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Tahir AH, Ding Y, Wan J, Shah MK, Janyaro H, Li XJ, Ding MX. Impact of electro-acupuncture on EAAT2 and NMDAR-2B expression in goats with visceral hypersensitivity. Heliyon 2024; 10:e40700. [PMID: 39717594 PMCID: PMC11665384 DOI: 10.1016/j.heliyon.2024.e40700] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/26/2023] [Revised: 11/24/2024] [Accepted: 11/25/2024] [Indexed: 12/25/2024] Open
Abstract
Objective This study evaluates the effect of electro-acupuncture (EA) on visceral hypersensitivity (VH) and the expression of N-methyl-D-aspartate receptor-2B (NMDAR-2B) and glutamate transporter EAAT2 in goats. Methods Twenty-four goats were divided into four groups: saline, 2, 4, 6-Trinitrobenzenesulfonic acid (TNBS), TNBS + EA, and sham EA. EA was administered at Zusanli (ST36) with 60 Hz and 1-3 mA on specified days. Electromyography (EMG) recorded visceromotor response to colorectal distention (CRD). Spinal cords were collected for immunohistochemistry, western blotting, and RT-PCR. The ileum was examined histologically. Results The repeated EA administration significantly attenuated VH (P < 0.05) in TNBS-treated goats without similar effects in the sham group. NMDAR-2B expression increased (P < 0.01), and EAAT2 expression decreased (P < 0.01) in the TNBS group compared to saline. EA increased the EAAT2 and decreased the NMDAR-2B expression (P < 0.01) compared to TNBS, with no change in the sham-EA group. Conclusion EA may alleviate VH by upregulating EAAT2 and downregulating NMDAR-2B in the spinal cord of TNBS-treated goats, indicating its potential for treating chronic visceral pain in gastrointestinal disorders.
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Affiliation(s)
- Adnan Hassan Tahir
- College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, Hubei, China
- Faculty of Veterinary and Animal Sciences, PMAS-Arid Agriculture University, Rawalpindi, Pakistan
| | - Yi Ding
- College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, Hubei, China
| | - Juan Wan
- College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, Hubei, China
- Gannan Innovation and Transformation Medical Research Institute, First Affiliated Hospital, Gannan Medical University, Ganzhou, Jiangxi, China
| | - Manoj Kumar Shah
- College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, Hubei, China
- Department of Pharmacology and Surgery, Institute of Agriculture and Animal Science, Rampur Chitwan, Nepal
| | - Habibullah Janyaro
- College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, Hubei, China
- Shaheed Benazir Bhutto University of Veterinary and Animal Sciences, Sakrand, Pakistan
| | - Xiao-Jing Li
- College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, Hubei, China
- School of Medicine, Shanghai University, Shanghai, China
| | - Ming-Xing Ding
- College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, Hubei, China
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Gut Microbiota Manipulation in Irritable Bowel Syndrome. Microorganisms 2022; 10:microorganisms10071332. [PMID: 35889051 PMCID: PMC9319495 DOI: 10.3390/microorganisms10071332] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/29/2022] [Revised: 06/24/2022] [Accepted: 06/29/2022] [Indexed: 02/05/2023] Open
Abstract
Increased knowledge suggests that disturbed gut microbiota, termed dysbiosis, might promote the development of irritable bowel syndrome (IBS) symptoms. Accordingly, gut microbiota manipulation has evolved in the last decade as a novel treatment strategy in order to improve IBS symptoms. In using different approaches, dietary management stands first in line, including dietary fiber supplements, prebiotics, and probiotics that are shown to change the composition of gut microbiota, fecal short-chain fatty acids and enteroendocrine cells densities and improve IBS symptoms. However, the exact mixture of beneficial bacteria for each individual remains to be identified. Prescribing nonabsorbable antibiotics still needs confirmation, although using rifaximin has been approved for diarrhea-predominant IBS. Fecal microbiota transplantation (FMT) has recently gained a lot of attention, and five out of seven placebo-controlled trials investigating FMT in IBS obtain promising results regarding symptom reduction and gut microbiota manipulation. However, more data, including larger cohorts and studying long-term effects, are needed before FMT can be regarded as a treatment for IBS in clinical practice.
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Hunskar GS, Rortveit G, Litleskare S, Eide GE, Hanevik K, Langeland N, Wensaas KA. Prevalence of fibromyalgia 10 years after infection with Giardia lamblia: a controlled prospective cohort study. Scand J Pain 2022; 22:348-355. [PMID: 34679267 DOI: 10.1515/sjpain-2021-0122] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/09/2021] [Accepted: 09/21/2021] [Indexed: 12/12/2022]
Abstract
OBJECTIVES To investigate whether acute infection with Giardia lamblia is associated with fibromyalgia 10 years after infection and whether fibromyalgia is associated with irritable bowel syndrome (IBS) and chronic fatigue (CF) in this setting. METHODS A cohort study was established after an outbreak of G. lamblia in Bergen, Norway, 2004. Laboratory-confirmed cases and a matched control group were followed for 10 years. The main outcome was fibromyalgia 10 years after giardiasis, defined by the 2016 revisions of the fibromyalgia diagnostic criteria using the Fibromyalgia Survey Questionnaire (FSQ). RESULTS The prevalence of fibromyalgia was 8.6% (49/572) among Giardia exposed compared to 3.1% (21/673) in controls (p<0.001). Unadjusted odds for having fibromyalgia was higher for Giardia exposed compared to controls (odds ratio (OR): 2.91, 95% confidence interval (CI): 1.72, 4.91), but adjusted for IBS and CF it was not (OR: 1.05, 95% CI: 0.57, 1.95). Among participants without CF the odds for fibromyalgia was 6.27 times higher for participants with IBS than those without (95% CI: 3.31, 11.91) regardless of exposure. Among participants without IBS the odds for fibromyalgia was 4.80 times higher for those with CF than those without (95% CI: 2.75, 8.37). CONCLUSIONS We found a higher prevalence of fibromyalgia among Giardia exposed compared to controls 10 years after the acute infection. Fibromyalgia was strongly associated with IBS and CF, and the difference between the exposed and controls can be attributed to the high prevalence of IBS and CF among the Giardia exposed. Notably, this study was not designed to establish causality between Giardia exposure and the outcomes.
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Affiliation(s)
- Gunnhild S Hunskar
- Department of Global Public Health and Primary Care, University of Bergen, Bergen, Norway
- Department of Dermatology, Haukeland University Hospital, Bergen, Norway
- Research Unit for General Practice, NORCE Norwegian Research Centre, Bergen, Norway
| | - Guri Rortveit
- Department of Global Public Health and Primary Care, University of Bergen, Bergen, Norway
- Research Unit for General Practice, NORCE Norwegian Research Centre, Bergen, Norway
| | - Sverre Litleskare
- Research Unit for General Practice, NORCE Norwegian Research Centre, Bergen, Norway
| | - Geir Egil Eide
- Department of Global Public Health and Primary Care, University of Bergen, Bergen, Norway
- Centre for Clinical Research, Haukeland University Hospital, Bergen, Norway
| | - Kurt Hanevik
- Norwegian National Advisory Unit for Tropical Infectious Diseases, Haukeland University Hospital, Bergen, Norway
- Department of Clinical Science, University of Bergen, Bergen, Norway
| | - Nina Langeland
- Norwegian National Advisory Unit for Tropical Infectious Diseases, Haukeland University Hospital, Bergen, Norway
- Department of Clinical Science, University of Bergen, Bergen, Norway
| | - Knut-Arne Wensaas
- Research Unit for General Practice, NORCE Norwegian Research Centre, Bergen, Norway
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Saha S, Sehgal K, Singh S, Grover M, Pardi D, Khanna S. Postinfection Irritable Bowel Syndrome Following Clostridioides difficile Infection: A Systematic-review and Meta-analysis. J Clin Gastroenterol 2022; 56:e84-e93. [PMID: 34049374 PMCID: PMC8627535 DOI: 10.1097/mcg.0000000000001536] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/09/2020] [Accepted: 02/19/2021] [Indexed: 02/03/2023]
Abstract
BACKGROUND Postinfection irritable bowel syndrome (PI-IBS) affects ~14% patients after acute bacterial enterocolitis. AIM The aim of this study was to conduct a systematic review and meta-analysis to find the prevalence of PI-IBS following Clostridioides difficile infection (CDI). METHODS We systematically searched Medline, Embase, and Web of Science from inception through January 20, 2020 for cohort studies assessing PI-IBS following CDI. Primary outcome was pooled prevalence calculated using inverse variance heterogeneity model [MetaXL (v. 5.3)]. A priori subgroup analyses were done [by irritable bowel syndrome (IBS) diagnostic criteria-Rome vs. others, time of IBS diagnosis-<6 or >6 mo, exclusion or inclusion of pre-existing IBS and CDI treatment-antibiotic with fecal microbiota transplantation vs. antibiotic only]. Heterogeneity was considered substantial if I2>50%. RESULTS From 2007 to 2019, 15 studies were included (10 prospective, 5 retrospective; 9 full-text, 6 abstracts). Data from 1218 patients were included in the quantitative analysis. Risk of bias was low in 7, medium in 4 and high in 4 studies. Pooled prevalence of PI-IBS was 21.1% (95% confidence interval, 8.2%-35.7%), I2=96%. Common PI-IBS subtypes were diarrhea-predominant in 46.3% (50) patients, and mixed in 33.3% (36) patients. Subgroup analyses by IBS diagnostic criteria, time of IBS diagnosis or CDI treatment did not significantly change the primary outcome (all P>0.05), nor decrease heterogeneity. Funnel plot analysis revealed publication bias. CONCLUSIONS Over 20% of patients develop PI-IBS after CDI. Factors such as diagnostic criteria for IBS and CDI treatment did not affect prevalence, though small numbers limit the confidence in these conclusions. Larger, well conducted studies are needed to study PI-IBS in CDI.
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Affiliation(s)
- Srishti Saha
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota, USA 55905
| | - Kanika Sehgal
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota, USA 55905
| | - Sumitabh Singh
- Division of Endocrinology, Mayo Clinic, Rochester, Minnesota, USA 55905
| | - Madhusudan Grover
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota, USA 55905
| | - Darrell Pardi
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota, USA 55905
| | - Sahil Khanna
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota, USA 55905
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Layer P, Andresen V, Allescher H, Bischoff SC, Claßen M, Elsenbruch S, Freitag M, Frieling T, Gebhard M, Goebel-Stengel M, Häuser W, Holtmann G, Keller J, Kreis ME, Kruis W, Langhorst J, Jansen PL, Madisch A, Mönnikes H, Müller-Lissner S, Niesler B, Pehl C, Pohl D, Raithel M, Röhrig-Herzog G, Schemann M, Schmiedel S, Schwille-Kiuntke J, Storr M, Preiß JC, Andus T, Buderus S, Ehlert U, Engel M, Enninger A, Fischbach W, Gillessen A, Gschossmann J, Gundling F, Haag S, Helwig U, Hollerbach S, Karaus M, Katschinski M, Krammer H, Kuhlbusch-Zicklam R, Matthes H, Menge D, Miehlke S, Posovszky MC, Schaefert R, Schmidt-Choudhury A, Schwandner O, Schweinlin A, Seidl H, Stengel A, Tesarz J, van der Voort I, Voderholzer W, von Boyen G, von Schönfeld J, Wedel T. Update S3-Leitlinie Reizdarmsyndrom: Definition, Pathophysiologie, Diagnostik und Therapie. Gemeinsame Leitlinie der Deutschen Gesellschaft für Gastroenterologie, Verdauungs- und Stoffwechselkrankheiten (DGVS) und der Deutschen Gesellschaft für Neurogastroenterologie und Motilität (DGNM) – Juni 2021 – AWMF-Registriernummer: 021/016. ZEITSCHRIFT FUR GASTROENTEROLOGIE 2021; 59:1323-1415. [PMID: 34891206 DOI: 10.1055/a-1591-4794] [Citation(s) in RCA: 22] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
Affiliation(s)
- P Layer
- Medizinische Klinik, Israelitisches Krankenhaus, Hamburg, Deutschland
| | - V Andresen
- Medizinische Klinik, Israelitisches Krankenhaus, Hamburg, Deutschland
| | - H Allescher
- Zentrum für Innere Medizin, Gastroent., Hepatologie u. Stoffwechsel, Klinikum Garmisch-Partenkirchen, Garmisch-Partenkirchen, Deutschland
| | - S C Bischoff
- Institut für Ernährungsmedizin, Universität Hohenheim, Stuttgart, Deutschland
| | - M Claßen
- Klinik für Kinder- und Jugendmedizin, Klinikum Links der Weser, Bremen, Deutschland
| | - S Elsenbruch
- Klinik für Neurologie, Translational Pain Research Unit, Universitätsklinikum Essen, Essen, Deutschland.,Abteilung für Medizinische Psychologie und Medizinische Soziologie, Ruhr-Universität Bochum, Bochum, Deutschland
| | - M Freitag
- Abteilung Allgemeinmedizin Department für Versorgungsforschung, Universität Oldenburg, Oldenburg, Deutschland
| | - T Frieling
- Medizinische Klinik II, Helios Klinikum Krefeld, Krefeld, Deutschland
| | - M Gebhard
- Gemeinschaftspraxis Pathologie-Hamburg, Hamburg, Deutschland
| | - M Goebel-Stengel
- Innere Medizin II, Helios Klinik Rottweil, Rottweil, und Innere Medizin VI, Psychosomat. Medizin u. Psychotherapie, Universitätsklinikum Tübingen, Tübingen, Deutschland
| | - W Häuser
- Innere Medizin I mit Schwerpunkt Gastroenterologie, Klinikum Saarbrücken, Saarbrücken, Deutschland
| | - G Holtmann
- Faculty of Medicine & Faculty of Health & Behavioural Sciences, Princess Alexandra Hospital, Brisbane, Australien
| | - J Keller
- Medizinische Klinik, Israelitisches Krankenhaus, Hamburg, Deutschland
| | - M E Kreis
- Klinik für Allgemein-, Viszeral- und Gefäßchirurgie, Charité - Universitätsmedizin Berlin, Campus Benjamin Franklin, Berlin, Deutschland
| | | | - J Langhorst
- Klinik für Integrative Medizin und Naturheilkunde, Sozialstiftung Bamberg, Klinikum am Bruderwald, Bamberg, Deutschland
| | - P Lynen Jansen
- Deutsche Gesellschaft für Gastroenterologie, Verdauungs- und Stoffwechselkrankheiten, Berlin, Deutschland
| | - A Madisch
- Klinik für Gastroenterologie, interventionelle Endoskopie und Diabetologie, Klinikum Siloah, Klinikum Region Hannover, Hannover, Deutschland
| | - H Mönnikes
- Klinik für Innere Medizin, Martin-Luther-Krankenhaus, Berlin, Deutschland
| | | | - B Niesler
- Abteilung Molekulare Humangenetik Institut für Humangenetik, Universitätsklinikum Heidelberg, Heidelberg, Deutschland
| | - C Pehl
- Medizinische Klinik, Krankenhaus Vilsbiburg, Vilsbiburg, Deutschland
| | - D Pohl
- Klinik für Gastroenterologie und Hepatologie, Universitätsspital Zürich, Zürich, Schweiz
| | - M Raithel
- Medizinische Klinik II m.S. Gastroenterologie und Onkologie, Waldkrankenhaus St. Marien, Erlangen, Deutschland
| | | | - M Schemann
- Lehrstuhl für Humanbiologie, TU München, Deutschland
| | - S Schmiedel
- I. Medizinische Klinik und Poliklinik Gastroenterologie, Universitätsklinikum Hamburg-Eppendorf, Deutschland
| | - J Schwille-Kiuntke
- Abteilung für Psychosomatische Medizin und Psychotherapie, Medizinische Universitätsklinik Tübingen, Tübingen, Deutschland.,Institut für Arbeitsmedizin, Sozialmedizin und Versorgungsforschung, Universitätsklinikum Tübingen, Tübingen, Deutschland
| | - M Storr
- Zentrum für Endoskopie, Gesundheitszentrum Starnberger See, Starnberg, Deutschland
| | - J C Preiß
- Klinik für Innere Medizin - Gastroenterologie, Diabetologie und Hepatologie, Vivantes Klinikum Neukölln, Berlin, Deutschland
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Edogawa S, Edwinson AL, Peters SA, Chikkamenahalli LL, Sundt WJ, Graves S, Gurunathan SV, Breen-Lyles MK, Johnson S, Dyer RB, Graham RP, Chen J, Kashyap P, Farrugia G, Grover M. Serine proteases as luminal mediators of intestinal barrier dysfunction and symptom severity in IBS. Gut 2020; 69:62-73. [PMID: 30923071 PMCID: PMC6765451 DOI: 10.1136/gutjnl-2018-317416] [Citation(s) in RCA: 53] [Impact Index Per Article: 10.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/16/2018] [Revised: 03/13/2019] [Accepted: 03/16/2019] [Indexed: 12/19/2022]
Abstract
OBJECTIVE The intestinal lumen contains several proteases. Our aim was to determine the role of faecal proteases in mediating barrier dysfunction and symptoms in IBS. DESIGN 39 patients with IBS and 25 healthy volunteers completed questionnaires, assessments of in vivo permeability, ex vivo colonic barrier function in Ussing chambers, tight junction (TJ) proteins, ultrastructural morphology and 16 s sequencing of faecal microbiota rRNA. A casein-based assay was used to measure proteolytic activity (PA) in faecal supernatants (FSNs). Colonic barrier function was determined in mice (ex-germ free) humanised with microbial communities associated with different human PA states. RESULTS Patients with IBS had higher faecal PA than healthy volunteers. 8/20 postinfection IBS (PI-IBS) and 3/19 constipation- predominant IBS had high PA (>95th percentile). High-PA patients had more and looser bowel movements, greater symptom severity and higher in vivo and ex vivo colonic permeability. High-PA FSNs increased paracellular permeability, decreased occludin and increased phosphorylated myosin light chain (pMLC) expression. Serine but not cysteine protease inhibitor significantly blocked high-PA FSN effects on barrier. The effects on barrier were diminished by pharmacological or siRNA inhibition of protease activated receptor-2 (PAR-2). Patients with high-PA IBS had lower occludin expression, wider TJs on biopsies and reduced microbial diversity than patients with low PA. Mice humanised with high-PA IBS microbiota had greater in vivo permeability than those with low-PA microbiota. CONCLUSION A subset of patients with IBS, especially in PI-IBS, has substantially high faecal PA, greater symptoms, impaired barrier and reduced microbial diversity. Commensal microbiota affects luminal PA that can influence host barrier function.
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Affiliation(s)
- Shoko Edogawa
- Division of Gastroenterology & Hepatology, Mayo Clinic, Rochester, MN, USA
| | - Adam L Edwinson
- Division of Gastroenterology & Hepatology, Mayo Clinic, Rochester, MN, USA
| | - Stephanie A Peters
- Division of Gastroenterology & Hepatology, Mayo Clinic, Rochester, MN, USA
| | | | - Wendy J Sundt
- Division of Gastroenterology & Hepatology, Mayo Clinic, Rochester, MN, USA
| | - Sara Graves
- Division of Gastroenterology & Hepatology, Mayo Clinic, Rochester, MN, USA
| | | | | | - Stephen Johnson
- Division of Biomedical Statistics and Informatics and Center for Individualized Medicine, Mayo Clinic, Rochester, MN, USA
| | - Roy B Dyer
- Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN, USA
| | - Rondell P. Graham
- Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN, USA
| | - Jun Chen
- Division of Biomedical Statistics and Informatics and Center for Individualized Medicine, Mayo Clinic, Rochester, MN, USA
| | - Purna Kashyap
- Division of Gastroenterology & Hepatology, Mayo Clinic, Rochester, MN, USA
| | - Gianrico Farrugia
- Division of Gastroenterology & Hepatology, Mayo Clinic, Jacksonville, FL, USA
| | - Madhusudan Grover
- Division of Gastroenterology & Hepatology, Mayo Clinic, Rochester, MN, USA,Correspondence: Madhusudan Grover, MD, Assistant Professor of Medicine and Physiology, Enteric NeuroScience Program, Division of Gastroenterology and Hepatology, Mayo Clinic, 200 First Street SW, Rochester, MN 55905, USA, Tel: 507-284-2478, Fax: 507-266-0350,
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Sharma SG, Sharma NR, Sharma M. Impact of Human Microbiome on Health. MICROBIAL DIVERSITY, INTERVENTIONS AND SCOPE 2020. [PMCID: PMC7315774 DOI: 10.1007/978-981-15-4099-8_20] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Indexed: 12/17/2022]
Abstract
The human genome in the recent years, by the advent of technological advancements, has emerged as a major prolocutor for reciprocity between the human body and the food consumed. As known, microbiome comprises all the genetic materials within a microbiota and can thereby be also referred to as metagenome of the microbiota. Contemporary researches have revealed the influence of microbiome not only on human mind and health status, but also in wide range of disease switching, ranging from cardio-metabolic diseases, allergies and obesities to life-threatening diseases such as cancer. Though the complete mechanism of many diseases is yet unclear, research works have revealed that the metabolites, nutrients and microbes can be regarded as the key players for such physiological state. The major approach of this chapter is to enlighten the interrelationship of the microbiome on the human health either in a synergistic or in an antagonistic manner.
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Affiliation(s)
- Shiwani Guleria Sharma
- School of Bioengineering and Biosciences, Lovely Professional Univeristy, Phagwara, Punjab India
| | - Neeta Raj Sharma
- School of Bioengineering and Biosciences, Lovely Professional Univeristy, Phagwara, Punjab India
| | - Mohit Sharma
- Molecular Genetics Laboratory, Dayanand Medical College and Hospital, Ludhiana, Punjab India
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8
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Litleskare S, Rortveit G, Eide GE, Emberland KE, Hanevik K, Langeland N, Wensaas K. Quality of life and its association with irritable bowel syndrome and fatigue ten years after giardiasis. Neurogastroenterol Motil 2019; 31:e13559. [PMID: 30767352 PMCID: PMC6849782 DOI: 10.1111/nmo.13559] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/26/2018] [Revised: 12/21/2018] [Accepted: 01/06/2019] [Indexed: 12/21/2022]
Abstract
BACKGROUND Gastroenteritis has been associated with complications such as irritable bowel syndrome (IBS) and chronic fatigue (CF). Little is known about the implications for quality of life (QoL) in this setting. The aims of this study were to evaluate the association between exposure to Giardia infection and QoL ten years after the infection, and how this related to IBS and CF. METHODS We followed 1252 patients with laboratory-verified Giardia lamblia infection and a matched control group for 10 years after an epidemic in Bergen, Norway, in 2004. The main outcome was QoL after ten years as defined by the Short-form 12 version 2 with a physical component summary (PCS) and a mental component summary (MCS), both with range 0-100 (T-score). Regression analyses were performed using mixed modeling. KEY RESULTS Mean PCS T-score in the exposed group (51.4; 95% CI: 50.6-52.1) was 2.8 T-score points (95% CI: -3.8 to -1.9, P < 0.001) lower than that in the control group (54.2; 95% CI: 53.7-54.8). The mean MCS T-score was also 2.8 T-score points (95% CI: -3.8 to -1.9, P < 0.001) lower among the exposed (48.9; 95% CI: 48.2-49.6) than the controls (51.7; 95% CI: 51.1-52.4). Further analyses found that the effect of Giardia exposure on QoL was mediated by IBS and CF. CONCLUSIONS & INFERENCES Exposure to Giardia infection was associated with a lower QoL ten years later as compared to a control group, an effect that was mediated by IBS and CF.
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Affiliation(s)
- Sverre Litleskare
- Department of Global Public Health and Primary CareUniversity of BergenBergenNorway,Research Unit for General PracticeNORCE Norwegian Research CentreBergenNorway
| | - Guri Rortveit
- Department of Global Public Health and Primary CareUniversity of BergenBergenNorway,Research Unit for General PracticeNORCE Norwegian Research CentreBergenNorway
| | - Geir Egil Eide
- Department of Global Public Health and Primary CareUniversity of BergenBergenNorway,Centre for Clinical ResearchHaukeland University HospitalBergenNorway
| | - Knut Erik Emberland
- Department of Global Public Health and Primary CareUniversity of BergenBergenNorway,Research Unit for General PracticeNORCE Norwegian Research CentreBergenNorway
| | - Kurt Hanevik
- National Centre for Tropical Infectious DiseasesHaukeland University HospitalBergenNorway,Department of Clinical ScienceUniversity of BergenBergenNorway
| | - Nina Langeland
- National Centre for Tropical Infectious DiseasesHaukeland University HospitalBergenNorway,Department of Clinical ScienceUniversity of BergenBergenNorway,Haraldsplass Deaconess HospitalBergenNorway
| | - Knut‐Arne Wensaas
- Research Unit for General PracticeNORCE Norwegian Research CentreBergenNorway
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9
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Edwinson AL, Grover M. Measurement of novel intestinal secretory and barrier pathways and effects of proteases. Neurogastroenterol Motil 2019; 31:e13547. [PMID: 30843358 PMCID: PMC6407641 DOI: 10.1111/nmo.13547] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/28/2018] [Revised: 12/02/2018] [Accepted: 12/17/2018] [Indexed: 02/08/2023]
Abstract
The epithelial lining of the gastrointestinal (GI) tract in conjunction with the enteric nervous system (ENS) plays an important role in mediating solute absorption and secretion. A dysregulated ionic movement across the epithelium can result in GI diseases that manifest as either watery diarrhea or constipation. Hirschsprung disease is an example of an ENS disorder characterized by absence of enteric ganglia in distal gut resulting in obstructive phenotype. Receptor rearranged during transfection (RET) gene variants are the most commonly recognized genetic associations with Hirschsprung disease. In this issue of Neurogastroenterology and Motility, Russell et al demonstrate that RET mediates colonic ion transport through modulation of cholinergic nerves. They go on to show inhibition of RET can attenuate accelerated transit in a rat model. Normalizing secretory and absorptive defects has been an attractive therapeutic strategy. In addition to the intrinsic regulation of secretory processes, luminal mediators like bile acids, short-chain fatty acids, and proteases can affect both secretion and barrier function of the intestinal epithelium. Elevated levels of proteases have been identified in a wide range of GI diseases including irritable bowel syndrome. Proteases are known to cause visceral hypersensitivity and barrier disruption in vitro and in animal models. The goals of this review are to describe fundamental concepts related to intestinal epithelial secretion, the utility of Ussing chambers to measure ionic mechanisms and to discuss examples of novel signaling pathways; namely the RET signaling cascade in secretomotor neurons and effects of luminal proteases on barrier and ionic secretion.
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Affiliation(s)
- Adam L. Edwinson
- Division of Gastroenterology & Hepatology, Mayo Clinic, Rochester, MN, USA
| | - Madhusudan Grover
- Division of Gastroenterology & Hepatology, Mayo Clinic, Rochester, MN, USA,Correspondence: Madhusudan Grover, MD, Assistant Professor of Medicine and Physiology, Enteric NeuroScience Program, Division of Gastroenterology and Hepatology, Mayo Clinic, 200 First Street SW, Rochester, MN 55905, USA, Tel: 507-284-2478, Fax: 507-266-0350,
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Lindsay L, DuPont HL, Moe CL, Alberer M, Hatz C, Kirby AE, Wu HM, Verstraeten T, Steffen R. Estimating the incidence of norovirus acute gastroenteritis among US and European international travelers to areas of moderate to high risk of traveler's diarrhea: a prospective cohort study protocol. BMC Infect Dis 2018; 18:605. [PMID: 30509202 PMCID: PMC6276235 DOI: 10.1186/s12879-018-3461-6] [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: 11/15/2017] [Accepted: 10/31/2018] [Indexed: 12/31/2022] Open
Abstract
Background Acute gastroenteritis (AGE) is the leading cause of illness among returning travelers seeking medical care. Multiple types of enteric pathogens can cause travel-acquired AGE and, while bacterial pathogens have a predominant role, the importance of viruses, such as norovirus, is increasingly recognized. There is a lack of information on travel-acquired norovirus incidence among symptomatic and asymptomatic individuals irrespective of healthcare-seeking behavior. Our aim is to estimate the incidence of travel-acquired AGE due to norovirus and to characterize the burden of disease among international travelers from the United States and Europe. Methods We describe a prospective cohort study implemented in five US and European sites to estimate the role of AGE due to norovirus among adult international travelers. We enrolled individuals aged 18 years and older who are traveling to regions of moderate-high risk of AGE, or via cruise ship with an international port stop, with a trip duration of 3–15 days. The study will generate a wide range of health and travel-related data for pre-, during, and up to 6-months post-travel. We will identify laboratory-confirmed travel-acquired norovirus infections among both symptomatic and asymptomatic individuals from self-collected whole stool samples tested via quantitative RT-PCR. Coinfections will be identified in a subset of travelers with AGE using a multiplex molecular-based assay. Discussion This study is unique in design and breadth of data collected. The prospective collection of health and behavioral data, as well as biologic samples from travelers irrespective of symptoms, will provide useful data to better understand the importance of norovirus AGE among international travelers. This study will provide data to estimate the incidence of norovirus infections and AGE and the risk of post-infectious sequelae in the 6-month post-travel period serving as a baseline for future norovirus AGE vaccination studies. This study will contribute valuable information to better understand the role of norovirus in travel-acquired AGE risk and the impact of these infections on a broad set of outcomes.
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Affiliation(s)
- Lisa Lindsay
- P95 Pharmacovigilance and Epidemiology Services, Koning Leopold III Laan 1, 3001, Leuven, Belgium.
| | - Herbert L DuPont
- University of Texas McGovern Medical School and School of Public Health, 1200 Pressler Street, Houston, TX, 77030, USA
| | - Christine L Moe
- Emory University, Rollins School of Public Health, 1518 Clifton Road NE, Atlanta, GA, 30322, USA
| | - Martin Alberer
- Division of Infectious Diseases and Tropical Medicine, University Hospital, Ludwig-Maximilians-University (LMU) Munich, Leopoldstrasse 5, 80802, Munich, Germany
| | - Christoph Hatz
- Swiss Tropical and Public Health Institute, Socinstrasse 57, 4056, Basel, Switzerland.,University of Basel, Petersplatz 1, 4001, Basel, Switzerland.,University of Zurich; Epidemiology, Biostatistics and Prevention Institute, WHO Collaborating Centre for Travellers' Health, Hirschengraben 84, 8001, Zurich, Switzerland
| | - Amy E Kirby
- Emory University, Rollins School of Public Health, 1518 Clifton Road NE, Atlanta, GA, 30322, USA
| | - Henry M Wu
- Emory University, Division of Infectious Diseases, Department of Medicine, 550 Peachtree Street NE MOT 7, Atlanta, GA, 30308, USA
| | - Thomas Verstraeten
- P95 Pharmacovigilance and Epidemiology Services, Koning Leopold III Laan 1, 3001, Leuven, Belgium
| | - Robert Steffen
- University of Texas McGovern Medical School and School of Public Health, 1200 Pressler Street, Houston, TX, 77030, USA.,University of Zurich; Epidemiology, Biostatistics and Prevention Institute, WHO Collaborating Centre for Travellers' Health, Hirschengraben 84, 8001, Zurich, Switzerland
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11
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Shariati A, Fallah F, Pormohammad A, Taghipour A, Safari H, Chirani AS, Sabour S, Alizadeh-Sani M, Azimi T. The possible role of bacteria, viruses, and parasites in initiation and exacerbation of irritable bowel syndrome. J Cell Physiol 2018; 234:8550-8569. [PMID: 30480810 DOI: 10.1002/jcp.27828] [Citation(s) in RCA: 39] [Impact Index Per Article: 5.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/17/2018] [Accepted: 11/06/2018] [Indexed: 12/11/2022]
Abstract
Irritable bowel syndrome (IBS) is a prolonged and disabling functional gastrointestinal disorder with the incidence rate of 18% in the world. IBS could seriously affect lifetime of patients and cause high economic burden on the community. The pathophysiology of the IBS is hardly understood, whereas several possible mechanisms, such as visceral hypersensitivity, irregular gut motility, abnormal brain-gut relations, and the role of infectious agents, are implicated in initiation and development of this syndrome. Different studies demonstrated an alteration in B-lymphocytes, mast cells (MC), T-lymphocytes, and cytokine concentrations in intestinal mucosa or systemic circulation that are likely to contribute to the formation of the IBS. Therefore, IBS could be developed in those with genetic predisposition. Infections' role in initiation and exacerbation of IBS has been investigated by quite several clinical studies; moreover, the possible role of some pathogens in development and exacerbation of this disease has been described. It appears that the main obligatory pathogens correspond with the IBS disease, Clostridium difficile, Escherichia coli, Mycobacterium avium subspecies paratuberculosis, Campylobacter concisus, Campylobacter jejuni, Chlamydia trachomatis, Helicobacter pylori, Pseudomonas aeruginosa, Salmonella spp, Shigella spp, and viruses, particularly noroviruses. A number of pathogenic parasites (Blastocystis, Dientamoeba fragilis, and Giardia lamblia) may also be involved in the progression and exacerbation of the disease. Based on the current knowledge, the current study concludes that the most common bacterial, viral, and parasitic pathogens may be involved in the development and progression of IBS.
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Affiliation(s)
- Aref Shariati
- Department of Microbiology, School of Medicine, Iran University of Medical Sciences, Tehran, Iran
| | - Fateme Fallah
- Department of Microbiology, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Ali Pormohammad
- Department of Microbiology, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Ali Taghipour
- Department of Medical Parasitology and Mycology, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Hossein Safari
- Health Promotion Research Center, Iran University of Medical Sciences, Tehran, Iran
| | - Alireza Salami Chirani
- Department of Microbiology, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Sahar Sabour
- Department of Microbiology, School of Medicine, Ardebil University of Medical Science, Ardebil, Iran
| | - Mahmood Alizadeh-Sani
- Student Research Committee, Department of Food Sciences and Technology, Faculty of Nutrition and Food Sciences, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Taher Azimi
- Department of Microbiology, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran.,Department of Pathobiology, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran
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12
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Mazzawi T, Lied GA, Sangnes DA, El-Salhy M, Hov JR, Gilja OH, Hatlebakk JG, Hausken T. The kinetics of gut microbial community composition in patients with irritable bowel syndrome following fecal microbiota transplantation. PLoS One 2018; 13:e0194904. [PMID: 30427836 PMCID: PMC6235238 DOI: 10.1371/journal.pone.0194904] [Citation(s) in RCA: 59] [Impact Index Per Article: 8.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/04/2017] [Accepted: 09/28/2018] [Indexed: 11/26/2022] Open
Abstract
Background Gut microbiota alterations are important in irritable bowel syndrome (IBS). The aim was to investigate the effect of fecal microbiota transplantation (FMT) on gut microbiota and the symptoms in patients with IBS. Material and methods The study included 13 IBS patients according to Rome III criteria and 13 healthy donors. Freshly donated feces were administered to the descending part of the duodenum via a gastroscope. Feces were collected from donors and patients before FMT, and from the patients at 1, 3 and 12 weeks and donors and patients at 20/28 weeks after FMT. Microbiota analysis was performed using GA-map Dysbiosis test (Genetic Analysis AS, Oslo, Norway). The patients completed the following questionnaires before and at the aforementioned weeks after FMT: IBS Symptom Questionnaire (IBS-SQ), IBS-Symptom Severity Scoring system (IBS-SSS), Short Form of Nepean Dyspepsia Index (SF-NDI), Bristol stool form scale, the Eysenck Personality Questionnaire-Neuroticism and Hospital Anxiety and Depression. Results Donors and IBS patients had significantly different bacterial strain signals before FMT (Ruminococcus gnavus, Actinobacteria and Bifidobacteria) that became non-significant after 3 weeks following FMT. The changes in gut microbiota were similar between donors and patients at 20/28 weeks after FMT. Thus, patients’ microbiota profiles became more-or-less similar to donors. The scores of all the questionnaires were significantly improved at all time points following FMT. No reported adverse effects. Conclusions FMT was associated with a change in gut microbiota and improvement in IBS symptoms and quality of life lasting for up to 28 weeks. Trial registration ClinicalTrials.gov ID:NCT03333291
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Affiliation(s)
- Tarek Mazzawi
- Section of Gastroenterology, Department of Medicine, Haukeland University Hospital, Bergen, Norway
- Norwegian Competence Centre for Functional Gastro-Intestinal Disorders, Section of Gastroenterology, Department of Medicine, Haukeland University Hospital, Bergen, Norway
- Center for Nutrition, Department of Clinical Medicine, University of Bergen, Bergen, Norway
- * E-mail:
| | - Gülen Arslan Lied
- Section of Gastroenterology, Department of Medicine, Haukeland University Hospital, Bergen, Norway
- Norwegian Competence Centre for Functional Gastro-Intestinal Disorders, Section of Gastroenterology, Department of Medicine, Haukeland University Hospital, Bergen, Norway
- Center for Nutrition, Department of Clinical Medicine, University of Bergen, Bergen, Norway
| | - Dag André Sangnes
- Section of Gastroenterology, Department of Medicine, Haukeland University Hospital, Bergen, Norway
| | - Magdy El-Salhy
- Norwegian Competence Centre for Functional Gastro-Intestinal Disorders, Section of Gastroenterology, Department of Medicine, Haukeland University Hospital, Bergen, Norway
- Center for Nutrition, Department of Clinical Medicine, University of Bergen, Bergen, Norway
- Section of Gastroenterology, Department of Medicine, Stord Hospital, Helse-Fonna, Stord, Norway
| | - Johannes R. Hov
- Norwegian PSC Research Center, Section of Gastroenterology and Research Institute of Internal Medicine, Division of Surgery, Inflammatory Diseases and Transplantation, Oslo University Hospital and University of Oslo, Oslo, Norway
| | - Odd Helge Gilja
- Section of Gastroenterology, Department of Medicine, Haukeland University Hospital, Bergen, Norway
- Norwegian Competence Centre for Functional Gastro-Intestinal Disorders, Section of Gastroenterology, Department of Medicine, Haukeland University Hospital, Bergen, Norway
- Center for Nutrition, Department of Clinical Medicine, University of Bergen, Bergen, Norway
| | - Jan Gunnar Hatlebakk
- Section of Gastroenterology, Department of Medicine, Haukeland University Hospital, Bergen, Norway
- Norwegian Competence Centre for Functional Gastro-Intestinal Disorders, Section of Gastroenterology, Department of Medicine, Haukeland University Hospital, Bergen, Norway
- Center for Nutrition, Department of Clinical Medicine, University of Bergen, Bergen, Norway
| | - Trygve Hausken
- Section of Gastroenterology, Department of Medicine, Haukeland University Hospital, Bergen, Norway
- Norwegian Competence Centre for Functional Gastro-Intestinal Disorders, Section of Gastroenterology, Department of Medicine, Haukeland University Hospital, Bergen, Norway
- Center for Nutrition, Department of Clinical Medicine, University of Bergen, Bergen, Norway
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Abstract
GOALS The goal of this study is to evaluate the association between early life infections and subsequent adult onset irritable bowel syndrome (IBS). BACKGROUND Infections during adulthood are a known risk factor for adult-onset IBS. This investigation examined the role of childhood infections and infection risk factors in the development of IBS symptoms. STUDY In total, 1010 subjects (509 outpatients with IBS, 501 matched controls) were mailed questionnaires regarding early-life infections during infancy (0 to 12 mo), toddler years (1 to 3 y), and child years (4 to 18 y). Comparisons between cases and controls were performed using logistic regression adjusting for age, gender, and somatization score. RESULTS Around 648 (64.2%) subjects responded. The median age was 51.3 years (range, 18.0 to 70.7 y) and 535 (83%) were female. Childhood (below 18 y) infections were common in cases and controls (98% vs. 98%; P=0.465), with no differences between cases and controls during infant, toddler, and child-age periods. For gastrointestinal infections experienced below 18 years, no differences were observed by infection type (bacterial, viral, or parasitic) or age group. Cases were more likely to report bronchitis by age 18 [43% vs. 25%; P=0.003; odds ratio, 1.73 (1.20-2.51)], but not other common infections. Regular antibiotic exposure was greater amongst cases (43%) than controls (30%) [P=0.09; odds ratio, 1.37 (0.96-1.96)]. The association between bronchitis and IBS case status remained significant after adjusting for antibiotic use (P=0.01). CONCLUSIONS Greater early childhood gastrointestinal infections rates were not observed in adult individuals with IBS compared with adult controls. The study does not support a statistically significant link between early life infections and IBS aside from bronchitis.
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Litleskare S, Rortveit G, Eide GE, Hanevik K, Langeland N, Wensaas KA. Prevalence of Irritable Bowel Syndrome and Chronic Fatigue 10 Years After Giardia Infection. Clin Gastroenterol Hepatol 2018; 16:1064-1072.e4. [PMID: 29378314 DOI: 10.1016/j.cgh.2018.01.022] [Citation(s) in RCA: 44] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/29/2017] [Revised: 01/09/2018] [Accepted: 01/10/2018] [Indexed: 12/13/2022]
Abstract
BACKGROUND & AIMS Irritable bowel syndrome (IBS) is a complication that can follow gastrointestinal infection, but it is not clear if patients also develop chronic fatigue. We investigated the prevalence and odds ratio of IBS and chronic fatigue 10 years after an outbreak of Giardia lamblia, compared with a control cohort, and changes in prevalence over time. METHODS We performed a prospective follow-up study of 1252 laboratory-confirmed cases of giardiasis (exposed), which developed in Bergen, Norway in 2004. Statistics Norway provided us with information from 2504 unexposed individuals from Bergen, matched by age and sex (controls). Questionnaires were mailed to participants 3, 6, and 10 years after the outbreak. Results from the 3- and 6-year follow-up analyses have been published previously. We report the 10-year data and changes in prevalence among time points, determined by logistic regression using generalized estimating equations. RESULTS The prevalence of IBS 10 years after the outbreak was 43% (n = 248) among 576 exposed individuals and 14% (n = 94) among 685 controls (adjusted odds ratio for development of IBS in exposed individuals, 4.74; 95% CI, 3.61-6.23). At this time point, the prevalence of chronic fatigue was 26% (n = 153) among 587 exposed individuals and 11% (n = 73) among 692 controls (adjusted odds ratio, 3.01; 95% CI, 2.22-4.08). The prevalence of IBS among exposed persons did not change significantly from 6 years after infection (40%) to 10 years after infection (43%; adjusted odds ratio for the change 1.03; 95% CI, 0.87-1.22). However, the prevalence of chronic fatigue decreased from 31% at 6 years after infection to 26% at 10 years after infection (adjusted odds ratio for the change 0.74; 95% CI, 0.61-0.90). CONCLUSION The prevalence of IBS did not change significantly from 6 years after an outbreak of Giardia lamblia infection in Norway to 10 years after. However, the prevalence of chronic fatigue decreased significantly from 6 to 10 years afterward. IBS and chronic fatigue were still associated with giardiasis 10 years after the outbreak.
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Affiliation(s)
- Sverre Litleskare
- Department of Global Public Health and Primary Care, University of Bergen, Bergen, Norway; Research Unit for General Practice, Uni Research Health, Bergen, Norway.
| | - Guri Rortveit
- Department of Global Public Health and Primary Care, University of Bergen, Bergen, Norway; Research Unit for General Practice, Uni Research Health, Bergen, Norway
| | - Geir Egil Eide
- Department of Global Public Health and Primary Care, University of Bergen, Bergen, Norway; Centre for Clinical Research, Haukeland University Hospital, Bergen, Norway
| | - Kurt Hanevik
- National Centre for Tropical Infectious Diseases, Haukeland University Hospital, Bergen, Norway; Department of Clinical Science, University of Bergen, Bergen, Norway
| | - Nina Langeland
- National Centre for Tropical Infectious Diseases, Haukeland University Hospital, Bergen, Norway; Department of Clinical Science, University of Bergen, Bergen, Norway
| | - Knut-Arne Wensaas
- Department of Global Public Health and Primary Care, University of Bergen, Bergen, Norway; Research Unit for General Practice, Uni Research Health, Bergen, Norway
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15
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Assemblages A and B of Giardia duodenalis reduce enteric glial cells in the small intestine in mice. Parasitol Res 2018; 117:2025-2033. [PMID: 29728828 DOI: 10.1007/s00436-018-5853-3] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/26/2017] [Accepted: 03/28/2018] [Indexed: 02/07/2023]
Abstract
Infection of Giardia duodenalis is one of the most common human parasitic disease worldwide. This infection may be related to important changes in the enteric nervous system. The objective of this study was to evaluate the myenteric and submucosal plexuses, the intestinal muscle layer, and gastrointestinal transit in mice infected with assemblages A and B of G. duodenalis. Swiss albino mice (Mus musculus) were infected with assemblages A and B of G. duodenalis for 15 days. Gastrointestinal transit time was evaluated before euthanasia. Duodenum and jejunum were removed for histological and immunohistochemical analyses. It was observed a reduction in the enteric glial cell count and a decrease in the ratio of enteric glial cells to neurons. The number of neurons did not change, but morphological changes were observed in the duodenum and jejunum in both plexuses, including an increase in the nuclear area and a reduction of cell bodies in the myenteric plexus and a decrease in the nuclear area in the submucosal plexus. A reduction of the thickness of the muscle layer was observed in the duodenum, with no significant differences in the gastrointestinal transit times. Assemblages A and B of G. duodenalis decrease the number of enteric glial cells in the myenteric and submucosal plexuses, decrease the thickness of the muscle layer, and change the morphology of neurons. Graphical abstract ᅟ.
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Keller J, Bassotti G, Clarke J, Dinning P, Fox M, Grover M, Hellström PM, Ke M, Layer P, Malagelada C, Parkman HP, Scott SM, Tack J, Simren M, Törnblom H, Camilleri M. Expert consensus document: Advances in the diagnosis and classification of gastric and intestinal motility disorders. Nat Rev Gastroenterol Hepatol 2018; 15:291-308. [PMID: 29622808 PMCID: PMC6646879 DOI: 10.1038/nrgastro.2018.7] [Citation(s) in RCA: 155] [Impact Index Per Article: 22.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
Disturbances of gastric, intestinal and colonic motor and sensory functions affect a large proportion of the population worldwide, impair quality of life and cause considerable health-care costs. Assessment of gastrointestinal motility in these patients can serve to establish diagnosis and to guide therapy. Major advances in diagnostic techniques during the past 5-10 years have led to this update about indications for and selection and performance of currently available tests. As symptoms have poor concordance with gastrointestinal motor dysfunction, clinical motility testing is indicated in patients in whom there is no evidence of causative mucosal or structural diseases such as inflammatory or malignant disease. Transit tests using radiopaque markers, scintigraphy, breath tests and wireless motility capsules are noninvasive. Other tests of gastrointestinal contractility or sensation usually require intubation, typically represent second-line investigations limited to patients with severe symptoms and are performed at only specialized centres. This Consensus Statement details recommended tests as well as useful clinical alternatives for investigation of gastric, small bowel and colonic motility. The article provides recommendations on how to classify gastrointestinal motor disorders on the basis of test results and describes how test results guide treatment decisions.
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Affiliation(s)
- Jutta Keller
- Israelitic Hospital, Academic Hospital University of Hamburg, Orchideenstieg 14, 22297 Hamburg, Germany
| | - Gabrio Bassotti
- University of Perugia, Piazza dell’Università, 1, 06121 Perugia, Italy
| | - John Clarke
- Stanford University, 900 Blake Wilbur Dr, Palo Alto, CA 94304, USA
| | - Phil Dinning
- Flinders Medical Centre, GPO Box 2100, Adelaide 5001, Australia
| | - Mark Fox
- University Hospital Zürich, Rämistrasse 100, 8091 Zürich, Switzerland, and St. Claraspital, Kleinriehenstrasse 30, 4058 Basel, Switzerland
| | | | - Per M. Hellström
- Uppsala University Hospital, Building 40, SE‑75185, Uppsala, Sweden
| | - Meiyun Ke
- Peking Union Medical College Hospital, No.1 Shuaifuyuan Wangfujing Dongcheng District, Beijing, 100730, China
| | - Peter Layer
- Israelitic Hospital, Academic Hospital University of Hamburg, Orchideenstieg 14, 22297 Hamburg, Germany
| | - Carolina Malagelada
- University of Barcelona, Passeig de la Vall d’Hebron, 119–129, 08035 Barcelona, Spain
| | - Henry P. Parkman
- Temple University Hospital, 3401 N Broad St, Philadelphia, PA 19140, USA
| | - S. Mark Scott
- Queen Mary University of London, The Wingate Institute, 26 Ashfield Street, Whitechapel, London E1 2AJ, UK
| | - Jan Tack
- University Hospital Gasthuisberg, University of Leuven, Herestraat 49, 3000 Leuven, Belgium
| | - Magnus Simren
- Sahlgrenska Academy, University of Gothenburg, Blå stråket 5, 41345 Gothenburg, Sweden
| | - Hans Törnblom
- Sahlgrenska Academy, University of Gothenburg, Blå stråket 5, 41345 Gothenburg, Sweden
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Effects of Alkaline-Reduced Drinking Water on Irritable Bowel Syndrome with Diarrhea: A Randomized Double-Blind, Placebo-Controlled Pilot Study. EVIDENCE-BASED COMPLEMENTARY AND ALTERNATIVE MEDICINE 2018; 2018:9147914. [PMID: 29849734 PMCID: PMC5925025 DOI: 10.1155/2018/9147914] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 11/03/2017] [Revised: 03/04/2018] [Accepted: 03/06/2018] [Indexed: 02/07/2023]
Abstract
Objectives The purpose of this study was to investigate whether the ingestion of alkaline-reduced water (ARW) is helpful in improving the symptoms of diarrhea-predominant irritable bowel syndrome (IBS). Methods Twenty-seven patients (male, 25.9%; mean, 41.7 years old) with diarrhea-predominant IBS were randomly allocated to two groups. For eight weeks, the ARW group (n = 13) ingested at least 2 liters/day of ARW, while the control group (n = 14) ingested placebo water. IBS symptom scores (quality-of-life, abdominal pain/discomfort), stool form, and frequency were assessed before and after treatment via questionnaires. Results Eight patients (61.5%) in the ARW group and six patients (42.9%) in the control group indicated that their symptoms had improved in more than four out of the eight weeks of treatment (p = 0.449). The IBS quality-of-life score significantly improved from 57.2 to 30.8 in the ARW group; this improvement was significantly greater than the slight improvement from 48.7 to 42.2 observed in the control group (p = 0.029). The abdominal pain score improved from 1.8 to 0.9 in the ARW group and from 1.8 to 1.1 in the control group, with no significant group difference (p = 0.232). Conclusions Drinking ARW for eight weeks improves the quality of life in patients with diarrhea-predominant IBS.
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Bassotti G, Macchioni L, Corazzi L, Marconi P, Fettucciari K. Clostridium difficile-related postinfectious IBS: a case of enteroglial microbiological stalking and/or the solution of a conundrum? Cell Mol Life Sci 2018; 75:1145-1149. [PMID: 29285574 PMCID: PMC11105427 DOI: 10.1007/s00018-017-2736-1] [Citation(s) in RCA: 22] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/31/2017] [Revised: 12/11/2017] [Accepted: 12/20/2017] [Indexed: 02/06/2023]
Abstract
Post-infectious irritable bowel syndrome is a well-defined pathological entity that develops in about one-third of subjects after an acute infection (bacterial, viral) or parasitic infestation. Only recently it has been documented that an high incidence of post-infectious irritable bowel syndrome occurs after Clostridium difficile infection. However, until now it is not known why in some patients recovered from this infection the gastrointestinal disturbances persist for months or years. Based on our in vitro studies on enteric glial cells exposed to the effects of C. difficile toxin B, we hypothesize that persistence of symptoms up to the development of irritable bowel syndrome might be due to a disturbance/impairment of the correct functions of the enteroglial intestinal network.
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Affiliation(s)
- Gabrio Bassotti
- Department of Medicine, University of Perugia Medical School, Perugia, Italy.
- Gastroenterology and Hepatology Section, Santa Maria della Misericordia Hospital, Piazzale Menghini, 1, 06156, San Sisto (Perugia), Italy.
| | - Lara Macchioni
- Department of Experimental Medicine, University of Perugia Medical School, Perugia, Italy
| | - Lanfranco Corazzi
- Department of Experimental Medicine, University of Perugia Medical School, Perugia, Italy
| | - Pierfrancesco Marconi
- Department of Experimental Medicine, University of Perugia Medical School, Perugia, Italy
| | - Katia Fettucciari
- Department of Experimental Medicine, University of Perugia Medical School, Perugia, Italy
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Campylobacter jejuni and associated immune mechanisms: short-term effects and long-term implications for infants in low-income countries. Curr Opin Infect Dis 2018; 30:322-328. [PMID: 28157786 DOI: 10.1097/qco.0000000000000364] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/17/2022]
Abstract
PURPOSE OF REVIEW Campylobacter jejuni is recognized as one of the most common causes of food-borne gastrointestinal illness worldwide, resulting in a self-limiting dysentery in developed countries. However, it is increasingly gaining attention due to its association with postinfectious complications such as Guillain-Barré Syndrome and recently recognized importance in early childhood diarrhea in developing countries. We hypothesize that the inflammation mediated by C. jejuni infection causes environmental enteric dysfunction, and with contribution from diet and the host, microbiome may be responsible for growth faltering in children and developmental disability. RECENT FINDINGS Diet plays a major role in the impact of C. jejuni infection, both by availability of micronutrients for the bacteria and host as well as shaping the microbiome that affords resistance. Early childhood repeated exposure to the bacterium results in inflammation that affords long-term immunity but, in the short term, can lead to malabsorption, oral vaccine failure, cognitive delay and increased under-5 mortality. SUMMARY As interest in C. jejuni increases, our understanding of its virulence mechanisms has improved. However, much work remains to be done to fully understand the implications of immune-mediated inflammation and its potential role in diseases such as environmental enteric dysfunction.
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Mazzawi T, El-Salhy M. Effect of diet and individual dietary guidance on gastrointestinal endocrine cells in patients with irritable bowel syndrome (Review). Int J Mol Med 2017; 40:943-952. [PMID: 28849091 PMCID: PMC5593462 DOI: 10.3892/ijmm.2017.3096] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/21/2017] [Accepted: 07/07/2017] [Indexed: 12/13/2022] Open
Abstract
Irritable bowel syndrome (IBS) is a common chronic gastrointestinal (GI) disorder that is characterized by a combination of abdominal pain or discomfort, bloating and alterations in bowel movements. This review presents recent developments concerning the roles of diet and GI endocrine cells in the pathophysiology of IBS and of individual dietary guidance in the management of IBS. Patients with IBS typically report that food aggravates their IBS symptoms. The interactions between specific types of foodstuffs rich in fermentable oligosaccharides, disaccharides, monosaccharides and polyols (FODMAPs) and GI endocrine cells induce changes in cell densities. Providing individual dietary guidance about a low FODMAP intake, high soluble-fiber intake, and changing the proportions of protein, fat and carbohydrates helps to reduce the symptoms experienced by patients with IBS and to improve their quality of life. These improvements are due to restoring the densities of the GI endocrine cells back to normal. The reported observations emphasize the role of GI endocrine cells in the pathophysiology of IBS and support the provision of dietary guidance as a first-line treatment for managing IBS.
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Affiliation(s)
- Tarek Mazzawi
- Division of Gastroenterology, Department of Clinical Medicine, University of Bergen, 5021 Bergen, Norway
| | - Magdy El-Salhy
- Division of Gastroenterology, Department of Clinical Medicine, University of Bergen, 5021 Bergen, Norway
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Sharman SK, Islam BN, Hou Y, Usry M, Bridges A, Singh N, Sridhar S, Rao S, Browning DD. Sildenafil normalizes bowel transit in preclinical models of constipation. PLoS One 2017; 12:e0176673. [PMID: 28448580 PMCID: PMC5407793 DOI: 10.1371/journal.pone.0176673] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/09/2016] [Accepted: 04/16/2017] [Indexed: 12/12/2022] Open
Abstract
Guanylyl cyclase-C (GC-C) agonists increase cGMP levels in the intestinal epithelium to promote secretion. This process underlies the utility of exogenous GC-C agonists such as linaclotide for the treatment of chronic idiopathic constipation (CIC) and irritable bowel syndrome with constipation (IBS-C). Because GC-C agonists have limited use in pediatric patients, there is a need for alternative cGMP-elevating agents that are effective in the intestine. The present study aimed to determine whether the PDE-5 inhibitor sildenafil has similar effects as linaclotide on preclinical models of constipation. Oral administration of sildenafil caused increased cGMP levels in mouse intestinal epithelium demonstrating that blocking cGMP-breakdown is an alternative approach to increase cGMP in the gut. Both linaclotide and sildenafil reduced proliferation and increased differentiation in colon mucosa, indicating common target pathways. The homeostatic effects of cGMP required gut turnover since maximal effects were observed after 3 days of treatment. Neither linaclotide nor sildenafil treatment affected intestinal transit or water content of fecal pellets in healthy mice. To test the effectiveness of cGMP elevation in a functional motility disorder model, mice were treated with dextran sulfate sodium (DSS) to induce colitis and were allowed to recover for several weeks. The recovered animals exhibited slower transit, but increased fecal water content. An acute dose of sildenafil was able to normalize transit and fecal water content in the DSS-recovery animal model, and also in loperamide-induced constipation. The higher fecal water content in the recovered animals was due to a compromised epithelial barrier, which was normalized by sildenafil treatment. Taken together our results show that sildenafil can have similar effects as linaclotide on the intestine, and may have therapeutic benefit to patients with CIC, IBS-C, and post-infectious IBS.
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Affiliation(s)
- Sarah K. Sharman
- Department of Biochemistry and Molecular Biology, Cancer Research Center, Augusta University, Augusta, Georgia, United States of America
| | - Bianca N. Islam
- Department of Biochemistry and Molecular Biology, Cancer Research Center, Augusta University, Augusta, Georgia, United States of America
| | - Yali Hou
- Department of Biochemistry and Molecular Biology, Cancer Research Center, Augusta University, Augusta, Georgia, United States of America
| | - Margaux Usry
- Department of Biochemistry and Molecular Biology, Cancer Research Center, Augusta University, Augusta, Georgia, United States of America
| | - Allison Bridges
- Department of Biochemistry and Molecular Biology, Cancer Research Center, Augusta University, Augusta, Georgia, United States of America
| | - Nagendra Singh
- Department of Biochemistry and Molecular Biology, Cancer Research Center, Augusta University, Augusta, Georgia, United States of America
| | - Subbaramiah Sridhar
- Department of Medicine, Division of Gastroenterology and Hepatology, Augusta University, Augusta, Georgia, United States of America
| | - Satish Rao
- Department of Medicine, Division of Gastroenterology and Hepatology, Augusta University, Augusta, Georgia, United States of America
| | - Darren D. Browning
- Department of Biochemistry and Molecular Biology, Cancer Research Center, Augusta University, Augusta, Georgia, United States of America
- * E-mail:
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Affiliation(s)
- Eamonn M M Quigley
- Lynda K and David M Underwood Center for Digestive Disorders, Division of Gastroenterology and Hepatology, Houston Methodist Hospital and Weill Cornell Medical College, Houston, Texas.
| | - Anthony J Lembo
- Harvard Medical School, Department of Medicine, Division of Gastroenterology, Beth Israel Deaconess Medical Center, Boston, Massachusetts
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Wouters MM, Van Wanrooy S, Nguyen A, Dooley J, Aguilera-Lizarraga J, Van Brabant W, Garcia-Perez JE, Van Oudenhove L, Van Ranst M, Verhaegen J, Liston A, Boeckxstaens G. Psychological comorbidity increases the risk for postinfectious IBS partly by enhanced susceptibility to develop infectious gastroenteritis. Gut 2016; 65:1279-88. [PMID: 26071133 DOI: 10.1136/gutjnl-2015-309460] [Citation(s) in RCA: 51] [Impact Index Per Article: 5.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/25/2015] [Accepted: 05/19/2015] [Indexed: 12/22/2022]
Abstract
OBJECTIVE Psychological factors increase the risk to develop postinfectious IBS (PI-IBS), but the mechanisms involved are unclear. As stress affects the immune system, we investigated the potential interaction between psychological factors, the immune response against infectious gastroenteritis (IGE) and the development of IGE and PI-IBS in a large cohort exposed to contaminated drinking water. DESIGN 18 620 people exposed to contaminated drinking water (norovirus, Giardia lamblia, Campylobacter jejuni) were invited to participate in a prospective controlled cohort study. They were asked to complete questionnaires assessing demographic, psychological and clinical data during the outbreak and 1 year later. At both time points, in-depth immune function (peripheral blood and rectal biopsies) was studied in a subgroup of subjects. RESULTS 1379 subjects completed the questionnaires during the outbreak, of which 271 developed IGE. Risk factors for IGE included younger age, pre-existing dyspepsia-like symptoms, anxiety and drinking contaminated tap water. Anxiety scores before the outbreak inversely correlated with interleukin-2-expressing CD4+ T cells (r=0.6, p=0.01, n=23). At follow-up, 34 of 172 (20%) IGE subjects developed IBS compared with 24/366 exposed participants (7%, p<0.0001, χ(2) test). A Th2 cytokine phenotype at time of infection was associated with increased risk for PI-IBS 1 year later. Except for increased B cell numbers, no evidence for systemic or rectal mucosal immune activation in PI-IBS was demonstrated at follow-up. CONCLUSIONS Our study shows that the increased risk of patients with psychological comorbidity to develop PI-IBS may partly result from an increased susceptibility to develop IGE, possibly resulting from a Th2-immune bias. TRIAL REGISTRATION NUMBER (ClinicalTrials.gov NCT01497847).
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Affiliation(s)
- Mira M Wouters
- Department of Clinical and Experimental Medicine, Translational Research Center for Gastrointestinal Disorders, University Hospital Leuven, KU Leuven, Leuven, Belgium
| | - Sander Van Wanrooy
- Department of Clinical and Experimental Medicine, Translational Research Center for Gastrointestinal Disorders, University Hospital Leuven, KU Leuven, Leuven, Belgium
| | - Anh Nguyen
- Department of Microbiology and Immunology, KU Leuven, Leuven, Belgium Autoimmune Genetics Laboratory, VIB, Leuven, Belgium
| | - James Dooley
- Department of Microbiology and Immunology, KU Leuven, Leuven, Belgium Autoimmune Genetics Laboratory, VIB, Leuven, Belgium
| | - Javier Aguilera-Lizarraga
- Department of Clinical and Experimental Medicine, Translational Research Center for Gastrointestinal Disorders, University Hospital Leuven, KU Leuven, Leuven, Belgium
| | - Winde Van Brabant
- Department of Clinical and Experimental Medicine, Translational Research Center for Gastrointestinal Disorders, University Hospital Leuven, KU Leuven, Leuven, Belgium
| | - Josselyn E Garcia-Perez
- Department of Microbiology and Immunology, KU Leuven, Leuven, Belgium Autoimmune Genetics Laboratory, VIB, Leuven, Belgium
| | - Lukas Van Oudenhove
- Department of Clinical and Experimental Medicine, Translational Research Center for Gastrointestinal Disorders, University Hospital Leuven, KU Leuven, Leuven, Belgium
| | - Marc Van Ranst
- Laboratory of Clinical Virology, Rega Institute for Medical Research, University Hospital Leuven, Leuven, Belgium
| | - Jan Verhaegen
- Department of Microbiology, University Hospital Leuven, KU Leuven, Leuven, Belgium
| | - Adrian Liston
- Department of Microbiology and Immunology, KU Leuven, Leuven, Belgium Autoimmune Genetics Laboratory, VIB, Leuven, Belgium
| | - Guy Boeckxstaens
- Department of Clinical and Experimental Medicine, Translational Research Center for Gastrointestinal Disorders, University Hospital Leuven, KU Leuven, Leuven, Belgium
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Putignani L, Del Chierico F, Vernocchi P, Cicala M, Cucchiara S, Dallapiccola B. Gut Microbiota Dysbiosis as Risk and Premorbid Factors of IBD and IBS Along the Childhood-Adulthood Transition. Inflamm Bowel Dis 2016; 22:487-504. [PMID: 26588090 DOI: 10.1097/mib.0000000000000602] [Citation(s) in RCA: 100] [Impact Index Per Article: 11.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
Gastrointestinal disorders, although clinically heterogeneous, share pathogenic mechanisms, including genetic susceptibility, impaired gut barrier function, altered microbiota, and environmental triggers (infections, social and behavioral factors, epigenetic control, and diet). Gut microbiota has been studied for inflammatory bowel disease (IBD) and irritable bowel syndrome (IBS) in either children or adults, while modifiable gut microbiota features, acting as risk and premorbid factors along the childhood-adulthood transition, have not been thoroughly investigated so far. Indeed, the relationship between variations of the entire host/microbiota/environmental scenario and clinical phenotypes is still not fully understood. In this respect, tracking gut dysbiosis grading may help deciphering host phenotype-genotype associations and microbiota shifts in an integrated top-down omics-based approach within large-scale pediatric and adult case-control cohorts. Large-scale gut microbiota signatures and host inflammation patterns may be integrated with dietary habits, under genetic and epigenetic constraints, providing gut dysbiosis profiles acting as risk predictors of IBD or IBS in preclinical cases. Tracking dysbiosis supports new personalized/stratified IBD and IBS prevention programmes, generating Decision Support System tools. They include (1) high risk or flare-up recurrence -omics-based dysbiosis profiles; (2) microbial and molecular biomarkers of health and disease; (3) -omics-based pipelines for laboratory medicine diagnostics; (4) health apps for self-management of score-based dietary profiles, which can be shared with clinicians for nutritional habit and lifestyle amendment; (5) -omics profiling data warehousing and public repositories for IBD and IBS profile consultation. Dysbiosis-related indexes can represent novel laboratory and clinical medicine tools preventing or postponing the disease, finally interfering with its natural history.
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Affiliation(s)
- Lorenza Putignani
- *Unit of Parasitology, Bambino Gesù Children's Hospital, IRCCS, Rome, Italy; †Unit of Metagenomics, Bambino Gesù Children's Hospital, IRCCS, Rome, Italy; ‡Gastroenterology Unit, University Campus Bio-Medico of Rome, Rome, Italy; §Department of Pediatrics, Center for Pediatric Inflammatory Bowel Disease, University of Rome "La Sapienza," Rome, Italy; and ‖Scientific Directorate, Bambino Gesù Children's Hospital, IRCCS, Rome, Italy
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Abstract
PURPOSE OF REVIEW The study reviews recent publications that build on previous studies showing that acute enteric infection can produce persistent dysfunction in the lower gut (postinfectious irritable bowel syndrome) and proximal gut (postinfectious functional dyspepsia). The review addresses risk factors, the pathophysiological basis of persistent gut dysfunction, and the factors that initiate and maintain it. RECENT FINDINGS Recent work has identified several loci of host genetic predisposition to these syndromes that focus attention on host immune responses that may lead to gut dysfunction, including changes in intestinal barrier function and cytokine responses to the initial infection. Human and animal studies identify changes in the serotonergic and cannabinoid pathways regulating visceral pain responses and gut motility. Recent work has also focused attention on the putative role of the intestinal microbiota or dysbiosis in maintaining gut dysfunction and this is reviewed in depth. SUMMARY The development of long-term consequences following an acute episode of gastroenteritis reflects a convergence of host factors that include genetic predisposition and psychological factors, as well as the development of intestinal dysbiosis. It is anticipated that future research will generate biomarkers of susceptibility as well as novel microbiota-directed preventive and therapeutic strategies.
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Paula H, Grover M, Halder SL, Locke GR, Schleck CD, Zinsmeister AR, Talley NJ. Non-enteric infections, antibiotic use, and risk of development of functional gastrointestinal disorders. Neurogastroenterol Motil 2015; 27:1580-6. [PMID: 26303310 PMCID: PMC4624515 DOI: 10.1111/nmo.12655] [Citation(s) in RCA: 47] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/29/2015] [Accepted: 07/17/2015] [Indexed: 12/11/2022]
Abstract
BACKGROUND Gastrointestinal infections are risk factors for irritable bowel syndrome (IBS) and functional dyspepsia (FD). We investigated whether non-enteric infections and antibiotic exposure are also associated with the development of functional gastrointestinal disorders (FGIDs). METHODS In a nested case-control study, random samples of Olmsted County, MN, were mailed valid self-report questionnaires from 1988 through 1994, and then follow-up questionnaires from 1995 through 2003. Survey responders who did not report any FGID symptoms at baseline, but then reported such symptoms in at least one subsequent survey, were classified as new-onset cases. Age-matched controls were individuals who did not have symptoms at either the initial or subsequent surveys. KEY RESULTS The overall response rate was 78% to the initial survey and 52% to the follow-up survey. Based on the responses, 316 participants had a new onset of an FGID (43 IBS constipation, 95 IBS diarrhea, 25 IBS mixed, and 153 other FGIDs, including FD) and 250 did not (controls). Around 76% (241/316) of cases reported a non-enteric infection vs 66% (166/250) of the controls. The frequency of enteric infections was similar between the two groups. Of the new FGID cases, 83% had a non-enteric infection that was treated with antibiotic. In a logistic regression model, treatment with antibiotics for a non-gastrointestinal infection was associated with the development of an FGID (odds ratio = 1.90; 95% CI: 1.21-2.98; p = 0.005), after adjusting for age and sex. CONCLUSIONS & INFERENCES Based on a case-control study, treatment of a non-gastrointestinal infection with antibiotics appears to be a risk factor for development of an FGID.
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Affiliation(s)
- Helga Paula
- Medizinisch-Diagnostische Laboratorium West OG, Vienna, Austria
| | - Madhusudan Grover
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN, USA
| | - Smita L. Halder
- Division of Gastroenterology, McMaster University, Hamilton, Ontario, Canada
| | - G. Richard Locke
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN, USA
| | - Cathy D. Schleck
- Division of Biomedical Statistics and Informatics, Mayo Clinic, Rochester, MN, USA
| | - Alan R. Zinsmeister
- Division of Biomedical Statistics and Informatics, Mayo Clinic, Rochester, MN, USA
| | - Nicholas J Talley
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN, USA,Faculty of Health and Medicine, University of Newcastle, New Lambton, NSW, Australia
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Marynowski M, Likońska A, Zatorski H, Fichna J. Role of environmental pollution in irritable bowel syndrome. World J Gastroenterol 2015; 21:11371-11378. [PMID: 26523104 PMCID: PMC4616213 DOI: 10.3748/wjg.v21.i40.11371] [Citation(s) in RCA: 23] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/22/2015] [Revised: 07/28/2015] [Accepted: 09/14/2015] [Indexed: 02/06/2023] Open
Abstract
Irritable bowel syndrome (IBS), with the prevalence of 10%-20 % of the population has become an emerging problem worldwide. IBS is a functional gastrointestinal (GI) disorder characterized by abdominal pain or discomfort and altered bowel habits. The etiology of IBS contains genetic, psychological, and immunological factors, and has not been fully elucidated; of note, recent studies also point at environmental pollution and its role in the development of functional GI diseases. In this review we focus on several environmental factors, such as bacterial contamination, air pollution, radiation and even stress as potential triggers of IBS. We discuss associated disturbances in homeostasis, such as changes in intestinal microbiome and related pathophysiological mechanisms. Based on the effect of environmental factors on the GI tract, we also propose novel targets in IBS treatment.
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Abstract
Despite an extensive body of reported information about peripheral and central mechanisms involved in the pathophysiology of IBS symptoms, no comprehensive disease model has emerged that would guide the development of novel, effective therapies. In this Review, we will first describe novel insights into some key components of brain-gut interactions, starting with the emerging findings of distinct functional and structural brain signatures of IBS. We will then point out emerging correlations between these brain networks and genomic, gastrointestinal, immune and gut-microbiome-related parameters. We will incorporate this new information, as well as the reported extensive literature on various peripheral mechanisms, into a systems-based disease model of IBS, and discuss the implications of such a model for improved understanding of the disorder, and for the development of more-effective treatment approaches in the future.
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Affiliation(s)
- Emeran A Mayer
- Department of Medicine, University of California at Los Angeles, 10833 Le Conte Avenue, Los Angeles, CA 90095-7378, USA
| | - Jennifer S Labus
- Department of Medicine, University of California at Los Angeles, 10833 Le Conte Avenue, Los Angeles, CA 90095-7378, USA
| | - Kirsten Tillisch
- Department of Medicine, University of California at Los Angeles, 10833 Le Conte Avenue, Los Angeles, CA 90095-7378, USA and West Los Angeles VA Medical Center, 11301 Wilshire Boulevard, Los Angeles, CA 90073, USA
| | - Steven W Cole
- Department of Medicine, University of California at Los Angeles, 10833 Le Conte Avenue, Los Angeles, CA 90095-7378, USA
| | - Pierre Baldi
- Institute for Genomics and Bioinformatics, University of California at Irvine, 4038 Bren Hall, Irvine, CA 92697-3435, USA
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Schwille-Kiuntke J, Enck P, Polster AV, Gaile M, Kremsner PG, Zanger P. Postinfectious irritable bowel syndrome after travelers' diarrhea--a cohort study. Neurogastroenterol Motil 2015; 27:1147-55. [PMID: 26009981 DOI: 10.1111/nmo.12601] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/05/2015] [Accepted: 04/24/2015] [Indexed: 12/19/2022]
Abstract
BACKGROUND There is sound evidence for the role of gastrointestinal infections in the development of postinfectious irritable bowel syndrome (PI-IBS), but understanding the interaction between mental factors and the infection remains incomplete. This study aims to (i) assess the occurrence of PI-IBS in a cohort of patients with self-reported travelers' diarrhea (TD), (ii) assess risk factors for PI-IBS development, and (iii) investigate the prognosis of PI-IBS after 1 year. METHODS Patients consulting the travel clinic at the University Hospital Tuebingen, Germany (in 2009 and 2010) were identified from records and questioned in follow-ups in 2011 and 2012. We used the Rome III modular questionnaire to assess IBS, the Hospital Anxiety and Depression Scale to assess anxiety and depression, and the Patient Health Questionnaire to assess somatization. KEY RESULTS We identified 529 eligible subjects from the clinical records. Of 135 subjects (age: 36.6 ± 14.6 years, 58.5% female) included in the study sample 6.7% (95% CI 3.0-11.1) had PI-IBS. We found more females (88.9% vs 56.3%, p = 0.08) and younger age subjects (mean 29.3 vs 37.1 years, p = 0.02) among the PI-IBS subjects. A multivariable regression model revealed vomiting at baseline and high somatization scores as strong and independent PI-IBS risk factors. One year later PI-IBS occurrence decreased to 3.3% (three cases of 90). CONCLUSIONS & INFERENCES Our findings underline the close linkage of mental and somatic processes for the manifestation of PI-IBS. Screening for psychiatric comorbidities in patients with severe gastrointestinal infections may allow identifying groups at high risk for PI-IBS.
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Affiliation(s)
- J Schwille-Kiuntke
- Department of Internal Medicine VI: Psychosomatic Medicine and Psychotherapy, University Hospital Tübingen, Tübingen, Germany
| | - P Enck
- Department of Internal Medicine VI: Psychosomatic Medicine and Psychotherapy, University Hospital Tübingen, Tübingen, Germany
| | - A V Polster
- Department of Internal Medicine VI: Psychosomatic Medicine and Psychotherapy, University Hospital Tübingen, Tübingen, Germany.,Department of Internal Medicine, University of Gothenburg, Gothenburg, Sweden
| | - M Gaile
- Department of Internal Medicine VII: Institute of Tropical Medicine, University Hospital Tübingen, Tübingen, Germany
| | - P G Kremsner
- Department of Internal Medicine VII: Institute of Tropical Medicine, University Hospital Tübingen, Tübingen, Germany
| | - P Zanger
- Department of Internal Medicine VII: Institute of Tropical Medicine, University Hospital Tübingen, Tübingen, Germany.,Institute of Public Health, University Hospital Heidelberg, Heidelberg, Germany
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Sayuk GS, Gyawali CP. Irritable bowel syndrome: modern concepts and management options. Am J Med 2015; 128:817-27. [PMID: 25731138 DOI: 10.1016/j.amjmed.2015.01.036] [Citation(s) in RCA: 32] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/01/2015] [Revised: 01/17/2015] [Accepted: 01/20/2015] [Indexed: 12/14/2022]
Abstract
Irritable bowel syndrome is the most common functional gastrointestinal disorder, manifesting as abdominal pain/discomfort and altered bowel function. Despite affecting as many as 20% of adults, a lack of understanding of etiopathogenesis and evaluation strategies results in diagnostic uncertainty, and in turn frustration of both the physician and the patient. This review summarizes the current literature on the diagnosis and management of irritable bowel syndrome, with attention to evidence-based approaches. A 4-step treatment strategy that has been used successfully in our tertiary referral practice is presented and should lead to successful therapeutic outcomes in the majority of patients with irritable bowel syndrome.
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Affiliation(s)
- Gregory S Sayuk
- Division of Gastroenterology, Washington University School of Medicine, St Louis, Mo; Department of Psychiatry, Washington University School of Medicine, St Louis, Mo; John Cochran Veteran Affairs Medical Center, St Louis, Mo
| | - C Prakash Gyawali
- Division of Gastroenterology, Washington University School of Medicine, St Louis, Mo.
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Kelly CR, Kahn S, Kashyap P, Laine L, Rubin D, Atreja A, Moore T, Wu G. Update on Fecal Microbiota Transplantation 2015: Indications, Methodologies, Mechanisms, and Outlook. Gastroenterology 2015; 149:223-37. [PMID: 25982290 PMCID: PMC4755303 DOI: 10.1053/j.gastro.2015.05.008] [Citation(s) in RCA: 418] [Impact Index Per Article: 41.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
The community of microorganisms within the human gut (or microbiota) is critical to health and functions with a level of complexity comparable to that of an organ system. Alterations of this ecology (or dysbiosis) have been implicated in a number of disease states, and the prototypical example is Clostridium difficile infection (CDI). Fecal microbiota transplantation (FMT) has been demonstrated to durably alter the gut microbiota of the recipient and has shown efficacy in the treatment of patients with recurrent CDI. There is hope that FMT may eventually prove beneficial for the treatment of other diseases associated with alterations in gut microbiota, such as inflammatory bowel disease, irritable bowel syndrome, and metabolic syndrome, to name a few. Although the basic principles that underlie the mechanisms by which FMT shows therapeutic efficacy in CDI are becoming apparent, further research is needed to understand the possible role of FMT in these other conditions. Although relatively simple to perform, questions regarding both short-term and long-term safety as well as the complex and rapidly evolving regulatory landscape has limited widespread use. Future work will focus on establishing best practices and more robust safety data than exist currently, as well as refining FMT beyond current "whole-stool" transplants to increase safety and tolerability. Encapsulated formulations, full-spectrum stool-based products, and defined microbial consortia are all in the immediate future.
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Affiliation(s)
- Colleen R Kelly
- Lifespan Women's Medicine Collaborative, The Miriam Hospital, Alpert Medical School of Brown University, Providence, Rhode Island.
| | - Stacy Kahn
- Inflammatory Bowel Disease Center, Section of Pediatric Gastroenterology, Hepatology, & Nutrition, University of Chicago, Chicago, Illinois
| | - Purna Kashyap
- Department of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota
| | - Loren Laine
- Section of Digestive Diseases, Yale School of Medicine, New Haven, Connecticut; Veterans Affairs Connecticut Healthcare System, West Haven, Connecticut
| | - David Rubin
- Inflammatory Bowel Disease Center, Section of Pediatric Gastroenterology, Hepatology, & Nutrition, University of Chicago, Chicago, Illinois
| | - Ashish Atreja
- Sinai AppLab, Division of Gastroenterology, Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, New York
| | - Thomas Moore
- Infectious Disease Consultants of Kansas, Wichita, Kansas
| | - Gary Wu
- Division of Gastroenterology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania
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Kaakoush NO, Castaño-Rodríguez N, Mitchell HM, Man SM. Global Epidemiology of Campylobacter Infection. Clin Microbiol Rev 2015; 28:687-720. [PMID: 26062576 PMCID: PMC4462680 DOI: 10.1128/cmr.00006-15] [Citation(s) in RCA: 950] [Impact Index Per Article: 95.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022] Open
Abstract
Campylobacter jejuni infection is one of the most widespread infectious diseases of the last century. The incidence and prevalence of campylobacteriosis have increased in both developed and developing countries over the last 10 years. The dramatic increase in North America, Europe, and Australia is alarming, and data from parts of Africa, Asia, and the Middle East indicate that campylobacteriosis is endemic in these areas, especially in children. In addition to C. jejuni, there is increasing recognition of the clinical importance of emerging Campylobacter species, including Campylobacter concisus and Campylobacter ureolyticus. Poultry is a major reservoir and source of transmission of campylobacteriosis to humans. Other risk factors include consumption of animal products and water, contact with animals, and international travel. Strategic implementation of multifaceted biocontrol measures to reduce the transmission of this group of pathogens is paramount for public health. Overall, campylobacteriosis is still one of the most important infectious diseases that is likely to challenge global health in the years to come. This review provides a comprehensive overview of the global epidemiology, transmission, and clinical relevance of Campylobacter infection.
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Affiliation(s)
- Nadeem O Kaakoush
- School of Biotechnology and Biomolecular Sciences, The University of New South Wales, Sydney, NSW, Australia
| | - Natalia Castaño-Rodríguez
- School of Biotechnology and Biomolecular Sciences, The University of New South Wales, Sydney, NSW, Australia
| | - Hazel M Mitchell
- School of Biotechnology and Biomolecular Sciences, The University of New South Wales, Sydney, NSW, Australia
| | - Si Ming Man
- School of Biotechnology and Biomolecular Sciences, The University of New South Wales, Sydney, NSW, Australia Department of Immunology, St. Jude Children's Research Hospital, Memphis, Tennessee, USA
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Mansueto P, D’Alcamo A, Seidita A, Carroccio A. Food allergy in irritable bowel syndrome: The case of non-celiac wheat sensitivity. World J Gastroenterol 2015; 21:7089-109. [PMID: 26109796 PMCID: PMC4476871 DOI: 10.3748/wjg.v21.i23.7089] [Citation(s) in RCA: 35] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/10/2015] [Revised: 04/04/2015] [Accepted: 05/07/2015] [Indexed: 02/06/2023] Open
Abstract
Irritable bowel syndrome (IBS) is one of the most common gastrointestinal disorders, having a prevalence of 12%-30% in the general population. Most patients with IBS attribute their symptoms to adverse food reactions. We review the role of diet in the pathogenesis of IBS and the importance of dietary factors in the management of these patients. The MEDLINE electronic database (1966 to Jan 2015) was searched using the following keywords: "food", "diet", "food allergy", "food hypersensitivity", "food intolerance", "IBS", "epidemiology", "pathogenesis", "pathophysiology", "diagnosis", "treatment". We found 153 eligible papers; 80 were excluded because: not written in English, exclusive biochemical and experimental research, case reports, reviews, and research otherwise not relevant to our specific interest. We selected 73 papers: 43 original papers, 26 reviews and 4 letters to the editor. These papers focused on IBS pathogenesis, the association between IBS and atopy, and between IBS and food allergy, the relationship between IBS and non-celiac wheat sensitivity, the role of diet in IBS. Pending further scientific evidence, a cautious approach is advisable but the concept of food allergy should be included as a possible cause of IBS, and a dietary approach may have a place in the routine clinical management of IBS.
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Schwille-Kiuntke J, Mazurak N, Enck P. Systematic review with meta-analysis: post-infectious irritable bowel syndrome after travellers' diarrhoea. Aliment Pharmacol Ther 2015; 41:1029-37. [PMID: 25871571 DOI: 10.1111/apt.13199] [Citation(s) in RCA: 71] [Impact Index Per Article: 7.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/17/2014] [Revised: 12/11/2014] [Accepted: 03/25/2015] [Indexed: 01/06/2023]
Abstract
BACKGROUND Gastrointestinal infection is known as a risk factor for the development of the irritable bowel syndrome (post-infectious irritable bowel syndrome, PI-IBS). The incidence of PI-IBS ranges between 3% and over 30% of people after infectious gastroenteritis. AIM To perform a meta-analysis pools and report data concerning the relative risk (RR) of PI-IBS after TD. METHODS Database search using Medline through PubMed, Scopus, EBM Reviews (Cochrane Database of Systematic Reviews) and PsycINFO was performed to identify relevant studies. Those that met the inclusion criteria were pooled. A random effects model (Mantel-Haenszel) was performed. RESULTS Six eligible studies were found. In three of six studies, the authors reported a statistically significant association of TD and PI-IBS. The pooled RR was 3.35 (95% CI: 2.22-5.05) with a significant overall effect (P < 0.00001). Overall PI-IBS incidence was 5.4% in TD subjects and 1.4% in healthy subjects. There was no significant heterogeneity within the pooled studies (I(2) = 5%). Self-reported TD alone resulted in an over 1.5-fold RR for PI-IBS compared to laboratory-confirmed TD [RR 3.90 (95% CI: 2.35-6.49) vs. RR 2.42 (95% CI: 1.22-4.78)]. CONCLUSIONS There is a strong association between travellers' diarrhoea and post-infectious irritable bowel syndrome. Self-reports of exposure seem to result in a higher post-infectious irritable bowel syndrome occurrence than laboratory-confirmed cases of travellers' diarrhoea, but further studies are needed to confirm this finding. Finally, potential influences of the selection of an appropriate study population on post-infectious irritable bowel syndrome epidemiology are discussed.
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Affiliation(s)
- J Schwille-Kiuntke
- Department of Internal Medicine VI: Psychosomatic Medicine and Psychotherapy, University Hospital Tuebingen, Tuebingen, Germany
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Robyn J, Rasschaert G, Pasmans F, Heyndrickx M. Thermotolerant Campylobacter during Broiler Rearing: Risk Factors and Intervention. Compr Rev Food Sci Food Saf 2015; 14:81-105. [PMID: 33401809 DOI: 10.1111/1541-4337.12124] [Citation(s) in RCA: 33] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/07/2014] [Accepted: 10/07/2014] [Indexed: 01/01/2023]
Abstract
Thermotolerant Campylobacters are one of the most important bacterial causative agents of human gastrointestinal illness worldwide. In most European Union (EU) member states human campylobacteriosis is mainly caused by infection with Campylobacter jejuni or Campylobacter coli following consumption or inadequate handling of Campylobacter-contaminated poultry meat. To date, no effective strategy to control Campylobacter colonization of broilers during rearing is available. In this review, we describe the public health problem posed by Campylobacter presence in broilers and list and critically review all currently known measures that have been researched to lower the numbers of Campylobacter bacteria in broilers during rearing. We also discuss the most promising measures and which measures should be investigated further. We end this review by elaborating on readily usable measures to lower Campylobacter introduction and Campylobacter numbers in a broiler flock.
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Affiliation(s)
- Joris Robyn
- the Inst. for Agricultural and Fisheries Research (ILVO), Technology and Food Science Unit, Brusselsesteenweg 370, Melle, Belgium
| | - Geertrui Rasschaert
- the Inst. for Agricultural and Fisheries Research (ILVO), Technology and Food Science Unit, Brusselsesteenweg 370, Melle, Belgium
| | - Frank Pasmans
- the Dept. of Pathology, Bacteriology and Avian Diseases, Faculty of Veterinary Medicine, Ghent Univ, Salisburylaan 133, Merelbeke, Belgium
| | - Marc Heyndrickx
- the Inst. for Agricultural and Fisheries Research (ILVO), Technology and Food Science Unit, Brusselsesteenweg 370, Melle, Belgium.,the Dept. of Pathology, Bacteriology and Avian Diseases, Faculty of Veterinary Medicine, Ghent Univ, Salisburylaan 133, Merelbeke, Belgium
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Joo YE. Alteration of fecal microbiota in patients with postinfectious irritable bowel syndrome. J Neurogastroenterol Motil 2015; 21:135-7. [PMID: 25611066 PMCID: PMC4288086 DOI: 10.5056/jnm14133] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/05/2014] [Revised: 12/28/2014] [Accepted: 12/28/2014] [Indexed: 12/16/2022] Open
Affiliation(s)
- Young Eun Joo
- Department of Internal Medicine, Chonnam National University Medical School, Gwangju, Korea
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Del Valle-Pinero AY, Sherwin LB, Anderson EM, Caudle RM, Henderson WA. Altered vasoactive intestinal peptides expression in irritable bowel syndrome patients and rats with trinitrobenzene sulfonic acid-induced colitis. World J Gastroenterol 2015; 21:155-163. [PMID: 25574088 PMCID: PMC4284331 DOI: 10.3748/wjg.v21.i1.155] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/09/2014] [Revised: 10/29/2014] [Accepted: 11/19/2014] [Indexed: 02/06/2023] Open
Abstract
AIM: To investigate the vasoactive intestinal peptides (VIP) expression in irritable bowel syndrome (IBS) and trinitrobenzene sulfonic acid (TNBS) induced colitis.
METHODS: The VIP gene expression and protein plasma levels were measured in adult participants (45.8% male) who met Rome III criteria for IBS for longer than 6 mo and in a rat model of colitis as induced by TNBS. Plasma and colons were collected from naïve and inflamed rats. Markers assessing inflammation (i.e., weight changes and myeloperoxidase levels) were assessed on days 2, 7, 14 and 28 and compared to controls. Visceral hypersensitivity of the rats was assessed with colo-rectal distension and mechanical threshold testing on hind paws. IBS patients (n = 12) were age, gender, race, and BMI-matched with healthy controls (n = 12). Peripheral whole blood and plasma from fasting participants was collected and VIP plasma levels were assayed using a VIP peptide-enzyme immunoassay. Human gene expression of VIP was analyzed using a custom PCR array.
RESULTS: TNBS induced colitis in the rats was confirmed with weight loss (13.7 ± 3.2 g) and increased myeloperoxidase activity. Visceral hypersensitivity to colo-rectal distension was increased in TNBS treated rats up to 21 d and resolved by day 28. Somatic hypersensitivity was also increased up to 14 d post TNBS induction of colitis. The expression of an inflammatory marker myeloperoxidase was significantly elevated in the intracellular granules of neutrophils in rat models following TNBS treatment compared to naïve rats. This confirmed the induction of inflammation in rats following TNBS treatment. VIP plasma concentration was significantly increased in rats following TNBS treatment as compared to naïve animals (P < 0.05). Likewise, the VIP gene expression from peripheral whole blood was significantly upregulated by 2.91-fold in IBS patients when compared to controls (P < 0.00001; 95%CI). VIP plasma protein was not significantly different when compared with controls (P = 0.193).
CONCLUSION: Alterations in VIP expression may play a role in IBS. Therefore, a better understanding of the physiology of VIP could lead to new therapeutics.
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Affiliation(s)
- Magnus Simrén
- Department of Internal Medicine and Clinical Nutrition, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden University of Gothenburg Centre for Person-Centred Care (GPCC), Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden
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