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Lemlijn-Slenter AHWM, van Iperen LP, Wijnands KAP, Wolter N, de Rijk AE, Masclee AAM. Is Health Status in Patients With Chronic Disorders of the Gastrointestinal System Disease-Specific? Results From an Integral Approach. Neurogastroenterol Motil 2025; 37:e15021. [PMID: 39962739 DOI: 10.1111/nmo.15021] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/31/2024] [Revised: 12/28/2024] [Accepted: 01/25/2025] [Indexed: 04/15/2025]
Abstract
BACKGROUND In patients with chronic disorders of the gastrointestinal (GI) system, integral health is disturbed in all dimensions: physical, mental, quality of life, participation, meaningfulness, and daily functioning. In this group, three large subgroups are distinguished: Inflammatory Bowel Diseases (IBD), Hepato-Pancreatico-Biliary diseases (HPB), and NeuroGastroenterology and Motility (NGM) disorders. Our aim was to compare integral health status between these three subgroups. For the NGM group, we focused on patients with documented motility disorders, not on patients with functional GI-disorders. We hypothesized that the NGM group will have lower scores for integral health status compared to the IBD and HPB groups. METHODS A prospective, observational, questionnaire study was performed in patients with chronic GI-system disorders (IBD, HPB, and NGM) attending the Maastricht University Medical Center outpatient department. Validated questionnaires and patient file data were used to quantify six health dimensions. KEY RESULTS Data from 416 patients were collected. In all domains, apart from meaningfulness, the NGM group (n = 93) had significantly (0.001 ≤ p ≤ 0.033) lower scores compared to the IBD (n = 174) and HPB (n = 149) groups. From the NGM group, 66% were malnourished, had symptoms of depression (36%) and anxiety (19%), and work participation was lowest (32%). Correlations between intra- and interdimensional parameters were moderate to strong apart from meaningfulness. CONCLUSIONS & INFERENCES Compared to patients with chronic IBD and HPB disorders, patients with NGM disorders have significantly lower scores in five of six dimensions of health: physical and mental well-being, quality of life, daily functioning, and participation.
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Affiliation(s)
- Anja H W M Lemlijn-Slenter
- Department of Gastroenterology - Hepatology, School of Nutrition and Translational Research in Metabolism (NUTRIM), Maastricht University Medical Center, Maastricht, the Netherlands
- Department of Social Medicine, Faculty of Health, Medicine and Life Sciences, Care and Public Health Research Institute (CAPHRI), Maastricht University, Maastricht, the Netherlands
- Department of Social Medical Affairs (SMZ), The Dutch Social Security Institute: The Institute for Employee Benefits Schemes (UWV), Amsterdam, the Netherlands
- Department of Research, Academic Knowledge Center Work and Health South-East Netherlands (AKAG-ZON), Heerlen, the Netherlands
| | - Luuk P van Iperen
- Department of Social Medicine, Faculty of Health, Medicine and Life Sciences, Care and Public Health Research Institute (CAPHRI), Maastricht University, Maastricht, the Netherlands
- Department of Research, Academic Knowledge Center Work and Health South-East Netherlands (AKAG-ZON), Heerlen, the Netherlands
| | - Karolina A P Wijnands
- Department of Social Medicine, Faculty of Health, Medicine and Life Sciences, Care and Public Health Research Institute (CAPHRI), Maastricht University, Maastricht, the Netherlands
- Department of Social Medical Affairs (SMZ), The Dutch Social Security Institute: The Institute for Employee Benefits Schemes (UWV), Amsterdam, the Netherlands
- Department of Research, Academic Knowledge Center Work and Health South-East Netherlands (AKAG-ZON), Heerlen, the Netherlands
| | - Nico Wolter
- Department of Gastroenterology - Hepatology, School of Nutrition and Translational Research in Metabolism (NUTRIM), Maastricht University Medical Center, Maastricht, the Netherlands
| | - Angelique E de Rijk
- Department of Social Medicine, Faculty of Health, Medicine and Life Sciences, Care and Public Health Research Institute (CAPHRI), Maastricht University, Maastricht, the Netherlands
- Department of Research, Academic Knowledge Center Work and Health South-East Netherlands (AKAG-ZON), Heerlen, the Netherlands
| | - Ad A M Masclee
- Department of Gastroenterology - Hepatology, School of Nutrition and Translational Research in Metabolism (NUTRIM), Maastricht University Medical Center, Maastricht, the Netherlands
- Department of Research, Academic Knowledge Center Work and Health South-East Netherlands (AKAG-ZON), Heerlen, the Netherlands
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Roimi M, Shrot A, Ilan R, Tenenbaum A, Epstein D, Bar-Lavie Y. The association between defecation frequency and mortality in critically ill patients with suspected sepsis in Israel. Acute Crit Care 2025; 40:38-45. [PMID: 39978952 PMCID: PMC11924406 DOI: 10.4266/acc.000696] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/22/2024] [Accepted: 11/04/2024] [Indexed: 02/22/2025] Open
Abstract
BACKGROUND The pivotal role of the gastrointestinal (GI) tract in sepsis is well recognized. This study aimed to evaluate the associations between defecation frequency as a basic assessment of GI function and the clinical outcomes of intensive care unit patients with suspected sepsis. METHODS This retrospective, single-center study included patients suspected of having sepsis. The number of defecations and consecutive days without defecation during the 72 hours preceding the suspected infection were assessed. The primary outcome was 30-day all-cause mortality. Multivariate regression analysis adjusting for potential confounders was employed to establish the associations between GI function and clinical outcomes. RESULTS The final analysis included 1,306 patients with a median age of 56.2 years (interquartile range [IQR], 39.6-69.1); 919 (70.4%) were male, and the median Acute Physiology and Chronic Health Evaluation II score was 22.0 (IQR, 17.0-27.0). The median Sequential Organ Failure Assessment score at the time of suspected infection was 5.0 (IQR, 3.0-7.0). Mortality rates were 20.3%, 28.0%, and 34.3% for patients with 0-2, 3-5, and >5 defecations, respectively (P<0.001). There was a strong correlation between the number of defecations and mortality (r=0.7, P=0.01). In multivariate analyses, each defecation was independently associated with increased mortality (adjusted odds ratio [aOR], 1.07; 95% CI, 1.01-1.12; P=0.01), while each consecutive day without a defecation was associated with reduced mortality (aOR, 0.83; 95% CI, 0.73-0.96; P=0.01). CONCLUSIONS A higher number of defecations in the 72 hours preceding suspected sepsis is associated with increased 30-day all-cause mortality, suggesting a potential association with GI tract dysfunction.
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Affiliation(s)
- Michael Roimi
- Division of Critical Care, Rambam Health Care Campus, Haifa, Israel
| | | | - Roy Ilan
- Division of Critical Care, Rambam Health Care Campus, Haifa, Israel
- Ruth and Bruce Rappaport Faculty of Medicine, Technion, Haifa, Israel
| | | | - Danny Epstein
- Division of Critical Care, Rambam Health Care Campus, Haifa, Israel
- Ruth and Bruce Rappaport Faculty of Medicine, Technion, Haifa, Israel
| | - Yaron Bar-Lavie
- Division of Critical Care, Rambam Health Care Campus, Haifa, Israel
- Ruth and Bruce Rappaport Faculty of Medicine, Technion, Haifa, Israel
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Escalante J, Artaiz O, Diwakarla S, McQuade RM. Leaky gut in systemic inflammation: exploring the link between gastrointestinal disorders and age-related diseases. GeroScience 2025; 47:1-22. [PMID: 39638978 PMCID: PMC11872833 DOI: 10.1007/s11357-024-01451-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/25/2023] [Accepted: 11/20/2024] [Indexed: 12/07/2024] Open
Abstract
Global average life expectancy has steadily increased over the last several decades and is projected to reach ~ 77 years by 2050. As it stands, the number of people > 60 years currently outnumbers children younger than 5 years, and by 2050, it is anticipated that the global population of people aged > 60 years will double, surpassing 2.1 billion. This demographic shift in our population is expected to have substantial consequences on health services globally due to the disease burden associated with aging. Osteoarthritis, chronic obstructive pulmonary disease, diabetes, cardiovascular disease, and cognitive decline associated with dementia are among the most common age-related diseases and contribute significantly to morbidity and mortality in the aged population. Many of these age-related diseases have been linked to chronic low-grade systemic inflammation which often accompanies aging. Gastrointestinal barrier dysfunction, also known as "leaky gut," has been shown to contribute to systemic inflammation in several diseases including inflammatory bowel disease and irritable bowel syndrome, but its role in the development and/or progression of chronic low-grade systemic inflammation during aging is unclear. This review outlines current literature on the leaky gut in aging, how leaky gut might contribute to systemic inflammation, and the links between gastrointestinal inflammatory diseases and common age-related diseases to provide insight into a potential relationship between the intestinal barrier and inflammation.
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Affiliation(s)
- Jonathan Escalante
- Gut-Barrier and Disease Laboratory, Department of Anatomy and Physiology, The University of Melbourne, Melbourne, VIC, 3021, Australia
| | - Olivia Artaiz
- Gut-Barrier and Disease Laboratory, Department of Anatomy and Physiology, The University of Melbourne, Melbourne, VIC, 3021, Australia
| | - Shanti Diwakarla
- Gut-Barrier and Disease Laboratory, Department of Anatomy and Physiology, The University of Melbourne, Melbourne, VIC, 3021, Australia
- The Florey Institute of Neuroscience and Mental Health, Parkville, VIC, 3010, Australia
| | - Rachel M McQuade
- Gut-Barrier and Disease Laboratory, Department of Anatomy and Physiology, The University of Melbourne, Melbourne, VIC, 3021, Australia.
- The Florey Institute of Neuroscience and Mental Health, Parkville, VIC, 3010, Australia.
- Australian Institute for Musculoskeletal Science (AIMSS), The Melbourne University and Western Health, Melbourne, VIC, 3021, Australia.
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König J, Roca Rubio MF, Forsgård RA, Rode J, Axelsson J, Grompone G, Brummer RJ. The effects of a 6-week intervention with Limosilactobacillus reuteri ATCC PTA 6475 alone and in combination with L. reuteri DSM 17938 on gut barrier function, immune markers, and symptoms in patients with IBS-D-An exploratory RCT. PLoS One 2024; 19:e0312464. [PMID: 39485760 PMCID: PMC11530048 DOI: 10.1371/journal.pone.0312464] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/07/2024] [Accepted: 10/05/2024] [Indexed: 11/03/2024] Open
Abstract
BACKGROUND An increased intestinal permeability is a common feature in patients with diarrhoea-predominant irritable bowel syndrome (IBS-D). Probiotics have shown to improve IBS symptoms and might also affect intestinal barrier function. AIM The aim of this study was to investigate the effects of a 6-week intervention with Limosilactobacillus reuteri ATCC PTA 6475 alone (single strain) or in combination with Limosilactobacillus reuteri DSM 17938 (dual strain) on gut barrier function, immune markers, and symptoms in IBS-D patients (ClinicalTrials.gov registration number: NCT03986476). METHODS 65 IBS-D patients were randomised into three groups (placebo, single strain, dual strain). Small and large intestinal permeability were assessed using a multi-sugar urinary recovery test. Blood, saliva, faecal samples, and several symptom scales were collected before, and after three and six weeks of intervention. RESULTS Small and large intestinal permeability as well as other markers of gut barrier function were not significantly affected by the probiotic interventions. Serum IL-6 levels showed a tendency to be reduced in the single strain group (descriptive p = 0.052). In addition, high-sensitivity C-reactive protein was significantly reduced in the dual strain group (p = 0.041). The participants in both treatment groups reported less gastrointestinal symptoms after three weeks, but this reached significance only in the dual strain group (total score: p = 0.032, pain subscore: p = 0.028). After six weeks, none of the assessed symptoms were significantly different from the placebo. CONCLUSION The probiotic compounds investigated in this study did not seem to affect IBS-D patients' gut barrier function, but showed potential anti-inflammatory and symptom-improving properties, which need to be confirmed in larger study cohorts.
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Affiliation(s)
- Julia König
- Nutrition-Gut-Brain Interactions Research Centre, Faculty of Health and Medicine, School of Medical Sciences, Örebro University, Örebro, Sweden
| | - María Fernanda Roca Rubio
- Nutrition-Gut-Brain Interactions Research Centre, Faculty of Health and Medicine, School of Medical Sciences, Örebro University, Örebro, Sweden
| | - Richard A. Forsgård
- Nutrition-Gut-Brain Interactions Research Centre, Faculty of Health and Medicine, School of Medical Sciences, Örebro University, Örebro, Sweden
| | - Julia Rode
- Nutrition-Gut-Brain Interactions Research Centre, Faculty of Health and Medicine, School of Medical Sciences, Örebro University, Örebro, Sweden
| | | | | | - Robert J. Brummer
- Nutrition-Gut-Brain Interactions Research Centre, Faculty of Health and Medicine, School of Medical Sciences, Örebro University, Örebro, Sweden
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Zhu L, Yang L, Liang Z, Shi W, Ma M, Chen J, Abdula Z, Gong X. Association between dietary calcium intake and constipation in a metabolic syndrome population: evidence from NHANES 2005-2010. Front Nutr 2024; 11:1422564. [PMID: 39539369 PMCID: PMC11557474 DOI: 10.3389/fnut.2024.1422564] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/08/2024] [Accepted: 10/18/2024] [Indexed: 11/16/2024] Open
Abstract
Background The global prevalence of Metabolic Syndrome (MetS) is increasing, primarily characterized by abdominal obesity, which significantly heightens the risk of cardiovascular diseases, gastrointestinal disorders, and cancers. Constipation is a common gastrointestinal issue that impacts both physiological and psychological health and worsens with age. Calcium, an essential mineral vital for human health, has been proven to be crucial not only for bone health but also beneficial for gastrointestinal health. However, the results regarding its impact on constipation are inconsistent. This study aimed to investigate the relationship between dietary calcium intake and constipation in individuals with MetS. Methods This cross-sectional study utilized data from the National Health and Nutrition Examination Survey (NHANES) from 2005 to 2010. Participants were assessed for MetS based on the International Diabetes Federation (IDF) criteria. Dietary calcium intake was evaluated through 24-h dietary recalls, and constipation was defined based on the frequency of bowel movements recorded in the bowel health questionnaire. The relationship between calcium intake and constipation was explored using logistic regression models with adjustment for covariates, and restricted cubic spline analyses were also used to investigate nonlinear relationships. Results The study included 4,838 adult participants with MetS. Adjusted logistic regression revealed that an increase in dietary calcium intake was significantly associated with a reduced risk of constipation (OR: 0.562, 95% CI: 0.379 to 0.835, p = 0.006). Compared to the lowest quartile, the highest quartile of dietary calcium intake significantly decreased the risk of constipation (OR: 0.282, 95% CI: 0.115 to 0.691, p = 0.008). Results from the restrictive cubic spline analysis indicated a negative linear association between dietary calcium intake and constipation risk (non-linearity p = 0.704). Conclusion The findings suggested that increased dietary calcium intake is associated with a decreased risk of constipation among MetS patients, emphasizing dietary calcium as a potentially modifiable factor for managing gastrointestinal symptoms in this population.
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Affiliation(s)
- Li Zhu
- Department of Anus and Intestine Surgery, People’s Hospital of Xinjiang Uygur Autonomous Region, Xinjiang Uygur Autonomous Region, Urumqi, China
| | - Long Yang
- Pediatric Cardiothoracic Surgery, First Affiliated Hospital of Xinjiang Medical University, Urumqi, China
| | - Zonghua Liang
- Department of Anus and Intestine Surgery, People’s Hospital of Xinjiang Uygur Autonomous Region, Xinjiang Uygur Autonomous Region, Urumqi, China
| | - Wen Shi
- Department of Anus and Intestine Surgery, People’s Hospital of Xinjiang Uygur Autonomous Region, Xinjiang Uygur Autonomous Region, Urumqi, China
| | - Ming Ma
- Research and Education Center, People’s Hospital of Xinjiang Uygur Autonomous Region, Urumqi, China
| | - Jingbo Chen
- Department of Traditional Chinese Medicine, People’s Hospital of Xinjiang Uygur Autonomous Region, Xinjiang Uygur Autonomous Region, Urumqi, China
| | - Zulipikaer Abdula
- Department of Anus and Intestine Surgery, People’s Hospital of Xinjiang Uygur Autonomous Region, Xinjiang Uygur Autonomous Region, Urumqi, China
| | - Xuchen Gong
- Department of Anus and Intestine Surgery, People’s Hospital of Xinjiang Uygur Autonomous Region, Xinjiang Uygur Autonomous Region, Urumqi, China
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Garicano Vilar E, López Oliva S, Penadés BF, Sánchez Niño GM, Terrén Lora A, Sanz Rojo S, Mauro Martín IS. Mediterranean Diet Effect on the Intestinal Microbiota, Symptoms, and Markers in Patients with Functional Gastrointestinal Disorders. Microorganisms 2024; 12:1969. [PMID: 39458278 PMCID: PMC11509143 DOI: 10.3390/microorganisms12101969] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/19/2024] [Revised: 09/10/2024] [Accepted: 09/19/2024] [Indexed: 10/28/2024] Open
Abstract
The Mediterranean diet (MD) has beneficial effects on the intestinal microbiota by the promotion of bacteria associated with a healthy gut. However, its impact on intestinal fungi, among others, is still unknown, and how it affects digestive symptoms and different biomarkers in patients with gastrointestinal (GI) disorders has hardly been explored. The present study evaluated the effect of the MD on gut microbial diversity and structure and intestinal symptoms and biomarkers after 6 weeks of dietary intervention in 46 patients with GI disorders. Dysbiosis in fungal composition and diversity was observed, with a significantly lower abundance of Sordariomycetes, Leotiomycetes, and Orbiliomycetes; a significantly higher abundance of Saccharomycetes; the Chytridiomycota and Mucoromycota phyla were significantly reduced; and the bacterial microbiota remained unchanged. In addition, various GI disorders decreased and associations between stool consistency and intestinal permeability were found with the bacterial genera Alistipes and Roseburia. Thus, the data suggest that MD can alter the fungal intestinal microbiota and improve GI disorders.
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Affiliation(s)
| | | | | | | | | | | | - Ismael San Mauro Martín
- Research Centers in Nutrition and Health (CINUSA Group), Paseo de la Habana 43, 28036 Madrid, Spain; (E.G.V.); (S.L.O.); (B.F.P.); (G.M.S.N.); (A.T.L.); (S.S.R.)
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Lemlijn-Slenter AHWM, Wijnands KAP, van der Hamsvoort G, van Iperen LP, Wolter N, de Rijk AE, Masclee AAM. Positive health: An integrated quantitative approach in patients with chronic gastrointestinal and hepato-pancreatico-biliary disorders. World J Gastroenterol 2024; 30:3418-3427. [PMID: 39091714 PMCID: PMC11290394 DOI: 10.3748/wjg.v30.i28.3418] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/01/2024] [Revised: 06/05/2024] [Accepted: 06/24/2024] [Indexed: 07/24/2024] Open
Abstract
BACKGROUND The concept of positive health (PH) supports an integrated approach for patients by taking into account six dimensions of health. This approach is especially relevant for patients with chronic disorders. Chronic gastrointestinal and hepato-pancreatico-biliary (GI-HPB) disorders are among the top-6 of the most prevalent chronically affected organ systems. The impact of chronic GI-HPB disorders on individuals may be disproportionally high because: (1) The affected organ system frequently contributes to a malnourished state; and (2) persons with chronic GI-HPB disorders are often younger than persons with chronic diseases in other organ systems. AIM To describe and quantify the dimensions of PH in patients with chronic GI-HPB disorders. METHODS Prospective, observational questionnaire study performed between 2019 and 2021 in 235 patients with a chronic GI-HPB disorder attending the Outpatient Department of the Maastricht University Medical Center. Validated questionnaires and data from patient files were used to quantify the six dimensions of PH. Internal consistency was tested with McDonald's Omega. Zero-order Pearson correlations and t-tests were used to assess associations and differences. A P value < 0.05 was considered significant. RESULTS The GI-HPB patients scored significantly worse in all dimensions of PH compared to control data or norm scores from the general population. Regarding quality of life, participation and daily functioning, GI-HPB patients scored in the same range as patients with chronic disorders in other organ systems, but depressive symptoms (in 35%) and malnutrition (in 45%) were more frequent in patients with chronic GI-HPB disorders. Intercorrelation scores between the six dimensions were only very weak to weak, forcing us to quantify each domain separately. CONCLUSION All six dimensions of PH are impaired in the GI-HPB patients. Malnutrition and depressive symptoms are more prevalent compared to patients with chronic disorders in other organ systems.
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Affiliation(s)
- Anja H W M Lemlijn-Slenter
- Department of Social Medicine, Faculty of Health, Medicine and Life sciences, Care and Public Health Research Institute Maastricht University, Maastricht 6200 MD, Limburg, Netherlands
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, School of Nutrition and Translational Research in Metabolism, Maastricht 6200 MD, Limburg, Netherlands
- Social Medical Affairs, Employee Insurance Agency (UWV), Heerlen 6400 AC, Limburg, Netherlands
- Department of Research, Academic Knowledge Center Work and Health South-East Netherlands (AKAG-ZON), Heerlen 6400 AC, Limburg, Netherlands
| | - Karolina A P Wijnands
- Department of Social Medicine, Faculty of Health, Medicine and Life sciences, Care and Public Health Research Institute Maastricht University, Maastricht 6200 MD, Limburg, Netherlands
- Social Medical Affairs, Employee Insurance Agency (UWV), Heerlen 6400 AC, Limburg, Netherlands
- Department of Research, Academic Knowledge Center Work and Health South-East Netherlands (AKAG-ZON), Heerlen 6400 AC, Limburg, Netherlands
| | - Gijs van der Hamsvoort
- Social Medical Affairs, Employee Insurance Agency (UWV), Heerlen 6400 AC, Limburg, Netherlands
| | - Luuk P van Iperen
- Department of Social Medicine, Faculty of Health, Medicine and Life sciences, Care and Public Health Research Institute Maastricht University, Maastricht 6200 MD, Limburg, Netherlands
| | - Nico Wolter
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, School of Nutrition and Translational Research in Metabolism, Maastricht 6200 MD, Limburg, Netherlands
| | - Angelique E de Rijk
- Department of Social Medicine, Faculty of Health, Medicine and Life sciences, Care and Public Health Research Institute Maastricht University, Maastricht 6200 MD, Limburg, Netherlands
- Department of Research, Academic Knowledge Center Work and Health South-East Netherlands (AKAG-ZON), Heerlen 6400 AC, Limburg, Netherlands
| | - Ad A M Masclee
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, School of Nutrition and Translational Research in Metabolism, Maastricht 6200 MD, Limburg, Netherlands
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Aliu A, Bosch DHCA, Keszthelyi D, Ardabili AR, Colombel JF, Sawyer R, Törnblom H, Hart A, Jonkers DMAE, Pierik MJ, Mujagic Z. Letter: Intestinal permeability accounting for ongoing gastrointestinal symptoms following endoscopic remission in IBD-Authors' reply. Aliment Pharmacol Ther 2024; 59:1646-1647. [PMID: 38726864 DOI: 10.1111/apt.18031] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/23/2024] [Accepted: 04/23/2024] [Indexed: 05/22/2024]
Abstract
LINKED CONTENTThis article is linked to Aliu et al papers. To view these articles, visit https://doi.org/10.1111/apt.17988 and https://doi.org/10.1111/apt.18027.
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Affiliation(s)
- Arta Aliu
- Department Gastroenterology and Hepatology, Maastricht University Medical Center, Maastricht, The Netherlands
- NUTRIM School of Nutrition and Translational Research in Metabolism, Faculty of Health, Medicine and Life Sciences, Maastricht University, Maastricht, The Netherlands
| | - Daan H C A Bosch
- Department Gastroenterology and Hepatology, Maastricht University Medical Center, Maastricht, The Netherlands
- NUTRIM School of Nutrition and Translational Research in Metabolism, Faculty of Health, Medicine and Life Sciences, Maastricht University, Maastricht, The Netherlands
| | - Daniel Keszthelyi
- Department Gastroenterology and Hepatology, Maastricht University Medical Center, Maastricht, The Netherlands
- NUTRIM School of Nutrition and Translational Research in Metabolism, Faculty of Health, Medicine and Life Sciences, Maastricht University, Maastricht, The Netherlands
| | - Ashkan Rezazadeh Ardabili
- Department Gastroenterology and Hepatology, Maastricht University Medical Center, Maastricht, The Netherlands
- NUTRIM School of Nutrition and Translational Research in Metabolism, Faculty of Health, Medicine and Life Sciences, Maastricht University, Maastricht, The Netherlands
| | - Jean-Frederic Colombel
- Department of Medicine, The Henry D. Janowitz Division of Gastroenterology, Icahn School of Medicine at Mount Sinai, New York, New York, USA
| | - Rachel Sawyer
- IBD Patient Advocacy, Founder of the Bottom Line IBD and IBD Women, London, UK
| | - Hans Törnblom
- Department of Molecular and Clinical Medicine, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden
| | - Ailsa Hart
- IBD Unit, St Mark's Hospital & Imperial College, London, UK
| | - Daisy M A E Jonkers
- Department Gastroenterology and Hepatology, Maastricht University Medical Center, Maastricht, The Netherlands
- NUTRIM School of Nutrition and Translational Research in Metabolism, Faculty of Health, Medicine and Life Sciences, Maastricht University, Maastricht, The Netherlands
| | - Marieke J Pierik
- Department Gastroenterology and Hepatology, Maastricht University Medical Center, Maastricht, The Netherlands
- NUTRIM School of Nutrition and Translational Research in Metabolism, Faculty of Health, Medicine and Life Sciences, Maastricht University, Maastricht, The Netherlands
| | - Zlatan Mujagic
- Department Gastroenterology and Hepatology, Maastricht University Medical Center, Maastricht, The Netherlands
- NUTRIM School of Nutrition and Translational Research in Metabolism, Faculty of Health, Medicine and Life Sciences, Maastricht University, Maastricht, The Netherlands
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9
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Zeng M, Hodges JK, Pokala A, Khalafi M, Sasaki GY, Pierson J, Cao S, Brock G, Yu Z, Zhu J, Vodovotz Y, Bruno RS. A green tea extract confection decreases circulating endotoxin and fasting glucose by improving gut barrier function but without affecting systemic inflammation: A double-blind, placebo-controlled randomized trial in healthy adults and adults with metabolic syndrome. Nutr Res 2024; 124:94-110. [PMID: 38430822 DOI: 10.1016/j.nutres.2024.02.001] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/28/2023] [Revised: 01/11/2024] [Accepted: 02/01/2024] [Indexed: 03/05/2024]
Abstract
Anti-inflammatory activities of catechin-rich green tea extract (GTE) in obese rodents protect against metabolic endotoxemia by decreasing intestinal permeability and absorption of gut-derived endotoxin. However, translation to human health has not been established. We hypothesized that GTE would reduce endotoxemia by decreasing gut permeability and intestinal and systemic inflammation in persons with metabolic syndrome (MetS) compared with healthy persons. A randomized, double-blind, placebo-controlled, crossover trial in healthy adults (n = 19, 34 ± 2 years) and adults with MetS (n = 21, 40 ± 3 years) examined 4-week administration of a decaffeinated GTE confection (890 mg/d total catechins) on serum endotoxin, intestinal permeability, gut and systemic inflammation, and cardiometabolic parameters. Compared with the placebo, the GTE confection decreased serum endotoxin (P = .023) in both healthy persons and those with MetS, while increasing concentrations of circulating catechins (P < .0001) and γ-valerolactones (P = .0001). Fecal calprotectin (P = .029) and myeloperoxidase (P = .048) concentrations were decreased by GTE regardless of health status. Following the ingestion of gut permeability probes, urinary lactose/mannitol (P = .043) but not sucralose/erythritol (P > .05) was decreased by GTE regardless of health status. No between-treatment differences (P > .05) were observed for plasma aminotransferases, blood pressure, plasma lipids, or body mass nor were plasma tumor necrosis factor-α, interleukin-6, or the ratio of lipopolysaccharide-binding protein/soluble cluster of differentiation-14 affected. However, fasting glucose in both study groups was decreased (P = .029) by the GTE confection compared with within-treatment arm baseline concentrations. These findings demonstrate that catechin-rich GTE is effective to decrease circulating endotoxin and improve glycemic control in healthy adults and those with MetS, likely by reducing gut inflammation and small intestinal permeability but without affecting systemic inflammation.
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Affiliation(s)
- Min Zeng
- Human Nutrition Program, The Ohio State University, Columbus, OH, 43210, USA
| | - Joanna K Hodges
- Human Nutrition Program, The Ohio State University, Columbus, OH, 43210, USA; Department of Nutritional Sciences, The Pennsylvania State University, State College, PA, 16801, USA
| | - Avinash Pokala
- Human Nutrition Program, The Ohio State University, Columbus, OH, 43210, USA
| | - Mona Khalafi
- Human Nutrition Program, The Ohio State University, Columbus, OH, 43210, USA
| | - Geoffrey Y Sasaki
- Human Nutrition Program, The Ohio State University, Columbus, OH, 43210, USA
| | - Jillian Pierson
- Human Nutrition Program, The Ohio State University, Columbus, OH, 43210, USA
| | - Sisi Cao
- Human Nutrition Program, The Ohio State University, Columbus, OH, 43210, USA
| | - Guy Brock
- Department of Biomedical Informatics, The Ohio State University, Columbus, OH, 43210, USA
| | - Zhongtang Yu
- Department of Animal Sciences, The Ohio State University, Columbus, OH, 43210, USA
| | - Jiangjiang Zhu
- Human Nutrition Program, The Ohio State University, Columbus, OH, 43210, USA
| | - Yael Vodovotz
- Department of Food Science and Technology, The Ohio State University, Columbus, OH, 43210, USA
| | - Richard S Bruno
- Human Nutrition Program, The Ohio State University, Columbus, OH, 43210, USA.
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10
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Acciarino A, Diwakarla S, Handreck J, Bergola C, Sahakian L, McQuade RM. The role of the gastrointestinal barrier in obesity-associated systemic inflammation. Obes Rev 2024; 25:e13673. [PMID: 38111141 DOI: 10.1111/obr.13673] [Citation(s) in RCA: 8] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/26/2023] [Revised: 10/05/2023] [Accepted: 10/27/2023] [Indexed: 12/20/2023]
Abstract
Systemic inflammation is a key contributor to the onset and progression of several obesity-associated diseases and is thought to predominantly arise from the hyperplasia and hypertrophy of white adipose tissue. However, a growing body of works suggests that early changes in the gastrointestinal (GI) barrier may contribute to both local, within the GI lining, and systemic inflammation in obesity. Intestinal barrier dysfunction is well-characterized in inflammatory GI disorders such as inflammatory bowel disease (IBD) and irritable bowel syndrome (IBS) and is known to contribute to systemic inflammation. Thus, drawing parallels between GI disorders, where intestinal permeability and systemic inflammation are prominent features, and obesity-induced GI manifestations may provide insights into the potential role of the intestinal barrier in systemic inflammation in obesity. This review summarizes the current literature surrounding intestinal barrier dysfunction in obesity and explores the potential role of intestinal hyperpermeability and intestinal barrier dysfunction in the development of systemic inflammation and GI dysfunction in obesity.
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Affiliation(s)
- Adriana Acciarino
- Gut Barrier and Disease Laboratory, Department of Anatomy and Physiology, The University of Melbourne, Melbourne, Victoria, Australia
- Department of Medicine, Western Health, The University of Melbourne, Melbourne, Victoria, Australia
| | - Shanti Diwakarla
- Gut Barrier and Disease Laboratory, Department of Anatomy and Physiology, The University of Melbourne, Melbourne, Victoria, Australia
- Department of Medicine, Western Health, The University of Melbourne, Melbourne, Victoria, Australia
| | - Jessica Handreck
- Gut Barrier and Disease Laboratory, Department of Anatomy and Physiology, The University of Melbourne, Melbourne, Victoria, Australia
- Department of Medicine, Western Health, The University of Melbourne, Melbourne, Victoria, Australia
| | - Cedrick Bergola
- Gut Barrier and Disease Laboratory, Department of Anatomy and Physiology, The University of Melbourne, Melbourne, Victoria, Australia
| | - Lauren Sahakian
- Gut Barrier and Disease Laboratory, Department of Anatomy and Physiology, The University of Melbourne, Melbourne, Victoria, Australia
| | - Rachel M McQuade
- Gut Barrier and Disease Laboratory, Department of Anatomy and Physiology, The University of Melbourne, Melbourne, Victoria, Australia
- Department of Medicine, Western Health, The University of Melbourne, Melbourne, Victoria, Australia
- Australian Institute for Musculoskeletal Science (AIMSS), Melbourne University, Melbourne, Victoria, Australia
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11
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Pinto S, Benincà E, Galazzo G, Jonkers D, Penders J, Bogaards JA. Heterogeneous associations of gut microbiota with Crohn's disease activity. Gut Microbes 2024; 16:2292239. [PMID: 38105519 PMCID: PMC10730216 DOI: 10.1080/19490976.2023.2292239] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/12/2023] [Accepted: 12/04/2023] [Indexed: 12/19/2023] Open
Abstract
The multi-factorial involvement of gut microbiota with Crohn's disease (CD) necessitates robust analysis to uncover possible associations with particular microbes. CD has been linked to specific bacteria, but reported associations vary widely across studies. This inconsistency may result from heterogeneous associations across individual patients, resulting in no apparent or only weak relationships with the means of bacterial abundances. We investigated the relationship between bacterial relative abundances and disease activity in a longitudinal cohort of CD patients (n = 57) and healthy controls (n = 15). We applied quantile regression, a statistical technique that allows investigation of possible relationships outside the mean response. We found several significant and mostly negative associations with CD, especially in lower quantiles of relative abundance on family or genus level. Associations found by quantile regression deviated from the mean response in relative abundances of Coriobacteriaceae, Pasteurellaceae, Peptostreptococcaceae, Prevotellaceae, and Ruminococcaceae. For the family Streptococcaceae we found a significant elevation in relative abundance for patients experiencing an exacerbation relative to those who remained without self-reported symptoms or measurable inflammation. Our analysis suggests that specific bacterial families are related to CD and exacerbation, but associations vary between patients due to heterogeneity in disease course, medication history, therapy response, gut microbiota composition and historical contingency. Our study underscores that microbial diversity is reduced in the gut of CD patients, but suggests that the process of diversity loss is rather irregular with respect to specific taxonomic groups. This novel insight may advance our ecological understanding of this complex disease.
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Affiliation(s)
- Susanne Pinto
- Biomedical Data Sciences, Leiden University Medical Center, Leiden, Netherlands
| | - Elisa Benincà
- Centre for Infectious Disease Control, National Institute for Public Health and the Environment (RIVM), Bilthoven, Netherlands
| | - Gianluca Galazzo
- School for Nutrition and Translational Research in Metabolism (NUTRIM), Maastricht University, Maastricht, Netherlands
- Department of Medical Microbiology, Infectious Diseases and Infection Prevention, Maastricht UMC, Maastricht, Netherlands
| | - Daisy Jonkers
- School for Nutrition and Translational Research in Metabolism (NUTRIM), Maastricht University, Maastricht, Netherlands
- Department of Gastroenterology-Hepatology, Maastricht UMC, Maastricht, Netherlands
| | - John Penders
- School for Nutrition and Translational Research in Metabolism (NUTRIM), Maastricht University, Maastricht, Netherlands
- Department of Medical Microbiology, Infectious Diseases and Infection Prevention, Maastricht UMC, Maastricht, Netherlands
| | - Johannes A. Bogaards
- Epidemiology and Data Science, Amsterdam UMC location Vrije Universiteit Amsterdam, Amsterdam, Netherlands
- Institute for Infection and Immunity (AII), Amsterdam UMC, Amsterdam, Netherlands
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12
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Yuan Y, Wang X, Huang S, Wang H, Shen G. Low-level inflammation, immunity, and brain-gut axis in IBS: unraveling the complex relationships. Gut Microbes 2023; 15:2263209. [PMID: 37786296 PMCID: PMC10549202 DOI: 10.1080/19490976.2023.2263209] [Citation(s) in RCA: 19] [Impact Index Per Article: 9.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/27/2023] [Accepted: 09/21/2023] [Indexed: 10/04/2023] Open
Abstract
Irritable bowel syndrome is a common functional gastrointestinal disorder, and it has been shown that the etiology of irritable bowel syndrome is a multifactorial complex of neurological, inflammatory, and immunological changes. There is growing evidence of low-grade chronic inflammation in irritable bowel patients. The peripheral action response of their intestinal immune factors is integrated into the central nervous system, while the microbiota interacts with the brain-gut axis contributing to the development of low-grade chronic inflammation. The objective of this review is to present a discussion about the impact of immune-brain-gut axis-inflammation interactions on irritable bowel syndrome, its clinical relevance in the course of irritable bowel syndrome disease, and possible therapeutic modalities.
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Affiliation(s)
- Yi Yuan
- School of Integrated Chinese and Western Medicine, Anhui University of Chinese Medicine, Hefei, China
| | - Xiyang Wang
- School of Integrated Chinese and Western Medicine, Anhui University of Chinese Medicine, Hefei, China
| | - Shun Huang
- School of Integrated Chinese and Western Medicine, Anhui University of Chinese Medicine, Hefei, China
| | - Hao Wang
- School of Integrated Chinese and Western Medicine, Anhui University of Chinese Medicine, Hefei, China
| | - Guoming Shen
- School of Integrated Chinese and Western Medicine, Anhui University of Chinese Medicine, Hefei, China
- Institute of Integrated Chinese and Western Medicine, Anhui University of Chinese Medicine, Hefei, China
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13
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La Torre D, Van Oudenhove L, Vanuytsel T, Verbeke K. Psychosocial stress-induced intestinal permeability in healthy humans: What is the evidence? Neurobiol Stress 2023; 27:100579. [PMID: 37842017 PMCID: PMC10569989 DOI: 10.1016/j.ynstr.2023.100579] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/08/2023] [Revised: 10/04/2023] [Accepted: 10/05/2023] [Indexed: 10/17/2023] Open
Abstract
An impaired intestinal barrier function can be detrimental to the host as it may allow the translocation of luminal antigens and toxins into the subepithelial tissue and bloodstream. In turn, this may cause local and systemic immune responses and lead to the development of pathologies. In vitro and animal studies strongly suggest that psychosocial stress is one of the factors that can increase intestinal permeability via mast-cell dependent mechanisms. Remarkably, studies have not been able to yield unequivocal evidence that such relation between stress and intestinal permeability also exists in (healthy) humans. In the current Review, we discuss the mechanisms that are involved in stress-induced intestinal permeability changes and postulate factors that influence these alterations and that may explain the translational difficulties from in vitro and animal to human studies. As human research differs highly from animal research in the extent to which stress can be applied and intestinal permeability can be measured, it remains difficult to draw conclusions about the presence of a relation between stress and intestinal permeability in (healthy) humans. Future studies should bear in mind these difficulties, and more research into in vivo methods to assess intestinal permeability are warranted.
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Affiliation(s)
- Danique La Torre
- Translational Research Center in Gastrointestinal Disorders (TARGID), Department of Chronic Diseases and Metabolism, Faculty of Medicine, KU Leuven, Leuven, Belgium
- Leuven Brain Institute, KU Leuven, Leuven, Belgium
| | - Lukas Van Oudenhove
- Translational Research Center in Gastrointestinal Disorders (TARGID), Department of Chronic Diseases and Metabolism, Faculty of Medicine, KU Leuven, Leuven, Belgium
- Leuven Brain Institute, KU Leuven, Leuven, Belgium
- Cognitive and Affective Neuroscience Lab, Department of Psychological and Brain Sciences, Dartmouth College, Hanover, NH, USA
| | - Tim Vanuytsel
- Translational Research Center in Gastrointestinal Disorders (TARGID), Department of Chronic Diseases and Metabolism, Faculty of Medicine, KU Leuven, Leuven, Belgium
- Division of Gastroenterology and Hepatology, Leuven University Hospital, Leuven, Belgium
| | - Kristin Verbeke
- Translational Research Center in Gastrointestinal Disorders (TARGID), Department of Chronic Diseases and Metabolism, Faculty of Medicine, KU Leuven, Leuven, Belgium
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14
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Tedjo DI, Wilbrink JA, Boekhorst J, Timmerman HM, Nienhuijs SW, Stronkhorst A, Savelkoul PHM, Masclee AAM, Penders J, Jonkers DMAE. Impact of Sleeve Gastrectomy on Fecal Microbiota in Individuals with Morbid Obesity. Microorganisms 2023; 11:2353. [PMID: 37764197 PMCID: PMC10537490 DOI: 10.3390/microorganisms11092353] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/03/2023] [Revised: 09/10/2023] [Accepted: 09/13/2023] [Indexed: 09/29/2023] Open
Abstract
BACKGROUND The intestinal microbiota plays an important role in the etiology of obesity. Sleeve gastrectomy (SG) is a frequently performed and effective therapy for morbid obesity. OBJECTIVE To investigate the effect of sleeve gastrectomy on the fecal microbiota of individuals with morbid obesity and to examine whether shifts in microbiota composition are associated with markers of inflammation and intestinal barrier function. METHODS Fecal and blood samples of healthy individuals (n = 27) and morbidly obese individuals pre-SG (n = 24), and at 2 months (n = 13) and 6 months post-SG (n = 9) were collected. The 16SrRNA gene was sequenced to assess microbiota composition. Fecal calprotectin, plasma inflammatory markers and intestinal permeability markers (multi-sugar test) were determined. RESULTS Fecal microbiota composition between morbidly obese and lean individuals was significantly different. The fecal microbiota composition changed significantly 2 and 6 months post-SG (p = 0.008) compared to pre-SG but not towards a more lean profile. The post-SG microbiota profile was characterized by an increase in facultative anaerobic bacteria, characteristic for the upper gastrointestinal tract. No correlations were found between inflammatory markers, intestinal permeability and microbial profile changes. CONCLUSIONS Fecal microbiota composition in morbidly obese individuals changed significantly following SG. This change might be explained by functional changes induced by the SG procedure.
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Affiliation(s)
- Danyta I. Tedjo
- Division Gastroenterology-Hepatology, School of Nutrition and Translational Research in Metabolism (NUTRIM), Maastricht University Medical Center+, 6229 Maastricht, The Netherlands; (D.I.T.); (J.A.W.); (D.M.A.E.J.)
- Department of Medical Microbiology, School of Nutrition and Translational Research in Metabolism (NUTRIM), Maastricht University Medical Center+, 6229 Maastricht, The Netherlands; (P.H.M.S.); (J.P.)
| | - Jennifer A. Wilbrink
- Division Gastroenterology-Hepatology, School of Nutrition and Translational Research in Metabolism (NUTRIM), Maastricht University Medical Center+, 6229 Maastricht, The Netherlands; (D.I.T.); (J.A.W.); (D.M.A.E.J.)
- Department of Gastroenterology, Zuyderland Ziekenhuis, 6162 Sittard-Geleen, The Netherlands
| | - Jos Boekhorst
- NIZO Food Research B.V., 6718 Ede, The Netherlands; (J.B.); (H.M.T.)
| | | | - Simon W. Nienhuijs
- Department of Surgery and Gastroenterology, Catharina Hospital, 5623 Eindhoven, The Netherlands; (S.W.N.); (A.S.)
| | - Arnold Stronkhorst
- Department of Surgery and Gastroenterology, Catharina Hospital, 5623 Eindhoven, The Netherlands; (S.W.N.); (A.S.)
| | - Paul H. M. Savelkoul
- Department of Medical Microbiology, School of Nutrition and Translational Research in Metabolism (NUTRIM), Maastricht University Medical Center+, 6229 Maastricht, The Netherlands; (P.H.M.S.); (J.P.)
- Department of Medical Microbiology & Infection Control, VU University Medical Center, 1081 Amsterdam, The Netherlands
| | - Ad A. M. Masclee
- Division Gastroenterology-Hepatology, School of Nutrition and Translational Research in Metabolism (NUTRIM), Maastricht University Medical Center+, 6229 Maastricht, The Netherlands; (D.I.T.); (J.A.W.); (D.M.A.E.J.)
| | - John Penders
- Department of Medical Microbiology, School of Nutrition and Translational Research in Metabolism (NUTRIM), Maastricht University Medical Center+, 6229 Maastricht, The Netherlands; (P.H.M.S.); (J.P.)
| | - Daisy M. A. E. Jonkers
- Division Gastroenterology-Hepatology, School of Nutrition and Translational Research in Metabolism (NUTRIM), Maastricht University Medical Center+, 6229 Maastricht, The Netherlands; (D.I.T.); (J.A.W.); (D.M.A.E.J.)
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15
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Kovaleva A, Poluektova E, Maslennikov R, Karchevskaya A, Shifrin O, Kiryukhin A, Tertychnyy A, Kovalev L, Kovaleva M, Lobanova O, Kudryavtseva A, Krasnov G, Fedorova M, Ivashkin V. Effect of Rebamipide on the Intestinal Barrier, Gut Microbiota Structure and Function, and Symptom Severity Associated with Irritable Bowel Syndrome and Functional Dyspepsia Overlap: A Randomized Controlled Trial. J Clin Med 2023; 12:6064. [PMID: 37763004 PMCID: PMC10531936 DOI: 10.3390/jcm12186064] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/27/2023] [Revised: 08/30/2023] [Accepted: 09/17/2023] [Indexed: 09/29/2023] Open
Abstract
Treatment of functional digestive disorders is not always effective. Therefore, a search for new application points for potential drugs is perspective. Our aim is to evaluate the effect of rebamipide on symptom severity, intestinal barrier status, and intestinal microbiota composition and function in patients with diarrheal variant of irritable bowel syndrome overlapping with functional dyspepsia (D-IBSoFD). Sixty patients were randomized to receive trimebutine (TRI group), trimebutine + rebamipide (T + R group), or rebamipide (REB group) for 2 months. At the beginning and end of the study, patients were assessed for general health (SF-36), severity of digestive symptoms (Gastrointestinal Symptom Rating and 7 × 7 scales), state of the intestinal barrier, and composition (16S rRNA gene sequencing) and function (short-chain fatty acid fecal content) of the gut microbiota. The severity of most digestive symptoms was reduced in the REB and T + R groups to levels similar to that observed in the TRI group. The duodenal and sigmoidal lymphocytic and sigmoidal eosinophilic infiltration was decreased only in the REB and T + R groups, not in the TRI group. Serum zonulin levels were significantly decreased only in the REB group. A decrease in intraepithelial lymphocytic infiltration in the duodenum correlated with a decrease in the severity of rumbling and flatulence, while a decrease in infiltration within the sigmoid colon correlated with improved stool consistency and decreased severity of the sensation of incomplete bowel emptying. In conclusion, rebamipide improves the intestinal barrier condition and symptoms in D-IBSoFD. The rebamipide effects are not inferior to those of trimebutine.
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Affiliation(s)
- Aleksandra Kovaleva
- Department of Introduction to Internal Diseases, Gastroenterology and Hepatology, Sechenov University, Pogodinskaya Str., 1, Bld. 1, 119435 Moscow, Russia; (A.K.); (E.P.)
| | - Elena Poluektova
- Department of Introduction to Internal Diseases, Gastroenterology and Hepatology, Sechenov University, Pogodinskaya Str., 1, Bld. 1, 119435 Moscow, Russia; (A.K.); (E.P.)
- The Scientific Community for Human Microbiome Research, Pogodinskaya Str., 1, Bld. 1, 119435 Moscow, Russia
| | - Roman Maslennikov
- Department of Introduction to Internal Diseases, Gastroenterology and Hepatology, Sechenov University, Pogodinskaya Str., 1, Bld. 1, 119435 Moscow, Russia; (A.K.); (E.P.)
- The Scientific Community for Human Microbiome Research, Pogodinskaya Str., 1, Bld. 1, 119435 Moscow, Russia
| | - Anna Karchevskaya
- Department of Introduction to Internal Diseases, Gastroenterology and Hepatology, Sechenov University, Pogodinskaya Str., 1, Bld. 1, 119435 Moscow, Russia; (A.K.); (E.P.)
- Laboratory of General and Clinical Neurophysiology, Institute of Higher Nervous Activity and Neurophysiology, Russian Academy of Sciences, 5A Butlerova Str., 117485 Moscow, Russia
- N.N. Burdenko National Medical Research Center of Neurosurgery, 16, 4th Tverskaya-Yamskaya St., 125047 Moscow, Russia
| | - Oleg Shifrin
- Department of Introduction to Internal Diseases, Gastroenterology and Hepatology, Sechenov University, Pogodinskaya Str., 1, Bld. 1, 119435 Moscow, Russia; (A.K.); (E.P.)
| | - Andrey Kiryukhin
- Endoscopy Unit, The Second University Clinic, Sechenov University, Pogodinskaya Str., 1, Bld. 1, 119435 Moscow, Russia
| | - Aleksandr Tertychnyy
- Institute of Clinical Morphology and Digital Pathology, Sechenov University, Trubetskaya Str., 8, Bld. 2, 119048 Moscow, Russia; (A.T.)
| | - Leonid Kovalev
- Laboratory of Structural Biochemistry of Protein, A.N. Bach Institute of Biochemistry, Research Center of Biotechnology, Russian Academy of Sciences, Leninsky Prospekt, 33, Bld. 2, 119071 Moscow, Russia
| | - Marina Kovaleva
- Laboratory of Structural Biochemistry of Protein, A.N. Bach Institute of Biochemistry, Research Center of Biotechnology, Russian Academy of Sciences, Leninsky Prospekt, 33, Bld. 2, 119071 Moscow, Russia
| | - Olga Lobanova
- Institute of Clinical Morphology and Digital Pathology, Sechenov University, Trubetskaya Str., 8, Bld. 2, 119048 Moscow, Russia; (A.T.)
| | - Anna Kudryavtseva
- Laboratory of Postgenomic Research, Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Vavilova Str., 32, Bld. 1, 119991 Moscow, Russia
| | - George Krasnov
- Laboratory of Postgenomic Research, Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Vavilova Str., 32, Bld. 1, 119991 Moscow, Russia
| | - Maria Fedorova
- Laboratory of Postgenomic Research, Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Vavilova Str., 32, Bld. 1, 119991 Moscow, Russia
| | - Vladimir Ivashkin
- Department of Introduction to Internal Diseases, Gastroenterology and Hepatology, Sechenov University, Pogodinskaya Str., 1, Bld. 1, 119435 Moscow, Russia; (A.K.); (E.P.)
- The Scientific Community for Human Microbiome Research, Pogodinskaya Str., 1, Bld. 1, 119435 Moscow, Russia
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16
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Maqoud F, Tricarico D, Mallamaci R, Orlando A, Russo F. The Role of Ion Channels in Functional Gastrointestinal Disorders (FGID): Evidence of Channelopathies and Potential Avenues for Future Research and Therapeutic Targets. Int J Mol Sci 2023; 24:11074. [PMID: 37446251 DOI: 10.3390/ijms241311074] [Citation(s) in RCA: 8] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/31/2023] [Revised: 06/29/2023] [Accepted: 06/30/2023] [Indexed: 07/15/2023] Open
Abstract
Several gastrointestinal (GI) tract abnormalities, including visceral hypersensitivity, motility, and intestinal permeability alterations, have been implicated in functional GI disorders (FGIDs). Ion channels play a crucial role in all the functions mentioned above. Hormones and natural molecules modulate these channels and represent targets of drugs and bacterial toxins. Mutations and abnormal functional expression of ion channel subunits can lead to diseases called channelopathies. These channelopathies in gastroenterology are gaining a strong interest, and the evidence of co-relationships is increasing. In this review, we describe the correlation status between channelopathies and FGIDs. Different findings are available. Among others, mutations in the ABCC7/CFTR gene have been described as a cause of constipation and diarrhea. Mutations of the SCN5A gene are instead associated with irritable bowel syndrome. In contrast, mutations of the TRPV1 and TRPA genes of the transient receptor potential (TRP) superfamily manifest hypersensitivity and visceral pain in sensory nerves. Recently, mice and humans affected by Cantu syndrome (CS), which is associated with the mutations of the KCNJ8 and ABCC9 genes encoding for the Kir6.1 and SUR2 subunits, showed dysfunction of contractility throughout the intestine and death in the mice after the weaning on solid food. The discovery of a correlation between channelopathies and FIGD opens new avenues for discovering new direct drug targets for specific channelopathies, leading to significant implications for diagnosing and treating functional GI diseases.
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Affiliation(s)
- Fatima Maqoud
- Functional Gastrointestinal Disorders Research Group, National Institute of Gastroenterology IRCCS "Saverio de Bellis", Castellana Grotte, 70013 Bari, Italy
| | - Domenico Tricarico
- Section of Pharmacology, Department of Pharmacy-Pharmaceutical Sciences, University of Bari Aldo Moro, 70125 Bari, Italy
| | - Rosanna Mallamaci
- Department of Biosciences, Biotechnologies and Environment University of Bari Aldo Moro, 70125 Bari, Italy
| | - Antonella Orlando
- Functional Gastrointestinal Disorders Research Group, National Institute of Gastroenterology IRCCS "Saverio de Bellis", Castellana Grotte, 70013 Bari, Italy
| | - Francesco Russo
- Functional Gastrointestinal Disorders Research Group, National Institute of Gastroenterology IRCCS "Saverio de Bellis", Castellana Grotte, 70013 Bari, Italy
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17
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Chi ZC. Progress in research of low-grade inflammation in irritable bowel syndrome. Shijie Huaren Xiaohua Zazhi 2022; 30:1051-1065. [DOI: 10.11569/wcjd.v30.i24.1051] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/27/2022] Open
Abstract
Irritable bowel syndrome (IBS) is a common intestinal disease with a prevalence of 10%-15%. However, its pathophysiology is still not completely clear, and it has long been considered as a functional disease. In recent years, it has been found that low-grade inflammation plays a pathogenic role in IBS. Studies have confirmed that there is persistent mucosal inflammation at the microscopic and molecular levels. This review discusses the evidence, role, and clinical relevance of mucosal inflammation in IBS. In addition to mucosal inflammation, neuroinflammation may lead to changes in neuroendocrine pathways and glucocorticoid receptor genes through the "gut-brain" axis, and thus cause IBS through proinflammatory phenotype and hypothalamic pituitary adrenal axis and 5-hydroxytryptamine dysfunction. The observation that IBS patients can benefit from anti-inflammatory therapy also confirms that IBS is associated with inflammation.
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Affiliation(s)
- Zhao-Chun Chi
- Department of Gastroenterology, Qingdao Municipal Hospital, Qingdao 266011, Shandong Province, China
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18
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de Graaf MCG, Scheijen JLJM, Spooren CEGM, Mujagic Z, Pierik MJ, Feskens EJM, Keszthelyi D, Schalkwijk CG, Jonkers DMAE. The Intake of Dicarbonyls and Advanced Glycation Endproducts as Part of the Habitual Diet Is Not Associated with Intestinal Inflammation in Inflammatory Bowel Disease and Irritable Bowel Syndrome Patients. Nutrients 2022; 15:nu15010083. [PMID: 36615740 PMCID: PMC9824683 DOI: 10.3390/nu15010083] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/17/2022] [Revised: 12/11/2022] [Accepted: 12/22/2022] [Indexed: 12/28/2022] Open
Abstract
A Western diet comprises high levels of dicarbonyls and advanced glycation endproducts (AGEs), which may contribute to flares and symptoms in inflammatory bowel disease (IBD) and irritable bowel syndrome (IBS). We therefore investigated the intake of dietary dicarbonyls and AGEs in IBD and IBS patients as part of the habitual diet, and their association with intestinal inflammation. Food frequency questionnaires from 238 IBD, 261 IBS as well as 195 healthy control (HC) subjects were used to calculate the intake of dicarbonyls methylglyoxal, glyoxal, and 3-deoxyglucosone, and of the AGEs Nε-(carboxymethyl)lysine, Nε-(1-carboxyethyl)lysine and methylglyoxal-derived hydroimidazolone-1. Intestinal inflammation was assessed using faecal calprotectin. The absolute dietary intake of all dicarbonyls and AGEs was higher in IBD and HC as compared to IBS (all p < 0.05). However, after energy-adjustment, only glyoxal was lower in IBD versus IBS and HC (p < 0.05). Faecal calprotectin was not significantly associated with dietary dicarbonyls and AGEs in either of the subgroups. The absolute intake of methylglyoxal was significantly higher in patients with low (<15 μg/g) compared to moderate calprotectin levels (15−<50 μg/g, p = 0.031). The concentrations of dietary dicarbonyls and AGEs generally present in the diet of Dutch patients with IBD or IBS are not associated with intestinal inflammation, although potential harmful effects might be counteracted by anti-inflammatory components in the food matrix.
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Affiliation(s)
- Marlijne C. G. de Graaf
- Division Gastroenterology-Hepatology, Department of Internal Medicine, Maastricht University Medical Center+, 6229 ER Maastricht, The Netherlands
- NUTRIM School of Nutrition and Translational Research in Metabolism, Faculty of Health, Medicine and Life Sciences, Maastricht University, 6229 ER Maastricht, The Netherlands
- Correspondence: ; Tel.: +31-43-38-84-237
| | - Jean L. J. M. Scheijen
- Department of Internal Medicine, Maastricht University Medical Center+, 6229 ER Maastricht, The Netherlands
- CARIM School for Cardiovascular Diseases, Faculty of Health, Medicine and Life Sciences, Maastricht University, 6229 ER Maastricht, The Netherlands
| | - Corinne E. G. M. Spooren
- Division Gastroenterology-Hepatology, Department of Internal Medicine, Maastricht University Medical Center+, 6229 ER Maastricht, The Netherlands
- NUTRIM School of Nutrition and Translational Research in Metabolism, Faculty of Health, Medicine and Life Sciences, Maastricht University, 6229 ER Maastricht, The Netherlands
| | - Zlatan Mujagic
- Division Gastroenterology-Hepatology, Department of Internal Medicine, Maastricht University Medical Center+, 6229 ER Maastricht, The Netherlands
- NUTRIM School of Nutrition and Translational Research in Metabolism, Faculty of Health, Medicine and Life Sciences, Maastricht University, 6229 ER Maastricht, The Netherlands
| | - Marieke J. Pierik
- Division Gastroenterology-Hepatology, Department of Internal Medicine, Maastricht University Medical Center+, 6229 ER Maastricht, The Netherlands
- NUTRIM School of Nutrition and Translational Research in Metabolism, Faculty of Health, Medicine and Life Sciences, Maastricht University, 6229 ER Maastricht, The Netherlands
| | - Edith J. M. Feskens
- Division of Human Nutrition and Health, Wageningen University & Research, 6708 WE Wageningen, The Netherlands
| | - Daniel Keszthelyi
- Division Gastroenterology-Hepatology, Department of Internal Medicine, Maastricht University Medical Center+, 6229 ER Maastricht, The Netherlands
- NUTRIM School of Nutrition and Translational Research in Metabolism, Faculty of Health, Medicine and Life Sciences, Maastricht University, 6229 ER Maastricht, The Netherlands
| | - Casper G. Schalkwijk
- Department of Internal Medicine, Maastricht University Medical Center+, 6229 ER Maastricht, The Netherlands
- CARIM School for Cardiovascular Diseases, Faculty of Health, Medicine and Life Sciences, Maastricht University, 6229 ER Maastricht, The Netherlands
| | - Daisy M. A. E. Jonkers
- Division Gastroenterology-Hepatology, Department of Internal Medicine, Maastricht University Medical Center+, 6229 ER Maastricht, The Netherlands
- NUTRIM School of Nutrition and Translational Research in Metabolism, Faculty of Health, Medicine and Life Sciences, Maastricht University, 6229 ER Maastricht, The Netherlands
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19
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Xu W, Zhang Z, Lu Y, Li M, Li J, Tao W. Traditional Chinese medicine Tongxie Yaofang treating irritable bowel syndrome with diarrhea and type 2 diabetes mellitus in rats with liver-depression and spleen-deficiency: A preliminary study. Front Nutr 2022; 9:968930. [PMID: 36438735 PMCID: PMC9686328 DOI: 10.3389/fnut.2022.968930] [Citation(s) in RCA: 11] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/14/2022] [Accepted: 10/10/2022] [Indexed: 10/05/2023] Open
Abstract
Tongxie Yaofang (TXYF), a Traditional Chinese Medicine (TCM) with four components as follows: Rhizoma Atractylodis Macrocephalae (baizhu), Radix Paeoniae Alba (baishao), Pericarpium Citri Reticulatae (chenpi) and Radix Saposhnikovia Divaricata (fangfeng), benefits irritable bowel syndrome (IBS). Nonetheless, proofs of this formula ameliorating D-IBS and T2DM are required. This research aimed at investigating the efficacy of TXYF in treating inflammation in rats with D-IBS and T2DM using animal models. In this study, gavage with high-fat diet, fasciculation, and senna was given to develop rat models with target diseases. To determine intestinal inflammations, major inflammatory factors, and intestinal permeability proteins, H&E staining, ELISA, and immunohistochemistry methods were employed, respectively. This study also utilized Western blot to discover potential inflammatory targets. Results of this research illustrates that TXYF treatment reduced the level of TNF-α, IL-1β, and IL-6, and raised the IL-10 concentration in liver-depressed spleende ficient rats with D-IBS and T2DM, indicating controlled inflammatory reactions. Staining analysis also showed improved disease states of animal models. Furthermore, efficient rebounds of claudin-1, an intestinal permeability-associated protein, were detected. Moreover, TXYF may treat D-IBS and T2DM in rats via the rage pathway.
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Affiliation(s)
- Weidong Xu
- Department of Traditional Chinese Medicine, Affiliated Hospital of Jiangsu University, Zhenjiang, China
- School of Pharmacy, Jiangsu University, Zhenjiang, China
| | - Zhiyi Zhang
- School of Pharmacy, Jiangsu University, Zhenjiang, China
| | - Ye Lu
- Department of Traditional Chinese Medicine, Affiliated Hospital of Jiangsu University, Zhenjiang, China
- School of Pharmacy, Jiangsu University, Zhenjiang, China
| | - Mengxi Li
- Department of Traditional Chinese Medicine, Affiliated Hospital of Jiangsu University, Zhenjiang, China
| | - Jiayao Li
- School of Pharmacy, Jiangsu University, Zhenjiang, China
| | - Wenhua Tao
- Department of Traditional Chinese Medicine, Affiliated Hospital of Jiangsu University, Zhenjiang, China
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20
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Tingö L, Hutchinson AN, Bergh C, Stiefvatter L, Schweinlin A, Jensen MG, Krüger K, Bischoff SC, Brummer RJ. Potential Modulation of Inflammation by Probiotic and Omega-3 Supplementation in Elderly with Chronic Low-Grade Inflammation—A Randomized, Placebo-Controlled Trial. Nutrients 2022; 14:nu14193998. [PMID: 36235651 PMCID: PMC9573426 DOI: 10.3390/nu14193998] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/15/2022] [Revised: 09/15/2022] [Accepted: 09/18/2022] [Indexed: 11/18/2022] Open
Abstract
Probiotic and omega-3 supplements have been shown to reduce inflammation, and dual supplementation may have synergistic health effects. We investigated if the novel combination of a multi-strain probiotic (containing B. lactis Bi-07, L. paracasei Lpc-37, L. acidophilus NCFM, and B. lactis Bl-04) alongside omega-3 supplements reduces low-grade inflammation as measured by high-sensitivity C-reactive protein (hs-CRP) in elderly participants in a proof-of-concept, randomized, placebo-controlled, parallel study (NCT04126330). In this case, 76 community-dwelling elderly participants (median: 71.0 years; IQR: 68.0–73.8) underwent an intervention with the dual supplement (n = 37) or placebo (n = 39) for eight weeks. In addition to hs-CRP, cytokine levels and intestinal permeability were also assessed at baseline and after the eight-week intervention. No significant difference was seen for hs-CRP between the dual supplement group and placebo. However, interestingly, supplementation did result in significant increases in the level of the anti-inflammatory marker IL-10. In addition, dual supplementation increased levels of valeric acid, further suggesting the potential of the supplements in reducing inflammation and conferring health benefits. Together, the results suggest that probiotic and omega-3 dual supplementation exerts modest effects on inflammation and may have potential use as a non-pharmacological treatment for low-grade inflammation in the elderly.
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Affiliation(s)
- Lina Tingö
- Nutrition-Gut-Brain Interactions Research Centre, School of Medical Sciences, Örebro University, 70362 Örebro, Sweden
- Food and Health Programme, Örebro University, 70362 Örebro, Sweden
- Division of Inflammation and Infection, Department of Biomedical and Clinical Sciences, Linköping University, 58183 Linköping, Sweden
| | - Ashley N. Hutchinson
- Nutrition-Gut-Brain Interactions Research Centre, School of Medical Sciences, Örebro University, 70362 Örebro, Sweden
- Correspondence: ; Tel.: +46-737-455-302
| | - Cecilia Bergh
- Clinical Epidemiology and Biostatistics, School of Medical Sciences, Örebro University, 70362 Örebro, Sweden
| | - Lena Stiefvatter
- Department of Nutritional Medicine and Prevention, University of Hohenheim, 70599 Stuttgart, Germany
| | - Anna Schweinlin
- Department of Nutritional Medicine and Prevention, University of Hohenheim, 70599 Stuttgart, Germany
| | | | - Kirsten Krüger
- Human Nutrition & Health, Department of Agrotechnology and Food Sciences, Wageningen University & Research, 9101 Wageningen, The Netherlands
| | - Stephan C. Bischoff
- Department of Nutritional Medicine and Prevention, University of Hohenheim, 70599 Stuttgart, Germany
| | - Robert J. Brummer
- Nutrition-Gut-Brain Interactions Research Centre, School of Medical Sciences, Örebro University, 70362 Örebro, Sweden
- Food and Health Programme, Örebro University, 70362 Örebro, Sweden
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21
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de Graaf MCG, Spooren CEGM, Hendrix EMB, Hesselink MAM, Feskens EJM, Smolinska A, Keszthelyi D, Pierik MJ, Mujagic Z, Jonkers DMAE. Diet Quality and Dietary Inflammatory Index in Dutch Inflammatory Bowel Disease and Irritable Bowel Syndrome Patients. Nutrients 2022; 14:nu14091945. [PMID: 35565912 PMCID: PMC9101333 DOI: 10.3390/nu14091945] [Citation(s) in RCA: 22] [Impact Index Per Article: 7.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/01/2022] [Revised: 04/29/2022] [Accepted: 05/04/2022] [Indexed: 02/01/2023] Open
Abstract
Inflammatory bowel disease (IBD) and irritable bowel syndrome (IBS) share common culprit foods and potential pathophysiological factors. However, how diet may contribute to disease course and whether this differs between both entities is unclear. We therefore investigated the association of dietary indices with intestinal inflammation and gastrointestinal symptoms in both IBD and IBS patients. Food frequency questionnaires from 238 IBD, 261 IBS and 195 healthy controls (HC) were available to calculate the overall diet quality by the Dutch Healthy Diet-Index 2015 (DHD-2015) and its inflammatory potential by the Adapted Dietary Inflammatory Index (ADII). Intestinal inflammation and symptoms were evaluated by faecal calprotectin and the Gastrointestinal Symptom Rating Scale, respectively. The DHD-2015 was lower in IBD and IBS versus HC (p < 0.001), being associated with calprotectin levels in IBD (b = −4.009, p = 0.006), and with abdominal pain (b = −0.012, p = 0.023) and reflux syndrome (b = −0.016, p = 0.004) in IBS. ADII scores were comparable between groups and were only associated with abdominal pain in IBD (b = 0.194, p = 0.004). In this side-by-side comparison, we found a lower diet quality that was differentially associated with disease characteristics in IBD versus IBS patients. Longitudinal studies are needed to further investigate the role of dietary factors in the development of flares and predominant symptoms.
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Affiliation(s)
- Marlijne C. G. de Graaf
- Division Gastroenterology-Hepatology, Department of Internal Medicine, Maastricht University Medical Center+, P.O. Box 5800, 6202 AZ Maastricht, The Netherlands; (C.E.G.M.S.); (E.M.B.H.); (M.A.M.H.); (D.K.); (M.J.P.); (Z.M.); (D.M.A.E.J.)
- NUTRIM School of Nutrition and Translational Research in Metabolism, Faculty of Health, Medicine and Life Sciences, Maastricht University, P.O. Box 616, 6200 MD Maastricht, The Netherlands;
- Correspondence: ; Tel.: +31-4338-84237
| | - Corinne E. G. M. Spooren
- Division Gastroenterology-Hepatology, Department of Internal Medicine, Maastricht University Medical Center+, P.O. Box 5800, 6202 AZ Maastricht, The Netherlands; (C.E.G.M.S.); (E.M.B.H.); (M.A.M.H.); (D.K.); (M.J.P.); (Z.M.); (D.M.A.E.J.)
- NUTRIM School of Nutrition and Translational Research in Metabolism, Faculty of Health, Medicine and Life Sciences, Maastricht University, P.O. Box 616, 6200 MD Maastricht, The Netherlands;
| | - Evelien M. B. Hendrix
- Division Gastroenterology-Hepatology, Department of Internal Medicine, Maastricht University Medical Center+, P.O. Box 5800, 6202 AZ Maastricht, The Netherlands; (C.E.G.M.S.); (E.M.B.H.); (M.A.M.H.); (D.K.); (M.J.P.); (Z.M.); (D.M.A.E.J.)
- NUTRIM School of Nutrition and Translational Research in Metabolism, Faculty of Health, Medicine and Life Sciences, Maastricht University, P.O. Box 616, 6200 MD Maastricht, The Netherlands;
| | - Martine A. M. Hesselink
- Division Gastroenterology-Hepatology, Department of Internal Medicine, Maastricht University Medical Center+, P.O. Box 5800, 6202 AZ Maastricht, The Netherlands; (C.E.G.M.S.); (E.M.B.H.); (M.A.M.H.); (D.K.); (M.J.P.); (Z.M.); (D.M.A.E.J.)
- NUTRIM School of Nutrition and Translational Research in Metabolism, Faculty of Health, Medicine and Life Sciences, Maastricht University, P.O. Box 616, 6200 MD Maastricht, The Netherlands;
| | - Edith J. M. Feskens
- Division of Human Nutrition and Health, Department of Agrotechnology and Food Sciences, Wageningen University & Research, P.O. Box 17, 6700 AA Wageningen, The Netherlands;
| | - Agnieszka Smolinska
- NUTRIM School of Nutrition and Translational Research in Metabolism, Faculty of Health, Medicine and Life Sciences, Maastricht University, P.O. Box 616, 6200 MD Maastricht, The Netherlands;
- Department of Pharmacology and Toxicology, Maastricht University, P.O. Box 616, 6200 MD Maastricht, The Netherlands
| | - Daniel Keszthelyi
- Division Gastroenterology-Hepatology, Department of Internal Medicine, Maastricht University Medical Center+, P.O. Box 5800, 6202 AZ Maastricht, The Netherlands; (C.E.G.M.S.); (E.M.B.H.); (M.A.M.H.); (D.K.); (M.J.P.); (Z.M.); (D.M.A.E.J.)
- NUTRIM School of Nutrition and Translational Research in Metabolism, Faculty of Health, Medicine and Life Sciences, Maastricht University, P.O. Box 616, 6200 MD Maastricht, The Netherlands;
| | - Marieke J. Pierik
- Division Gastroenterology-Hepatology, Department of Internal Medicine, Maastricht University Medical Center+, P.O. Box 5800, 6202 AZ Maastricht, The Netherlands; (C.E.G.M.S.); (E.M.B.H.); (M.A.M.H.); (D.K.); (M.J.P.); (Z.M.); (D.M.A.E.J.)
- NUTRIM School of Nutrition and Translational Research in Metabolism, Faculty of Health, Medicine and Life Sciences, Maastricht University, P.O. Box 616, 6200 MD Maastricht, The Netherlands;
| | - Zlatan Mujagic
- Division Gastroenterology-Hepatology, Department of Internal Medicine, Maastricht University Medical Center+, P.O. Box 5800, 6202 AZ Maastricht, The Netherlands; (C.E.G.M.S.); (E.M.B.H.); (M.A.M.H.); (D.K.); (M.J.P.); (Z.M.); (D.M.A.E.J.)
- NUTRIM School of Nutrition and Translational Research in Metabolism, Faculty of Health, Medicine and Life Sciences, Maastricht University, P.O. Box 616, 6200 MD Maastricht, The Netherlands;
| | - Daisy M. A. E. Jonkers
- Division Gastroenterology-Hepatology, Department of Internal Medicine, Maastricht University Medical Center+, P.O. Box 5800, 6202 AZ Maastricht, The Netherlands; (C.E.G.M.S.); (E.M.B.H.); (M.A.M.H.); (D.K.); (M.J.P.); (Z.M.); (D.M.A.E.J.)
- NUTRIM School of Nutrition and Translational Research in Metabolism, Faculty of Health, Medicine and Life Sciences, Maastricht University, P.O. Box 616, 6200 MD Maastricht, The Netherlands;
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22
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Burns GL, Talley NJ, Keely S. Immune responses in the irritable bowel syndromes: time to consider the small intestine. BMC Med 2022; 20:115. [PMID: 35354471 PMCID: PMC8969236 DOI: 10.1186/s12916-022-02301-8] [Citation(s) in RCA: 22] [Impact Index Per Article: 7.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/25/2021] [Accepted: 02/15/2022] [Indexed: 11/10/2022] Open
Abstract
BACKGROUND Irritable bowel syndrome (IBS) is considered a disorder of gut-brain interaction (DGBI), presenting as chronic abdominal pain and altered defaecation. Symptoms are often food related. Much work in the field has focused on identifying physiological, immune and microbial abnormalities in the colon of patients; however, evidence of small intestinal immune activation and microbial imbalance has been reported in small studies. The significance of such findings has been largely underappreciated despite a growing body of work implicating small intestinal homeostatic imbalance in the pathogenesis of DGBIs. MAIN TEXT Small intestinal mechanosensation is a characteristic feature of IBS. Furthermore, altered small intestinal barrier functions have been demonstrated in IBS patients with the diarrhoea-predominant subtype. Small intestinal bacterial overgrowth and increased populations of small intestinal mast cells are frequently associated with IBS, implicating microbial imbalance and low-grade inflammation in the pathogenesis of IBS. Furthermore, reports of localised food hypersensitivity responses in IBS patients implicate the small intestine as the site of immune-microbial-food interactions. CONCLUSIONS Given the association of IBS symptoms with food intake in a large proportion of patients and the emerging evidence of immune activation in these patients, the current literature suggests the pathogenesis of IBS is not limited to the colon but rather may involve dysfunction of the entire intestinal tract. It remains unclear if regional variation in IBS pathology explains the various symptom phenotypes and further work should consider the intestinal tract as a whole to answer this question.
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Affiliation(s)
- Grace L Burns
- NHMRC Centre of Research Excellence in Digestive Health, The University of Newcastle, Callaghan, New South Wales, Australia.,College of Health, Medicine and Wellbeing, The University of Newcastle, Callaghan, New South Wales, Australia.,Immune Health Program, Hunter Medical Research Institute, New Lambton Heights, New South Wales, Australia
| | - Nicholas J Talley
- NHMRC Centre of Research Excellence in Digestive Health, The University of Newcastle, Callaghan, New South Wales, Australia.,College of Health, Medicine and Wellbeing, The University of Newcastle, Callaghan, New South Wales, Australia.,Immune Health Program, Hunter Medical Research Institute, New Lambton Heights, New South Wales, Australia
| | - Simon Keely
- NHMRC Centre of Research Excellence in Digestive Health, The University of Newcastle, Callaghan, New South Wales, Australia. .,College of Health, Medicine and Wellbeing, The University of Newcastle, Callaghan, New South Wales, Australia. .,Immune Health Program, Hunter Medical Research Institute, New Lambton Heights, New South Wales, Australia.
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23
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Wauters L, Ceulemans M, Schol J, Farré R, Tack J, Vanuytsel T. The Role of Leaky Gut in Functional Dyspepsia. Front Neurosci 2022; 16:851012. [PMID: 35422683 PMCID: PMC9002356 DOI: 10.3389/fnins.2022.851012] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/08/2022] [Accepted: 03/07/2022] [Indexed: 12/12/2022] Open
Abstract
Patients with functional dyspepsia (FD) complain of epigastric symptoms with no identifiable cause. Increased intestinal permeability has been described in these patients, especially in the proximal small bowel or duodenum, and was associated with mucosal immune activation and symptoms. In this review, we discuss duodenal barrier function, including techniques currently applied in FD research. We summarize the available data on duodenal permeability in FD and factors associated to increased permeability, including mucosal eosinophils, mast cells, luminal and systemic factors. While the increased influx of antigens into the duodenal mucosa could result in local immune activation, clinical evidence for a causal role of permeability is lacking in the absence of specific barrier-protective treatments. As both existing and novel treatments, including proton pump inhibitors (PPI) and pre- or probiotics may impact duodenal barrier function, it is important to recognize and study these alterations to improve the knowledge and management of FD.
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Affiliation(s)
- Lucas Wauters
- Department of Gastroenterology and Hepatology, University Hospitals Leuven, Leuven, Belgium
- Translational Research Center for Gastrointestinal Disorders (TARGID), Department of Chronic Diseases and Metabolism, KU Leuven, Leuven, Belgium
- *Correspondence: Lucas Wauters,
| | - Matthias Ceulemans
- Translational Research Center for Gastrointestinal Disorders (TARGID), Department of Chronic Diseases and Metabolism, KU Leuven, Leuven, Belgium
| | - Jolien Schol
- Department of Gastroenterology and Hepatology, University Hospitals Leuven, Leuven, Belgium
- Translational Research Center for Gastrointestinal Disorders (TARGID), Department of Chronic Diseases and Metabolism, KU Leuven, Leuven, Belgium
| | - Ricard Farré
- Translational Research Center for Gastrointestinal Disorders (TARGID), Department of Chronic Diseases and Metabolism, KU Leuven, Leuven, Belgium
| | - Jan Tack
- Department of Gastroenterology and Hepatology, University Hospitals Leuven, Leuven, Belgium
- Translational Research Center for Gastrointestinal Disorders (TARGID), Department of Chronic Diseases and Metabolism, KU Leuven, Leuven, Belgium
| | - Tim Vanuytsel
- Department of Gastroenterology and Hepatology, University Hospitals Leuven, Leuven, Belgium
- Translational Research Center for Gastrointestinal Disorders (TARGID), Department of Chronic Diseases and Metabolism, KU Leuven, Leuven, Belgium
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24
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Mendoza-Martínez VM, Zavala-Solares MR, Espinosa-Flores AJ, León-Barrera KL, Alcántara-Suárez R, Carrillo-Ruíz JD, Escobedo G, Roldan-Valadez E, Esquivel-Velázquez M, Meléndez-Mier G, Bueno-Hernández N. Is a Non-Caloric Sweetener-Free Diet Good to Treat Functional Gastrointestinal Disorder Symptoms? A Randomized Controlled Trial. Nutrients 2022; 14:1095. [PMID: 35268070 PMCID: PMC8912523 DOI: 10.3390/nu14051095] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/16/2022] [Revised: 02/28/2022] [Accepted: 03/03/2022] [Indexed: 02/05/2023] Open
Abstract
Background: A diet containing non-caloric sweeteners (NCS) could reduce calorie intake; conversely, some animal studies suggest that NCS consumption may increase functional gastrointestinal disorder symptoms (FGDs). This study aimed to compare the effect of consuming a diet containing NCS (c-NCS) versus a non-caloric sweetener-free diet (NCS-f) on FGDs. Methods: We conducted a randomized, controlled, parallel-group study using two different diets for five weeks: the c-NCS diet contained 50−100 mg/day NCS, whereas the NCS-f diet had less than 10 mg/day NCS. At the beginning of the study (PreTx) and at the end (PostTx), we assessed FGDs, dietary intake, and NCS consumption. Results: The percentage of participants with diarrhea (PreTx = 19% vs. PstTx = 56%; p = 0.02), post-prandial discomfort (PreTx = 9% vs. PstTx = 39%; p = 0.02), constipation (PreTx = 30% vs. PostTx = 56%; p < 0.01), and burning (PreTx = 13% vs. PostTx = 33%; p < 0.01) increased in the c-NCS diet group. Conversely, abdominal pain (PreTx = 15% vs. PostTx = 3%; p = 0.04), post-prandial discomfort (PreTx = 26% vs. PostTx = 6%; p = 0.02), burning (PreTx = 15% vs. PostTx = 0%; p = 0.02), early satiety (PreTx = 18% vs. PostTx = 3%; p < 0.01), and epigastric pain (PreTx = 38% vs. PostTx = 3%; p < 0.01) decreased in the NCS-f diet group. Conclusion: A c-NCS diet is associated with increased FGDs, including diarrhea, post-prandial discomfort, constipation, and burning or retrosternal pain. The NCS-f diet also decreased FGDs, as well as abdominal pain, post-prandial discomfort, burning or retrosternal pain, early satiety, and epigastric pain.
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Affiliation(s)
- Viridiana Montsserrat Mendoza-Martínez
- Proteomics and Metabolomics Laboratory, Research Division, General Hospital of Mexico “Dr. Eduardo Liceaga”, Mexico City 06720, Mexico; (V.M.M.-M.); (A.J.E.-F.); (K.L.L.-B.); (M.E.-V.)
| | | | - Aranza Jhosadara Espinosa-Flores
- Proteomics and Metabolomics Laboratory, Research Division, General Hospital of Mexico “Dr. Eduardo Liceaga”, Mexico City 06720, Mexico; (V.M.M.-M.); (A.J.E.-F.); (K.L.L.-B.); (M.E.-V.)
| | - Karen Lorena León-Barrera
- Proteomics and Metabolomics Laboratory, Research Division, General Hospital of Mexico “Dr. Eduardo Liceaga”, Mexico City 06720, Mexico; (V.M.M.-M.); (A.J.E.-F.); (K.L.L.-B.); (M.E.-V.)
| | - Raúl Alcántara-Suárez
- Laboratory of Immunometabolism, Research Division, General Hospital of Mexico “Dr. Eduardo Liceaga”, Mexico City 06720, Mexico; (R.A.-S.); (G.E.)
| | - José Damián Carrillo-Ruíz
- Neurology and Neurosurgery Unit, General Hospital of Mexico “Dr. Eduardo Liceaga”, Mexico City 06720, Mexico;
- Faculty of Health Sciences, Mexico Anahuac University, Huixquilucan 52786, Mexico
| | - Galileo Escobedo
- Laboratory of Immunometabolism, Research Division, General Hospital of Mexico “Dr. Eduardo Liceaga”, Mexico City 06720, Mexico; (R.A.-S.); (G.E.)
| | - Ernesto Roldan-Valadez
- Research Division, General Hospital of Mexico “Dr. Eduardo Liceaga”, Mexico City 06720, Mexico;
| | - Marcela Esquivel-Velázquez
- Proteomics and Metabolomics Laboratory, Research Division, General Hospital of Mexico “Dr. Eduardo Liceaga”, Mexico City 06720, Mexico; (V.M.M.-M.); (A.J.E.-F.); (K.L.L.-B.); (M.E.-V.)
| | - Guillermo Meléndez-Mier
- School of Public Health and Nutrition (FASPyN), Autonomous University of Nuevo Leon, Nuevo Leon 64460, Mexico
| | - Nallely Bueno-Hernández
- Proteomics and Metabolomics Laboratory, Research Division, General Hospital of Mexico “Dr. Eduardo Liceaga”, Mexico City 06720, Mexico; (V.M.M.-M.); (A.J.E.-F.); (K.L.L.-B.); (M.E.-V.)
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25
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Pretorius L, Van Staden ADP, Van der Merwe JJ, Henning N, Smith C. Alterations to microbial secretome by estrogen may contribute to sex bias in irritable bowel syndrome. Inflammopharmacology 2022; 30:267-281. [PMID: 35022916 DOI: 10.1007/s10787-021-00906-8] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/22/2021] [Accepted: 11/30/2021] [Indexed: 12/17/2022]
Abstract
INTRODUCTION Irritable bowel syndrome (IBS) is a female predominant functional gastrointestinal disorder, underpinned by microbial dysbiosis and microinflammation. We suggest that changes in trace amine (TA) load and metabolism may link together diet, inflammation and sex in this context. METHODS The effect of E2 treatment on microbial growth and TA generation was assessed using liquid chromatography and tandem mass spectrometry methodology. To investigate the effects of TAs on the gut, WST-1, prostaglandin E2 and tight junction protein dynamics were investigated in TA treated (HT-29) colon epithelial monolayer cultures. RESULTS Differential E2-dependent alterations of the TA production capabilities of microbes were observed. Significantly, E2 treatment resulted in a 50% increase in tryptamine secretion from a probiotic microbe (p < 0.0001). Moreover, in vitro experiments indicated that TA treatment exerted type-specific effects in the gut, e.g., reducing mitochondrial functionality, even at low doses of tryptamine (p < 0.0001) and ρ-tyramine (p < 0.001). Additionally, prostaglandin E2 levels were significantly increased following ρ-tyramine and agmatine treatment (p < 0.05). In terms of functionality, all investigated TAs resulted in occludin redistribution and loss of zona occludens-1 and occludin co-localization. CONCLUSION Increases in the gastrointestinal TA load may contribute to a relatively pro-inflammatory outcome in the intestine, along with tight junction protein disruption. Additionally, fluctuating levels of endogenous E2 may modulate microbially-derived TA levels, potentially explaining exaggerating gastrointestinal symptomology in females during low E2 phases. Thus, current data warrants subsequent investigations in appropriate in vivo models to fully elucidate the role of the trace aminergic system in the sex bias observed in IBS.
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Affiliation(s)
- Lesha Pretorius
- Department of Physiological Sciences, Faculty of Science, Stellenbosch University, Stellenbosch, South Africa
| | - Anton du Preez Van Staden
- Department of Microbiology, Faculty of Science, Stellenbosch University, Stellenbosch, South Africa.,Division of Clinical Pharmacology, Department of Medicine, Faculty of Medicine and Health Sciences, Stellenbosch University, Stellenbosch, South Africa
| | - Johannes J Van der Merwe
- Division of Clinical Pharmacology, Department of Medicine, Faculty of Medicine and Health Sciences, Stellenbosch University, Stellenbosch, South Africa.,LabSPACE, Midrand, South Africa
| | - Natasha Henning
- Division of Clinical Pharmacology, Department of Medicine, Faculty of Medicine and Health Sciences, Stellenbosch University, Stellenbosch, South Africa
| | - Carine Smith
- Division of Clinical Pharmacology, Department of Medicine, Faculty of Medicine and Health Sciences, Stellenbosch University, Stellenbosch, South Africa.
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Mujagic Z, Kasapi M, Jonkers DMAE, Garcia-Perez I, Vork L, Weerts ZZR, Serrano-Contreras JI, Zhernakova A, Kurilshikov A, Scotcher J, Holmes E, Wijmenga C, Keszthelyi D, Nicholson JK, Posma JM, Masclee AAM. Integrated fecal microbiome-metabolome signatures reflect stress and serotonin metabolism in irritable bowel syndrome. Gut Microbes 2022; 14:2063016. [PMID: 35446234 PMCID: PMC9037519 DOI: 10.1080/19490976.2022.2063016] [Citation(s) in RCA: 29] [Impact Index Per Article: 9.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/09/2023] Open
Abstract
To gain insight into the complex microbiome-gut-brain axis in irritable bowel syndrome (IBS), several modalities of biological and clinical data must be combined. We aimed to identify profiles of fecal microbiota and metabolites associated with IBS and to delineate specific phenotypes of IBS that represent potential pathophysiological mechanisms. Fecal metabolites were measured using proton nuclear magnetic resonance (1H-NMR) spectroscopy and gut microbiome using shotgun metagenomic sequencing (MGS) in a combined dataset of 142 IBS patients and 120 healthy controls (HCs) with extensive clinical, biological and phenotype information. Data were analyzed using support vector classification and regression and kernel t-SNE. Microbiome and metabolome profiles could distinguish IBS and HC with an area-under-the-receiver-operator-curve of 77.3% and 79.5%, respectively, but this could be improved by combining microbiota and metabolites to 83.6%. No significant differences in predictive ability of the microbiome-metabolome data were observed between the three classical, stool pattern-based, IBS subtypes. However, unsupervised clustering showed distinct subsets of IBS patients based on fecal microbiome-metabolome data. These clusters could be related plasma levels of serotonin and its metabolite 5-hydroxyindoleacetate, effects of psychological stress on gastrointestinal (GI) symptoms, onset of IBS after stressful events, medical history of previous abdominal surgery, dietary caloric intake and IBS symptom duration. Furthermore, pathways in metabolic reaction networks were integrated with microbiota data, that reflect the host-microbiome interactions in IBS. The identified microbiome-metabolome signatures for IBS, associated with altered serotonin metabolism and unfavorable stress response related to GI symptoms, support the microbiota-gut-brain link in the pathogenesis of IBS.
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Affiliation(s)
- Zlatan Mujagic
- Division Gastroenterology-Hepatology, Maastricht University Medical Center+, Maastricht, The Netherlands,Nutrim School for Nutrition and Translational Research in Metabolism, Maastricht University, Maastricht, The Netherlands,Division of Systems Medicine, Department of Metabolism, Digestion and Reproduction, Faculty of Medicine, South Kensington Campus, Imperial College London, London, UK,CONTACT Zlatan Mujagic Division Gastroenterology-Hepatology, Maastricht University Medical Center+, Maastricht, The Netherlands
| | - Melpomeni Kasapi
- Division of Systems Medicine, Department of Metabolism, Digestion and Reproduction, Faculty of Medicine, South Kensington Campus, Imperial College London, London, UK
| | - Daisy MAE Jonkers
- Division Gastroenterology-Hepatology, Maastricht University Medical Center+, Maastricht, The Netherlands,Nutrim School for Nutrition and Translational Research in Metabolism, Maastricht University, Maastricht, The Netherlands
| | - Isabel Garcia-Perez
- Division of Digestive Diseases, Department of Metabolism, Digestion and Reproduction, Faculty of Medicine, Hammersmith Campus, Imperial College London, London, UK
| | - Lisa Vork
- Division Gastroenterology-Hepatology, Maastricht University Medical Center+, Maastricht, The Netherlands,Nutrim School for Nutrition and Translational Research in Metabolism, Maastricht University, Maastricht, The Netherlands
| | - Zsa Zsa R.M. Weerts
- Division Gastroenterology-Hepatology, Maastricht University Medical Center+, Maastricht, The Netherlands,Nutrim School for Nutrition and Translational Research in Metabolism, Maastricht University, Maastricht, The Netherlands
| | - Jose Ivan Serrano-Contreras
- Division of Systems Medicine, Department of Metabolism, Digestion and Reproduction, Faculty of Medicine, South Kensington Campus, Imperial College London, London, UK
| | - Alexandra Zhernakova
- Department of Genetics, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands
| | - Alexander Kurilshikov
- Department of Genetics, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands
| | - Jamie Scotcher
- Division of Systems Medicine, Department of Metabolism, Digestion and Reproduction, Faculty of Medicine, South Kensington Campus, Imperial College London, London, UK
| | - Elaine Holmes
- Division of Digestive Diseases, Department of Metabolism, Digestion and Reproduction, Faculty of Medicine, Hammersmith Campus, Imperial College London, London, UK,The Australian National Phenome Center, Harry Perkins Institute, Murdoch University, Perth, Australia
| | - Cisca Wijmenga
- Department of Genetics, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands
| | - Daniel Keszthelyi
- Division Gastroenterology-Hepatology, Maastricht University Medical Center+, Maastricht, The Netherlands,Nutrim School for Nutrition and Translational Research in Metabolism, Maastricht University, Maastricht, The Netherlands
| | - Jeremy K Nicholson
- The Australian National Phenome Center, Harry Perkins Institute, Murdoch University, Perth, Australia
| | - Joram M Posma
- Division of Systems Medicine, Department of Metabolism, Digestion and Reproduction, Faculty of Medicine, South Kensington Campus, Imperial College London, London, UK
| | - Ad AM Masclee
- Division Gastroenterology-Hepatology, Maastricht University Medical Center+, Maastricht, The Netherlands,Nutrim School for Nutrition and Translational Research in Metabolism, Maastricht University, Maastricht, The Netherlands
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27
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Grover M, Berumen A, Peters S, Wei T, Breen-Lyles M, Harmsen WS, Busciglio I, Burton D, Vazquez Roque M, DeVault KR, Camilleri M, Wallace M, Dasari S, Neumann H, Houghton LA. Intestinal chemosensitivity in irritable bowel syndrome associates with small intestinal TRPV channel expression. Aliment Pharmacol Ther 2021; 54:1179-1192. [PMID: 34472640 DOI: 10.1111/apt.16591] [Citation(s) in RCA: 18] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/05/2021] [Revised: 05/26/2021] [Accepted: 08/17/2021] [Indexed: 12/15/2022]
Abstract
BACKGROUND Irritable bowel syndrome (IBS) patients often experience meal-associated symptoms. However, the underlying mechanisms are unclear. AIM To determine small intestinal mechanisms of lipid-induced symptoms and rectal hypersensitivity in IBS METHODS: We recruited 26 IBS patients (12 IBS-C, 14 IBS-D) and 15 healthy volunteers (HV). In vivo permeability was assessed using saccharide excretion assay. Rectal sensitivity was assessed using a barostat before and after small bowel lipid infusion; symptoms were assessed throughout. Next, an extended upper endoscopy with probe-based confocal laser endomicroscopy (pCLE) was performed with changes induced by lipids. Duodenal and jejunal mucosal biopsies were obtained for transcriptomics. RESULTS Following lipid infusion, a higher proportion of HV than IBS patients reported no pain, no nausea, no fullness and no urgency (P < 0.05 for all). In a model adjusted for sex and anxiety, IBS-C and IBS-D patients had lower thresholds for first rectal sensation (P = 0.0007) and pain (P = 0.004) than HV. In vivo small intestinal permeability and mean pCLE scores were similar between IBS patients and HV. Post-lipid, pCLE scores were higher than pre-lipid but were not different between groups. Baseline duodenal transient receptor potential vanilloid (TRPV) 1 and 3 expression was increased in IBS-D, and TRPV3 in IBS-C. Duodenal TRPV1 expression correlated with abdominal pain (r = 0.51, FDR = 0.01), and inversely with first rectal sensation (r = -0.48, FDR = 0.01) and pain (r = -0.41, FDR = 0.02) thresholds. CONCLUSION Lipid infusion elicits a greater symptom response in IBS patients than HV, which is associated with small intestinal expression of TRPV channels. TRPV-mediated small intestinal chemosensitivity may mediate post-meal symptoms in IBS.
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Affiliation(s)
- Madhusudan Grover
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota, USA
| | - Antonio Berumen
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota, USA
| | - Stephanie Peters
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota, USA
| | - Ting Wei
- Health Sciences Research, Mayo Clinic, Rochester, Minnesota, USA
| | - Margaret Breen-Lyles
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota, USA
| | - William S Harmsen
- Division of Biomedical Statistics and Informatics, Mayo Clinic, Rochester, Minnesota, USA
| | - Irene Busciglio
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota, USA
| | - Duane Burton
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota, USA
| | - Maria Vazquez Roque
- Division of Gastroenterology and Hepatology, Mayo Clinic, Jacksonville, Florida, USA
| | - Kenneth R DeVault
- Division of Gastroenterology and Hepatology, Mayo Clinic, Jacksonville, Florida, USA
| | - Michael Camilleri
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota, USA
| | - Michael Wallace
- Division of Gastroenterology and Hepatology, Mayo Clinic, Jacksonville, Florida, USA
| | - Surendra Dasari
- Health Sciences Research, Mayo Clinic, Rochester, Minnesota, USA
| | - Helmut Neumann
- Department of Medicine I, University Medical Center Mainz, Mainz, Germany.,GastroZentrum Lippe, Bad Salzuflen, Germany
| | - Lesley A Houghton
- Division of Gastroenterology and Hepatology, Mayo Clinic, Jacksonville, Florida, USA.,Leeds Institute of Medical Research at St James's, University of Leeds, Leeds, UK
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28
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Pinart M, Nimptsch K, Forslund SK, Schlicht K, Gueimonde M, Brigidi P, Turroni S, Ahrens W, Hebestreit A, Wolters M, Dötsch A, Nöthlings U, Oluwagbemigun K, Cuadrat RRC, Schulze MB, Standl M, Schloter M, De Angelis M, Iozzo P, Guzzardi MA, Vlaemynck G, Penders J, Jonkers DMAE, Stemmer M, Chiesa G, Cavalieri D, De Filippo C, Ercolini D, De Filippis F, Ribet D, Achamrah N, Tavolacci MP, Déchelotte P, Bouwman J, Laudes M, Pischon T. Identification and Characterization of Human Observational Studies in Nutritional Epidemiology on Gut Microbiomics for Joint Data Analysis. Nutrients 2021; 13:3292. [PMID: 34579168 PMCID: PMC8466729 DOI: 10.3390/nu13093292] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/22/2021] [Revised: 09/10/2021] [Accepted: 09/17/2021] [Indexed: 01/16/2023] Open
Abstract
In any research field, data access and data integration are major challenges that even large, well-established consortia face. Although data sharing initiatives are increasing, joint data analyses on nutrition and microbiomics in health and disease are still scarce. We aimed to identify observational studies with data on nutrition and gut microbiome composition from the Intestinal Microbiomics (INTIMIC) Knowledge Platform following the findable, accessible, interoperable, and reusable (FAIR) principles. An adapted template from the European Nutritional Phenotype Assessment and Data Sharing Initiative (ENPADASI) consortium was used to collect microbiome-specific information and other related factors. In total, 23 studies (17 longitudinal and 6 cross-sectional) were identified from Italy (7), Germany (6), Netherlands (3), Spain (2), Belgium (1), and France (1) or multiple countries (3). Of these, 21 studies collected information on both dietary intake (24 h dietary recall, food frequency questionnaire (FFQ), or Food Records) and gut microbiome. All studies collected stool samples. The most often used sequencing platform was Illumina MiSeq, and the preferred hypervariable regions of the 16S rRNA gene were V3-V4 or V4. The combination of datasets will allow for sufficiently powered investigations to increase the knowledge and understanding of the relationship between food and gut microbiome in health and disease.
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Affiliation(s)
- Mariona Pinart
- Molecular Epidemiology Research Group, Max Delbrück Center for Molecular Medicine in the Helmholtz Association (MDC), 13125 Berlin, Germany; (M.P.); (T.P.)
| | - Katharina Nimptsch
- Molecular Epidemiology Research Group, Max Delbrück Center for Molecular Medicine in the Helmholtz Association (MDC), 13125 Berlin, Germany; (M.P.); (T.P.)
| | - Sofia K. Forslund
- Experimental and Clinical Research Center, A Cooperation of Charité-Universitätsmedizin Berlin and Max Delbrück Center for Molecular Medicine, Lindenberger Weg 80, 13125 Berlin, Germany;
- Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, Berlin Institute of Health, 10117 Berlin, Germany
- Host-Microbiome Factors in Cardiovascular Disease Lab, Max Delbrück Center for Molecular Medicine in the Helmholtz Association (MDC), 13125 Berlin, Germany
- German Centre for Cardiovascular Research (DZHK), Partner Site Berlin, 10785 Berlin, Germany
- Berlin Institute of Health (BIH), 10178 Berlin, Germany
- Structural and Computational Biology Unit, European Molecular Biology Laboratory, 69117 Heidelberg, Germany
| | - Kristina Schlicht
- Institute of Diabetes and Clinical Metabolic Research, University of Kiel, 24105 Kiel, Germany; (K.S.); (M.L.)
| | - Miguel Gueimonde
- Department of Microbiology and Biochemistry of Dairy Products, IPLA-CSIC, 33300 Villaviciosa, Spain;
- Diet, Microbiota and Health Group, Instituto de Investigación Sanitaria del Principado de Asturias (ISPA), 33011 Oviedo, Spain
| | - Patrizia Brigidi
- Department of Medical and Surgical Sciences, University of Bologna, Via Massarenti 9, 40138 Bologna, Italy;
| | - Silvia Turroni
- Department of Pharmacy and Biotechnology, University of Bologna, Via Belmeloro 6, 40126 Bologna, Italy;
| | - Wolfgang Ahrens
- Leibniz Institute for Prevention Research and Epidemiology-BIPS, 28359 Bremen, Germany; (W.A.); (A.H.); (M.W.)
- Institute of Statistics, Bremen University, 28359 Bremen, Germany
| | - Antje Hebestreit
- Leibniz Institute for Prevention Research and Epidemiology-BIPS, 28359 Bremen, Germany; (W.A.); (A.H.); (M.W.)
| | - Maike Wolters
- Leibniz Institute for Prevention Research and Epidemiology-BIPS, 28359 Bremen, Germany; (W.A.); (A.H.); (M.W.)
| | - Andreas Dötsch
- Department of Physiology and Biochemistry of Nutrition, Max Rubner-Institut (MRI)-Federal Research Institute of Nutrition and Food, 76131 Karlsruhe, Germany;
| | - Ute Nöthlings
- Nutritional Epidemiology Unit, Institute of Nutrition and Food Sciences, University of Bonn, 53115 Bonn, Germany; (U.N.); (K.O.)
| | - Kolade Oluwagbemigun
- Nutritional Epidemiology Unit, Institute of Nutrition and Food Sciences, University of Bonn, 53115 Bonn, Germany; (U.N.); (K.O.)
| | - Rafael R. C. Cuadrat
- Department of Molecular Epidemiology, German Institute of Human Nutrition Potsdam-Rehbruecke, 14558 Nuthetal, Germany; (R.R.C.C.); (M.B.S.)
| | - Matthias B. Schulze
- Department of Molecular Epidemiology, German Institute of Human Nutrition Potsdam-Rehbruecke, 14558 Nuthetal, Germany; (R.R.C.C.); (M.B.S.)
- Institute of Nutritional Science, University of Potsdam, 14558 Potsdam, Germany
- German Center for Diabetes Research (DZD), 85764 Neuherberg, Germany
| | - Marie Standl
- Institute of Epidemiology, Helmholtz Zentrum München-German Research Center for Environmental Health, 85764 Neuherberg, Germany;
| | - Michael Schloter
- Research Unit for Comparative Microbiome Analysis, Helmholtz Zentrum München-German Research Center for Environmental Health, 85764 Neuherberg, Germany;
| | - Maria De Angelis
- Department of Soil, Plant and Food Sciences, University of Bari Aldo Moro, 70126 Bari, Italy;
| | - Patricia Iozzo
- Institute of Clinical Physiology, National Research Council, Via Moruzzi 1, 56124 Pisa, Italy; (P.I.); (M.A.G.)
| | - Maria Angela Guzzardi
- Institute of Clinical Physiology, National Research Council, Via Moruzzi 1, 56124 Pisa, Italy; (P.I.); (M.A.G.)
| | - Geertrui Vlaemynck
- Department Technology and Food, Flanders Research Institute for Agriculture, Fisheries and Food, 9090 Melle, Belgium;
| | - John Penders
- Department of Medical Microbiology, School of Nutrition and Translational Research in Metabolism (NUTRIM) and Care and Public Health Research Institute (CAPHRI), Maastricht University Medical Center, 6200 MD Maastricht, The Netherlands;
| | - Daisy M. A. E. Jonkers
- Department of Internal Medicine, Division Gastroenterology-Hepatology, NUTRIM School of Nutrition and Translational Research in Metabolism, Maastricht University Medical Center, 6200 MD Maastricht, The Netherlands;
| | - Maya Stemmer
- Department of Industrial Engineering and Management, Ben-Gurion University of the Negev, Beer-Sheva P.O. Box 653, Israel;
| | - Giulia Chiesa
- Department of Pharmacological and Biomolecular Sciences, Università degli Studi di Milano, 20133 Milan, Italy;
| | - Duccio Cavalieri
- Department of Biology, University of Florence, Via Madonna del Piano 6, 50019 Florence, Italy;
| | - Carlotta De Filippo
- Institute of Agricultural Biology and Biotechnology National Research Council, Via Moruzzi 1, 56124 Pisa, Italy;
| | - Danilo Ercolini
- Department of Agricultural Sciences, University of Naples Federico II, 80055 Portici, Italy; (D.E.); (F.D.F.)
- Task Force on Microbiome Studies, University of Naples Federico II, 80134 Naples, Italy
| | - Francesca De Filippis
- Department of Agricultural Sciences, University of Naples Federico II, 80055 Portici, Italy; (D.E.); (F.D.F.)
- Task Force on Microbiome Studies, University of Naples Federico II, 80134 Naples, Italy
| | - David Ribet
- INSERM UMR 1073 “Nutrition, Inflammation and Gut-Brain Axis Dysfunctions”, UNIROUEN, Normandie University, 76000 Rouen, France; (D.R.); (N.A.); (M.-P.T.); (P.D.)
| | - Najate Achamrah
- INSERM UMR 1073 “Nutrition, Inflammation and Gut-Brain Axis Dysfunctions”, UNIROUEN, Normandie University, 76000 Rouen, France; (D.R.); (N.A.); (M.-P.T.); (P.D.)
- Department of Nutrition, CHU Rouen, 76000 Rouen, France
| | - Marie-Pierre Tavolacci
- INSERM UMR 1073 “Nutrition, Inflammation and Gut-Brain Axis Dysfunctions”, UNIROUEN, Normandie University, 76000 Rouen, France; (D.R.); (N.A.); (M.-P.T.); (P.D.)
- INSERM CIC-CRB 1404, CHU Rouen, 76000 Rouen, France
| | - Pierre Déchelotte
- INSERM UMR 1073 “Nutrition, Inflammation and Gut-Brain Axis Dysfunctions”, UNIROUEN, Normandie University, 76000 Rouen, France; (D.R.); (N.A.); (M.-P.T.); (P.D.)
- Department of Nutrition, CHU Rouen, 76000 Rouen, France
| | - Jildau Bouwman
- Microbiology and Systems Biology Group, TNO, Utrechtseweg 48, 3704 HE Zeist, The Netherlands;
| | - Matthias Laudes
- Institute of Diabetes and Clinical Metabolic Research, University of Kiel, 24105 Kiel, Germany; (K.S.); (M.L.)
| | - Tobias Pischon
- Molecular Epidemiology Research Group, Max Delbrück Center for Molecular Medicine in the Helmholtz Association (MDC), 13125 Berlin, Germany; (M.P.); (T.P.)
- Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, Berlin Institute of Health, 10117 Berlin, Germany
- German Centre for Cardiovascular Research (DZHK), Partner Site Berlin, 10785 Berlin, Germany
- Biobank Technology Platform, Max Delbrück Center for Molecular Medicine in the Helmholtz Association (MDC), 13125 Berlin, Germany
- Biobank Core Facility, Berlin Institute of Health at Charité-Universitätsmedizin Berlin, 10178 Berlin, Germany
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Abstract
Advances in bioinformatics have facilitated investigation of the role of gut microbiota in patients with irritable bowel syndrome (IBS). This article describes the evidence from epidemiologic and clinical observational studies highlighting the link between IBS and gut microbiome by investigating postinfection IBS, small intestinal bacterial overgrowth, and microbial dysbiosis. It highlights the effects of gut microbiota on mechanisms implicated in the pathophysiology of IBS, including gut-brain axis, visceral hypersensitivity, motility, epithelial barrier, and immune activation. In addition, it summarizes the current evidence on microbiome-guided therapies in IBS, including probiotics, antibiotics, diet, and fecal microbiota transplant.
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Affiliation(s)
- Prashant Singh
- Division of Gastroenterology and Hepatology, University of Michigan, MSBR1, Room 6520 B, 1150 West Medical Center Drive, Ann Arbor, MI 48109, USA.
| | - Anthony Lembo
- Division of Gastroenterology and Hepatology, Beth Israel Deaconess Medical Center, Rabb/Rose 1, 330 Brookline Avenue, Boston, MA 02215, USA
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30
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Sauna dehydration as a new physiological challenge model for intestinal barrier function. Sci Rep 2021; 11:15514. [PMID: 34330970 PMCID: PMC8324874 DOI: 10.1038/s41598-021-94814-0] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/20/2021] [Accepted: 07/16/2021] [Indexed: 12/15/2022] Open
Abstract
The intestinal barrier plays a crucial role in maintaining gut health, and an increased permeability has been linked to several intestinal and extra-intestinal disorders. There is an increasing demand for interventions aimed at strengthening this barrier and for in vivo challenge models to assess their efficiency. This study investigated the effect of sauna-induced dehydration on intestinal barrier function (clinicaltrials.gov: NCT03620825). Twenty healthy subjects underwent three conditions in random order: (1) Sauna dehydration (loss of 3% body weight), (2) non-steroidal anti-inflammatory drug (NSAID) intake, (3) negative control. Intestinal permeability was assessed by a multi-sugar urinary recovery test, while intestinal damage, bacterial translocation and cytokines were assessed by plasma markers. The sauna dehydration protocol resulted in an increase in gastroduodenal and small intestinal permeability. Presumably, this increase occurred without substantial damage to the enterocytes as plasma intestinal fatty acid-binding protein (I-FABP) and liver fatty acid-binding protein (L-FABP) were not affected. In addition, we observed significant increases in levels of lipopolysaccharide-binding protein (LBP), IL-6 and IL-8, while sCD14, IL-10, IFN-ɣ and TNF-α were not affected. These results suggest that sauna dehydration increased intestinal permeability and could be applied as a new physiological in vivo challenge model for intestinal barrier function.
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31
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Roca Rubio MF, Eriksson U, Brummer RJ, König J. Short intense psychological stress induced by skydiving does not impair intestinal barrier function. PLoS One 2021; 16:e0254280. [PMID: 34237102 PMCID: PMC8266057 DOI: 10.1371/journal.pone.0254280] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/03/2020] [Accepted: 06/23/2021] [Indexed: 12/22/2022] Open
Abstract
Background and aim Psychological stress has been shown to increase intestinal permeability and is associated with the development of gastrointestinal disorders. This study aimed to investigate skydiving as an alternative model to analyse the effect of acute psychological stress on intestinal barrier function. Materials and methods Twenty healthy subjects participated in a tandem skydive followed by a negative control visit, of which 19 (9 females and 10 males, 25.9 ± 3.7 years) were included in the study. Intestinal permeability was assessed by a multi-sugar urinary recovery test. Sucrose recovery and lactulose/rhamnose ratio in 0-5h urine indicated gastroduodenal and small intestinal permeability, respectively, and sucralose/erythritol ratio in 5-24h urine indicated colonic permeability. Blood samples were taken to assess markers associated with barrier function. This study has been registered at ClinicalTrials.gov (NCT03644979) on August 23, 2018. Results Skydiving resulted in a significant increase in salivary cortisol levels directly after skydiving compared to the control visit. Cortisol levels were still increased two hours after landing, while cortisol levels before skydiving were not significantly different from the baseline at the control visit. Skydiving did not induce a significant increase in gastroduodenal, small intestinal or colonic permeability. There was also no significant increase in plasma intestinal and liver fatty acid-binding proteins, suggesting no damage to the enterocytes. Discussion These results show that the acute intense psychological stress induced by skydiving does not affect intestinal permeability in healthy subjects. Future models aiming to investigate the effect of stress on human intestinal barrier function should consider a more sustained exposure to the psychological stressor.
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Affiliation(s)
- Maria Fernanda Roca Rubio
- Nutrition-Gut-Brain Interactions Research Centre, Faculty of Medicine and Health, School of Medical Sciences, Örebro University, Örebro, Sweden
- * E-mail:
| | - Ulrika Eriksson
- Man-Technology-Environment Research Centre, School of Science and Technology, Örebro University, Örebro, Sweden
| | - Robert J. Brummer
- Nutrition-Gut-Brain Interactions Research Centre, Faculty of Medicine and Health, School of Medical Sciences, Örebro University, Örebro, Sweden
| | - Julia König
- Nutrition-Gut-Brain Interactions Research Centre, Faculty of Medicine and Health, School of Medical Sciences, Örebro University, Örebro, Sweden
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32
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Stevens Y, Pinheiro I, Salden B, Duysburgh C, Bolca S, Degroote J, Majdeddin M, Van Noten N, Gleize B, Caris-Veyrat C, Michiels J, Jonkers D, Troost F, Possemiers S, Masclee A. Effect of a carotenoid-producing Bacillus strain on intestinal barrier integrity and systemic delivery of carotenoids: A randomised trial in animals and humans. J Funct Foods 2021. [DOI: 10.1016/j.jff.2021.104445] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/24/2022] Open
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Tatucu-Babet OA, Forsyth A, Udy A, Radcliffe J, Benheim D, Calkin C, Ridley EJ, Gantner D, Jois M, Itsiopoulos C, Tierney AC. Use of a sensitive multisugar test for measuring segmental intestinal permeability in critically ill, mechanically ventilated adults: A pilot study. JPEN J Parenter Enteral Nutr 2021; 46:454-461. [PMID: 33760268 DOI: 10.1002/jpen.2110] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/07/2022]
Abstract
BACKGROUND Increased intestinal permeability (IP) is associated with sepsis in the intensive care unit (ICU). This study aimed to pilot a sensitive multisugar test to measure IP in the nonfasted state. METHODS Critically ill, mechanically ventilated adults were recruited from 2 ICUs in Australia. Measurements were completed within 3 days of admission using a multisugar test measuring gastroduodenal (sucrose recovery), small-bowel (lactulose-rhamnose [L-R] and lactulose-mannitol [L-M] ratios), and whole-gut permeability (sucralose-erythritol ratio) in 24-hour urine samples. Urinary sugar concentrations were compared at baseline and after sugar ingestion, and IP sugar recoveries and ratios were explored in relation to known confounders, including renal function. RESULTS Twenty-one critically ill patients (12 males; median, 57 years) participated. Group median concentrations of all sugars were higher following sugar administration; however, sucrose and mannitol increases were not statistically significant. Within individual patients, sucrose and mannitol concentrations were higher in baseline than after sugar ingestion in 9 (43%) and 4 (19%) patients, respectively. Patients with impaired (n = 9) vs normal (n = 12) renal function had a higher L-R ratio (median, 0.130 vs 0.047; P = .003), lower rhamnose recovery (median, 15% vs 24%; P = .007), and no difference in lactulose recovery. CONCLUSION Small-bowel and whole-gut permeability measurements are possible to complete in the nonfasted state, whereas gastroduodenal permeability could not be measured reliably. For small-bowel IP measurements, the L-R ratio is preferred over the L-M ratio. Alterations in renal function may reduce the reliability of the multisugar IP test, warranting further exploration.
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Affiliation(s)
- Oana A Tatucu-Babet
- Department of Dietetics, Nutrition and Sport, La Trobe University, Melbourne, Australia.,Australian and New Zealand Intensive Care Research Centre, School of Public Health and Preventative Medicine, Monash University, Melbourne, Australia
| | - Adrienne Forsyth
- Department of Dietetics, Nutrition and Sport, La Trobe University, Melbourne, Australia
| | - Andrew Udy
- Australian and New Zealand Intensive Care Research Centre, School of Public Health and Preventative Medicine, Monash University, Melbourne, Australia.,Intensive Care Unit, Alfred Hospital, Melbourne, Victoria, Australia
| | - Jessica Radcliffe
- Department of Dietetics, Nutrition and Sport, La Trobe University, Melbourne, Australia.,Senior Scientist Group Nutrition, Immunity and Metabolism, Department of Nutrition and Gerontology, German Institute of Human Nutrition, Potsdam-Rehbrücke, Potsdam, Germany
| | - Devin Benheim
- Department of Physiology, Anatomy and Microbiology, La Trobe University, Melbourne, Australia
| | | | - Emma J Ridley
- Australian and New Zealand Intensive Care Research Centre, School of Public Health and Preventative Medicine, Monash University, Melbourne, Australia.,Nutrition Department, Alfred Health, Melbourne, Australia
| | - Dashiell Gantner
- Australian and New Zealand Intensive Care Research Centre, School of Public Health and Preventative Medicine, Monash University, Melbourne, Australia.,Intensive Care Unit, Alfred Hospital, Melbourne, Victoria, Australia
| | - Markandeya Jois
- Department of Physiology, Anatomy and Microbiology, La Trobe University, Melbourne, Australia
| | - Catherine Itsiopoulos
- Department of Dietetics, Nutrition and Sport, La Trobe University, Melbourne, Australia.,School of Health and Biomedical Sciences, College of STEM, RMIT University, Melbourne, Australia
| | - Audrey C Tierney
- Department of Dietetics, Nutrition and Sport, La Trobe University, Melbourne, Australia.,School of Allied Health and Health Implementation Science and Technology Centre, Health Research Institute, University of Limerick, Limerick, Ireland
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Hanning N, Edwinson AL, Ceuleers H, Peters SA, De Man JG, Hassett LC, De Winter BY, Grover M. Intestinal barrier dysfunction in irritable bowel syndrome: a systematic review. Therap Adv Gastroenterol 2021; 14:1756284821993586. [PMID: 33717210 PMCID: PMC7925957 DOI: 10.1177/1756284821993586] [Citation(s) in RCA: 114] [Impact Index Per Article: 28.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/30/2020] [Accepted: 01/19/2021] [Indexed: 02/04/2023] Open
Abstract
BACKGROUND AND AIM Irritable bowel syndrome (IBS) is a complex and heterogeneous disorder. Sensory, motor and barrier dysfunctions are the key physiological endophenotypes of IBS. Our aim is to review studies evaluating barrier dysfunction in adults and children with IBS, as well as to link those changes with IBS symptomatology and quality of life. METHODS A comprehensive and systematic review of multiple databases was performed up to March 2020 to identify studies comparing intestinal permeability in IBS patients with healthy controls. Both in vivo and in vitro studies were considered. RESULTS We identified 66 studies, of which 27 used intestinal probes to quantify barrier function. The prevalence of barrier dysfunction differed between PI-IBS (17-50%), IBS-D (37-62%) and IBS-C (4-25%). At a group level, permeability was increased compared with healthy controls in IBS-D (9/13 studies) and PI-IBS (4/4 studies), but only a minority of IBS-C (2/7 studies) and not in the only IBS-M study. All four studies in children with IBS demonstrated loss of barrier function. A heterogeneous set of tight junction genes were found to be altered in small and large intestines of adults with IBS, but these have not been evaluated in children. Positive associations were identified between barrier dysfunction and bowel disturbances (6/9 studies), abdominal pain (9/13 studies), overall symptom severity (1/6 studies), depression and anxiety (1/1 study) and quality of life (1/4 studies). Fecal slurry or supernatants of IBS patients were found to induce barrier disruption in animal models (5/6 studies). CONCLUSIONS Barrier dysfunction is present in a significant proportion of adult and all pediatric IBS studies, especially in the IBS-D and PI-IBS subtype. The majority of studies indicated a positive association between loss of barrier function and symptoms such as abdominal pain and changes in the bowel function.
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Affiliation(s)
- Nikita Hanning
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota, USA
- Laboratory of Experimental Medicine and Pediatrics (LEMP) and Infla-Med, research consortium of excellence, University of Antwerp, Antwerp, Belgium
| | - Adam L. Edwinson
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota, USA
| | - Hannah Ceuleers
- Laboratory of Experimental Medicine and Pediatrics (LEMP) and Infla-Med, research consortium of excellence, University of Antwerp, Antwerp, Belgium
| | - Stephanie A. Peters
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota, USA
| | - Joris G. De Man
- Laboratory of Experimental Medicine and Pediatrics (LEMP) and Infla-Med, research consortium of excellence, University of Antwerp, Antwerp, Belgium
| | | | - Benedicte Y. De Winter
- Division of Gastroenterology, Laboratory of Experimental Medicine and Pediatrics, Universiteitsplein 1, Antwerp, 2610, Belgium
- Department of Gastroenterology and Hepatology, Antwerp University Hospital (UZA), Antwerp, Belgium
| | - Madhusudan Grover
- Department of Medicine and Physiology, Enteric NeuroScience Program, 200 First St SW, Rochester, MN 55905, USA
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Mujagic Z, Jonkers DMAE, Masclee AAM, Keszthelyi D. A Key Role for the Small Bowel in Irritable Bowel Syndrome Pathophysiology: Time to Refocus? Clin Gastroenterol Hepatol 2021; 19:409-410. [PMID: 32200082 DOI: 10.1016/j.cgh.2020.03.026] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/20/2020] [Revised: 03/04/2020] [Accepted: 03/05/2020] [Indexed: 02/07/2023]
Affiliation(s)
- Zlatan Mujagic
- Division of Gastroenterology-Hepatology, NUTRIM School of Nutrition and, Translational Research in Metabolism, Maastricht University Medical Center, Maastricht, The Netherlands
| | - Daisy M A E Jonkers
- Division of Gastroenterology-Hepatology, NUTRIM School of Nutrition and, Translational Research in Metabolism, Maastricht University Medical Center, Maastricht, The Netherlands
| | - Ad A M Masclee
- Division of Gastroenterology-Hepatology, NUTRIM School of Nutrition and, Translational Research in Metabolism, Maastricht University Medical Center, Maastricht, The Netherlands
| | - Daniel Keszthelyi
- Division of Gastroenterology-Hepatology, NUTRIM School of Nutrition and, Translational Research in Metabolism, Maastricht University Medical Center, Maastricht, The Netherlands
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Do Sex Differences in Physiology Confer a Female Advantage in Ultra-Endurance Sport? Sports Med 2021; 51:895-915. [PMID: 33502701 DOI: 10.1007/s40279-020-01417-2] [Citation(s) in RCA: 55] [Impact Index Per Article: 13.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 12/20/2020] [Indexed: 01/09/2023]
Abstract
Ultra-endurance has been defined as any exercise bout that exceeds 6 h. A number of exceptional, record-breaking performances by female athletes in ultra-endurance sport have roused speculation that they might be predisposed to success in such events. Indeed, while the male-to-female performance gap in traditional endurance sport (e.g., marathon) remains at ~ 10%, the disparity in ultra-endurance competition has been reported as low as 4% despite the markedly lower number of female participants. Moreover, females generally outperform males in extreme-distance swimming. The issue is complex, however, with many sports-specific considerations and caveats. This review summarizes the sex-based differences in physiological functions and draws attention to those which likely determine success in extreme exercise endeavors. The aim is to provide a balanced discussion of the female versus male predisposition to ultra-endurance sport. Herein, we discuss sex-based differences in muscle morphology and fatigability, respiratory-neuromechanical function, substrate utilization, oxygen utilization, gastrointestinal structure and function, and hormonal control. The literature indicates that while females exhibit numerous phenotypes that would be expected to confer an advantage in ultra-endurance competition (e.g., greater fatigue resistance, greater substrate efficiency, and lower energetic demands), they also exhibit several characteristics that unequivocally impinge on performance (e.g., lower O2-carrying capacity, increased prevalence of GI distress, and sex-hormone effects on cellular function/injury risk). Crucially, the advantageous traits may only manifest as ergogenic in the extreme endurance events which, paradoxically, are those that females less often contest. The title question should be revisited in the coming years, when/if the number of female participants increases.
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Hu Z, Li M, Yao L, Wang Y, Wang E, Yuan J, Wang F, Yang K, Bian Z, Zhong LLD. The level and prevalence of depression and anxiety among patients with different subtypes of irritable bowel syndrome: a network meta-analysis. BMC Gastroenterol 2021; 21:23. [PMID: 33413140 PMCID: PMC7791666 DOI: 10.1186/s12876-020-01593-5] [Citation(s) in RCA: 58] [Impact Index Per Article: 14.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/19/2020] [Accepted: 12/21/2020] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Irritable bowel syndrome (IBS) is a very common functional bowel disorder. However, the difference of depression and anxiety comorbidities among different IBS subtypes is still not well evaluated. This study aims to investigate the difference in the level and prevalence of depression and anxiety among healthy controls and patients with different subtypes of IBS. METHODS PubMed, EMBASE and the Cochrane library were searched systematically until August 17, 2020. Studies that investigated depression and/or anxiety levels or prevalence among different IBS-subtype patients measured at baseline or the same point were included. Network meta-analysis was conducted to analyze standardized mean difference (SMD) of anxiety and depression levels, and single arm meta-analysis was performed for prevalence of anxiety and depression among different IBS subtypes. RESULTS Eighteen studies involving 7095 participants were included. Network meta-analyses results showed healthy controls had a lower level of depression than IBS with mixed symptoms of constipation and diarrhea (IBS-M) [SMD = - 1.57; 95% confidence interval (CI) - 2.21, - 0.92], IBS with constipation (IBS-C) (SMD = - 1.53; 95% CI - 2.13, - 0.93) and IBS with diarrhea (IBS-D)(SMD = - 1.41; 95% CI - 1.97, - 0.85), while no significant difference was found between IBS unclassified (IBS-U) and healthy controls (SMD = - 0.58; 95% CI - 2.15, 1.00). There was also no significant difference in the level of depression among different IBS subtypes patients. The results of anxiety were similar to depression. Ranking probability showed that IBS-M was associated with the highest level of depression and anxiety symptoms, followed by IBS-C/IBS-D and IBS-U. Single-arm meta-analysis showed IBS-C had the highest prevalence of depression (38%) and anxiety (40%), followed by IBS-D, IBS-M and IBS-U. CONCLUSION The results indicated that IBS-M was more likely to be associated with a higher level of depression and anxiety, and the prevalence of depression and anxiety in IBS-C was highest. The psychological screening and appropriate psychotherapy are needed for patients with IBS-C, IBS-D and IBS-M instead of IBS-U.
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Affiliation(s)
- Zhichao Hu
- Hong Kong Chinese Medicine Clinical Study Center, School of Chinese Medicine, Hong Kong Baptist University, 7 Baptist University Road, Kowloon, 999077, Hong Kong SAR, China
| | - Meixuan Li
- Evidence-Based Medicine Center, School of Basic Medical Sciences, Lanzhou University, Lanzhou, 730000, China
| | - Liang Yao
- Department of Health Research Methods, Evidence and Impact, McMaster University, Hamilton, ON, L8S 4L8, Canada
| | - Yinshu Wang
- Institute of Digestive Diseases, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, 200032, China
| | - Enkang Wang
- Institute of Digestive Diseases, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, 200032, China
| | - Jianye Yuan
- Institute of Digestive Diseases, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, 200032, China
| | - Fengyun Wang
- Xiyuan Hospital, China Academy of Chinese Medicinal Sciences, Beijing, 100091, China
| | - Kehu Yang
- Evidence-Based Medicine Center, School of Basic Medical Sciences, Lanzhou University, Lanzhou, 730000, China
| | - Zhaoxiang Bian
- Hong Kong Chinese Medicine Clinical Study Center, School of Chinese Medicine, Hong Kong Baptist University, 7 Baptist University Road, Kowloon, 999077, Hong Kong SAR, China.
| | - Linda L D Zhong
- Hong Kong Chinese Medicine Clinical Study Center, School of Chinese Medicine, Hong Kong Baptist University, 7 Baptist University Road, Kowloon, 999077, Hong Kong SAR, China.
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Talley NJ, Alexander JL, Walker MM, Jones MP, Hugerth LW, Engstrand L, Agréus L, Powell N, Andreasson A. Ileocolonic Histopathological and Microbial Alterations in the Irritable Bowel Syndrome: A Nested Community Case-Control Study. Clin Transl Gastroenterol 2020; 12:e00296. [PMID: 33464728 PMCID: PMC8345925 DOI: 10.14309/ctg.0000000000000296] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/27/2020] [Accepted: 11/23/2020] [Indexed: 12/31/2022] Open
Abstract
INTRODUCTION Histopathological alterations in the ileum and colon in irritable bowel syndrome (IBS) are controversial, and normal values are poorly established. We hypothesized that changes in mucosal immune cells characterize IBS and key changes in immune composition are associated with the mucosa-associated microbiota (MaM). METHODS A nested case-control study (48 IBS and 106 controls included) from 745 colonoscopy participants in a random population sample. Intraepithelial lymphocytes (IELs)/100 enterocytes and eosinophils/5 nonoverlapping high-power fields counted; mast cells identified by immunocytochemistry (CD117)/5 high-power fields. Paneth cells quantified per 5 crypts. 16S rRNA gene amplicon sequencing performed on available sigmoid MaM, n = 55 and fecal microbiota, n = 20. Microbiota profiles compared between samples with high and low IEL counts. RESULTS IBS had increased IELs in the terminal ileum (relative risk ratio = 1.70, 95% confidence interval 1.08-2.76, P = 0.022 adjusted for age, sex, and smoking). Cecal IELs were increased in IBS-diarrhea (relative risk ratio = 2.03, 95% confidence interval 1.13-3.63, P = 0.017). No difference was observed in alpha diversity of MaM or fecal microbiota based on IEL count. There was no difference in beta diversity of the MaM according to IEL count in the terminal ileal (TI) (P = 0.079). High TI IEL counts associated with a significant expansion of the genus Blautia (P = 0.024) and unclassified Clostridiales (P = 0.036) in colon MaM. DISCUSSION A modest but significant increase in IELs was observed in IBS vs. controls in a population-based setting. Subtle TI and cecal inflammation may play a pathogenic role in IBS but needs confirmation. Modest but discernible differences in the colonic MaM were seen according to TI IEL count but not IBS status.
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Affiliation(s)
- Nicholas J. Talley
- Faculty of Health and Medicine, University of Newcastle, Newcastle, Australia
- NHMRC Center of Research Excellence in Digestive Health Newcastle, Australia
| | | | - Marjorie M. Walker
- NHMRC Center of Research Excellence in Digestive Health Newcastle, Australia
- Department of Anatomical Pathology, University of Newcastle, Newcastle, Australia
| | - Michael P. Jones
- NHMRC Center of Research Excellence in Digestive Health Newcastle, Australia
- Department of Psychology, Macquarie University, North Ryde, Australia
| | - Luisa W. Hugerth
- Center for Translational Microbiome Research, CTMR, Department of Microbiology, Tumor and Cell Biology (MTC), Karolinska Institutet, Science for Life Laboratory, Solna, Sweden
| | - Lars Engstrand
- Center for Translational Microbiome Research, CTMR, Department of Microbiology, Tumor and Cell Biology (MTC), Karolinska Institutet, Science for Life Laboratory, Solna, Sweden
| | - Lars Agréus
- Division for Family Medicine and Primary Care, Karolinska Institutet, Huddinge, Sweden
| | - Nicholas Powell
- NHMRC Center of Research Excellence in Digestive Health Newcastle, Australia
- Division of Digestive Disease, Imperial College London, London, UK
| | - Anna Andreasson
- Department of Psychology, Macquarie University, North Ryde, Australia
- Stress Research Institute, Stockholm University, Stockholm, Sweden
- Department of Medicine Solna, Karolinska Institutet, Solna, Sweden
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Muehler A, Slizgi JR, Kohlhof H, Groeppel M, Peelen E, Vitt D. Clinical relevance of intestinal barrier dysfunction in common gastrointestinal diseases. World J Gastrointest Pathophysiol 2020; 11:114-130. [PMID: 33362939 PMCID: PMC7739114 DOI: 10.4291/wjgp.v11.i6.114] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/21/2020] [Revised: 10/07/2020] [Accepted: 10/27/2020] [Indexed: 02/06/2023] Open
Abstract
The intestinal barrier is a complex and well-controlled physiological construct designed to separate luminal contents from the bowel wall. In this review, we focus on the intestinal barrier’s relationship with the host’s immune system interaction and the external environment, specifically the microbiome. The bowel allows the host to obtain nutrients vital to survival while protecting itself from harmful pathogens, luminal antigens, or other pro-inflammatory factors. Control over barrier function and the luminal milieu is maintained at the biochemical, cellular, and immunological level. However, disruption to this highly regulated environment can cause disease. Recent advances to the field have progressed the mechanistic understanding of compromised intestinal barrier function in the context of gastrointestinal pathology. There are numerous examples where bowel barrier dysfunction and the resulting interaction between the microbiome and the immune system has disease-triggering consequences. The purpose of this review is to summarize the clinical relevance of intestinal barrier dysfunction in common gastrointestinal and related diseases. This may help highlight the importance of restoring barrier function as a therapeutic mechanism of action in gastrointestinal pathology.
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Noninvasive Biomarkers of Gut Barrier Function in Patients Suffering from Diarrhea Predominant-IBS: An Update. DISEASE MARKERS 2020; 2020:2886268. [PMID: 33110455 PMCID: PMC7582069 DOI: 10.1155/2020/2886268] [Citation(s) in RCA: 23] [Impact Index Per Article: 4.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Received: 01/31/2020] [Revised: 09/23/2020] [Accepted: 10/07/2020] [Indexed: 12/14/2022]
Abstract
The intestinal barrier plays a crucial role in the absorption of nutrients and in preventing the entry of pathogenic microorganisms and toxic molecules. Several studies have shown a compromised intestinal barrier associated with low-grade inflammation in the small intestinal mucosa in celiac disease, inflammatory bowel disease, and irritable bowel syndrome (IBS), particularly in IBS with diarrhea (IBS-D). In light of these new data, IBS is no longer considered a functional disease but rather a heterogeneous syndrome that has yet to be carefully studied. Therefore, investigating the integrity and function of the intestinal barrier is now essential to improving knowledge of the pathophysiology of IBS-D and to improving the management of IBS-D patients. However, the study of the intestinal barrier must clarify some still unsolved methodological aspects and propose standardised assays before becoming a useful diagnostic tool. In this framework, this review will discuss data about the tests that noninvasively evaluate the integrity and functionality of the human intestinal barrier, paying particular attention to patients with IBS-D, in both clinical and research situations.
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Caviglia GP, Tucci A, Pellicano R, Fagoonee S, Rosso C, Abate ML, Olivero A, Armandi A, Vanni E, Saracco GM, Bugianesi E, Astegiano M, Ribaldone DG. Clinical Response and Changes of Cytokines and Zonulin Levels in Patients with Diarrhoea-Predominant Irritable Bowel Syndrome Treated with Bifidobacterium Longum ES1 for 8 or 12 Weeks: A Preliminary Report. J Clin Med 2020; 9:2353. [PMID: 32717980 PMCID: PMC7464152 DOI: 10.3390/jcm9082353] [Citation(s) in RCA: 24] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/16/2020] [Revised: 07/21/2020] [Accepted: 07/22/2020] [Indexed: 12/12/2022] Open
Abstract
Bifidobacterium longum (B. longum) ES1 is a probiotic strain capable of modulating microbiome composition, anti-inflammatory activity and intestinal barrier function. We investigated the use of B. Longum ES1 in the treatment of patients with diarrhoea-predominant irritable bowel syndrome (IBS-D). Sixteen patients were treated for 8 or 12 weeks with B. Longum ES1 (1 × 109 CFU/day). Serum zonulin and cytokines were measured at baseline (T0) and at the end of therapy (T1). Clinical response to therapy was assessed by IBS Severity Scoring System. Interleukin (IL)-6, IL-8, IL-12p70 and tumor necrosis factor (TNF) α levels decreased from T0 to T1, irrespective of treatment duration (p < 0.05), while zonulin levels diminished only in patients treated for 12 weeks (p = 0.036). Clinical response was observed in 5/16 patients (31%): 4/8 (50%) treated for 12 weeks and 1/8 (13%) treated for 8 weeks. Abdominal pain improved only in patients treated for 12 weeks (5/8 vs. 0/8, p = 0.025), while stool consistency improved regardless of therapy duration (p < 0.001). In conclusion, the results of this pilot study showed, in IBS-D patients treated for 12 weeks with B. longum ES1, a reduction in the levels of pro-inflammatory cytokines, and intestinal permeability as well as an improvement in gastrointestinal symptoms, but further studies including a placebo-control group are necessary to prove a causal link.
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Affiliation(s)
- Gian Paolo Caviglia
- Department of Medical Sciences, University of Turin, 10124 Turin, Italy; (C.R.); (M.L.A.); (A.O.); (G.M.S.); (E.B.)
| | - Alessandra Tucci
- Unit of Gastroenterology, Città della Salute e della Scienza di Torino—Molinette Hospital, 10126 Turin, Italy; (A.T.); (R.P.); (A.A.); (E.V.); (M.A.)
| | - Rinaldo Pellicano
- Unit of Gastroenterology, Città della Salute e della Scienza di Torino—Molinette Hospital, 10126 Turin, Italy; (A.T.); (R.P.); (A.A.); (E.V.); (M.A.)
| | - Sharmila Fagoonee
- Institute of Biostructure and Bioimaging, CNR c/o Molecular Biotechnology Centre, 10126 Turin, Italy;
| | - Chiara Rosso
- Department of Medical Sciences, University of Turin, 10124 Turin, Italy; (C.R.); (M.L.A.); (A.O.); (G.M.S.); (E.B.)
| | - Maria Lorena Abate
- Department of Medical Sciences, University of Turin, 10124 Turin, Italy; (C.R.); (M.L.A.); (A.O.); (G.M.S.); (E.B.)
| | - Antonella Olivero
- Department of Medical Sciences, University of Turin, 10124 Turin, Italy; (C.R.); (M.L.A.); (A.O.); (G.M.S.); (E.B.)
| | - Angelo Armandi
- Unit of Gastroenterology, Città della Salute e della Scienza di Torino—Molinette Hospital, 10126 Turin, Italy; (A.T.); (R.P.); (A.A.); (E.V.); (M.A.)
| | - Ester Vanni
- Unit of Gastroenterology, Città della Salute e della Scienza di Torino—Molinette Hospital, 10126 Turin, Italy; (A.T.); (R.P.); (A.A.); (E.V.); (M.A.)
| | - Giorgio Maria Saracco
- Department of Medical Sciences, University of Turin, 10124 Turin, Italy; (C.R.); (M.L.A.); (A.O.); (G.M.S.); (E.B.)
| | - Elisabetta Bugianesi
- Department of Medical Sciences, University of Turin, 10124 Turin, Italy; (C.R.); (M.L.A.); (A.O.); (G.M.S.); (E.B.)
| | - Marco Astegiano
- Unit of Gastroenterology, Città della Salute e della Scienza di Torino—Molinette Hospital, 10126 Turin, Italy; (A.T.); (R.P.); (A.A.); (E.V.); (M.A.)
| | - Davide Giuseppe Ribaldone
- Department of Medical Sciences, University of Turin, 10124 Turin, Italy; (C.R.); (M.L.A.); (A.O.); (G.M.S.); (E.B.)
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Vork L, Keszthelyi D, van Kuijk SM, Quetglas EG, Törnblom H, Simrén M, Aziz Q, Corsetti M, Tack J, Mujagic Z, Leue C, Kruimel JW, Masclee AA. Patient-Specific Stress-Abdominal Pain Interaction in Irritable Bowel Syndrome: An Exploratory Experience Sampling Method Study. Clin Transl Gastroenterol 2020; 11:e00209. [PMID: 32764210 PMCID: PMC7386351 DOI: 10.14309/ctg.0000000000000209] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/20/2019] [Accepted: 06/17/2020] [Indexed: 12/12/2022] Open
Abstract
INTRODUCTION Gastrointestinal symptoms in irritable bowel syndrome (IBS) have been correlated with psychological factors using retrospective symptom assessment. However, real-time symptom assessment might reveal the interplay between abdominal and affective symptoms more reliably in a longitudinal perspective. The aim was to evaluate the association between stress and abdominal pain, using the Experience Sampling Method (ESM) as a real-time, repeated measurement method. METHODS Thirty-seven patients with IBS (26 women; mean age 36.7 years) and 36 healthy controls (HC; 24 women; mean age 31.1 years) completed an electronic ESM during 7 consecutive days. Abdominal pain and stress were scored on an 11-point Numeric Rating Scale at a maximum of 10 random moments each day. RESULTS Abdominal pain scores were 2.21 points higher in patients with IBS compared with those in HC (P < 0.001), whereas stress levels did not differ significantly (B: 0.250, P = 0.406). In IBS, a 1-point increase in stress was associated with, on average, 0.10 points increase in abdominal pain (P = 0.017). In HC, this was only 0.02 (P = 0.002). Stress levels at t = -1 were not a significant predictor for abdominal pain at t = 0 in both groups, and vice versa. DISCUSSION Our results demonstrate a positive association between real-time stress and abdominal pain scores and indicate a difference in response to stress and not a difference in experienced stress per se. Furthermore, an in-the-moment rather than a longitudinal association is suggested. This study underlines the importance of considering the individual flow of daily life and supports the use of real-time measurement when interpreting potential influencers of abdominal symptoms in IBS.
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Affiliation(s)
- Lisa Vork
- Division of Gastroenterology-Hepatology, Department of Internal Medicine, NUTRIM School of Nutrition and Translational Research in Metabolism, Maastricht University Medical Center, Maastricht, the Netherlands
| | - Daniel Keszthelyi
- Division of Gastroenterology-Hepatology, Department of Internal Medicine, NUTRIM School of Nutrition and Translational Research in Metabolism, Maastricht University Medical Center, Maastricht, the Netherlands
| | - Sander M.J. van Kuijk
- Clinical Epidemiology and Medical Technology Assessment, Maastricht University Medical Center, Maastricht, the Netherlands
| | - Emilio G. Quetglas
- Medical Intelligence, Early Clinical Development, Grünenthal GmBH, Aachen, Germany
| | - Hans Törnblom
- Department of Internal Medicine, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden
| | - Magnus Simrén
- Department of Internal Medicine, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden
| | - Qasim Aziz
- Wingate Institute of Neurogastroenterology, Centre for Neuroscience and Trauma, Blizard Institute, Barts and the London School of Medicine & Dentistry, Queen Mary University of London, London, United Kingdom
| | - Maura Corsetti
- Nottingham Digestive Diseases Biomedical Research Unit, National Institute for Health Research, Nottingham University Hospitals NHS Trust, University of Nottingham, Nottingham, United Kingdom
| | - Jan Tack
- Translational Research Center for Gastrointestinal Disorders (TARGID), Department of Clinical and Experimental Medicine, University of Leuven, Leuven, Belgium
| | - Zlatan Mujagic
- Division of Gastroenterology-Hepatology, Department of Internal Medicine, NUTRIM School of Nutrition and Translational Research in Metabolism, Maastricht University Medical Center, Maastricht, the Netherlands
| | - Carsten Leue
- Department of Psychiatry and Psychology, Maastricht University Medical Center, Maastricht, the Netherlands
| | - Joanna W. Kruimel
- Division of Gastroenterology-Hepatology, Department of Internal Medicine, NUTRIM School of Nutrition and Translational Research in Metabolism, Maastricht University Medical Center, Maastricht, the Netherlands
| | - Ad A.M. Masclee
- Division of Gastroenterology-Hepatology, Department of Internal Medicine, NUTRIM School of Nutrition and Translational Research in Metabolism, Maastricht University Medical Center, Maastricht, the Netherlands
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Wilms E, Troost FJ, Elizalde M, Winkens B, de Vos P, Mujagic Z, Jonkers DMAE, Masclee AAM. Intestinal barrier function is maintained with aging - a comprehensive study in healthy subjects and irritable bowel syndrome patients. Sci Rep 2020; 10:475. [PMID: 31949225 PMCID: PMC6965102 DOI: 10.1038/s41598-019-57106-2] [Citation(s) in RCA: 50] [Impact Index Per Article: 10.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/18/2019] [Accepted: 12/19/2019] [Indexed: 01/12/2023] Open
Abstract
Animal studies have shown that intestinal barrier function is compromised with aging. We aimed to assess the effects of aging on intestinal barrier function in humans in vivo and ex vivo. In this cross-sectional study, healthy subjects and subjects with irritable bowel syndrome (IBS) of older (65–75 years) and young adult age (18–40 years) were compared. In vivo gastrointestinal site-specific permeability was assessed by a multi-sugar test, taking into account potential confounders. Sigmoid biopsies were collected from subgroups of healthy young adults and elderly for ex vivo Ussing chamber experiments, gene transcription of barrier-related genes and staining of junctional proteins. No significant differences between healthy young adults and elderly were found for small intestinal, colonic and whole gut permeability (P ≥ 0.142). In IBS patients, gastroduodenal and colonic permeability did not differ significantly (P ≥ 0.400), but small intestinal and whole gut permeability were higher in elderly versus young adults (P ≤ 0.009), mainly driven by the IBS-diarrhea subtype. Ussing chamber experiments with or without stressor (P ≥ 0.052), and relative expression of intestinal barrier-related genes (P ≥ 0.264) showed no significant differences between healthy elderly and young adults, as confirmed by immunofluorescent stainings. Overall, the functional capacity of the intestinal barrier is maintained in elderly.
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Affiliation(s)
- Ellen Wilms
- Division Gastroenterology-Hepatology, Department of Internal Medicine; NUTRIM School of Nutrition and Translational Research in Metabolism, Maastricht University, Maastricht, The Netherlands. .,Top Institute Food and Nutrition, Wageningen, The Netherlands.
| | - Freddy J Troost
- Division Gastroenterology-Hepatology, Department of Internal Medicine; NUTRIM School of Nutrition and Translational Research in Metabolism, Maastricht University, Maastricht, The Netherlands.,Food Innovation and Health Research, Centre for Healthy Eating and Food Innovation, Maastricht University, Venlo, The Netherlands
| | - Montserrat Elizalde
- Division Gastroenterology-Hepatology, Department of Internal Medicine; NUTRIM School of Nutrition and Translational Research in Metabolism, Maastricht University, Maastricht, The Netherlands
| | - Bjorn Winkens
- Department of Methodology and Statistics; CAPHRI, Care and Public Health Research Institute, Maastricht University Medical Center, Maastricht, The Netherlands
| | - Paul de Vos
- Top Institute Food and Nutrition, Wageningen, The Netherlands.,Department of Pathology and Medical Biology, section Immunoendocrinology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands
| | - Zlatan Mujagic
- Division Gastroenterology-Hepatology, Department of Internal Medicine; NUTRIM School of Nutrition and Translational Research in Metabolism, Maastricht University, Maastricht, The Netherlands
| | - Daisy M A E Jonkers
- Division Gastroenterology-Hepatology, Department of Internal Medicine; NUTRIM School of Nutrition and Translational Research in Metabolism, Maastricht University, Maastricht, The Netherlands
| | - Ad A M Masclee
- Division Gastroenterology-Hepatology, Department of Internal Medicine; NUTRIM School of Nutrition and Translational Research in Metabolism, Maastricht University, Maastricht, The Netherlands
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Potential Determinants of Gastrointestinal Dysfunction in Autism Spectrum Disorders. REVIEW JOURNAL OF AUTISM AND DEVELOPMENTAL DISORDERS 2019. [DOI: 10.1007/s40489-019-00187-6] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/01/2023]
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Leech B, McIntyre E, Steel A, Sibbritt D. Risk factors associated with intestinal permeability in an adult population: A systematic review. Int J Clin Pract 2019; 73:e13385. [PMID: 31243854 DOI: 10.1111/ijcp.13385] [Citation(s) in RCA: 39] [Impact Index Per Article: 6.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/20/2019] [Revised: 06/04/2019] [Accepted: 06/16/2019] [Indexed: 12/12/2022] Open
Abstract
BACKGROUND Increased intestinal permeability (IP) involves the loss of integrity between the cells of the small intestine. IP has been suggested to contribute to the pathogenesis and exacerbation of many chronic diseases. Many potential risk factors for IP are proposed in contemporary literature. The purpose of this review is to identify the most significant risk factors for IP. METHODS A systematic search of literature published up until September 2018 in the PubMed, EMBASE, CINAHL, and Scopus databases was conducted. RESULTS A total of 47 articles met the inclusion criteria. Elevated levels of proinflammatory markers, dyslipidaemia, hyperglycaemia, insulin resistance, anthropometric measurements resembling obesity, advanced disease severity, comorbidity and the consumption of a Western-style diet were identified as the strongest risk factors for altered intestinal integrity. The risk of IP increases when coupled with a multiple disease state or combined with other environmental risk factors. Furthermore, many of the identified risk factors such as anthropometric measurements and biomarkers were external from intestinal health and rather resembled a metabolic-like condition. CONCLUSIONS This review identified a number of potential risk factors for IP, ranging from biomarkers to anthropometric measurements, demographics, dietary intake and chronic diseases. These risk factors warrant the attention of clinicians and other healthcare providers to aid the identification of potential patients at risk of altered IP. Further research needs to examine whether the identified risk factors are homogeneous with the diagnosis of IP or whether the disease state influences the association.
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Affiliation(s)
- Bradley Leech
- Faculty of Health, Australian Research Centre in Complementary and Integrative Medicine, University of Technology Sydney, Ultimo, New South Wales, Australia
| | - Erica McIntyre
- Faculty of Health, Australian Research Centre in Complementary and Integrative Medicine, University of Technology Sydney, Ultimo, New South Wales, Australia
| | - Amie Steel
- Faculty of Health, Australian Research Centre in Complementary and Integrative Medicine, University of Technology Sydney, Ultimo, New South Wales, Australia
| | - David Sibbritt
- Faculty of Health, Australian Research Centre in Complementary and Integrative Medicine, University of Technology Sydney, Ultimo, New South Wales, Australia
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Galazzo G, Tedjo DI, Wintjens DSJ, Savelkoul PHM, Masclee AAM, Bodelier AGL, Pierik MJ, Jonkers DMAE, Penders J. Faecal Microbiota Dynamics and their Relation to Disease Course in Crohn's Disease. J Crohns Colitis 2019; 13:1273-1282. [PMID: 30810207 PMCID: PMC6764104 DOI: 10.1093/ecco-jcc/jjz049] [Citation(s) in RCA: 39] [Impact Index Per Article: 6.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
Abstract
BACKGROUND Microbial shifts have been associated with disease activity in Crohn's disease [CD], but findings on specific taxa are inconsistent. This may be due to differences in applied methods and cross-sectional study designs. We prospectively examined the faecal microbiota in adult CD patients with changing or stable disease course over time. METHODS Faeces were collected at two time-points from 15 healthy control individuals [HCs], 35 CD patients who were in remission and who maintained remission [RRs], and 22 CD patients during remission and also during subsequent exacerbation [RAs]. The microbial composition was assessed by 16S rRNA [V4] gene sequencing. RESULTS Compared with HCs, patients with CD had a lower microbial richness [p = 0.0002] and diversity [p = 0.005]. Moreover, the microbial community structure of a subset of patients, clustered apart from HCs, was characterized by low microbial diversity and Faecalibacterium abundance. Patients within this cluster did not differ with respect to long-term disease course compared with patients with a 'healthy-appearing' microbiota.Over time, microbial richness and diversity did not change in RR versus RA patients. Although the microbial community structure of both RR and RA patients was less stable over time compared with that of HCs, no differences were observed between the patient groups [p = 0.17]; nor was the stability impacted by Montreal classification, medication use, or surgery. CONCLUSION The altered microbiota composition and stability in CD was neither associated with disease activity nor long-term disease course, questioning its involvement in the development of an exacerbation. The aberrant microbiota composition in a subset of CD patients warrants further exploration of a more microbiota-driven etiology in this group.
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Affiliation(s)
- Gianluca Galazzo
- School of Nutrition and Translational Research in Metabolism [NUTRIM], Department of Medical Microbiology, Maastricht University Medical Center+, Maastricht, The Netherlands,School of Public Health and Primary Care [Caphri], Department of Medical Microbiology, Maastricht University Medical Center+, Maastricht, The Netherlands
| | - Danyta I Tedjo
- School of Nutrition and Translational Research in Metabolism [NUTRIM], Department of Medical Microbiology, Maastricht University Medical Center+, Maastricht, The Netherlands,School of Nutrition and Translational Research in Metabolism [NUTRIM], Division Gastroenterology–Hepatology, Maastricht University Medical Center+, Maastricht, The Netherlands
| | - Dion S J Wintjens
- School of Nutrition and Translational Research in Metabolism [NUTRIM], Division Gastroenterology–Hepatology, Maastricht University Medical Center+, Maastricht, The Netherlands,Department of Internal Medicine, Division of Gastroenterology and Hepatology, Maastricht University Medical Centre+, Maastricht, The Netherlands
| | - Paul H M Savelkoul
- School of Nutrition and Translational Research in Metabolism [NUTRIM], Department of Medical Microbiology, Maastricht University Medical Center+, Maastricht, The Netherlands,School of Public Health and Primary Care [Caphri], Department of Medical Microbiology, Maastricht University Medical Center+, Maastricht, The Netherlands,Department of Medical Microbiology & Infection control, Amsterdam UMC, Vrije Universiteit, Amsterdam, The Netherlands
| | - Ad A M Masclee
- School of Nutrition and Translational Research in Metabolism [NUTRIM], Division Gastroenterology–Hepatology, Maastricht University Medical Center+, Maastricht, The Netherlands,Department of Internal Medicine, Division of Gastroenterology and Hepatology, Maastricht University Medical Centre+, Maastricht, The Netherlands
| | | | - Marie J Pierik
- School of Nutrition and Translational Research in Metabolism [NUTRIM], Division Gastroenterology–Hepatology, Maastricht University Medical Center+, Maastricht, The Netherlands,Department of Internal Medicine, Division of Gastroenterology and Hepatology, Maastricht University Medical Centre+, Maastricht, The Netherlands
| | - Daisy M A E Jonkers
- School of Nutrition and Translational Research in Metabolism [NUTRIM], Division Gastroenterology–Hepatology, Maastricht University Medical Center+, Maastricht, The Netherlands,Department of Internal Medicine, Division of Gastroenterology and Hepatology, Maastricht University Medical Centre+, Maastricht, The Netherlands
| | - John Penders
- School of Nutrition and Translational Research in Metabolism [NUTRIM], Department of Medical Microbiology, Maastricht University Medical Center+, Maastricht, The Netherlands,School of Public Health and Primary Care [Caphri], Department of Medical Microbiology, Maastricht University Medical Center+, Maastricht, The Netherlands,Corresponding authors: J. Penders, Department of Medical Microbiology, Maastricht University Medical Center+, PO 5800, 6202 AZ, Maastricht, The Netherlands. Tel: +31-(0)433875134; Fax: +31-(0)433676643;
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Camilleri M, Lyle BJ, Madsen KL, Sonnenburg J, Verbeke K, Wu GD. Role for diet in normal gut barrier function: developing guidance within the framework of food-labeling regulations. Am J Physiol Gastrointest Liver Physiol 2019; 317:G17-G39. [PMID: 31125257 PMCID: PMC6689735 DOI: 10.1152/ajpgi.00063.2019] [Citation(s) in RCA: 59] [Impact Index Per Article: 9.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
A reduction in intestinal barrier function is currently believed to play an important role in pathogenesis of many diseases, as it facilitates passage of injurious factors such as lipopolysaccharide, peptidoglycan, whole bacteria, and other toxins to traverse the barrier to damage the intestine or enter the portal circulation. Currently available evidence in animal models and in vitro systems has shown that certain dietary interventions can be used to reinforce the intestinal barrier to prevent the development of disease. The relevance of these studies to human health is unknown. Herein, we define the components of the intestinal barrier, review available modalities to assess its structure and function in humans, and review the available evidence in model systems or perturbations in humans that diet can be used to fortify intestinal barrier function. Acknowledging the technical challenges and the present gaps in knowledge, we provide a conceptual framework by which evidence could be developed to support the notion that diet can reinforce human intestinal barrier function to restore normal function and potentially reduce the risk for disease. Such evidence would provide information on the development of healthier diets and serve to provide a framework by which federal agencies such as the US Food and Drug Administration can evaluate evidence linking diet with normal human structure/function claims focused on reducing risk of disease in the general public.
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Affiliation(s)
- Michael Camilleri
- 1Clinical Enteric Neuroscience Translational and Epidemiological Research, Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota
| | - Barbara J. Lyle
- 2International Life Sciences Institute North America, Washington, DC,3School of Professional Studies, Northwestern University, Evanston, Illinois
| | - Karen L. Madsen
- 4Department of Medicine, University of Alberta, Edmonton, Alberta, Canada
| | - Justin Sonnenburg
- 5Department of Microbiology and Immunology, Stanford University School of Medicine, Stanford, California
| | - Kristin Verbeke
- 6Translational Research in Gastrointestinal Disorders, Katholieke Universiteit Leuven, Leuven, Belgium
| | - Gary D. Wu
- 7Division of Gastroenterology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania
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Mohajeri MH, Brummer RJM, Rastall RA, Weersma RK, Harmsen HJM, Faas M, Eggersdorfer M. The role of the microbiome for human health: from basic science to clinical applications. Eur J Nutr 2019; 57:1-14. [PMID: 29748817 PMCID: PMC5962619 DOI: 10.1007/s00394-018-1703-4] [Citation(s) in RCA: 260] [Impact Index Per Article: 43.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
The 2017 annual symposium organized by the University Medical Center Groningen in The Netherlands focused on the role of the gut microbiome in human health and disease. Experts from academia and industry examined interactions of prebiotics, probiotics, or vitamins with the gut microbiome in health and disease, the development of the microbiome in early-life and the role of the microbiome on the gut–brain axis. The gut microbiota changes dramatically during pregnancy and intrinsic factors (such as stress), in addition to extrinsic factors (such as diet, and drugs) influence the composition and activity of the gut microbiome throughout life. Microbial metabolites, e.g. short-chain fatty acids affect gut–brain signaling and the immune response. The gut microbiota has a regulatory role on anxiety, mood, cognition and pain which is exerted via the gut–brain axis. Ingestion of prebiotics or probiotics has been used to treat a range of conditions including constipation, allergic reactions and infections in infancy, and IBS. Fecal microbiota transplantation (FMT) highly effective for treating recurrent Clostridium difficile infections. The gut microbiome affects virtually all aspects of human health, but the degree of scientific evidence, the models and technologies and the understanding of mechanisms of action vary considerably from one benefit area to the other. For a clinical practice to be broadly accepted, the mode of action, the therapeutic window, and potential side effects need to thoroughly be investigated. This calls for further coordinated state-of-the art research to better understand and document the human gut microbiome’s effects on human health.
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Affiliation(s)
- M Hasan Mohajeri
- DSM Nutritional Products Ltd, Kaiseraugst, Switzerland.
- University of Zurich, Irchel, Zurich, Switzerland.
| | | | - Robert A Rastall
- Department of Food and Nutritional Sciences, University of Reading, Reading, UK
| | - Rinse K Weersma
- Department of Gastroenterology and Hepatology, University of Groningen and University Medical Center Groningen, Groningen, The Netherlands
| | - Hermie J M Harmsen
- Department of Medical Microbiology, University Medical Center Groningen, Groningen, The Netherlands
| | - Marijke Faas
- Department of Pathology and Medical Biology, University Medical Center Groningen, Groningen, The Netherlands
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Intestinal Permeability Measured by Urinary Sucrose Excretion Correlates with Serum Zonulin and Faecal Calprotectin Concentrations in UC Patients in Remission. J Nutr Metab 2019; 2019:2472754. [PMID: 31061734 PMCID: PMC6466955 DOI: 10.1155/2019/2472754] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/05/2018] [Revised: 01/25/2019] [Accepted: 02/14/2019] [Indexed: 12/18/2022] Open
Abstract
Background and Aims Ulcerative colitis (UC) is associated with an increased intestinal permeability, possibly through a dysbiosis of intestinal bacteria. We investigated which markers are most relevant to assess intestinal permeability in UC patients and whether probiotics had an effect on these markers. Methods In this twelve-week placebo-controlled randomized double-blind study, twenty-five subjects with UC in remission received either placebo or a multispecies probiotics. Samples of blood, urine, and faeces were taken at baseline, week 6, and week 12 to assess intestinal permeability and inflammation. Diaries and Bristol stool scale were kept to record stool frequency and consistency. Quality of life was scored from 32–224 with the inflammatory bowel disease questionnaire (IBD-Q). Results This group of UC patients, in clinical remission, did not show increased intestinal permeability at baseline of this study. During the study, no significant group or time effects were found for intestinal permeability measured by the 5-sugar absorption test, serum zonulin, and faecal zonulin. Likewise, the inflammatory markers C-reactive protein (CRP), calprotectin, and the cytokines IFNγ, TNFα, IL-6, and IL-10 were not significantly affected. Stool frequency and consistency were not significantly affected either. The IBD-Q score, 194 for the probiotics group and 195 for the placebo group, remained unaffected. Correlations were tested between all outcomes; urinary sucrose excretion was significantly correlated with serum zonulin (r = 0.62) and faecal calprotectin (r = 0.55). Faecal zonulin was not significantly correlated with any of the other markers. Conclusion Serum zonulin may be a more relevant biomarker of intestinal permeability than faecal zonulin, due to its correlation with other biomarkers of intestinal permeability. UC patients in remission did not show an effect of the probiotic treatment or a change in gut permeability. This should not discourage further studies because effects might be present during active disease or shortly after a flare up.
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Gajula P, Quigley EM. Overlapping irritable bowel syndrome and inflammatory bowel disease. MINERVA GASTROENTERO 2019; 65:107-115. [PMID: 30746927 DOI: 10.23736/s1121-421x.19.02559-5] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
The pathogenesis of irritable bowel-type symptoms occurring in patients with inflammatory bowel disease who are in apparent remission continues to generate scientific controversy and the interpretation and management of these symptoms, so distressing to the sufferer, represent major challenges for the clinician. On the one hand, these symptoms often satisfy Rome IV criteria for IBS and their occurrence correlates highly with anxiety, a known trigger for IBS. On the other hand, recent studies have shown that many of these patients exhibit subtle inflammatory changes. These observations beg the question: are these symptoms "true" IBS superimposed on IBD, or an active but subclinical form of IBD? While it is certain that earlier studies failed to detect subclinical inflammation, it is also evident that even with the use of sensitive biomarkers for inflammation, such as calprotectin and lactoferrin backed up by pan-endoscopy and biopsy to exclude ongoing inflammatory activity in its most subtle form, the prevalence of IBS-type symptoms remains higher than expected in the IBD patient. Pending further definition of its etiology and pathology, we coined the term irritable inflammatory bowel syndrome (IIBS) to refer to this phenomenon. Here we explore the risk factors for this entity, sift through clues to its pathogenesis and attempt to provide, albeit bereft of a robust evidence base, an approach to its management.
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Affiliation(s)
- Prianka Gajula
- Department of Medicine, Houston Methodist Hospital and Weill Cornell Medical College, Houston, TX, USA
| | - Eamonn M Quigley
- Division of Gastroenterology and Hepatology, Lynda K. and David M. Underwood Center for Digestive Disorders, Houston Methodist Hospital and Weill Cornell Medical College, Houston, TX, USA -
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