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Rahaman MM, Wangchuk P, Sarker S. A systematic review on the role of gut microbiome in inflammatory bowel disease: Spotlight on virome and plant metabolites. Microb Pathog 2025; 205:107608. [PMID: 40250496 DOI: 10.1016/j.micpath.2025.107608] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/02/2024] [Revised: 04/14/2025] [Accepted: 04/16/2025] [Indexed: 04/20/2025]
Abstract
Inflammatory bowel diseases (IBD), including ulcerative colitis and Crohn's disease, arise from various factors such as dietary, genetic, immunological, and microbiological influences. The gut microbiota plays a crucial role in the development and treatment of IBD, though the exact mechanisms remain uncertain. Current research has yet to definitively establish the beneficial effects of the microbiome on IBD. Bacteria and viruses (both prokaryotic and eukaryotic) are key components of the microbiome uniquely related to IBD. Numerous studies suggest that dysbiosis of the microbiota, including bacteria, viruses, and bacteriophages, contributes to IBD pathogenesis. Conversely, some research indicates that bacteria and bacteriophages may positively impact IBD outcomes. Additionally, plant metabolites play a crucial role in alleviating IBD due to their anti-inflammatory and microbiome-modulating properties. This systematic review discusses the role of the microbiome in IBD pathogenesis and evaluates the potential connection between plant metabolites and the microbiome in the context of IBD pathophysiology.
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Affiliation(s)
- Md Mizanur Rahaman
- Biomedical Sciences and Molecular Biology, College of Medicine and Dentistry, James Cook University, Townsville, QLD, 4811, Australia; Australian Institute of Tropical Health and Medicine, James Cook University, Townsville, QLD, 4811, Australia
| | - Phurpa Wangchuk
- College of Science and Engineering, James Cook University, Nguma Bada campus, McGregor Rd, Smithfield, Cairns, QLD 4878, Australia; Australian Institute of Tropical Health and Medicine, James Cook University, Nguma Bada campus, McGregor Rd, Smithfield, Cairns, QLD, 4878, Australia
| | - Subir Sarker
- Biomedical Sciences and Molecular Biology, College of Medicine and Dentistry, James Cook University, Townsville, QLD, 4811, Australia; Australian Institute of Tropical Health and Medicine, James Cook University, Townsville, QLD, 4811, Australia.
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Chatterjee P, Canale V, King SJ, Shawki A, Lei H, Haddad M, Gries CM, McGovern DP, Borneman J, McCole DF. The JAK inhibitor, Tofacitinib, Corrects the Overexpression of CEACAM6 and Limits Susceptibility to AIEC Caused by Reduced Activity of the IBD Associated Gene, PTPN2. MEDRXIV : THE PREPRINT SERVER FOR HEALTH SCIENCES 2024:2024.09.26.24314341. [PMID: 39399045 PMCID: PMC11469354 DOI: 10.1101/2024.09.26.24314341] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Indexed: 10/15/2024]
Abstract
Background and Aims A cohort of patients with inflammatory bowel disease (IBD) exhibit expansion of the gut pathobiont, adherent-invasive E. coli (AIEC). Loss of activity of the IBD susceptibility gene, protein tyrosine phosphatase type 2 (PTPN2), results in dysbiosis of the gut microbiota both in human subjects and mice. Further, constitutive Ptpn2 knock-out (Ptpn2-KO) mice display expansion of AIEC compared to wildtype littermates. CEACAM6, a host cell surface glycoprotein, is exploited by AIEC to attach to and enter intestinal epithelial cells (IECs). Here, we investigate the role of IEC-specific PTPN2 in restricting AIEC invasion. Methods Biopsies from IBD patients heterozygous (CT) or homozygous (CC) for the PTPN2 SNP (single nucleotide polymorphism) rs1893217 were processed for immunohistochemistry. HT-29 intestinal epithelial cells (IEC) were transfected with control shRNA (PTPN2-CTL), or a shRNA targeted towards PTPN2 (PTPN2-KD). The rs1893217 SNP was inserted (PTPN2-KI), or a complete knock-out of PTPN2 (PTPN2-KO) was generated, with CRISPR-Cas9 gene editing of Caco-2BBe IEC lines. Adherence and invasion assays were performed with either the human IBD AIEC isolate, LF82, or a novel fluorescent-tagged mouse adherent-invasive E. coli (mAIECred) at multiplicity of infection (MOI) of 10. IL-6 and the pan-JAK inhibitor tofacitinib were administered to interrogate JAK-STAT signaling. Protein expression was determined by western blotting and densitometry. Results CEACAM6 expression was elevated (colon and ileum) in IBD patients carrying the PTPN2 rs1893217 SNP (CT, CC) compared to wildtype (TT) IBD patients. HT-29 and Caco-2BBe cell lines deficient in PTPN2 expressed significantly higher levels of CEACAM6. Further, PTPN2-KI and PTPN2-KO cell lines also displayed greater adherence and invasion by AIEC LF82 and higher mAIECred invasion. CEACAM6 expression was further elevated after administration of IL-6 in PTPN2-deficient cell lines compared to untreated controls. Silencing of STAT1 and 3 partially reduced CEACAM6 protein expression. Tofacitinib significantly reduced the elevated CEACAM6 protein expression and the higher AIEC adherence and invasion in PTPN2-KI and PTPN2-KO cell lines compared to DMSO controls. Conclusion Our findings highlight a crucial role for PTPN2 in restricting pathobiont entry into host cells. Our study also describes a role for the FDA-approved drug, tofacitinib (Xeljanz) in correcting the JAK-STAT-mediated over-expression of CEACAM6, used by pathobionts as an entry portal into host cells. These findings suggest a role for JAK-inhibitors in mitigating AIEC colonization in IBD-susceptible hosts.
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Affiliation(s)
- Pritha Chatterjee
- Division of Biomedical Sciences, University of California, Riverside, Riverside, California
| | - Vinicius Canale
- Division of Biomedical Sciences, University of California, Riverside, Riverside, California
| | - Stephanie J. King
- Division of Biomedical Sciences, University of California, Riverside, Riverside, California
| | - Ali Shawki
- Division of Biomedical Sciences, University of California, Riverside, Riverside, California
| | - Hillmin Lei
- Division of Biomedical Sciences, University of California, Riverside, Riverside, California
| | - Michael Haddad
- Department of Biology, University of California, Riverside, Riverside, California
| | - Casey M. Gries
- Division of Biomedical Sciences, University of California, Riverside, Riverside, California
| | - Dermot P.B. McGovern
- Department of Gastroenterology, Cedars-Sinai Medical Center, Los Angeles, California
| | - James Borneman
- Department of Microbiology and Plant Pathology, University of California, Riverside, California
| | - Declan F. McCole
- Division of Biomedical Sciences, University of California, Riverside, Riverside, California
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Weng MT, Hsiung CY, Wei SC, Chen Y. Nanotechnology for Targeted Inflammatory Bowel Disease Therapy: Challenges and Opportunities. WILEY INTERDISCIPLINARY REVIEWS. NANOMEDICINE AND NANOBIOTECHNOLOGY 2024; 16:e1999. [PMID: 39439396 DOI: 10.1002/wnan.1999] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 05/24/2024] [Accepted: 09/13/2024] [Indexed: 10/25/2024]
Abstract
Inflammatory bowel disease (IBD) is a complex and recurring inflammatory disorder that affects the gastrointestinal tract and is influenced by genetic predisposition, immune dysregulation, the gut microbiota, and environmental factors. Advanced therapies, such as biologics and small molecules, target diverse immune pathways to manage IBD. Nanoparticle (NP)-based drugs have emerged as effective tools, offering controlled drug release and targeted delivery. This review highlights NP modifications for anti-inflammatory purposes, utilizing changes such as those in size, charge, redox reactions, and ligand-receptor interactions in drug delivery systems. By using pathological and microenvironmental cues to guide NP design, precise targeting can be achieved. In IBD, a crucial aspect of NP intervention is targeting specific types of cells, such as immune and epithelial cells, to address compromised intestinal barrier function and reduce overactive immune responses. This review also addresses current challenges and future prospects, with the goal of advancing the development of NP-mediated strategies for IBD treatment.
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Affiliation(s)
- Meng-Tzu Weng
- Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan
- Department of Medical Research, National Taiwan University Hospital, Hsin-Chu Branch, Hsinchu, Taiwan
| | - Chia-Yueh Hsiung
- Institute of Biomedical Engineering, National Tsing Hua University, Hsinchu, Taiwan
| | - Shu-Chen Wei
- Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan
| | - Yunching Chen
- Institute of Biomedical Engineering, National Tsing Hua University, Hsinchu, Taiwan
- Department of Chemistry, National Tsing Hua University, Hsinchu, Taiwan
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Zhang Y, Kang Q, He L, Chan KI, Gu H, Xue W, Zhong Z, Tan W. Exploring the immunometabolic potential of Danggui Buxue Decoction for the treatment of IBD-related colorectal cancer. Chin Med 2024; 19:117. [PMID: 39210410 PMCID: PMC11360867 DOI: 10.1186/s13020-024-00978-y] [Citation(s) in RCA: 3] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/27/2024] [Accepted: 08/07/2024] [Indexed: 09/04/2024] Open
Abstract
Danggui Buxue (DGBX) decoction is a classical prescription composed of Astragali Radix (AR) and Angelicae Sinensis Radix (ASR), used to enrich blood, and nourish Qi in Chinese medicine, with the potential to recover energy and stimulate metabolism. Chronic inflammation is a risk factor in the development of inflammatory bowel disease (IBD)-related colorectal cancer (CRC). More importantly, AR and ASR have anti-inflammatory and anti-cancer activities, as well as prefiguring a potential effect on inflammation-cancer transformation. We, therefore, aimed to review the immunometabolism potential of DGBX decoction and its components in this malignant transformation, to provide a helpful complement to manage the risk of IBD-CRC. The present study investigates the multifaceted roles of DGBX decoction and its entire components AR and ASR, including anti-inflammation effects, anti-cancer properties, immune regulation, and metabolic regulation. This assessment is informed by a synthesis of scholarly literature, with more than two hundred articles retrieved from PubMed, Web of Science, and Scopus databases within the past two decades. The search strategy employed utilized keywords such as "Danggui Buxue", "Astragali Radix", "Angelicae Sinensis Radix", "Inflammation", and "Metabolism", alongside the related synonyms, with a particular emphasis on high-quality research and studies yielding significant findings. The potential of DGBX decoction in modulating immunometabolism holds promise for the treatment of IBD-related CRC. It is particularly relevant given the heterogeneity of CRC and the growing trend towards personalized medicine, but the precise and detailed mechanism necessitate further in vivo validation and extensive clinical studies to substantiate the immunometabolic modulation and delineate the pathways involved.
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Affiliation(s)
- Yang Zhang
- School of Pharmacy, Lanzhou University, Lanzhou, 730000, China
| | - Qianming Kang
- School of Pharmacy, Lanzhou University, Lanzhou, 730000, China
| | - Luying He
- School of Pharmacy, Lanzhou University, Lanzhou, 730000, China
| | - Ka Iong Chan
- Macao Centre for Research and Development in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macao, 999078, SAR, China
| | - Hui Gu
- School of Pharmacy, Lanzhou University, Lanzhou, 730000, China
| | - Wenjing Xue
- School of Pharmacy, Lanzhou University, Lanzhou, 730000, China
| | - Zhangfeng Zhong
- Macao Centre for Research and Development in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macao, 999078, SAR, China.
| | - Wen Tan
- School of Pharmacy, Lanzhou University, Lanzhou, 730000, China.
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Lakshimi VI, Kavitha M. New Insights into Prospective Health Potential of ω-3 PUFAs. Curr Nutr Rep 2023; 12:813-829. [PMID: 37996669 DOI: 10.1007/s13668-023-00508-6] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 11/09/2023] [Indexed: 11/25/2023]
Abstract
PURPOSE OF REVIEW Docosahexaenoic acid and eicosapentaenoic acid are the two essential long-chain ω-3 polyunsaturated fatty acids (ω-3 PUFAs) promoting human health which are obtained from diet or supplementation. The eicosanoids derived from ω-6 and ω-3 PUFAs have opposite characteristics of pro- and anti-inflammatory activities. The proinflammatory effects of ω-6 PUFAs are behind the pathology of the adverse health conditions of PUFA metabolism like cardiovascular diseases, neurological disorders, and inflammatory diseases. A balanced ω-6 to ω-3 ratio of 1-4:1 is critical to prevent the associated disorders. But due to modern agricultural practices, there is a disastrous shift in this ratio to 10-20:1. This review primarily aims to discuss the myriad health potentials of ω-3 PUFAs uncovered through recent research. It further manifests the importance of maintaining a balanced ω-6 to ω-3 PUFA ratio. RECENT FINDINGS ω-3 PUFAs exhibit protective effects against diabetes mellitus-associated complications including diabetic retinopathy, diabetic nephropathy, and proteinuria. COVID-19 is also not an exception to the health benefits of ω-3 PUFAs. Supplementation of ω-3 PUFAs improved the respiratory and clinical symptoms in COVID-19 patients. ω-3 PUFAs exhibit a variety of health benefits including anti-inflammatory property and antimicrobial property and are effective in protecting against various health conditions like atherosclerosis, cardiovascular diseases, diabetes mellitus, COVID-19, and neurological disorders. In the present review, various health potentials of ω-3 PUFAs are extensively reviewed and summarized. Further, the importance of a balanced ω-6 to ω-3 PUFA ratio has been emphasized besides stating the diverse sources of ω-3 PUFA.
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Affiliation(s)
- V Iswareya Lakshimi
- School of Biosciences and Technology, Vellore Institute of Technology, Vellore, 632014, Tamil Nadu, India
| | - M Kavitha
- School of Biosciences and Technology, Vellore Institute of Technology, Vellore, 632014, Tamil Nadu, India.
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Zheng Y, Li ZB, Wu ZY, Zhang KJ, Liao YJ, Wang X, Cen ZX, Dai SX, Ma WJ. Vitamin D levels in the assessment of Crohn's disease activity and their relation to nutritional status and inflammation. J Hum Nutr Diet 2023; 36:1159-1169. [PMID: 36670516 DOI: 10.1111/jhn.13139] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/17/2022] [Accepted: 01/03/2023] [Indexed: 01/22/2023]
Abstract
BACKGROUND Crohn's disease (CD) is frequently associated with malnutrition, inflammation and a deficiency of vitamin D (VD) with the relationships between these symptoms being poorly defined. VD is a modulator of the immune system and is associated with the onset of CD and disease activity. The level of serum VD may have potential in the assessment of CD activity. This study aimed to evaluate the relationships between VD, nutritional status and inflammation, and to identify more accurate VD thresholds. METHODS The study included 76 outpatients with CD diagnosed between October 2018 and October 2020 and 76 healthy volunteers. Levels of serum 25(OH)D and nutritional indicators, as well as biochemical and disease activity assessments, were conducted. RESULTS Patients with CD and healthy participants were found to differ significantly in their 25(OH)D levels as well in levels of nutritional and inflammatory indicators. The optimal VD cut-off value was found to be 46.81 nmol/L for CD development and 35.32 nmol/L for disease activity. Levels of 25(OH)D were correlated with both nutritional status and inflammation. CONCLUSIONS The VD level is likely to be a useful additional tool in the evaluation of CD patients and predicting the disease activity and clinical response. The VD level may relate both to the nutritional status and levels of inflammation in CD patients, and disease progression.
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Affiliation(s)
- Y Zheng
- Department of Nutrition, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Southern Medical University, Guangzhou, China
| | - Z-B Li
- Department of Clinical Medicine, The Second School of Clinical Medicine, Southern Medical University, Guangzhou, China
| | - Z-Y Wu
- Department of Clinical Medicine, The Second School of Clinical Medicine, Southern Medical University, Guangzhou, China
| | - K-J Zhang
- Department of Gastroenterology, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangdong Provincial Geriatrics Institute, National Key Clinical Specialty, Southern Medical University, Guangzhou, China
| | - Y-J Liao
- Department of Clinical Medicine, The Second School of Clinical Medicine, Southern Medical University, Guangzhou, China
| | - X Wang
- Department of Nutrition, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Southern Medical University, Guangzhou, China
| | - Z-X Cen
- Department of Nutrition, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Southern Medical University, Guangzhou, China
| | - S-X Dai
- Department of Gastroenterology, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangdong Provincial Geriatrics Institute, National Key Clinical Specialty, Southern Medical University, Guangzhou, China
| | - W-J Ma
- Department of Nutrition, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Southern Medical University, Guangzhou, China
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Zhou S, Chai P, Dong X, Liang Z, Yang Z, Li J, Teng G, Sun S, Xu M, Zheng ZJ, Wang J, Zhang Z, Chen K. Drinking water quality and inflammatory bowel disease: a prospective cohort study. ENVIRONMENTAL SCIENCE AND POLLUTION RESEARCH INTERNATIONAL 2023; 30:71171-71183. [PMID: 37160856 DOI: 10.1007/s11356-023-27460-w] [Citation(s) in RCA: 9] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 03/06/2023] [Accepted: 05/02/2023] [Indexed: 05/11/2023]
Abstract
Environmental factors, such as drinking water and diets, play an important role in the development of inflammatory bowel disease (IBD). This study aimed to investigate the associations of metal elements and disinfectants in drinking water with the risk of inflammatory bowel disease (IBD) and to assess whether diet influences these associations. We conducted a prospective cohort study including 22,824 participants free from IBD from the Yinzhou cohort study in the 2016-2022 period with an average follow-up of 5.24 years. The metal and disinfectant concentrations were measured in local pipeline terminal tap water samples. Cox regression models adjusted for multi-level covariates were used to estimate adjusted hazard ratios (aHRs) and 95% confidence intervals (95% CIs). During an average follow-up period of 5.24 years, 46 cases of IBD were identified. For every 1 standard deviation (SD) increase in the concentration of manganese, mercury, selenium, sulfur tetraoxide (SO4), chlorine, and nitrate nitrogen (NO3_N) were associated with a higher risk of IBD with the HRs of 1.45 (95% CI: 1.14 to 1.84), 1.51 (95% CI: 1.24-1.82), 1.29 (95% CI: 1.03-1.61), 1.52 (95% CI: 1.26-1.83), 1.26 (95% CI: 1.18-1.34), and 1.66 (95% CI: 1.32-2.09), whereas zinc and fluorine were inversely associated with IBD with the HRs of 0.42 (95% CI: 0.24 to 0.73) and 0.68 (95% CI: 0.54-0.84), respectively. Stronger associations were observed in females, higher income groups, low education groups, former drinkers, and participants who never drink tea. Diets have a moderating effect on the associations of metal and nonmetal elements with the risk of IBD. We found significant associations between exposure to metals and disinfectants and IBD. Diets regulated the associations to some extent.
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Affiliation(s)
- Shuduo Zhou
- Department of Global Health, School of Public Health, Peking University, 38 Xue Yuan Road, Haidian District, Beijing, 100191, China
- Institute for Global Health and Development, Peking University, Beijing, China
| | - Pengfei Chai
- The Center for Disease Control and Prevention of Yinzhou District, Ningbo, Zhejiang, China
| | - Xuejie Dong
- Department of Global Health, School of Public Health, Peking University, 38 Xue Yuan Road, Haidian District, Beijing, 100191, China
- Institute for Global Health and Development, Peking University, Beijing, China
| | - Zhisheng Liang
- Department of Global Health, School of Public Health, Peking University, 38 Xue Yuan Road, Haidian District, Beijing, 100191, China
| | - Zongming Yang
- Department of Epidemiology and Biostatistics, Zhejiang University School of Public Health, Hangzhou, 310058, China
| | - Junxia Li
- Department of Gastroenterology, Peking University First Hospital, Beijing, 100034, China
| | - Guigen Teng
- Department of Gastroenterology, Peking University First Hospital, Beijing, 100034, China
| | - Shengzhi Sun
- School of Public Health, Capital Medical University, Beijing, 100069, China
| | - Ming Xu
- Department of Global Health, School of Public Health, Peking University, 38 Xue Yuan Road, Haidian District, Beijing, 100191, China
- Institute for Global Health and Development, Peking University, Beijing, China
| | - Zhi-Jie Zheng
- Department of Global Health, School of Public Health, Peking University, 38 Xue Yuan Road, Haidian District, Beijing, 100191, China
- Institute for Global Health and Development, Peking University, Beijing, China
| | - Jianbing Wang
- Department of Epidemiology and Biostatistics, Zhejiang University School of Public Health, Hangzhou, 310058, China
- Department of Epidemiology and Biostatistics, and National Clinical Research Center for Child Health of the Children's Hospital, Zhejiang University School of Medicine, Hangzhou, 310058, China
| | - Zhenyu Zhang
- Department of Global Health, School of Public Health, Peking University, 38 Xue Yuan Road, Haidian District, Beijing, 100191, China.
- Institute for Global Health and Development, Peking University, Beijing, China.
| | - Kun Chen
- Department of Epidemiology and Biostatistics, Zhejiang University School of Public Health, Hangzhou, 310058, China
- Department of Epidemiology and Biostatistics, and Cancer Institute of the Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, 310058, China
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Mak JWY, Sun Y, Limsrivilai J, Abdullah M, Kaibullayeva J, Balderramo D, Vergara BI, Paudel MS, Banerjee R, Hilmi I, Ali RAR, Wei SC, Ng KK, Altuwaijri M, Kelly P, Yamamoto-Furusho JK, Kotze PG, Ahuja V, Chong VH, Dao HV, Abbey Y, Ching JYL, Ho A, Chan AKW, Bernstein CN, Gearry RB, Abreu M, Rubin DT, Dotan I, Hracs L, Kaplan GG, Ng SC. Development of the global inflammatory bowel disease visualization of epidemiology studies in the 21 st century (GIVES-21). BMC Med Res Methodol 2023; 23:129. [PMID: 37231405 DOI: 10.1186/s12874-023-01944-2] [Citation(s) in RCA: 17] [Impact Index Per Article: 8.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/17/2023] [Accepted: 05/10/2023] [Indexed: 05/27/2023] Open
Abstract
BACKGROUND There is a rapid increase in the incidence of inflammatory bowel diseases (IBD) in newly industrialized countries, yet epidemiological data is incomplete. We herein report the methodology adopted to study the incidence of IBD in newly industrialized countries and to evaluate the effect of environmental factors including diet on IBD development. METHODS Global IBD Visualization of Epidemiology Studies in the 21st Century (GIVES-21) is a population-based cohort of newly diagnosed persons with Crohn's disease and ulcerative colitis in Asia, Africa, and Latin America to be followed prospectively for 12 months. New cases were ascertained from multiple sources and were entered into a secured online system. Cases were confirmed using standard diagnostic criteria. In addition, endoscopy, pathology and pharmacy records from each local site were searched to ensure completeness of case capture. Validated environmental and dietary questionnaires were used to determine exposure in incident cases prior to diagnosis. RESULTS Through November 2022, 106 hospitals from 24 regions (16 Asia; 6 Latin America; 2 Africa) have joined the GIVES-21 Consortium. To date, over 290 incident cases have been reported. All patients have demographic data, clinical disease characteristics, and disease course data including healthcare utilization, medication history and environmental and dietary exposures data collected. We have established a comprehensive platform and infrastructure required to examine disease incidence, risk factors and disease course of IBD in the real-world setting. CONCLUSIONS The GIVES-21 consortium offers a unique opportunity to investigate the epidemiology of IBD and explores new clinical research questions on the association between environmental and dietary factors and IBD development in newly industrialized countries.
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Affiliation(s)
- Joyce W Y Mak
- Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong SAR, China
| | - Yang Sun
- The First Affiliated Hospital of Kunming Medical University, Kunming, People's Republic of China
| | | | | | - Jamilya Kaibullayeva
- Research Institute of Cardiology and Internal Diseases, Asfendiyarov Kazakh National Medical University, Almaty, Kazakhstan
| | | | | | | | - Rupa Banerjee
- Asian Institute of Gastroenterology, Hyderabad, India
| | - Ida Hilmi
- University of Malaya, Kuala Lumpur, Malaysia
| | | | - Shu Chen Wei
- National Taiwan University Hospital, Taipei, Taiwan
| | - Ka Kei Ng
- Conde S. Januário Hospital, Macao SAR, China
| | - Mansour Altuwaijri
- Division of Gastroenterology, Department of Medicine, College of Medicine, King Saud University, Riyadh, Saudi Arabia
| | - Paul Kelly
- Tropical Gastroenterology & Nutrition Group, University of Zambia School of Medicine, Lusaka, Zambia
| | | | | | - Vineet Ahuja
- All India Institute of Medical Sciences, Asian Institute of Gastroenterology, Hyderabad, India
| | | | | | | | - Jessica Y L Ching
- Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong SAR, China
| | - Agnes Ho
- Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong SAR, China
| | - Alicia K W Chan
- Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong SAR, China
| | - Charles N Bernstein
- University of Manitoba IBD Clinical and Research Center, Winnipeg, MB, Canada
| | - Richard B Gearry
- Department of Medicine, University of Otago, Christchurch, New Zealand
| | - Maria Abreu
- Department of Medicine, University of Miami Miller School of Medicine, Florida, USA
| | - David T Rubin
- Inflammatory Bowel Disease Center, University of Chicago Medicine, Chicago, IL, USA
| | - Iris Dotan
- Division of Gastroenterology, Rabin Medical Center, Petah-Tikva, Israel, Affiliated to the Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
| | - Lindsay Hracs
- Division of Gastroenterology and Hepatology, Department of Medicine, University of Calgary, Calgary, AB, Canada
| | - Gilaad G Kaplan
- Division of Gastroenterology and Hepatology, Department of Medicine, University of Calgary, Calgary, AB, Canada
| | - Siew C Ng
- Department of Medicine and Therapeutics, State Key Laboratory of Digestive Disease, The Chinese University of Hong Kong, Hong Kong SAR, China.
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Li M, Liu Y, Weigmann B. Biodegradable Polymeric Nanoparticles Loaded with Flavonoids: A Promising Therapy for Inflammatory Bowel Disease. Int J Mol Sci 2023; 24:4454. [PMID: 36901885 PMCID: PMC10003013 DOI: 10.3390/ijms24054454] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/28/2022] [Revised: 02/17/2023] [Accepted: 02/21/2023] [Indexed: 02/26/2023] Open
Abstract
Inflammatory bowel disease (IBD) is a group of disorders that cause chronic non-specific inflammation in the gastrointestinal (GI) tract, primarily affecting the ileum and colon. The incidence of IBD has risen sharply in recent years. Despite continuous research efforts over the past decades, the aetiology of IBD is still not fully understood and only a limited number of drugs are available for its treatment. Flavonoids, a ubiquitous class of natural chemicals found in plants, have been widely used in the prevention and treatment of IBD. However, their therapeutic efficacy is unsatisfactory due to poor solubility, instability, rapid metabolism, and rapid systemic elimination. With the development of nanomedicine, nanocarriers can efficiently encapsulate various flavonoids and subsequently form nanoparticles (NPs), which greatly improves the stability and bioavailability of flavonoids. Recently, progress has also been made in the methodology of biodegradable polymers that can be used to fabricate NPs. As a result, NPs can significantly enhance the preventive or therapeutic effects of flavonoids on IBD. In this review, we aim to evaluate the therapeutic effect of flavonoid NPs on IBD. Furthermore, we discuss possible challenges and future perspectives.
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Affiliation(s)
- Mingrui Li
- Department of Medicine 1, Kussmaul Campus for Medical Research, University of Erlangen-Nürnberg, 91052 Erlangen, Germany
| | - Ying Liu
- Department of Medicine 1, Kussmaul Campus for Medical Research, University of Erlangen-Nürnberg, 91052 Erlangen, Germany
| | - Benno Weigmann
- Department of Medicine 1, Kussmaul Campus for Medical Research, University of Erlangen-Nürnberg, 91052 Erlangen, Germany
- Medical Immunology Campus Erlangen, Friedrich-Alexander University Erlangen-Nürnberg, 91052 Erlangen, Germany
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10
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Muacevic A, Adler JR. Isotretinoin-Induced Inflammatory Bowel Disease: Is There a Real Association? Cureus 2022; 14:e29825. [PMID: 36337815 PMCID: PMC9626370 DOI: 10.7759/cureus.29825] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 10/02/2022] [Indexed: 11/26/2022] Open
Abstract
Inflammatory bowel disease (IBD) is an autoimmune inflammatory disorder that affects the gastrointestinal system with an annual increase in incidence and prevalence worldwide. While the precise cause behind IBD remains obscured, certain genetic susceptibilities, in addition to environmental factors, may trigger the stimulation of the immunoinflammatory system against the gastrointestinal system, eventually resulting in IBD. Furthermore, certain medications have been proposed to increase the risk of developing IBD, such as isotretinoin. IBD has been reported during the post-marketing phase of isotretinoin. Subsequently, IBD development was added as a potential gastrointestinal adverse effect of isotretinoin. This review article aims to evaluate the possible association between isotretinoin exposure and the development of inflammatory bowel disease. We enrolled 32 relevant studies, including case reports, case-control, and cohort studies. The results were critically analyzed and reviewed by independent authors to answer the research question and achieve the primary endpoint.
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11
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Einfluss des Rauchens auf den Gastrointestinaltrakt. DIE RADIOLOGIE 2022; 62:772-780. [PMID: 35736999 PMCID: PMC9433359 DOI: 10.1007/s00117-022-01017-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Accepted: 05/19/2022] [Indexed: 11/18/2022]
Abstract
Hintergrund Nikotin ist ein hochwirksames Suchtgift, das bei regelmäßiger Einnahme chronische oder unheilbare Erkrankungen und somit eine eingeschränkte Lebensqualität zur Folge haben kann. Fragestellung Das Ziel dieser Übersichtsarbeit besteht darin, mögliche gesundheitliche Folgen des Rauchens auf den Gastrointestinaltrakt aufzuzeigen und einen Überblick über raucherassoziierte neoplastische und nichtneoplastische gastrointestinale Erkrankungen zu geben. Material und Methode Anhand einer ausführlichen Literaturrecherche wird der aktuelle Wissensstand zu raucherassoziierten Folgen auf den Gastrointestinaltrakt dargestellt. Ergebnisse Rauchen ist ein wesentlicher Risikofaktor für die Entstehung neoplastischer und nichtneoplastischer Erkrankungen des gesamten Gastrointestinaltrakts. Diese weisen in der radiologischen Bildgebung allerdings keine spezifischen, raucherassoziierten Merkmale auf. Schlussfolgerung Die Kenntnis einer Raucheranamnese sowie möglicher Auswirkungen von Nikotin auf den Gastrointestinaltrakt können in der radiologischen Bildinterpretation hilfreich sein sowie die diagnostische Entscheidungsfähigkeit und Genauigkeit verbessern.
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12
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Inflammatory auto-immune diseases of the intestine and their management by natural bioactive compounds. Biomed Pharmacother 2022; 151:113158. [PMID: 35644116 DOI: 10.1016/j.biopha.2022.113158] [Citation(s) in RCA: 19] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/23/2022] [Revised: 05/08/2022] [Accepted: 05/16/2022] [Indexed: 11/20/2022] Open
Abstract
Autoimmune diseases are caused by the overactivity of the immune system towards self-constituents. Risk factors of autoimmune diseases are multiple and include genetic, epigenetic, environmental, and psychological. Autoimmune chronic inflammatory bowel diseases, including celiac and inflammatory diseases (Crohn's disease and ulcerative colitis), constitute a significant health problem worldwide. Besides the complexity of the symptoms of these diseases, their treatments have only been palliative. Numerous investigations showed that natural phytochemicals could be promising strategies to fight against these autoimmune diseases. In this respect, plant-derived natural compounds such as flavonoids, phenolic acids, and terpenoids exhibited significant effects against three autoimmune diseases affecting the intestine, particularly bowel diseases. This review focuses on the role of natural compounds obtained from medicinal plants in modulating inflammatory auto-immune diseases of the intestine. It covers the most recent literature related to the effect of these natural compounds in the treatment and prevention of auto-immune diseases of the intestine.
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13
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Resveratrol and resveratrol nano-delivery systems in the treatment of inflammatory bowel disease. J Nutr Biochem 2022; 109:109101. [PMID: 35777588 DOI: 10.1016/j.jnutbio.2022.109101] [Citation(s) in RCA: 47] [Impact Index Per Article: 15.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/08/2021] [Revised: 04/04/2022] [Accepted: 06/08/2022] [Indexed: 12/22/2022]
Abstract
Inflammatory bowel disease (IBD) is a chronic disorder associated with the inflammation in the digestive tract. The exact cause of IBD is unknown; nevertheless, in IBD, the homeostasis of key regulatory factors involved in intestinal immunity has been documented to be disrupted. Despite the lack of a viable treatment for IBD, synthetic drugs and monoclonal antibodies are currently used to treat it. However, these treatments have side effects, and the high relapse rate limits their usage. Dietary polyphenols constitute a great variety of compounds and have shown an array of biological properties. Resveratrol is a natural polyphenol found in grapevines and berries. The therapeutic ability of resveratrol against IBD is amply demonstrated in many in vivo studies. Resveratrol can interact with several molecular targets (Nf-kB, SIRT1, mTOR, HIF-1α, miRNAs, and TNF-α) and effectively prevent/ alleviate IBD symptoms with promising results. Although resveratrol has profound anti-inflammatory properties against IBD, its therapeutic employment is limited due to its low water solubility, less chemical stability, less bioavailability, and rapid metabolism in vivo. Hence, resveratrol encapsulation using different carries and its controlled release has become a promising strategy to overcome limitations. Herein, we meticulously review, talk-over the anti-inflammatory effect and mechanisms of resveratrol in IBD. We further provide the latest information on resveratrol formulations and nano-delivery systems used in oral delivery of resveratrol for the treatment of IBD and offer our view on future research on resveratrol in IBD treatment.
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14
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Wan Y, Zhang B. The Impact of Zinc and Zinc Homeostasis on the Intestinal Mucosal Barrier and Intestinal Diseases. Biomolecules 2022; 12:biom12070900. [PMID: 35883455 PMCID: PMC9313088 DOI: 10.3390/biom12070900] [Citation(s) in RCA: 49] [Impact Index Per Article: 16.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/13/2022] [Revised: 06/06/2022] [Accepted: 06/11/2022] [Indexed: 02/04/2023] Open
Abstract
Zinc is an essential trace element for living organisms, and zinc homeostasis is essential for the maintenance of the normal physiological functions of cells and organisms. The intestine is the main location for zinc absorption and excretion, while zinc and zinc homeostasis is also of great significance to the structure and function of the intestinal mucosal barrier. Zinc excess or deficiency and zinc homeostatic imbalance are all associated with many intestinal diseases, such as IBD (inflammatory bowel disease), IBS (irritable bowel syndrome), and CRC (colorectal cancer). In this review, we describe the role of zinc and zinc homeostasis in the intestinal mucosal barrier and the relevance of zinc homeostasis to gastrointestinal diseases.
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15
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Homolak J, Nikolić M, Potoč D, Živković M, Bakula D, Budimir I, Pavić I, Hrabar D, Ljubičić N, Vražić D. The onset of ulcerative colitis upon Helicobacter pylori eradication in a 72-year-old woman: report of a rare case with a 3-year follow-up. BMC Gastroenterol 2021; 21:303. [PMID: 34332529 PMCID: PMC8325205 DOI: 10.1186/s12876-021-01876-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/04/2021] [Accepted: 07/06/2021] [Indexed: 11/10/2022] Open
Abstract
BACKGROUND Epidemiological studies suggest an inverse association between H. pylori infection/exposure and inflammatory bowel disease prevalence/incidence, however, there are no reports of individual patients who developed a "non-transient" ulcerative colitis (UC) following H. pylori eradication. CASE PRESENTATION We report a case of a 72-year-old female with an elderly-onset UC developed upon H. pylori eradication and a 3-year follow-up of the progression to steroid-dependent colitis complicated with enteropathic arthritis and final containment of the disease with golimumab. In our patient, H. pylori eradication was associated with the development of pancolitis that evolved into clinically, endoscopically, and pathohistologically confirmed UC. CONCLUSIONS The case of our patient provides a unique clinical context for a growing body of literature suggesting molecular mechanisms involved in the interaction of genes, environment, and microbiota to be of critical importance in the etiopathogenesis of UC, and thus, provides a valuable set of complementary translational information for preclinical and epidemiological research on the topic.
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Affiliation(s)
- J Homolak
- Department of Pharmacology, University of Zagreb School of Medicine, Zagreb, Croatia
| | - M Nikolić
- Gastroenterology and Hepatology Unit, University Hospital Centre "Sestre Milosrdnice", Vinogradska 29, 10000, Zagreb, Croatia. .,University of Zagreb School of Dental Medicine, Zagreb, Croatia.
| | - D Potoč
- University of Zagreb School of Dental Medicine, Zagreb, Croatia
| | - M Živković
- Gastroenterology and Hepatology Unit, University Hospital Centre "Sestre Milosrdnice", Vinogradska 29, 10000, Zagreb, Croatia
| | - D Bakula
- Gastroenterology and Hepatology Unit, University Hospital Centre "Sestre Milosrdnice", Vinogradska 29, 10000, Zagreb, Croatia
| | - I Budimir
- Gastroenterology and Hepatology Unit, University Hospital Centre "Sestre Milosrdnice", Vinogradska 29, 10000, Zagreb, Croatia.,University of Zagreb School of Medicine, Zagreb, Croatia
| | - I Pavić
- Department of Pathology, University Hospital Centre "Sestre Milosrdnice", Zagreb, Croatia
| | - D Hrabar
- Gastroenterology and Hepatology Unit, University Hospital Centre "Sestre Milosrdnice", Vinogradska 29, 10000, Zagreb, Croatia.,University of Zagreb School of Medicine, Zagreb, Croatia
| | - N Ljubičić
- Gastroenterology and Hepatology Unit, University Hospital Centre "Sestre Milosrdnice", Vinogradska 29, 10000, Zagreb, Croatia.,University of Zagreb School of Dental Medicine, Zagreb, Croatia.,University of Zagreb School of Medicine, Zagreb, Croatia
| | - D Vražić
- Department of Periodontology, University of Zagreb School of Dental Medicine, Zagreb, Croatia
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16
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Mahlich J, May M, Feig C, Straub V, Schmelz R. Persistence With Biologic Therapy and Associated Costs of Patients With Inflammatory Bowel Disease: A German Retrospective Claims Data Analysis. CROHN'S & COLITIS 360 2021; 3:otab011. [PMID: 36778945 PMCID: PMC9802337 DOI: 10.1093/crocol/otab011] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/30/2020] [Indexed: 12/22/2022] Open
Abstract
Background In recent years, biologic agents became a relevant and promising treatment option for inflammatory bowel diseases (IBDs). However, high treatment costs and moderate remission rates lead to a high interest in treatment persistence and corresponding economic consequences. Methods A retrospective health claims data analysis was conducted including biologic naive patients diagnosed with IBD between 2013 and 2018. Observation points were at 12 and 18 months of follow-up, starting from the first biologic prescription. Nonpersistence was defined as either no further prescription or prescription of another biologic agent within the days of supply per original prescription. Biologic agents included were Adalimumab, Golimumab, Infliximab, Ustekinumab, and Vedolizumab. Results In total, 1444 patients with IBD were included in this analysis, mostly treated with Adalimumab (46.9%) and Infliximab (39.9%) as their first biologic treatment. After 12 months, 72.2% of patients were still persistent with their initial biologic treatment with the highest shares for Infliximab (74%) and Vedolizumab (72.4%). 27.8% of patients were nonpersistent, mostly due to a switch of biologic agent (75.8%). Cox regression identified female, hospitalizations, and simultaneous prescriptions of corticosteroids and immunomodulators as risk factors for nonpersistence. Treatment costs per year were approximately 3000€ higher for nonpersistent patients (27,146€) than for persistent patients (23,839€), mostly due to inpatient treatment costs. Conclusions The persistence of biologic therapy in this study was rather high at 72% after 12 months, while nonpersistence was mostly due to switches to other biologic agents. Lack of persistence is associated with increased cost, mostly due to nonbiologic medication and inpatient treatment.
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Affiliation(s)
- Joerg Mahlich
- Health Economics and Outcomes Research, Janssen-Cilag GmbH, Neuss, Germany,Düsseldorf Institute for Competition Economics (DICE), DICE, Heinrich-Heine-University Düsseldorf, Düsseldorf, Germany,Address correspondence to: Joerg Mahlich, PhD, Janssen-Cilag, Johnson & Johnson Platz 1, 41470 Neuss, Germany ()
| | - Melanie May
- Health Economics, HGC Healthcare Consultants GmbH, Duesseldorf, Germany
| | - Chiara Feig
- Health Economics, HGC Healthcare Consultants GmbH, Duesseldorf, Germany
| | - Vincent Straub
- Health Economics, HGC Healthcare Consultants GmbH, Duesseldorf, Germany
| | - Renate Schmelz
- Medical Department, Universitätsklinikum Carl Gustav Carus, Technical University Dresden, Dresden, Germany
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17
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Direito R, Rocha J, Sepodes B, Eduardo-Figueira M. Phenolic Compounds Impact on Rheumatoid Arthritis, Inflammatory Bowel Disease and Microbiota Modulation. Pharmaceutics 2021; 13:pharmaceutics13020145. [PMID: 33499333 PMCID: PMC7912052 DOI: 10.3390/pharmaceutics13020145] [Citation(s) in RCA: 24] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/11/2020] [Revised: 12/30/2020] [Accepted: 01/18/2021] [Indexed: 12/21/2022] Open
Abstract
Non-communicable chronic diseases (NCDs) are nowadays the principal cause of death, especially in most industrialized nations. These illnesses have increased exponentially with the consumption of diets very high in fat and sugar, not to mention stress and physical inactivity among other factors. The potential impact of suboptimal diets on NCDs’ morbidity and mortality rates brings to the forefront the necessity for a new way of improving dietary habits. The literature provides extensive scientific work that presents evidence that phenolic compounds from diets have antioxidant, anti-inflammatory and antiproliferative activities that impact human health. Gut microbiota modulation by some phenolic compounds leads to favorable changes in abundance, diversity, and in the immune system. However, polyphenol’s limited bioavailability needs to be overcome, highlighting their application in new delivery systems and providing their health benefits in well-established ways such as health maintenance, treatment or adjuvant to conventional pharmacological treatments. In this context, novel dietary approaches, including new food supplements, have emerged to prevent diseases and preserve health.
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Affiliation(s)
- Rosa Direito
- Research Institute for Medicines (iMed.ULisboa), Faculdade de Farmácia, Universidade de Lisboa, Av. Prof. Gama Pinto, 1649-003 Lisbon, Portugal; (J.R.); (B.S.); (M.E.-F.)
- Correspondence: ; Tel.: +351-96-3654-899
| | - João Rocha
- Research Institute for Medicines (iMed.ULisboa), Faculdade de Farmácia, Universidade de Lisboa, Av. Prof. Gama Pinto, 1649-003 Lisbon, Portugal; (J.R.); (B.S.); (M.E.-F.)
- Department of Pharmacy, Pharmacology and Health Technologies, Faculdade de Farmácia, Universidade de Lisboa, Av. Prof. Gama Pinto, 1649-003 Lisbon, Portugal
| | - Bruno Sepodes
- Research Institute for Medicines (iMed.ULisboa), Faculdade de Farmácia, Universidade de Lisboa, Av. Prof. Gama Pinto, 1649-003 Lisbon, Portugal; (J.R.); (B.S.); (M.E.-F.)
- Department of Pharmacy, Pharmacology and Health Technologies, Faculdade de Farmácia, Universidade de Lisboa, Av. Prof. Gama Pinto, 1649-003 Lisbon, Portugal
| | - Maria Eduardo-Figueira
- Research Institute for Medicines (iMed.ULisboa), Faculdade de Farmácia, Universidade de Lisboa, Av. Prof. Gama Pinto, 1649-003 Lisbon, Portugal; (J.R.); (B.S.); (M.E.-F.)
- Department of Pharmaceutical Sciences and Medicines, Faculdade de Farmácia, Universidade de Lisboa, Av. Prof. Gama Pinto, 1649-003 Lisbon, Portugal
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18
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The Association between Drinking Water Quality and Inflammatory Bowel Disease-A Study in Eastern Croatia. INTERNATIONAL JOURNAL OF ENVIRONMENTAL RESEARCH AND PUBLIC HEALTH 2020; 17:ijerph17228495. [PMID: 33207850 PMCID: PMC7697303 DOI: 10.3390/ijerph17228495] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 10/01/2020] [Revised: 11/12/2020] [Accepted: 11/13/2020] [Indexed: 01/22/2023]
Abstract
The incidence rate of inflammatory bowel disease (IBD) is becoming a global health problem that could be caused by changes in environmental and lifestyle habits. The study aimed to identify the association between the quality of drinking water, i.e., physiochemical and biological aspects of the phenotype and activity of IBD in Eastern Croatia. The study included 312 patients (63.4% ulcerative colitis, UC, and 36.6% Crohn's disease, CD) from the area of Eastern Croatia. The data were collected by questionnaires and the analysis of the water safety, based on 65 samples of drinking water by the patient's water supply method (public supply, rural water supply, and private well). IBD was active in 38.0% patients (34.0% CD and 40.0% UC). Significant differences (p = 0.001) were observed in the distribution of patients, according to counties in which they lived in. The largest deviation was noted in coliform bacteria, Escherichia coli, and enterococci bacteria, Fe, Al, and nitrate in rural water supply and private wells, although, without significant impact on IBD phenotype and activity. The hazard quotient (HQ) simulations showed that children are a sensitive group, regarding exposure to nitrates in drinking water over a long period of time, so there is a need for further monitoring and analysis of this issue.
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19
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Marotto D, Atzeni F, Ardizzone S, Monteleone G, Giorgi V, Sarzi-Puttini P. Extra-intestinal manifestations of inflammatory bowel diseases. Pharmacol Res 2020; 161:105206. [PMID: 32998068 DOI: 10.1016/j.phrs.2020.105206] [Citation(s) in RCA: 25] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/30/2020] [Revised: 09/12/2020] [Accepted: 09/12/2020] [Indexed: 01/01/2023]
Abstract
Inflammatory bowel disease (IBDs), including the two main subtypes of Crohn's disease and ulcerative colitis, not only affects the gastrointestinal system, but also has a wide range of extra-intestinal manifestations (EIMs) that are major sources of morbidity and disability, and therefore represent what can be considered a real syndrome. The pathogenetic mechanisms underlying these EIMs are unknown, but some may share a common pathogenesis with IBD and others may be due to IBD treatment. The aim of this review is to examine our current knowledge of IBD EIMs and their treatment.
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Affiliation(s)
- Daniela Marotto
- Rheumatology Unit, P. Dettori Hospital, AST Sardegna, Tempio Pausania, Italy.
| | - Fabiola Atzeni
- Rheumatology Unit, University of Messina, Messina, Italy
| | - Sandro Ardizzone
- Gastroenterology Unit, Internal Medicine Department, ASST Fatebenefratelli-Sacco, Milan University School of Medicine, Milan, Italy
| | - Giovanni Monteleone
- Department of Systems Medicine, University of Rome "TOR VERGATA", Rome, Italy
| | - Valeria Giorgi
- Rheumatology Unit, Internal Medicine Department, ASST Fatebenefratelli-Sacco, Milan University School of Medicine, Milan, Italy
| | - Piercarlo Sarzi-Puttini
- Rheumatology Unit, Internal Medicine Department, ASST Fatebenefratelli-Sacco, Milan University School of Medicine, Milan, Italy
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20
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Barra M, Danino T, Garrido D. Engineered Probiotics for Detection and Treatment of Inflammatory Intestinal Diseases. Front Bioeng Biotechnol 2020; 8:265. [PMID: 32296696 PMCID: PMC7137092 DOI: 10.3389/fbioe.2020.00265] [Citation(s) in RCA: 50] [Impact Index Per Article: 10.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/19/2019] [Accepted: 03/13/2020] [Indexed: 12/14/2022] Open
Abstract
Inflammatory intestinal diseases such as Crohn's disease and ulcerative colitis have seen an increase in their prevalence in developing countries throughout the current decade. These are caused by a combination of genetic and environmental factors, altered immune response, intestinal epithelium disruption and dysbiosis in the gut microbiome. Current therapies are mainly focused on treating symptoms and are often expensive and ineffective in the long term. Recently, there has been an increase in our understanding of the relevance of the gut microbiome and its impact on human health. Advances in the use of probiotics and synthetic biology have led to the development of intestinal biosensors, bacteria engineered to detect inflammation biomarkers, that work as diagnostic tools. Additionally, live biotherapeutics have been engineered as delivery vehicles to produce treatment in situ avoiding common complications and side effects of current therapies. These genetic constructs often express a therapeutic substance constitutively, but others could be regulated externally by specific substrates, making the production of their treatment more efficient. Additionally, certain probiotics detecting specific biomarkers in situ and responding by generating a therapeutic substance are beginning to be developed. While most studies are still in the laboratory stage, a few modified probiotics have been tested in humans. These advances indicate that live biotherapeutics could have great potential as new treatments for inflammatory intestinal diseases.
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Affiliation(s)
- Maria Barra
- Department of Chemical and Bioprocess Engineering, School of Engineering, Pontificia Universidad Católica de Chile, Santiago, Chile
| | - Tal Danino
- Department of Biomedical Engineering, Columbia University, New York, NY, United States
| | - Daniel Garrido
- Department of Chemical and Bioprocess Engineering, School of Engineering, Pontificia Universidad Católica de Chile, Santiago, Chile
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Abstract
Inflammatory bowel disease (IBD) is a chronic immune-mediated inflammatory condition primarily involving the gastrointestinal tract. It includes Crohn's disease (CD), ulcerative colitis (UC), and a less common phenotype-indeterminate colitis. It is thought to result from a complex interplay of environmental, microbial, and host factors including genetic factors, although the exact mechanism is not known. Dietary factors have been shown to play a role in the pathogenesis of IBD and can potentially alter the intestinal microbiota as well as disrupt the immune function in the gut. CD is characterized by transmural inflammation, sometimes associated with granulomatous lesions, and involves the entire gastrointestinal tract but often spares the rectum. UC is characterized by mucosal inflammation typically confined to the colon and rectum. Although IBD is mostly seen in western world, recent data suggests that the incidence and prevalence are increasing worldwide. Enteral nutrition has been shown to be effective in inducing remission in pediatric population with CD; however, there is mixed data in adult population. Nutritional deficiencies such as vitamin D and zinc deficiency are often noted in IBD patients. Several extraintestinal manifestations are noted in patients with IBD. Some of them parallel with the disease activity and others are independent of the disease course. Assessment of IBD disease activity clinically, radiologically, if indicated, biochemically and endoscopically is important to guide therapy in IBD. To ensure comprehensive care, it is important to assess associated conditions such as nutritional and psychological well-being, as well as age appropriate health maintenance status prior to starting treatment for IBD. Several biologic agents including anti-tumor necrosis factor alpha (anti-TNF-α) drugs, anti-integrins, and antibodies to the p40 subunit of IL12/23 are approved for induction and maintenance of remission of IBD. Steroids are also often used for induction. Anti-metabolites and thiopurines are also useful either as monotherapy or in combination regimens. Potential side effects of anti-TNF-α drugs such as serious infections, malignancy, worsening of heart failure, and infusion-related reactions should be considered prior to starting these drugs. Anti-TNF-α drugs with or without immunomodulators (azathioprine, 6-mercaptopurine, methotrexate) are often used for the induction and maintenance of remission. Treating to target of endoscopic and clinical remission provides the best long-term outcomes. Our knowledge and understanding of IBD has grown significantly. However, there are several unanswered questions on pathogenesis, disease behavior, and drivers of inflammation in various patient subgroups which require further research.
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22
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A Comprehensive Review and Update on the Pathogenesis of Inflammatory Bowel Disease. J Immunol Res 2019; 2019:7247238. [PMID: 31886308 PMCID: PMC6914932 DOI: 10.1155/2019/7247238] [Citation(s) in RCA: 607] [Impact Index Per Article: 101.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/15/2019] [Accepted: 11/15/2019] [Indexed: 12/13/2022] Open
Abstract
Inflammatory bowel disease (IBD) is a chronic and life-threating inflammatory disease of gastroenteric tissue characterized by episodes of intestinal inflammation. The pathogenesis of IBD is complex. Recent studies have greatly improved our knowledge of the pathophysiology of IBD, leading to great advances in the treatment as well as diagnosis of IBD. In this review, we have systemically reviewed the pathogenesis of IBD and highlighted recent advances in host genetic factors, gut microbiota, and environmental factors and, especially, in abnormal innate and adaptive immune responses and their interactions, which may hold the keys to identify novel predictive or prognostic biomarkers and develop new therapies.
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23
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Zhang L, Wu TT. Inflammatory Bowel Disease. SURGICAL PATHOLOGY OF NON-NEOPLASTIC GASTROINTESTINAL DISEASES 2019:373-424. [DOI: 10.1007/978-3-030-15573-5_15] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/03/2025]
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24
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Zvolensky M, Jardin C, Farris SG, Kauffman B, Bakhshaie J, Garey L, Manning K, Rogers AH, Mayorga NA. Gut interpretations: how difficulties in emotion regulation may help explain the relation of visceral sensitivity with depression and anxiety among young adults with gastrointestinal symptoms. PSYCHOL HEALTH MED 2018; 23:840-845. [PMID: 29580068 DOI: 10.1080/13548506.2018.1455984] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 10/17/2022]
Abstract
It is widely recognized that abdominal pain and discomfort are common problems in the United States and are often associated with negative quality of life. The prevalence of anxiety/depression elevations and disorders among persons with gastrointestinal disturbances (GI) is estimated to be at least two to three times the rate in the general population. Visceral sensitivity reflects anxiety about GI sensations and its accompanying contexts and often leads to worsening of sensations (e.g. bloating, upset stomach, diarrhea). Among individuals with GI symptoms, visceral sensitivity may be associated with interpreting common sensations as catastrophic which may be related to greater difficulties with emotion dysregulation (e.g. severe anxiety and depression). The current study evaluated the indirect association of visceral sensitivity via emotion dysregulation in relation to depression, anxious arousal, and social anxiety symptoms among 344 young adults with a current history of GI symptoms and problems. Results indicated an indirect effect of visceral sensitivity via emotion dysregulation. These findings provide novel empirical support for the association of visceral sensitivity with emotional distress symptoms among young adults with GI symptoms. Based on the results, targeting emotion dysregulation may be a promising health promotion tactic among young adults with GI symptoms and disorders.
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Affiliation(s)
- Michael Zvolensky
- a Department of Psychology , University of Houston , Houston , TX , USA
- b University of Texas M.D. Anderson Cancer Center , Houston , TX , USA
| | - Charles Jardin
- a Department of Psychology , University of Houston , Houston , TX , USA
| | - Samantha G Farris
- c Department of Psychiatry and Human Behavior , The Warren Alpert Medical School of Brown University , Providence , RI , USA
- d Centers for Behavioral and Preventative Medicine , The Miriam Hospital , Providence , RI , USA
- e Butler Hospital , Providence , RI , USA
| | - Brooke Kauffman
- a Department of Psychology , University of Houston , Houston , TX , USA
| | - Jafar Bakhshaie
- a Department of Psychology , University of Houston , Houston , TX , USA
| | - Lorra Garey
- a Department of Psychology , University of Houston , Houston , TX , USA
| | - Kara Manning
- a Department of Psychology , University of Houston , Houston , TX , USA
| | - Andrew H Rogers
- a Department of Psychology , University of Houston , Houston , TX , USA
| | - Nubia A Mayorga
- a Department of Psychology , University of Houston , Houston , TX , USA
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Schiffenbauer A, Faghihi-Kashani S, O'Hanlon TP, Flegel WA, Adams SD, Targoff IN, Oddis CV, Ytterberg SR, Aggarwal R, Christopher-Stine L, Shamim EA, Dellaripa PF, Danoff SK, Mammen AL, Miller FW. The effect of cigarette smoking on the clinical and serological phenotypes of polymyositis and dermatomyositis. Semin Arthritis Rheum 2018; 48:504-512. [PMID: 29703532 DOI: 10.1016/j.semarthrit.2018.02.003] [Citation(s) in RCA: 29] [Impact Index Per Article: 4.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/18/2017] [Revised: 11/29/2017] [Accepted: 02/12/2018] [Indexed: 11/20/2022]
Abstract
OBJECTIVE Cigarette smoking is associated with immune-mediated disorders. We explored the contribution of smoking to polymyositis (PM) and dermatomyositis (DM) phenotypes and attempted to determine whether cigarette smoking effects differ by race and genotype. METHODS Associations of tobacco smoking with disease features, autoantibodies, HLA types, and race were evaluated using multiple logistic regressions in 465 patients. RESULTS Caucasian ever-smokers (n = 140) were more likely to have PM (adjusted OR = 2.24, 95% CI: 1.41\x963.57), anti-synthetase (adjusted OR = 1.93, 95% CI: 1.12\x963.34) and anti-Jo-1 autoantibodies (adjusted OR = 1.94, 95% CI: 1.08\x963.46) and less likely to have anti-p155/140 autoantibodies (adjusted OR = 0.36, 95% CI: 0.14\x960.92). In Caucasians, ever-smokers had a greater interstitial lung disease (ILD) frequency than never-smokers, while in African-Americans this relationship was inverted, but neither trend reached statistical significance. Pack-years of cigarette smoking showed significant positive associations with PM (adjusted OR = 1.02, 95% CI: 1.002\x961.04) and ILD (adjusted OR = 1.02, 95% CI: 1.001\x961.03) and was inversely associated with anti-p155/140 autoantibodies (adjusted OR = 0.93, 95% CI: 0.87\x960.99) in Caucasians. Caucasian heavy smokers (=20 pack-years) were more likely to have PM (adjusted OR = 2.52, 95% CI: 1.25\x965.09), ILD (adjusted OR = 2.48, 95% CI: 1.23\x965.00) and anti-Jo-1 autoantibodies (adjusted OR = 2.65, 95% CI: 1.16\x966.08) than never-smokers. In Caucasians, compared to never-smokers without HLA-DRB1*03:01 allele, ever-smokers with HLA-DRB1*03:01 allele had the highest odds of PM, ILD, ASA, and anti-Jo-1 autoantibodies. Risks for those with only one of these two factors were intermediate. An inverse pattern was observed regarding anti-p155/140 autoantibodies. CONCLUSION Tobacco smoking was associated with clinical and autoantibody phenotypes in Caucasians. Our findings also suggest possible interactions among HLA-DRB1*03:01 and smoking on the risk of PM and ILD, as well as, anti-synthetase, anti-Jo-1, and anti-p155/140 autoantibodies in Caucasians.
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Affiliation(s)
- Adam Schiffenbauer
- Environmental Autoimmunity Group, National Institute of Environmental Health Sciences, National Institutes of Health, Bethesda, MD.
| | - Sara Faghihi-Kashani
- Environmental Autoimmunity Group, National Institute of Environmental Health Sciences, National Institutes of Health, Bethesda, MD
| | - Terrence P O'Hanlon
- Environmental Autoimmunity Group, National Institute of Environmental Health Sciences, National Institutes of Health, Bethesda, MD
| | - Willy A Flegel
- Department of Transfusion Medicine, NIH Clinical Center, National Institutes of Health, Bethesda, MD
| | - Sharon D Adams
- Department of Transfusion Medicine, NIH Clinical Center, National Institutes of Health, Bethesda, MD
| | - Ira N Targoff
- Veterans Affairs Medical Center, University of Oklahoma Health Sciences Center, Oklahoma Medical Research Foundation, Oklahoma City, OK
| | - Chester V Oddis
- Myositis Center, University of Pittsburgh School of Medicine, Pittsburgh, PA
| | | | - Rohit Aggarwal
- Myositis Center, University of Pittsburgh School of Medicine, Pittsburgh, PA
| | - Lisa Christopher-Stine
- Johns Hopkins Myositis Center, Johns Hopkins University School of Medicine, Baltimore, MD; Departments of Neurology and Medicine, Johns Hopkins University School of Medicine, Baltimore, MD
| | - Ejaz A Shamim
- Department of Neurology, Mid-Atlantic Permanente Research Institute, Kaiser Permanente, Rockville, MD
| | - Paul F Dellaripa
- Division of Rheumatology, Immunology, and Allergy, Brigham and Women's Hospital, Boston, MA
| | - Sonye K Danoff
- Division of Pulmonary and Critical Care Medicine, Johns Hopkins School of Medicine, Baltimore, MD
| | - Andrew L Mammen
- Departments of Neurology and Medicine, Johns Hopkins University School of Medicine, Baltimore, MD; National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, MD
| | - Frederick W Miller
- Environmental Autoimmunity Group, National Institute of Environmental Health Sciences, National Institutes of Health, Bethesda, MD
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Zvolensky MJ, Bakhshaie J, Norton PJ, Smits JA, Buckner JD, Garey L, Manning K. Visceral sensitivity, anxiety, and smoking among treatment-seeking smokers. Addict Behav 2017; 75:1-6. [PMID: 28654824 PMCID: PMC10062190 DOI: 10.1016/j.addbeh.2017.06.014] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/14/2017] [Revised: 06/09/2017] [Accepted: 06/19/2017] [Indexed: 01/22/2023]
Abstract
It is widely recognized that smoking is related to abdominal pain and discomfort, as well as gastrointestinal disorders. Research has shown that visceral sensitivity, experiencing anxiety around gastrointestinal sensations, is associated with poorer gastrointestinal health and related health outcomes. Visceral sensitivity also increases anxiety symptoms and mediates the relation with other risk factors, including gastrointestinal distress. No work to date, however, has evaluated visceral sensitivity in the context of smoking despite the strong association between smoking and poor physical and mental health. The current study sought to examine visceral sensitivity as a unique predictor of cigarette dependence, threat-related smoking abstinence expectancies (somatic symptoms and harmful consequences), and perceived barriers for cessation via anxiety symptoms. Eighty-four treatment seeking adult daily smokers (Mage=45.1years [SD=10.4]; 71.6% male) participated in this study. There was a statistically significant indirect effect of visceral sensitivity via general anxiety symptoms on cigarette dependence (b=0.02, SE=0.01, Bootstrapped 95% CI [0.006, 0.05]), smoking abstinence somatic expectancies (b=0.10, SE=0.03, Bootstrapped 95% CI [0.03, 0.19]), smoking abstinence harmful experiences (b=0.13, SE=0.05, Bootstrapped 95% CI [0.03, 0.25]), and barriers to cessation (b=0.05, SE=0.06, Bootstrapped 95% CI [0.01, 0.13]). Overall, the present study serves as an initial investigation into the nature of the associations between visceral sensitivity, anxiety symptoms, and clinically significant smoking processes among treatment-seeking smokers. Future work is needed to explore the extent to which anxiety accounts for relations between visceral sensitivity and other smoking processes (e.g., withdrawal, cessation outcome).
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Salgado VCL, Luiz RR, Boechat N, Schorr BC, Leão IS, Nunes T, Zaltman C. Crohn's disease environmental factors in the developing world: A case-control study in a statewide catchment area in Brazil. World J Gastroenterol 2017; 23:5549-5556. [PMID: 28852314 PMCID: PMC5558118 DOI: 10.3748/wjg.v23.i30.5549] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/14/2017] [Revised: 05/10/2017] [Accepted: 07/04/2017] [Indexed: 02/06/2023] Open
Abstract
AIM To identify environmental risk factors associated with the development of Crohn's disease (CD) in order to re-assess the hygiene hypothesis. METHODS A hospital-based, case-control study was carried out with CD patients (n = 145) and controls (n = 163) representing a socioeconomically diverse statewide catchment area in Brazil. Controls were recruited from caregivers of patients seen in different outpatient clinics at the same hospital. A multi-item survey with 94 questions regarding family history of CD, perinatal and childhood circumstances, living conditions, tobacco use and familial socioeconomic status was carried out by interviewers. RESULTS On the univariate analysis, predictive variables for CD included being male, under age of 40, a high education level, urban dweller, smaller family size, exposure to enteric pathogens and user of treated water (P < 0.005). On the multivariate analysis, variables significantly associated with CD were male gender (OR = 2.09), under age 40 (OR = 3.10), white (OR = 2.32), from a small family in childhood (OR = 2.34) and adulthood (OR = 3.02), absence of viral infections in childhood (OR = 2.23), exposure to enteric pathogens (OR = 2.41), having had an appendectomy (OR = 2.47) and prior or current smoker (OR = 2.83/1.12). CONCLUSION Most variables supporting the "hygiene hypothesis" are associated with the development of CD but are not independent predictors of the diagnosis.
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Aranda-Olmedo I, Ruiz R, Peinado MJ, Rubio LA. A pea (Pisum sativum L.) seed albumin extract prevents colonic DSS induced dysbiosis in mice. J Funct Foods 2017. [DOI: 10.1016/j.jff.2017.05.038] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023] Open
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Yin W, Ludvigsson JF, Liu Z, Roosaar A, Axéll T, Ye W. Inverse Association Between Poor Oral Health and Inflammatory Bowel Diseases. Clin Gastroenterol Hepatol 2017; 15:525-531. [PMID: 27392757 DOI: 10.1016/j.cgh.2016.06.024] [Citation(s) in RCA: 19] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/18/2016] [Revised: 05/22/2016] [Accepted: 06/12/2016] [Indexed: 02/07/2023]
Abstract
BACKGROUND & AIMS The hygiene hypothesis (a lack of childhood exposure to microorganisms increases susceptibility to allergic diseases by altering immune development) has been proposed as an explanation for the increasing incidence of inflammatory bowel disease (IBD). However, there are few data on the relationship between oral hygiene and development of IBD, and study results have been inconsistent. We investigated the association between poor oral health and risks of IBD, ulcerative colitis (UC), and Crohn's disease (CD). METHODS We performed a population-based cohort study of 20,162 individuals followed for 40 years (from 1973 to 2012). Residents of 2 municipalities of Uppsala County, Sweden (N = 30,118), 15 years or older, were invited, and among them 20,333 were examined for tooth loss, dental plaques, and oral mucosal lesions at the time of study entry. Other exposure data were collected from questionnaires. Patients who later developed IBD (UC or CD) were identified by international classification codes from Swedish National Patient and Cause of Death Registers. Cox proportional hazards regression was used to estimate hazard ratios for IBD, UC, and CD. RESULTS From National Patient and Cause of Death Registers, we identified 209 individuals who developed IBD (142 developed UC and 67 developed CD), with an incidence rate of 37.3 per 100,000 person-years. We found an inverse relationship between poor oral health and IBD, especially in individuals with severe oral problems. Loss of 5-6 teeth of the 6 teeth examined was associated with a lower risk of IBD (hazard ratio, 0.56; 95% confidence interval, 0.32-0.98). Having dental plaques that covered more than 33% of tooth surface was negatively associated with CD (hazard ratio, 0.32; 95% confidence interval, 0.10-0.97). CONCLUSIONS In a population-based cohort study of more than 20,000 people in Sweden, we associated poor oral health with reduced risk of future IBD.
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Affiliation(s)
- Weiyao Yin
- Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden; Department of Reproductive Endocrinology, West China Second University Hospital, Sichuan University, Chengdu, China.
| | - Jonas F Ludvigsson
- Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden; Department of Pediatrics, Örebro University Hospital, Örebro, Sweden
| | - Zhiwei Liu
- Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden
| | - Ann Roosaar
- Department of Dental Medicine, Karolinska Institutet, Stockholm, Sweden
| | - Tony Axéll
- Maxillofacial Unit, Halmstad Hospital Halland, Halmstad, Sweden
| | - Weimin Ye
- Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
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Inflammatory Bowel Diseases. GASTROINTESTINAL TISSUE 2017. [DOI: 10.1016/b978-0-12-805377-5.00007-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/03/2025]
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Yan Y, Wang Z, Greenwald J, Kothapalli KSD, Park HG, Liu R, Mendralla E, Lawrence P, Wang X, Brenna JT. BCFA suppresses LPS induced IL-8 mRNA expression in human intestinal epithelial cells. Prostaglandins Leukot Essent Fatty Acids 2017; 116:27-31. [PMID: 28088291 DOI: 10.1016/j.plefa.2016.12.001] [Citation(s) in RCA: 69] [Impact Index Per Article: 8.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/02/2016] [Revised: 11/29/2016] [Accepted: 12/01/2016] [Indexed: 12/28/2022]
Abstract
Branched chain fatty acids (BCFA) are components of common food fats and are major constituents of the normal term human newborn GI tract. Polyunsaturated fatty acids (PUFA) have been suggested to reduce the risk and development of inflammatory bowel diseases (IBD); however, little is known about the influence of BCFA on inflammation. We investigated the effect of BCFA on interleukin (IL)-8 and NF-κB production in a human intestinal epithelial cell line (Caco-2). Cells were pre-treated with specific BCFA, or DHA, or EPA, and then activated with lipopolysaccharide (LPS). Both anteiso- and iso- BCFA reduce IL-8. Anteiso-BCFA more effectively suppressed IL-8 than iso-BCFA in LPS stimulated Caco-2 cells. However BCFA in general were less effective than DHA or EPA. Activated BCFA-treated cells expressed less of the cell surface Toll-like receptor 4 (TLR-4) compared to controls. These are the first data to show the reduction of pro-inflammatory markers in human cells mediated by BCFA.
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Affiliation(s)
- Y Yan
- State Key Laboratory of Food Science and Technology, Synergetic Innovation Center of Food Safety and Nutrition, School of Food Science and Technology, Jiangnan University, Wuxi 214122, China; Division of Nutritional Sciences, Cornell University, Ithaca, NY 14853, USA
| | - Z Wang
- Division of Nutritional Sciences, Cornell University, Ithaca, NY 14853, USA
| | - J Greenwald
- Division of Nutritional Sciences, Cornell University, Ithaca, NY 14853, USA
| | - K S D Kothapalli
- Division of Nutritional Sciences, Cornell University, Ithaca, NY 14853, USA
| | - H G Park
- Division of Nutritional Sciences, Cornell University, Ithaca, NY 14853, USA
| | - R Liu
- State Key Laboratory of Food Science and Technology, Synergetic Innovation Center of Food Safety and Nutrition, School of Food Science and Technology, Jiangnan University, Wuxi 214122, China
| | - E Mendralla
- Division of Nutritional Sciences, Cornell University, Ithaca, NY 14853, USA
| | - P Lawrence
- Division of Nutritional Sciences, Cornell University, Ithaca, NY 14853, USA
| | - X Wang
- State Key Laboratory of Food Science and Technology, Synergetic Innovation Center of Food Safety and Nutrition, School of Food Science and Technology, Jiangnan University, Wuxi 214122, China.
| | - J T Brenna
- Division of Nutritional Sciences, Cornell University, Ithaca, NY 14853, USA.
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Liu J, Li LQ, Zeng J, Cao GD, Jiang Z. Associations of fucosyltransferase 2 gene polymorphism with susceptibility to inflammatory bowel disease: A meta-analysis. Shijie Huaren Xiaohua Zazhi 2016; 24:4075-4084. [DOI: 10.11569/wcjd.v24.i29.4075] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
AIM To explore the relationship between fucosyltransferase 2 (FUT2) A385T and G428A gene polymorphisms and susceptibility to inflammatory bowel disease(IBD).
METHODS Databases including Embase, PubMed, EBM Reviews, Ovid, Springer, CNKI, and WanFang were searched for articles evaluating the relationship between FUT2 gene polymorphism and susceptibility to IBD. Available data were extracted and quality of the included studies was evaluated. Meta-analysis was conducted by using Review Manager 5.3 and Stata 12.0. Begg's funnel plot was used to assess the published bias of articles.
RESULTS Totally 10 articles were included, including 3682 cases and 5470 controls. Each genetic model in ulcerative colitis (UC) was as follows: dominant model [(AA + AT) vs TT: OR = 0.60 (95%CI: 0.43-0.85); (GG + GA) vs AA: OR = 0.51 (95%CI: 0.38-0.70)]; recessive model [(AT + TT) vs AA: OR = 0.96 (95%CI: 0.73-1.25); (GA + AA) vs GG: OR = 0.70 (95%CI: 0.36-1.36)]; codominant model [AA vs TT: OR = 1.02 (95%CI: 0.82-1.27); GG vs AA: OR = 1.23 (95%CI: 0.93-1.63)]; allele genetic model [A vs T: OR = 1.06 (95%CI: 0.95-1.17); G vs A: OR = 1.18 (95%CI: 0.68-2.04)]. Each genetic model in Crohn's disease (CD) was as follows: dominant model [(AA + AT) vs TT: OR = 0.60 (95%CI: 0.43-0.85); (GG + GA) vs AA: OR = 0.51 (95%CI: 0.38-0.70)]; recessive model [(AT + TT) vs AA]: OR = 0.99 (95%CI: 0.73-1.35); (GA + AA) vs GG: OR = 1.49 (95%CI: 1.17-1.91)]; codominant model [AA vs TT: OR = 1.37 (95%CI: 0.95-1.98); GG vs AA: OR = 0.46 (95%CI: 0.33-0.65)]; allele genetic model [G vs A: OR = 0.67 (95%CI: 0.57-0.79); G vs A: OR = 0.67 (95%CI: 0.57-0.79)].
CONCLUSION FUT2 A385T and G428A polymorphisms are not significantly related with IBD. In Asians, the TT on A385T confers a significant risk for developing CD. FUT2 G428A polymorphism is related with CD, and the allele gene A confers a risk for developing CD.
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Matini L, Ogden J. A qualitative study of patients’ experience of living with inflammatory bowel disease: A preliminary focus on the notion of adaptation. J Health Psychol 2016; 21:2493-2502. [DOI: 10.1177/1359105315580463] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/18/2022] Open
Abstract
This study investigates the lived experience of inflammatory bowel disease with the aim of examining the process of adapting to life with inflammatory bowel disease. Adaptation is often referred to as the desirable outcome in chronic illnesses such as inflammatory bowel disease; yet little is known as to how this is achieved. A total of 10 Crohn’s and 12 ulcerative colitis patients recruited from online support networks participated in individual, semi-structured interviews. The study has identified the notion of a ‘new normal’ as central to adaptation, whereby patients seek to recover a sense of normality by finding an equilibrium between their lives before and after diagnosis.
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Gómez-Gómez GJ, Masedo &A, Yela C, Martínez-Montiel MDP, Casís B. Current stage in inflammatory bowel disease: What is next? World J Gastroenterol 2015; 21:11282-11303. [PMID: 26525013 PMCID: PMC4616205 DOI: 10.3748/wjg.v21.i40.11282] [Citation(s) in RCA: 26] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/01/2015] [Revised: 07/12/2015] [Accepted: 09/02/2015] [Indexed: 02/06/2023] Open
Abstract
In recent years, the incidence of inflammatory bowel disease (IBD) has been on the rise, extending to countries where it was infrequent in the past. As a result, the gap between high and low incidence countries is decreasing. The disease, therefore, has an important economic impact on the healthcare system. Advances in recent years in pharmacogenetics and clinical pharmacology have allowed for the development of treatment strategies adjusted to the patient profile. Concurrently, new drugs aimed at inflammatory targets have been developed that may expand future treatment options. This review examines advances in the optimization of existing drug treatments and the development of novel treatment options for IBD.
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Reifen R, Karlinsky A, Stark AH, Berkovich Z, Nyska A. α-Linolenic acid (ALA) is an anti-inflammatory agent in inflammatory bowel disease. J Nutr Biochem 2015; 26:1632-40. [PMID: 26350254 DOI: 10.1016/j.jnutbio.2015.08.006] [Citation(s) in RCA: 81] [Impact Index Per Article: 8.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/02/2015] [Revised: 08/05/2015] [Accepted: 08/05/2015] [Indexed: 12/12/2022]
Abstract
Studies suggest that consumption of omega-3 (n-3) polyunsaturated fatty acids (PUFA) plays a protective role in inflammatory bowel disease; however, the use of plant-derived oils rich in α-linolenic acid (ALA) has not been widely investigated. The aims of this study were to test the effects of two different sources of (n-3) PUFA, fish and plant-derived oils, in two animal models of experimental colitis and to determine whether the (n-3) PUFA-enriched diets could ameliorate the inflammatory status. Rats were fed diets rich in corn, fish or sage oil with or without vitamin A supplementation for 3weeks then colitis was induced by adding dextran sodium sulfate to the drinking water or by injecting 2,4,6-trinitrobenzene sulfonic acid. We show that colitic rats fed the sage oil diets had a lower inflammatory response, improved histological repair and had less necrotic damage in the mucosa when compared to the corn and fish oil groups. Colonic damage and myeloperoxidase activity were significantly lower. Colonic mRNA levels of pro-inflammatory genes including interleukin IL-6, cyclooxygenase 2 and tumor necrosis factor α were markedly down-regulated in rats fed fish and sage oils compared to control. These results were supported by experiments in the human colonic epithelial cell line Caco-2, where ALA supplementation was shown to be effective in inhibiting inflammation induced by IL-1β by down-regulating mRNA levels of pro-inflammatory genes including IL-8, COX2 and inducible nitric oxide synthase. Taken together, these results suggest that plant-derived oil rich in ALA could ameliorate the inflammatory damage in colitis.
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Affiliation(s)
- Ram Reifen
- The School of Nutritional Sciences, The Robert H. Smith Faculty of Agriculture, Food and Environment, The Hebrew University of Jerusalem, Rehovot, Israel.
| | - Anna Karlinsky
- The School of Nutritional Sciences, The Robert H. Smith Faculty of Agriculture, Food and Environment, The Hebrew University of Jerusalem, Rehovot, Israel
| | - Aliza H Stark
- The School of Nutritional Sciences, The Robert H. Smith Faculty of Agriculture, Food and Environment, The Hebrew University of Jerusalem, Rehovot, Israel
| | - Zipi Berkovich
- The School of Nutritional Sciences, The Robert H. Smith Faculty of Agriculture, Food and Environment, The Hebrew University of Jerusalem, Rehovot, Israel
| | - Abraham Nyska
- Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel
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Lakatos PL, Burisch J. Environment and invironment in IBDs: partners in crime. Gut 2015; 64:1009-1010. [PMID: 25336112 DOI: 10.1136/gutjnl-2014-308460] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/30/2014] [Accepted: 10/01/2014] [Indexed: 01/28/2023]
Affiliation(s)
| | - Johan Burisch
- Gastrounit, Medical Section, Hvidovre University Hospital, Hvidovre, Denmark
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Utrilla MP, Peinado MJ, Ruiz R, Rodriguez-Nogales A, Algieri F, Rodriguez-Cabezas ME, Clemente A, Galvez J, Rubio LA. Pea (Pisum sativum L.) seed albumin extracts show anti-inflammatory effect in the DSS model of mouse colitis. Mol Nutr Food Res 2015; 59:807-19. [PMID: 25626675 DOI: 10.1002/mnfr.201400630] [Citation(s) in RCA: 59] [Impact Index Per Article: 5.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/08/2014] [Revised: 01/15/2015] [Accepted: 01/16/2015] [Indexed: 01/10/2023]
Abstract
SCOPE This study investigates the preventive effects of two pea (Pisum sativum) seed albumin extracts, either in the presence (pea seed extract [PSE]) or absence (albumin fraction from PSE [AF-PSE]) of soluble polysaccharides, in the dextran sodium sulfate (DSS) induced colitis in mice. METHODS AND RESULTS Male C57BL/6J mice were assigned to five groups: one noncolitic and four colitic. Colitis was induced by incorporating DSS (3.5%) in the drinking water for 4 days, after which DSS was removed. Treated groups received orally PSE (15 g/kg⋅day), or AF-PSE (1.5 g/kg⋅day), or pure soy Bowman-Birk inhibitor (BBI; 50 mg/kg⋅day), starting 2 wk before colitis induction, and maintained for 9 days after. All treated groups showed intestinal anti-inflammatory effect, evidenced by reduced microscopic histological damage in comparison with untreated colitic mice. The treatments ameliorated the colonic mRNA expression of different proinflammatory markers: cytokines, inducible enzymes, metalloproteinases, adhesion molecules, and toll-like receptors, as well as proteins involved in maintaining the epithelial barrier function. Furthermore, the administration of PSE, AF-PSE, or soy BBI restored bacterial counts, partially or totally, to values in healthy mice. CONCLUSION PSE and AF-PSE ameliorated DSS-induced damage to mice, their effects being due, at least partially, to the presence of active BBI.
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Affiliation(s)
- Ma Pilar Utrilla
- CIBER-EHD, Department of Pharmacology, ibs. GRANADA, Center for Biomedical Research (CIBM), University of Granada, Granada, Spain
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Moum B, Hovde Ø, Høivik ML. What have we learnt about the role of the environment and natural course of IBD in the new millennium? 20-year follow-up of the IBSEN cohort. Dig Dis 2014; 32 Suppl 1:2-9. [PMID: 25531347 DOI: 10.1159/000367818] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/02/2023]
Abstract
The incidence and prevalence of IBD, both Crohn's disease (CD) and ulcerative colitis (UC), have increased in recent years, especially in industrialized countries. Still, the etiology of IBD remains largely unknown. Most research on IBD before the 1990s was conducted on selected patient populations. Selected patient populations are likely to introduce important bias and limit the interpretation and generalizability. The inclusion of both incident and prevalent cases or the inclusion of incident cases over long periods of time (decades) might also introduce bias due to changes in treatment regimens and socioeconomic factors over timer (time-trend bias). Consequently, the choice of a well-characterized population-based inception cohort provides the best opportunity to describe the natural course of a disease. The IBSEN (Inflammatory Bowel Disease in South-Eastern Norway) study followed a large population-based cohort of newly diagnosed IBD patients for 20 years and has contributed significantly to the knowledge of the natural course of IBD.
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Affiliation(s)
- Bjørn Moum
- Department of Gastroenterology, Oslo University Hospital Ullevål, Oslo, Norway
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Becker HM, Apladas A, Scharl M, Fried M, Rogler G. Probiotic Escherichia coli Nissle 1917 and commensal E. coli K12 differentially affect the inflammasome in intestinal epithelial cells. Digestion 2014; 89:110-8. [PMID: 24503609 DOI: 10.1159/000357521] [Citation(s) in RCA: 29] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/10/2013] [Accepted: 11/22/2013] [Indexed: 02/04/2023]
Abstract
BACKGROUND The probiotic bacterial strain Escherichia coli Nissle 1917 (EcN) is used for the treatment of ulcerative colitis (UC), diarrhea and constipation. Its beneficial effects in the treatment of UC have been demonstrated in several controlled clinical studies; however, the mechanism of action on the cellular level is still not completely clear. The intracellular pattern recognition receptor NLRP3 is expressed in intestinal epithelial cells (IEC), activates caspase-1 within the inflammasome complex and has been implicated to play a role in the etiology of inflammatory bowel diseases. METHODS Probiotic EcN and commensal E. coli K12 were applied to IEC in vitro. Inflammasome activation, interleukin (IL)-18 release and caspase-1 activation were determined by coimmunoprecipitation, Western blot and ELISA. Apoptosis was investigated by Western blot. RESULTS Incubation of Caco-2 cells with EcN resulted in lower inflammasome activation and subsequent secretion of mature IL-18 as compared to the commensal strain K12. Induction of apoptosis as determined by cleavage of caspase-3 and poly (ADP-ribose) polymerase were lower in EcN-stimulated cells. Autophagy was induced by both bacterial strains, but to a higher extent by K12. CONCLUSION These findings indicate that genetically very similar E. coli strains differ markedly in their ability to activate the inflammasome.
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Affiliation(s)
- Helen M Becker
- Division of Gastroenterology and Hepatology, University Hospital Zurich
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do Carmo AM, Santos FM, Ortiz-Agostinho CL, Nishitokukado I, Frota CS, Gomes FU, de Arruda Leite AZ, Pannuti CS, Boas LSV, Teixeira MG, Sipahi AM. Cytomegalovirus infection in inflammatory bowel disease is not associated with worsening of intestinal inflammatory activity. PLoS One 2014; 9:e111574. [PMID: 25387236 PMCID: PMC4227676 DOI: 10.1371/journal.pone.0111574] [Citation(s) in RCA: 23] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/06/2014] [Accepted: 09/20/2014] [Indexed: 12/15/2022] Open
Abstract
BACKGROUND Cytomegalovirus is highly prevalent virus and usually occurs in immunocompromised patients. The pathophysiology and treatment of inflammatory bowel disease often induce a state of immunosuppression. Because this, there are still doubts and controversies about the relationship between inflammatory bowel disease and cytomegalovirus. AIM Evaluate the frequency of cytomegalovirus in patients with inflammatory bowel disease and identify correlations. METHODS Patients with inflammatory bowel disease underwent an interview, review of records and collection of blood and fecal samples. The search for cytomegalovirus was performed by IgG and IgM blood serology, by real-time PCR in the blood and by qualitative PCR in feces. Results were correlated with red blood cell levels, C-reactive protein levels, erythrocyte sedimentation rates and fecal calprotectin levels for each patient. RESULTS Among the 400 eligible patients, 249 had Crohn's disease, and 151 had ulcerative colitis. In the group of Crohn's disease, 67 of the patients had moderate or severe disease, but 126 patients presented with active disease, based on the evaluation of the fecal calprotectin. In patients with ulcerative colitis, only 21 patients had moderate disease, but 76 patients presented with active disease, based on the evaluation of the fecal calprotectin. A large majority of patients had positive CMV IgG. Overall, 10 patients had positive CMV IgM, and 9 patients had a positive qualitative detection of CMV DNA by PCR in the feces. All 400 patients returned negative results after the quantitative detection of CMV DNA in blood by real-time PCR. Analyzing the 19 patients with active infections, we only found that such an association occurred with the use of combined therapy (anti-TNF-alpha + azathioprine). CONCLUSION The findings show that latent cytomegalovirus infections are frequent and active cytomegalovirus infection is rare. We did not find any association between an active infection of CMV and inflammatory bowel disease activity.
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Affiliation(s)
- Alexandre Medeiros do Carmo
- Departamento de Gastroenterologia, Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo – LIM 07, São Paulo, São Paulo, Brazil
| | - Fabiana Maria Santos
- Departamento de Gastroenterologia, Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo – LIM 07, São Paulo, São Paulo, Brazil
| | - Carmen Lucia Ortiz-Agostinho
- Departamento de Gastroenterologia, Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo – LIM 07, São Paulo, São Paulo, Brazil
| | - Iêda Nishitokukado
- Departamento de Gastroenterologia, Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo – LIM 07, São Paulo, São Paulo, Brazil
| | - Cintia S. Frota
- Departamento de Gastroenterologia, Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo – LIM 07, São Paulo, São Paulo, Brazil
| | - Flavia Ubeda Gomes
- Departamento de Gastroenterologia, Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo – LIM 07, São Paulo, São Paulo, Brazil
| | - André Zonetti de Arruda Leite
- Departamento de Gastroenterologia, Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo – LIM 07, São Paulo, São Paulo, Brazil
| | - Claudio Sérgio Pannuti
- Instituto de Medicina Tropical e Departamento de Doenças Infecciosas e Parasitarias (LIM-HC) da Faculdade de Medicina da Universidade de São Paulo, São Paulo, São Paulo, Brazil
| | - Lucy Santos Vilas Boas
- Instituto de Medicina Tropical e Hospital das Clínicas da Faculdade de Medicina (LIM-HC), Universidade de São Paulo, São Paulo, São Paulo, Brazil
| | - Magaly Gemio Teixeira
- Departamento de Cirurgia do Serviço de Cirurgia do Cólon Reto e Ânus, Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo, São Paulo, São Paulo, Brazil
| | - Aytan Miranda Sipahi
- Departamento de Gastroenterologia, Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo – LIM 07, São Paulo, São Paulo, Brazil
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Ananthakrishnan AN, Khalili H, Konijeti GG, Higuchi LM, de Silva P, Fuchs CS, Richter JM, Schernhammer ES, Chan AT. Sleep duration affects risk for ulcerative colitis: a prospective cohort study. Clin Gastroenterol Hepatol 2014; 12:1879-86. [PMID: 24780288 PMCID: PMC4209312 DOI: 10.1016/j.cgh.2014.04.021] [Citation(s) in RCA: 73] [Impact Index Per Article: 6.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/04/2014] [Accepted: 04/04/2014] [Indexed: 02/07/2023]
Abstract
BACKGROUND & AIMS Sleep deprivation is associated with production of inflammatory cytokines. Disturbed sleep quality has been associated with increased risk of disease flare in patients with Crohn's disease (CD) or ulcerative colitis (UC). However, the association between sleep and risk of incident CD and UC has not been previously examined. METHODS We conducted a prospective study of women who were enrolled in the Nurses' Health Study (NHS) I since 1976 and NHS II since 1989 and followed through detailed biennial questionnaires with >90% follow-up. We examined the association of sleep duration reported in 1986 in NHS I and 2001 in NHS II with incident CD and UC, diagnosed through 2010, in NHS I and 2009 in NHS II. Cox proportional hazards models adjusting for potential confounders were used to calculate hazard ratios and 95% confidence intervals (CIs). RESULTS Among 151,871 women, we confirmed 191 cases of CD (incidence, 8/100,000 person-years) and 230 cases of UC (incidence, 10/100,000 person-years) over 2,292,849 person-years. Compared with women with reported usual sleep durations of 7-8 h/day (incidence, 8/100,000 person-years), women with reported sleep duration <6 h/day (11/100,000 person-years) or >9 h/day (20/100,000 person-years) had a higher incidence of UC (P < .05). The multivariate hazard ratios for UC were 1.51 (95% CI, 1.10-2.09) for sleep durations <6 h/day and 2.05 (95% CI, 1.44-2.92) for sleep durations >9 h/day, compared with sleep durations of 7-8 h/day. In contrast, sleep duration did not modify risk of CD. Duration of rotating night shift work was not associated with CD or UC. CONCLUSIONS On the basis of data from the NHS I and II, less than 6 hours sleep/day and more than 9 hours sleep/day are each associated with an increased risk of UC. Further studies are needed to evaluate sleep as a modifiable risk factor in the pathogenesis and progression of IBD.
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Affiliation(s)
- Ashwin N Ananthakrishnan
- Division of Gastroenterology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts.
| | - Hamed Khalili
- Division of Gastroenterology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts
| | - Gauree G Konijeti
- Division of Gastroenterology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts
| | - Leslie M Higuchi
- Division of Gastroenterology and Nutrition, Children's Hospital Boston and Harvard Medical School, Boston, Massachusetts
| | - Punyanganie de Silva
- Division of Gastroenterology, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts
| | - Charles S Fuchs
- Division of Gastroenterology and Nutrition, Children's Hospital Boston and Harvard Medical School, Boston, Massachusetts; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts; Channing Division of Network Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts
| | - James M Richter
- Division of Gastroenterology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts
| | - Eva S Schernhammer
- Channing Division of Network Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts; Division of Sleep Medicine, Harvard Medical School, Boston, Massachusetts
| | - Andrew T Chan
- Division of Gastroenterology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts; Channing Division of Network Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts
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Elitsur Y, Alrazzak BA, Preston D, Demetieva Y. Does Helicobacter pylori protect against eosinophilic esophagitis in children? Helicobacter 2014; 19:367-71. [PMID: 24750254 DOI: 10.1111/hel.12129] [Citation(s) in RCA: 33] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Abstract
BACKGROUND Helicobacter pylori infection and eosinophilic esophagitis (EoE) in children seem to have a reversed association with socioeconomic status (hygienic condition) and allergy conditions. While Hp infection (Hp) is highly associated with poor hygiene and/or poor socioeconomic status, but not with allergic conditions (asthma, rhinitis, etc.), EoE has the opposite epidemiological relationship (high association with allergy but low with low hygienic conditions). AIM To investigate the association between Hp infection and EoE in children. METHODS A retrospective chart review of all children who undergo the first upper endoscopy procedure in the gastroenterology clinic, between 2007 and 2012, was performed. Demographic, endoscopic and histological data were collected. The data was divided into 4 diagnostic groups: Hp infection, EoE, reflux esophagitis, and children who had normal histology. The relationship between Hp positive children and the other groups was performed. RESULTS A total of 966 charts were available for review. Esophagitis, idiopathic gastritis, EoE, and Hp infection were detected in 268 (28%), 480 (49%), 62 (6%), and 31 (3%) children, respectively. The mean age of the EoE group was significantly lower compared to all reference groups (p < .002), but no significant different was detected among the reference groups (gastritis, GERD, and Hp infection; p = 1.00). Simple logistic regression analysis using Hp infection as a predictor for EoE did not find a significant relationship between these two variables (p-value = .471, OR = 0.478, 95% CI 0.06-3.56). However, multivariable logistic regression analysis between EoE and the reference groups indicated a significant negative relationship between Hp infection and EoE (p-value = .023, adjusted OR = 0.096, 95%CI 0.013-0.72). Neither gastritis nor GER showed significant relationship with EoE (p-values are 1.000 and .992, respectively). CONCLUSION A reversed association between Hp and EoE was found in a cohort of West Virginia children. The possible explanations for these findings are discussed.
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Affiliation(s)
- Yoram Elitsur
- Gastroenterology Division, Department of Pediatrics, Marshall University School of Medicine, Huntington, WV, USA
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Li Y, Tian Y, Zhu W, Gong J, Gu L, Zhang W, Guo Z, Li N, Li J. Cesarean delivery and risk of inflammatory bowel disease: a systematic review and meta-analysis. Scand J Gastroenterol 2014; 49:834-844. [PMID: 24940636 DOI: 10.3109/00365521.2014.910834] [Citation(s) in RCA: 36] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/04/2023]
Abstract
OBJECTIVE It has been considered that cesarean delivery is a risk factor for the two subtypes of inflammatory bowel diseases (IBDs): Crohn's disease (CD) and ulcerative colitis (UC). The aim of this meta-analysis was to examine the relationship between cesarean delivery and the development of IBD. MATERIAL AND METHODS We searched the articles retrieved by PubMed, MEDLINE and EMBASE databases to identify observational studies regarding the relationship between cesarean section and the development of CD and/or UC. Pooled odds ratios were calculated for each relationship. RESULTS Nine studies evaluated the potential association between cesarean delivery and the development of IBD and met all of our inclusion criteria. The pooled data from six included studies indicated cesarean delivery was a risk factor for CD (95% confidence interval [CI]: 1.12-1.70; p = 0.003). Likewise, we observed a positive association between cesarean delivery and pediatric CD (95% CI: 1.06-1.35; p = 0.005). However, results from the four included studies for UC indicated the rate of cesarean section in UC patients was not higher than that of control subjects (95% CI: 0.87-1.32; p = 0.54). Overall, we did not observe a positive relationship between cesarean delivery and IBD (95% CI: 0.99-1.30; p = 0.08). CONCLUSION Results of this meta-analysis support the hypothesis that cesarean delivery was associated with the risk of CD but not of UC. The total rate of cesarean delivery of IBD patients was similar with that of control subjects.
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Affiliation(s)
- Yi Li
- Department of General Surgery, Jinling Hospital, Medical School of Nanjing University , No. 305 East Zhongshan Road, Nanjing , PR China
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Festen EAM, Weersma RK. How will insights from genetics translate to clinical practice in inflammatory bowel disease? Best Pract Res Clin Gastroenterol 2014; 28:387-97. [PMID: 24913379 DOI: 10.1016/j.bpg.2014.04.002] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/28/2014] [Revised: 04/05/2014] [Accepted: 04/13/2014] [Indexed: 02/07/2023]
Abstract
Inflammatory bowel disease, consisting of Crohn's disease and ulcerative colitis, is a chronic inflammatory disease of the gut, which arises through an excessive immune response to the normal gut flora in a genetically susceptible host. The disease affects predominantly young adults and due to its chronic and relapsing nature gives rise to a high disease burden both financially, physically and psychologically. Current therapy still cannot prevent the need for surgical intervention in more than half of IBD patients. Consequently, advances in IBD therapy are of high importance. Recently, several new forms of targeted therapy have been introduced, which should improve surgery-free prognosis of IBD patients. Recent identification of genetic risk variants for IBD has led to new insights into the biological mechanisms of the disease, which will, in the future, lead to new targeted therapy. In the meantime repositioning of drugs from biologically similar diseases towards IBD might lead to new IBD therapies.
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Affiliation(s)
- E A M Festen
- University of Groningen, University Medical Centre Groningen, Department of Gastroenterology and Hepatology, Groningen, The Netherlands; University of Groningen, University Medical Centre Groningen, Department of Genetics, The Netherlands
| | - R K Weersma
- University of Groningen, University Medical Centre Groningen, Department of Gastroenterology and Hepatology, Groningen, The Netherlands.
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Abstract
IBD is a chronic disorder with disease onset ranging from early childhood to beyond the sixth decade of life. The factors that determine the age of onset currently remain unexplained. Is timing of occurrence a random event or is it indicative of different pathophysiological pathways leading to different phenotypes across the age spectrum? Over the past decade, several studies have suggested that the characteristics and natural history of IBD seem to be different according to age of onset. This heterogeneity suggests that the respective contributions of genetics, host immune system and environment to the aetiology and phenotype of Crohn's disease and ulcerative colitis are different across ages. Critical reviews that focus on differences characterizing IBD between age groups are scarce. Therefore, this Review updates the knowledge of the differences in epidemiology, clinical characteristics, and natural history of paediatric, adult and elderly-onset IBD. In addition, potential differences in host-gene-microbial interactions according to age are highlighted.
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Le Leu RK, Young GP, Hu Y, Winter J, Conlon MA. Dietary red meat aggravates dextran sulfate sodium-induced colitis in mice whereas resistant starch attenuates inflammation. Dig Dis Sci 2013; 58:3475-82. [PMID: 23990000 DOI: 10.1007/s10620-013-2844-1] [Citation(s) in RCA: 52] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/06/2013] [Accepted: 08/09/2013] [Indexed: 02/06/2023]
Abstract
BACKGROUND Although a genetic component has been identified as a risk factor for developing inflammatory bowel disease, there is evidence that dietary factors also play a role in the development of this disease. AIMS The aim of this study was to determine the effects of feeding a red meat diet with and without resistant starch (RS) to mice with dextran sulfate sodium (DSS)-induced colitis. METHODS Colonic experimental colitis was induced in Balb/c mice using DSS. The severity of colitis was evaluated based on a disease activity index (based on bodyweight loss, stool consistency, rectal bleeding, and overall condition of the animal) and a histological score. Estimations were made of numbers of a range of different bacteria in the treatment pools of cecal digesta using quantitative real-time PCR. RESULTS Consumption of a diet high in red meat increased DSS-induced colitis as evidenced by higher disease activity and histopathological scores. Addition of RS to the red meat diet exerted a beneficial effect in acute DSS-induced colitis. Subjective analysis of numbers of a range of bacterial targets suggest changes in the gut microbiota abundance were induced by red meat and RS treatments and these changes could contribute to the reported outcomes. CONCLUSIONS A dietary intake of red meat aggravates DSS-induced colitis whereas co-consumption of resistant starch reduces the severity of colitis.
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Affiliation(s)
- Richard K Le Leu
- Preventative Health National Research Flagship, CSIRO, and CSIRO Animal, Food and Health Sciences, Adelaide, SA, Australia,
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Alvarez-Lobos M, Pizarro DP, Palavecino CE, Espinoza A, Sebastián VP, Alvarado JC, Ibañez P, Quintana C, Díaz O, Kalergis AM, Bueno SM. Role of Salmonella enterica exposure in Chilean Crohn's disease patients. World J Gastroenterol 2013; 19:5855-5862. [PMID: 24124330 PMCID: PMC3793139 DOI: 10.3748/wjg.v19.i35.5855] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/04/2013] [Revised: 04/24/2013] [Accepted: 07/19/2013] [Indexed: 02/06/2023] Open
Abstract
AIM: To study the association between exposure to Salmonella enterica (SE) and Crohn’s disease (CD) and its clinical implications in Chilean patients.
METHODS: Ninety-four unrelated Chilean CD patients from CAREI (Active Cohort Registry of Inflammatory Bowel Disease) presenting to a single inflammatory bowel disease (IBD) unit of a University Hospital were prospectively included in this study. A complete clinical evaluation, including smoking history, was performed at the initial visit, and all the important data of clinical evolution of CD were obtained. Blood samples from these CD patients and 88 healthy sex- and age-matched control subjects were analyzed for exposure to SE and for their NOD2/CARD15 gene status using the presence of anti-Salmonella lipopolysaccharide antibodies [immunoglobulin-G type (IgG)] and polymerase chain reaction (PCR), respectively. We also evaluated exposure to SE in 90 sex- and age-matched patients without CD, but with known smoking status (30 smokers, 30 non-smokers, and 30 former smokers).
RESULTS: CD patients comprised 54 females and 40 males, aged 35.5 ± 15.2 years at diagnosis with a mean follow-up of 9.0 ± 6.8 years. CD was inflammatory in 59 patients (62.7%), stricturing in 24 (25.5%) and penetrating in 15 (15.5%). Thirty cases (31.9%) had lesions in the ileum, 29 (30.8%) had ileocolonic lesions, 32 (34.0%) had colonic lesions and 23 (24.4%) had perianal disease. Sixteen CD patients (17%) were exposed to SE compared to 15 (17%) of 88 healthy control subjects (P = 0.8). Thirty-one CD patients (32.9%) were smokers, and 7 (7.4%) were former smokers at diagnosis. In the group exposed to SE, 10 of 16 patients (62.5%) were active smokers compared to 21 of 78 patients (26.9%) in the unexposed group (P = 0.01). On the other hand, 10 of 31 smoking patients (32%) were exposed to SE compared to 5 of 56 nonsmoking patients (9%), and one of the seven former smokers (14%) (P = 0.01). In the group of 90 patients without CD, but whose smoking status was known, there was no difference in exposure to SE [3 of 30 smokers (10%), 5 of 30 non-smokers (16%), and 5 of 30 former smokers (16%); P = 0.6]. There were no differences in disease severity between CD patients with and those without anti-SE IgG antibodies, estimated as the appearance of stricturing [2 (12.5%) vs 22 (28.2%); P = 0.2] or penetrating lesions [2 (12.5%) vs 13 (16.6%); P = 1.0]; or the need for immunosuppressants [11 (68.7%) vs 55 (70.5%); P = 1.0], anti-tumor necrosis factor therapy [1 (6.2%) vs 7 (8.9%); P = 1.0], hospitalization [13 (81.2%) vs 58 (74.3%); P = 0.7], or surgery [3 (18.7%) vs 12 (15.3%); P = 0.3), respectively]. No other factors were associated with SE, including NOD2/CARD15 gene status. Seventeen CD patients (18%) had at least one mutation of the NOD2/CARD15 gene.
CONCLUSION: Our study found no association between exposure to SE and CD. We observed a positive correlation between SE exposure and cigarette smoking in Chilean patients with CD, but not with disease severity.
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Sleep disturbance and risk of active disease in patients with Crohn's disease and ulcerative colitis. Clin Gastroenterol Hepatol 2013; 11:965-71. [PMID: 23376797 PMCID: PMC3659204 DOI: 10.1016/j.cgh.2013.01.021] [Citation(s) in RCA: 191] [Impact Index Per Article: 15.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/11/2012] [Revised: 01/14/2013] [Accepted: 01/18/2013] [Indexed: 02/07/2023]
Abstract
BACKGROUND & AIMS Impairment of sleep quality is common in patients with inflammatory bowel diseases (IBDs) (eg, Crohn's disease [CD] and ulcerative colitis [UC]), even during clinical remission. Sleep impairment can activate inflammatory pathways. Few prospective studies have examined the role of sleep disturbance on risk of relapse in IBD. METHODS We analyzed data from 3173 patients with IBD (1798 in clinical remission at baseline) participating in the Crohn's and Colitis Foundation of America Partners study, a longitudinal, Internet-based cohort. Sleep disturbance was measured using a subset of questions from the Patient Reported Outcomes Measurement Information Systems sleep disturbance questionnaire. Disease activity was assessed using the short Crohn's Disease Activity Index and the simple clinical colitis activity index for CD and UC, respectively. Logistic regression was used to identify predictors of sleep quality and examine the effect of sleep quality at baseline among patients in remission on risk of active disease at 6 months. RESULTS Disease activity, depression, female sex, smoking, and use of corticosteroids or narcotics were associated with sleep disturbance at enrollment. Among 1291 patients whose CD was in remission at baseline, those with impaired sleep had a 2-fold increase in risk of active disease at 6 months (adjusted odds ratio, 2.00; 95% confidence interval, 1.45-2.76); however, no effect was observed in patients with UC (odds ratio, 1.14; 95% confidence interval, 0.75-1.74). These findings persisted in a number of sensitivity analyses. CONCLUSIONS Sleep disturbance was associated with an increased risk of disease flares in CD but not UC. These findings indicate that the evaluation and treatment of sleep disturbance in patients with CD might improve outcomes.
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Abstract
Inflammatory bowel diseases [IBD; Crohn's disease (CD), ulcerative colitis (UC)] are chronic immunologically mediated diseases that are due to a dysregulated immune response to intestinal flora in a genetically susceptible host. Despite advances in genetics, the likelihood of occurrence of disease remains incompletely explained and there appears to be a strong role for the environment in mediating risk of disease. Smoking remains the most widely studied and replicated risk factor, contributing to increased risk and severity of CD while conferring protection against UC. Recent data has suggested novel risk factors. Lower plasma vitamin D is associated with an increased risk of Crohn's disease, and vitamin D supplementation may prevent relapse of disease. Several medications including oral contraceptives, post-menopausal hormone replacement, aspirin, NSAIDs, and antibiotics may increase risk of CD or UC with the mechanisms of effect remaining inadequately defined. There is continuing evidence that depression and psychosocial stress may play a role in the pathogenesis of both CD and UC, while at the same time also increasing risk for disease flares. There is also a growing understanding of the role of diet on IBD, in particular through its effect on the microbiome. Animal protein intake and n-6 fatty acids may increase risk of UC while n-3 fatty acids and dietary fiber may confer protection. The effect of diet on established disease remains poorly studied. There is need for routine measurement of a spectrum of environmental exposures in prospective studies to further our understanding.
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Chen CY, Lee KT, Charles Tzu-Chi L, Lai WT, Huang YB. Epidemiology and Disease Burden of Ulcerative Colitis in Taiwan: A Nationwide Population-Based Study. Value Health Reg Issues 2013; 2:127-134. [PMID: 29702840 DOI: 10.1016/j.vhri.2013.02.006] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/18/2022]
Abstract
OBJECTIVES A rising trend of incidence and prevalence of ulcerative colitis (UC) had been noticed in Asian countries. We conducted this study to investigate the epidemiology and medical burden of UC in Taiwan. METHODS In this 10-year retrospective database study, we identified cases of patients with UC during 1998 to 2008 from the Taiwan National Health Insurance Research Database. Patients who had a catastrophic illness certificate were included in epidemiology and medical burden calculation. RESULTS There were 1522 cases identified in our study period. The incidence increased twofold from 0.37 per 100,000 in 1998 to 0.78 per 100,000 in 2008. The incidence and prevalence had an increasing trend in our population. The cases onset age was 45.0 years on average. In our survey, most of the top 20 coexisting diseases were gastrointestinally relevant diseases, anemia (9.99%), and hypertension (7.69%). There were more than 70% patients using mesalamine, and the medical expenditure on mesalamine occupied the highest position in patients with UC. The average medical expenditure of patients with UC had a decreasing trend after 2001. CONCLUSIONS This study had the largest sample and the longest study period for the epidemiology and medical burden estimation of UC in Taiwan. The incidence rates and medicine use of patients with UC had a definite rising trend across the years in Taiwan. Patients with anemia or choric diseases were observed in our population. More surveillance of UC-related diseases and health care costs need to be conducted in the future.
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Affiliation(s)
- Chung-Yu Chen
- School of Pharmacy, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Kun-Tai Lee
- Division of Cardiology, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan
| | - Lee Charles Tzu-Chi
- Department of Public Health, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Wen-Ter Lai
- Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan
| | - Yaw-Bin Huang
- Graduate Institute of Clinical Pharmacy, Kaohsiung Medical University, Kaohsiung, Taiwan; Department of Pharmacy, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan.
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