediators increased Caco-2 permeability via a downregulation of tight junction gene expression. Blood vessel density and vascular permeability were increased in the IBS colonic mucosa. IBS mucosal mediators increased permeability in human umbilical vein endothelial cell monolayers through the activation of protease-activated receptor-2 and histone deacetylase 11, resulting in vascular endothelial cadherin downregulation. Permeability changes correlated with intestinal and behavioral symptoms and health-related quality of life of patients with IBS. CONCLUSIONS Epithelial and vascular barriers are compromised in patients with IBS and contribute to clinical manifestations.
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Affiliation(s)
| | - Cesare Cremon
- IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy
| | - Giovanni Marasco
- IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy; Department of Medical and Surgical Sciences, University of Bologna, Bologna, Italy
| | - Edoardo Savarino
- Department of Surgery, Oncology, and Gastroenterology of the University of Padova, Padova, Italy
| | - Simone Guglielmetti
- Department of Food, Environmental and Nutritional Sciences, Università degli Studi di Milano, Milan, Italy
| | - Francesca Bonomini
- Department of Medical and Surgical Sciences, University of Bologna, Bologna, Italy
| | - Marta Palombo
- Department of Medical and Surgical Sciences, University of Bologna, Bologna, Italy
| | - Daniele Fuschi
- IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy
| | - Luca Rotondo
- IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy
| | - Giacomo Mantegazza
- Department of Food, Environmental and Nutritional Sciences, Università degli Studi di Milano, Milan, Italy
| | - Robin Duncan
- Department of Food, Environmental and Nutritional Sciences, Università degli Studi di Milano, Milan, Italy
| | - Antonio di Sabatino
- Department of Internal Medicine and Medical Therapeutics, University of Pavia, Pavia, Italy; Department of Internal Medicine 1, IRCCS San Matteo Hospital Foundation, Pavia, Italy
| | - Sabrina Valente
- Department of Medical and Surgical Sciences, University of Bologna, Bologna, Italy
| | - Gianandrea Pasquinelli
- IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy; Department of Medical and Surgical Sciences, University of Bologna, Bologna, Italy
| | - Nathalie Vergnolle
- IRSD, Université de Toulouse, INSERM, INRA, ENVT, Univ Toulouse III-Paul Sabatier (UPS), Toulouse, France
| | - Vincenzo Stanghellini
- IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy; Department of Medical and Surgical Sciences, University of Bologna, Bologna, Italy
| | - Stephen M Collins
- Department of Medicine, Farncombe Family Digestive Health Research Institute, McMaster University, Hamilton, Ontario, Canada
| | - Giovanni Barbara
- IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy; Department of Medical and Surgical Sciences, University of Bologna, Bologna, Italy.
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Ishioh M, Nozu T, Miyagishi S, Igarashi S, Funayama T, Ueno N, Okumura T. Brain histamine improves colonic hyperpermeability through the basal forebrain cholinergic neurons, adenosine A2B receptors and vagus nerve in rats. Biochem Pharmacol 2024; 224:116201. [PMID: 38608783 DOI: 10.1016/j.bcp.2024.116201] [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: 12/29/2023] [Revised: 03/20/2024] [Accepted: 04/09/2024] [Indexed: 04/14/2024]
Abstract
Intestinal barrier dysfunction, leaky gut, is implicated in various diseases, including irritable bowel syndrome (IBS) and neurodegenerative conditions like Alzheimer's disease. Our recent investigation revealed that basal forebrain cholinergic neurons (BFCNs), critical for cognitive function, receive signals from butyrate and orexin, playing a role in regulating intestinal barrier function through adenosine A2B signaling and the vagus. This study explores the involvement and function of brain histamine, linked to BFCNs, in the regulation of intestinal barrier function. Colonic permeability, assessed by quantifying absorbed Evans blue in rat colonic tissue, showed that histamine did not affect increased colonic permeability induced by LPS when administered subcutaneously. However, intracisternal histamine administration improved colonic hyperpermeability. Elevating endogenous histamine levels in the brain with SKF91488, a histamine N-methyltransferase inhibitor, also improved colonic hyperpermeability. This effect was abolished by intracisternal chlorpheniramine, an histamine H1 receptor antagonist, not ranitidine, an H2 receptor antagonist. The SKF91488-induced improvement in colonic hyperpermeability was blocked by vagotomy, intracisternal pirenzepine (suppressing BFCNs activity), or alloxazine (an adenosine A2B receptor antagonist). Additionally, intracisternal chlorpheniramine injection eliminated butyrate-induced improvement in colonic hyperpermeability. These findings suggest that brain histamine, acting via the histamine H1 receptor, regulates intestinal barrier function involving BFCNs, adenosine A2B signaling, and the vagus. Brain histamine appears to centrally regulate intestinal barrier function influenced by butyrate, differentiating its actions from peripheral histamine in conditions like IBS, where mast cell-derived histamine induces leaky gut. Brain histamine emerges as a potential pharmacological target for diseases associated with leaky gut, such as dementia and IBS.
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Affiliation(s)
- Masatomo Ishioh
- Division of Metabolism, Biosystemic Science, Gastroenterology and Hematology/Oncology, Department of Medicine, Asahikawa Medical University, Japan; Department of General Medicine, Asahikawa Medical University, Japan.
| | - Tsukasa Nozu
- Department of General Medicine, Asahikawa Medical University, Japan; Department of Regional Medicine and Education, Asahikawa Medical University, Japan; Center for Medical Education, Asahikawa Medical University, Japan
| | - Saori Miyagishi
- Department of General Medicine, Asahikawa Medical University, Japan
| | - Sho Igarashi
- Division of Metabolism, Biosystemic Science, Gastroenterology and Hematology/Oncology, Department of Medicine, Asahikawa Medical University, Japan
| | - Takuya Funayama
- Division of Metabolism, Biosystemic Science, Gastroenterology and Hematology/Oncology, Department of Medicine, Asahikawa Medical University, Japan
| | - Nobuhiro Ueno
- Division of Metabolism, Biosystemic Science, Gastroenterology and Hematology/Oncology, Department of Medicine, Asahikawa Medical University, Japan; Department of General Medicine, Asahikawa Medical University, Japan
| | - Toshikatsu Okumura
- Division of Metabolism, Biosystemic Science, Gastroenterology and Hematology/Oncology, Department of Medicine, Asahikawa Medical University, Japan; Department of General Medicine, Asahikawa Medical University, Japan
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Wade U, Pascual-Figal DA, Rabbani F, Ernst M, Albert A, Janssens I, Dierckxsens Y, Iqtadar S, Khokhar NA, Kanwal A, Khan A. The Possible Synergistic Pharmacological Effect of an Oral Berberine (BBR) and Curcumin (CUR) Complementary Therapy Alleviates Symptoms of Irritable Bowel Syndrome (IBS): Results from a Real-Life, Routine Clinical Practice Settings-Based Study. Nutrients 2024; 16:1204. [PMID: 38674895 PMCID: PMC11053504 DOI: 10.3390/nu16081204] [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: 03/12/2024] [Revised: 04/11/2024] [Accepted: 04/14/2024] [Indexed: 04/28/2024] Open
Abstract
Irritable bowel syndrome (IBS) is a prevalent chronic functional gastrointestinal disorder, characterised by recurrent abdominal discomfort and altered bowel movements. IBS cause a significantly negative impact on quality of life (QoL). Growing pharmacological evidence suggests that berberine (BBR) and curcumin (CUR) may mitigate IBS symptoms through multiple complementary synergistic mechanisms, resulting in the attenuation of intestinal inflammation and regulation of bowel motility and gut functions. In the present observational study conducted under real-life routine clinical practice settings, 146 patients diagnosed with IBS were enrolled by general practitioner clinics and pharmacies in Belgium. For the first time, this study assessed the potential synergistic pharmacological effect of a combined oral BBR/CUR supplement (Enterofytol® PLUS, containing 200 mg BBR and 49 mg CUR) (two tablets daily for 2 months), serving as complementary therapy in the management of IBS. Following the 2-month supplementation, significant improvements were observed in the patients' IBS severity index (IBSSI) (47.5%) and all the primary IBS symptoms, such as abdominal discomfort (47.2%), distension (48.0%), intestinal transit (46.8%), and QoL (48.1%) (all p < 0.0001). The improvement in the patients' IBSSI was independent of age, sex, and IBS sub-types. The patients' weekly maximum stool passage frequency decreased significantly (p < 0.0001), and the stool status normalized (p < 0.0001). The patients' need for concomitant conventional IBS treatment decreased notably: antispasmodics by 64.0% and antidiarrhoeals by 64.6%. Minor adverse effects were reported by a small proportion (7.1%) of patients, mostly gastrointestinal. The majority (93.1%) experienced symptom improvement or resolution, with a high satisfaction rate (82.6%) and willingness to continue the supplementation (79.0%). These findings support the potential synergistic pharmacological role of BBR and CUR in IBS, and their co-supplementation may alleviate IBS symptoms and improve QoL.
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Affiliation(s)
- Ursula Wade
- Department of Basic and Clinical Neuroscience, Kings College London, London SE5 9RT, UK;
| | - Domingo A. Pascual-Figal
- Hospital Universitario Virgen de la Arrixaca, IMIB-Arrixaca, Universidad de Murcia, 30120 Murcia, Spain;
| | - Fazale Rabbani
- Lady Reading Hospital, Peshawar 25000, Pakistan; (F.R.); (A.K.)
| | - Marie Ernst
- Biostatistics and Research Methods Center (B-STAT), CHU of Liège and University of Liège, 4000 Liège, Belgium (A.A.)
| | - Adelin Albert
- Biostatistics and Research Methods Center (B-STAT), CHU of Liège and University of Liège, 4000 Liège, Belgium (A.A.)
| | | | | | - Somia Iqtadar
- Department of Medicine, King Edward Medical University, Lahore 54000, Pakistan;
| | - Nisar A. Khokhar
- Department of Medicine, Bilawal Medical College, Liaquat University of Medical and Health Sciences, Jamshoro 76090, Pakistan;
| | - Ayesha Kanwal
- Lady Reading Hospital, Peshawar 25000, Pakistan; (F.R.); (A.K.)
| | - Amjad Khan
- Department of Biochemistry, Liaquat University of Medical and Health Sciences, Jamshoro 76090, Pakistan
- Department of Oncology, University of Oxford, Oxford OX3 7DQ, UK
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Osadchuk MA, Mironova ED, Kireeva NV. Expression of motilin and vasoactive intestinal peptide in the mucosa of the sigmoid colon in patients with diverticular disease of the large intestine and irritable bowel syndrome. EXPERIMENTAL AND CLINICAL GASTROENTEROLOGY 2024:68-74. [DOI: 10.31146/1682-8658-ecg-217-9-68-74] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/06/2025]
Affiliation(s)
- M. A. Osadchuk
- Federal State Autonomous Educational Institution of Higher Education I. M. Sechenov First Moscow State Medical University of the Ministry of Health of the Russian Federation (Sechenov University)
| | - E. D. Mironova
- Federal State Autonomous Educational Institution of Higher Education I. M. Sechenov First Moscow State Medical University of the Ministry of Health of the Russian Federation (Sechenov University)
| | - N. V. Kireeva
- Federal State Autonomous Educational Institution of Higher Education I. M. Sechenov First Moscow State Medical University of the Ministry of Health of the Russian Federation (Sechenov University)
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Leite G, de Freitas Germano J, Morales W, Weitsman S, Barlow GM, Parodi G, Pimentel ML, Villanueva-Millan MJ, Sanchez M, Ayyad S, Rezaie A, Mathur R, Pimentel M. Cytolethal distending toxin B inoculation leads to distinct gut microtypes and IBS-D-like microRNA-mediated gene expression changes in a rodent model. Gut Microbes 2024; 16:2293170. [PMID: 38108386 PMCID: PMC10730147 DOI: 10.1080/19490976.2023.2293170] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/21/2023] [Accepted: 12/06/2023] [Indexed: 12/19/2023] Open
Abstract
Diarrhea-predominant irritable bowel syndrome (IBS-D), associated with increased intestinal permeability, inflammation, and small intestinal bacterial overgrowth, can be triggered by acute gastroenteritis. Cytolethal distending toxin B (CdtB) is produced by gastroenteritis-causing pathogens and may underlie IBS-D development, through molecular mimicry with vinculin. Here, we examine the effects of exposure to CdtB alone on gut microbiome composition, host intestinal gene expression, and IBS-D-like phenotypes in a rat model. CdtB-inoculated rats exhibited increased anti-CdtB levels, which correlated with increased stool wet weights, pro-inflammatory cytokines (TNFα, IL2) and predicted microbial metabolic pathways including inflammatory responses, TNF responses, and diarrhea. Three distinct ileal microbiome profiles (microtypes) were identified in CdtB-inoculated rats. The first microtype (most like controls) had altered relative abundance (RA) of genera Bifidobacterium, Lactococcus, and Rothia. The second had lower microbial diversity, higher Escherichia-Shigella RA, higher absolute E. coli abundance, and altered host ileal tissue expression of immune-response and TNF-response genes compared to controls. The third microtype had higher microbial diversity, higher RA of hydrogen sulfide (H2S)-producer Desulfovibrio, and increased expression of H2S-associated pain/serotonin response genes. All CdtB-inoculated rats exhibited decreased ileal expression of cell junction component mRNAs, including vinculin-associated proteins. Significantly, cluster-specific microRNA-mRNA interactions controlling intestinal permeability, visceral hypersensitivity/pain, and gastrointestinal motility genes, including several previously associated with IBS were seen. These findings demonstrate that exposure to CdtB toxin alone results in IBS-like phenotypes including inflammation and diarrhea-like stool, decreased expression of intestinal barrier components, and altered ileal microtypes that influenced changes in microRNA-modulated gene expression and predicted metabolic pathways consistent with specific IBS-D symptoms.
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Affiliation(s)
- Gabriela Leite
- Medically Associated Science and Technology (MAST) Program, Cedars-Sinai, Los Angeles, CA, USA
| | | | - Walter Morales
- Medically Associated Science and Technology (MAST) Program, Cedars-Sinai, Los Angeles, CA, USA
| | - Stacy Weitsman
- Medically Associated Science and Technology (MAST) Program, Cedars-Sinai, Los Angeles, CA, USA
| | - Gillian M Barlow
- Medically Associated Science and Technology (MAST) Program, Cedars-Sinai, Los Angeles, CA, USA
| | - Gonzalo Parodi
- Medically Associated Science and Technology (MAST) Program, Cedars-Sinai, Los Angeles, CA, USA
| | - Maya L Pimentel
- Medically Associated Science and Technology (MAST) Program, Cedars-Sinai, Los Angeles, CA, USA
| | | | - Maritza Sanchez
- Medically Associated Science and Technology (MAST) Program, Cedars-Sinai, Los Angeles, CA, USA
| | - Sarah Ayyad
- Medically Associated Science and Technology (MAST) Program, Cedars-Sinai, Los Angeles, CA, USA
| | - Ali Rezaie
- Medically Associated Science and Technology (MAST) Program, Cedars-Sinai, Los Angeles, CA, USA
- Karsh Division of Gastroenterology and Hepatology, Department of Medicine, Cedars-Sinai, Los Angeles, CA, USA
| | - Ruchi Mathur
- Medically Associated Science and Technology (MAST) Program, Cedars-Sinai, Los Angeles, CA, USA
- Division of Endocrinology, Diabetes, and Metabolism, Department of Medicine, Cedars-Sinai, Los Angeles, CA, USA
| | - Mark Pimentel
- Medically Associated Science and Technology (MAST) Program, Cedars-Sinai, Los Angeles, CA, USA
- Karsh Division of Gastroenterology and Hepatology, Department of Medicine, Cedars-Sinai, Los Angeles, CA, USA
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Thomas-Dupont P, Velázquez-Soto H, Izaguirre-Hernández IY, Amieva-Balmori M, Triana-Romero A, Islas-Vázquez L, Jiménez-Martínez MDC, Remes-Troche JM. Obesity Contributes to Inflammation in Patients with IBS via Complement Component 3 and C-Reactive Protein. Nutrients 2022; 14:nu14245227. [PMID: 36558394 PMCID: PMC9781895 DOI: 10.3390/nu14245227] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/13/2022] [Revised: 11/24/2022] [Accepted: 12/01/2022] [Indexed: 12/13/2022] Open
Abstract
Irritable Bowel Syndrome (IBS) is usually a lifelong state that disturbs the digestive system. IBS has been linked to low-grade inflammation and the release of inflammatory mediators into the bloodstream. This could be associated with the degree of obesity presented by patients with IBS. Reports imply that IBS is more frequent in obese patients than in the overall population, with a prevalence of up to 31%. Here, we evaluated the serum levels of immunological and inflammation molecules and their correlation with Body Mass Index in IBS patients and the healthy control (HC). Seventy-nine serum samples of the IBS patients and thirty-five of the HC group were analyzed to determine the levels of each molecule and compare them with their BMI. Serum levels of C3 and C4 were significantly increased in IBS patients. C3 and C4 levels were higher in IBS-M and IBS-D subtypes compared with the HC group. When patients were grouped by BMI, a positive correlation between serum C3 (r = 0.49, p < 0.0001) and CRP (r = 0.40, p < 0.001) levels was found. Our results show, for the first time, a correlation between immunological molecules and BMI in IBS patients, suggesting that the inflammatory nature of obesity could contribute to the development of the symptoms in IBS through the stimulation and release of proteins as complement components and CRP.
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Affiliation(s)
- Pablo Thomas-Dupont
- Instituto de Investigaciones Médico-Biológicas, Universidad Veracruzana, Veracruz 91700, Mexico
| | - Henry Velázquez-Soto
- Departamento de Inmunología y Unidad de Investigación, Instituto de Oftalmología “Conde de Valencia”, Ciudad de México 06800, Mexico
| | | | - Mercedes Amieva-Balmori
- Instituto de Investigaciones Médico-Biológicas, Universidad Veracruzana, Veracruz 91700, Mexico
| | - Arturo Triana-Romero
- Instituto de Investigaciones Médico-Biológicas, Universidad Veracruzana, Veracruz 91700, Mexico
| | - Lorenzo Islas-Vázquez
- Departamento de Inmunología y Unidad de Investigación, Instituto de Oftalmología “Conde de Valencia”, Ciudad de México 06800, Mexico
| | - María del Carmen Jiménez-Martínez
- Departamento de Inmunología y Unidad de Investigación, Instituto de Oftalmología “Conde de Valencia”, Ciudad de México 06800, Mexico
- Departamento de Bioquímica, Facultad de Medicina, Universidad Nacional Autónoma de México, Ciudad de México 04510, Mexico
| | - José María Remes-Troche
- Instituto de Investigaciones Médico-Biológicas, Universidad Veracruzana, Veracruz 91700, Mexico
- Correspondence: ; Tel.: +52-228-842-17-00 (ext. 26421)
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Hasler WL, Grabauskas G, Singh P, Owyang C. Mast cell mediation of visceral sensation and permeability in irritable bowel syndrome. Neurogastroenterol Motil 2022; 34:e14339. [PMID: 35315179 PMCID: PMC9286860 DOI: 10.1111/nmo.14339] [Citation(s) in RCA: 44] [Impact Index Per Article: 14.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/16/2021] [Revised: 11/09/2021] [Accepted: 12/03/2021] [Indexed: 12/13/2022]
Abstract
Abnormalities of mast cell structure or function may play prominent roles in irritable bowel syndrome (IBS) symptom genesis. Mast cells show close apposition to sensory nerves and release bioactive substances in response to varied stimuli including infection, stress, and other neuroendocrine factors. Most studies focus on patients who develop IBS after enteric infection or who report diarrhea-predominant symptoms. Three topics underlying IBS pathogenesis have been emphasized in recent investigations. Visceral hypersensitivity to luminal stimulation is found in most IBS patients and may contribute to abdominal pain. Mast cell dysfunction also may disrupt epithelial barrier function which alters mucosal permeability potentially leading to altered bowel function and pain. Mast cell products including histamine, proteases, prostaglandins, and cytokines may participate in hypersensitivity and permeability defects, especially with diarrhea-predominant IBS. Recent experimental evidence indicates that the pronociceptive effects of histamine and proteases are mediated by the generation of prostaglandins in the mast cell. Enteric microbiome interactions including increased mucosal bacterial translocation may activate mast cells to elicit inflammatory responses underlying some of these pathogenic effects. Therapies to alter mast cell activity (mast cell stabilizers) or function (histamine antagonists) have shown modest benefits in IBS. Future investigations will seek to define patient subsets with greater potential to respond to therapies that address visceral hypersensitivity, epithelial permeability defects, and microbiome alterations secondary to mast cell dysfunction in IBS.
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Affiliation(s)
- William L. Hasler
- Division of Gastroenterology and HepatologyUniversity of Michigan Health SystemAnn ArborMichiganUSA
| | - Gintautas Grabauskas
- Division of Gastroenterology and HepatologyUniversity of Michigan Health SystemAnn ArborMichiganUSA
| | - Prashant Singh
- Division of Gastroenterology and HepatologyUniversity of Michigan Health SystemAnn ArborMichiganUSA
| | - Chung Owyang
- Division of Gastroenterology and HepatologyUniversity of Michigan Health SystemAnn ArborMichiganUSA
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9
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Frequency of Bowel Movements and Risk of Diverticulitis. Clin Gastroenterol Hepatol 2022; 20:325-333.e5. [PMID: 33418133 PMCID: PMC8957846 DOI: 10.1016/j.cgh.2021.01.003] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/28/2020] [Revised: 12/29/2020] [Accepted: 01/01/2021] [Indexed: 02/07/2023]
Abstract
OBJECTIVE The etiology of diverticulitis is poorly understood. The long-held belief that constipation and low-fiber diet are risk factors for diverticulosis has recently been challenged by studies that suggest that more frequent bowel movements predispose to diverticulosis. We aim to prospectively explore the association between bowel movement frequency and incident diverticulitis. DESIGN We studied participants of the Nurses' Health Study (NHS) and Health Professional Follow-up Study (HPFS). Participants' medical history, lifestyle factors and diet were used in Cox proportional hazards regression models to estimate multivariable-adjusted hazard ratios(HRs) and 95% confidence intervals(CI). RESULTS In the NHS during over 24 years of follow-up encompassing 1,299,922 person-years, we documented 5,214 incident cases of diverticulitis, and in the HPFS over 14 years encompassing 368,661 person-years of follow-up, we documented 390 incident cases of diverticulitis. We observed an inverse association between the frequency of bowel movements and risk of diverticulitis. In the NHS, compared with women who had daily bowel movements, those with more than once daily bowel movements had a HR of 1.30 (95% CI, 1.19, 1.42) and those with less frequent bowel movements had a HR of 0.89 (95% CI, 0.82, 0.95; p-trend < 0.0001). In the HPFS, the corresponding HRs were 1.29 (95% CI, 1.04, 1.59) and 0.61 (95% CI, 0.36, 1.03; p-trend = 0.003). The association between bowel movements and diverticulitis was not modified by categories of age, BMI, physical activity, laxative use or fiber intake. CONCLUSION More frequent bowel movements appear to be a risk factor for subsequent diverticulitis both in men and women. Further studies are needed to understand the potential mechanisms that may underlie this association.
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Ostrowska L, Wasiluk D, Lieners CFJ, Gałęcka M, Bartnicka A, Tveiten D. Igg Food Antibody Guided Elimination-Rotation Diet Was More Effective than FODMAP Diet and Control Diet in the Treatment of Women with Mixed IBS-Results from an Open Label Study. J Clin Med 2021; 10:4317. [PMID: 34640335 PMCID: PMC8509634 DOI: 10.3390/jcm10194317] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/28/2021] [Revised: 09/15/2021] [Accepted: 09/17/2021] [Indexed: 12/12/2022] Open
Abstract
Irritable bowel syndrome (IBS) is a chronic disease with recurrent abdominal pain, disturbed bowel emptying, and changes in stool consistency. We compared the effectiveness of three different dietary treatment plans (G1-FM-low FODMAP diet, G2-IP IgG based elimination-rotation-diet, and as control group, the G3-K control diet recommended by an attending gastroenterologist) in treating patients diagnosed with mixed irritable bowel syndrome. A total of seventy-three female patients diagnosed with a mixed form of irritable bowel syndrome (IBS-M) were enrolled in the study. The diet of each patient in Group 1 (G1-FM) and 2 (G2-IP) was determined individually during a meeting with a dietitian. Patients from Group 3 (G3-K) received nutrition advice from a gastroenterologist. Significant differences in the reduction of IBS symptoms were found between the groups. IBS symptoms as well as comorbid symptoms significantly improved or disappeared completely in the G2-IP group (idiopathic abdominal pain, p < 0.001; abdominal pain after a meal, p < 0.001; abdominal pain during defecation, p = 0.008), while in the G1-FM group, some of the IBS symptoms significantly improved (mucus in stool, p = 0.031; bloating, p < 0.001). In group G3-K no significant improvement was seen. Based on the results of this open-label study, it was concluded that various dietary interventions in the treatment of IBS-M patients do not uniformly affect the course and outcomes of disease management. Rotation diets based on IgG show significantly better results compared to other diets.
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Affiliation(s)
- Lucyna Ostrowska
- Department of Dietetics and Clinical Nutrition, Medical University of Bialystok, ul. Mieszka I 4B, 15-054 Bialystok, Poland;
| | - Diana Wasiluk
- Department of Dietetics and Clinical Nutrition, Medical University of Bialystok, ul. Mieszka I 4B, 15-054 Bialystok, Poland;
| | - Camille F. J. Lieners
- Institute of Microecology, ul. Sielska 10, 60-129 Poznan, Poland; (C.F.J.L.); (M.G.); (A.B.)
| | - Mirosława Gałęcka
- Institute of Microecology, ul. Sielska 10, 60-129 Poznan, Poland; (C.F.J.L.); (M.G.); (A.B.)
| | - Anna Bartnicka
- Institute of Microecology, ul. Sielska 10, 60-129 Poznan, Poland; (C.F.J.L.); (M.G.); (A.B.)
| | - Dag Tveiten
- Lab1 Medical Laboratory, Elias Smiths vei 10, 1337 Sandvika, Norway;
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The Influence of Bifidobacterium bifidum and Bacteroides fragilis on Enteric Glial Cell-Derived Neurotrophic Factors and Inflammasome. Inflammation 2021; 43:2166-2177. [PMID: 32638263 DOI: 10.1007/s10753-020-01284-z] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/20/2022]
Abstract
Enteric glial cells (EGCs) and enteric glial-derived neurotrophic factor (GDNF) are directly involved in intestinal inflammation. In this study, we sought to examine the possible mechanisms for how Bifidobacterium bifidum (B.b.) and Bacteroides fragilis (B.f.) influence EGC regulation. In this study, lipopolysaccharide (LPS) and interferon-γ (IFN-γ) were used as exogenous stimuli of EGCs to establish an intestinal inflammation model. After stimulation with LPS and IFN-γ, B.b. and B.f. supernatants were used to activate EGCs and to examine EGC immune mechanisms. For this purpose, qRT-PCR, western blotting, and laser scanning confocal microscopy (LSCM) were used to detect the expression of NLRP3, NLRP6, NGF, NT-3, IL-18, IL-1β, and caspase-1. We found that EGCs, after stimulation with LPS and IFN-γ, could express NLRP3, NLRP6, NT-3, NGF, IL-18, IL-1β, and caspase-1 through LSCM. In intestinal inflammation, B.b. and B.f. could trigger an increase in NGF and NT-3 expression in EGCs in order to protect the intestine. Furthermore, B.b. and B.f. could upregulate NLRP3 expression in EGCs and promote an inflammatory response. B.b. had a dual regulatory role in EGC NLRP6 expression, while B.f. inhibited NLRP6 protein expression. Moreover, B.b. could decrease the expression of IL-18, IL-1β, and caspase-1 in EGCs in order to inhibit the inflammatory response. Contrary to this, B.f. could upregulate IL-18, IL-1β, and caspase-1 expression in EGCs in order to promote the inflammatory response. B.b. and B.f. can influence the expression of NGF, NT-3, NLRP3, NLRP6, IL-18, IL-1β, and caspase-1 in EGCs in order to inhibit or promote intestinal inflammation.
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12
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McEvoy MA, Attia JR, Oldmeadow C, Holliday E, Smith WT, Mangoni AA, Peel R, Hancock SJ, Walker MM, Talley NJ. Serum L-arginine and endogenous methylarginine concentrations predict irritable bowel syndrome in adults: A nested case-control study. United European Gastroenterol J 2021; 9:809-818. [PMID: 34431615 PMCID: PMC8435254 DOI: 10.1002/ueg2.12137] [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] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/27/2021] [Accepted: 07/07/2021] [Indexed: 12/17/2022] Open
Abstract
BACKGROUND & AIMS: Nitric oxide, a major inhibitory nonadrenergic, noncholinergic neurotransmitter that relaxes smooth muscle, may be implicated in the pathophysiology of visceral hypersensitivity in irritable bowel syndrome (IBS). Impaired bioavailability of the nitric oxide precursor molecule L-arginine and higher concentrations of methylarginines (endogenous inhibitors of nitric oxide synthesis) are known to impair nitric oxide synthesis in numerous gastrointestinal cell types. We therefore examined serum concentrations of L-arginine and the methylarginines in a nested case-control study, to assess whether these factors are associated with adult IBS. METHODS Data on clinical characteristics, methylarginines, and L-arginine (measured using LC-MS/MS) were collected from a random population-based cohort of Australian adults (median age = 64 years; IQR = 60-70). Cases of IBS, defined according to Rome III criteria (N = 156), and controls (N = 332) were identified from within the cohort at the 5-year follow-up. RESULTS In adjusted logistic regression analyses, L-arginine, asymmetric dimethylarginine, symmetric dimethylarginine, L-arginine/asymmetric dimethylarginine ratio, and Kessler-10 psychological distress scores were significantly associated with IBS (p < 0.05). [Correction added on 18 September 2021, after first online publication: In the preceding sentence, the value (p > 0.05) has been changed to (p < 0.05)]. Similar results were found for IBS subtypes. Higher serum L-arginine concentration had the strongest association with IBS diagnosis, with an odds ratio of 9.03 for those with serum L-arginine at the 75th (84 μmol/L) versus 25th (46 μmol/L) percentile (95% CI: 5.99-13.62). L-arginine had the best discriminative ability with a bias-adjusted area under the receiver operator characteristic curve of 0.859. CONCLUSIONS Higher serum concentrations of L-arginine and endogenous methylarginines are strongly associated with IBS in adults.
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Affiliation(s)
- Mark A. McEvoy
- La Trobe Rural Health SchoolCollege of Science, Health and EngineeringLa Trobe UniversityBendigoVictoriaAustralia
| | - John R. Attia
- Hunter Medical Research InstituteSchool of Medicine and Public HealthUniversity of NewcastleCallaghanNew South WalesAustralia
- NHMRC Centre for Research Excellence in Digestive HealthUniversity of NewcastleCallaghanNew South WalesAustralia
| | - Christopher Oldmeadow
- Hunter Medical Research InstituteSchool of Medicine and Public HealthUniversity of NewcastleCallaghanNew South WalesAustralia
- NHMRC Centre for Research Excellence in Digestive HealthUniversity of NewcastleCallaghanNew South WalesAustralia
| | - Elizabeth Holliday
- Hunter Medical Research InstituteSchool of Medicine and Public HealthUniversity of NewcastleCallaghanNew South WalesAustralia
- NHMRC Centre for Research Excellence in Digestive HealthUniversity of NewcastleCallaghanNew South WalesAustralia
| | - Wayne T. Smith
- School of Medicine & Public HealthUniversity of NewcastleCallaghanNew South WalesAustralia
| | - Arduino A. Mangoni
- Discipline of Clinical PharmacologyCollege of Medicine and Public HealthFlinders University and Flinders Medical CentreAdeliadeSouth AustraliaAustralia
| | - Roseanne Peel
- Hunter Medical Research InstituteSchool of Medicine and Public HealthUniversity of NewcastleCallaghanNew South WalesAustralia
- NHMRC Centre for Research Excellence in Digestive HealthUniversity of NewcastleCallaghanNew South WalesAustralia
| | - Stephen J. Hancock
- Hunter Medical Research InstituteSchool of Medicine and Public HealthUniversity of NewcastleCallaghanNew South WalesAustralia
- NHMRC Centre for Research Excellence in Digestive HealthUniversity of NewcastleCallaghanNew South WalesAustralia
| | - Marjorie M. Walker
- School of Medicine & Public HealthUniversity of NewcastleCallaghanNew South WalesAustralia
| | - Nicholas J. Talley
- NHMRC Centre for Research Excellence in Digestive HealthUniversity of NewcastleCallaghanNew South WalesAustralia
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13
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Cai T, Wang X, Li B, Xiong F, Wu H, Yang X. Deciphering the synergistic network regulation of active components from SiNiSan against irritable bowel syndrome via a comprehensive strategy: Combined effects of synephrine, paeoniflorin and naringin. PHYTOMEDICINE : INTERNATIONAL JOURNAL OF PHYTOTHERAPY AND PHYTOPHARMACOLOGY 2021; 86:153527. [PMID: 33845366 DOI: 10.1016/j.phymed.2021.153527] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 11/01/2020] [Revised: 02/17/2021] [Accepted: 02/22/2021] [Indexed: 05/15/2023]
Abstract
BACKGROUND SiNiSan (SNS) is an ancient Chinese herbal prescription, and the current clinical treatment of irritable bowel syndrome (IBS) is effective. In the previous study of the research team, the multi-functional co-synergism of SNS against IBS was presented. Some potential drug targets and candidate ligands were predicted. PURPOSE This study attempts to explore the crucial ingredient combinations from SNS formula and reveal their synergistic mechanism for IBS therapy. MATERIALS AND METHODS In present study, a comprehensive strategy was performed to reveal IBS related pathways and biological modules, and explore synergistic effects of the ingredients, including ADME (absorption, distribution, metabolism, excretion) screening, Text mining, Venn analysis, Gene ontology (GO) analysis, Pathway cluster analysis, Molecular docking, Network construction and Experimental verification in visceral hypersensitivity (VHS) rats. RESULTS Three compressed IBS signal pathways were derived from ClueGO KEGG analysis of 63 IBS genes, including Neuroactive ligand-receptor interaction, Inflammatory mediator regulation of TRP (transient receptor potential) channels and Serotonergic synapse. A multi-module network, composed of four IBS therapeutic modules (psychological, inflammation, neuroendocrine and cross-talk modules), was revealed by Target-Pathway network. Nine kernel targets were considered closely associated with the IBS pathways, including ADRA2A, HTR2A, F2RL1, F2RL3, TRPV1, PKC, PKA, IL-1Β and NGF. In silico analysis revealed that three crucial ingredients (synephrine, paeoniflorin and naringin) were assumed to coordinate the network of those IBS therapeutic modules by acting on these kernel targets in the important pathways. In vivo experimental results showed that the crucial ingredient combinations synergistically affected the expressions of the kernel biological molecules, and improved the minimum capacity threshold of AWR in VHS rats. CONCLUSION The study proposes the important IBS associated pathways and the network regulation mechanisms of the crucial ingredients. It reveals the multi-target synergistic effect of the crucial ingredient combinations for the novel therapy on IBS.
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Affiliation(s)
- Tingting Cai
- School of Food Science and Pharmaceutical Engineering, Nanjing Normal University, Nanjing 210023, China
| | - Xiang Wang
- School of Food Science and Pharmaceutical Engineering, Nanjing Normal University, Nanjing 210023, China
| | - Bangjie Li
- College of Life Sciences, Nanjing Normal University, Nanjing 210023, China
| | - Fei Xiong
- School of Food Science and Pharmaceutical Engineering, Nanjing Normal University, Nanjing 210023, China
| | - Hao Wu
- School of Food Science and Pharmaceutical Engineering, Nanjing Normal University, Nanjing 210023, China
| | - Xinghao Yang
- College of Life Sciences, Nanjing Normal University, Nanjing 210023, China.
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14
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Hagan M, Hayee BH, Rodriguez-Mateos A. (Poly)phenols in Inflammatory Bowel Disease and Irritable Bowel Syndrome: A Review. Molecules 2021; 26:1843. [PMID: 33805938 PMCID: PMC8036772 DOI: 10.3390/molecules26071843] [Citation(s) in RCA: 16] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/09/2021] [Revised: 03/22/2021] [Accepted: 03/23/2021] [Indexed: 12/12/2022] Open
Abstract
(Poly)phenols (PPs) may have a therapeutic benefit in gastrointestinal (GI) disorders, such as irritable bowel syndrome (IBS) or inflammatory bowel disease (IBD). The aim of this review is to summarise the evidence-base in this regard. Observational evidence does not give a clear indication that PP intake has a preventative role for IBD or IBS, while interventional studies suggest these compounds may confer symptomatic and health-related quality of life improvements in known patients. There are inconsistent results for effects on markers of inflammation, but there are promising reports of endoscopic improvement. Work on the effects of PPs on intestinal permeability and oxidative stress is limited and therefore conclusions cannot be formed. Future work on the use of PPs in IBD and IBS will strengthen the understanding of clinical and mechanistic effects.
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Affiliation(s)
- Marilyn Hagan
- Department of Nutrition and Dietetics, Royal Papworth Hospital NHS Foundation Trust, Cambridge CB2 0AY, UK;
| | - Bu' Hussain Hayee
- Department of Gastroenterology, King’s College Hospital NHS Foundation Trust, London SE5 9RS, UK;
| | - Ana Rodriguez-Mateos
- Department of Nutritional Sciences, Faculty of Life Sciences and Medicine, King’s College London, London WC2R 2LS, UK
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15
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Impact of 2'-Fucosyllactose on Gut Microbiota Composition in Adults with Chronic Gastrointestinal Conditions: Batch Culture Fermentation Model and Pilot Clinical Trial Findings. Nutrients 2021; 13:nu13030938. [PMID: 33799455 PMCID: PMC7998190 DOI: 10.3390/nu13030938] [Citation(s) in RCA: 23] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/29/2021] [Revised: 03/06/2021] [Accepted: 03/11/2021] [Indexed: 02/07/2023] Open
Abstract
Intestinal dysbiosis has been described in patients with certain gastrointestinal conditions including irritable bowel syndrome (IBS) and ulcerative colitis. 2′-fucosyllactose (2′-FL), a prebiotic human milk oligosaccharide, is considered bifidogenic and butyrogenic. To assess prebiotic effects of 2′-FL, alone or in combination with probiotic strains (potential synbiotics), in vitro experiments were conducted on stool from healthy, IBS, and ulcerative colitis adult donors. In anaerobic batch culture fermenters, Bifidobacterium and Eubacterium rectale-Clostridium coccoides counts, and short-chain fatty acids (SCFAs) including butyrate increased during fermentation with 2′-FL and some of the 2′-FL/probiotic combinations. In a subsequent open-label pilot trial, the effect of a 2′-FL-containing nutritional formula was evaluated in twelve adults with IBS or ulcerative colitis. Gastrointestinal Quality of Life Index (GIQLI) total and gastrointestinal symptoms domain scores, stool counts of Bifidobacterium and Faecalibacterium prausnitzii, and stool SCFAs including butyrate, increased after six weeks of intervention. Consistent with documented effects of 2′-FL, the batch culture fermentation experiments demonstrated bifidogenic and butyrogenic effects of 2′-FL during fermentation with human stool samples. Consumption of the 2′-FL-containing nutritional formula by adults with IBS or ulcerative colitis was associated with improvements in intra- and extra-intestinal symptoms, and bifidogenic and butyrogenic effects.
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16
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Soltani S, Keshteli AH, Esmaillzadeh A, Adibi P. Adherence to Dietary Approaches to Stop Hypertension Eating Plan and Prevalence of Irritable Bowel Syndrome in Adults. J Neurogastroenterol Motil 2021; 27:78-86. [PMID: 33380554 PMCID: PMC7786080 DOI: 10.5056/jnm20007] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/15/2020] [Revised: 06/26/2020] [Accepted: 07/31/2020] [Indexed: 12/13/2022] Open
Abstract
Background/Aims Despite huge evidence on the link between adherence to dietary approaches to stop hypertension (DASH) eating pattern and several metabolic abnormalities, the association of this diet with irritable bowel syndrome (IBS) has not been investigated so far. We aim to examine the association between adherence to the DASH diet and prevalence of IBS symptoms and subtypes in adults. Methods This cross-sectional study was done among 3362 adult people in Isfahan, Iran. Usual dietary intakes were assessed using a validated 106-item dish-based semi-quantitative food frequency questionnaire. To investigate participants’ adherence to DASH-style diet, we created DASH score based on 8 main foods and nutrients emphasized or minimized in the DASH diet. Participants were classified into 3 categories according to their DASH-style diet scores. A validated modified Persian version of the Rome III questionnaire was applied for assessment of IBS. Results Totally, 22.2% of study participants were affected by IBS. After adjustment for potential confounding factors, we found that participants in the highest tertile of DASH score had lower odds of IBS (OR, 0.65; 95% CI, 0.50-0.83) compared with those in the lowest tertile. The same findings were also reached for IBS with constipation (OR for the highest vs the lowest tertile of DASH-style diet = 0.56; 95% CI, 0.38-0.85). No significant association was seen between adherence to DASH-style diet and IBS with diarrhea (OR, 1.31; 95% CI, 0.83-2.06). Conclusions We found a significant inverse association between adherence to DASH dietary pattern and odds of IBS and IBS with constipation. Further prospective studies are required to confirm these findings.
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Affiliation(s)
- Sanaz Soltani
- Students' Scientific Research Center, Tehran University of Medical Sciences, Tehran, Iran.,Department of Community Nutrition, School of Nutritional Sciences and Dietetics, Tehran University of Medical Sciences, Tehran, Iran
| | - Ammar H Keshteli
- Department of Medicine, University of Alberta, Edmonton, Alberta, Canada.,Integrative Functional Gastroenterology Research Center, Isfahan University of Medical Sciences, Isfahan, Iran
| | - Ahmad Esmaillzadeh
- Department of Community Nutrition, School of Nutritional Sciences and Dietetics, Tehran University of Medical Sciences, Tehran, Iran.,Obesity and Eating Habits Research Center, Endocrinology and Metabolism Molecular Cellular Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran.,Department of Community Nutrition, Isfahan University of Medical Sciences, Isfahan, Iran
| | - Peyman Adibi
- Integrative Functional Gastroenterology Research Center, Isfahan University of Medical Sciences, Isfahan, Iran
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17
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Szałwińska P, Włodarczyk J, Spinelli A, Fichna J, Włodarczyk M. IBS-Symptoms in IBD Patients-Manifestation of Concomitant or Different Entities. J Clin Med 2020; 10:jcm10010031. [PMID: 33374388 PMCID: PMC7794700 DOI: 10.3390/jcm10010031] [Citation(s) in RCA: 28] [Impact Index Per Article: 5.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/04/2020] [Revised: 12/14/2020] [Accepted: 12/22/2020] [Indexed: 12/12/2022] Open
Abstract
Irritable bowel syndrome (IBS) is a functional heterogenous disease with a multifactorial pathogenesis. It is characterized by abdominal pain, discomfort, and alteration in gut motility. The occurrence of similar symptoms was observed in patients in clinical remission of inflammatory bowel diseases (IBD) that is Crohn's disease (CD) and ulcerative colitis (UC), which pathogenesis is also not fully understood. Hence, arose the question if these symptoms are "true IBS" imposed on IBD, or is it a subclinical form of IBD or even pre-IBD? In this article, based on a narrative overview of the literature, we try to find an answer to this query by discussing the pathogenesis and overlaps between these conditions.
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Affiliation(s)
- Patrycja Szałwińska
- Department of Biochemistry, Medical University of Lodz, Mazowiecka 6/8, 92-215 Lodz, Poland; (P.S.); (J.W.); (J.F.)
| | - Jakub Włodarczyk
- Department of Biochemistry, Medical University of Lodz, Mazowiecka 6/8, 92-215 Lodz, Poland; (P.S.); (J.W.); (J.F.)
- Department of General and Colorectal Surgery, Medical University of Lodz, Haller Square 1, 90-624 Lodz, Poland
| | - Antonino Spinelli
- Colon and Rectal Surgery Division, Humanitas Clinical and Research Center IRCCS, Rozzano, 20089 Milano, Italy;
- Department of Biomedical Sciences, Humanitas University, Pieve Emanuele, 20090 Milano, Italy
| | - Jakub Fichna
- Department of Biochemistry, Medical University of Lodz, Mazowiecka 6/8, 92-215 Lodz, Poland; (P.S.); (J.W.); (J.F.)
| | - Marcin Włodarczyk
- Department of General and Colorectal Surgery, Medical University of Lodz, Haller Square 1, 90-624 Lodz, Poland
- Correspondence:
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van der Lugt T, Opperhuizen A, Bast A, Vrolijk MF. Dietary Advanced Glycation Endproducts and the Gastrointestinal Tract. Nutrients 2020; 12:nu12092814. [PMID: 32937858 PMCID: PMC7551018 DOI: 10.3390/nu12092814] [Citation(s) in RCA: 24] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/27/2020] [Revised: 09/10/2020] [Accepted: 09/11/2020] [Indexed: 12/19/2022] Open
Abstract
The prevalence of inflammatory bowel diseases (IBD) is increasing in the world. The introduction of the Western diet has been suggested as a potential explanation of increased prevalence. The Western diet includes highly processed food products, and often include thermal treatment. During thermal treatment, the Maillard reaction can occur, leading to the formation of dietary advanced glycation endproducts (dAGEs). In this review, different biological effects of dAGEs are discussed, including their digestion, absorption, formation, and degradation in the gastrointestinal tract, with an emphasis on their pro-inflammatory effects. In addition, potential mechanisms in the inflammatory effects of dAGEs are discussed. This review also specifically elaborates on the involvement of the effects of dAGEs in IBD and focuses on evidence regarding the involvement of dAGEs in the symptoms of IBD. Finally, knowledge gaps that still need to be filled are identified.
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Affiliation(s)
- Timme van der Lugt
- Department of Pharmacology and Toxicology, Maastricht University, 6229 ER Maastricht, The Netherlands;
- Office for Risk Assessment and Research, Netherlands Food and Consumer Product Safety Authority (NVWA), 3540 AA Utrecht, The Netherlands
- Correspondence:
| | - Antoon Opperhuizen
- Department of Pharmacology and Toxicology, Maastricht University, 6229 ER Maastricht, The Netherlands;
- Office for Risk Assessment and Research, Netherlands Food and Consumer Product Safety Authority (NVWA), 3540 AA Utrecht, The Netherlands
| | - Aalt Bast
- Department of Pharmacology and Toxicology, Maastricht University, 6229 ER Maastricht, The Netherlands;
- Campus Venlo, Maastricht University, 5911 BV Venlo, The Netherlands; (A.B.); (M.F.V.)
| | - Misha F. Vrolijk
- Campus Venlo, Maastricht University, 5911 BV Venlo, The Netherlands; (A.B.); (M.F.V.)
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Clinical Response and Changes of Cytokines and Zonulin Levels in Patients with Diarrhoea-Predominant Irritable Bowel Syndrome Treated with Bifidobacterium Longum ES1 for 8 or 12 Weeks: A Preliminary Report. J Clin Med 2020; 9:jcm9082353. [PMID: 32717980 PMCID: PMC7464152 DOI: 10.3390/jcm9082353] [Citation(s) in RCA: 20] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/16/2020] [Revised: 07/21/2020] [Accepted: 07/22/2020] [Indexed: 12/12/2022] Open
Abstract
Bifidobacterium longum (B. longum) ES1 is a probiotic strain capable of modulating microbiome composition, anti-inflammatory activity and intestinal barrier function. We investigated the use of B. Longum ES1 in the treatment of patients with diarrhoea-predominant irritable bowel syndrome (IBS-D). Sixteen patients were treated for 8 or 12 weeks with B. Longum ES1 (1 × 109 CFU/day). Serum zonulin and cytokines were measured at baseline (T0) and at the end of therapy (T1). Clinical response to therapy was assessed by IBS Severity Scoring System. Interleukin (IL)-6, IL-8, IL-12p70 and tumor necrosis factor (TNF) α levels decreased from T0 to T1, irrespective of treatment duration (p < 0.05), while zonulin levels diminished only in patients treated for 12 weeks (p = 0.036). Clinical response was observed in 5/16 patients (31%): 4/8 (50%) treated for 12 weeks and 1/8 (13%) treated for 8 weeks. Abdominal pain improved only in patients treated for 12 weeks (5/8 vs. 0/8, p = 0.025), while stool consistency improved regardless of therapy duration (p < 0.001). In conclusion, the results of this pilot study showed, in IBS-D patients treated for 12 weeks with B. longum ES1, a reduction in the levels of pro-inflammatory cytokines, and intestinal permeability as well as an improvement in gastrointestinal symptoms, but further studies including a placebo-control group are necessary to prove a causal link.
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The Effects on Immune Function and Digestive Health of Consuming the Skin and Flesh of Zespri® SunGold Kiwifruit (Actinidia Chinensis var. Chinensis ‘Zesy002’) in Healthy and IBS-Constipated Individuals. Nutrients 2020; 12:nu12051453. [PMID: 32443433 PMCID: PMC7284715 DOI: 10.3390/nu12051453] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/07/2020] [Revised: 05/12/2020] [Accepted: 05/14/2020] [Indexed: 12/12/2022] Open
Abstract
Irritable bowel syndrome (IBS) is a common gastrointestinal disorder that results in constipation (IBS-C) or diarrhoea with abdominal pain, flatulence, nausea and bloating. Kiwifruit (Actinidia spp.) are nutrient-dense fruit with a number of reported health benefits that include lowering glycaemic response, improving cardiovascular and inflammatory biomarkers, and enhancing gut comfort and laxation. This study investigated the effect of consuming three whole Zespri® SunGold kiwifruit (Actinidia chinensis var. chinensis ‘Zesy002’) with or without skin on cytokine production and immune and gut health in healthy people and those with IBS-C symptoms. This study enrolled thirty-eight participants in a 16 week randomized cross-over study (19 healthy and 19 participants with IBS-C). Participants were randomized to consume either three kiwifruit without eating the skin or three kiwifruit including the skin for 4 weeks each, with a 4 week washout in between each intervention. There was a significant decrease in the pro-inflammatory cytokine, TNF-α, for both the healthy and the IBS-C participants when they consumed whole kiwifruit and skin, and also for the healthy participants when they ate whole kiwifruit without the skin (p < 0.001). The kiwifruit interventions increased bowel frequency and significantly reduced the gastrointestinal symptom rating scale constipation and Birmingham IBS pain scores for both participant groups. We have demonstrated that consuming the skin of SunGold kiwifruit might have beneficial effects on gastrointestinal health that are not produced by consuming the flesh alone.
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Theodorou V, Beaufrand C, Yvon S, Laforge G, Burmeister Y, Müller A, Seilheimer B, Bueno L, Eutamene H. The multicomponent medication Spascupreel attenuates stress-induced gut dysfunction in rats. Neurogastroenterol Motil 2020; 32:e13798. [PMID: 32059072 PMCID: PMC7217055 DOI: 10.1111/nmo.13798] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/11/2019] [Revised: 12/13/2019] [Accepted: 12/23/2019] [Indexed: 12/20/2022]
Abstract
BACKGROUND Irritable bowel syndrome (IBS) is a common disorder worldwide. It is characterized by abdominal pain/discomfort and changes in bowel habits. Due to the multifactorial pathophysiology and the heterogeneity of IBS patients, appropriate treatment of IBS is still a challenge. Spascupreel (SP-11), as a multicomponent medication, has the potential to modulate multiple pathophysiological pathways simultaneously. Therefore, the objective of the current study was to investigate the effects of oral SP-11 treatment on stress-induced changes of peripheral and central functions in a rat model mimicking human IBS. METHODS Naïve Wistar rats were treated with SP-11 (0.9 tab/kg) or NaCl 0.9% by oral gavage for 4 days before 2-hour partial restraint stress (PRS) procedure. Twenty minutes after PRS, central and peripheral stress-induced changes affecting IBS were assessed. These include the hypothalamic-pituitary-adrenal (HPA) axis response through plasma ACTH and corticosterone measurements, visceral pain in response to colorectal distension, gut permeability, colonic mast cell number, and sensitization as well as gut transit time. RESULTS Treatment with SP-11 reduced the HPA axis activation in response to PRS. At the gut level, a reduction in colonic hypersensitivity to colorectal distension, a normalization of gut transit time acceleration, a reduced mast cell sensitization, and a trend toward reduced gut hyperpermeability were observed. CONCLUSIONS These data suggest that stress-induced IBS signs can be reduced using SP-11 in rats. The observed effects and the good tolerability of the drug make SP-11 an innovative candidate in the management of IBS.
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Affiliation(s)
- Vassilia Theodorou
- INRAToxAlimUMR 1331Neuro‐Gastroenterology and Nutrition GroupENVTINP‐PurpanUPSUniversité de ToulouseToulouseFrance
| | - Catherine Beaufrand
- INRAToxAlimUMR 1331Neuro‐Gastroenterology and Nutrition GroupENVTINP‐PurpanUPSUniversité de ToulouseToulouseFrance
| | - Sophie Yvon
- INRAToxAlimUMR 1331Neuro‐Gastroenterology and Nutrition GroupENVTINP‐PurpanUPSUniversité de ToulouseToulouseFrance
| | - Guylaine Laforge
- INRAToxAlimUMR 1331Neuro‐Gastroenterology and Nutrition GroupENVTINP‐PurpanUPSUniversité de ToulouseToulouseFrance
| | | | | | | | | | - Helene Eutamene
- INRAToxAlimUMR 1331Neuro‐Gastroenterology and Nutrition GroupENVTINP‐PurpanUPSUniversité de ToulouseToulouseFrance
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Osadchuk MA, Svistunov AA, Kireeva NV, Osadchuk MM. [Functional diseases of the gastrointestinal tract in the context with overlapping functional disorders: current status of the problem]. TERAPEVT ARKH 2020; 92:111-118. [PMID: 32598728 DOI: 10.26442/00403660.2020.02.000458] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/26/2020] [Indexed: 12/12/2022]
Abstract
Functional diseases of the gastrointestinal tract cause significant damage to the health care system. Their frequent combination in the same patient with the migration of clinical symptoms throughout the digestive tube is accompanied by continuous exacerbations, refractory to the therapy and severe psychosocial disorders. This review provides data on the main etiopathogenetic factors, clinical manifestations, course features and management tactics for patients with overlapping for the most common functional diseases of the gastrointestinal tract.
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Affiliation(s)
- M A Osadchuk
- Federal State Autonomous Educational Institution of Higher Education I.M. Sechenov First Moscow State Medical University (Sechenov University), Department of Polyclinic Therapy
| | - A A Svistunov
- Federal State Autonomous Educational Institution of Higher Education I.M. Sechenov First Moscow State Medical University (Sechenov University), Department of Polyclinic Therapy
| | - N V Kireeva
- Federal State Autonomous Educational Institution of Higher Education I.M. Sechenov First Moscow State Medical University (Sechenov University), Department of Polyclinic Therapy
| | - M M Osadchuk
- State Budgetary Healthcare Institution of Moscow «City Polyclinic №52», of the Moscow City Healthcare Department
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Kageyama Y, Shimokawa Y, Kawauchi K, Morimoto M, Aida K, Akiyama T, Nakamura T. Higher Prevalence of Nickel and Palladium Hypersensitivity in Patients with Ulcerative Colitis. Int Arch Allergy Immunol 2020; 181:456-461. [PMID: 32316004 DOI: 10.1159/000506633] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/06/2019] [Accepted: 02/17/2020] [Indexed: 11/19/2022] Open
Abstract
BACKGROUND The etiology of ulcerative colitis (UC) remains elusive even though many genetic and environmental pathogenic factors have been reported. Aberrant inflammatory responses mediated by specific subsets of T cells have been observed in ulcerative lesions of UC patients. OBJECTIVES To elucidate the involvement of a delayed-type hypersensitivity reaction in UC, we focused on dental metal hypersensitivity, a T cell-mediated, delayed-type allergic reaction that causes oral contact mucositis and systemic cutaneous inflammation. METHOD We recruited 65 Japanese UC patients and 22 healthy controls (HC) and used the in vitro lymphocyte stimulation test to quantify their sensitivity to zinc, gold, nickel, and palladium - the metals that have been widely used in dentistry. All subjects were users of metallic dental implants and/or prostheses containing zinc, gold, nickel, and/or palladium as major constituents. RESULTS Sixty percent of the UC patients were hypersensitive to at least one metal species, whereas 32% of the HC were hypersensitive to only a single metal species. The overall incidence of metal hypersensitivity was significantly higher for UC patients than for HC. Furthermore, a significantly greater proportion of UC patients were hypersensitive to nickel or palladium. The severity of the sensitivity to nickel and palladium was also significantly greater for UC patients than for HC. CONCLUSIONS This pilot study demonstrates that UC patients have a significantly higher incidence of hypersensitivity to nickel and palladium, suggesting the possible involvement of dental metal hypersensitivity in UC pathogenesis.
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Affiliation(s)
| | | | | | | | | | - Tetsu Akiyama
- Laboratory of Molecular and Genetic Information, Institute for Quantitative Biosciences, The University of Tokyo, Tokyo, Japan
| | - Tsutomu Nakamura
- Takanawa Clinic, Tokyo, Japan, .,Laboratory of Molecular and Genetic Information, Institute for Quantitative Biosciences, The University of Tokyo, Tokyo, Japan,
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Balmus IM, Ciobica A, Cojocariu R, Luca AC, Gorgan L. Irritable Bowel Syndrome and Neurological Deficiencies: Is There A Relationship? The Possible Relevance of the Oxidative Stress Status. ACTA ACUST UNITED AC 2020; 56:medicina56040175. [PMID: 32295083 PMCID: PMC7230401 DOI: 10.3390/medicina56040175] [Citation(s) in RCA: 17] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/10/2020] [Revised: 04/06/2020] [Accepted: 04/08/2020] [Indexed: 12/12/2022]
Abstract
Background: Irritable bowel syndrome (IBS) is one of the most common functional gastrointestinal disorders, exhibiting complex and controversial pathological features. Both oxidative stress and inflammation-related reactive oxygen species production may be involved in IBS pathological development. Thus, we focused on several aspects regarding the causes of oxidative stress occurrence in IBS. Additionally, in the molecular context of oxidative changes, we tried to discuss these possible neurological implications in IBS. Methods: The literature search included the main available databases (e.g., ScienceDirect, Pubmed/Medline, Embase, and Google Scholar). Articles in the English language were taken into consideration. Our screening was conducted based on several words such as “irritable bowel syndrome”, “gut brain axis”, “oxidative stress”, “neuroendocrine”, and combinations. Results: While no consistent evidence suggests clear pathway mechanisms, it seems that the inflammatory response may also be relevant in IBS. The mild implication of oxidative stress in IBS has been described through clinical studies and some animal models, revealing changes in the main markers such as antioxidant status and peroxidation markers. Moreover, it seems that the neurological structures involved in the brain-gut axis may be affected in IBS rather than the local gut tissue and functionality. Due to a gut-brain axis bidirectional communication error, a correlation between neurological impairment, emotional over-responsiveness, mild inflammatory patterns, and oxidative stress can be suggested. Conclusions: Therefore, there is a possible correlation between neurological impairment, emotional over-responsiveness, mild inflammatory patterns, and oxidative stress that are not followed by tissue destruction in IBS patients. Moreover, it is not yet clear whether oxidative stress, inflammation, or neurological impairments are key determinants or in which way these three interact in IBS pathology. However, the conditions in which oxidative imbalances occur may be an interesting research lead in order to find possible explanations for IBS development.
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Affiliation(s)
- Ioana-Miruna Balmus
- Department of Interdisciplinary Research in Science, “Alexandru Ioan Cuza” University of Iasi, Carol I Avenue, No. 11, 700506 Iași, Romania;
- Department of Research, Faculty of Biology, “Alexandru Ioan Cuza” University of Iasi, Carol I Avenue, 20A, 700506 Iași, Romania
| | - Alin Ciobica
- Department of Research, Faculty of Biology, “Alexandru Ioan Cuza” University of Iasi, Carol I Avenue, 20A, 700506 Iași, Romania
- Correspondence: (A.C.); (A.-C.L.)
| | - Roxana Cojocariu
- Department of Biology, Faculty of Biology, “Alexandru Ioan Cuza” University of Iasi, Carol I Avenue, 20A, 700506 Iași, Romania; (R.C.); (L.G.)
| | - Alina-Costina Luca
- Faculty of Medicine, “Gr. T. Popa” University of Medicine and Pharmacy, 16th University Street, 700115 Iași, Romania
- Correspondence: (A.C.); (A.-C.L.)
| | - Lucian Gorgan
- Department of Biology, Faculty of Biology, “Alexandru Ioan Cuza” University of Iasi, Carol I Avenue, 20A, 700506 Iași, Romania; (R.C.); (L.G.)
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El-Salhy M. Possible role of intestinal stem cells in the pathophysiology of irritable bowel syndrome. World J Gastroenterol 2020; 26:1427-1438. [PMID: 32308344 PMCID: PMC7152517 DOI: 10.3748/wjg.v26.i13.1427] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/03/2019] [Revised: 03/12/2020] [Accepted: 03/14/2020] [Indexed: 02/06/2023] Open
Abstract
The pathophysiology of irritable bowel syndrome (IBS) is not completely understood. However, several factors are known to play a role in pathophysiology of IBS such as genetics, diet, gut microbiota, gut endocrine cells, stress and low-grade inflammation. Understanding the pathophysiology of IBS may open the way for new treatment approaches. Low density of intestinal stem cells and low differentiation toward enteroendocrine cells has been reported recently in patients with IBS. These abnormalities are believed to be the cause of the low density of enteroendocrine cells seen in patients with IBS. Enteroendocrine cells regulate gastrointestinal motility, secretion, absorption and visceral sensitivity. Gastrointestinal dysmotility, abnormal absorption/secretion and visceral hypersensitivity are all seen in patients with IBS and haven been attributed to the low density the intestinal enteroendocrine cells in these patients. The present review conducted a literature search in Medline (PubMed) covering the last ten years until November 2019, where articles in English were included. Articles about the intestinal stem cells and their possible role in the pathophysiology of IBS are discussed in the present review. The present review discusses the assumption that intestinal stem cells play a central role in the pathophysiology of IBS and that the other factors known to contribute to the pathophysiology of IBS such as genetics, diet gut microbiota, stress, and low-grade inflammation exert their effects through affecting the intestinal stem cells. It reports further the data that support this assumption on genetics, diet, gut microbiota, stress with depletion of glutamine, and inflammation.
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Affiliation(s)
- Magdy El-Salhy
- Section for Gastroenterology, Department of Medicine, Stord Hospital, Stord 54 09, Norway
- Department of Clinical Medicine, University of Bergen, Bergen 50 21, Norway
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Robles-Medranda C, Oleas R, Valero M, Puga-Tejada M, Soria-Alcívar M, Ospina J, Alvarado-Escobar H, Muñoz-Jurado G, Baquerizo-Burgos J, Pitanga-Lukashok H. Confocal laser endomicroscopy detects colonic inflammation in patients with irritable bowel syndrome: a prospective study. Endosc Int Open 2020; 8:E550-E557. [PMID: 32258379 PMCID: PMC7089800 DOI: 10.1055/a-1119-6327] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/19/2019] [Accepted: 12/20/2019] [Indexed: 12/17/2022] Open
Abstract
Background and aims Irritable bowel syndrome (IBS) is considered to be a functional disease, but recent data indicate measurable organic alterations. We aimed to determine the presence of colorectal mucosa microinflammation in vivo via probe-confocal laser endomicroscopy (pCLE) and histological evaluation in IBS patients. Methods This was a prospective, controlled, nonrandomized single-blind diagnostic trial performed in a tertiary institution. pCLE images and targeted biopsy of each colon segment obtained during colonoscopies of IBS patients and controls were analyzed for inflammatory changes. Biopsies were classified using the Geboes scale, and the odds ratio and overall diagnostic accuracy were calculated. Results During the 15-month study period, 37 patients were allocated to each group. The mean age was 53.1 ± 14.3 years; 64.9 % were female. Signs of colonic mucosa inflammation were evident on 65.8 % of pCLE images from IBS patients compared to 23.4 % of images from controls (OR 6.28; 4.14-9.52; P < 0.001). In total, 20/37 patients had microinflammation via pCLE in ≥ 3 colon segments in the IBS group, compared to 1/37 in the control group. A Geboes score > 0 was attributed to 60.8 % of biopsies from patients in the IBS group compared to 27.5 % of biopsies from the control group. The sensitivity, specificity, positive and negative predictive values, observed and interrater agreement of pCLE-detected inflammatory changes in IBS using histology as gold standard were 76 %, 91 %, 76 %, 91 %, 86.5 %, and 66.8 %, respectively. Conclusions Patients with IBS have a six-fold higher prevalence of colorectal mucosa microinflammation than healthy controls. pCLE might be a reliable method to detect colorectal mucosa microinflammation in IBS patients.
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Affiliation(s)
- Carlos Robles-Medranda
- Gastroenterology and Endoscopy Division, Instituto Ecuatoriano de Enfermedades Digestivas (IECED), Guayaquil, Ecuador
| | - Roberto Oleas
- Gastroenterology and Endoscopy Division, Instituto Ecuatoriano de Enfermedades Digestivas (IECED), Guayaquil, Ecuador
| | - Manuel Valero
- Gastroenterology and Endoscopy Division, Instituto Ecuatoriano de Enfermedades Digestivas (IECED), Guayaquil, Ecuador
| | - Miguel Puga-Tejada
- Gastroenterology and Endoscopy Division, Instituto Ecuatoriano de Enfermedades Digestivas (IECED), Guayaquil, Ecuador
| | - Miguel Soria-Alcívar
- Gastroenterology and Endoscopy Division, Instituto Ecuatoriano de Enfermedades Digestivas (IECED), Guayaquil, Ecuador
| | - Jesenia Ospina
- Gastroenterology and Endoscopy Division, Instituto Ecuatoriano de Enfermedades Digestivas (IECED), Guayaquil, Ecuador
| | - Haydee Alvarado-Escobar
- Gastroenterology and Endoscopy Division, Instituto Ecuatoriano de Enfermedades Digestivas (IECED), Guayaquil, Ecuador
| | - Guillermo Muñoz-Jurado
- Gastroenterology and Endoscopy Division, Instituto Ecuatoriano de Enfermedades Digestivas (IECED), Guayaquil, Ecuador
| | - Jorge Baquerizo-Burgos
- Gastroenterology and Endoscopy Division, Instituto Ecuatoriano de Enfermedades Digestivas (IECED), Guayaquil, Ecuador
| | - Hannah Pitanga-Lukashok
- Gastroenterology and Endoscopy Division, Instituto Ecuatoriano de Enfermedades Digestivas (IECED), Guayaquil, Ecuador
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Liu Y, Yuan X, Li L, Lin L, Zuo X, Cong Y, Li Y. Increased Ileal Immunoglobulin A Production and Immunoglobulin A-Coated Bacteria in Diarrhea-Predominant Irritable Bowel Syndrome. Clin Transl Gastroenterol 2020; 11:e00146. [PMID: 32352710 PMCID: PMC7145038 DOI: 10.14309/ctg.0000000000000146] [Citation(s) in RCA: 23] [Impact Index Per Article: 4.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/12/2022] Open
Abstract
OBJECTIVES Immune activation and intestinal microbial dysbiosis could induce diarrhea-predominant irritable bowel syndrome (IBS-D). We examined the roles of ileal immunoglobulin A (IgA) and IgA-coated bacteria in IBS-D pathogenesis. METHODS Peripheral blood, fecal samples, and ileal and cecal biopsies were collected from 32 healthy volunteers and 44 patients with IBS-D. Quantitative reverse transcriptase polymerase chain reaction was used to assess differential gene expression. IgA levels in the blood and fecal samples were quantified by an enzyme-linked immunosorbent assay. IgA cells were assessed by immunofluorescence imaging. Flow-cytometry-based IgA bacterial cell sorting and 16S rRNA gene sequencing (IgA-SEQ) was used to isolate and identify fecal IgA bacteria. RESULTS Fecal IgA, particularly IgA1, was upregulated in patients with IBS-D. IgA class switch and B cell-activating factor-receptor were increased in the terminal ileum of patients. The intestinal microbiota composition was altered in patients compared with that in controls. IgA-SEQ showed that the proportion of fecal IgA-coated bacteria was increased significantly in patients with IBS-D. IgA bacteria in patients with IBS-D showed higher abundances of Escherichia-Shigella, Granulicatella, and Haemophilus compared with healthy controls and IgA bacteria in patients with IBS-D. The Escherichia-Shigella IgA coating index was positively correlated with anxiety and depression. The Escherichia-Shigella relative abundance, luminal IgA activity, and some altered IgA-coated bacteria were positively associated with the clinical manifestations of IBS-D. DISCUSSION Microbial dysbiosis may promote the terminal ileal mucosa to produce higher levels of IgA, increasing the proportion of IgA-coated bacteria by activating IgA class switching, which might regulate local inflammation and clinical manifestations in IBS-D. IgA may mediate the effects of microbial dysbiosis on the pathogenesis of IBS-D.
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Affiliation(s)
- Yi Liu
- Department of Gastroenterology, Qilu Hospital of Shandong University, Jinan, Shandong, China
- Department of Gastroenterology, the Affiliated Hospital of Qingdao University, Qingdao, Shandong, China
| | - Xunyi Yuan
- Department of General Surgery, Qilu Hospital of Shandong University, Jinan, Shandong, China
| | - Lixiang Li
- Department of Gastroenterology, Qilu Hospital of Shandong University, Jinan, Shandong, China
- Laboratory of Translational Gastroenterology, Qilu Hospital of Shandong University, Jinan, Shandong, China
| | - Lin Lin
- Department of Gastroenterology, Qilu Hospital of Shandong University, Jinan, Shandong, China
| | - Xiuli Zuo
- Department of Gastroenterology, Qilu Hospital of Shandong University, Jinan, Shandong, China
| | - Yingzi Cong
- Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, Texas, USA
- Department of Pathology, University of Texas Medical Branch, Galveston, Texas, USA
| | - Yanqing Li
- Department of Gastroenterology, Qilu Hospital of Shandong University, Jinan, Shandong, China
- Laboratory of Translational Gastroenterology, Qilu Hospital of Shandong University, Jinan, Shandong, China
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Pensabene L, Salvatore S, Turco R, Tarsitano F, Concolino D, Baldassarre ME, Borrelli O, Thapar N, Vandenplas Y, Staiano A, Saps M. Low FODMAPs diet for functional abdominal pain disorders in children: critical review of current knowledge. JORNAL DE PEDIATRIA (VERSÃO EM PORTUGUÊS) 2019. [DOI: 10.1016/j.jpedp.2019.05.019] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022] Open
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Pensabene L, Salvatore S, Turco R, Tarsitano F, Concolino D, Baldassarre ME, Borrelli O, Thapar N, Vandenplas Y, Staiano A, Saps M. Low FODMAPs diet for functional abdominal pain disorders in children: critical review of current knowledge. J Pediatr (Rio J) 2019; 95:642-656. [PMID: 31028745 DOI: 10.1016/j.jped.2019.03.004] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/01/2019] [Accepted: 03/13/2019] [Indexed: 02/07/2023] Open
Abstract
OBJECTIVE This narrative review aimed to provide practitioners a synthesis of the current knowledge on the role of a low Fermentable Oligosaccharides Disaccharides Monosaccharides and Polyols diet in reducing symptoms associated with functional abdominal pain disorders in children. This review is focused on the pathophysiology, efficacy and criticism of low Fermentable Oligosaccharides Disaccharides Monosaccharides and Polyols diet in children. SOURCES Cochrane Database, Pubmed and Embase were searched using specific terms for Fermentable Oligosaccharides Disaccharides Monosaccharides and Polyols diet interventions and functional abdominal pain disorders. SUMMARY OF THE FINDINGS In children, only one Randomized Control Trial and one open-label study reported positive results of low Fermentable Oligosaccharides Disaccharides Monosaccharides and Polyols diet; one Randomized Control Trial showed exacerbation of symptoms with fructans in children with Irritable Bowel Syndrome; no effect was found for the lactose-free diet whilst fructose-restricted diets were effective in 5/6 studies. CONCLUSIONS In children there are few trials evaluating low Fermentable Oligosaccharides Disaccharides Monosaccharides and Polyols in functional abdominal pain disorders, with encouraging data on the therapeutic efficacy particularly of fructose-restricted diet. Additional efforts are still needed to fill this research gap and clarify the most efficient way for tailoring dietary restrictions based on the patient's tolerance and/or identification of potential biomarkers of low Fermentable Oligosaccharides Disaccharides Monosaccharides and Polyols efficacy, to maintain nutritional adequacy and to simplify the adherence to diet by labeling Fermentable Oligosaccharides Disaccharides Monosaccharides and Polyols content in commercial products.
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Affiliation(s)
- Licia Pensabene
- University "Magna Graecia" of Catanzaro, Pediatric Unit, Department of Medical and Surgical Sciences, Catanzaro, Italy.
| | - Silvia Salvatore
- University of Insubria, Section of Pediatrics, Department of Medicine and Surgery, Varese, Italy
| | - Rossella Turco
- University of Naples "Federico II", Section of Pediatrics, Department of Translational Medical Science, Naples, Italy
| | - Flora Tarsitano
- University "Magna Graecia" of Catanzaro, Pediatric Unit, Department of Medical and Surgical Sciences, Catanzaro, Italy
| | - Daniela Concolino
- University "Magna Graecia" of Catanzaro, Pediatric Unit, Department of Medical and Surgical Sciences, Catanzaro, Italy
| | | | - Osvaldo Borrelli
- Great Ormond Street Hospital for Children, Neurogastroenterology and Motility Unit, Department of Gastroenterology, London, United Kingdom
| | - Nikhil Thapar
- Great Ormond Street Hospital for Children, Neurogastroenterology and Motility Unit, Department of Gastroenterology, London, United Kingdom
| | - Yvan Vandenplas
- Universitair Ziekenhuis Brussel, Vrije Universiteit Brussel, KidZ Health Castle, Brussels, Belgium
| | - Annamaria Staiano
- University of Naples "Federico II", Section of Pediatrics, Department of Translational Medical Science, Naples, Italy
| | - Miguel Saps
- University of Miami, Holtz Children's Hospital, Miller School of Medicine, Division of Pediatric Gastroenterology, Hepatology and Nutrition, Miami, United States
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Choung RS, Murray JA. The Role for Food Allergies in the Pathogenesis of Irritable Bowel Syndrome: Understanding Mechanisms of Intestinal Mucosal Responses Against Food Antigens. Gastroenterology 2019; 157:15-17. [PMID: 31145873 DOI: 10.1053/j.gastro.2019.05.042] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
Affiliation(s)
- Rok Seon Choung
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota
| | - Joseph A Murray
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota.
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Zhang Y, Ma ZF, Zhang H, Pan B, Li Y, Majid HA, Lee YY. Low fermentable oligosaccharides, disaccharides, monosaccharides, and polypols diet and irritable bowel syndrome in Asia. JGH Open 2019; 3:173-178. [PMID: 31061894 PMCID: PMC6487812 DOI: 10.1002/jgh3.12125] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/04/2018] [Accepted: 11/07/2018] [Indexed: 02/06/2023]
Abstract
Functional bowel disorders, including irritable bowel syndrome (IBS), are a chronic condition that can significantly reduce patients' quality of life. Therefore, this paper will review the roles of a low fermentable oligosaccharides, disaccharides, monosaccharides, and polypols (FODMAP) diet in treating IBS, particularly in an Asian setting. About 20% of the general population is diagnosed with IBS. However, there are limited effective medical therapies available for treating IBS. Therefore, IBS presents a major challenge to the health-care providers. Recently, there is an increasing interest in the use of a diet low in FODMAP for the treatment of IBS. A low FODMAP diet can decrease the delivery of readily fermentable substrates to the small intestine and colon, thereby improving functional gastrointestinal symptoms.
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Affiliation(s)
- Yihe Zhang
- Division of MedicineSchool of Life and Medical Sciences, University College LondonLondonUK
| | - Zheng Feei Ma
- Department of Health and Environmental SciencesXi'an Jiaotong‐Liverpool UniversitySuzhouChina
- School of Medical Sciences, Universiti Sains MalaysiaKota BharuMalaysia
| | - Hongxia Zhang
- Department of Food ScienceUniversity of OtagoDunedinNew Zealand
| | - Binyu Pan
- Department of Clinical NutritionThe First People's Hospital of Wujiang DistrictSuzhouChina
| | - Yeshan Li
- Department of Respiratory and Critical Care MedicineThe Second People's Hospital of WuhuWuhuChina
| | - Hazreen A Majid
- Department of Social and Preventive Medicine, Faculty of MedicineUniversity of MalayaKuala LumpurMalaysia
| | - Yeong Yeh Lee
- School of Medical Sciences, Universiti Sains MalaysiaKota BharuMalaysia
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Akhondi N, Memar Montazerin S, Soltani S, Saneei P, Hassanzadeh Keshteli A, Esmaillzadeh A, Adibi P. General and abdominal obesity in relation to the prevalence of irritable bowel syndrome. Neurogastroenterol Motil 2019; 31:e13549. [PMID: 30657237 DOI: 10.1111/nmo.13549] [Citation(s) in RCA: 26] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/17/2018] [Accepted: 12/17/2018] [Indexed: 02/08/2023]
Abstract
BACKGROUND Earlier studies on the obesity-IBS association have mostly been reported from Western nations, and limited data are available in this regard from developing countries. This study was performed to examine the association of general and abdominal obesity with Irritable bowel syndrome (IBS) in a Middle Eastern population. METHODS In this cross-sectional study, 4763 Iranian adults participated. Data on self-reported anthropometric measurements were collected, and BMI was calculated. Overweight and obesity were defined as 25 ≤ BMI < 30 and BMI ≥ 30 kg/m2 , respectively. Also, we used WC measurements to define the three categories of normal (<94 cm in men <80 cm in women), abdominal overweight (94 ≤ WC < 102 in men and 80 ≤ WC < 88 in women), and abdominal obesity (WC ≥ 102 cm in men and WC ≥ 88 cm in women). Assessment of different GI symptoms including those related to IBS was done using a validated Persian version of the Rome III questionnaire. IBS was defined as the presence of recurrent abdominal pain or discomfort at least sometimes in the last 3 months associated with 2 or more of the following features: improvement with defecation, pain onset associated with a change in frequency of stool, and pain onset associated with a change in form (appearance) of stool. KEY RESULTS Irritable bowel syndrome was more prevalent among individuals with abdominal obesity compared with normal subjects (23.8% vs 19%). Neither in crude nor in adjusted models, we found any significant association between overweight and obesity and IBS [for overweight: OR: 0.95, 95% CI: 0.66-1.36 and for obesity: OR: 1.06, 95% CI: 0.85-1.31]. We observed a significant positive association between abdominally overweight and IBS in crude model (OR: 1.31, 95% CI: 1.09-1.60); however, this association became non-significant after adjustment for potential confounders (OR: 1.09, 95% CI: 0.82-1.44). Across BMI categories, neither in crude nor in adjusted models, we did not find any significant association between overweight (OR: 0.89, 95% CI: 0.62-1.27), obesity (OR: 1.05, 95% CI: 0.58-1.87), and abdominal pain severity. Abdominal overweight (OR: 0.96, 95% CI: 0.65-1.40) and obesity (OR: 1.61, 95% CI: 0.67-1.63) were not associated with abdominal pain severity. CONCLUSIONS AND INFERENCES It is concluded that general or abdominal obesity was not associated with odds of IBS. Future longitudinal studies are needed to clarify the association between obesity and IBS.
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Affiliation(s)
- Negin Akhondi
- Isfahan Medical Student Research Committee, Isfahan University of Medical Sciences, Isfahan, Iran
| | - Sahar Memar Montazerin
- Isfahan Medical Student Research Committee, Isfahan University of Medical Sciences, Isfahan, Iran
| | - Sanaz Soltani
- Students' Scientific Research Center, Tehran University of Medical Sciences, Tehran, Iran.,Department of Community Nutrition, School of Nutritional Sciences and Dietetics, Tehran University of Medical Sciences, Tehran, Iran
| | - Parvane Saneei
- Department of Community Nutrition, School of Nutrition and Food Science, Isfahan University of Medical Sciences, Isfahan, Iran
| | | | - Ahmad Esmaillzadeh
- Department of Community Nutrition, School of Nutritional Sciences and Dietetics, Tehran University of Medical Sciences, Tehran, Iran.,Obesity and Eating Habits Research Center, Endocrinology and Metabolism Molecular Cellular Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran.,Food Security Research Center, Department of Community Nutrition, School of Nutrition and Food Science, Isfahan University of Medical Sciences, Isfahan, Iran
| | - Peyman Adibi
- Integrative Functional Gastroenterology Research Center, Isfahan University of Medical Sciences, Isfahan, Iran
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İliaz R, Akyüz F, Yeğen G, Örmeci A, Göktürk S, Akyüz Ü, Baran B, Mutluay Ö, Evirgen S, Karaca Ç, Demir K, Beşışık F, Güllüoğlu M, Kaymakoğlu S. Does the number of mucosal immune cells differ in irritable bowel syndrome and its subtypes? TURKISH JOURNAL OF GASTROENTEROLOGY 2019; 29:384-391. [PMID: 30249551 DOI: 10.5152/tjg.2018.17491] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/22/2022]
Abstract
BACKGROUND/AIMS Recently, mucosal inflammation has been proposed to be one of the mechanisms underlying the pathophysiology of irritable bowel syndrome (IBS); however, there are controversial results regarding this hypotheses. Our aim was to evaluate immune cell infiltration in rectal and ileal biopsy specimens of patients with IBS and to compare it with those of healthy controls. MATERIALS AND METHODS In total, 36 patients with IBS (15 with diarrhea and 21 with constipation) and 16 healthy volunteers were enrolled. Ileocolonoscopy and ileal/rectal biopsies were performed. Rectal and terminal ileal biopsy specimens were evaluated for mucosal immune cell infiltration using immunohistochemical analysis. Serotonin positivity as well as counts of intraepithelial lymphocytes (IEL) and CD4+, CD8+, CD20+, and CD3+ cells were determined by a single pathologist who is an expert in the gastrointestinal system. RESULTS CD3+ and CD4+ cell counts in rectal and terminal ileal biopsy specimens were lower in the IBS group than in the controls. Conversely, there was no statistically significant difference between the IBS and control groups in terms of serotonin positivity as well as counts of IEL and CD20+ and CD8+ cells. Comparison between the IBS subgroups revealed a higher number of IEL in rectal biopsy specimens of the diarrhea dominant group. In the IBS subgroups, immune cell counts in terminal ileal and rectal biopsy specimens showed a positive correlation. CONCLUSION IBS and its subgroups showed lower immune cell counts than the controls in our study. These results indicate that there is no significant mucosal inflammation in homogeneous groups of patients with IBS. Rectal biopsies may be sufficient for the evaluation of inflammation in IBS.
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Affiliation(s)
- Raim İliaz
- Department of Gastroenterology, İstanbul University İstanbul School of Medicine, İstanbul, Turkey
| | - Filiz Akyüz
- Department of Gastroenterology, İstanbul University İstanbul School of Medicine, İstanbul, Turkey
| | - Gülçin Yeğen
- Department of Pathology, İstanbul University İstanbul School of Medicine, İstanbul, Turkey
| | - Aslı Örmeci
- Department of Gastroenterology, İstanbul University İstanbul School of Medicine, İstanbul, Turkey
| | - Suut Göktürk
- Department of Gastroenterology, İstanbul University İstanbul School of Medicine, İstanbul, Turkey
| | - Ümit Akyüz
- Department of Gastroenterology, Yeditepe University School of Medicine, İstanbul, Turkey
| | - Bülent Baran
- Department of Gastroenterology, İstanbul University İstanbul School of Medicine, İstanbul, Turkey
| | - Özlem Mutluay
- Department of Gastroenterology, İstanbul University İstanbul School of Medicine, İstanbul, Turkey
| | - Sami Evirgen
- Department of Gastroenterology, İstanbul University İstanbul School of Medicine, İstanbul, Turkey
| | - Çetin Karaca
- Department of Gastroenterology, İstanbul University İstanbul School of Medicine, İstanbul, Turkey
| | - Kadir Demir
- Department of Gastroenterology, İstanbul University İstanbul School of Medicine, İstanbul, Turkey
| | - Fatih Beşışık
- Department of Gastroenterology, İstanbul University İstanbul School of Medicine, İstanbul, Turkey
| | - Mine Güllüoğlu
- Department of Pathology, İstanbul University İstanbul School of Medicine, İstanbul, Turkey
| | - Sabahattin Kaymakoğlu
- Department of Gastroenterology, İstanbul University İstanbul School of Medicine, İstanbul, Turkey
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Kim HJ. Do Toll-like Receptors Play a New Role as a Biomarker of Irritable Bowel Syndrome? J Neurogastroenterol Motil 2018; 24:510-511. [PMID: 30347933 PMCID: PMC6175550 DOI: 10.5056/jnm18153] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/11/2018] [Accepted: 09/13/2018] [Indexed: 12/22/2022] Open
Affiliation(s)
- Hyun Jin Kim
- Department of Internal Medicine, Gyeongsang National University Changwon Hospital, Changwon, Gyeongsangnam-do, Korea
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35
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Turco R, Salvatore S, Miele E, Romano C, Marseglia GL, Staiano A. Does a low FODMAPs diet reduce symptoms of functional abdominal pain disorders? A systematic review in adult and paediatric population, on behalf of Italian Society of Pediatrics. Ital J Pediatr 2018; 44:53. [PMID: 29764491 PMCID: PMC5952847 DOI: 10.1186/s13052-018-0495-8] [Citation(s) in RCA: 27] [Impact Index Per Article: 3.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/13/2018] [Accepted: 05/08/2018] [Indexed: 02/08/2023] Open
Abstract
Background Despite the rising of the Functional Gastrointestinal Disorders (FGIDs)’ incidence in the last years, the etio-pathogenesis of FGIDs remains unclear. The diet seems to play an important role in these disorders. Indeed, at least two thirds of adult patients with Irritable Bowel Syndrome (IBS) and of children with FGIDs perceive their GI symptoms to be food-related. In particular, in the last years, more interest has been focused in the low Fermentable Oligosaccharides, Disaccharides, Monosaccharides, and Polyol (FODMAPs) diet. Aims To provide a systematic review on the efficacy of a low FODMAPs diet in reducing symptoms associated with functional abdominal pain disorders. Methods Cochrane Library, MEDLINE (via Pubmed), and EMBASE databases from inception to June 2017 were searched. We included randomized controlled trials (RCTs), prospective and retrospective studies, systematic reviews and meta-analyses, reporting the efficacy of the FODMAPs diet intervention in FGIDs patients. Results Nineteen studies were eligible. A FODMAPs-restricted diet is beneficial in 12/13 intervention trials. The low FODMAPs diet improves overall GI symptoms, especially abdominal pain and bloating. In children, only one study reported positive results of a low FODMAPs diet. No effect was found for the lactose free diet whilst fructose-restricted diet was effective in 3/4 studies. The duration of the intervention was very different among the studies, ranging from 2 days to 16 months, and from 3 and 9 weeks for the RCTs. The majority of the trials presented differences in symptoms scoring scales, diet, food diaries, and food frequencies questionnaire. Conclusions The FODMAPs-restricted diet may be an effective dietary intervention for reducing IBS symptoms in adults. In children, there are promising data, although only one randomized double-blind study exists and further data are needed to better clarify the role of FODMAPs and fructose-restricted diet in IBS. The current evidence does not support the use of a lactose-restricted diet in children with FGIDs.
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Affiliation(s)
- Rossella Turco
- Department of Translational Medical Science, Section of Pediatrics, University of Naples "Federico II", Via S. Pansini 5, 80131, Naples, Italy
| | - Silvia Salvatore
- Department of Medicine and Surgery, Section of Pediatrics, University of Insubria, Varese, Italy
| | - Erasmo Miele
- Department of Translational Medical Science, Section of Pediatrics, University of Naples "Federico II", Via S. Pansini 5, 80131, Naples, Italy
| | - Claudio Romano
- Endoscopy and Gastroenterology Unit, Department of Pediatrics, University of Messina, Messina, Italy
| | - Gian Luigi Marseglia
- Department of Science Clinical-Surgery Diagnostic and Paediatric of University of Pavia, Pavia, Italy
| | - Annamaria Staiano
- Department of Translational Medical Science, Section of Pediatrics, University of Naples "Federico II", Via S. Pansini 5, 80131, Naples, Italy.
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Abstract
Gut barrier disruption is often implicated in pathogenesis associated with burn and other traumatic injuries. In this study, the authors examined whether therapeutic intervention with mesalamine (5-aminosalicylic acid [5-ASA]), a common anti-inflammatory treatment for patients with inflammatory bowel disease, reduces intestinal inflammation and maintains normal barrier integrity after burn injury. Male C57BL/6 mice were administered an approximately 20% TBSA dorsal scald burn and resuscitated with either 1 ml normal saline or 100 mg/kg of 5-ASA dissolved in saline. The authors examined intestinal transit and permeability along with the levels of small intestine epithelial cell proinflammatory cytokines and tight junction protein expression 1 day after burn injury in the presence or absence of 5-ASA. A significant decrease in intestinal transit was observed 1 day after burn injury, which accompanied a significant increase in gut permeability. The authors found a substantial increase in the levels of interleukin (IL)-6 (by ~1.5-fold) and IL-18 (by ~2.5-fold) in the small intestine epithelial cells 1 day after injury. Furthermore, burn injury decreases the expression of the tight junction proteins claudin-4, claudin-8, and occludin. Treatment with 5-ASA after burn injury prevented the burn-induced increase in permeability, partially restored normal intestinal transit, normalized the levels of the proinflammatory cytokines IL-6 and IL-18, and restored tight junction protein expression of claudin-4 and occludin compared with that of sham levels. Together these findings suggest that 5-ASA can potentially be used as treatment to decrease intestinal inflammation and normalize intestinal function after burn injury.
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Kuchnia AJ, Conlon B, Greenberg N. Natural Bioactive Food Components for Improving Enteral Tube Feeding Tolerance in Adult Patient Populations. Nutr Clin Pract 2018; 33:107-120. [PMID: 28820648 DOI: 10.1177/0884533617722164] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/16/2023] Open
Abstract
Tube feeding (TF) is the most common form of nutrition support. In recent years, TF administration has increased among patient populations within and outside hospital settings, in part due to greater insurance coverage, reduced use of parenteral nutrition, and improved formularies suitable for sole source nutrition. With increasing life expectancy and improved access to TFs, the number of adults dependent on enteral nutrition is expected to grow. However, enteral TF intolerance (ETFI) is the most common complication of TFs, typically presenting with at least 1 adverse gastrointestinal event, including nausea, diarrhea, and constipation. ETFI often leads to reductions in TF volume with associated energy and protein deficits. Potentially ensuing malnutrition is a major public health concern due its effects on increased risk of morbidity and mortality, infections, prolonged hospital length of stay, and higher healthcare costs. As such, there is a need for intervention strategies to prevent and reduce ETFI. Incorporating whole foods with bioactive properties is a promising strategy. Emerging research has elucidated bioactive properties of whole foods with specific benefits for the prevention and management of adverse gastrointestinal events commonly associated with TFs. However, lack of evidence-based recommendations and technological challenges have limited the use of such foods in commercial TF formulas. This review addresses research gaps by discussing 5 whole foods (rhubarb, banana, curcumin, peppermint oil, and ginger) with bioactive attributes identified through literature searches and clinical experience as having substantial scientific rationale to consider their application for ETFI in adult populations.
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Affiliation(s)
- Adam J Kuchnia
- Department of Food Science and Nutrition, University of Minnesota-Twin Cities, Saint Paul, Minnesota, USA
| | - Beth Conlon
- Nestlé Nutrition R&D Centers Inc, Bridgewater, New Jersey, USA
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Greenwood-Van Meerveld B, Johnson AC. Mechanisms of Stress-induced Visceral Pain. J Neurogastroenterol Motil 2018; 24:7-18. [PMID: 29291604 PMCID: PMC5753899 DOI: 10.5056/jnm17137] [Citation(s) in RCA: 65] [Impact Index Per Article: 9.3] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/28/2017] [Accepted: 12/04/2017] [Indexed: 12/13/2022] Open
Abstract
Evidence suggests that long-term stress facilitates visceral pain through sensitization of pain pathways and promotes chronic visceral pain disorders such as the irritable bowel syndrome (IBS). This review will describe the importance of stress in exacerbating IBS-induced abdominal pain. Additionally, we will briefly review our understanding of the activation of the hypothalamic-pituitary-adrenal axis by both chronic adult stress and following early life stress in the pathogenesis of IBS. The review will focus on the glucocorticoid receptor and corticotropin-releasing hormone-mediated mechanisms in the amygdala involved in stress-induced visceral hypersensitivity. One potential mechanism underlying persistent effects of stress on visceral sensitivity could be epigenetic modulation of gene expression. While there are relatively few studies examining epigenetically mediated mechanisms involved in stress-induced visceral nociception, alterations in DNA methylation and histone acetylation patterns within the brain, have been linked to alterations in nociceptive signaling via increased expression of pro-nociceptive neurotransmitters. This review will discuss the latest studies investigating the long-term effects of stress on visceral sensitivity. Additionally, we will critically review the importance of experimental models of adult stress and early life stress in enhancing our understanding of the basic molecular mechanisms of nociceptive processing.
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Affiliation(s)
- Beverley Greenwood-Van Meerveld
- Oklahoma Center for Neuroscience, University of Oklahoma Health Science Center, Oklahoma City, OK,
USA
- Department of Physiology, University of Oklahoma Health Science Center, Oklahoma City, OK,
USA
- VA Medical Center, University of Oklahoma Health Science Center, Oklahoma City, OK,
USA
| | - Anthony C Johnson
- VA Medical Center, University of Oklahoma Health Science Center, Oklahoma City, OK,
USA
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39
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Pesce M, D'Alessandro A, Borrelli O, Gigli S, Seguella L, Cuomo R, Esposito G, Sarnelli G. Endocannabinoid-related compounds in gastrointestinal diseases. J Cell Mol Med 2017; 22:706-715. [PMID: 28990365 PMCID: PMC5783846 DOI: 10.1111/jcmm.13359] [Citation(s) in RCA: 24] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/29/2017] [Accepted: 07/23/2017] [Indexed: 12/14/2022] Open
Abstract
The endocannabinoid system (ECS) is an endogenous signalling pathway involved in the control of several gastrointestinal (GI) functions at both peripheral and central levels. In recent years, it has become apparent that the ECS is pivotal in the regulation of GI motility, secretion and sensitivity, but endocannabinoids (ECs) are also involved in the regulation of intestinal inflammation and mucosal barrier permeability, suggesting their role in the pathophysiology of both functional and organic GI disorders. Genetic studies in patients with irritable bowel syndrome (IBS) or inflammatory bowel disease have indeed shown significant associations with polymorphisms or mutation in genes encoding for cannabinoid receptor or enzyme responsible for their catabolism, respectively. Furthermore, ongoing clinical trials are testing EC agonists/antagonists in the achievement of symptomatic relief from a number of GI symptoms. Despite this evidence, there is a lack of supportive RCTs and relevant data in human beings, and hence, the possible therapeutic application of these compounds is raising ethical, political and economic concerns. More recently, the identification of several EC-like compounds able to modulate ECS function without the typical central side effects of cannabino-mimetics has paved the way for emerging peripherally acting drugs. This review summarizes the possible mechanisms linking the ECS to GI disorders and describes the most recent advances in the manipulation of the ECS in the treatment of GI diseases.
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Affiliation(s)
- Marcella Pesce
- Department of Clinical Medicine and Surgery, 'Federico II' University of Naples, Naples, Italy.,Division of Neurogastroenterology & Motility, Great Ormond Street Hospital and University of College (UCL), London, UK
| | - Alessandra D'Alessandro
- Department of Clinical Medicine and Surgery, 'Federico II' University of Naples, Naples, Italy
| | - Osvaldo Borrelli
- Division of Neurogastroenterology & Motility, Great Ormond Street Hospital and University of College (UCL), London, UK
| | - Stefano Gigli
- Department of Physiology and Pharmacology 'Vittorio Erspamer', La Sapienza University of Rome, Rome, Italy
| | - Luisa Seguella
- Department of Physiology and Pharmacology 'Vittorio Erspamer', La Sapienza University of Rome, Rome, Italy
| | - Rosario Cuomo
- Department of Clinical Medicine and Surgery, 'Federico II' University of Naples, Naples, Italy
| | - Giuseppe Esposito
- Department of Physiology and Pharmacology 'Vittorio Erspamer', La Sapienza University of Rome, Rome, Italy
| | - Giovanni Sarnelli
- Department of Clinical Medicine and Surgery, 'Federico II' University of Naples, Naples, Italy
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40
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Li ZY, Zhang N, Wen S, Zhang J, Sun XL, Fan XM, Sun YH. Decreased glucagon-like peptide-1 correlates with abdominal pain in patients with constipation-predominant irritable bowel syndrome. Clin Res Hepatol Gastroenterol 2017; 41:459-465. [PMID: 28215540 DOI: 10.1016/j.clinre.2016.12.007] [Citation(s) in RCA: 21] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/27/2016] [Revised: 10/26/2016] [Accepted: 12/15/2016] [Indexed: 02/04/2023]
Abstract
BACKGROUND AND OBJECTIVE The glucagon-like peptide-1 (GLP-1) analog, ROSE-010, plays a critical role in alleviating abdominal pain in patients with irritable bowel syndrome (IBS); however, the underling mechanism is unclear. In the present study, we determined the serum GLP-1 level in patients with constipation-predominant IBS (IBS-C). The relationship between GLP-1 and abdominal pain was investigated. In addition, the expression of the GLP-1 receptor in the colon was determined. METHODS Rectosigmoid biopsies were gathered from 38 patients with IBS-C who met the Rome III criteria, and 22 healthy controls. Abdominal pain was quantified by a validated questionnaire. Serum GLP-1 was measured by ELISA and correlated with abdominal pain scores. The presence of the GLP-1 receptor in the colonic mucosa was assessed by immunohistochemistry. RESULTS Serum GLP-1 was substantially decreased in patients with IBS-C. Decreased serum GLP-1 had a negative correlation with the abdominal pain scores. Biopsies from patients with IBS-C revealed a significant down-regulation of the GLP-1 receptor in colonic mucosa compared with control subjects. CONCLUSIONS Decreased serum GLP-1 correlates with abdominal pain in patients with IBS-C. Decreased expression of GLP-1 and GLP-1 receptor may be the basis for alleviation of abdominal pain in patients with IBS-C by ROSE-010.
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Affiliation(s)
- Zheng-Yang Li
- Department of Gastroenterology, Dalian friendship Hospital, Dalian, Liaoning 116001, PR China
| | - Na Zhang
- Department of Gastroenterology, Dalian friendship Hospital, Dalian, Liaoning 116001, PR China
| | - Shuang Wen
- Department of Gastroenterology, Dalian friendship Hospital, Dalian, Liaoning 116001, PR China
| | - Jing Zhang
- Department of Gastroenterology, Dalian friendship Hospital, Dalian, Liaoning 116001, PR China
| | - Xiu-Li Sun
- Department of Gastroenterology, Dalian friendship Hospital, Dalian, Liaoning 116001, PR China
| | - Xiao-Ming Fan
- Department of Gastroenterology, Jinshan hospital of Fudan University, Shanghai 201508, PR China.
| | - Yong-Hong Sun
- Department of Gastroenterology, Dalian friendship Hospital, Dalian, Liaoning 116001, PR China.
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41
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Hattay P, Prusator DK, Tran L, Greenwood-Van Meerveld B. Psychological stress-induced colonic barrier dysfunction: Role of immune-mediated mechanisms. Neurogastroenterol Motil 2017; 29. [PMID: 28300333 DOI: 10.1111/nmo.13043] [Citation(s) in RCA: 18] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/25/2016] [Accepted: 01/09/2017] [Indexed: 02/08/2023]
Abstract
BACKGROUND Evidence suggests that patients with irritable bowel syndrome (IBS) exhibit increases in gut permeability and alterations in tight junction (TJ) protein expression. Although psychological stress worsens IBS symptoms, the mechanisms by which stress enhances gut permeability and affects TJ protein expression remain to be determined. Here, we test the hypothesis that chronic intermittent psychological stress activates the release of proinflammatory cytokines to alter TJ proteins and promotes increased gut permeability. METHODS Male Fischer-344 rats were subjected to 1 hour of water avoidance stress (WAS) or SHAM stress per day for 7 days. Following the stress protocol, colonic permeability was measured via transepithelial electrical resistance (TEER) and macromolecular flux of horseradish peroxidase (HRP). In tissue isolated from rats exposed to the WAS or SHAM stress, TJ proteins claudin-2, junctional adhesion molecule-A (JAM-A) and zonula occluden-1 (ZO-1) were measured via Western blotting, histological appearance of the colonic segments was assessed via hematoxylin and eosin staining, and an inflammatory cytokine panel was quantified via quantitative reverse transcription-polymerase chain reaction. KEY RESULTS Repetitive daily exposure to WAS decreased the TEER, increased the macromolecular flux of HRP, and altered the expression of claudin-2, JAM-A and ZO-1 proteins within colonic tissue compared to SHAM controls. In the absence of a histologically defined inflammation, the cytokine profiles of WAS-treated animals revealed an increase in interleukin-1β and tumor necrosis factor (TNF)-α. Subsequent analysis revealed a significant positive correlation between TNF-α and expression of TJ protein claudin-2. CONCLUSIONS & INFERENCES Our findings suggest that chronic stress increases colonic permeability via sub-inflammatory cytokine-mediated remodeling of TJ protein expression.
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Affiliation(s)
- P Hattay
- Oklahoma Center for Neuroscience, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA
| | - D K Prusator
- Oklahoma Center for Neuroscience, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA
| | - L Tran
- Oklahoma Center for Neuroscience, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA
| | - B Greenwood-Van Meerveld
- Oklahoma Center for Neuroscience, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA.,VA Medical Center, Oklahoma City, OK, USA.,Department of Physiology, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA
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Alt F, Chong PW, Teng E, Uebelhack R. Evaluation of Benefit and Tolerability of IQP-CL-101 (Xanthofen) in the Symptomatic Improvement of Irritable Bowel Syndrome: A Double-Blinded, Randomised, Placebo-Controlled Clinical Trial. Phytother Res 2017; 31:1056-1062. [PMID: 28508427 PMCID: PMC5518189 DOI: 10.1002/ptr.5826] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/11/2017] [Revised: 04/05/2017] [Accepted: 04/07/2017] [Indexed: 12/17/2022]
Abstract
Irritable bowel syndrome (IBS) is a functional bowel disorder of unknown aetiology. There is currently no known cure, and pharmacological interventions are usually targeting symptomatic relief, where natural and herbal remedies also play a role. This study aimed to evaluate the benefit and tolerability of IQP-CL-101 in symptomatic IBS relief. A double-blinded, randomised, placebo-controlled trial was conducted over 8 weeks. A total of 99 subjects fulfilling ROME-III criteria for IBS were randomised into two groups, given either two IQP-CL-101 softgels or matching placebo twice daily before main meals. The primary endpoint was the difference in change of IBS Symptom Severity Score (IBS-SSS) after an 8-week intake of IQP-CL-101 compared to placebo. After 8 weeks, subjects on IQP-CL-101 showed a significant reduction in IBS-SSS (113.0 ± 64.9-point reduction) compared to subjects on placebo (38.7 ± 64.5-point reduction) (p < 0.001). A significant improvement could be seen as early as 4 weeks. No serious adverse events were reported throughout. IQP-CL-101 can be considered beneficial in the improvement of IBS symptom severity, regardless of IBS type, and therefore able to improve quality of life in patients suffering from abdominal pain and discomfort. © 2017 The Authors. Phytotherapy Research published by John Wiley & Sons Ltd.
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Affiliation(s)
- Felix Alt
- analyze & realize GmbH, Berlin, Germany
| | | | - Emily Teng
- InQpharm Europe Ltd, E-16, Plaza Mont Kiara, 2 Jalan Kiara, Kuala Lumpur, 50480, Malaysia
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McCullough R, McCullough J. Deciphering the pathophysiology of irritable bowel syndrome and functional gastrointestinal disorders-an alternative model for pathogenesis: cytokine controlled transepithelial multi-feedback loop. Transl Gastroenterol Hepatol 2017; 2:18. [PMID: 28447053 PMCID: PMC5388621 DOI: 10.21037/tgh.2017.03.02] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/24/2017] [Accepted: 02/23/2017] [Indexed: 12/12/2022] Open
Abstract
A working theoretical model for irritable bowel syndrome (IBS) and other functional gastrointestinal disorders (FGIDs) does not exist, hampered by the lack of any clear cut invention that address all symptom and signs of the disease. Reports of cessation of symptom and signs of both major types of IBS have been published using a non-systemic, topically active agent-high potency polymerized cross-linked sucralfate (HPPCLS). The unique clinical effect of this non-systemic agent restricted to the luminal surface of the gut provides opportunity to elaborate on an alternative working model for the pathogenesis of IBS and FGIDs. While the chemical determinants of HPPCLS and the mucosal lining contribute to the clinical effects, the sequence of events resides in the functional interplay among elements within the mucosa itself. The proposed model assumes that failure of a pre-existing genomic-controlled surveillance of the epithelium localized to the luminal surface triggers primary and secondary immune activation of inflammation intent on restoring epithelial homeostasis. Delayed restoration of homeostasis results in all the symptoms, signs and likely molecular events that characterize IBS and FGIDs.
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Affiliation(s)
- Ricky McCullough
- Translational Medicine Clinic and Research Center, Storrs CT 06368, USA
- Department of Medicine, Providence VA Medical Center, Brown University School of Medicine, Providence, RI, USA
| | - Jeremiah McCullough
- Medicinal Chemistry, School of Pharmacy, University of Connecticut, Storrs CT 06268, USA
- Department of Molecular and Cell Biology, University of Connecticut, Storrs CT 06268, USA
- Department of Physiology and Neurobiology, University of Connecticut, Storrs CT 06268, USA
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44
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Mechanism of development of depression and probiotics as adjuvant therapy for its prevention and management. ACTA ACUST UNITED AC 2017. [DOI: 10.1016/j.mhp.2017.01.003] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/19/2022]
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45
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Beatty JK, Akierman SV, Motta JP, Muise S, Workentine ML, Harrison JJ, Bhargava A, Beck PL, Rioux KP, McKnight GW, Wallace JL, Buret AG. Giardia duodenalis induces pathogenic dysbiosis of human intestinal microbiota biofilms. Int J Parasitol 2017; 47:311-326. [PMID: 28237889 DOI: 10.1016/j.ijpara.2016.11.010] [Citation(s) in RCA: 110] [Impact Index Per Article: 13.8] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/26/2016] [Revised: 11/12/2016] [Accepted: 11/17/2016] [Indexed: 02/07/2023]
Abstract
Giardia duodenalis is a prevalent cause of acute diarrheal disease worldwide. However, recent outbreaks in Italy and Norway have revealed a link between giardiasis and the subsequent development of chronic post-infectious irritable bowel syndrome. While the mechanisms underlying the causation of post-infectious irritable bowel syndrome remain obscure, recent findings suggest that alterations in gut microbiota communities are linked to the pathophysiology of irritable bowel syndrome. In the present study, we use a laboratory biofilm system to culture and enrich mucosal microbiota from human intestinal biopsies. Subsequently, we show that co-culture with Giardia induces disturbances in biofilm species composition and biofilm structure resulting in microbiota communities that are intrinsically dysbiotic - even after the clearance of Giardia. These microbiota abnormalities were mediated in part by secretory-excretory Giardia cysteine proteases. Using in vitro cell culture and germ-free murine infection models, we show that Giardia-induced disruptions of microbiota promote bacterial invasion, resulting in epithelial apoptosis, tight junctional disruption, and bacterial translocation across an intestinal epithelial barrier. Additionally, these dysbiotic microbiota communities resulted in increased activation of the Toll-like receptor 4 signalling pathway, and overproduction of the pro-inflammatory cytokine IL-1beta in humanized germ-free mice. Previous studies that have sought explanations and risk factors for the development of post-infectious irritable bowel syndrome have focused on features of enteropathogens and attributes of the infected host. We propose that polymicrobial interactions involving Giardia and gut microbiota may cause persistent dysbiosis, offering a new interpretation of the reasons why those afflicted with giardiasis are predisposed to gastrointestinal disorders post-infection.
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Affiliation(s)
- Jennifer K Beatty
- Department of Biological Sciences, University of Calgary, 2500 University Drive NW, Calgary, Alberta T2N 4N1, Canada
| | - Sarah V Akierman
- Department of Biological Sciences, University of Calgary, 2500 University Drive NW, Calgary, Alberta T2N 4N1, Canada
| | - Jean-Paul Motta
- Department of Biological Sciences, University of Calgary, 2500 University Drive NW, Calgary, Alberta T2N 4N1, Canada; Department of Physiology & Pharmacology, University of Calgary, 3330 Hospital Drive NW, Calgary, Alberta T2N 4N1, Canada
| | - Stacy Muise
- Department of Biological Sciences, University of Calgary, 2500 University Drive NW, Calgary, Alberta T2N 4N1, Canada
| | - Matthew L Workentine
- Department of Biological Sciences, University of Calgary, 2500 University Drive NW, Calgary, Alberta T2N 4N1, Canada
| | - Joe J Harrison
- Department of Biological Sciences, University of Calgary, 2500 University Drive NW, Calgary, Alberta T2N 4N1, Canada
| | - Amol Bhargava
- Department of Biological Sciences, University of Calgary, 2500 University Drive NW, Calgary, Alberta T2N 4N1, Canada
| | - Paul L Beck
- Department of Medicine, Division of Gastroenterology, University of Calgary, 3330 Hospital Drive NW, Calgary, Alberta T2N 4N1, Canada
| | - Kevin P Rioux
- Department of Medicine, Division of Gastroenterology, University of Calgary, 3330 Hospital Drive NW, Calgary, Alberta T2N 4N1, Canada
| | - Gordon Webb McKnight
- Department of Medicine, McMaster University, 1280 Main Street West, Hamilton, Ontario L8S 4K1, Canada
| | - John L Wallace
- Department of Physiology & Pharmacology, University of Calgary, 3330 Hospital Drive NW, Calgary, Alberta T2N 4N1, Canada
| | - Andre G Buret
- Department of Biological Sciences, University of Calgary, 2500 University Drive NW, Calgary, Alberta T2N 4N1, Canada; Department of Physiology & Pharmacology, University of Calgary, 3330 Hospital Drive NW, Calgary, Alberta T2N 4N1, Canada.
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46
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Dong X, Chu D, Wang Z. Leukocyte-mediated Delivery of Nanotherapeutics in Inflammatory and Tumor Sites. Theranostics 2017; 7:751-763. [PMID: 28255364 PMCID: PMC5327647 DOI: 10.7150/thno.18069] [Citation(s) in RCA: 103] [Impact Index Per Article: 12.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/25/2016] [Accepted: 11/19/2016] [Indexed: 12/22/2022] Open
Abstract
Nanotechnology has become a powerful tool to potentially translate nanomedicine from bench to bedside. Nanotherapeutics are nanoparticles (NPs) loaded with drugs and possess the property of tissue targeting after surfaces of NPs are bio-functionalized. Designing smaller size of nanotherapeutics is presumed to increase tumor targeting based on the EPR (enhanced permeability and retention) effect. Since the immune systems possess a defence mechanism to fight diseases, there is an emerging concept that NPs selectively target immune cells to mediate the active delivery of drugs into sites of disease. In this review, we will focus on a key question of how nanotherapeutics specifically target immune cells and hijack them as a delivery vehicle to transport nanotherapeutics into disease tissues, thus possibly improving current therapies in inflammation, immune disorders and cancers. We will also discuss the challenges and opportunities for this new strategy of leukocyte-mediated delivery of nanotherapeutics.
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Affiliation(s)
| | | | - Zhenjia Wang
- Department of Pharmaceutical Sciences, College of Pharmacy, Washington State University, Spokane, Washington, USA 99202
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47
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GÜÇLÜ M, AĞAN AF. Relationship of peripheral blood neutrophil to lymphocyteratio and irritable bowel syndrome. Turk J Med Sci 2017; 47:1067-1071. [DOI: 10.3906/sag-1509-44] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/03/2022] Open
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Selmanovic S, Beganlic A, Salihefendic N, Ljuca F, Softic A, Smajic E. Therapeutic Effects of Curcumin on Ultrasonic Morphological Characteristics of Liver in Patients with Metabolic Syndrome. Acta Inform Med 2017; 25:169-174. [PMID: 29114108 PMCID: PMC5639892 DOI: 10.5455/aim.2017.25.169-174] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/06/2023] Open
Abstract
Introduction: Metabolic syndrome (METS) represent a simultaneous presence of multiple metabolic disorders in one person. Prevalence is increasing worldwide, which is probably related to increased obesity and sedentary lifestyle. Non-alcoholic steatosis or “fatty liver” is a metabolic disease caused by fat dysfunction. It can be a sign of some other disease, and can often be found in patients with metabolic disorders. Ultrasound is an acceptable method for the identification of fatty steatosis. There is evidence that when turmeric is used as a herbal diet, with its active metabolite of curcumin, can repair fatty acidosis and thus prevent progression of fatty steatosis complications such as cirrhosis and liver cancer. Goal. The aim of the study was to determine the effects of 400 mg curcuminaddition to the nutrition on ultrasound morphological characteristics of the liver in METS patients. Methodology: A prospective cohort study was conducted on 100 subjects with METS, treated in the family medicine practice of the Tuzla Canton, aged 35-70 years. The therapeutic effects of 400 mg curcumin on ultrasound-morphological characteristics of the liver were followed, validated by ultrasound in 50 respondents of experimental groups with METS. The data were processed by the IBM SPSS Statistics 21 statistical analysis program using parametric techniques andStudent’s t-test for paired samples. Results: There were 65% of women in the study. There were no statistically significant differences in the age of respondents within the analyzed groups. The use of 400 mg curcumin per day was statistically significantly improved ultrasound morphological characteristics of the liver in subjects with METS. Conclusion: All respondents with METS who used curcumin had beneficial effects on the morphological characteristics of the liver. Curcumin had stronger effects on subjects with METS and DM type 2 than others.
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Affiliation(s)
| | | | | | - Farid Ljuca
- Medical Faculty, Tuzla University, Tuzla, Bosnia and Herzegovina
| | - Albina Softic
- Hausarztpraxis R. Pürckhauer & Kollegen, Sontheim an der Brenz, Germany
| | - Elvisa Smajic
- Primary Health Care Center Tuzla, Tuzla, Bosnia and Herzegovina
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Li Y, Su X, Wu P, Wang J, Guo Y, Zhu J, Wang Q, Chen J, Yang F, Wei W. Proteomics analysis of IBS-D with spleen and kidney yang deficiency. JOURNAL OF TRADITIONAL CHINESE MEDICAL SCIENCES 2017. [DOI: 10.1016/j.jtcms.2017.05.006] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/19/2022] Open
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50
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Darbaky Y, Evrard B, Patrier S, Falenta J, Garcin S, Tridon A, Dapoigny M, Silberberg C, Nivoliez A, Diop L. Oral probiotic treatment of Lactobacillus rhamnosus Lcr35 ® prevents visceral hypersensitivity to a colonic inflammation and an acute psychological stress. J Appl Microbiol 2016; 122:188-200. [PMID: 27718511 DOI: 10.1111/jam.13320] [Citation(s) in RCA: 21] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/24/2016] [Revised: 09/05/2016] [Accepted: 10/05/2016] [Indexed: 12/16/2022]
Abstract
AIMS This study evaluated the efficacy of a repeated oral treatment with two active pharmaceutical ingredients (Lcr Lenio® and Lcr Restituo® ) derivated from the probiotic bacterial strain Lactobacillus rhamnosus Lcr35® in two animal models mimicking different features of irritable bowel syndrome (IBS). IBS is characterized by visceral pain associated with alteration of bowel transit. IBS patients present visceral hypersensitivity with peripheral and central origins. METHODS AND RESULTS The injection of 2,4,6-trinitrobenzenesulfonic acid (TNBS) into the proximal colon as well as an acute partial restraint stress (PRS) produces colonic hypersensitivity measured in conscious rats by a decrease in pain threshold in response to distal colonic distension. Visceral hypersensitivity was produced by injection of TNBS 7 days before colonic distension or by acute PRS on testing day. Treatments were performed once a day during eight consecutive days. CONCLUSIONS This study indicates that an 8-day probiotic treatment (Lcr Lenio and Lcr Restituo) produces an antihypersensitivity activity in both TNBS and PRS visceral pain models. As this probiotic strain attenuates peripherally and centrally induced visceral hypersensitivity in rats, it may be active in treatment of IBS symptoms. An immunomodulatory effect of the probiotics was highlighted in the TNBS model on the IL-23 secretion, suggesting a mechanism of action involving a regulation of the local IL-23/Th17 immune activation. SIGNIFICANCE AND IMPACT OF THE STUDY Two formulas of Lcr35® probiotic strain show very encouraging results for the treatment of IBS patients. Further studies are needed to better understand the role and mechanisms of probiotics on the pathogenesis of IBS.
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Affiliation(s)
| | - B Evrard
- Laboratoire d'Immunologie, Université d'Auvergne-Clermont 1, Clermont-Ferrand, France
| | - S Patrier
- Département Recherche et Développement-Biose®, Arpajon-sur-Cère, France
| | - J Falenta
- Laboratoire d'Immunologie, Université d'Auvergne-Clermont 1, Clermont-Ferrand, France
| | - S Garcin
- Laboratoire d'Immunologie, Université d'Auvergne-Clermont 1, Clermont-Ferrand, France
| | - A Tridon
- Laboratoire d'Immunologie, Université d'Auvergne-Clermont 1, Clermont-Ferrand, France
| | - M Dapoigny
- Médecine Digestive, Centre Hospitalier Universitaire (CHU) Estaing, CHU Clermont Université, Clermont-Ferrand, France
| | | | - A Nivoliez
- Département Recherche et Développement-Biose®, Arpajon-sur-Cère, France
| | - L Diop
- ANS Biotech, Riom, France
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