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Dryden GW, Dryden SM. Synergistic Benefits of Dietary Strategies in the Management of IBD. Curr Gastroenterol Rep 2025; 27:8. [PMID: 39702516 DOI: 10.1007/s11894-024-00949-1] [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] [Accepted: 10/08/2024] [Indexed: 12/21/2024]
Abstract
PURPOSE OF REVIEW Inflammatory bowel disease (IBD) patients commonly inquire about the role of diet in the onset and management of their disease process. This review sought to assess the impact of the inflammatory bowel diseases on the nutritional state of patients and evaluate the evidence supporting nutritional interventions as therapy. RECENT FINDINGS The role of nutrition has evolved from one of deficient nutrient and calorie replacement alone into a proactive therapeutic for treating active inflammatory disease symptoms. The realization that initiating total parenteral nutrition (TPN) in place of oral take could improve disease symptoms provided the first indication that food intake played a causative role in the IBD. The evolution of TPN to enteral nutrition improved tolerance and reduced side effects but clouded the role of oral intake in the pathophysiology of IBD. Advanced understanding of the role of the microbiota in IBD combined with recognition of the influence of nutrients on microbial composition have ushered in a new era of food as therapy. The role of nutrition in IBD has evolved significantly over the past 30-40 years. From complete elimination of oral intake to the carefully curated menu intended to mold the intestinal microbiota to a non-inflammatory milieu has revolutionized the approach to dietary intervention. Additional studies are warranted to optimize dietary intervention strategies.
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Affiliation(s)
- Gerald W Dryden
- Department of Medicine, University of Louisville, 505 S. Hancock Street, Room 519, Louisville, KY, 40202, USA.
| | - Sara M Dryden
- Department of Anesthesiology, University of North Carolina, N2198 UNC Hospitals, CB# 7010, Chapel Hill, NC, 27599, USA
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2
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Magen-Rimon R, Cohen M, Rosen I, Spector-Cohen I, Garah J, Weiss R, Shaoul R. Adipokine Profiles and Their Association with Body Composition and Disease Activity in Pediatric Crohn's Disease. Dig Dis Sci 2025:10.1007/s10620-025-08941-z. [PMID: 40299289 DOI: 10.1007/s10620-025-08941-z] [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: 11/13/2024] [Accepted: 02/18/2025] [Indexed: 04/30/2025]
Abstract
OBJECTIVES Emerging evidence implicates an important role for visceral fat, particularly "creeping fat," in the pathogeneses and progression of inflammatory bowel diseases (IBD), specifically Crohn's disease (CD). In this study, we aimed to explore the association between body composition, adipocytokine profiles, and disease activity in pediatric CD patients. METHODS We recruited patients with active and quiescent CD, aged 6-18, along with age matched healthy controls. Body composition was analyzed via bio-impedance analysis, and adipocytokines were assessed by ELISA-multiplex. RESULTS Patients with active CD exhibited significantly elevated levels of adiponectin and resistin compared to healthy controls and patients in remission even upon adjustment for body composition indices. Leptin correlated only with body composition and not with disease activity. Patients with active CD had relatively higher percentage of body fat and total body fat than the other groups. CONCLUSIONS This study underscores the complex interactions between adipocytokine profiles and disease activity in CD. Further studies are needed to investigate the potential mechanistic role of adiponectin and resistin in CD pathogenesis.
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Affiliation(s)
- Ramit Magen-Rimon
- Faculty of Medicine, Technion Israel Institute of Technology, Haifa, Israel.
- Pediatric Gastroenterology & Nutrition Institute, Ruth Children's Hospital, Rambam Medical Center, Haifa, Israel.
| | - Michal Cohen
- Faculty of Medicine, Technion Israel Institute of Technology, Haifa, Israel
- Pediatric Endocrinology Institute, Ruth Children's Hospital, Rambam Medical Center, Haifa, Israel
| | - Irit Rosen
- Pediatric Gastroenterology & Nutrition Institute, Ruth Children's Hospital, Rambam Medical Center, Haifa, Israel
| | - Inna Spector-Cohen
- Faculty of Medicine, Technion Israel Institute of Technology, Haifa, Israel
- Pediatric Gastroenterology & Nutrition Institute, Ruth Children's Hospital, Rambam Medical Center, Haifa, Israel
| | - Jamal Garah
- Pediatric Gastroenterology & Nutrition Institute, Ruth Children's Hospital, Rambam Medical Center, Haifa, Israel
| | - Ram Weiss
- Faculty of Medicine, Technion Israel Institute of Technology, Haifa, Israel
- Department of Pediatrics, Ruth Children's Hospital, Rambam Medical Center, Haifa, Israel
| | - Ron Shaoul
- Faculty of Medicine, Technion Israel Institute of Technology, Haifa, Israel
- Pediatric Gastroenterology & Nutrition Institute, Ruth Children's Hospital, Rambam Medical Center, Haifa, Israel
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Desai A, Khataniar H, Hashash JG, Farraye FA, Regueiro M, Kochhar GS. Effectiveness and Safety of Semaglutide for Weight Loss in Patients With Inflammatory Bowel Disease and Obesity. Inflamm Bowel Dis 2025; 31:696-705. [PMID: 38642103 DOI: 10.1093/ibd/izae090] [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: 01/22/2024] [Indexed: 04/22/2024]
Abstract
BACKGROUND Semaglutide, a glucagon-like peptide-1 receptor agonist, has shown sustained and clinically significant weight loss in the general population. There are limited data on outcomes of its use in patients with inflammatory bowel disease (IBD). METHODS A retrospective cohort study was conducted between June 4, 2021, and December 11, 2023, using TriNetX, a U.S. multi-institutional database in patients with obesity who had IBD compared with patients without IBD. The primary aim was to assess the mean total body weight (TBW) change between 6 and 15 months from initiation of semaglutide compared with baseline between the 2 cohorts. One-to-one (1:1) propensity score matching was performed for demographics, comorbid conditions, smoking status, and mean body mass index. A 2-sample t test was performed to assess mean TBW change from baseline, with a P value <.05 considered to be statistically significant. We also compared the risk of IBD-specific outcomes with and without semaglutide use in patients with IBD. RESULTS Out of 47 424 patients with IBD and obesity, 150 (0.3%) patients were prescribed semaglutide (mean age 47.4 ± 12.2 years; mean TBW 237 ± 54.8 pounds; mean body mass index 36.9 ± 6.5 kg/m2; 66% Crohn's disease). There was no difference in mean TBW change after initiation of semaglutide in the IBD and non-IBD cohorts (-16 ± 13.4 pounds vs -18 ± 12.7 pounds; P = .24). There was no difference in mean TBW change between 6 and 12 months (-16 ± 13 pounds vs -15 ± 11.2 pounds; P = .24) and 12 and 15 months (-20 ± 13.2 pounds vs -21 ± 15.3 pounds; P = .49) between the 2 cohorts. There was no difference in the risk of oral or intravenous steroid use and any-cause hospitalization in the semaglutide group compared with the group without semaglutide use in patients with IBD. CONCLUSION Semaglutide use is effective in patients with IBD and obesity similar to patients without IBD, with >5% mean weight loss. There was no increased risk of IBD-specific adverse events with semaglutide use.
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Affiliation(s)
- Aakash Desai
- Division of Gastroenterology and Hepatology, Mayo Clinic, Jacksonville, FL, USA
| | | | - Jana G Hashash
- Division of Gastroenterology and Hepatology, Mayo Clinic, Jacksonville, FL, USA
| | - Francis A Farraye
- Division of Gastroenterology and Hepatology, Mayo Clinic, Jacksonville, FL, USA
| | - Miguel Regueiro
- Division of Gastroenterology, Hepatology and Nutrition, Cleveland Clinic Foundation, Cleveland, OH, USA
| | - Gursimran S Kochhar
- Division of Gastroenterology, Hepatology and Nutrition, Allegheny Health Network, Pittsburgh, PA, USA
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Cañete F, Vela E, Calafat M, Piera J, Mañosa M, Domènech E. Severe obesity, a susceptibility factor for developing inflammatory bowel disease: results of a population-based study. J Crohns Colitis 2025; 19:jjaf010. [PMID: 39826088 DOI: 10.1093/ecco-jcc/jjaf010] [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: 10/16/2024] [Indexed: 01/20/2025]
Abstract
BACKGROUND AND AIMS Inflammatory bowel disease (IBD) develops in genetically susceptible individuals exposed to certain environmental factors, of which only a few have been established. We aimed to assess whether bariatric surgery (BS) and severe obesity are associated with an increased risk of developing IBD. METHODS Adults diagnosed with obesity or severe obesity between 2005 and 2020 were identified from the Catalan Health Surveillance System; those diagnosed with IBD prior to the diagnosis of obesity or severe obesity were excluded. Individuals who had undergone BS and those with a new diagnosis of IBD were identified and their likelihood of developing IBD was analyzed. RESULTS A total of 93 473 individuals with severe obesity, 1 009 256 with obesity and 14 698 who underwent BS were identified. The incidence rates of IBD among individuals who had undergone BS prior to IBD diagnosis was 0.84 cases per 1000 person-years, 0.90 cases per 1000 person-years among individuals with severe obesity without BS and 0.60 cases per 1000 person-years in individuals with obesity. In the multivariable regression analysis, severe obesity (hazard ratio [HR] 1.46; 95% confidence interval [95%CI] 1.31-1.62), BS (HR 1.57; 95%CI 1.25-1.97), and smoking habit (HR 1.57; 95%CI 1.46-1.69) were risk factors for developing IBD (as well as for Crohn's disease and ulcerative colitis). CONCLUSIONS Severe obesity and BS were independent risk factors for the development of IBD. noninvasive screening for IBD seems to be warranted in this population.
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Affiliation(s)
- Fiorella Cañete
- Servei d'Aparell Digestiu, Hospital Universitari Germans Trias i Pujol, Badalona, Catalonia, Spain
- CIBERehd, Madrid, Spain
| | - Emili Vela
- Servei Català de la Salut (CatSalut) and Digitalization for the Sustainability of the Healthcare System (DS3), IDIBELL, Barcelona, Catalonia, Spain
| | - Margalida Calafat
- Servei d'Aparell Digestiu, Hospital Universitari Germans Trias i Pujol, Badalona, Catalonia, Spain
- CIBERehd, Madrid, Spain
| | - Jordi Piera
- Servei Català de la Salut (CatSalut) and Digitalization for the Sustainability of the Healthcare System (DS3), IDIBELL, Barcelona, Catalonia, Spain
| | - Míriam Mañosa
- Servei d'Aparell Digestiu, Hospital Universitari Germans Trias i Pujol, Badalona, Catalonia, Spain
- CIBERehd, Madrid, Spain
| | - Eugeni Domènech
- Servei d'Aparell Digestiu, Hospital Universitari Germans Trias i Pujol, Badalona, Catalonia, Spain
- CIBERehd, Madrid, Spain
- Departament de Medicina, Universitat Autònoma de Barcelona, Barcelona, Spain
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Marra M, Mallardo M, Nigro E, Cioffi I, Leo C, Guarino AD, Castiglione F, Pasanisi F, Daniele A. Adiponectin and HMW Oligomers in Relation to Inflammatory Markers in Crohn's Disease Patients. Biomedicines 2025; 13:273. [PMID: 40002687 PMCID: PMC11853605 DOI: 10.3390/biomedicines13020273] [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: 12/17/2024] [Revised: 01/13/2025] [Accepted: 01/15/2025] [Indexed: 02/27/2025] Open
Abstract
Background/Objectives: Crohn's disease (CD), a chronic inflammatory gastrointestinal illness, is the result of genetics and environmental factors. Adipose tissue has recently been found to play a significant role in CD. Methods: here, we examined the relationship between adiponectin, HMW oligomers, and CD in 92 patients. Results: first, we verified that the patients' therapies had no influence on the nutritional and biochemical variables. Correlation analysis between HMW adiponectin and nutritional parameters found no relationship; therefore, we investigated its relationship with CD severity and inflammatory markers. Based on adiponectin, we divided patients into tertiles and found that CDAI was lowest in the second and third tertile [I: <19.3 (n = 31); II: 19.3-22.2 (n = 31); III: >22.2 (n = 30)]. Furthermore, IL-6 and CRP were higher in the second and third tertile, while lymphocytes were lower in the second and third tertile. Correlation analysis showed that both adiponectin and HMW oligomers were inversely related to lymphocytes and directly related to CRP. A ROC curve evidenced that patients carrying adiponectin values ≤ 19 performed well in predicting worse CDAI and lymphocyte values (AUCs: 0.826 and 0.806). Next, we divided CD patients into tertiles based on HMW adiponectin, finding that IL-6 was highest in the second and third tertile. Lymphocytes were lowest in the third tertile while CRP values were substantially higher. Conclusions: altogether, these data suggest a biological role for adiponectin and HMW oligomers in CD severity and inflammatory status. However, the molecular effects related to adiponectin in CD remain unclear and further studies are needed to clarify its applicability as a biomarker.
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Affiliation(s)
- Maurizio Marra
- Department of Clinical Medicine and Surgery, University of Naples “Federico II”, Via Pansini 5, 80131 Naples, Italy; (M.M.); (I.C.); (F.P.)
| | - Marta Mallardo
- Department of Molecular and Biotechnological Medicine, University of Naples “Federico II”, 80138 Naples, Italy; (M.M.); (A.D.)
- CEINGE-Biotechnologies Advances S.c.a r.l., Via G. Salvatore 486, 80145 Naples, Italy
| | - Ersilia Nigro
- CEINGE-Biotechnologies Advances S.c.a r.l., Via G. Salvatore 486, 80145 Naples, Italy
- Dipartimento di Scienze e Tecnologie Ambientali, Biologiche, Farmaceutiche, Università della Campania “Luigi Vanvitelli”, Via Vivaldi 43, 81100 Caserta, Italy
| | - Iolanda Cioffi
- Department of Clinical Medicine and Surgery, University of Naples “Federico II”, Via Pansini 5, 80131 Naples, Italy; (M.M.); (I.C.); (F.P.)
- Division of Human Nutrition, Department of Food, Environmental and Nutritional Sciences—DEFENS, Università Degli Studi di Milano, Celoria 2, 20133 Milan, Italy
| | - Camilla Leo
- Gastroenterology Unit, Department of Clinical Medicine and Surgery, “Federico II” University, 80131 Naples, Italy; (C.L.); (A.D.G.); (F.C.)
| | - Alessia Dalila Guarino
- Gastroenterology Unit, Department of Clinical Medicine and Surgery, “Federico II” University, 80131 Naples, Italy; (C.L.); (A.D.G.); (F.C.)
| | - Fabiana Castiglione
- Gastroenterology Unit, Department of Clinical Medicine and Surgery, “Federico II” University, 80131 Naples, Italy; (C.L.); (A.D.G.); (F.C.)
| | - Fabrizio Pasanisi
- Department of Clinical Medicine and Surgery, University of Naples “Federico II”, Via Pansini 5, 80131 Naples, Italy; (M.M.); (I.C.); (F.P.)
| | - Aurora Daniele
- Department of Molecular and Biotechnological Medicine, University of Naples “Federico II”, 80138 Naples, Italy; (M.M.); (A.D.)
- CEINGE-Biotechnologies Advances S.c.a r.l., Via G. Salvatore 486, 80145 Naples, Italy
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Yamamoto S, Yoshida N, Sakurai N, Ichikawa A, Takeshita K, Okada Y. Differentiation Between Ulcerative Colitis and Crohn's Disease Using Abdominal Computed Tomography in Patients With First-Time Inflammatory Bowel Disease. Cureus 2024; 16:e59691. [PMID: 38840987 PMCID: PMC11151137 DOI: 10.7759/cureus.59691] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 05/03/2024] [Indexed: 06/07/2024] Open
Abstract
Background Ulcerative colitis (UC) and Crohn's disease (CD) are classified as inflammatory bowel diseases (IBDs). However, they have different pathogeneses and treatment strategies and need to be differentiated. Purpose To determine the feasibility of differentiating UC from CD in patients with first-time IBD based on simple abdominal computed tomography (CT) findings. Methods We conducted a retrospective study of patients diagnosed with IBD for the first time at our hospital between January and December 2021. Age, sex, white blood cell count, albumin concentration, C-reactive protein concentration, visceral fat area, subcutaneous fat area, and psoas major volume were extracted and used to differentiate the two groups. Results Forty-three patients were selected. Their mean age was 35.60 ± 17.19 years, and 32 were male, while 11 were female. The visceral fat cross-sectional area was 51.80 cm2 for UC and 21.10 cm2 for CD (p < 0.01). The subcutaneous fat cross-sectional area was 108.30 cm2 for UC and 66.30 cm2 for CD (p = 0.049). The total protein concentration was 6.15 g/L for UC and 6.60 g/L for CD (p = 0.012). Receiver operating characteristic curve analysis of the visceral and subcutaneous fat cross-sectional areas showed areas under the curve, 95% confidence intervals, sensitivities, and specificities of 0.750 and 0.675, 0.603-0.897 and 0.507-0.844, 0.810 and 1.00, and 0.591 and 0.409, respectively, at cutoffs of 26.53 and 36.6 cm2. Conclusions The visceral and subcutaneous fat cross-sectional areas determined with simple abdominal CT can differentiate UC from CD in patients with first-time IBD.
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Affiliation(s)
- Shinji Yamamoto
- Department of Radiological Technology, Japan Community Healthcare Organization (JCHO) Tokyo Yamate Medical Center, Tokyo, JPN
| | - Nobukiyo Yoshida
- Department of Radiological Technology, Niigata University of Health and Welfare, Niigata, JPN
| | - Noriko Sakurai
- Department of Radiological Technology, Niigata University of Health and Welfare, Niigata, JPN
| | - Atsushi Ichikawa
- Department of Radiological Technology, Nihon University Itabashi Hospital, Tokyo, JPN
| | - Koji Takeshita
- Department of Radiology, Japan Community Healthcare Organization (JCHO) Tokyo Yamate Medical Center, Tokyo, JPN
| | - Yukinori Okada
- Department of Radiology, St. Marianna University School of Medicine, Kawasaki, JPN
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Johnson AM, Harmsen WS, Aniwan S, Tremaine WJ, Raffals LE, Dayyeh BKA, Loftus EV. Prevalence and Impact of Obesity in a Population-Based Cohort of Patients With Crohn's Disease. J Clin Gastroenterol 2024; 58:176-182. [PMID: 36728679 PMCID: PMC10310887 DOI: 10.1097/mcg.0000000000001821] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/11/2022] [Accepted: 11/22/2022] [Indexed: 02/03/2023]
Abstract
BACKGROUND Obesity is on the rise within the inflammatory bowel disease population. The impact obesity has on the natural history of Crohn's disease (CD) is not well-understood. We aimed to describe the prevalence of obesity in a population-based cohort of newly diagnosed patients with CD, and the impact obesity had on disease phenotype and outcomes of corticosteroid use, hospitalization, intestinal resection, and development of fistulizing or penetrating disease. MATERIALS AND METHODS A chart review was performed on Olmsted County, Minnesota residents diagnosed with CD between 1970 and 2010. Data were collected on demographics, body mass index, CD location and behavior, CD-related hospitalizations, corticosteroid use, and intestinal resection. The proportion of individuals considered obese at the time of CD diagnosis was evaluated over time, and CD-associated complications were assessed with Kaplan-Meier survival analysis. RESULTS We identified 334 individuals diagnosed with CD between 1970 and 2010, of whom 156 (46.7%) were either overweight (27.8%) or obese (18.9%) at the time of diagnosis. The proportion of patients considered obese at the time of their diagnosis of CD increased 2-3 fold over the course of the study period. However, obesity did not have a significant impact on the future risk of corticosteroid use, hospitalization, intestinal resection, or development of penetrating and stricturing complications. CONCLUSIONS Obesity is on the rise in patients with CD, although in this cohort, there did not appear to be any negative association with future CD-related outcomes. Further prospective studies, ideally including obesity measures such as visceral adipose tissue assessment, are warranted to understand the implications of the rising prevalence of obesity on CD outcomes.
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Affiliation(s)
- Amanda M. Johnson
- Division of Gastroenterology and Hepatology, Mayo Clinic, 200 First Street Southwest, Rochester, MN 55905, USA
| | - W. Scott Harmsen
- Biostatistics and Informatics, Mayo Clinic, 200 First Street Southwest, Rochester, MN 55905, USA
| | - Satimai Aniwan
- Division of Gastroenterology and Hepatology, Mayo Clinic, 200 First Street Southwest, Rochester, MN 55905, USA
- Division of Gastroenterology, Chulalongkorn University, King Chulalongkorn Memorial Hospital, Thai Red Cross Society, Bangkok 10330, Thailand
| | - William J. Tremaine
- Division of Gastroenterology and Hepatology, Mayo Clinic, 200 First Street Southwest, Rochester, MN 55905, USA
| | - Laura E. Raffals
- Division of Gastroenterology and Hepatology, Mayo Clinic, 200 First Street Southwest, Rochester, MN 55905, USA
| | - Barham K. Abu Dayyeh
- Division of Gastroenterology and Hepatology, Mayo Clinic, 200 First Street Southwest, Rochester, MN 55905, USA
| | - Edward V. Loftus
- Division of Gastroenterology and Hepatology, Mayo Clinic, 200 First Street Southwest, Rochester, MN 55905, USA
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Wang Y, Luo Z, Zhou Z, Zhong Y, Zhang R, Shen X, Huang L, He W, Lin J, Fang J, Huang Q, Wang H, Zhang Z, Mao R, Feng ST, Li X, Huang B, Li Z, Zhang J, Chen Z. CT-based radiomics signature of visceral adipose tissue and bowel lesions for identifying patients with Crohn's disease resistant to infliximab. Insights Imaging 2024; 15:28. [PMID: 38289416 PMCID: PMC10828370 DOI: 10.1186/s13244-023-01581-9] [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: 09/01/2023] [Accepted: 11/25/2023] [Indexed: 02/02/2024] Open
Abstract
PURPOSE To develop a CT-based radiomics model combining with VAT and bowel features to improve the predictive efficacy of IFX therapy on the basis of bowel model. METHODS This retrospective study included 231 CD patients (training cohort, n = 112; internal validation cohort, n = 48; external validation cohort, n = 71) from two tertiary centers. Machine-learning VAT model and bowel model were developed separately to identify CD patients with primary nonresponse to IFX. A comprehensive model incorporating VAT and bowel radiomics features was further established to verify whether CT features extracted from VAT would improve the predictive efficacy of bowel model. Area under the curve (AUC) and decision curve analysis were used to compare the prediction performance. Clinical utility was assessed by integrated differentiation improvement (IDI). RESULTS VAT model and bowel model exhibited comparable performance for identifying patients with primary nonresponse in both internal (AUC: VAT model vs bowel model, 0.737 (95% CI, 0.590-0.854) vs. 0.832 (95% CI, 0.750-0.896)) and external validation cohort [AUC: VAT model vs. bowel model, 0.714 (95% CI, 0.595-0.815) vs. 0.799 (95% CI, 0.687-0.885)), exhibiting a relatively good net benefit. The comprehensive model incorporating VAT into bowel model yielded a satisfactory predictive efficacy in both internal (AUC, 0.840 (95% CI, 0.706-0.930)) and external validation cohort (AUC, 0.833 (95% CI, 0.726-0.911)), significantly better than bowel alone (IDI = 4.2% and 3.7% in internal and external validation cohorts, both p < 0.05). CONCLUSION VAT has an effect on IFX treatment response. It improves the performance for identification of CD patients at high risk of primary nonresponse to IFX therapy with selected features from RM. CRITICAL RELEVANCE STATEMENT Our radiomics model (RM) for VAT-bowel analysis captured the pathophysiological changes occurring in VAT and whole bowel lesion, which could help to identify CD patients who would not response to infliximab at the beginning of therapy. KEY POINTS • Radiomics signatures with VAT and bowel alone or in combination predicting infliximab efficacy. • VAT features contribute to the prediction of IFX treatment efficacy. • Comprehensive model improved the performance compared with the bowel model alone.
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Affiliation(s)
- Yangdi Wang
- Department of Radiology, The First Affiliated Hospital, Sun Yat-Sen University, 58 Zhongshan II Road, Guangzhou, Guangdong, 510080, People's Republic of China
| | - Zixin Luo
- Medical AI Lab, School of Biomedical Engineering, Shenzhen University Medical School, Shenzhen University, Shenzhen, Guangdong, People's Republic of China
| | - Zhengran Zhou
- Zhongshan School of Medicine, Sun Yat-Sen University, 74 Zhongshan II Road, Guangzhou, Guangdong, People's Republic of China
| | - Yingkui Zhong
- Department of Gastroenterology, The Sixth Affiliated Hospital, Sun Yat-Sen University, Yuancun Er Heng Road, No. 26, Guangzhou, Guangdong, People's Republic of China
| | - Ruonan Zhang
- Department of Radiology, The First Affiliated Hospital, Sun Yat-Sen University, 58 Zhongshan II Road, Guangzhou, Guangdong, 510080, People's Republic of China
| | - Xiaodi Shen
- Department of Radiology, The First Affiliated Hospital, Sun Yat-Sen University, 58 Zhongshan II Road, Guangzhou, Guangdong, 510080, People's Republic of China
| | - Lili Huang
- Department of Radiology, The First Affiliated Hospital, Sun Yat-Sen University, 58 Zhongshan II Road, Guangzhou, Guangdong, 510080, People's Republic of China
| | - Weitao He
- Department of Radiology, The First Affiliated Hospital, Sun Yat-Sen University, 58 Zhongshan II Road, Guangzhou, Guangdong, 510080, People's Republic of China
| | - Jinjiang Lin
- Department of Radiology, The First Affiliated Hospital, Sun Yat-Sen University, 58 Zhongshan II Road, Guangzhou, Guangdong, 510080, People's Republic of China
| | - Jiayu Fang
- Department of Radiology, The First Affiliated Hospital, Sun Yat-Sen University, 58 Zhongshan II Road, Guangzhou, Guangdong, 510080, People's Republic of China
| | - Qiapeng Huang
- Department of Gastrointestinal Surgery, The First Affiliated Hospital, Sun Yat-Sen University, 58 Zhongshan II Road, Guangzhou, Guangdong, People's Republic of China
| | - Haipeng Wang
- Medical AI Lab, School of Biomedical Engineering, Shenzhen University Medical School, Shenzhen University, Shenzhen, Guangdong, People's Republic of China
| | - Zhuya Zhang
- Medical AI Lab, School of Biomedical Engineering, Shenzhen University Medical School, Shenzhen University, Shenzhen, Guangdong, People's Republic of China
| | - Ren Mao
- Department of Gastroenterology, The First Affiliated Hospital, Sun Yat-Sen University, 58 Zhongshan II Road, Guangzhou, Guangdong, People's Republic of China
| | - Shi-Ting Feng
- Department of Radiology, The First Affiliated Hospital, Sun Yat-Sen University, 58 Zhongshan II Road, Guangzhou, Guangdong, 510080, People's Republic of China
| | - Xuehua Li
- Department of Radiology, The First Affiliated Hospital, Sun Yat-Sen University, 58 Zhongshan II Road, Guangzhou, Guangdong, 510080, People's Republic of China
| | - Bingsheng Huang
- Medical AI Lab, School of Biomedical Engineering, Shenzhen University Medical School, Shenzhen University, Shenzhen, Guangdong, People's Republic of China
| | - Zhoulei Li
- Department of Radiology, The First Affiliated Hospital, Sun Yat-Sen University, 58 Zhongshan II Road, Guangzhou, Guangdong, 510080, People's Republic of China.
| | - Jian Zhang
- Shenzhen-Hong Kong Institute of Brain Science-Shenzhen Fundamental Research Institutions, Shenzhen, Guangdong, People's Republic of China.
- Health Science Center, School of Biomedical Engineering, Shenzhen University, Shenzhen, Guangdong, People's Republic of China.
| | - Zhihui Chen
- Department of Gastrointestinal Surgery, The First Affiliated Hospital, Sun Yat-Sen University, 58 Zhongshan II Road, Guangzhou, Guangdong, People's Republic of China.
- Guangxi Hospital Division of The First Affiliated Hospital, Sun Yat-sen University, Nanning, Guangxi, People's Republic of China.
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9
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Schineis CHW, Pozios I, Boubaris K, Weixler B, Kamphues C, Margonis GA, Kreis ME, Strobel RM, Beyer K, Seifarth C, Luitjens J, Kaufmann D, Lauscher JC. Role of visceral fat on postoperative complications and relapse in patients with Crohn's disease after ileocecal resection: Is it overrated? Int J Colorectal Dis 2024; 39:20. [PMID: 38240842 PMCID: PMC10798911 DOI: 10.1007/s00384-023-04586-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 12/21/2023] [Indexed: 01/22/2024]
Abstract
INTRODUCTION The role of visceral fat in disease development, particularly in Crohn´s disease (CD), is significant. However, its preoperative prognostic value for postoperative complications and CD relapse after ileocecal resection (ICR) remains unknown. This study aims to assess the predictive potential of preoperatively measured visceral and subcutaneous fat in postoperative complications and CD recurrence using magnetic resonance imaging (MRI). The primary endpoint was postoperative anastomotic leakage of the ileocolonic anastomosis, with secondary endpoints evaluating postoperative complications according to the Clavien Dindo classification and CD recurrence at the anastomosis. METHODS We conducted a retrospective analysis of 347 CD patients who underwent ICR at our tertiary referral center between 2010 and 2020. We included 223 patients with high-quality preoperative MRI scans, recording demographics, postoperative outcomes, and CD recurrence rates at the anastomosis. To assess adipose tissue distribution, we measured total fat area (TFA), visceral fat area (VFA), subcutaneous fat area (SFA), and abdominal circumference (AC) at the lumbar 3 (L3) level using MRI cross-sectional images. Ratios of these values were calculated. RESULTS None of the radiological variables showed an association with anastomotic leakage (TFA p = 0.932, VFA p = 0.982, SFA p = 0.951, SFA/TFA p = 0.422, VFA/TFA p = 0.422), postoperative complications, or CD recurrence (TFA p = 0.264, VFA p = 0.916, SFA p = 0.103, SFA/TFA p = 0.059, VFA/TFA p = 0.059). CONCLUSIONS Radiological visceral obesity variables were associated with postoperative outcomes or clinical recurrence in CD patients undergoing ICR. Preoperative measurement of visceral fat measurement is not specific for predicting postoperative complications or CD relapse.
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Affiliation(s)
- Christian Hans Wolfgang Schineis
- Department of General and Visceral Surgery, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, 12203, Berlin, Germany.
| | - Ioannis Pozios
- Department of General and Visceral Surgery, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, 12203, Berlin, Germany
| | - Katharina Boubaris
- Department of General and Visceral Surgery, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, 12203, Berlin, Germany
| | - Benjamin Weixler
- Department of General and Visceral Surgery, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, 12203, Berlin, Germany
| | - Carsten Kamphues
- Department of General- and Visceral Surgery, Schloßparkklinik, Berlin, Germany
| | | | - Martin Ernst Kreis
- Department of General and Visceral Surgery, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, 12203, Berlin, Germany
| | - Rahel Maria Strobel
- Department of General and Visceral Surgery, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, 12203, Berlin, Germany
| | - Katharina Beyer
- Department of General and Visceral Surgery, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, 12203, Berlin, Germany
| | - Claudia Seifarth
- Department of General and Visceral Surgery, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, 12203, Berlin, Germany
| | - Jan Luitjens
- Department of Diagnostic and Interventional Radiology and Neuroradiology, University Hospital Augsburg, Augsburg, Germany
| | - David Kaufmann
- Department of Diagnostic and Interventional Radiology and Neuroradiology, University Hospital Augsburg, Augsburg, Germany
| | - Johannes Christian Lauscher
- Department of General and Visceral Surgery, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, 12203, Berlin, Germany
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10
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Wojcik-Grzybek D, Sliwowski Z, Kwiecien S, Ginter G, Surmiak M, Hubalewska-Mazgaj M, Chmura A, Wojcik A, Kosciolek T, Danielak A, Targosz A, Strzalka M, Szczyrk U, Ptak-Belowska A, Magierowski M, Bilski J, Brzozowski T. Alkaline Phosphatase Relieves Colitis in Obese Mice Subjected to Forced Exercise via Its Anti-Inflammatory and Intestinal Microbiota-Shaping Properties. Int J Mol Sci 2024; 25:703. [PMID: 38255781 PMCID: PMC10815191 DOI: 10.3390/ijms25020703] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/11/2023] [Revised: 12/28/2023] [Accepted: 01/02/2024] [Indexed: 01/24/2024] Open
Abstract
Intestinal alkaline phosphatase (IAP) is an enzyme that plays a protective role in the gut. This study investigated the effect of IAP treatment on experimental colitis in mice subjected to forced exercise on a high-fat diet. C57BL/6 mice with TNBS colitis were fed a high-fat diet and subjected to forced treadmill exercise with or without IAP treatment. Disease activity, oxidative stress, inflammatory cytokines, and gut microbiota were assessed. Forced exercise exacerbated colitis in obese mice, as evidenced by increased disease activity index (DAI), oxidative stress markers, and proinflammatory adipokines and cytokines. IAP treatment significantly reduced these effects and promoted the expression of barrier proteins in the colonic mucosa. Additionally, IAP treatment altered the gut microbiota composition, favoring beneficial Verrucomicrobiota and reducing pathogenic Clostridia and Odoribacter. IAP treatment ameliorates the worsening effect of forced exercise on murine colitis by attenuating oxidative stress, downregulating proinflammatory biomarkers, and modulating the gut microbiota. IAP warrants further investigation as a potential therapeutic strategy for ulcerative colitis.
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Affiliation(s)
- Dagmara Wojcik-Grzybek
- Department of Physiology, Faculty of Medicine, Jagiellonian University Medical College, 31-531 Cracow, Poland; (D.W.-G.); (S.K.); (G.G.)
| | - Zbigniew Sliwowski
- Department of Physiology, Faculty of Medicine, Jagiellonian University Medical College, 31-531 Cracow, Poland; (D.W.-G.); (S.K.); (G.G.)
| | - Slawomir Kwiecien
- Department of Physiology, Faculty of Medicine, Jagiellonian University Medical College, 31-531 Cracow, Poland; (D.W.-G.); (S.K.); (G.G.)
| | - Grzegorz Ginter
- Department of Physiology, Faculty of Medicine, Jagiellonian University Medical College, 31-531 Cracow, Poland; (D.W.-G.); (S.K.); (G.G.)
| | - Marcin Surmiak
- Department of Internal Medicine, Faculty of Medicine, Jagiellonian University Medical College, 31-008 Cracow, Poland
| | - Magdalena Hubalewska-Mazgaj
- Department of Physiology, Faculty of Medicine, Jagiellonian University Medical College, 31-531 Cracow, Poland; (D.W.-G.); (S.K.); (G.G.)
| | - Anna Chmura
- Department of Physiology, Faculty of Medicine, Jagiellonian University Medical College, 31-531 Cracow, Poland; (D.W.-G.); (S.K.); (G.G.)
| | - Adrianna Wojcik
- Department of Physiology, Faculty of Medicine, Jagiellonian University Medical College, 31-531 Cracow, Poland; (D.W.-G.); (S.K.); (G.G.)
| | - Tomasz Kosciolek
- Malopolska Centre of Biotechnology, Jagiellonian University, 30-387 Cracow, Poland
| | - Aleksandra Danielak
- Department of Physiology, Faculty of Medicine, Jagiellonian University Medical College, 31-531 Cracow, Poland; (D.W.-G.); (S.K.); (G.G.)
| | - Aneta Targosz
- Department of Physiology, Faculty of Medicine, Jagiellonian University Medical College, 31-531 Cracow, Poland; (D.W.-G.); (S.K.); (G.G.)
| | - Malgorzata Strzalka
- Department of Physiology, Faculty of Medicine, Jagiellonian University Medical College, 31-531 Cracow, Poland; (D.W.-G.); (S.K.); (G.G.)
| | - Urszula Szczyrk
- Department of Physiology, Faculty of Medicine, Jagiellonian University Medical College, 31-531 Cracow, Poland; (D.W.-G.); (S.K.); (G.G.)
| | - Agata Ptak-Belowska
- Department of Physiology, Faculty of Medicine, Jagiellonian University Medical College, 31-531 Cracow, Poland; (D.W.-G.); (S.K.); (G.G.)
| | - Marcin Magierowski
- Department of Physiology, Faculty of Medicine, Jagiellonian University Medical College, 31-531 Cracow, Poland; (D.W.-G.); (S.K.); (G.G.)
| | - Jan Bilski
- Department of Biomechanics and Kinesiology, Chair of Biomedical Sciences, Faculty of Health Sciences, Jagiellonian University Medical College, 31-008 Cracow, Poland;
| | - Tomasz Brzozowski
- Department of Physiology, Faculty of Medicine, Jagiellonian University Medical College, 31-531 Cracow, Poland; (D.W.-G.); (S.K.); (G.G.)
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11
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Kaazan P, Seow W, Yong S, Heilbronn LK, Segal JP. The Impact of Obesity on Inflammatory Bowel Disease. Biomedicines 2023; 11:3256. [PMID: 38137477 PMCID: PMC10740941 DOI: 10.3390/biomedicines11123256] [Citation(s) in RCA: 7] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/14/2023] [Revised: 12/01/2023] [Accepted: 12/05/2023] [Indexed: 12/24/2023] Open
Abstract
Obesity is prevalent in the inflammatory bowel disease (IBD) population, particularly in newly developed countries where both IBD and obesity in the general population are on the rise. The role of obesity in the pathogenesis of IBD was entertained but results from available studies are conflicting. It does, however, appear to negatively influence disease course whilst impacting on our medical and surgical therapies. The pro-inflammatory profile of the visceral adipose tissue might play a role in the pathogenesis and course of Crohn's Disease (CD). Interestingly, isolating the mesentery from the surgical anastomosis using a KONO-S technique significantly decreases anastomotic recurrence rate. Anti-obesity therapy is not widely used in IBD but was suggested as an adjunctive therapy in those patients. In this review, we aimed to highlight the epidemiology of obesity in IBD and to describe its influence on disease course and outcomes.
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Affiliation(s)
- Patricia Kaazan
- Faculty of Health and Medical Sciences, School of Medicine, University of Adelaide, Adelaide, SA 5005, Australia (S.Y.)
- South Australian Health and Medical Research Institute, Adelaide, SA 5000, Australia
- IBDSA, Tennyson Centre, Kurralta Park, SA 5037, Australia
| | - Warren Seow
- Faculty of Health and Medical Sciences, School of Medicine, University of Adelaide, Adelaide, SA 5005, Australia (S.Y.)
- Department of Surgery, Flinders Medical Centre, Adelaide, SA 5042, Australia
| | - Shaanan Yong
- Faculty of Health and Medical Sciences, School of Medicine, University of Adelaide, Adelaide, SA 5005, Australia (S.Y.)
| | - Leonie K. Heilbronn
- Faculty of Health and Medical Sciences, School of Medicine, University of Adelaide, Adelaide, SA 5005, Australia (S.Y.)
- South Australian Health and Medical Research Institute, Adelaide, SA 5000, Australia
| | - Jonathan P. Segal
- Department of Gastroenterology, Royal Melbourne Hospital, Melbourne, VIC 3052, Australia;
- Department of Medicine, University of Melbourne, Melbourne, VIC 3052, Australia
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12
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Hwang N, Kang D, Shin SJ, Yoon BK, Chun J, Kim JW, Fang S. Creeping fat exhibits distinct Inflammation-specific adipogenic preadipocytes in Crohn's disease. Front Immunol 2023; 14:1198905. [PMID: 38111581 PMCID: PMC10725931 DOI: 10.3389/fimmu.2023.1198905] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/02/2023] [Accepted: 11/17/2023] [Indexed: 12/20/2023] Open
Abstract
Creeping fat (CrF) is an extraintestinal manifestation observed in patients with Crohn's disease (CD). It is characterized by the accumulation of mesenteric adipose tissue (MAT) that wraps around the intestinal wall. Although the role of CrF in CD is still debated, multiple studies have highlighted a correlation between CrF and inflammation, as well as fibrostenosais of the intestine, which contributes to the worsening of CD symptoms. However, the mechanism underlying the potential role of CrF in the development of Crohn's fibrosis remains an enigma. This study aimed to analyze CrF comprehensively using single-cell RNA sequencing analysis. The data was compared with transcriptomic data from adipose tissue in other disease conditions, such as ulcerative colitis, lymphedema, and obesity. Our analysis classified two lineages of preadipocyte (PAC) clusters responsible for adipogenesis and fibrosis in CrF. Committed PACs in CrF showed increased cytokine expression in response to bacterial stimuli, potentially worsening inflammation in patients with CD. We also observed an increase in fibrotic activity in PAC clusters in CrF. Co-analyzing the data from patients with lymphedema, we found that pro-fibrotic PACs featured upregulated pentraxin-3 expression, suggesting a potential target for the treatment of fibrosis in CrF. Furthermore, PACs in CrF exhibited a distinct increase in cell-to-cell communication via cytokines related to inflammation and fibrosis, such as CCL, LIGHT, PDGF, MIF, and SEMA3. Interestingly, these interactions also increased in PACs of the lymphedema, whereas the increased MIF signal of PACs was found to be a distinct characteristic of CrF. In immune cell clusters in CrF, we observed high immune activity of pro-inflammatory macrophages, antigen-presenting macrophages, B cells, and IgG+ plasma cells. Finally, we have demonstrated elevated IgG+ plasma cell infiltration and increased pentraxin-3 protein levels in the fibrotic regions of CrF in CD patients when compared to MAT from both UC patients and healthy individuals. These findings provide new insights into the transcriptomic features related to the inflammation of cells in CrF and suggest potential targets for attenuating fibrosis in CD.
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Affiliation(s)
- Nahee Hwang
- Department of Biochemistry and Molecular Biology, Yonsei University College of Medicine, Seoul, Republic of Korea
- Graduate School of Medical Science, Brain Korea 21 Project, Yonsei University College of Medicine, Seoul, Republic of Korea
- Chronic Intractable Disease for Systems Medicine Research Center, Yonsei University College of Medicine, Seoul, Republic of Korea
| | - Dongwoo Kang
- Department of Medicine, Yonsei University College of Medicine, Seoul, Republic of Korea
| | - Su-Jin Shin
- Department of Pathology, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul, Republic of Korea
| | - Bo Kyung Yoon
- Department of Biochemistry and Molecular Biology, Yonsei University College of Medicine, Seoul, Republic of Korea
- Chronic Intractable Disease for Systems Medicine Research Center, Yonsei University College of Medicine, Seoul, Republic of Korea
| | - Jaeyoung Chun
- Department of Internal Medicine, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul, Republic of Korea
| | - Jae-woo Kim
- Department of Biochemistry and Molecular Biology, Yonsei University College of Medicine, Seoul, Republic of Korea
- Chronic Intractable Disease for Systems Medicine Research Center, Yonsei University College of Medicine, Seoul, Republic of Korea
| | - Sungsoon Fang
- Graduate School of Medical Science, Brain Korea 21 Project, Yonsei University College of Medicine, Seoul, Republic of Korea
- Chronic Intractable Disease for Systems Medicine Research Center, Yonsei University College of Medicine, Seoul, Republic of Korea
- Department of Biomedical Sciences, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul, Republic of Korea
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13
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Steigleder KM, Pascoal LB, Siqueira NSN, Simino LADP, Ayrizono MDLS, Ferreira MM, Fagundes JJ, Azevedo ATD, Torsoni AS, Leal RF. Mathematical Models Including microRNA Levels of Mesenteric Adipose Tissue May Predict Postoperative Relapse in Crohn's Disease Patients. GASTRO HEP ADVANCES 2023; 3:17-30. [PMID: 39132178 PMCID: PMC11307883 DOI: 10.1016/j.gastha.2023.08.020] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 03/27/2023] [Accepted: 08/21/2023] [Indexed: 08/13/2024]
Abstract
Background and Aims Recent evidence suggests that the mesenteric adipose tissue (MAT) near the affected intestine may play a role in Crohn's disease (CD) pathophysiology. Modulation of several transcripts has already been identified in the MAT of CD in the literature. Therefore, our aim was to validate the microRNA (miRNA) transcript levels and their target genes in the MAT of active CD patients and correlate them with clinical and epidemiological data. Methods Samples from the MAT of surgical specimens from 25 active CD patients were obtained. The control group comprised fifteen patients who underwent surgery for other diseases, except inflammatory bowel diseases. Transcriptional levels of miRNA and their target genes were assessed by quantitative real-time polymerase chain reaction. The correlation between transcripts and clinical characteristics was obtained using multiple linear regression. The mathematical models (M) underwent a statistical filter to ensure robustness and reliability (P value < .05; adjusted R-squared (Rˆ2)> .99; correct predictions of more than 60%). Results miRNA-650 and miRNA-29c were upregulated in the MAT of CD compared to the control group (P < .0001 and P = .0032, respectively), besides presenting decreased levels of their target genes. Two were target genes of the miRNA-650: glutamine-fructose-6-phosphate transaminase 2 (P = .012) and aldehyde dehydrogenase 4 family (P = .0035); and 4 were targets of the miRNA-29c: cell death-inducing DFFA-like effector c (P = .001), E2F transcription factor-1 (P = .007), hypoxia-inducible factor 3 subunit alpha (P = .0029), and pyruvate dehydrogenase kinase 4 (P = .0054). We found 2 M with statistical strength and robustness. The performance test identified one model with 100% accuracy for predicting the month of recurrence and determining patients with less risk of early relapse after surgery. Conclusion We demonstrate that miRNA-650 and miRNA-29c and some of their target genes, besides clinical and epidemiological variables, may be useful in a model to predict when disease relapse may occur in CD patients who underwent surgery. These findings constitute a potential tool to guide postoperative clinical management.
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Affiliation(s)
- Karine Mariane Steigleder
- Inflammatory Bowel Diseases Research Laboratory, Gastrocenter, Colorectal Surgery Unit, Surgery Department, School of Medical Sciences, University of Campinas (Unicamp), Campinas, São Paulo, Brazil
| | - Lívia Bitencourt Pascoal
- Inflammatory Bowel Diseases Research Laboratory, Gastrocenter, Colorectal Surgery Unit, Surgery Department, School of Medical Sciences, University of Campinas (Unicamp), Campinas, São Paulo, Brazil
| | - Natália Souza Nunes Siqueira
- Inflammatory Bowel Diseases Research Laboratory, Gastrocenter, Colorectal Surgery Unit, Surgery Department, School of Medical Sciences, University of Campinas (Unicamp), Campinas, São Paulo, Brazil
| | - Laís Angélica de Paula Simino
- Laboratory of Metabolic Disorders, School of Applied Sciences, University of Campinas (Unicamp), Limeira, São Paulo, Brazil
| | - Maria de Lourdes Setsuko Ayrizono
- Inflammatory Bowel Diseases Research Laboratory, Gastrocenter, Colorectal Surgery Unit, Surgery Department, School of Medical Sciences, University of Campinas (Unicamp), Campinas, São Paulo, Brazil
| | - Marciane Milanski Ferreira
- Laboratory of Metabolic Disorders, School of Applied Sciences, University of Campinas (Unicamp), Limeira, São Paulo, Brazil
| | - João José Fagundes
- Inflammatory Bowel Diseases Research Laboratory, Gastrocenter, Colorectal Surgery Unit, Surgery Department, School of Medical Sciences, University of Campinas (Unicamp), Campinas, São Paulo, Brazil
| | - Aníbal Tavares de Azevedo
- Simulation Laboratory, School of Applied Sciences, University of Campinas (Unicamp), Limeira, Brazil
| | - Adriana Souza Torsoni
- Laboratory of Metabolic Disorders, School of Applied Sciences, University of Campinas (Unicamp), Limeira, São Paulo, Brazil
| | - Raquel Franco Leal
- Inflammatory Bowel Diseases Research Laboratory, Gastrocenter, Colorectal Surgery Unit, Surgery Department, School of Medical Sciences, University of Campinas (Unicamp), Campinas, São Paulo, Brazil
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14
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Nagayoshi K, Mizuuchi Y, Zhang J, Hisano K, Tamura K, Sada M, Nakata K, Ohuchida K, Nakamura M. Strong impact of sarcopenic state defined by skeletal muscle mass index on postoperative complication of Crohn's disease patients. Surg Open Sci 2023; 15:54-59. [PMID: 37609367 PMCID: PMC10440350 DOI: 10.1016/j.sopen.2023.07.022] [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: 05/01/2023] [Revised: 07/27/2023] [Accepted: 07/29/2023] [Indexed: 08/24/2023] Open
Abstract
Background Malnutrition impacts the clinical course of Crohn's disease; however, there is little evidence of its influence on perioperative adverse events. We assessed whether nutritional indicators are associated with postoperative complications in surgical treatment of Crohn's disease. Methods 137 patients with Crohn's disease who underwent surgical treatment between January 2011 and December 2020 were included. Skeletal muscle index was calculated by a single CT slice. We analyzed the risk factors for adverse events. Results 37 % of patients had postoperative complications. Adverse events occurred more frequently in patients with high serum C-reactive protein, low serum albumin, prognostic nutritional index <38.3, skeletal muscle index <38.9 cm2/m2, abdominoperineal resection, long surgical duration, and mass hemorrhage. Among patients with skeletal muscle index <38.9 cm2/m2, patients who experienced adverse events had higher visceral fat index compared with those who did not (0.85 vs. 0.45, P = 0.04). Multivariate analysis revealed that skeletal muscle index <38.9 cm2/m2 and low serum albumin were the independent risk factors for postoperative complications (Odds ratio, 2.85; 95 % confidence interval, 1.13-7.16; P = 0.03, 2.62; 1.09-6.26; P = 0.03, respectively). Separated by sex, low serum albumin (<3.5 and <2.8 g/dL, male and female, respectively) and skeletal muscle index (<38.9 and <36.6 cm2/m2, male and female, respectively) were statistically related to postoperative complications. Conclusions Skeletal muscle index is the most useful nutritional predictor of postoperative complications in Crohn's disease patients among other nutritional indices. We believe that these patients are at high risk of postoperative complications and need appropriate nutritional support in the perioperative period.
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Affiliation(s)
- Kinuko Nagayoshi
- Department of Surgery and Oncology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
| | - Yusuke Mizuuchi
- Department of Surgery and Oncology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
| | - Jinghui Zhang
- Department of Surgery and Oncology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
| | - Kyoko Hisano
- Department of Surgery and Oncology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
| | - Koji Tamura
- Department of Surgery and Oncology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
| | - Masafumi Sada
- Department of Surgery and Oncology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
| | - Kohei Nakata
- Department of Surgery and Oncology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
| | - Kenoki Ohuchida
- Department of Surgery and Oncology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
| | - Masafumi Nakamura
- Department of Surgery and Oncology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
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15
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Zuo L, Geng Z, Song X, Li J, Wang Y, Zhang X, Ge S, Wang L, Liu G, Zhang L, Xu M, Zhao Y, Shen L, Ge Y, Wu R, Hu J. Browning of Mesenteric White Adipose Tissue in Crohn's Disease: A New Pathological Change and Therapeutic Target. J Crohns Colitis 2023; 17:1179-1192. [PMID: 36932969 DOI: 10.1093/ecco-jcc/jjad046] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/24/2022] [Indexed: 03/19/2023]
Abstract
BACKROUND Hypertrophic mesenteric adipose tissue [htMAT] is a distinctive hallmark of Crohn's disease [CD], and it affects enteritis via inflammatory adipokine secretion by dysfunctional white adipocytes. White adipocytes can become beige adipocytes, which are characterized by active lipid consumption and favourable endocrine function, via white adipocyte browning. Our study aimed to determine whether white adipocyte browning occurs in htMAT and its role in CD. METHODS White adipocyte browning was examined in MAT samples from CD patients and controls. Human MAT explants and primary mesenteric adipocytes were cultured for in vitro experiments. Mice with 2,4,6-trinitrobenzenesulphonic acid solution [TNBS]-induced colitis were used for in vivo studies. A β3-adrenergic receptor agonist [CL316,243] was used to induce white adipocyte browning, and IL-4/STAT6 signalling was analysed to explore the mechanism underlying the anti-inflammatory activity of beige adipocytes. RESULTS White adipocyte browning was observed in htMAT from CD patients, as shown by the appearance of uncoupling protein 1 [UCP1]-positive multilocular [beige] adipocytes with lipid-depleting activity and anti-inflammatory endocrine profiles. Both human MAT and primary mesenteric adipocytes from CD patients and controls could be induced to undergo browning, which increased their lipid-depleting and anti-inflammatory activities in vitro. Inducing MAT browning ameliorated mesenteric hypertrophy and inflammation as well as colitis in TNBS-treated mice in vivo. The anti-inflammatory activity of beige adipocytes was at least partially related to STAT6 signalling activation via the autocrine and paracrine effects of IL-4. CONCLUSION White adipocyte browning is a newly identified pathological change in htMAT of CD patients and a possible therapeutic target.
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Affiliation(s)
- Lugen Zuo
- Department of Gastrointestinal Surgery, First Affiliated Hospital of Bengbu Medical College, Bengbu, Anhui, China
| | - Zhijun Geng
- Department of Central Laboratory, First Affiliated Hospital of Bengbu Medical College, Bengbu, China
| | - Xue Song
- Department of Central Laboratory, First Affiliated Hospital of Bengbu Medical College, Bengbu, China
| | - Jing Li
- Department of Clinical Laboratory, First Affiliated Hospital of Bengbu Medical College, Bengbu, China
| | - Yueyue Wang
- Department of Clinical Laboratory, First Affiliated Hospital of Bengbu Medical College, Bengbu, China
| | - Xiaofeng Zhang
- Department of Central Laboratory, First Affiliated Hospital of Bengbu Medical College, Bengbu, China
| | - Sitang Ge
- Department of Gastrointestinal Surgery, First Affiliated Hospital of Bengbu Medical College, Bengbu, Anhui, China
| | - Lian Wang
- Department of Central Laboratory, First Affiliated Hospital of Bengbu Medical College, Bengbu, China
| | - Guangyong Liu
- Anhui Key Laboratory of Tissue Transplantation, Bengbu Medical College, Bengbu, China
| | - Lele Zhang
- Anhui Key Laboratory of Tissue Transplantation, Bengbu Medical College, Bengbu, China
| | - Mengyu Xu
- Anhui Key Laboratory of Tissue Transplantation, Bengbu Medical College, Bengbu, China
| | - Yajing Zhao
- Anhui Key Laboratory of Tissue Transplantation, Bengbu Medical College, Bengbu, China
| | - Li Shen
- Anhui Key Laboratory of Tissue Transplantation, Bengbu Medical College, Bengbu, China
| | - Yuanyuan Ge
- Department of Colorectal Surgery, The Third Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, China
| | - Rong Wu
- Department of General Surgery, Southeast University Zhongda Hospital, Nanjing, China
| | - Jianguo Hu
- Department of Central Laboratory, First Affiliated Hospital of Bengbu Medical College, Bengbu, China
- Department of Clinical Laboratory, First Affiliated Hospital of Bengbu Medical College, Bengbu, China
- Anhui Key Laboratory of Tissue Transplantation, Bengbu Medical College, Bengbu, China
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16
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Bikbavova GR, Livzan MA, Lisyutenko NS, Martynenko OV, Indutny AV. Prevalence of overweight and obesity in patients with ulcerative colitis: a case-control study. EXPERIMENTAL AND CLINICAL GASTROENTEROLOGY 2023:6-11. [DOI: 10.31146/1682-8658-ecg-212-4-6-11] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 09/17/2024]
Abstract
The incidence and prevalence of inflammatory bowel diseases (IBD) is growing in parallel with the obesity pandemic. The geography of the distribution of obesity and IBD on the planet have common features. In recent years, there has been information about the epidemiological interaction of predisposing factors to obesity and ulcerative colitis (UC). The aim of the study was to assess the prevalence of overweight and obesity in patients with UC in the Western Siberia region. Materials and methods: a case-control study of 165 ulcerative colitis was conducted in 56 healthy volunteers of comparable gender and age. Body mass index (BMI) was calculated using the formula: weight (kg)/weight (m2). Results: only in 7.9% of patients with UC BMI corresponded to a lack of body weight, in 48% BMI within normal parameters, in 43% of cases BMI corresponded to overweight and obesity. At the same time, the average values and median BMI in UC patients with acute and chronic course of the disease are close to the upper values of normal values. There are no gender differences in BMI compared to the control group. The BMI of patients with severe attack is significantly less than the BMI of patients with moderate attack. Hormonal dependence and resistance, the use of GIBP did not have a significant effect on the BMI of UC patients. In patients with UC, when compared with the control group, there are significantly more patients with type 2 diabetes mellitus. However, there was no significant relationship between the severity of the current attack among UC patients and the presence of type 2 diabetes mellitus in them. When comparing the group of patients with UC with the control group, there were no significant differences in the frequency of occurrence of NAFLD, cholelithiasis, coronary heart disease, arterial hypertension, while in patients with continuously recurrent UC, liver damage characteristic of NAFLD is significantly more common.
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17
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Tamura H. IgA nephropathy associated with Crohn's disease. World J Methodol 2023; 13:67-78. [PMID: 37456980 PMCID: PMC10348078 DOI: 10.5662/wjm.v13.i3.67] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/24/2023] [Revised: 04/16/2023] [Accepted: 05/12/2023] [Indexed: 06/20/2023] Open
Abstract
The relationship between IgA nephropathy (IgAN) and Crohn’s disease was reported. IgAN is the most common primary glomerulonephritis and one of the leading causes of chronic kidney disease and end-stage renal failure, and up to 50% of cases progressed to end-stage renal disease within 25 years after IgAN diagnosis. However, specific and effective therapeutic strategies are still lacking. In this review, we discuss the possibility of the mechanism involved in IgAN associated with Crohn’s disease based on the findings of basic and clinical studies. Although the etiology of IgAN associated with Crohn’s disease is not permanent and various factors are thought to be involved, the stabilization of the disease condition of Crohn’s disease is believed to help treat IgAN.
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Affiliation(s)
- Hiroshi Tamura
- Department of Pediatrics, Kumamoto University, Kumamoto 8608556, Japan
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18
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Mc Gettigan N, Allen K, Saeidi R, O’ Toole A, Boland K. A systematic review of the effect of structured exercise on inflammation and body composition in inflammatory bowel disease. Int J Colorectal Dis 2023; 38:143. [PMID: 37227593 PMCID: PMC10212817 DOI: 10.1007/s00384-023-04437-2] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 05/09/2023] [Indexed: 05/26/2023]
Abstract
PURPOSE Given the substantial risk of treatment failure in inflammatory bowel disease (IBD), adjuvant therapies may play a role in disease management. We aim to carry out a systematic review to examine the effects of structured exercise on the inflammatory response in patients with IBD. Our secondary aim is to examine the effect of structured exercise programmes on body composition given both an increase in visceral obesity and the presence of sarcopenia have deleterious effects on outcomes in IBD. METHODS A systematic review was carried out following the Methodological Expectations of Cochrane Intervention Reviews (MECIR) manual and the Cochrane Handbook for Systematic Reviews of Interventions. Title/Abstract and MeSH Terms were used to search for relevant studies. RESULTS In total, 1516 records were screened for eligibility, and 148 records were reviewed for eligibility, of which 16 were included and a further 7 studies were identified from hand searching references. Four studies included body composition outcomes, and 14 studies reviewed the inflammatory response to exercise. CONCLUSION Further studies of adequate duration are required to include patients with more active disease to demonstrate an inflammatory response to exercise. Body composition measurements including muscle mass and visceral adiposity may play a key role in response to medical therapy in IBD and should be included as exploratory outcomes in future studies. A meta-analysis was not carried out due to the significant heterogeneity amongst studies.
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Affiliation(s)
- Neasa Mc Gettigan
- Department of Medicine, Royal College of Surgeons in Ireland, Dublin, Ireland
- Department of Gastroenterology, Beaumont Hospital, Dublin, Ireland
| | - Kathryn Allen
- Department of Gastroenterology, Beaumont Hospital, Dublin, Ireland
| | - Reza Saeidi
- Department of Medicine, Royal College of Surgeons in Ireland, Dublin, Ireland
- Department of Gastroenterology, Beaumont Hospital, Dublin, Ireland
| | - Aoibhlinn O’ Toole
- Department of Medicine, Royal College of Surgeons in Ireland, Dublin, Ireland
- Department of Gastroenterology, Beaumont Hospital, Dublin, Ireland
| | - Karen Boland
- Department of Medicine, Royal College of Surgeons in Ireland, Dublin, Ireland
- Department of Gastroenterology, Beaumont Hospital, Dublin, Ireland
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Kono M, Shatila M, Xu G, Lu Y, Mathew A, Mohajir W, Varatharajalu K, Qiao W, Thomas AS, Wang Y. Obesity Measured via Body Mass Index May Be Associated with Increased Incidence but Not Worse Outcomes of Immune-Mediated Diarrhea and Colitis. Cancers (Basel) 2023; 15:2329. [PMID: 37190257 PMCID: PMC10136922 DOI: 10.3390/cancers15082329] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/13/2023] [Revised: 04/07/2023] [Accepted: 04/12/2023] [Indexed: 05/17/2023] Open
Abstract
Obesity defined by high body mass index (BMI) has traditionally been associated with gastrointestinal inflammatory processes but has recently been correlated with better survival in patients receiving immune checkpoint inhibitors (ICI). We sought to investigate the association between BMI and immune-mediated diarrhea and colitis (IMDC) outcomes and whether BMI reflects body fat content on abdominal imaging. This retrospective, single-center study included cancer patients with ICI exposure who developed IMDC and had BMI and abdominal computed tomography (CT) obtained within 30 days before initiating ICI from April 2011 to December 2019. BMI was categorized as <25, ≥25 but <30, and ≥30. Visceral fat area (VFA), subcutaneous fat area (SFA), total fat area (TFA: VFA+SFA), and visceral to subcutaneous fat (V/S) ratio were obtained from CT at the umbilical level. Our sample comprised 202 patients; 127 patients (62.9%) received CTLA-4 monotherapy or a combination, and 75 (37.1%) received PD-1/PD-L1 monotherapy. Higher BMIs ≥ 30 were associated with a higher incidence of IMDC than BMIs ≤ 25 (11.4% vs. 7.9%, respectively; p = 0.029). Higher grades of colitis (grade 3-4) correlated with lower BMI (p = 0.03). BMI level was not associated with other IMDC characteristics or did not influence overall survival (p = 0.83). BMI is strongly correlated with VFA, SFA, and TFA (p < 0.0001). Higher BMI at ICI initiation was linked to a higher incidence of IMDC but did not appear to affect outcomes. BMI strongly correlated with body fat parameters measured by abdominal imaging, suggesting its reliability as an obesity index.
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Affiliation(s)
- Miho Kono
- Department of Gastroenterology, Hepatology and Nutrition, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA
| | - Malek Shatila
- Department of Gastroenterology, Hepatology and Nutrition, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA
| | - Guofan Xu
- Department of Nuclear Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA
| | - Yang Lu
- Department of Nuclear Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA
| | - Antony Mathew
- Department of Internal Medicine, The University of Texas Health Science Center at Houston, Houston, TX 77030, USA
| | - Wasay Mohajir
- Department of Internal Medicine, The University of Texas Health Science Center at Houston, Houston, TX 77030, USA
| | - Krishnavathana Varatharajalu
- Department of Gastroenterology, Hepatology and Nutrition, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA
| | - Wei Qiao
- Department of Biostatistics, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA
| | - Anusha S. Thomas
- Department of Gastroenterology, Hepatology and Nutrition, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA
| | - Yinghong Wang
- Department of Gastroenterology, Hepatology and Nutrition, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA
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20
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Bashllari R, Molonia MS, Muscarà C, Speciale A, Wilde PJ, Saija A, Cimino F. Cyanidin-3-O-glucoside protects intestinal epithelial cells from palmitate-induced lipotoxicity. Arch Physiol Biochem 2023; 129:379-386. [PMID: 33021853 DOI: 10.1080/13813455.2020.1828480] [Citation(s) in RCA: 19] [Impact Index Per Article: 9.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/21/2022]
Abstract
CONTEXT Increased free fatty acids (FFAs) levels, typical in obesity condition, can contribute to systemic lipotoxicity and inflammation adversely influencing Inflammatory Bowel Disease development and progression. Anthocyanins possess health promoting properties mainly associated to the induction of Nrf2-regulated cytoprotective proteins. OBJECTIVE Using a novel experimental model, we evaluated the in vitro intracellular mechanisms involved in FFAs modulation of intestinal epithelial lipotoxicity and the protective effects of cyanidin-3-O-glucoside (C3G) in Caco-2 cells. RESULTS Caco-2 exposed to palmitic acid (PA) in the serosal (basolateral) side showed a combined state of epithelial inflammation, inducing NF-κB pathway and downstream cytokines, that was reverted by C3G apical pre-treatment. In addition, PA altered intracellular redox status and induced reactive oxygen species that were reduced by C3G via the redox-sensitive Nrf2 signalling. DISCUSSION AND CONCLUSION Results suggest that anti-inflammatory properties of anthocyanins, mediated by Nrf2, could represent an interesting tool for intestinal inflammatory disorders.
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Affiliation(s)
- Romina Bashllari
- Department of Chemical, Biological, Pharmaceutical and Environmental Sciences, University of Messina, Messina, Italy
| | - Maria Sofia Molonia
- Department of Chemical, Biological, Pharmaceutical and Environmental Sciences, University of Messina, Messina, Italy
- "Prof. Antonio Imbesi" Foundation, University of Messina, Messina, Italy
| | - Claudia Muscarà
- Department of Chemical, Biological, Pharmaceutical and Environmental Sciences, University of Messina, Messina, Italy
| | - Antonio Speciale
- Department of Chemical, Biological, Pharmaceutical and Environmental Sciences, University of Messina, Messina, Italy
| | - Peter J Wilde
- Food Innovation and Health Programme, Quadram Institute Bioscience, Norwich Research Park, UK
| | - Antonella Saija
- Department of Chemical, Biological, Pharmaceutical and Environmental Sciences, University of Messina, Messina, Italy
| | - Francesco Cimino
- Department of Chemical, Biological, Pharmaceutical and Environmental Sciences, University of Messina, Messina, Italy
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21
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Wang Y, Yao D, He Y, He Q, Li Y. Earlier anti-TNF therapy reduces the risk of malnutrition associated with alterations in body composition in patients with Crohn's disease. Front Nutr 2023; 10:1114758. [PMID: 36824176 PMCID: PMC9942154 DOI: 10.3389/fnut.2023.1114758] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/09/2022] [Accepted: 01/18/2023] [Indexed: 02/10/2023] Open
Abstract
Background Anti-TNF therapy has been found to exert an influence on long-term nutritional status and even reverse malnutrition in patients with Crohn's disease. Aims to observe the effect of anti-TNF therapy on nutritional status in patients with Crohn's disease, investigate the correlation between the timing of anti-TNF therapy and the human body composition and examine independent body composition factors for predicting malnutrition in these patients. Methods This was a retrospective study of 115 patients with Crohn's disease. Body composition parameters were assessed by bioelectrical impedance analysis. The nutritional status of the patients was determined by NRS2002 and MNA. Results The BMI, BFMI, FFMI, BCMI, SMI, BMC, intracellular water, protein and BMR were significantly lower in patients without any biologic agents (p < 0.05). Negative correlations were found between BMC, intracellular water, extracellular water, protein and BMR and the interval between the first symptom and first dose by Spearman's correlation analysis (r < 0, p < 0.05). Low BMI (OR 0.602, 95% CI 0.434-0.836, p = 0.002), low FFMI (OR 0.678, 95% CI 0.507-0.906, p = 0.009), and low BCMI (OR 0.564, 95% CI 0.367-0.868, p = 0.009) were independent risk factors for malnutrition in Crohn's disease patients. Anti-TNF therapy tended to reduce the malnutrition probability as assessed by Cox regression analysis (OR: 0.217, 95% CI 0.057-0.821, p = 0.024). Conclusion Body composition analysis is predictive of malnutrition in patients with Crohn's disease. Early application of anti-TNF therapy significantly affected skeletal muscle mass, fat mass and bone mineral content, supporting their long-term nutritional status and reducing their probability of malnutrition.
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Affiliation(s)
- Yuexin Wang
- Department of General Surgery, Shanghai Jiao Tong University School of Medicine Affiliated Ninth People's Hospital, Shanghai, China
| | - Danhua Yao
- Department of General Surgery, Shanghai Jiao Tong University School of Medicine Affiliated Ninth People's Hospital, Shanghai, China
| | - Yining He
- Biostatistics Office of Clinical Research Unit, Shanghai Jiao Tong University School of Medicine Affiliated Ninth People's Hospital, Shanghai, China
| | - Qi He
- Department of General Surgery, Shanghai Jiao Tong University School of Medicine Affiliated Ninth People's Hospital, Shanghai, China,*Correspondence: Qi He, ✉
| | - Yousheng Li
- Department of General Surgery, Shanghai Jiao Tong University School of Medicine Affiliated Ninth People's Hospital, Shanghai, China,Yousheng Li, ✉
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22
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Di Candido F. Quality of Life in Inflammatory Bowel Diseases (IBDs) Patients after Surgery. Rev Recent Clin Trials 2022; 17:227-239. [PMID: 35959618 DOI: 10.2174/1574887117666220811143426] [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: 11/07/2021] [Revised: 04/09/2022] [Accepted: 05/11/2022] [Indexed: 01/15/2023]
Abstract
Inflammatory Bowel Diseases (IBDs) are chronic, relapsing and disabling diseases that affect the gastrointestinal tract. This relapsing course is often unpredictable with severe flares and the need for intensive medical treatment, hospitalization, or emergent/urgent surgery, all of which significantly impact patients' quality of life (QoL). QoL in IBD patients is significantly lower than in the general population, and depression and anxiety have been shown to have a higher prevalence than in healthy individuals, especially during disease flares. Complications requiring hospitalization and repeated surgeries are not uncommon during the disease course and significantly affect QoL in IBD patients. Patient-reported outcome measures (PROMs) can be used to measure the impact of chronic disease on QoL from the patient's perspective. The use of PROMs in IBD patients undergoing surgery could help to investigate the impact of the surgical procedure on QoL and determine whether there is any improvement or worsening. This review summarizes the use of PROMs to assess QoL after various surgical procedures required for IBD treatment.
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Affiliation(s)
- Francesca Di Candido
- Division of General and Emergency Surgery, ASST Nord Milano, Sesto San Giovanni Hospital, Viale Matteotti, 83 - 20099 Sesto San Giovanni (MI) - Italy
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23
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Mc Gettigan N, Hanley M, Skelly F, Dowling J, Dunne R, Morrin MM, McCaffrey N, O'Toole A, Boland K. Impact of a physician-led exercise programme on quality of life, muscle mass and clinical response in inflammatory bowel disease patients during induction with disease-modifying therapy: a study protocol. BMJ Open Gastroenterol 2022. [DOI: 10.1136/bmjgast-2022-000959] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/04/2022] Open
Abstract
IntroductionBiologic and small-molecule therapies have revolutionised the treatment of moderate-to-severe inflammatory bowel disease (IBD). A significant proportion of patients experience early or delayed treatment failure. Patients with IBD with greater visceral obesity are less likely to respond to biologics. Sarcopenia has been identified as a predictor of disease severity and need for rescue therapy in acute severe ulcerative colitis. The aim of this study is to assess the feasibility of a physician-derived exercise programme in patients with IBD commencing biologic or small-molecule therapy in addition to the effect on physical fitness, body composition and objective measures of quality of life, fatigue scores and disease activity.Methods and analysisThis is a randomised controlled feasibility study comparing the effects of a physician-derived exercise programme and standard medical care (biologic/small-molecule therapy) with standard care alone in patients with moderate to severe IBD. Patients with IBD in the intervention group will undergo a structured exercise programme for 20 weeks. Both IBD groups will carry out body composition, disease activity and quality-of-life assessments at baseline, week 12 and week 26. The primary objective is to assess the feasibility of the physician-derived exercise programme in patients with IBD commencing disease-modifying therapies. Secondary endpoints include a change in cardiorespiratory fitness, disease activity/inflammation, fatigue, health-related quality of life outcomes and body composition between the two IBD groups. Exploratory endpoints include validation of anterior thigh ultrasound for sarcopenia screening, assessment of proinflammatory cytokines and markers of immunometabolism.Ethics and disseminationThis study has received ethical approval from the Beaumont Hospital Ethics committee on 22 October 2021 (reference number 21/21). Data generated or analysed during this study will be published as an article and supplementary appendix in relevant medical journals. The data will also be presented at national and international conferences.Trial registration numberNCT05174754.
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24
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Xiong S, Whitehurst CE, Li L, Heo GS, Lai CW, Jain U, Muegge BD, Espenschied ST, Musich RJ, Chen M, Liu Y, Liu TC, Stappenbeck TS. Reverse translation approach generates a signature of penetrating fibrosis in Crohn's disease that is associated with anti-TNF response. Gut 2022; 71:1289-1301. [PMID: 34261752 DOI: 10.1136/gutjnl-2020-323405] [Citation(s) in RCA: 16] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/19/2020] [Accepted: 06/28/2021] [Indexed: 12/14/2022]
Abstract
OBJECTIVE Fibrosis is a common feature of Crohn's disease (CD) which can involve the mesenteric fat. However, the molecular signature of this process remains unclear. Our goal was to define the transcriptional signature of mesenteric fibrosis in CD subjects and to model mesenteric fibrosis in mice to improve our understanding of CD pathogenesis. DESIGN We performed histological and transcriptional analysis of fibrosis in CD samples. We modelled a CD-like fibrosis phenotype by performing repeated colonic biopsies in mice and analysed the model by histology, type I collagen-targeted positron emission tomography (PET) and global gene expression. We generated a gene set list of essential features of mesenteric fibrosis and compared it to mucosal biopsy datasets from inflammatory bowel disease patients to identify a refined gene set that correlated with clinical outcomes. RESULTS Mesenteric fibrosis in CD was interconnected to areas of fibrosis in all layers of the intestine, defined as penetrating fibrosis. We found a transcriptional signature of differentially expressed genes enriched in areas of the mesenteric fat of CD subjects with high levels of fibrosis. Mice subjected to repeated colonic biopsies showed penetrating fibrosis as shown by histology, PET imaging and transcriptional analysis. Finally, we composed a composite 24-gene set list that was linked to inflammatory fibroblasts and correlated with treatment response. CONCLUSION We linked histopathological and molecular features of CD penetrating fibrosis to a mouse model of repeated biopsy injuries. This experimental system provides an innovative approach for functional investigations of underlying profibrotic mechanisms and therapeutic concepts in CD.
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Affiliation(s)
- Shanshan Xiong
- Department of Gastroenterology, Sun Yat-sen University First Affiliated Hospital, Guangzhou, China
| | - Charles E Whitehurst
- Department of Immunology and Respiratory Diseases Research, Boehringer Ingelheim Pharmaceuticals Inc, Ridgefield, Connecticut, USA
| | - Li Li
- Department of Global Computational Biology and Digital Sciences, Boehringer Ingelheim Pharmaceuticals Inc, Ridgefield, Connecticut, USA
| | - Gyu Seong Heo
- Washington University in St Louis, St Louis, Missouri, USA
| | - Chin-Wen Lai
- Washington University in St Louis, St Louis, Missouri, USA
| | - Umang Jain
- Washington University in St Louis, St Louis, Missouri, USA
| | - Brian D Muegge
- Washington University in St Louis, St Louis, Missouri, USA
| | | | - Ryan J Musich
- Inflammation and Immunity, Cleveland Clinic, Cleveland, Ohio, USA
| | - Minhu Chen
- Department of Gastroenterology, Sun Yat-sen University First Affiliated Hospital, Guangzhou, China
| | - Yongjian Liu
- Washington University in St Louis, St Louis, Missouri, USA
| | - Ta-Chiang Liu
- Department of Pathology and Immunology, Washington University in St Louis School of Medicine, St Louis, Missouri, USA
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Li J, Zuo L, Geng Z, Li Q, Cheng Y, Yang Z, Shi R, Zhou Y, Nie W, Wang Y, Zhang X, Ge S, Song X, Hu J. Pygopus2 ameliorates mesenteric adipocyte poor differentiation to alleviate Crohn's disease -like colitis via the Axin2/GSK3β pathway. Cell Prolif 2022; 55:e13292. [PMID: 35707871 PMCID: PMC9528773 DOI: 10.1111/cpr.13292] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/06/2022] [Revised: 05/29/2022] [Accepted: 05/31/2022] [Indexed: 12/21/2022] Open
Abstract
Objectives Crohn's disease (CD) mesenteric adipose tissue (MAT) inflammation affects enteritis through the interaction between the mesentery and intestine, and we previously found that poorly differentiated mesenteric adipocytes were related to its inflammatory features. Pygopus2 (Pygo2) is a key negative regulator of adipocyte differentiation. We aimed to determine whether Pygo2 participates in CD mesenteric lesions and whether Pygo2 knockdown would be beneficial in a CD model (Il‐10−/− mice). Methods Pygo2 expression in MAT from control and CD patients and Il‐10−/− mice was measured by immunohistochemistry. Lentiviral transfection was used to regulate Pygo2 expression in Il‐10−/− mice, and the effects on mesenteric adipocyte differentiation, inflammation, and dysfunction during spontaneous colitis, as well as the possible mechanism, were investigated. Results Pygo2 expression was increased in MAT from CD patients and Il‐10−/− mice, and its expression correlated with poor adipocyte differentiation and inflammation. Pygo2 knockdown significantly ameliorated colitis in Il‐10−/− mice. Moreover, the downregulation of Pygo2 gene expression could promote adipocyte differentiation and inhibit adipocyte inflammation in vivo and in vitro, and the effects were at least partly mediated by the Axis inhibition protein 2 (Axin2)/glycogen synthase kinase 3 beta (GSK3β) pathway. Conclusions The increase in Pygo2 may be related to mesenteric adipocyte poor differentiation and inflammatory features of CD, and Pygo2 inhibition could alleviate CD‐like colitis by improving mesenteric lesions by regulating the Axin2/GSK3β pathway.
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Affiliation(s)
- Jing Li
- Department of Clinical Laboratory, First Affiliated Hospital of Bengbu Medical College, Bengbu, China
| | - Lugen Zuo
- Department of Gastrointestinal Surgery, First Affiliated Hospital of Bengbu Medical College, Bengbu, China
| | - Zhijun Geng
- Department of Central Laboratory, First Affiliated Hospital of Bengbu Medical College, Bengbu, China
| | - Qingqing Li
- Department of Clinical Laboratory, First Affiliated Hospital of Bengbu Medical College, Bengbu, China
| | - Yang Cheng
- Department of Clinical Laboratory, First Affiliated Hospital of Bengbu Medical College, Bengbu, China
| | - Zi Yang
- Department of Gastrointestinal Surgery, First Affiliated Hospital of Bengbu Medical College, Bengbu, China
| | - Ruohan Shi
- Department of Clinical Medicine, Bengbu Medical College, Bengbu, China
| | - Yueqing Zhou
- Department of Clinical Medicine, Bengbu Medical College, Bengbu, China
| | - Wenhu Nie
- Department of Clinical Medicine, Bengbu Medical College, Bengbu, China
| | - Yueyue Wang
- Department of Clinical Laboratory, First Affiliated Hospital of Bengbu Medical College, Bengbu, China
| | - Xiaofeng Zhang
- Department of Central Laboratory, First Affiliated Hospital of Bengbu Medical College, Bengbu, China
| | - Sitang Ge
- Department of Gastrointestinal Surgery, First Affiliated Hospital of Bengbu Medical College, Bengbu, China
| | - Xue Song
- Department of Central Laboratory, First Affiliated Hospital of Bengbu Medical College, Bengbu, China
| | - Jianguo Hu
- Department of Clinical Laboratory, First Affiliated Hospital of Bengbu Medical College, Bengbu, China
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Liu Q, Zhang X, Ko HM, Stocker D, Ellman J, Chen J, Hao Y, Bhardwaj S, Liang Y, Cho J, Colombel JF, Taouli B, Harpaz N. Constrictive and Hypertrophic Strictures in Ileal Crohn's Disease. Clin Gastroenterol Hepatol 2022; 20:e1292-e1304. [PMID: 34400338 DOI: 10.1016/j.cgh.2021.08.012] [Citation(s) in RCA: 10] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/13/2021] [Revised: 08/05/2021] [Accepted: 08/09/2021] [Indexed: 02/07/2023]
Abstract
BACKGROUND & AIMS Strictures in Crohn's disease (CD) are classically attributed to fibromuscular hypertrophy of the intestinal wall. We have identified and characterized CD-related ileal strictures that result instead from mural constriction (ie, reduced external circumference). METHODS Twenty-four strictures and internal controls from 17 adults with obstructive CD were analyzed by cross-sectional morphometry. RESULTS The stricture-to-control circumference ratios (CRs) ranged from 0.53 to 1.7. Six strictures with CR ≥1.0, designated hypertrophic, had concentrically thickened walls, mean 3-fold increases in cross-sectional area and stainable fibromucular tissue, and high transmural inflammation scores. In contrast, 18 strictures with CR <1.0, designated constrictive, had thin, pliant walls, cross-sectional areas and stainable fibromuscular tissue comparable with control values, and low transmural inflammation scores. Eight mildly constrictive strictures also showed mild fibromuscular mural expansion that fell short of statistical significance. Twelve of 18 constrictive strictures (67%) occurred multiply (2-4 strictures per specimen) in contrast with hypertrophic strictures, all of which occurred singly (P = .01). Constriction correlated quantitatively with circumferential serosal fat wrapping (P = .003) and was associated with myenteric lymphocytic plexitis (P = .02). Disease duration was shortest among subjects with constrictive strictures and correlated with increasing circumference (CR ≤0.8, 6.3 ± 6.2 years; CR >0.8, 8.7 ± 6.4 years; and CR ≥1.00, 13.7 ± 5.0 years, respectively; P = .03). CONCLUSIONS Constrictive ileal strictures in CD differ pathologically and clinically from hypertrophic strictures, featuring little or no fibromuscular mural expansion, frequent multiplicity, and earlier onset. Mesenteric fat wrapping and myenteric plexitis may contribute to their pathogenesis. Pathologic manifestations of constriction and hypertrophy can coexist, suggesting that stricture heterogeneity may be shaped in part by the dynamics of constrictive and hypertrophic processes.
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Affiliation(s)
- Qingqing Liu
- Department of Pathology, Molecular and Cell-based Medicine, Icahn School of Medicine at Mount Sinai, New York, New York
| | - Xiaofei Zhang
- Department of Pathology and Laboratory Medicine, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin
| | - Huaibin Mabel Ko
- Department of Pathology, Molecular and Cell-based Medicine, Icahn School of Medicine at Mount Sinai, New York, New York; Dr Henry D. Janowitz Division of Gastroenterology, Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, New York
| | - Daniel Stocker
- Department of Diagnostic, Molecular and Interventional Radiology, Icahn School of Medicine at Mount Sinai, New York, New York
| | - Jordan Ellman
- Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, New York
| | - Joyce Chen
- Department of Pathology, Molecular and Cell-based Medicine, Icahn School of Medicine at Mount Sinai, New York, New York
| | - Yansheng Hao
- Department of Pathology, Molecular and Cell-based Medicine, Icahn School of Medicine at Mount Sinai, New York, New York
| | - Swati Bhardwaj
- Department of Pathology, Molecular and Cell-based Medicine, Icahn School of Medicine at Mount Sinai, New York, New York
| | - Yuanxin Liang
- Department of Pathology, Molecular and Cell-based Medicine, Icahn School of Medicine at Mount Sinai, New York, New York
| | - Judy Cho
- Dr Henry D. Janowitz Division of Gastroenterology, Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, New York; Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, New York
| | - Jean Frederic Colombel
- Dr Henry D. Janowitz Division of Gastroenterology, Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, New York
| | - Bachir Taouli
- Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, New York; Department of Diagnostic, Molecular and Interventional Radiology, Icahn School of Medicine at Mount Sinai, New York, New York
| | - Noam Harpaz
- Department of Pathology, Molecular and Cell-based Medicine, Icahn School of Medicine at Mount Sinai, New York, New York; Dr Henry D. Janowitz Division of Gastroenterology, Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, New York.
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Chuck W, Shadbolt BF, Nordin F, Subramaniam K. BMI is important in predicting the loss of response in inflammatory bowel disease patients on tumour necrosis factor-α inhibitors. Eur J Gastroenterol Hepatol 2022; 34:622-629. [PMID: 35352694 DOI: 10.1097/meg.0000000000002371] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/10/2022]
Abstract
INTRODUCTION Obesity is an emerging phenomenon among patients with inflammatory bowel disease (IBD). This study aims to evaluate whether the response to tumour necrosis factor-α (TNF-α) inhibitors (infliximab and adalimumab) could be influenced by BMI in IBD. METHODS We identified a cohort of 181 IBD patients attending a single-tertiary centre, naive to biologic therapy and stratified them according to their BMI. The primary outcome is the first occurrence of loss of response (LOR). RESULTS The median BMI was 26 kg/m2 (15-63 kg/m2). Approximately 68% of patients had LOR on both adalimumab (ADA) (n = 52) and infliximab (IFX) (n = 71). However, 83% on ADA with BMI ≥30 kg/m2 had LOR compared to 61% on IFX with BMI ≥30 kg/m2. For patients on ADA, Cox regression analysis revealed that after accounting for age, sex, disease type, duration of disease, fistulising disease, smoking status, haemoglobin, C-reactive protein, albumin and platelet levels, there were statistically significant associations between BMI (≥30 kg/m2 vs. <30 kg/m2) and LOR [P = 0.010; hazard ratio (HR) 3.2; confidence interval (CI), 1.3-7.6]. However, for patients on IFX, after accounting for the same factors, the only significant factor was the association of lower rate of LOR with higher albumin levels (P = 0.024; HR 0.95; CI, 0.91-0.99). There was an increased accelerated time to LOR for patients on ADA with BMI ≥30 kg/m2 compared to BMI <30 kg/m2 (P = 0.026). However, there was no difference in time to LOR for patients on IFX (P = 0.177). CONCLUSION BMI is important in predicting the LOR among IBD patients on TNF-α inhibitors, especially among patients receiving ADA.
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Affiliation(s)
- Winnie Chuck
- Gastroenterology and Hepatology Unit, Canberra Hospital
| | | | - Fariza Nordin
- Gastroenterology and Hepatology Unit, Canberra Hospital
| | - Kavitha Subramaniam
- Gastroenterology and Hepatology Unit, Canberra Hospital
- ANU Medical School, Australian National University, Canberra, Australian Capital Territory, Australia
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Abstract
BACKGROUND Rates of obesity are increasing worldwide, as is the incidence of inflammatory bowel disease (IBD). Obesity is now considered an inflammatory state. Visceral adiposity in particular may be associated with a more severe inflammatory phenotype in IBD. AIM The aim of this review article is to summarise the current literature on the association between visceral adiposity and outcomes in inflammatory bowel disease METHODS: To collect relevant articles, PubMed/MEDLINE and Embase searches were performed using Boolean search phrases. Grey literature and manual searches were also performed. Abstracts were selected by two independent reviewers based on pre-determined criteria. Full text articles were reviewed, and data extracted and assessed. RESULTS One hundred twenty-seven abstracts were obtained through the initial search, with 85 abstracts reviewed and 22 full text articles included. Characteristics are included in Table 1. Most of these were retrospective studies and of moderate or weak quality. Studies suggested visceral fat content is higher in Crohn's disease than in healthy controls. Visceral adiposity was associated with an increased risk of complex Crohn's disease phenotype (OR 26.1 95% CI 2-75.4; p = 0.02). Post-operative recurrence was higher in patients with higher visceral fat indices (RR 2.1; CI 1.5-3; p = 0.012). There were conflicting data regarding the effect of visceral adiposity on post-operative complications and the efficacy of medical therapy. Table 1 Study characteristics Author Year Country Study type Study numbers Control group Disease type Methodology e.g. CT Body composition measurements Results Argeny [24] 2018 Austria Retrospective cohort N = 95 N/A Crohn's disease CT; L3 level Visceral fat area (cm2) Visceral fat index (VFA/m2) No association between VFA or VFI and short-term post-operative outcomes Bryant [30] 2018 Australia Prospective cohort N = 110 N/A Crohn's disease and UC DXA Visceral adipose tissue (VAT) (cm3) Visceral adipose tissue (grams) VAT/height index (cm3/m2) VAT:subcutaneous adipose tissue ratio Fat mass index (kg/m2) VAT and VHI increased significantly over 24 months Bryant [13] 2018 Australia Prospective cohort N = 72 N/A Crohn's disease; female DXA Visceral adipose tissue (VAT) (cm3) Visceral adipose tissue (grams) VAT/height index (cm3/m2) VAT:subcutaneous adipose tissue ratio VAT:SAT positively associated with stricturing disease Adiposity not associated with fistulising disease phenotype VAT:SAT significantly associated with faecal calprotectin in L3 phenotype VAT:SAT significantly negatively associated with VHI and QoL over 24 months Buning [25] 2015 Germany Case control N = 50 N = 19 healthy controls Crohn's disease MRI US VAT Thickness of abdominal fat Distance to posterior wall of aorta Area of inferior part of perirenal fat VAT accumulation was higher in CD patients vs healthy controls VAT and VAT/fat mass ratio higher in patients in short-term remission vs long-term remission VAT/FM higher in stricturing/fistulising disease vs inflammatory subtype No association between VAT/FM and CDAI, HBI or anti-TNF treatment Connolly [26] 2014 US Retrospective cohort N = 143 N/A Crohn's disease CT (L1-L5 level) Visceral/intra-abdominal adiposity (VA) Subcutaneous adiposity (SA) VA not associated with post-operative morbidity Decreased SA and increased visceral/subcutaneous ratio were predictive of post-op complications. (p = 0.02; p < 0.001) Cravo [27] 2017 Portugal Retrospective cohort N = 71 N/A Crohn's disease CT (L3 level) Smooth muscle area (cm2) Visceral fat area (cm2) Subcutaneous fat area (cm2) Visceral fat index Muscle radiation attenuation L2 phenotype associated with lower muscle attenuation and higher visceral fat index (non-significant) B2/B3/surgery - significantly lower muscle attenuation. VFI associated with increased risk of complicated phenotype. (OR 26.1; 95% CI 1-75; p = 0.02) Ding [17] 2016 US Retrospective cohort N = 164 N/A Crohn's disease CT (L3 level) Visceral fat area (cm2) Subcutaneous fat area Total fat area Visceral obesity associated with longer duration of surgery, increased intra-operative blood loss and longer length of bowel resected Higher complication rates in patients with visceral obesity (p < 0.001) VFA independent risk factor of adverse post-op outcomes Ding [14] 2017 Retrospective cohort N = 106 N/A Crohn's disease CT (L3 level) Visceral fat area Subcutaneous fat area Skeletal muscle area Skeletal muscle index Visceral obesity and myopenic obesity not significantly associated with risk of primary non-response Body composition factors not associated with secondary loss of response Erhayiem [18] 2011 UK Retrospective cohort N = 50 N/A Crohn's disease CT (L4 level) Mesenteric fat index (visceral:subcutaneous area ratio)N = 50 Mesenteric fat index was significantly higher in complicated Crohn's disease. ROC analysis for MFI in identifying complicated Crohn's disease: AUC = 0.95 (95% CI 0.89-1.0) Feng [28] 2018 China Retrospective cohort N = 80 Non-IBD GI patients Crohn's disease CT-energy spectral Visceral fat area (cm2) Subcutaneous fat area (cm2) Mesenteric fat index No significant difference in VFA between Crohn's disease cohort and control group. (p = 0.669). ROC analysis: detection of disease based on VFA and MFI: AUC 0.776 Sensitivity 77.5% Specificity 67.5% Hafraoui [16] 1998 France/Belgium Prospective N = 43 Healthy volunteers n = 13 Intestinal resection n = 9 Crohn's disease MRI (umbilicus) Total abdominal fat (cm2) Intra-abdominal fat (cm2) Subcutaneous fat (cm2) Ratio of intra-abdominal:total fat area was significantly higher in patients with Crohn's vs controls. (p = 0.012) No correlation between abdominal fat tissue and disease activity, duration or steroid therapy Holt [29] 2017 Australia/New Zealand RCT N = 44 N = 11 placebo group Crohn's disease CT/MRI (L3, L4-5 levels) Visceral adipose tissue area Subcutaneous adipose tissue area Skeletal muscle area Visceral adipose tissue/height index VHI > 1.5 times gender mean was specific for endoscopic recurrence (100%) with sensitivity of 29%. PPV = 1 (0.59-1.00) There was no significant difference in disease activity at 18 months post-resection based on VHI > 1.5 gender mean Li [31] 2015 China Retrospective cohort N = 72 N/A Crohn's disease CT (umbilicus) Visceral fat area (cm2) Subcutaneous fat area (cm2) Mesenteric fat index Post-op recurrence was more frequent with high VFA values. (p = 0.019) VFA and MFI were independent risk factors for post-operative recurrence. (p = 0.013 and p = 0.028, respectively) High VFA and high MFI were significantly higher in patients with endoscopic activity (p = 0.023) Liu [32] 2016 Retrospective case-control N = 59 N = 30 (< 15% increase VFA) IBD with IPAA CT (L3) Visceral fat area Subcutaneous fat area No difference in pouchitis, pouch sinus formation and composite adverse pouch outcomes between the 2 groups with and without VFA increase > 15%. Excessive VAT gain was an independent risk factor for the composite adverse pouch outcomes. (OR 12.6 (95% CI 1.19-133.5) Magro [33] 2018 Brazil Cross-sectional study N = 78 N = 28 Health control Crohn's disease DEXA Fat and lean masses Visceral fat (kg) Visceral fat/BMI Visceral fat per %body fat VF was higher in Crohn's disease group (p = 0.004) compared to controls Parmentier-Decrucq [34] 2009 Prospective study N = 132 N/A Crohn's disease MRI Subcutaneous fat Visceral fat Total abdominal fat increased 18% in Crohn's disease patients treated with infliximab induction therapy Shen [35] 2018 China Retrospective N = 97 N/A Crohn's disease CT (umbilicus) Subcutaneous fat area Visceral fat area Mesenteric fat index VFA and MFI were significantly lower in patients with mucosal healing (post-infliximab). (p < 0.0001) SFA was not significantly different VFA correlated with CDAI (p < 0.001) and was an independent predictive factor for mucosal healing Stidham [15] 2015 Retrospective N = 269 N/A Crohn's disease CT(T10-L5) Subcutaneous fat volume Visceral fat volume No significant difference in visceral fat volume between patients with surgical complications Thiberge [36] 2018 France Retrospective N = 149 N/A Crohn's disease CT (L3 level) Skeletal muscle index Visceral adiposity index Subcutaneous adiposity index SAI and VAI were significantly lower in patients who underwent surgery or who died in 6 months post-CT(p = 0.009 and p < 0.001) VanDerSloot [37] 2017 Cohort study N/A Crohn's disease CT (T11-S5) Visceral adipose tissue volume Non-significant trend toward increased risk of surgery and penetrating disease with increasing VAT Wei [38] 2018 China Retrospective N = 86 N/A IBD post-resection CT (L3 level) Visceral adipose volume Subcutaneous adipose volume Increased visceral:subcutaneous fat ratio was associated with increased procalcitonin levels on post-op days 1, 3 and 5 Yadav [39] 2017 India Prospective N = 97 N/A IBD CT (L4 level) Visceral fat area Subcutaneous fat area No statistically significant correlation between visceral fat and disease behaviour in Crohn's disease N/A not applicable, VFA visceral fat area, VFI visceral fat index, VAT visceral adipose tissue, VHI visceral adipose tissue to height index, SAT subcutaneous adipose tissue, DXA dual-energy X-ray absorptiometry, CT computer tomography, MRI magnetic resonance imaging, US ultrasound, CDAI Crohn's disease activity index, HBI Harvey-Bradshaw Index, anti-TNF anti-tumour necrosis factor, SA subcutaneous adiposity, ROC receiver operating curve, AUC area under the curve, MFI mesenteric fat index, SAI subcutaneous adiposity index, PPV positive predictive value CONCLUSION: Visceral adiposity appears to be increased in Crohn's disease with some evidence that it is also associated with more complex disease phenotypes. There is also a signal that post-operative recurrence rates are affected by increasing mesenteric adiposity. There is a relative lack of data in UC patients and further high-quality studies are necessary to elucidate the relationship between visceral adiposity and IBD and the implications for patient outcomes.
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Johnson AM, Loftus EV. Obesity in inflammatory bowel disease: A review of its role in the pathogenesis, natural history, and treatment of IBD. Saudi J Gastroenterol 2021; 27:183-190. [PMID: 34169900 PMCID: PMC8448008 DOI: 10.4103/sjg.sjg_30_21] [Citation(s) in RCA: 22] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/21/2022] Open
Abstract
In contrast to previous perceptions that inflammatory bowel disease (IBD) patients are generally malnourished and underweight, there is mounting evidence to suggest that rates of obesity in IBD now mirror that of the general population. IBD is an immune-mediated condition that appears to develop in individuals who have not only a genetic predisposition to immune dysregulation but also likely exposure to various environmental factors which further potentiate this risk. With the surge in obesity alongside the rising incidence of IBD, particularly in developing nations, the role that obesity may play, not only in the pathogenesis but also in the natural history of disease has become a topic of growing interest. Currently available data exploring obesity's impact on the natural history of IBD are largely conflicting, potentially limited by the use of body mass index as a surrogate measure of obesity at varying time points throughout the disease course. While there are pharmacokinetic data to suggest possible detrimental effects that obesity may have on the response to medical therapy, results in this realm are also inconsistent. Moreover, not only is it unclear whether weight loss improves IBD outcomes, little is known about the safety and efficacy of available weight-loss strategies in this population. For these reasons, it becomes increasingly important to further understand the nature of any interaction between obesity and IBD.
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Affiliation(s)
- Amanda M. Johnson
- Division of Gastroenterology and Hepatology, Mayo Clinic, 200 First Street Southwest, Rochester, MN, USA,Address for correspondence: Dr. Amanda M. Johnson, Division of Gastroenterology and Hepatology, Mayo Clinic, 200 First Street Southwest, Rochester, MN - 55905, USA. E-mail:
| | - Edward V. Loftus
- Division of Gastroenterology and Hepatology, Mayo Clinic, 200 First Street Southwest, Rochester, MN, USA
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Intestinal Alkaline Phosphatase Combined with Voluntary Physical Activity Alleviates Experimental Colitis in Obese Mice. Involvement of Oxidative Stress, Myokines, Adipokines and Proinflammatory Biomarkers. Antioxidants (Basel) 2021; 10:antiox10020240. [PMID: 33557311 PMCID: PMC7914798 DOI: 10.3390/antiox10020240] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/28/2020] [Revised: 01/20/2021] [Accepted: 01/29/2021] [Indexed: 01/01/2023] Open
Abstract
Intestinal alkaline phosphatase (IAP) is an essential mucosal defense factor involved in the process of maintenance of gut homeostasis. We determined the effect of moderate exercise (voluntary wheel running) with or without treatment with IAP on the course of experimental murine 2,4,6-trinitrobenzenesulfonic acid (TNBS) colitis by assessing disease activity index (DAI), colonic blood flow (CBF), plasma myokine irisin levels and the colonic and adipose tissue expression of proinflammatory cytokines, markers of oxidative stress (SOD2, GPx) and adipokines in mice fed a standard diet (SD) or high-fat diet (HFD). Macroscopic and microscopic colitis in sedentary SD mice was accompanied by a significant decrease in CBF, and a significant increase in the colonic expression of tumor necrosis factor-alpha (TNF-α), IL-6, IL-1β and leptin mRNAs and decrease in the mRNA expression of adiponectin. These effects were aggravated in sedentary HFD mice but reduced in exercising animals, potentiated by concomitant treatment with IAP, especially in obese mice. Exercising HFD mice demonstrated a substantial increase in the mRNA for adiponectin and a decrease in mRNA leptin expression in intestinal mucosa and mesenteric fat as compared to sedentary animals. The expression of SOD2 and GPx mRNAs was significantly decreased in adipose tissue in HFD mice, but these effects were reversed in exercising mice with IAP administration. Our study shows for the first time that the combination of voluntary exercise and oral IAP treatment synergistically favored healing of intestinal inflammation, strengthened the antioxidant defense and ameliorated the course of experimental colitis; thus, IAP may represent a novel adjuvant therapy to alleviate inflammatory bowel disease (IBD) in humans.
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de Carvalho LGF, Lima WG, Coelho LGV, Cardoso VN, Fernandes SOA. Circulating Leptin Levels as a Potential Biomarker in Inflammatory Bowel Diseases: A Systematic Review and Meta-Analysis. Inflamm Bowel Dis 2021; 27:169-181. [PMID: 32095814 DOI: 10.1093/ibd/izaa037] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/23/2019] [Indexed: 12/20/2022]
Abstract
BACKGROUND The differential diagnosis of inflammatory bowel diseases (IBDs) between Crohn's disease (CD) and ulcerative colitis (UC) is important for designing an effective therapeutic regimen. However, without any adequate gold standard method for differential diagnosis currently, therapeutic design remains a major challenge in clinical practice. In this context, recent studies have showed that circulating leptin stands out as a potential biomarker for the categorization of IBDs. Thus, we aimed to summarize the current understanding of the prognostic and diagnostic value of serum leptin in patients with IBDs. METHODS A systematic search was performed in PubMed/MEDLINE, Scopus, Cochrane Library, and Web of Science databases. Articles that aimed to study the relationship between circulating levels of leptin and IBDs were included. Finally, the meta-analysis was performed with the mean serum leptin levels in patients with IBDs and healthy controls using RevMan 5.3 software, with I2 > 50% as a criterion for substantial heterogeneity. RESULTS Nineteen studies were included. Serum leptin levels among patients with IBDs and healthy controls did not show a significant difference (95% CI, -2.15 to 0.57; I2, 86%, P ≤ 0.00001). Similarly, there was no association of leptin levels with the activity of IBDs (95% CI, -0.24 to 0.06; I2, 50%; P = 0.13). However, serum leptin levels were significantly higher in patients with CD than those in patients with UC (95% CI, -2.09 to -0.37; I2, 7%; P ≤ 0.36). CONCLUSION This review suggested that serum leptin levels might be a promising biomarker to help in the differentiation between CD and UC.
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Affiliation(s)
- Larissa Gabriela Ferreira de Carvalho
- Laboratório de radioisótopos, Departamento de Análises Clínicas e Toxicológicas, Faculdade de Farmácia, Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brazil
| | - William Gustavo Lima
- Laboratório de radioisótopos, Departamento de Análises Clínicas e Toxicológicas, Faculdade de Farmácia, Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brazil
| | - Luiz Gonzaga Vaz Coelho
- Instituto ALFA de Gastrenterologia, Hospital das Clínicas, Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brazil
| | - Valbert Nascimento Cardoso
- Laboratório de radioisótopos, Departamento de Análises Clínicas e Toxicológicas, Faculdade de Farmácia, Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brazil
| | - Simone Odília Antunes Fernandes
- Laboratório de radioisótopos, Departamento de Análises Clínicas e Toxicológicas, Faculdade de Farmácia, Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brazil
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Li XH, Feng ST, Cao QH, Coffey JC, Baker ME, Huang L, Fang ZN, Qiu Y, Lu BL, Chen ZH, Li Y, Bettenworth D, Iacucci M, Sun CH, Ghosh S, Rieder F, Chen MH, Li ZP, Mao R. Degree of Creeping Fat Assessed by Computed Tomography Enterography is Associated with Intestinal Fibrotic Stricture in Patients with Crohn's Disease: A Potentially Novel Mesenteric Creeping Fat Index. J Crohns Colitis 2021; 15:1161-1173. [PMID: 33411893 PMCID: PMC8427713 DOI: 10.1093/ecco-jcc/jjab005] [Citation(s) in RCA: 49] [Impact Index Per Article: 12.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
BACKGROUND AND AIMS Emerging evidence points to a link between creeping fat and the pathogenesis of Crohn's disease [CD]. Non-invasive assessment of the severity of creeping fat on cross-sectional imaging modality has seldom been investigated. This study aimed to develop and characterize a novel mesenteric creeping fat index [MCFI] based on computed tomography [CT] in CD patients. METHODS MCFI was developed based on vascular findings on CT in a retrospective cohort [n = 91] and validated in a prospective cohort [n = 30]. The severity of creeping fat was graded based on the extent to which mesenteric fat extended around the intestinal circumference using the vessels in the fat as a marker. The accuracy of MCFI was assessed by comparing it with the degree of creeping fat observed in surgical specimens. The relationship between MCFI and fibrostenosis was characterized by determining if these correlated. The accuracy of MCFI was compared with other radiographic indices [i.e. visceral to subcutaneous fat area ratio and fibrofatty proliferation score]. RESULTS In the retrospective cohort, MCFI had moderate accuracy in differentiating moderate-severe from mild fibrostenosis (area under the receiver operating characteristic [ROC] curve [AUC] = 0.799; p = 0.000). ROC analysis in the retrospective cohort identified a threshold MCFI of > 3 which accurately differentiated fibrostenosis severity in the prospective cohort [AUC = 0.756; p = 0.018]. An excellent correlation was shown between MCFI and the extent of fat wrapping in specimens in the prospective cohort [r = 0.840, p = 0.000]. Neither visceral to subcutaneous fat area ratio nor fibrofatty proliferation score correlated well with the degree of intestinal fibrosis. CONCLUSIONS MCFI can accurately characterize the extent of mesenteric fat wrapping in surgical specimens. It may become another non-invasive measure of CD fibrostenosis.
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Affiliation(s)
- Xue-Hua Li
- Department of Radiology, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, Guangdong, People’s Republic of China
| | - Shi-Ting Feng
- Department of Radiology, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, Guangdong, People’s Republic of China
| | - Qing-Hua Cao
- Department of Pathology, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, Guangdong, People’s Republic of China
| | - J Calvin Coffey
- Department of Surgery, University Hospital Group Limerick and School of Medicine, University of Limerick, Limerick, Ireland
| | - Mark E Baker
- Section of Abdominal Imaging, Imaging Institute, Digestive Disease Institute and Cancer Institute, Cleveland Clinic, Cleveland, Ohio, USA
| | - Li Huang
- Department of Radiology, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, Guangdong, People’s Republic of China
| | - Zhuang-Nian Fang
- Department of Radiology, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, Guangdong, People’s Republic of China
| | - Yun Qiu
- Department of Gastroenterology, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, Guangdong, People’s Republic of China
| | - Bao-Lan Lu
- Department of Radiology, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, Guangdong, People’s Republic of China
| | - Zhi-Hui Chen
- Department of Gastrointestinal and Pancreatic Surgery, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, Guangdong, People’s Republic of China
| | - Yi Li
- Center for Inflammatory Bowel Diseases, Department of General Surgery, Jinling Hospital, Medical School of Nanjing University, Nanjing, Jiangsu, People’s Republic of China
| | - Dominik Bettenworth
- Department of Medicine B for Gastroenterology and Hepatology, University Hospital Münster, Münster, Germany
| | - Marietta Iacucci
- NIHR Biomedical Research Institute, Institute of Translational Medicine, University of Birmingham and University Hospitals Birmingham NHS Foundation Trust, UK
| | - Can-Hui Sun
- Department of Radiology, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, Guangdong, People’s Republic of China
| | - Subrata Ghosh
- NIHR Biomedical Research Institute, Institute of Translational Medicine, University of Birmingham and University Hospitals Birmingham NHS Foundation Trust, UK
| | - Florian Rieder
- Department of Gastroenterology, Hepatology and Nutrition, Digestive Diseases and Surgery Institute, Cleveland Clinic, Cleveland, Ohio, USA
| | - Min-Hu Chen
- Department of Gastroenterology, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, Guangdong, People’s Republic of China
| | - Zi-Ping Li
- Department of Radiology, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, Guangdong, People’s Republic of China
| | - Ren Mao
- Department of Gastroenterology, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, Guangdong, People’s Republic of China,Department of Gastroenterology, Hepatology and Nutrition, Digestive Diseases and Surgery Institute, Cleveland Clinic, Cleveland, Ohio, USA,Corresponding author: Ren Mao, The First Affiliated Hospital, Sun Yat-Sen University, 58 Zhongshan Road 2nd, Guangzhou 510080, People’s Republic of China; Department of Gastroenterology, Hepatology and Nutrition, Digestive Diseases and Surgery Institute, Cleveland Clinic, Cleveland, Ohio, USA. Tel: 86-20-87755766-8471; Fax: 86-20-87615805;
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Gao XH, Yu GY, Khan F, Li JQ, Stocchi L, Hull TL, Shen B. Greater Peripouch Fat Area on CT Image Is Associated with Chronic Pouchitis and Pouch Failure in Inflammatory Bowel Diseases Patients. Dig Dis Sci 2020; 65:3660-3671. [PMID: 32500285 DOI: 10.1007/s10620-020-06363-7] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/26/2020] [Accepted: 05/21/2020] [Indexed: 01/17/2023]
Abstract
BACKGROUND The causes of chronic antibiotic refractory pouchitis (CARP) and pouch failure in inflammatory bowel disease (IBD) patients remain unknown. Our previous small study showed peripouch fat area measured by MRI was associated with pouchitis. AIMS To explore the relationship between peripouch fat area on CT imaging and pouch outcomes. METHODS This is a historical cohort study. Demographic, clinical, and radiographic data of IBD patients with abdominal CT scans after pouch surgery between 2002 and 2017 were collected. Peripouch fat areas and mesenteric peripouch fat areas were measured on CT images at the middle pouch level. RESULTS A total of 435 IBD patients were included. Patients with higher peripouch fat areas had a higher prevalence of CARP. Univariate analyses demonstrated that long duration of the pouch, high weight or body mass index, the presence of primary sclerosing cholangitis or other autoimmune disorders, and greater peripouch fat area or mesenteric peripouch fat area were risk factors for CARP. Multivariable analyses demonstrated that the presence of primary sclerosing cholangitis or autoimmuned disorders, and greater peripouch fat area (odds ratio [OR] 1.031; 95% confidence interval [CI] 1.016-1.047, P < 0.001) or mesenteric peripouch fat area were independent risk factors for CARP. Of the 435 patients, 139 (32.0%) had two or more CT scans. Multivariable Cox proportional hazard analyses showed that "peripouch fat area increase ≥ 15%" (OR 3.808, 95%CI 1.703-8.517, P = 0.001) was an independent predictor of pouch failure. CONCLUSIONS A great peripouch fat area measured on CT image is associated with a higher prevalence of CARP, and the accumulation of peripouch fat is a risk factor for pouch failure. The assessment of peripouch fat may be used to monitor the disease course of the ileal pouch.
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Affiliation(s)
- Xian-Hua Gao
- Department of Colorectal Surgery, The Cleveland Clinic Foundation, Cleveland, OH, USA
- Department of Colorectal Surgery, Changhai Hospital, Shanghai, China
| | - Guan-Yu Yu
- Department of Colorectal Surgery, Changhai Hospital, Shanghai, China
| | - Freeha Khan
- Department of Gastroenterology/Hepatology, The Cleveland Clinic Foundation, Cleveland, OH, USA
| | - Jin-Qiao Li
- Department of Colorectal Surgery, Changhai Hospital, Shanghai, China
| | - Luca Stocchi
- Department of Colorectal Surgery, The Cleveland Clinic Foundation, Cleveland, OH, USA
| | - Tracy L Hull
- Department of Colorectal Surgery, The Cleveland Clinic Foundation, Cleveland, OH, USA
| | - Bo Shen
- Department of Gastroenterology/Hepatology, The Cleveland Clinic Foundation, Cleveland, OH, USA.
- The Inflammatory Bowel Disease Center at Columbia, Columbia University Irving Medical Center, 161 Fort Washington Ave Suite 843, New York, NY, 10032, USA.
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Johnson AM, Loftus EV. Impact of Obesity on the Management of Inflammatory Bowel Disease. Gastroenterol Hepatol (N Y) 2020; 16:350-359. [PMID: 34035739 PMCID: PMC8132647] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 06/12/2023]
Abstract
The worldwide prevalence of obesity has reached staggering proportions, and the inflammatory bowel disease (IBD) population has not been immune to this trend, with obesity rates estimated to be between 15% and 40%. With the concurrent rise in incidence of IBD itself, there are biologically plausible mechanisms that suggest a potential role of obesity in the pathogenesis of IBD, although epidemiologic data on this issue are conflicting. Similarly, studies exploring the impact that obesity may have on the natural history of disease have produced inconsistent results. Some studies suggest higher and others lower rates of surgery in obese Crohn's disease patients, other studies suggest a higher risk of surgery in obese ulcerative colitis patients, and yet other studies reveal no difference in outcomes regarding hospitalization or surgery for either group. Regardless of its impact on the pathogenesis or natural history of IBD, the rising prevalence of obesity in this population results in a need to better understand the effect it has on IBD management. Although pharmacologic data suggest that obesity may influence the absorption, distribution, and clearance of the available therapeutic agents, the actual clinical consequences that these differences have on disease management are less clear. Finally, it is possible that weight loss interventions for obesity could have an impact on the clinical course of IBD.
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Affiliation(s)
- Amanda M Johnson
- Division of Gastroenterology and Hepatology, Mayo Clinic College of Medicine and Mayo Clinic, Rochester, Minnesota
| | - Edward V Loftus
- Division of Gastroenterology and Hepatology, Mayo Clinic College of Medicine and Mayo Clinic, Rochester, Minnesota
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Serena C, Millan M, Ejarque M, Saera-Vila A, Maymó-Masip E, Núñez-Roa C, Monfort-Ferré D, Terrón-Puig M, Bautista M, Menacho M, Martí M, Espin E, Vendrell J, Fernández-Veledo S. Adipose stem cells from patients with Crohn's disease show a distinctive DNA methylation pattern. Clin Epigenetics 2020; 12:53. [PMID: 32252817 PMCID: PMC7137346 DOI: 10.1186/s13148-020-00843-3] [Citation(s) in RCA: 22] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/13/2019] [Accepted: 03/24/2020] [Indexed: 12/22/2022] Open
Abstract
Background Crohn’s disease (CD) is characterized by persistent inflammation and ulceration of the small or large bowel, and expansion of mesenteric adipose tissue, termed creeping fat (CF). We previously demonstrated that human adipose-derived stem cells (hASCs) from CF of patients with CD exhibit dysfunctional phenotypes, including a pro-inflammatory profile, high phagocytic capacity, and weak immunosuppressive properties. Importantly, these phenotypes persist in patients in remission and are found in all adipose depots explored including subcutaneous fat. We hypothesized that changes in hASCs are a consequence of epigenetic modifications. Methods We applied epigenome-wide profiling with a methylation array (Illumina EPIC/850k array) and gene expression analysis to explore the impact of CD on the methylation signature of hASCs isolated from the subcutaneous fat of patients with CD and healthy controls (n = 7 and 5, respectively; cohort I). Differentially methylated positions (p value cutoff < 1 × 10−4 and ten or more DMPs per gene) and regions (inclusion threshold 0.2, p value cutoff < 1 × 10−2 and more than 2 DMRs per gene) were identified using dmpfinder and Bumphunter (minfi), respectively. Changes in the expression of differentially methylated genes in hASCs were validated in a second cohort (n = 10/10 inactive and active CD and 10 controls; including patients from cohort I) and also in peripheral blood mononuclear cells (PBMCs) of patients with active/inactive CD and of healthy controls (cohort III; n = 30 independent subjects). Results We found a distinct DNA methylation landscape in hASCs from patients with CD, leading to changes in the expression of differentially methylated genes involved in immune response, metabolic, cell differentiation, and development processes. Notably, the expression of several of these genes in hASCs and PBMCs such as tumor necrosis factor alpha (TNFA) and PR domain zinc finger protein 16 (PRDM16) were not restored to normal (healthy) levels after disease remission. Conclusions hASCs of patients with CD exhibit a unique DNA methylation and gene expression profile, but the expression of several genes are only partially restored in patients with inactive CD, both in hASCs and PBMCs. Understanding how CD shapes the functionality of hASCs is critical for investigating the complex pathophysiology of this disease, as well as for the success of cell-based therapies. Graphical abstract Human adipose-stem cells isolated from subcutaneous fat of patients with Crohn’s disease exhibit an altered DNA methylation pattern and gene expression profile compared with those isolated from healthy individuals, with immune system, cell differentiation, metabolic and development processes identified as the main pathways affected. Interestingly, the gene expression of several genes involved in these pathways is only partially restored to control levels in patients with inactive Crohn’s disease, both in human adipose-stem cells and peripheral blood mononuclear cells. Understanding how Crohn’s disease shapes the functionality of human adipose-stem cells is critical for investigating the complex pathophysiology of this disease, as well as for the success of cell-based therapies.
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Affiliation(s)
- Carolina Serena
- Institut d´Investigació Sanitària Pere Virgili, Hospital Universitari Joan XXIII, Dr Mallafré Guasch, 4, 43007, Tarragona, Spain.,CIBER de Diabetes y Enfermedades Metabólicas Asociadas (CIBERDEM), Instituto de Salud Carlos III, 28014, Madrid, Spain
| | - Monica Millan
- Colorectal Surgery Unit, Hospital Universitari Joan XXIII, 43007, Tarragona, Spain.,Colorectal Surgery Unit, Hospital Universitari La Fe, Valencia, Spain
| | - Miriam Ejarque
- Institut d´Investigació Sanitària Pere Virgili, Hospital Universitari Joan XXIII, Dr Mallafré Guasch, 4, 43007, Tarragona, Spain.,CIBER de Diabetes y Enfermedades Metabólicas Asociadas (CIBERDEM), Instituto de Salud Carlos III, 28014, Madrid, Spain
| | - Alfonso Saera-Vila
- Institut d´Investigació Sanitària Pere Virgili, Hospital Universitari Joan XXIII, Dr Mallafré Guasch, 4, 43007, Tarragona, Spain
| | - Elsa Maymó-Masip
- Institut d´Investigació Sanitària Pere Virgili, Hospital Universitari Joan XXIII, Dr Mallafré Guasch, 4, 43007, Tarragona, Spain.,CIBER de Diabetes y Enfermedades Metabólicas Asociadas (CIBERDEM), Instituto de Salud Carlos III, 28014, Madrid, Spain
| | - Catalina Núñez-Roa
- Institut d´Investigació Sanitària Pere Virgili, Hospital Universitari Joan XXIII, Dr Mallafré Guasch, 4, 43007, Tarragona, Spain.,CIBER de Diabetes y Enfermedades Metabólicas Asociadas (CIBERDEM), Instituto de Salud Carlos III, 28014, Madrid, Spain
| | - Diandra Monfort-Ferré
- Institut d´Investigació Sanitària Pere Virgili, Hospital Universitari Joan XXIII, Dr Mallafré Guasch, 4, 43007, Tarragona, Spain
| | - Margarida Terrón-Puig
- Institut d´Investigació Sanitària Pere Virgili, Hospital Universitari Joan XXIII, Dr Mallafré Guasch, 4, 43007, Tarragona, Spain.,CIBER de Diabetes y Enfermedades Metabólicas Asociadas (CIBERDEM), Instituto de Salud Carlos III, 28014, Madrid, Spain
| | - Michelle Bautista
- Digestive Unit, Hospital Universitari Joan XXIII, 43007, Tarragona, Spain
| | - Margarita Menacho
- Digestive Unit, Hospital Universitari Joan XXIII, 43007, Tarragona, Spain
| | - Marc Martí
- Colorectal Surgery Unit, General Surgery Service, Hospital Valle de Hebron, Universitat Autonoma de Barcelona, 08035, Barcelona, Spain
| | - Eloy Espin
- Colorectal Surgery Unit, General Surgery Service, Hospital Valle de Hebron, Universitat Autonoma de Barcelona, 08035, Barcelona, Spain
| | - Joan Vendrell
- Institut d´Investigació Sanitària Pere Virgili, Hospital Universitari Joan XXIII, Dr Mallafré Guasch, 4, 43007, Tarragona, Spain. .,CIBER de Diabetes y Enfermedades Metabólicas Asociadas (CIBERDEM), Instituto de Salud Carlos III, 28014, Madrid, Spain. .,Universitat Rovira i Virgili, Tarragona, Spain.
| | - Sonia Fernández-Veledo
- Institut d´Investigació Sanitària Pere Virgili, Hospital Universitari Joan XXIII, Dr Mallafré Guasch, 4, 43007, Tarragona, Spain. .,CIBER de Diabetes y Enfermedades Metabólicas Asociadas (CIBERDEM), Instituto de Salud Carlos III, 28014, Madrid, Spain.
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Whole transcriptional analysis identifies markers of B, T and plasma cell signaling pathways in the mesenteric adipose tissue associated with Crohn's disease. J Transl Med 2020; 18:44. [PMID: 32000799 PMCID: PMC6993458 DOI: 10.1186/s12967-020-02220-3] [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: 10/12/2019] [Accepted: 01/10/2020] [Indexed: 12/21/2022] Open
Abstract
Background Crohn’s disease (CD) is a multifactorial disease characterized by chronic intestinal inflammation. The increased visceral adiposity near the affected intestinal area, of which mesenteric adipose tissue (MAT) is the main component, is a feature of CD. Both protective and pathological roles have been attributed to this disease-associated tissue in CD. To understand the contribution of MAT to CD pathophysiology, a molecular and cellular signature of disease-associated MAT in CD patients was provided. Methods We performed an observational study with whole transcriptional analysis by RNA sequencing (RNA-seq) of MAT and ileal mucosa from CD patients with active disease and controls. qPCR and immunohistology were performed for validation analysis. Results RNA-seq identified 17 significantly regulated genes (|FC| > 1.5; FDR < 0.05) in CD-MAT compared to non-IBD controls, with a marked upregulation of plasma cell genes (i.e., IGLL5, MZB1, CD79A, POU2AF1, FCRL5, JCHAIN, DERL3, SDC1, PIM2). A less strict statistical cutoff value (|FC| > 1.5, nominal p ≤ 0.05) yielded a larger list of 651 genes in CD-MAT compared to controls. CD ileum showed the significant regulation compared to control ileum of 849 genes (|FC| > 1.5; FDR < 0.05) or 2654 genes (|FC| > 1.5, nominal p ≤ 0.05). Ingenuity Pathway Analysis revealed the significant regulation of pathways related to T- and B cell functionality in the MAT of CD patients. Despite the differences between the MAT and ileal signatures of CD patients, we identified a subset of 204 genes significantly modulated in both tissues compared to controls. This common signature included genes related to the plasma cell signature. Genes such as S100A8, S100A9 (calprotectin) and IL1B, which are associated with acute inflammatory response, were exclusively regulated in the ileal mucosa of CD disease. In contrast, some genes encoding for lymphocyte receptors such as MS4A1, CD3D and CD79A were exclusively regulated in CD-MAT, exhibiting a different pattern of immune cell activation compared to the ileal mucosa in CD patients. qPCR and immunohistology confirmed the presence of large infiltrates of CD3+ CD20+ lymphocytes and CD138+ plasma cells in CD-MAT. Conclusion Our data strongly supports the role of CD-associated MAT as a site for T-, B- and plasma cell activation, and suggests that it could also act as a reservoir of memory immune responses.
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Dai ZH, Xu XT, Ran ZH. Associations Between Obesity and the Effectiveness of Anti–Tumor Necrosis Factor-α Agents in Inflammatory Bowel Disease Patients: A Literature Review and Meta-analysis. Ann Pharmacother 2020; 54:729-741. [DOI: 10.1177/1060028019900660] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/04/2023] Open
Abstract
Background: A total of 15% to 40% of adult inflammatory bowel disease (IBD) patients are obese. The influence of obesity on anti-tumor necrosis factor-α (anti-TNF-α) treatment in IBD patients is not consistent. Objective: To determine the association between obesity and the efficacy of anti-TNF treatment in IBD patients. Methods: We performed a systematic search from January 1990 through November 2019 on MEDLINE, Web of Science, Google Scholar, ClinicalTrials.gov, and Cochrane library. We included randomized controlled trials and observational cohort studies that investigated the outcome of anti-TNF treatment in IBD patients with stratification according to body mass index or body weight. The odds ratio (OR) and its 95% CI were calculated. Results: In this pooled meta-analysis, we observed that obesity increased the odds of failure of anti-TNF therapy (OR = 1.195; 95% CI = 1.034-1.380; P = 0.015; I2 = 47.8%). After performing subgroup analyses, obesity was associated with higher odds of anti-TNF treatment failure in ulcerative colitis (UC) patients (OR = 1.413; 95% CI = 1.008-1.980; P = 0.045; I2 = 20.0%) but not in Crohn’s disease patients (OR = 1.099; 95% CI = 0.928-1.300). Obesity significantly increased the odds of treatment failure of both dose-fixed and weight-based anti-TNF agents (OR = 1.121, 95% CI = 1.027-1.224, P = 0.011, and OR = 1.449, 95% CI = 1.006-2.087, P = 0.046, respectively). Conclusion and Relevance: In our meta-analysis, obesity was associated with the inferior response of anti-TNF treatments in UC patients. Clinicians should be aware that obese UC patients may require higher doses in anti-TNF treatment.
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Affiliation(s)
- Zhang-han Dai
- Division of Gastroenterology and Hepatology, Key Laboratory of Gastroenterology and Hepatology, Ministry of Health, Inflammatory Bowel Disease Research Center, Renji Hospital, School of Medicine, Shanghai Institute of Digestive Disease, Shanghai Jiao Tong University, Shanghai, China
| | - Xi-tao Xu
- Division of Gastroenterology and Hepatology, Key Laboratory of Gastroenterology and Hepatology, Ministry of Health, Inflammatory Bowel Disease Research Center, Renji Hospital, School of Medicine, Shanghai Institute of Digestive Disease, Shanghai Jiao Tong University, Shanghai, China
| | - Zhi-hua Ran
- Division of Gastroenterology and Hepatology, Key Laboratory of Gastroenterology and Hepatology, Ministry of Health, Inflammatory Bowel Disease Research Center, Renji Hospital, School of Medicine, Shanghai Institute of Digestive Disease, Shanghai Jiao Tong University, Shanghai, China
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Role of Obesity, Mesenteric Adipose Tissue, and Adipokines in Inflammatory Bowel Diseases. Biomolecules 2019; 9:biom9120780. [PMID: 31779136 PMCID: PMC6995528 DOI: 10.3390/biom9120780] [Citation(s) in RCA: 76] [Impact Index Per Article: 12.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/01/2019] [Revised: 11/14/2019] [Accepted: 11/15/2019] [Indexed: 12/11/2022] Open
Abstract
Inflammatory bowel diseases (IBDs) are a group of disorders which include ulcerative colitis and Crohn's disease. Obesity is becoming increasingly more common among patients with inflammatory bowel disease and plays a role in the development and course of the disease. This is especially true in the case of Crohn's disease. The recent results indicate a special role of visceral adipose tissue and particularly mesenteric adipose tissue, also known as "creeping fat", in pathomechanism, leading to intestinal inflammation. The involvement of altered adipocyte function and the deregulated production of adipokines, such as leptin and adiponectin, has been suggested in pathogenesis of IBD. In this review, we discuss the epidemiology and pathophysiology of obesity in IBD, the influence of a Western diet on the course of Crohn's disease and colitis in IBD patients and animal's models, and the potential role of adipokines in these disorders. Since altered body composition, decrease of skeletal muscle mass, and development of pathologically changed mesenteric white adipose tissue are well-known features of IBD and especially of Crohn's disease, we discuss the possible crosstalk between adipokines and myokines released from skeletal muscle during exercise with moderate or forced intensity. The emerging role of microbiota and the antioxidative and anti-inflammatory enzymes such as intestinal alkaline phosphatase is also discussed, in order to open new avenues for the therapy against intestinal perturbations associated with IBD.
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Gao XH, Li JQ, Khan F, Chouhan H, Yu GY, Remer E, Stocchi L, Hull TL, Shen B. Difference in the frequency of pouchitis between ulcerative colitis and familial adenomatous polyposis: is the explanation in peripouch fat? Colorectal Dis 2019; 21:1032-1044. [PMID: 30985958 DOI: 10.1111/codi.14651] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/24/2018] [Accepted: 02/27/2019] [Indexed: 02/08/2023]
Abstract
AIM Patients with ulcerative colitis (UC) have an unexplained higher incidence of pouchitis and a greater amount of peripouch fat compared with patients with familial adenomatous polyposis (FAP). The aims of this study were to compare the peripouch fat areas between patients with UC and patients with FAP, and to explore relationship between peripouch fat and pouchitis or chronic antibiotic-refractory pouchitis (CARP). METHOD Patients with an abdominal CT image from our prospectively maintained Pouch Database were included. Abdominal fat and peripouch fat were measured on CT images at different levels or planes. Comparisons of peripouch fat and CARP were performed before and after propensity score matching. RESULTS A total of 277 patients with UC and 40 patients with FAP were included. Compared with patients with FAP, patients with UC were found to have a higher incidence of pouchitis (58.5% vs 15.0%, P < 0.001) and CARP (24.5% vs 2.5%, P = 0.002) and a higher total peripouch fat area (P = 0.030) and mesenteric peripouch fat area (P = 0.022) at Level-3. Univariate and multivariate analyses showed that diagnosis (UC vs FAP) and peripouch fat areas at Level-3 and Level-5 were independent risk factors for CARP. With propensity score matching, 38 pairs of patients with UC and FAP were matched successfully. After matching, patients with UC were found to have higher total peripouch fat area and higher mesenteric peripouch fat area at Level-3, and a higher incidence of pouchitis (57.9% vs 13.2%, P < 0.001) and CARP (23.7% vs 2.6%, P = 0.007). CONCLUSION Our study demonstrates that patients with UC have more peripouch fat than those with FAP, which may explain the difference in the frequency of pouchitis and CARP between these groups of patients.
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Affiliation(s)
- X H Gao
- Department of Colorectal Surgery, the Cleveland Clinic Foundation, Cleveland, Ohio, USA.,Department of Colorectal Surgery, Changhai Hospital, Shanghai, China
| | - J Q Li
- Department of Colorectal Surgery, Changhai Hospital, Shanghai, China
| | - F Khan
- Department of Gastroenterology/Hepatology/Nutritionthe, Cleveland Clinic Foundation, Cleveland, Ohio, USA
| | - H Chouhan
- Department of Colorectal Surgery, the Cleveland Clinic Foundation, Cleveland, Ohio, USA
| | - G Y Yu
- Department of Colorectal Surgery, Changhai Hospital, Shanghai, China
| | - E Remer
- Department of Abdominal Imaging, the Cleveland Clinic Foundation, Cleveland, Ohio, USA
| | - L Stocchi
- Department of Colorectal Surgery, the Cleveland Clinic Foundation, Cleveland, Ohio, USA
| | - T L Hull
- Department of Colorectal Surgery, the Cleveland Clinic Foundation, Cleveland, Ohio, USA
| | - B Shen
- Department of Gastroenterology/Hepatology/Nutritionthe, Cleveland Clinic Foundation, Cleveland, Ohio, USA
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Rahmani J, Kord-Varkaneh H, Hekmatdoost A, Thompson J, Clark C, Salehisahlabadi A, Day AS, Jacobson K. Body mass index and risk of inflammatory bowel disease: A systematic review and dose-response meta-analysis of cohort studies of over a million participants. Obes Rev 2019; 20:1312-1320. [PMID: 31190427 DOI: 10.1111/obr.12875] [Citation(s) in RCA: 41] [Impact Index Per Article: 6.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/11/2019] [Revised: 03/25/2019] [Accepted: 04/10/2019] [Indexed: 12/28/2022]
Abstract
The relationship between body mass index (BMI) and risk of inflammatory bowel disease (IBD) is controversial. We performed a dose-response meta-analysis to investigate the association between BMI and risk of incident ulcerative colitis (UC) and Crohn's disease (CD) using prospective cohort studies. A systematic search was conducted in MEDLINE/PubMed, SCOPUS, Cochrane, and Web of Science databases from inception to January 2019. DerSimonian and Laird random-effects model was used to estimate combined hazard ratios (HRs). Overall, 882 articles were screened, and 42 full-text articles were reviewed for inclusion using the study eligibility criteria. Five studies evaluated the association between BMI and IBD with 1 044 517 participants. Pooled results showed a significant association between participants affected by obesity and risk of CD (HR: 1.42, 95% CI: 1.18-1.71, I2 : 0.00). There was a significant nonlinear association between BMI and risk of CD (P = .01, coeff = 0.5024). Pooled results did not show any significant association between being underweight and risk of UC (HR: 1.07, 95% CI: 0.96-1.19, I2 : 0.00) or CD (HR: 1.11, 95% CI: 0.93-1.31, I2 : 12.8). There was no difference in the risk for UC among participants affected by obesity compared with participants categorized as having normal BMI (HR: 0.96, 95% CI: 0.80-1.14, I2 : 8.0). This systematic review and meta-analysis identified significant dose-response relationship between being affected by obesity, as a risk factor, and incidence of CD.
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Affiliation(s)
- Jamal Rahmani
- Department of Community Nutrition, Faculty of Nutrition and Food Technology, National Nutrition and Food Technology Research Institute, Student Research Committee, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Hamed Kord-Varkaneh
- Department of Clinical Nutrition and Dietetics, Faculty of Nutrition and Food Technology, National Nutrition and Food Technology Research Institute, Student Research Committee, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Azita Hekmatdoost
- Department of Pediatrics, BC Children's Hospital, University of British Columbia, Vancouver, Canada
| | - Jacqueline Thompson
- Nuffield Department of Orthopaedics, Rheumatology & Musculoskeletal Sciences, University of Oxford, Oxford, UK
| | - Cain Clark
- School of Life Sciences, Coventry University, Coventry, UK
| | - Ammar Salehisahlabadi
- Department of Clinical Nutrition and Dietetics, Faculty of Nutrition and Food Technology, National Nutrition and Food Technology Research Institute, Student Research Committee, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Andrew S Day
- Department of Paediatrics, University of Otago, Christchurch, New Zealand
| | - Kevan Jacobson
- Department of Pediatrics, BC Children's Hospital, University of British Columbia, Vancouver, Canada
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The Role of Adipose Tissue in the Pathogenesis and Therapeutic Outcomes of Inflammatory Bowel Disease. Cells 2019; 8:cells8060628. [PMID: 31234447 PMCID: PMC6627060 DOI: 10.3390/cells8060628] [Citation(s) in RCA: 49] [Impact Index Per Article: 8.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/31/2019] [Revised: 06/16/2019] [Accepted: 06/18/2019] [Indexed: 02/06/2023] Open
Abstract
Though historically regarded as an inert energy store, adipose tissue is a complex endocrine organ, which is increasingly implicated in the pathogenesis of inflammatory bowel disease (IBD). Accumulating evidence points to visceral adipose tissue and specifically to its mesenteric component, or “creeping fat” as impacting on the disease course through its immunomodulatory properties. On the one hand, mesenteric fat acts as a physical barrier to inflammation and is involved in controlling host immune response to translocation of gut bacteria. On the other hand, however, there exists a strong link between visceral fat and complicated course of the disease with unfavorable therapeutic outcomes. Furthermore, “creeping fat” appears to play different roles in different IBD phenotypes, with the greatest pathogenetic contribution probably to an ileal form of Crohn’s disease. In this review, we summarize and discuss the existing literature on the subject and identify high-priority areas for future research. It may be that a better understanding of the role of mesenteric fat in IBD will determine new therapeutic targets and translate into improved clinical outcomes.
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Bilski J, Mazur-Bialy A, Wojcik D, Magierowski M, Surmiak M, Kwiecien S, Magierowska K, Hubalewska-Mazgaj M, Sliwowski Z, Brzozowski T. Effect of Forced Physical Activity on the Severity of Experimental Colitis in Normal Weight and Obese Mice. Involvement of Oxidative Stress and Proinflammatory Biomarkers. Nutrients 2019; 11:1127. [PMID: 31117199 PMCID: PMC6567060 DOI: 10.3390/nu11051127] [Citation(s) in RCA: 18] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/01/2019] [Revised: 05/16/2019] [Accepted: 05/17/2019] [Indexed: 12/16/2022] Open
Abstract
Inflammatory bowel diseases are a heterogeneous group of disorders represented by two major phenotypic forms, Crohn's disease and ulcerative colitis. Cross talk between adipokines and myokines, as well as changes in intestinal microcirculation, was proposed in pathogenesis of these disorders. C57BL/6 male mice were fed ad libitum for 12 weeks a standard (SD) or high-fat diet (HFD). After the adaptation period, two groups of animals fed SD or HFD were subjected to 6 weeks of the forced treadmill exercise and the experimental colitis was induced in both groups of sedentary and exercising mice fed SD and HFD by intra-colonic administration of 2,4,6-trinitrobenzenesulfonic acid. The disease activity index (DAI), colonic blood flow (CBF), the weight of animals, caloric intake, the mesenteric fad pad, the colonic oxidative stress markers malondialdehyde (MDA), reduced glutathione (GSH), and superoxide dismutase (SOD) activity and intestinal expression and protein content of proinflammatory markers were evaluated. Macroscopic and microscopic colitis in sedentary SD mice was accompanied by a significant fall in CBF and exacerbated in those fed a HFD. The contents of MDA, GSH, and SOD activity were significantly increased in both SD and HFD fed mice with treadmill exercise as compared with sedentary mice. In sedentary HFD mice a significant increase in the intestinal oxidative stress parameters and mucosal expression of IL-1β, TNF-α, IL-17, IFNγ, IL-6, and IL-10 protein were observed and these effects were aggravated in mice subjected to forced treadmill exercise. The mucosal expression of mRNA for TNF-α, IL-1β, iNOS, COX-2, SOD-1, SOD-2, GPx mRNAs, and the hypoxia inducible factor (HIF)-1α protein expression were upregulated in colonic mucosa of treadmill exercising HFD mice with colitis compared with those without exercise. We conclude that forced treadmill running exacerbates the severity of colonic damage in obese mice due to a fall in colonic microcirculation, an increase in oxidative stress, and the rise in expression and activity of proinflammatory biomarkers.
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Affiliation(s)
- Jan Bilski
- Department of Ergonomics and Exercise Physiology, Faculty of Health Sciences, Jagiellonian University Medical College, 20 Grzegorzecka Street, 31-531 Cracow, Poland.
| | - Agnieszka Mazur-Bialy
- Department of Ergonomics and Exercise Physiology, Faculty of Health Sciences, Jagiellonian University Medical College, 20 Grzegorzecka Street, 31-531 Cracow, Poland.
| | - Dagmara Wojcik
- Department of Physiology, Faculty of Medicine, Jagiellonian University Medical College, 16 Grzegorzecka Street, 31-531 Cracow, Poland.
| | - Marcin Magierowski
- Department of Physiology, Faculty of Medicine, Jagiellonian University Medical College, 16 Grzegorzecka Street, 31-531 Cracow, Poland.
| | - Marcin Surmiak
- Department of Physiology, Faculty of Medicine, Jagiellonian University Medical College, 16 Grzegorzecka Street, 31-531 Cracow, Poland.
| | - Slawomir Kwiecien
- Department of Physiology, Faculty of Medicine, Jagiellonian University Medical College, 16 Grzegorzecka Street, 31-531 Cracow, Poland.
| | - Katarzyna Magierowska
- Department of Physiology, Faculty of Medicine, Jagiellonian University Medical College, 16 Grzegorzecka Street, 31-531 Cracow, Poland.
| | - Magdalena Hubalewska-Mazgaj
- Department of Physiology, Faculty of Medicine, Jagiellonian University Medical College, 16 Grzegorzecka Street, 31-531 Cracow, Poland.
| | - Zbigniew Sliwowski
- Department of Physiology, Faculty of Medicine, Jagiellonian University Medical College, 16 Grzegorzecka Street, 31-531 Cracow, Poland.
| | - Tomasz Brzozowski
- Department of Physiology, Faculty of Medicine, Jagiellonian University Medical College, 16 Grzegorzecka Street, 31-531 Cracow, Poland.
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Bryant RV, Schultz CG, Ooi S, Goess C, Costello SP, Vincent AD, Schoeman S, Lim A, Bartholomeusz FD, Travis SPL, Andrews JM. Authors' reply: The Association Between Visceral Adipose Tissue and Stricturing Crohn's Disease Behavior, Fecal Calprotectin and Quality of Life. Inflamm Bowel Dis 2019; 25:e62-e63. [PMID: 30380064 DOI: 10.1093/ibd/izy338] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/09/2022]
Affiliation(s)
- Robert Venning Bryant
- IBD Service, Department of Gastroenterology and Hepatology, The Queen Elizabeth Hospital, Woodville South, South Australia, Australia.,School of Medicine, Faculty of Health Sciences, University of Adelaide, Adelaide, South Australia, Australia
| | - Christopher G Schultz
- Department of Nuclear Medicine, PET and Bone Densitometry, Royal Adelaide Hospital, Adelaide, South Australia, Australia
| | - Soong Ooi
- IBD Service, Department of Gastroenterology and Hepatology, Royal Adelaide Hospital, Adelaide, South Australia, Australia
| | - Charlotte Goess
- IBD Service, Department of Gastroenterology and Hepatology, Royal Adelaide Hospital, Adelaide, South Australia, Australia
| | - Samuel Paul Costello
- IBD Service, Department of Gastroenterology and Hepatology, The Queen Elizabeth Hospital, Woodville South, South Australia, Australia.,School of Medicine, Faculty of Health Sciences, University of Adelaide, Adelaide, South Australia, Australia
| | - Andrew D Vincent
- Freemasons Foundation Centre for Men's Health, School of Medicine, University of Adelaide, Adelaide, South Australia, Australia
| | - Scott Schoeman
- IBD Service, Department of Gastroenterology and Hepatology, The Queen Elizabeth Hospital, Woodville South, South Australia, Australia
| | - Amanda Lim
- IBD Service, Department of Gastroenterology and Hepatology, The Queen Elizabeth Hospital, Woodville South, South Australia, Australia
| | - Francis Dylan Bartholomeusz
- Department of Nuclear Medicine, PET and Bone Densitometry, Royal Adelaide Hospital, Adelaide, South Australia, Australia
| | - Simon P L Travis
- Translational Gastroenterology Unit, John Radcliffe Hospital, Oxford, Oxfordshire, United Kingdom
| | - Jane Mary Andrews
- School of Medicine, Faculty of Health Sciences, University of Adelaide, Adelaide, South Australia, Australia.,IBD Service, Department of Gastroenterology and Hepatology, Royal Adelaide Hospital, Adelaide, South Australia, Australia
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Bryant RV, Schultz CG, Ooi S, Goess C, Costello SP, Vincent AD, Schoeman S, Lim A, Bartholomeusz FD, Travis SPL, Andrews JM. Visceral Adipose Tissue Is Associated With Stricturing Crohn's Disease Behavior, Fecal Calprotectin, and Quality of Life. Inflamm Bowel Dis 2019; 25:592-600. [PMID: 30215805 DOI: 10.1093/ibd/izy278] [Citation(s) in RCA: 38] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/23/2018] [Indexed: 02/06/2023]
Abstract
BACKGROUND Visceral adipose tissue (VAT) has been proposed to play a pathogenic role in Crohn's disease (CD); however, prospective clinical data are lacking. The aim was to evaluate whether VAT, beyond body mass index (BMI), is associated with CD behavior, disease activity, quality of life (QoL), or outcomes. METHODS Body composition data and clinical, anthropometric, disease activity (fecal calprotectin [FC]), and QoL scores were gathered prospectively on adults with CD at 0, 12, and 24 months. BMI and, VAT metrics (visceral adipose tissue volume [cm3]/height [m2] index and VAT:subcutaneous adipose tissue [SAT] ratio) were calculated. Inflammatory bowel disease-related surgery and hospitalization were recorded over extended follow-up (median, 51 months). Multivariable linear mixed effects and logistic regression analyses were performed. RESULTS Ninety-seven participants were assessed at baseline (55% male; median age, 31 years), 84 at 12 months, and 72 at 24 months. VAT:SAT was positively associated with stricturing disease behavior (log odds ratio [OR], 1.7; 95% confidence interval [CI], 0.32 to 3; P = 0.01) and elevated FC in patients with ileocolonic disease (β, 1.3; 95% CI, 0.32 to 2.3; P = 0.01). VAT:SAT was associated with lower QoL, particularly in those with ileal disease (β, -12; 95% CI, -19 to -4.5; P = 0.05). However, no prospective associations were observed between serial VAT measurements and time to surgery or hospitalization. No correlations were found between BMI and disease behavior, activity, or QoL. CONCLUSIONS VAT:SAT, rather than BMI, is associated with stricturing CD behavior, elevated FC, and reduced QoL in a disease distribution-dependent manner. Further studies are required to substantiate the role of VAT as a useful biomarker in CD.
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Affiliation(s)
- Robert Venning Bryant
- IBD Service, Department of Gastroenterology and Hepatology, The Queen Elizabeth Hospital, Woodville South, South Australia.,School of Medicine, Faculty of Health Sciences, University of Adelaide, Adelaide, South Australia
| | - Christopher G Schultz
- Department of Nuclear Medicine, PET and Bone Densitometry, Royal Adelaide Hospital, Adelaide, South Australia
| | - Soong Ooi
- IBD Service, Department of Gastroenterology and Hepatology, Royal Adelaide Hospital, Adelaide, South Australia
| | - Charlotte Goess
- IBD Service, Department of Gastroenterology and Hepatology, Royal Adelaide Hospital, Adelaide, South Australia
| | - Samuel Paul Costello
- IBD Service, Department of Gastroenterology and Hepatology, The Queen Elizabeth Hospital, Woodville South, South Australia.,School of Medicine, Faculty of Health Sciences, University of Adelaide, Adelaide, South Australia
| | - Andrew D Vincent
- Freemasons Foundation Centre for Men's Health, School of Medicine, University of Adelaide, Adelaide, South Australia
| | - Scott Schoeman
- IBD Service, Department of Gastroenterology and Hepatology, The Queen Elizabeth Hospital, Woodville South, South Australia
| | - Amanda Lim
- IBD Service, Department of Gastroenterology and Hepatology, The Queen Elizabeth Hospital, Woodville South, South Australia
| | - Francis Dylan Bartholomeusz
- Department of Nuclear Medicine, PET and Bone Densitometry, Royal Adelaide Hospital, Adelaide, South Australia
| | - Simon P L Travis
- Translational Gastroenterology Unit, John Radcliffe Hospital, Oxford, Oxfordshire, UK
| | - Jane Mary Andrews
- School of Medicine, Faculty of Health Sciences, University of Adelaide, Adelaide, South Australia.,IBD Service, Department of Gastroenterology and Hepatology, Royal Adelaide Hospital, Adelaide, South Australia
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45
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Preventive Effect of Spontaneous Physical Activity on the Gut-Adipose Tissue in a Mouse Model That Mimics Crohn's Disease Susceptibility. Cells 2019; 8:cells8010033. [PMID: 30634469 PMCID: PMC6356941 DOI: 10.3390/cells8010033] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/30/2018] [Revised: 12/23/2018] [Accepted: 01/03/2019] [Indexed: 12/14/2022] Open
Abstract
Crohn’s disease is characterized by abnormal ileal colonization by adherent-invasive E. coli (AIEC) and expansion of mesenteric adipose tissue. This study assessed the preventive effect of spontaneous physical activity (PA) on the gut-adipose tissue in a mouse model that mimics Crohn’s disease susceptibility. Thirty-five CEABAC10 male mice performed spontaneous PA (wheel group; n = 24) or not (controls; n = 11) for 12 weeks. At week 12, mice were orally challenged with the AIEC LF82 strain for 6 days. Body composition, glycaemic control, intestinal permeability, gut microbiota composition, and fecal short-chain fatty acids were assessed in both groups. Animals were fed a high fat/high sugar diet throughout the study. After exposure to AIEC, mesenteric adipose tissue weight was lower in the wheel group. Tight junction proteins expression increased with spontaneous PA, whereas systemic lipopolysaccharides were negatively correlated with the covered distance. Bifidobacterium and Lactobacillus decreased in controls, whereas Oscillospira and Ruminococcus increased in the wheel group. Fecal propionate and butyrate were also higher in the wheel group. In conclusion, spontaneous physical activity promotes healthy gut microbiota composition changes and increases short-chain fatty acids in CEABAC10 mice fed a Western diet and exposed to AIEC to mimic Crohn’s disease.
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Coffey CJ, Kiernan MG, Sahebally SM, Jarrar A, Burke JP, Kiely PA, Shen B, Waldron D, Peirce C, Moloney M, Skelly M, Tibbitts P, Hidayat H, Faul PN, Healy V, O’Leary PD, Walsh LG, Dockery P, O’Connell RP, Martin ST, Shanahan F, Fiocchi C, Dunne CP. Inclusion of the Mesentery in Ileocolic Resection for Crohn's Disease is Associated With Reduced Surgical Recurrence. J Crohns Colitis 2018; 12:1139-1150. [PMID: 29309546 PMCID: PMC6225977 DOI: 10.1093/ecco-jcc/jjx187] [Citation(s) in RCA: 227] [Impact Index Per Article: 32.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/19/2022]
Abstract
BACKGROUND AND AIMS Inclusion of the mesentery during resection for colorectal cancer is associated with improved outcomes but has yet to be evaluated in Crohn's disease. This study aimed to determine the rate of surgical recurrence after inclusion of mesentery during ileocolic resection for Crohn's disease. METHODS Surgical recurrence rates were compared between two cohorts. Cohort A [n = 30] underwent conventional ileocolic resection where the mesentery was divided flush with the intestine. Cohort B [n = 34] underwent resection which included excision of the mesentery. The relationship between mesenteric disease severity and surgical recurrence was determined in a separate cohort [n = 94]. A mesenteric disease activity index was developed to quantify disease severity. This was correlated with the Crohn's disease activity index and the fibrocyte percentage in circulating white cells. RESULTS Cumulative reoperation rates were 40% and 2.9% in cohorts A and B [P = 0.003], respectively. Surgical technique was an independent determinant of outcome [P = 0.007]. Length of resected intestine was shorter in cohort B, whilst lymph node yield was higher [12.25 ± 13 versus 2.4 ± 2.9, P = 0.002]. Advanced mesenteric disease predicted increased surgical recurrence [Hazard Ratio 4.7, 95% Confidence Interval: 1.71-13.01, P = 0.003]. The mesenteric disease activity index correlated with the mucosal disease activity index [r = 0.76, p < 0.0001] and the Crohn's disease activity index [r = 0.70, p < 0.0001]. The mesenteric disease activity index was significantly worse in smokers and correlated with increases in circulating fibrocytes. CONCLUSIONS Inclusion of mesentery in ileocolic resection for Crohn's disease is associated with reduced recurrence requiring reoperation.
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Affiliation(s)
- Calvin J Coffey
- Department of Surgery, University Hospital Limerick, Limerick, Ireland,Graduate Entry Medical School, University of Limerick, Limerick, Ireland,Centre for Interventions in Infection, Inflammation and Immunity [4i], University of Limerick, Limerick, Ireland,Corresponding author: Professor J. Calvin Coffey, PhD, FRCSI, Surgical Professorial Unit, University Hospital Limerick, Limerick, Ireland. Tel.: +353-61-482412; fax: +353-61-482410;
| | - Miranda G Kiernan
- Graduate Entry Medical School, University of Limerick, Limerick, Ireland,Centre for Interventions in Infection, Inflammation and Immunity [4i], University of Limerick, Limerick, Ireland
| | - Shaheel M Sahebally
- Department of Surgery, University Hospital Limerick, Limerick, Ireland,Graduate Entry Medical School, University of Limerick, Limerick, Ireland,Centre for Interventions in Infection, Inflammation and Immunity [4i], University of Limerick, Limerick, Ireland
| | - Awad Jarrar
- Lerner College of Medicine, Cleveland Clinic Foundation, Cleveland, OH, USA
| | - John P Burke
- Centre for Colorectal Disease, St Vincent’s University Hospital, Dublin, Ireland,School of Medicine, University College Dublin, Dublin, Ireland
| | - Patrick A Kiely
- Graduate Entry Medical School, University of Limerick, Limerick, Ireland,Centre for Interventions in Infection, Inflammation and Immunity [4i], University of Limerick, Limerick, Ireland,Health Research Institute [HRI], University of Limerick, Limerick, Ireland
| | - Bo Shen
- Lerner College of Medicine, Cleveland Clinic Foundation, Cleveland, OH, USA,Departments of Gastroenterology/Hepatology, Digestive Disease and Surgery Institute, Cleveland Clinic Foundation, Cleveland, OH, USA
| | - David Waldron
- Department of Surgery, University Hospital Limerick, Limerick, Ireland
| | - Colin Peirce
- Department of Surgery, University Hospital Limerick, Limerick, Ireland
| | - Manus Moloney
- Department of Gastroenterology, University Hospitals Limerick, Limerick, Ireland
| | - Maeve Skelly
- Department of Gastroenterology, University Hospitals Limerick, Limerick, Ireland
| | - Paul Tibbitts
- Department of Surgery, University Hospital Limerick, Limerick, Ireland,Graduate Entry Medical School, University of Limerick, Limerick, Ireland
| | - Hena Hidayat
- Department of Surgery, University Hospital Limerick, Limerick, Ireland
| | - Peter N Faul
- Department of Pathology, University Hospitals Limerick, Limerick, Ireland
| | - Vourneen Healy
- Department of Pathology, University Hospitals Limerick, Limerick, Ireland
| | - Peter D O’Leary
- Department of Surgery, University Hospital Limerick, Limerick, Ireland
| | - Leon G Walsh
- Department of Surgery, University Hospital Limerick, Limerick, Ireland,Graduate Entry Medical School, University of Limerick, Limerick, Ireland,Centre for Interventions in Infection, Inflammation and Immunity [4i], University of Limerick, Limerick, Ireland
| | - Peter Dockery
- Department of Anatomy, National University of Ireland Galway, Galway, Ireland
| | - Ronan P O’Connell
- Centre for Colorectal Disease, St Vincent’s University Hospital, Dublin, Ireland,School of Medicine, University College Dublin, Dublin, Ireland
| | - Sean T Martin
- Centre for Colorectal Disease, St Vincent’s University Hospital, Dublin, Ireland
| | - Fergus Shanahan
- Department of Medicine, Alimentary Pharmabiotic Centre, University College Cork, Cork, Ireland
| | - Claudio Fiocchi
- Departments of Gastroenterology/Hepatology, Digestive Disease and Surgery Institute, Cleveland Clinic Foundation, Cleveland, OH, USA,Department of Pathobiology, Lerner Research Institute, Cleveland Clinic Foundation, Cleveland, OH, USA
| | - Colum P Dunne
- Graduate Entry Medical School, University of Limerick, Limerick, Ireland,Centre for Interventions in Infection, Inflammation and Immunity [4i], University of Limerick, Limerick, Ireland
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Cañete F, Mañosa M, Clos A, Cabré E, Domènech E. Review article: the relationship between obesity, bariatric surgery, and inflammatory bowel disease. Aliment Pharmacol Ther 2018; 48:807-816. [PMID: 30178869 DOI: 10.1111/apt.14956] [Citation(s) in RCA: 19] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/10/2018] [Revised: 06/07/2018] [Accepted: 08/01/2018] [Indexed: 02/06/2023]
Abstract
BACKGROUND The convoluted relationship between obesity, bariatric surgery and inflammatory bowel disease (IBD) is of increasing interest. AIM To analyse evidence regarding the role of bariatric surgery in the development of de novo IBD and its impact on clinical outcomes and safety in patients with established IBD. METHODS A PubMed/Medline search was performed to identify studies reporting the development of IBD after bariatric surgery and the outcomes of IBD patients after bariatric surgery. RESULTS Eighty patients were reported to have developed de novo IBD after bariatric surgery (21% ulcerative colitis [UC], 75% Crohn's disease [CD]), mostly females. Roux-en-Y gastric bypass was the most frequent bariatric technique (80%). Symptoms related to IBD occurred within 1 month and 16 years after surgery. Regarding patients with known IBD undergoing bariatric surgery, 60 patients (35 CD, 24 UC, and 1 unclassified colitis) have been reported. Sleeve gastrectomy was the most frequent bariatric procedure, particularly in CD patients. Acute flares after surgery were observed in only four UC patients. In addition, two retrospective population-based studies described perioperative outcomes of bariatric surgery on IBD patients, demonstrating only a significant increase in small bowel obstruction in these patients. CONCLUSIONS Bariatric surgery in carefully selected patients with established IBD is technically feasible and probably safe. Development of de novo IBD should be taken into account in individuals with previous bariatric surgery who develop diarrhoea, anaemia or excessive weight loss.
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Affiliation(s)
- Fiorella Cañete
- IBD Unit, Gastroenterology Department, Hospital Universitari Germans Trias i Pujol, Badalona, Catalonia, Spain.,Centro de Investigaciones Biomédicas en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Barcelona, Catalonia, Spain.,Universitat Autònoma de Barcelona, Barcelona, Spain
| | - Míriam Mañosa
- IBD Unit, Gastroenterology Department, Hospital Universitari Germans Trias i Pujol, Badalona, Catalonia, Spain.,Centro de Investigaciones Biomédicas en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Barcelona, Catalonia, Spain
| | - Ariadna Clos
- IBD Unit, Gastroenterology Department, Hospital Universitari Germans Trias i Pujol, Badalona, Catalonia, Spain
| | - Eduard Cabré
- IBD Unit, Gastroenterology Department, Hospital Universitari Germans Trias i Pujol, Badalona, Catalonia, Spain.,Centro de Investigaciones Biomédicas en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Barcelona, Catalonia, Spain
| | - Eugeni Domènech
- IBD Unit, Gastroenterology Department, Hospital Universitari Germans Trias i Pujol, Badalona, Catalonia, Spain.,Centro de Investigaciones Biomédicas en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Barcelona, Catalonia, Spain
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48
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Zielińska A, Siwiński P, Sobolewska-Włodarczyk A, Wiśniewska-Jarosińska M, Fichna J, Włodarczyk M. The role of adipose tissue in the pathogenesis of Crohn's disease. Pharmacol Rep 2018; 71:105-111. [PMID: 30513401 DOI: 10.1016/j.pharep.2018.09.011] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/06/2018] [Revised: 08/10/2018] [Accepted: 09/27/2018] [Indexed: 02/07/2023]
Abstract
Crohn's disease (CD) is a chronic, immune system-mediated inflammatory disease affecting gastrointestinal (GI) tract. The pathogenesis of the intestinal lesions is not entirely explained and understood: excessive activation of the immune system may come as a result of the interaction of environmental, genetic and infectious factors and the mediation of abnormal intestinal flora. The main objective of the current study is to further identify the role of adipose tissue in the pathogenesis of CD. Alterations in body fat distribution, accumulation of intra-abdominal white adipose tissue (WAT) and mesenteric obesity are well-known features of CD. Up to date, data concerning the role of WAT in the pathogenesis of CD is limited with only a few studies on the relationship between WAT and the course of the disease, as well as pro- and anti-inflammatory cytokine profile and general immune system functioning. In this review, we focus on the importance of physiological and pathophysiological WAT functions and secreted adipokines, which seem to have a vital role in the inflammatory and fibrotic processes in CD sufferers.
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Affiliation(s)
- Anna Zielińska
- Department of Biochemistry, Faculty of Medicine, Medical University of Lodz, Łódź, Poland
| | - Paweł Siwiński
- Department of General and Colorectal Surgery, Faculty of Military Medicine, Medical University of Lodz, Łódź, Poland
| | - Aleksandra Sobolewska-Włodarczyk
- Department of Biochemistry, Faculty of Medicine, Medical University of Lodz, Łódź, Poland; Department of Gastroenterology, Faculty of Military Medicine, Medical University of Lodz, Łódź, Poland
| | | | - Jakub Fichna
- Department of Biochemistry, Faculty of Medicine, Medical University of Lodz, Łódź, Poland
| | - Marcin Włodarczyk
- Department of Biochemistry, Faculty of Medicine, Medical University of Lodz, Łódź, Poland; Department of General and Colorectal Surgery, Faculty of Military Medicine, Medical University of Lodz, Łódź, Poland.
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Obesity in Inflammatory Bowel Disease: Gains in Adiposity despite High Prevalence of Myopenia and Osteopenia. Nutrients 2018; 10:nu10091192. [PMID: 30200405 PMCID: PMC6163971 DOI: 10.3390/nu10091192] [Citation(s) in RCA: 49] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/28/2018] [Revised: 08/18/2018] [Accepted: 08/21/2018] [Indexed: 02/07/2023] Open
Abstract
BACKGROUND Rising rates of obesity have been reported in patients with inflammatory bowel disease (IBD); however, prospective data is lacking. The aim of this study is to prospectively evaluate body composition in adults with IBD over 24 months. METHODS Whole body dual energy X-ray absorptiometry (DXA) data was performed at 0 months, 12 months, and 24 months. Bone mineral density (BMD), fat mass index (FMI (kg)/height (m²)), appendicular skeletal muscle index (ASMI (kg)/height (m²)), visceral adipose tissue and the visceral adipose height index (VHI, VAT area (cm³)/height (m²)), and clinical and anthropometric assessments were performed at each time point. Multivariable linear mixed effects regression analyses were performed. RESULTS Initially, 154 participants were assessed at baseline (70% Crohn's disease, 55% male, median age 31 years), of whom 129 underwent repeated DXA at 12 months, and 110 underwent repeated DXA at 24 months. Amongst those undergoing repeated DXA, their body mass index (BMI) significantly increased over time, such that by 24 months, 62% of patients were overweight or obese (annual change BMI β = 0.43, 95%CI = [0.18, 0.67], p = 0.0006). Gains in BMI related to increases in both FMI and VHI (β = 0.33, 95%CI = [0.14, 0.53], p = 0.0007; β = 0.08, 95%CI = [0.02, 0.13], p = 0.001; respectively), whereas ASMI decreased (β = -0.07, 95%CI = [-0.12, -0.01], p = 0.01) with a concordant rise in rates of myopenia (OR = 3.1 95%CI = [1.2, 7.7]; p = 0.01). Rates of osteopenia and osteoporosis were high (37%), but remained unchanged over time (p = 0.23). CONCLUSION Increasing rates of obesity in patients with IBD coincide with decreases in lean muscle mass over time, while high rates of osteopenia remain stable. These previously undocumented issues warrant attention in routine care to prevent avoidable morbidity.
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50
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Ge Y, Li Y, Gong J, Zhu W. Mesenteric organ lymphatics and inflammatory bowel disease. Ann Anat 2018; 218:199-204. [PMID: 29723582 DOI: 10.1016/j.aanat.2018.03.006] [Citation(s) in RCA: 18] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/13/2017] [Revised: 02/14/2018] [Accepted: 03/01/2018] [Indexed: 12/20/2022]
Abstract
Inflammatory bowel disease (IBD) is a complex gastrointestinal disorder and its etiology is unclear yet. Current theory in IBD is focused on genetics, immunity and intestinal microbes. Emerging clinical evidence and experimental results suggest that morphologic abnormalities and dysfunction of mesenteric lymphatics may have potential roles in the pathogenesis and disease course of IBD. In this review, we summarize the findings of specific investigations of the lymphatics and explore its role in IBD.
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Affiliation(s)
- Yuanyuan Ge
- Department of General Surgery, Jinling Hospital, Medical School of Nanjing University, No. 305 East Zhongshan Road, Nanjing, 210002 PR China
| | - Yi Li
- Department of General Surgery, Jinling Hospital, Medical School of Nanjing University, No. 305 East Zhongshan Road, Nanjing, 210002 PR China.
| | - Jianfeng Gong
- Department of General Surgery, Jinling Hospital, Medical School of Nanjing University, No. 305 East Zhongshan Road, Nanjing, 210002 PR China
| | - Weiming Zhu
- Department of General Surgery, Jinling Hospital, Medical School of Nanjing University, No. 305 East Zhongshan Road, Nanjing, 210002 PR China
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