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1
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Gildner TE, Urlacher SS, Nemeth KL, Beauregard JA, Pfaff Nash M, Zhang A, Waimon S, Cepon-Robins TJ. Dual burden of infectious and chronic disease in low-resource U.S. communities: examining relationships between infection, adiposity, and inflammation. Ann Hum Biol 2024; 51:2368851. [PMID: 38934696 DOI: 10.1080/03014460.2024.2368851] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/14/2023] [Accepted: 06/03/2024] [Indexed: 06/28/2024]
Abstract
BACKGROUND Rising global obesity rates are linked with inflammation and associated morbidities. These negative outcomes are generally more common in low-resource communities within high-income countries; however, it is unclear how frequent infectious disease exposures in these settings may influence the relationship between adiposity and inflammation. AIM We test associations between adiposity measures and distinct forms of inflammation among adults (n = 80) living in low-resource U.S. communities experiencing high levels of obesity and pathogen exposure. SUBJECTS AND METHODS Adiposity measures included BMI and percent body fat. Inflammation measures included systemic inflammation (C-reactive protein [CRP]) and localised intestinal inflammation (faecal calprotectin [FC]). The relationship between a condition characterised by elevated inflammation (Helicobacter pylori infection) and adiposity was also considered. RESULTS Adiposity was not significantly related to FC concentration. However, both adiposity measures were positively related with odds of CRP elevation and H. pylori infection was associated with significantly lower adiposity measures (all p < 0.05). CONCLUSION For this disadvantaged U.S. sample, the association between adiposity and inflammation varies by the systemic/localised nature of inflammation and the likely underlying cause of inflammation. Defining these associations will improve understanding of how rising obesity rates shape long-term health inequities, with implications for more effective intervention design.
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Affiliation(s)
- Theresa E Gildner
- Department of Anthropology, Washington University in St. Louis, St. Louis, MO, USA
| | - Samuel S Urlacher
- Department of Anthropology, Baylor University, Waco, TX, USA
- Child and Brain Development Program, CIFAR, Toronto, Canada
| | - Katherine L Nemeth
- Department of Anthropology, Washington University in St. Louis, St. Louis, MO, USA
| | - Jade A Beauregard
- Department of Anthropology, Washington University in St. Louis, St. Louis, MO, USA
| | | | - Angela Zhang
- Department of Anthropology, Washington University in St. Louis, St. Louis, MO, USA
| | - Sophie Waimon
- Department of Anthropology, Washington University in St. Louis, St. Louis, MO, USA
| | - Tara J Cepon-Robins
- Department of Anthropology, University of Colorado Colorado Springs, Colorado Springs, CO, USA
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2
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Tung KK, Chen ST, Lee CH, Tung CF, Wei JCC. Calprotectin in spondyloarthritis and gut inflammation, is it clinically meaningful? Int J Rheum Dis 2023; 26:609-612. [PMID: 37002903 DOI: 10.1111/1756-185x.14619] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/12/2022] [Revised: 01/18/2023] [Accepted: 02/06/2023] [Indexed: 04/04/2023]
Affiliation(s)
- Kuan-Kai Tung
- Department of Orthopedics, Taichung Veterans General Hospital, Taichung, Taiwan
| | - Shih-Tien Chen
- Department of Gastroenterology and Hepatology, Chia-Yi Hospital, Ministry of Health and Welfare, Chiayi, Taiwan
| | - Cheng-Hung Lee
- Department of Orthopedics, Taichung Veterans General Hospital, Taichung, Taiwan
- Post Baccalaureate Medicine, School of Medicine, National Chung Hsing University, Taichung, Taiwan
- Department of Food Science and Technology, Hung Kuang University, Taichung, Taiwan
| | - Chun-Fang Tung
- Division of Gastroenterology, Department of Internal Medicine, Taichung Veterans General Hospital, Taichung, Taiwan
- School of Medicine, National Yang-Ming Chao-Tung University, Taipei, Taiwan
| | - James Cheng-Chung Wei
- Department of Allergy, Immunology & Rheumatology, Chung Shan Medical University Hospital, Taichung, Taiwan
- Institute of Medicine, College of Medicine, Chung Shan Medical University, Taichung, Taiwan
- Graduate Institute of Integrated Medicine, China Medical University, Taichung, Taiwan
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3
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Campos JF, Resende GG, Ferrari MDLA. Answer to "comment on fecal calprotectin as a biomarker of microscopic bowel inflammation in patients with spondyloarthritis". Int J Rheum Dis 2023; 26:175-176. [PMID: 36239090 DOI: 10.1111/1756-185x.14458] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/25/2022] [Accepted: 09/28/2022] [Indexed: 01/04/2023]
Affiliation(s)
- Júlia Faria Campos
- Instituto Alfa de Gastroenterologia, Hospital das Clínicas, Universidade Federal, de Minas Gerais, Belo Horizonte, Brazil
| | - Gustavo Gomes Resende
- Departamento de Reumatologia, Hospital das Clínicas, Universidade Federal de, Minas Gerais, Belo Horizonte, Brazil
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Pai A, Lee YH, Ko MY, Chen PK. Comment on fecal calprotectin as a biomarker of microscopic bowel inflammation in patients with spondyloarthritis. Int J Rheum Dis 2023; 26:172-174. [PMID: 36239091 DOI: 10.1111/1756-185x.14460] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/08/2022] [Revised: 08/09/2022] [Accepted: 08/10/2022] [Indexed: 01/04/2023]
Affiliation(s)
- Allen Pai
- New Drug, New Medical Device, New Medical Technology Clinical Trial Management Center, Chung Shan Medical University Hospital, Taichung, Taiwan.,Department of Public Health, National Taiwan University, Taipei, Taiwan
| | - Yung-Heng Lee
- Department of Senior Services Industry Management, Minghsin University of Science and Technology, Hsinchu, Taiwan.,Department of Recreation and Sport Management, Shu-Te University, Kaohsiung, Taiwan.,Department of Orthopedics, Cishan Hospital, Ministry of Health and Welfare, Kaohsiung, Taiwan
| | - Meng-Yu Ko
- Division of Gastroenterology and Hepatology, Changhua Christian Hospital, Changhua, Taiwan.,Institute of Medicine, Chung Shan Medical University, Taichung, Taiwan
| | - Po-Ku Chen
- Chung Shan Medical University Hospital, Chung Shan Medical University, Taichung, Taiwan.,Department of Integrated Chinese and Western Medicine, Chung Shan Medical University Hospital, Taichung, Taiwan
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Jendraszak M, Gałęcka M, Kotwicka M, Schwiertz A, Regdos A, Pazgrat-Patan M, Andrusiewicz M. Impact of Biometric Patient Data, Probiotic Supplementation, and Selected Gut Microorganisms on Calprotectin, Zonulin, and sIgA Concentrations in the Stool of Adults Aged 18-74 Years. Biomolecules 2022; 12:biom12121781. [PMID: 36551209 PMCID: PMC9775524 DOI: 10.3390/biom12121781] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/02/2022] [Revised: 11/25/2022] [Accepted: 11/28/2022] [Indexed: 12/02/2022] Open
Abstract
Alterations to the intestinal barrier may be involved in the pathogenesis of various chronic diseases. The diagnosis of mucosal barrier disruption has become a new therapeutic target for disease prevention. The aim of this study was to determine whether various patient demographic and biometric data, often not included in diagnostic analyses, may affect calprotectin, zonulin, and sIgA biomarker values. Stool markers' levels in 160 samples were measured colorimetrically. The analysis of twenty key bacteria (15 genera and 5 species) was carried out on the basis of diagnostic tests, including cultures and molecular tests. The concentrations of selected markers were within reference ranges for most patients. The sIgA level was significantly lower in participants declaring probiotics supplementation (p = 0.0464). We did not observe differences in gastrointestinal discomfort in participants. We found significant differences in the sIgA level between the 29-55 years and >55 years age-related intervals groups (p = 0.0191), together with a significant decreasing trend (p = 0.0337) in age-dependent sIgA concentration. We observed complex interdependencies and relationships between their microbiota and the analyzed biomarkers. For correct clinical application, standardized values of calprotectin and sIgA should be determined, especially in elderly patients. We observed a correlation between the composition of the gut community and biomarker levels, although it requires further in-depth analysis.
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Affiliation(s)
- Magdalena Jendraszak
- Chair and Department of Cell Biology, Poznan University of Medical Sciences, Rokietnicka 5D, 60-806 Poznań, Poland
- Correspondence: (M.J.); (M.A.)
| | | | - Małgorzata Kotwicka
- Chair and Department of Cell Biology, Poznan University of Medical Sciences, Rokietnicka 5D, 60-806 Poznań, Poland
| | | | | | | | - Mirosław Andrusiewicz
- Chair and Department of Cell Biology, Poznan University of Medical Sciences, Rokietnicka 5D, 60-806 Poznań, Poland
- Correspondence: (M.J.); (M.A.)
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Koutoukidis DA, Jebb SA, Zimmerman M, Otunla A, Henry JA, Ferrey A, Schofield E, Kinton J, Aveyard P, Marchesi JR. The association of weight loss with changes in the gut microbiota diversity, composition, and intestinal permeability: a systematic review and meta-analysis. Gut Microbes 2022; 14:2020068. [PMID: 35040746 PMCID: PMC8796717 DOI: 10.1080/19490976.2021.2020068] [Citation(s) in RCA: 66] [Impact Index Per Article: 22.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/07/2023] Open
Abstract
The gut microbiome may be a mediator between obesity and health outcomes. However, it is unclear how intentional weight loss changes the gut microbiota and intestinal permeability. We aimed to systematically review and quantify this association. We searched Medline, Embase, CINAHL, Cochrane databases, and trial registries until June 2020 (PROSPERO: CRD42020205292). We included trials of weight loss interventions (energy-restricted diets, pharmacotherapy, bariatric surgery) reporting on the microbiome. Two reviewers independently completed screening, extraction, and risk assessment with the ROBINS-I tool. Pooled standardized mean differences (SMDs) were obtained from random-effects meta-analyses. Forty-seven trials with 1,916 participants (81% female) and a median follow-up of 6 months (range: 2-24) were included. Based on imprecise evidence but with fairly consistent direction of effect, weight loss was associated with a statistically significant increase in α-diversity [SMD: 0.4 (95% CI: 0.2, 0.6], p < .0001, I2 = 70%, n = 30 studies) and a statistically significant reduction in intestinal permeability [SMD: -0.7 (95% CI: -0.9, -0.4), p < .0001, I2 = 83%, n = 17 studies]. Each kg of weight loss was associated with a 0.012 (95% CI: 0.0003, 0.024, p = .045) increase in α-diversity and a -0.017 (95% CI: -0.034, -0.001, p = .038) reduction in intestinal permeability. There was clear evidence of increases in the relative abundance of Akkermansia, but no clear evidence of changes in individual phyla, species, or fecal short-chain fatty acids. Restricting the analyses to the studies with lower risk of bias did not materially alter the estimates. Increasing weight loss is positively associated with increases in gut microbiota α-diversity and reductions in intestinal permeability.
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Affiliation(s)
- Dimitrios A Koutoukidis
- Nuffield Department of Primary Care Health Sciences, University of Oxford, Oxford, UK,NIHR Oxford Biomedical Research Centre, Oxford University Hospitals NHS Foundation Trust, Oxford, UK,CONTACT Dimitrios A Koutoukidis University of OxfordOxfordUnited Kingdom
| | - Susan A Jebb
- Nuffield Department of Primary Care Health Sciences, University of Oxford, Oxford, UK,NIHR Oxford Biomedical Research Centre, Oxford University Hospitals NHS Foundation Trust, Oxford, UK
| | - Matthew Zimmerman
- Nuffield Department of Primary Care Health Sciences, University of Oxford, Oxford, UK
| | - Afolarin Otunla
- Nuffield Department of Primary Care Health Sciences, University of Oxford, Oxford, UK
| | - J. Aaron Henry
- Nuffield Department of Primary Care Health Sciences, University of Oxford, Oxford, UK
| | - Anne Ferrey
- Nuffield Department of Primary Care Health Sciences, University of Oxford, Oxford, UK
| | - Ella Schofield
- Nuffield Department of Primary Care Health Sciences, University of Oxford, Oxford, UK
| | - Jade Kinton
- Nuffield Department of Primary Care Health Sciences, University of Oxford, Oxford, UK
| | - Paul Aveyard
- Nuffield Department of Primary Care Health Sciences, University of Oxford, Oxford, UK,NIHR Oxford Biomedical Research Centre, Oxford University Hospitals NHS Foundation Trust, Oxford, UK
| | - Julian R. Marchesi
- Department of Metabolism, Digestion and Reproduction, Imperial College London, London, UK
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D'Amico F, Rubin DT, Kotze PG, Magro F, Siegmund B, Kobayashi T, Olivera PA, Bossuyt P, Pouillon L, Louis E, Domènech E, Ghosh S, Danese S, Peyrin‐Biroulet L. International consensus on methodological issues in standardization of fecal calprotectin measurement in inflammatory bowel diseases. United European Gastroenterol J 2021; 9:451-460. [PMID: 33961734 PMCID: PMC8259254 DOI: 10.1002/ueg2.12069] [Citation(s) in RCA: 51] [Impact Index Per Article: 12.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/18/2021] [Accepted: 02/26/2021] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Fecal calprotectin (FC) is a non-invasive marker of gut inflammation which is frequently used to guide therapeutic decisions in patients with inflammatory bowel diseases (IBD). Each step of FC measurement can influence the results, leading to misinterpretations and potentially impacting the management of IBD patients. To date, there is high heterogeneity between FC measurements and no current method is universally accepted as a standard. AIMS Our aim was to provide clear position statementsabout the pre-analytical and the analytical phases of FC measurement to homogenize FC levels and to minimize variability and risk of misinterpretation through aninternational consensus. MATERIALS & METHODS Fourteen physicians with expertise in the field of IBD and FC from 11 countries attended a virtual international consensus meeting on July 17th, 2020. A systematic literature was conducted and the literature evidence was shared and discussedamong the participants. Statements were formulated, discussed, and voted. Statements were considered approved if all participants agreed. RESULTS Nine statements were formulated and approved. Based on the available evidence, quantitative tests should be preferred for measuring FC. Furthermore, FC measurement, if possible, should always be performed with the same method and factors influencing FC levels should be taken into account when interpreting the results. DISCUSSION FC has an increasingly important role in the management of patients with IBD. However, large multicenter studies should be conducted to define the reproducibility and to confirm the diagnostic accuracy of the available FC tests. CONCLUSION FC concentrations guide clinicians' treatment decisions. Our statements have a relevant impact in daily practice and could be applied in clinical trials to standardize FC measurement.
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Affiliation(s)
- Ferdinando D'Amico
- Department of Biomedical SciencesHumanitas UniversityMilanItaly
- Department of Gastroenterology and Inserm U1256Nutrition – Genetics and Exposure to Environmental RisksUniversity Hospital of NancyUniversity of LorraineVandoeuvre‐lès‐NancyFrance
| | - David T. Rubin
- Section of Gastroenterology, Hepatology and NutritionUniversity of Chicago Department of MedicineChicagoIllinoisUSA
| | | | - Fernando Magro
- Department of GastroenterologyCentro Hospitalar São JoãoPortoPortugal
| | - Britta Siegmund
- Medizinische Klinik m. S. Gastroenterologie, Infektiologie und RheumatologieCharité ‐ Universitätsmedizin BerlinCorporate Member of Freie Universität BerlinHumboldt‐Universität zu Berlinand Berlin Institute of HealthBerlinGermany
| | - Taku Kobayashi
- Center for Advanced IBD Research and TreatmentKitasato University Kitasato Institute HospitalTokyoJapan
| | - Pablo A. Olivera
- Gastroenterology SectionDepartment of Internal MedicineCentro de Educación Médica e Investigaciones Clínicas (CEMIC)Buenos AiresArgentina
| | - Peter Bossuyt
- Imelda GI Clinical Research CenterImelda General HospitalBonheidenBelgium
| | - Lieven Pouillon
- Imelda GI Clinical Research CenterImelda General HospitalBonheidenBelgium
| | - Edouard Louis
- Department of GastroenterologyCHU Liège University HospitalLiègeBelgium
| | - Eugeni Domènech
- Gastroenterology DepartmentHospital Universitari Germans Trias i PujolBadalonaCataloniaSpain
- Departament de MedicinaUniversitat Autònoma de BarcelonaBarcelonaSpain
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD)MadridSpain
| | - Subrata Ghosh
- NIHR Biomedical Research CentreUniversity of Birmingham and University Hospitals NHS Foundation TrustBirminghamUK
| | - Silvio Danese
- Department of Biomedical SciencesHumanitas UniversityMilanItaly
- IBD CenterHumanitas Research HospitalIRCCSMilanItaly
| | - Laurent Peyrin‐Biroulet
- Department of Gastroenterology and Inserm U1256Nutrition – Genetics and Exposure to Environmental RisksUniversity Hospital of NancyUniversity of LorraineVandoeuvre‐lès‐NancyFrance
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Westerink F, Huibregtse I, De Hoog M, Bruin S, Meesters E, Brandjes D, Gerdes V. Faecal Inflammatory Biomarkers and Gastrointestinal Symptoms after Bariatric Surgery: A Longitudinal Study. Inflamm Intest Dis 2021; 6:109-116. [PMID: 34124182 DOI: 10.1159/000514576] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/19/2020] [Accepted: 12/29/2020] [Indexed: 11/19/2022] Open
Abstract
Background Bariatric surgery induces various gastrointestinal (GI) modifications. We performed the first study longitudinally assessing the effect of bariatric surgery on faecal inflammatory biomarker levels and its relation with GI complaints. Method Faecal calprotectin, lactoferrin, and calgranulin-C levels were determined in 41 patients (34 Roux-en-Y [RYGB], 7 sleeves) before and at 6-16 weeks, 6 months, and 1 year after surgery. Changes in biomarker levels and percentage of patients above reference value were determined. Gastrointestinal symptom rating scale (GSRS) was used to assess GI complaints at corresponding time points. The postoperative relation between GSRS score and biomarker levels above reference value was investigated. Results After RYGB, median calprotectin levels are significantly higher (>188, 104-415 μg/g) than before surgery (40, 19-78 μg/g; p < 0.001), and over 90% of patients have levels above reference value 1 year after surgery. Median lactoferrin was 0.4 (0.2-1.6) μg/g before, and >5.9 (1.8-13.6) μg/g after surgery (p < 0.001). Median calgranulin-C levels remained far below the reference value and were 0.13 (0.05-0.24) μg/g before and <0.23 (0.06-0.33) μg/g after surgery. Similar results were found after sleeve gastrectomy. No difference was seen in GSRS score for patients with calprotectin and lactoferrin levels above reference values. Conclusion Faecal inflammatory biomarkers calprotectin and lactoferrin, but not calgranulin-C, rise above reference values shortly after bariatric surgery and remain elevated in the majority of patients. The discrepancy between calprotectin and calgranulin-C levels suggests no GI inflammation. Furthermore, patients after RYGB with biomarkers above the population reference value do not seem to have more GI complaints.
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Affiliation(s)
- Floris Westerink
- Department of internal medicine, Amsterdam University Medical Centre, Amsterdam, The Netherlands
| | - Inge Huibregtse
- Department of gastroenterology, Netherlands Cancer Institute, Antoni van Leeuwenhoek, Amsterdam, The Netherlands
| | | | - Sjoerd Bruin
- Department of surgery, Spaarne Gasthuis, Hoofddorp, The Netherlands
| | - Eelco Meesters
- Department of internal medicine, Spaarne Gasthuis, Hoofddorp, The Netherlands
| | - Desiderius Brandjes
- Department of internal medicine, Amsterdam University Medical Centre, Amsterdam, The Netherlands
| | - Victor Gerdes
- Department of internal medicine, Amsterdam University Medical Centre, Amsterdam, The Netherlands.,Department of internal medicine, Spaarne Gasthuis, Hoofddorp, The Netherlands
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Heilmann RM, Guard MM, Toresson L, Unterer S, Grellet A, Grützner N, Suchodolski JS, Steiner JM. Association of clinical characteristics and lifestyle factors with fecal S100/calgranulin concentrations in healthy dogs. Vet Med Sci 2021; 7:1131-1143. [PMID: 33751838 PMCID: PMC8294382 DOI: 10.1002/vms3.469] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/18/2020] [Revised: 02/10/2021] [Accepted: 02/22/2021] [Indexed: 02/06/2023] Open
Abstract
Background Fecal S100/calgranulin (S100A12 and calprotectin) concentrations are useful markers of gastrointestinal inflammation in dogs. In people, fecal S100/calgranulin concentrations are affected by age, obesity, diet and other lifestyle factors. Knowledge about the effects of such factors on fecal S100/calgranulin concentrations in dogs is currently scarce. Objective To evaluate the association between several factors and fecal S100/calgranulin concentrations in a large cohort of healthy adult dogs. Methods Single‐spot fecal samples from 181 healthy pet dogs and data derived from a standard questionnaire served to evaluate the effect of age, sex, reproductive status, body weight and body condition, breed type and size, vaccination, endoparasite treatment, diet, environment and travel history on fecal S100/calgranulin concentrations and the fecal calgranulin ratio (fCalR). Results Univariate analysis showed a significant association of reproductive status (in female dogs) and breed size with fecal S100A12, fecal calprotectin and fCalR. Breed type was linked to fecal S100A12 concentrations and fCalR; recent vaccination (particularly with a vaccine against canine parvovirus) to fCalR. In multivariate models, breed size was linked to fecal S100A12 and calprotectin concentrations, and recent vaccination affected S100A12 concentrations. Conclusions Breed size, recent vaccination and reproductive status in female dogs can affect fecal S100/calgranulin concentrations, and these biomarkers should be interpreted in light of those confounding factors. The utility of reference intervals for fecal canine S100/calgranulin concentrations might be improved through stratification by sex/reproductive status and breed size. Fecal canine S100/calgranulin concentrations are not confounded by age, body condition, deworming, diet, environment or travel history.
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Affiliation(s)
- Romy M Heilmann
- Department for Small Animals, Veterinary Teaching Hospital, College of Veterinary Medicine, University of Leipzig, Leipzig, Germany.,School of Veterinary Science, Massey University, Palmerston North, New Zealand
| | - Melissa M Guard
- Gastrointestinal Laboratory, College of Veterinary Medicine and Biomedical Sciences, Texas A&M University, College Station, TX, USA
| | - Linda Toresson
- Evidensia Specialist Animal Hospital, Helsingborg, Sweden.,Department of Equine and Small Animal Medicine, Faculty of Veterinary Medicine, Helsinki University, Helsinki, Finland
| | - Stefan Unterer
- Clinic of Small Animal Internal Medicine, Center for Clinical Veterinary Medicine, Ludwig-Maximilians-University, Munich, Germany
| | - Aurélien Grellet
- NeoCare, UMR INRA/ENVT 1225 IHAP, Reproduction, Université de Toulouse, Toulouse, France
| | - Niels Grützner
- School of Veterinary Science, Massey University, Palmerston North, New Zealand.,Clinic for Swine and Small Ruminants, Forensic Medicine and Ambulatory Service, University of Veterinary Medicine Hannover, Hannover, Germany
| | - Jan S Suchodolski
- Gastrointestinal Laboratory, College of Veterinary Medicine and Biomedical Sciences, Texas A&M University, College Station, TX, USA
| | - Joerg M Steiner
- Gastrointestinal Laboratory, College of Veterinary Medicine and Biomedical Sciences, Texas A&M University, College Station, TX, USA
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Kirchgesner J. Paving the way towards a weight-loss intervention study in obese patients with inflammatory bowel disease. United European Gastroenterol J 2020; 8:1143-1144. [PMID: 33045939 DOI: 10.1177/2050640620965113] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/15/2022] Open
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11
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Zhang X, Browman G, Siu W, Basen-Engquist KM, Hanash SM, Hoffman KL, Okhuysen PC, Scheet P, Petrosino JF, Kopetz S, Daniel CR. The BE GONE trial study protocol: a randomized crossover dietary intervention of dry beans targeting the gut microbiome of overweight and obese patients with a history of colorectal polyps or cancer. BMC Cancer 2019; 19:1233. [PMID: 31852462 PMCID: PMC6921460 DOI: 10.1186/s12885-019-6400-z] [Citation(s) in RCA: 15] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/07/2019] [Accepted: 11/22/2019] [Indexed: 12/13/2022] Open
Abstract
BACKGROUND Mouse and human studies support the promise of dry beans to improve metabolic health and to lower cancer risk. In overweight/obese patients with a history of colorectal polyps or cancer, the Beans to Enrich the Gut microbiome vs. Obesity's Negative Effects (BE GONE) trial will test whether and how an increase in the consumption of pre-cooked, canned dry beans within the context of usual diet and lifestyle can enhance the gut landscape to improve metabolic health and reduce cancer risk. METHODS/DESIGN This randomized crossover trial is designed to characterize changes in (1) host markers spanning lipid metabolism, inflammation, and obesity-related cancer risk; (2) compositional and functional profiles of the fecal microbiome; and (3) host and microbial metabolites. With each subject serving as their own control, the trial will compare the participant's usual diet with (intervention) and without (control) dry beans. Canned, pre-cooked dry beans are provided to participants and the usual diet continually assessed and monitored. Following a 4-week run-in and equilibration period, each participant provides a total of 5 fasting blood and 6 stool samples over a total period of 16 weeks. The intervention consists of a 2-week ramp-up of dry bean intake to 1 cup/d, which is then continued for an additional 6 weeks. Intra- and inter-individual outcomes are assessed across each crossover period with consideration of the joint or modifying effects of the usual diet and baseline microbiome. DISCUSSION The BE GONE trial is evaluating a scalable dietary prevention strategy targeting the gut microbiome of high-risk patients to mitigate the metabolic and inflammatory effects of adiposity that influence colorectal cancer risk, recurrence, and survival. The overarching scientific goal is to further elucidate interactions between diet, the gut microbiome, and host metabolism. Improved understanding of the diet-microbiota interplay and effective means to target these relationships will be key to the future of clinical and public health approaches to cancer and other major diet- and obesity-related diseases. TRIAL REGISTRATION This protocol is registered with the U.S. National Institutes of Health trial registry, ClinicalTrials.gov, under the identifier NCT02843425. First posted July 25, 2016; last verified January 25, 2019.
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Affiliation(s)
- Xiaotao Zhang
- Department of Epidemiology, Division of Cancer Prevention and Population Sciences, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd, Unit 1340, Houston, TX, TX 77030, USA
- Department of Medicine, Epidemiology and Population Science, Baylor College of Medicine, Houston, TX, USA
| | - Gladys Browman
- Department of Epidemiology, Division of Cancer Prevention and Population Sciences, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd, Unit 1340, Houston, TX, TX 77030, USA
| | - Wesley Siu
- Department of Epidemiology, Division of Cancer Prevention and Population Sciences, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd, Unit 1340, Houston, TX, TX 77030, USA
- Rollins School of Public Health, Emory University, Atlanta, GA, USA
| | - Karen M Basen-Engquist
- Department of Behavioral Science, Division of Cancer Prevention and Population Sciences, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Samir M Hanash
- Department of Clinical Cancer Prevention, Division of Cancer Prevention and Population Sciences, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Kristi L Hoffman
- Alkek Center for Metagenomics and Microbiome Research, Department of Molecular Virology and Microbiology, Baylor College of Medicine, Houston, TX, USA
| | - Pablo C Okhuysen
- Department of Infectious Diseases, Infection Control, and Employee Health, Division of Internal Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Paul Scheet
- Department of Epidemiology, Division of Cancer Prevention and Population Sciences, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd, Unit 1340, Houston, TX, TX 77030, USA
| | - Joseph F Petrosino
- Alkek Center for Metagenomics and Microbiome Research, Department of Molecular Virology and Microbiology, Baylor College of Medicine, Houston, TX, USA
| | - Scott Kopetz
- Department of Gastrointestinal Medical Oncology, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Carrie R Daniel
- Department of Epidemiology, Division of Cancer Prevention and Population Sciences, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd, Unit 1340, Houston, TX, TX 77030, USA.
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Wilbrink J, Bernards N, Mujagic Z, van Avesaat M, Pijls K, Klaassen T, van Eijk H, Nienhuijs S, Stronkhorst A, Wilms E, Troost F, Masclee A. Intestinal barrier function in morbid obesity: results of a prospective study on the effect of sleeve gastrectomy. Int J Obes (Lond) 2019; 44:368-376. [PMID: 31819200 DOI: 10.1038/s41366-019-0492-z] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/04/2018] [Revised: 10/31/2019] [Accepted: 11/17/2019] [Indexed: 11/09/2022]
Abstract
BACKGROUND Obesity has been associated with impaired intestinal barrier function. It is not known whether bariatric surgery leads to changes in intestinal barrier function. We hypothesized that obesity is associated with disturbances in gastrointestinal barrier function, and that after bariatric surgery barrier function will improve. METHODS Prospective single center study in which we assessed segmental gut permeability by urinary recovery of a multisugar drink in 27 morbidly obese (BMI 43.3 ± 1.1 kg/m2) and 27 age and gender matched lean subjects (BMI 22.9 ± 0.43 kg/m2). Fecal calprotectin, SCFAs, plasma cytokines, and hsCRP were assessed as inflammatory and metabolic markers. Comparisons: (a) morbidly obese subjects vs. controls and (b) 2 and 6 months postsleeve vs. presleeve gastrectomy (n = 14). In another group of 10 morbidly obese and 11 matched lean subjects colonic and ileal biopsies were obtained in order to measure gene transcription of tight junction proteins. RESULTS Gastroduodenal permeability (urinary sucrose recovery) was significantly increased in obese vs. lean controls (p < 0.05). Small intestinal and colonic permeability (urinary recovery of lactulose/L-rhamnose and sucralose/erythritol, respectively) in obese subjects were not significantly different from controls. Morbidly obese subjects had a proinflammatory systemic and intestinal profile compared with lean subjects. After sleeve gastrectomy BMI decreased significantly (p < 0.001). Postsleeve gastroduodenal permeability normalized to values that do not differ from lean controls. CONCLUSIONS Gastroduodenal permeability, but not small intestinal or colonic permeability, is significantly increased in morbidly obese patients. After sleeve gastrectomy, gastroduodenal permeability normalized to values in the range of lean controls. Thus, the proximal gastrointestinal barrier is compromised in morbid obesity and is associated with a proinflammatory intestinal and systemic profile.
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Affiliation(s)
- Jennifer Wilbrink
- Division of Gastroenterology-Hepatology, Maastricht University Medical Center, Maastricht, The Netherlands. .,Department of Gastroenterology-Hepatology, Catharina Hospital, Eindhoven, The Netherlands. .,Department of Gastroenterology-Hepatology, Zuyderland Medical Centre Sittard-Geleen, Sittard-Geleen, The Netherlands. .,NUTRIM School of Nutrition and Translational Research in Metabolism, Maastricht, The Netherlands.
| | - Nienke Bernards
- Department of Gastroenterology-Hepatology, Catharina Hospital, Eindhoven, The Netherlands
| | - Zlatan Mujagic
- Division of Gastroenterology-Hepatology, Maastricht University Medical Center, Maastricht, The Netherlands.,NUTRIM School of Nutrition and Translational Research in Metabolism, Maastricht, The Netherlands
| | - Mark van Avesaat
- Division of Gastroenterology-Hepatology, Maastricht University Medical Center, Maastricht, The Netherlands.,NUTRIM School of Nutrition and Translational Research in Metabolism, Maastricht, The Netherlands
| | - Kirsten Pijls
- Division of Gastroenterology-Hepatology, Maastricht University Medical Center, Maastricht, The Netherlands.,NUTRIM School of Nutrition and Translational Research in Metabolism, Maastricht, The Netherlands
| | - Tim Klaassen
- Division of Gastroenterology-Hepatology, Maastricht University Medical Center, Maastricht, The Netherlands.,NUTRIM School of Nutrition and Translational Research in Metabolism, Maastricht, The Netherlands
| | - Hans van Eijk
- Department of Surgery, Maastricht University Medical Center, Maastricht, The Netherlands
| | - Simon Nienhuijs
- Department of Surgery, Catharina Hospital, Eindhoven, The Netherlands
| | - Arnold Stronkhorst
- Department of Gastroenterology-Hepatology, Catharina Hospital, Eindhoven, The Netherlands
| | - Ellen Wilms
- Division of Gastroenterology-Hepatology, Maastricht University Medical Center, Maastricht, The Netherlands.,NUTRIM School of Nutrition and Translational Research in Metabolism, Maastricht, The Netherlands
| | - Freddy Troost
- Division of Gastroenterology-Hepatology, Maastricht University Medical Center, Maastricht, The Netherlands.,NUTRIM School of Nutrition and Translational Research in Metabolism, Maastricht, The Netherlands
| | - Ad Masclee
- Division of Gastroenterology-Hepatology, Maastricht University Medical Center, Maastricht, The Netherlands.,NUTRIM School of Nutrition and Translational Research in Metabolism, Maastricht, The Netherlands
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Breininger SP, Malcomson FC, Afshar S, Turnbull DM, Greaves L, Mathers JC. Effects of obesity and weight loss on mitochondrial structure and function and implications for colorectal cancer risk. Proc Nutr Soc 2019; 78:426-437. [PMID: 30898183 PMCID: PMC6685789 DOI: 10.1017/s0029665119000533] [Citation(s) in RCA: 21] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/26/2022]
Abstract
Colorectal cancer (CRC) is the third most common cancer globally. CRC risk is increased by obesity, and by its lifestyle determinants notably physical inactivity and poor nutrition. Obesity results in increased inflammation and oxidative stress which cause genomic damage and contribute to mitochondrial dysregulation and CRC risk. The mitochondrial dysfunction associated with obesity includes abnormal mitochondrial size, morphology and reduced autophagy, mitochondrial biogenesis and expression of key mitochondrial regulators. Although there is strong evidence that increased adiposity increases CRC risk, evidence for the effects of intentional weight loss on CRC risk is much more limited. In model systems, energy depletion leads to enhanced mitochondrial integrity, capacity, function and biogenesis but the effects of obesity and weight loss on mitochondria in the human colon are not known. We are using weight loss following bariatric surgery to investigate the effects of altered adiposity on mitochondrial structure and function in human colonocytes. In summary, there is strong and consistent evidence in model systems and more limited evidence in human subjects that over-feeding and/or obesity result in mitochondrial dysfunction and that weight loss might mitigate or reverse some of these effects.
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Affiliation(s)
- S P Breininger
- Human Nutrition Research Centre,Newcastle University,Newcastle upon Tyne NE2 4HH,UK
| | - F C Malcomson
- Human Nutrition Research Centre,Newcastle University,Newcastle upon Tyne NE2 4HH,UK
| | - S Afshar
- Human Nutrition Research Centre,Newcastle University,Newcastle upon Tyne NE2 4HH,UK
| | - D M Turnbull
- Wellcome Trust Centre for Mitochondrial Research, Institute of Neuroscience, Newcastle University,Newcastle upon Tyne NE2 4HH,UK
| | - L Greaves
- Wellcome Trust Centre for Mitochondrial Research, Institute of Neuroscience, Newcastle University,Newcastle upon Tyne NE2 4HH,UK
| | - J C Mathers
- Human Nutrition Research Centre,Newcastle University,Newcastle upon Tyne NE2 4HH,UK
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Jeong SJ. The role of fecal calprotectin in pediatric disease. KOREAN JOURNAL OF PEDIATRICS 2019; 62:287-291. [PMID: 30999729 PMCID: PMC6702112 DOI: 10.3345/kjp.2019.00059] [Citation(s) in RCA: 15] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 01/14/2019] [Accepted: 03/28/2019] [Indexed: 12/13/2022]
Abstract
Fecal calprotectin (FC) is a calcium- and zinc-binding protein of the S100 family, mainly expressed by neutrophils and released during inflammation. FC became an increasingly useful tool both for gastroenterologists and for general practitioners for distinguishing inflammatory bowel disease (IBD) from irritable bowel syndrome. Increasing evidences support the use of this biomarker for diagnosis, follow-up and evaluation of response to therapy of several pediatric gastrointestinal diseases, ranging from IBD to nonspecific colitis and necrotizing enterocolitis. This article summarizes the current literature on the use of FC in clinical practice.
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Affiliation(s)
- Su Jin Jeong
- Department of Pediatrics, Bundang CHA Medical Center, CHA University School of Medicine, Seongnam, Korea
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15
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Abstract
PURPOSE The impact of weight loss on obesity-related colorectal cancer (CRC) risk is not well defined. Previous studies have suggested that Roux-en-Y gastric bypass (RYGB) surgery may have an unexpected adverse impact on CRC risk. This study aimed to investigate the impact of RYGB on biomarkers of CRC risk. MATERIALS AND METHODS Rectal mucosal biopsies and blood were obtained from patients undergoing RYGB (n = 22) and non-obese control participants (n = 20) at baseline and at a median of 6.5 months after surgery. Markers of systemic inflammation and glucose homeostasis were measured. Expression of pro-inflammatory genes and proto-oncogenes in the rectal mucosa was quantified using qPCR. Crypt cell proliferation state of the rectal mucosa was assessed by counting mitotic figures in whole micro-dissected crypts. RESULTS At 6.5 months post-surgery, participants had lost 29 kg body mass and showed improvements in markers of glucose homeostasis and in systemic inflammation. Expression of pro-inflammatory genes in the rectal mucosa did not increase and COX-1 expression fell significantly (P = 0.019). The mean number of mitoses per crypt decreased from 6.5 to 4.3 (P = 0.028) after RYGB. CONCLUSION RYGB in obese adults led to lower rectal crypt cell proliferation, reduced systemic and mucosal markers of inflammation and improvements in glucose regulation. These consistent findings of reduced markers of tumourigenic potential suggest that surgically induced weight loss may lower CRC risk.
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Efficacy of an Anthocyanin and Prebiotic Blend on Intestinal Environment in Obese Male and Female Subjects. J Nutr Metab 2018; 2018:7497260. [PMID: 30302287 PMCID: PMC6158948 DOI: 10.1155/2018/7497260] [Citation(s) in RCA: 25] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/19/2018] [Revised: 07/06/2018] [Accepted: 08/01/2018] [Indexed: 12/19/2022] Open
Abstract
Background Anthocyanins and prebiotics impact overall health and wellness, likely through modulation of the microbiota and the intestinal ecosystem. Objectives An 8-week open-label study in male and female volunteers with uncomplicated obesity was designed to study the efficacy of an anthocyanin and prebiotic blend in modulating intestinal microbiota and intestinal inflammation. Results After 8 weeks of daily supplementation, participants had a significant decrease in Firmicutes (p < 0.001) and Actinobacteria (p < 0.001) and a significant increase in Bacteroidetes (p < 0.001). Bowel habits were improved as evidenced by reductions in the severity of bloating (p < 0.05), gas (p=0.035), and abdominal pain (p=0.015) as well as significant improvements in stool consistency (p < 0.05). Finally, a nonsignificant decrease in the inflammatory marker fecal calprotectin was seen (p=0.107). The supplement was safe and well tolerated. Conclusions The results suggest that regular consumption of the anthocyanin-prebiotic blend positively modulated the intestinal ecosystem and provided insights into the mechanisms of action and its impact on health benefits.
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Peng S, Sun X, Wang X, Wang H, Shan Z, Teng W, Li C. Myeloid related proteins are up-regulated in autoimmune thyroid diseases and activate toll-like receptor 4 and pro-inflammatory cytokines in vitro. Int Immunopharmacol 2018; 59:217-226. [PMID: 29656212 DOI: 10.1016/j.intimp.2018.04.009] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/18/2018] [Revised: 03/12/2018] [Accepted: 04/05/2018] [Indexed: 12/11/2022]
Abstract
PURPOSE Myeloid-related protein (MRP) family plays an important role in the promotion of cell proliferation and the production of inflammatory cytokines. We investigated the expression of MRP6, MRP8 and MRP14 in thyroid tissues, serum, and peripheral blood monocular cells (PBMCs) in patients with autoimmune thyroid diseases (AITD). METHOD The expression of MRP6, MRP8, and MRP14 was investigated using immunohistochemical staining and quantitative real-time polymerase chain reaction in the thyroid glands of 7 patients with Graves' disease (GD), 8 with Hashimoto's thyroiditis (HT), and 7 healthy controls (HC). The serum levels of MRP8/MRP14 complex and MRP6 were investigated in 30 patients with GD, 36 with HT, and 30 with HC. The mRNA expression of MRP proteins in PBMCs was also explored. PBMCs from each group were incubated with MPRs and their effect on Toll-like receptor 4(TLR4) expression and their effect on the levels of the pro-inflammatory cytokines in supernatant were analyzed upon incubating with TLR4 and signaling pathways inhibitors. RESULTS Serum levels of MRP8/MRP14 and MRP6 were up-regulated in patients with AITD. In addition, mRNA expression of MRP proteins in PBMCs and the thyroid gland was markedly elevated in AITD patients. MRP6 and MPR8 promoted the secretion of TNF-α and IL-6 in cultured PBMCs, and this elevation was more pronounced in AITD patients; we also found that this up-regulation was regulated by TLR4/phosphoinositide 3-kinase/nuclear factor-κB signaling pathway. CONCLUSION The expression of MRP proteins was elevated in AITD patients. Therefore, an MRP-TLR4 dependent signaling may play an important role in the pathogenesis of AITD.
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Affiliation(s)
- Shiqiao Peng
- Department of Endocrinology and Metabolism, Institute of Endocrinology, Liaoning Provincial Key Laboratory of Endocrine Diseases, The First Affiliated Hospital of China Medical University, Shenyang, Liaoning 110001, PR China
| | - Xuren Sun
- Department of Gastroenterology, The First Affiliated Hospital of China Medical University, Shenyang, Liaoning 110001, PR China
| | - Xinyi Wang
- Department of Laboratory Medicine, The First Affiliated Hospital of China Medical University, Shenyang, Liaoning 110001, PR China
| | - Haoyu Wang
- Department of Endocrinology and Metabolism, Institute of Endocrinology, Liaoning Provincial Key Laboratory of Endocrine Diseases, The First Affiliated Hospital of China Medical University, Shenyang, Liaoning 110001, PR China
| | - Zhongyan Shan
- Department of Endocrinology and Metabolism, Institute of Endocrinology, Liaoning Provincial Key Laboratory of Endocrine Diseases, The First Affiliated Hospital of China Medical University, Shenyang, Liaoning 110001, PR China
| | - Weiping Teng
- Department of Endocrinology and Metabolism, Institute of Endocrinology, Liaoning Provincial Key Laboratory of Endocrine Diseases, The First Affiliated Hospital of China Medical University, Shenyang, Liaoning 110001, PR China.
| | - Chenyan Li
- Department of Endocrinology and Metabolism, Institute of Endocrinology, Liaoning Provincial Key Laboratory of Endocrine Diseases, The First Affiliated Hospital of China Medical University, Shenyang, Liaoning 110001, PR China.
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Abstract
PURPOSE OF REVIEW The review summarizes our current understanding of how obesity impacts diagnostic studies and therapies used in inflammatory bowel disease (IBD) as well as the safety and efficacy of medical and surgical weight loss therapies in the obese IBD patient. RECENT FINDINGS Many of the diagnostic tools we rely on in the identification and monitoring of IBD can be altered by obesity. Obesity is associated with increased acute phase proteins and fecal calprotectin. It can be more difficult to obtain and interpret cross sectional imaging of obese patients. Recent studies have also shown that common therapies used to treat IBD may be less effective in the obese population and may impact comorbid disease. Our understanding of how best to measure obesity is evolving. In addition to BMI, studies now include measures of visceral adiposity and subcutaneous to visceral adiposity ratios. An emerging area of interest is the safety and efficacy of obesity treatment including bariatric surgery in patients with IBD. A remaining question is how weight loss may alter the course of IBD. SUMMARY The proportion of obese IBD patients is on the rise. Caring for this population requires a better understanding of how obesity impacts diagnostic testing and therapeutic strategies. The approach to weight loss in this population is complex and future studies are needed to determine the safety of medical or surgical weight loss and its impact on the course of disease.
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Fecal Calprotectin, Elastase, and Alpha-1-Antitrypsin Levels After Roux-en-Y Gastric Bypass; Calprotectin Is Significantly Elevated in the Majority of Patients. Obes Surg 2017; 26:2974-2980. [PMID: 27216731 PMCID: PMC5118387 DOI: 10.1007/s11695-016-2222-0] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/14/2023]
Abstract
BACKGROUND Roux-en-Y gastric bypass (RYGB) causes several alterations in gastrointestinal function. We hypothesized that levels of three commonly used fecal tests change after RYGB. METHODS Fecal levels of calprotectin, elastase, and alpha-1-antitrypsin were determined in 122 patients without signs of gastrointestinal disease 1 to 2 years after RYGB. Medians, distribution of values, and the percentage of patients with levels above or below reference values were determined. RESULTS Median fecal calprotectin level was 163.5 (<30-1587) μg/g; in 87 % of patients, it was above the reference value (<50 μg/g). Median fecal elastase level was 444 (<15-647) μg/g; 13 % was below the reference value (>200 μg/g). Median fecal alpha-1-antitrypsin level was 0.51 (<0.20-2.20) mg/g, comparable to the reference values. CONCLUSIONS Fecal calprotectin levels are significantly higher than the reference value in most patients after RYGB. Fecal elastase is significantly lower. This might indicate that the validity of fecal calprotectin testing is impaired after RYGB and the specificity for fecal elastase is decreased. Clinical awareness of altered fecal markers after RYGB is essential to prevent unnecessary diagnostic tests, such as colonoscopy. Fecal alpha-1-antitrypsin is not influenced by RYGB.
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Ohlsson B, Roth B, Larsson E, Höglund P. Calprotectin in serum and zonulin in serum and feces are elevated after introduction of a diet with lower carbohydrate content and higher fiber, fat and protein contents. Biomed Rep 2017; 6:411-422. [PMID: 28413639 PMCID: PMC5374938 DOI: 10.3892/br.2017.865] [Citation(s) in RCA: 31] [Impact Index Per Article: 3.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/21/2016] [Accepted: 02/01/2017] [Indexed: 01/12/2023] Open
Abstract
Calprotectin is a marker of inflammation and zonulin is a marker of intestinal permeability. Diets with lower carbohydrate content and higher contents of fat, fiber and protein, e.g., Okinawan-based diet, are considered to reduce inflammation and intestinal permeability. The aim of the present study was to evaluate calprotectin and zonulin levels in serum and feces after intervention with an Okinawan-based Nordic diet. Thirty patients (17 women) with type 2 diabetes, mean age 57.5±8.2 years, BMI 29.9±4.1 kg/m2, were served the diet during 12 weeks, and were followed for another 16 weeks. Anthropometric and metabolic parameters were registered. Fasting levels of calprotectin and zonulin in serum and feces, and hormones in plasma, were measured by Luminex or ELISA before study start and after 12 and 28 weeks. Calprotectin in serum tended to be increased (P=0.074) after 12 weeks. Zonulin in serum and feces were elevated after 12 weeks (P=0.019 vs. P<0.001), and remained elevated in serum after 28 weeks (P=0.014). In contrast to baseline, there was a correlation between calprotectin and zonulin in serum and feces after dietary intervention (P=0.025 vs. P=0.079). Energy percentage of protein in breakfast correlated with serum calprotectin (P=0.008) and tended to correlate with serum zonulin (P=0.059). Calprotectin in serum tended to be elevated, and zonulin in serum and feces are elevated after introduction of an Okinawan-based Nordic diet. These biomarkers correlate with energy percentage of protein.
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Affiliation(s)
- Bodil Ohlsson
- Department of Internal Medicine, Skane University Hospital, Malmo, Sweden
| | - Bodil Roth
- Department of Internal Medicine, Skane University Hospital, Malmo, Sweden
| | - Ewa Larsson
- Department of Cardiothoracic Surgery, Lund University, Skane University Hospital, Lund, Sweden
| | - Peter Höglund
- Department of Clinical Chemistry and Pharmacology, Lund University, Skane University Hospital, Lund, Sweden
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Faecal calprotectin: factors affecting levels and its potential role as a surrogate marker for risk of development of Crohn's Disease. BMC Gastroenterol 2016; 16:126. [PMID: 27717310 PMCID: PMC5054545 DOI: 10.1186/s12876-016-0535-z] [Citation(s) in RCA: 23] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/12/2016] [Accepted: 09/20/2016] [Indexed: 12/19/2022] Open
Abstract
Background Faecal calprotectin (FC) is one of the most widely used non-invasive tests for the diagnosis and assessment of Crohn’s disease (CD) activity. Despite this, factors other than disease activity which affect levels have not been extensively reviewed. This is of importance when using FC in the diagnostic setting but also may be of utility in studying the aetiology of disease. Objectives Our review outlines environmental risk factors that affect FC levels influencing diagnostic accuracy and how these may be associated with risk of developing CD. FC as a surrogate marker could be used to validate risk factors established in case control studies where prospective studies are not feasible. Proof of this concept is provided by our identification of obesity as being associated with elevated FC, our subsequent confirmation of obesity as risk factor for CD and the subsequent verification in prospective studies, as well as associations of lack of physical activity and dietary fibre intake with elevated FC levels and their subsequent confirmation as risk factors in prospective studies. Conclusion We believe that FC is likely to prove a useful surrogate marker for risk of developing CD. This review has given a theoretical basis for considering the epidemiological determinants of CD which to date has been missing.
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Pavlidis P, Powell N, Vincent RP, Ehrlich D, Bjarnason I, Hayee B. Systematic review: bile acids and intestinal inflammation-luminal aggressors or regulators of mucosal defence? Aliment Pharmacol Ther 2015. [PMID: 26223936 DOI: 10.1111/apt.13333] [Citation(s) in RCA: 106] [Impact Index Per Article: 10.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
BACKGROUND Inflammatory bowel diseases (IBD), comprising Crohn's disease and ulcerative colitis (UC), are chronic conditions attributed to an aberrant immune response to luminal triggers. Recently, published work suggests a pathogenic role for bile acids in this context. AIM To perform a systematic review of studies investigating the role of bile acids in intestinal inflammation and present potentially relevant clinical implications. METHODS Pubmed search for English language articles published up to May 2015. Terms used were: 'bile', 'bile acid', 'barrier', 'small bowel injury', 'Crohn's' and 'colitis'. RESULTS Experimental studies support a variable role for bile acids in intestinal barrier homoeostasis. This may be attributed to different physicochemical properties, variable effects on epithelia and immune cells via bile acids-specific receptors, or through a cross-talk with the gut microbiome. A reduction in the bile acids pool, with lower concentrations of secondary forms, has been recognised for some time in Crohn's disease and associated to ileal dysfunction and bile acids malabsorption. Recent work suggests that these changes, including an increase in sulphated forms, are related to inflammatory activity in both Crohn's disease and UC. The detrimental effects of 'western diet' elements such as emulsifiers and fat, which have been implicated in the development of the current IBD and obesity epidemics, may also be bile acid-mediated. CONCLUSIONS Although there are only a few observational clinical studies to support an interaction, in vivo human and animal studies support an association between bile acids metabolism, the gut microbiome and intestinal inflammation. This may well prove to have significant diagnostic and therapeutic implications.
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Affiliation(s)
- P Pavlidis
- Department of Gastroenterology, King's College Hospital, London, UK
| | - N Powell
- Division of Transplantation and Mucosal Biology, King's College London, London, UK
| | - R P Vincent
- Department of Biochemistry, King's College Hospital, London, UK
| | - D Ehrlich
- Centre of Host-Microbiome Interactions, King's College London, London, UK
| | - I Bjarnason
- Department of Gastroenterology, King's College Hospital, London, UK
| | - B Hayee
- Department of Gastroenterology, King's College Hospital, London, UK
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Alexandre L, Long E, Beales ILP. Pathophysiological mechanisms linking obesity and esophageal adenocarcinoma. World J Gastrointest Pathophysiol 2014; 5:534-549. [PMID: 25400997 PMCID: PMC4231518 DOI: 10.4291/wjgp.v5.i4.534] [Citation(s) in RCA: 51] [Impact Index Per Article: 4.6] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/06/2014] [Revised: 08/07/2014] [Accepted: 09/04/2014] [Indexed: 02/06/2023] Open
Abstract
In recent decades there has been a dramatic rise in the incidence of esophageal adenocarcinoma (EAC) in the developed world. Over approximately the same period there has also been an increase in the prevalence of obesity. Obesity, especially visceral obesity, is an important independent risk factor for the development of gastro-esophageal reflux disease, Barrett's esophagus and EAC. Although the simplest explanation is that this mediated by the mechanical effects of abdominal obesity promoting gastro-esophageal reflux, the epidemiological data suggest that the EAC-promoting effects are independent of reflux. Several, not mutually exclusive, mechanisms have been implicated, which may have different effects at various points along the reflux-Barrett's-cancer pathway. These mechanisms include a reduction in the prevalence of Helicobacter pylori infection enhancing gastric acidity and possibly appetite by increasing gastric ghrelin secretion, induction of both low-grade systemic inflammation by factors secreted by adipose tissue and the metabolic syndrome with insulin-resistance. Obesity is associated with enhanced secretion of leptin and decreased secretion of adiponectin from adipose tissue and both increased leptin and decreased adiponectin have been shown to be independent risk factors for progression to EAC. Leptin and adiponectin have a set of mutually antagonistic actions on Barrett's cells which appear to influence the progression of malignant behaviour. At present no drugs are of proven benefit to prevent obesity associated EAC. Roux-en-Y reconstruction is the preferred bariatric surgical option for weight loss in patients with reflux. Statins and aspirin may have chemopreventative effects and are indicated for their circulatory benefits.
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Abstract
The incidence of oesophageal adenocarcinoma has increased dramatically in the developed world in the last half century. Over approximately the same period there has been an increase in the prevalence of obesity. Multiple epidemiological studies and meta-analyses have confirmed that obesity, especially abdominal, visceral obesity, is a risk factor for gastro-oesophageal reflux, Barrett's oesophagus and oesophageal adenocarcinoma. Although visceral obesity enhances gastro-oesophageal reflux, the available data also show that visceral obesity increases the risk of Barrett's oesophagus and adenocarcinoma via reflux-independent mechanisms. Several possible mechanisms could link obesity with the risk of oesophageal adenocarcinoma in addition to mechanical effects increasing reflux. These include reduced gastric Helicobacter pylori infection, altered intestinal microbiome, factors related to lifestyle, the metabolic syndrome and associated low-grade inflammation induced by obesity and the secretion of mediators by adipocytes which may directly influence the oesophageal epithelium. Of these adipocyte-derived mediators, increased leptin levels have been independently associated with progression to oesophageal adenocarcinoma and in laboratory studies leptin enhances malignant behaviours in cell lines. Adiponectin is also secreted by adipocytes and levels decline with obesity: decreased serum adiponectin levels are associated with malignant progression in Barrett's oesophagus and experimentally adiponectin exerts anticancer effects in Barrett's cell lines and inhibits growth factor signalling. At present there are no proven chemopreventative interventions that may reduce the incidence of obesity-associated oesophageal cancer: observational studies suggest that the combined use of a statin and aspirin or another cyclo-oxygenase inhibitor is associated with a significantly reduced cancer incidence in patients with Barrett's oesophagus.
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Affiliation(s)
- Elizabeth Long
- Norwich Medical School, University of East Anglia, Norwich NR4 7TJ, UK
| | - Ian L P Beales
- Norwich Medical School, University of East Anglia, Norwich NR4 7TJ, UK
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Scalera A, Di Minno MND, Tarantino G. What does irritable bowel syndrome share with non-alcoholic fatty liver disease? World J Gastroenterol 2013; 19:5402-5420. [PMID: 24023483 PMCID: PMC3761093 DOI: 10.3748/wjg.v19.i33.5402] [Citation(s) in RCA: 20] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/25/2013] [Revised: 06/05/2013] [Accepted: 07/23/2013] [Indexed: 02/06/2023] Open
Abstract
Non-alcoholic fatty liver disease (NAFLD) and irritable bowel syndrome (IBS) are two very common diseases in the general population. To date, there are no studies that highlight a direct link between NAFLD and IBS, but some recent reports have found an interesting correlation between obesity and IBS. A systematic PubMed database search was conducted highlighting that common mechanisms are involved in many of the local and systemic manifestations of NAFLD, leading to an increased cardiovascular risk, and IBS, leading to microbial dysbiosis, impaired intestinal barrier and altered intestinal motility. It is not known when considering local and systemic inflammation/immune system activation, which one has greater importance in NAFLD and IBS pathogenesis. Also, the nervous system is implicated. In fact, inflammation participates in the development of mood disorders, such as anxiety and depression, characteristics of obesity and consequently of NAFLD and, on the other hand, in intestinal hypersensitivity and dysmotility.
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