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1
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Qiao T, Wen XH. Exploring gut microbiota as a novel therapeutic target in Crohn's disease: Insights and emerging strategies. World J Gastroenterol 2025; 31:100827. [PMID: 39811502 PMCID: PMC11684203 DOI: 10.3748/wjg.v31.i2.100827] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/28/2024] [Revised: 09/30/2024] [Accepted: 11/15/2024] [Indexed: 12/18/2024] Open
Abstract
Extensive research has investigated the etiology of Crohn's disease (CD), encompassing genetic predisposition, lifestyle factors, and environmental triggers. Recently, the gut microbiome, recognized as the human body's second-largest gene pool, has garnered significant attention for its crucial role in the pathogenesis of CD. This paper investigates the mechanisms underlying CD, focusing on the role of 'creeping fat' in disease progression and exploring emerging therapeutic strategies, including fecal microbiota transplantation, enteral nutrition, and therapeutic diets. Creeping fat has been identified as a unique pathological feature of CD and has recently been found to be associated with dysbiosis of the gut microbiome. We characterize this dysbiotic state by identifying key microbiome-bacteria, fungi, viruses, and archaea, and their contributions to CD pathogenesis. Additionally, this paper reviews contemporary therapies, emphasizing the potential of biological therapies like fecal microbiota transplantation and dietary interventions. By elucidating the complex interactions between host-microbiome dynamics and CD pathology, this article aims to advance our understanding of the disease and guide the development of more effective therapeutic strategies for managing CD.
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Affiliation(s)
- Tong Qiao
- Department of Clinical Medicine, Jinan University, Guangzhou 510632, Guangdong Province, China
| | - Xian-Hui Wen
- College of Life Science and Technology, Jinan University, Guangzhou 510632, Guangdong Province, China
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2
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Patnaik S, Durairajan SSK, Singh AK, Krishnamoorthi S, Iyaswamy A, Mandavi SP, Jeewon R, Williams LL. Role of Candida species in pathogenesis, immune regulation, and prognostic tools for managing ulcerative colitis and Crohn's disease. World J Gastroenterol 2024; 30:5212-5220. [PMID: 39735273 PMCID: PMC11612695 DOI: 10.3748/wjg.v30.i48.5212] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/05/2024] [Revised: 10/25/2024] [Accepted: 11/13/2024] [Indexed: 11/29/2024] Open
Abstract
The gut microbiome plays a key role in the pathogenesis and disease activity of inflammatory bowel disease (IBD). While research has focused on the bacterial microbiome, recent studies have shifted towards host genetics and host-fungal interactions. The mycobiota is a vital component of the gastrointestinal microbial community and plays a significant role in immune regulation. Among fungi, Candida species, particularly Candida albicans (C. albicans), have been extensively studied due to their dual role as gut commensals and invasive pathogens. Recent findings indicate that various strains of C. albicans exhibit considerable differences in virulence factors, impacting IBD's pathophysiology. Intestinal fungal dysbiosis and antifungal mucosal immunity may be associated to IBD, especially Crohn's disease (CD). This article discusses intestinal fungal dysbiosis and antifungal immunity in healthy individuals and CD patients. It discusses factors influencing the mycobiome's role in IBD pathogenesis and highlights significant contributions from the scientific community aimed at enhancing understanding of the mycobiome and encouraging further research and targeted intervention studies on specific fungal populations. Our article also provided insights into a recent study by Wu et al in the World Journal of Gastroenterology regarding the role of the gut microbiota in the pathogenesis of CD.
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Affiliation(s)
- Supriti Patnaik
- Molecular Mycology and Neurodegenerative Disease Research Laboratory, Department of Microbiology, Central University of Tamil Nadu, Thiruvarur 610005, India
| | - Siva Sundara Kumar Durairajan
- Molecular Mycology and Neurodegenerative Disease Research Laboratory, Department of Microbiology, Central University of Tamil Nadu, Thiruvarur 610005, India
- School of Biomedical Sciences, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong SAR, China
| | - Abhay Kumar Singh
- Molecular Mycology and Neurodegenerative Disease Research Laboratory, Department of Microbiology, Central University of Tamil Nadu, Thiruvarur 610005, India
| | - Senthilkumar Krishnamoorthi
- Mr. & Mrs Ko Chi-Ming Centre for Parkinson’s Disease Research, School of Chinese Medicine, Hong Kong Baptist University, Hong Kong SAR, China
| | - Ashok Iyaswamy
- Mr. & Mrs Ko Chi-Ming Centre for Parkinson’s Disease Research, School of Chinese Medicine, Hong Kong Baptist University, Hong Kong SAR, China
- Department of Biochemistry, Karpagam Academy of Higher Education, Coimbatore 641021, India
| | - Shiva Prasad Mandavi
- Department of Chemistry, Central University of Tamil Nadu, Tiruvarur 610005, India
| | - Rajesh Jeewon
- Department of Health Sciences, Faculty of Medicine and Health Sciences, University of Mauritius, Reduit 80837, Mauritius
- Department of Zoology, College of Science, King Saud University, Riyadh 11451, Saudi Arabia
| | - Leonard L Williams
- Center for Excellence in Post Harvest Technologies, North Carolina Agricultural and Technical State University, The North Carolina Research Campus, Kannapolis, NC 28081, United States
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Yin Y, Hu Y, Li Y, Peng X, Liao H, Shen W, Li L. Prevalence and Clinical Relevance of Anti-FcεRI Autoantibody in Crohn's Disease. J Asthma Allergy 2024; 17:833-845. [PMID: 39281094 PMCID: PMC11402341 DOI: 10.2147/jaa.s476501] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/27/2024] [Accepted: 09/03/2024] [Indexed: 09/18/2024] Open
Abstract
Background Mast cells can be activated in various ways and were shown to be involved in the development of Crohn's disease (CD). The diagnosis of CD is still challenging, and seeking novel biomarkers is a worthwhile endeavor. Methods An indirect enzyme-linked immunosorbent assay (ELISA) was successfully established for semi-quantitative detection of IgG anti-FcεRI in serum using human FcεRIα coated microplates and an enzyme-labeled anti-human IgG as secondary antibodies. The optimal working conditions were explored, followed by conducting the method evaluation. The serum samples and clinical data of 117 CD patients and 75 healthy controls were collected. IgE was measured by the rate turbidity turbidimetry; IgG anti-IgE and IgG anti-FcεRI were detected by ELISA. IgG anti-pancreatic antibody (PAB) and anti-Saccharomyces cerevisiae antibody (ASCA) were determined by indirect immunofluorescence assay. Data were analyzed concerning the clinical characteristics. Results IgG anti-FcεRI was an effective marker for CD (P < 0.001), but IgE and IgG anti-IgE (P = 0.089, 0.219, respectively) were not. There was a positive correlation between anti-IgE and anti-FcεRI (R = 0.380, P < 0.001). Anti-FcεRI positive patients behaved with higher disease activity [OR: 1.478 (1.200~1.821), P < 0.001], but were less likely to be located in L4 among Montreal classification [OR: 0.253 (0.077~0.837), P = 0.024]. Existing indicators, PAB and ASCA, behaved with high specificity (both > 95%) with low sensitivity (both < 30%). The combination of anti-FcεRI with existing markers significantly improved the diagnostic efficiency [AUC: 0.879 (0.831~0.928)]. Conclusion An ELISA for the detection of anti-FcεRI was established and validated, which may contribute to facilitating research on Crohn's diseases. Anti-FcεRI positive CD patients were associated with higher disease activity indices, suggesting its potential value in the diagnosis and management of CD.
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Affiliation(s)
- Yue Yin
- Department of Laboratory Medicine, Shanghai General Hospital, Shanghai, People's Republic of China
| | - Yusen Hu
- Department of Gastroenterology, Shanghai General Hospital, Shanghai, People's Republic of China
| | - Yanning Li
- Department of Laboratory Medicine, Shanghai General Hospital, Shanghai, People's Republic of China
| | - Xia Peng
- Department of Laboratory Medicine, Shanghai General Hospital, Shanghai, People's Republic of China
| | - Huanjin Liao
- Department of Laboratory Medicine, Shanghai General Hospital, Shanghai, People's Republic of China
| | - Wei Shen
- Department of Laboratory Medicine, Shanghai Jiao Tong University School of Medicine Affiliated Renji Hospital, Shanghai, People's Republic of China
| | - Li Li
- Department of Laboratory Medicine, Shanghai General Hospital, Shanghai, People's Republic of China
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Bai X, Chen S, Chi X, Xie B, Guo X, Feng H, Wei P, Zhang D, Xie S, Xie T, Chen Y, Gou M, Qiao Q, Liu X, Jin W, Xu W, Zhao Z, Xing Q, Wang X, Zhang X, Dong C. Reciprocal regulation of T follicular helper cells and dendritic cells drives colitis development. Nat Immunol 2024; 25:1383-1394. [PMID: 38942990 DOI: 10.1038/s41590-024-01882-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/07/2023] [Accepted: 05/22/2024] [Indexed: 06/30/2024]
Abstract
The immunological mechanisms underlying chronic colitis are poorly understood. T follicular helper (TFH) cells are critical in helping B cells during germinal center reactions. In a T cell transfer colitis model, a lymphoid structure composed of mature dendritic cells (DCs) and TFH cells was found within T cell zones of colonic lymphoid follicles. TFH cells were required for mature DC accumulation, the formation of DC-T cell clusters and colitis development. Moreover, DCs promoted TFH cell differentiation, contributing to colitis development. A lineage-tracing analysis showed that, following migration to the lamina propria, TFH cells transdifferentiated into long-lived pathogenic TH1 cells, promoting colitis development. Our findings have therefore demonstrated the reciprocal regulation of TFH cells and DCs in colonic lymphoid follicles, which is critical in chronic colitis pathogenesis.
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Affiliation(s)
- Xue Bai
- New Cornerstone Science Laboratory, Shanghai Immune Therapy Institute, Shanghai Jiao Tong University School of Medicine-Affiliated Renji Hospital, Shanghai, China
- Institute of Immunology and School of Medicine, Tsinghua University, Beijing, China
| | - Sijie Chen
- Bioinformatics Division, BNRIST and Department of Automation, MOE Key Laboratory of Bioinformatics, Tsinghua University, Beijing, China
| | - Xinxin Chi
- Institute of Immunology and School of Medicine, Tsinghua University, Beijing, China
| | - Bowen Xie
- Institute of Immunology and School of Medicine, Tsinghua University, Beijing, China
| | - Xinyi Guo
- New Cornerstone Science Laboratory, Shanghai Immune Therapy Institute, Shanghai Jiao Tong University School of Medicine-Affiliated Renji Hospital, Shanghai, China
- Institute of Immunology and School of Medicine, Tsinghua University, Beijing, China
| | - Han Feng
- Institute of Immunology and School of Medicine, Tsinghua University, Beijing, China
| | - Peng Wei
- Institute of Immunology and School of Medicine, Tsinghua University, Beijing, China
| | - Di Zhang
- Department of Pathology, The First Hospital of China Medical University and College of Basic Medical Sciences of China Medical University, Shenyang, China
| | - Shan Xie
- Department of Gastroenterology, Beijing Tsinghua Changgung Hospital, School of Clinical Medicine, Tsinghua University, Beijing, China
| | - Tian Xie
- Institute of Immunology and School of Medicine, Tsinghua University, Beijing, China
| | - Yongzhen Chen
- Institute of Immunology and School of Medicine, Tsinghua University, Beijing, China
| | - Mengting Gou
- New Cornerstone Science Laboratory, Shanghai Immune Therapy Institute, Shanghai Jiao Tong University School of Medicine-Affiliated Renji Hospital, Shanghai, China
| | - Qin Qiao
- Institute of Immunology and School of Medicine, Tsinghua University, Beijing, China
| | - Xinwei Liu
- Institute of Immunology and School of Medicine, Tsinghua University, Beijing, China
| | - Wei Jin
- Institute of Immunology and School of Medicine, Tsinghua University, Beijing, China
| | - Wei Xu
- Institute of Immunology and School of Medicine, Tsinghua University, Beijing, China
| | - Zixuan Zhao
- Institute of Immunology and School of Medicine, Tsinghua University, Beijing, China
| | - Qi Xing
- New Cornerstone Science Laboratory, Shanghai Immune Therapy Institute, Shanghai Jiao Tong University School of Medicine-Affiliated Renji Hospital, Shanghai, China
- Institute of Immunology and School of Medicine, Tsinghua University, Beijing, China
| | - Xiaohu Wang
- Institute of Immunology and School of Medicine, Tsinghua University, Beijing, China
| | - Xuegong Zhang
- Bioinformatics Division, BNRIST and Department of Automation, MOE Key Laboratory of Bioinformatics, Tsinghua University, Beijing, China
- Center for Synthetic and Systems Biology, School of Life Sciences and School of Medicine, Tsinghua University, Beijing, China
| | - Chen Dong
- New Cornerstone Science Laboratory, Shanghai Immune Therapy Institute, Shanghai Jiao Tong University School of Medicine-Affiliated Renji Hospital, Shanghai, China.
- Research Unit of Immune Regulation and Immune Diseases of Chinese Academy of Medical Sciences, Shanghai Jiao Tong University School of Medicine-Affiliated Renji Hospital, Shanghai, China.
- Westlake University School of Medicine, Hangzhou, China.
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Mestrovic A, Perkovic N, Bozic D, Kumric M, Vilovic M, Bozic J. Precision Medicine in Inflammatory Bowel Disease: A Spotlight on Emerging Molecular Biomarkers. Biomedicines 2024; 12:1520. [PMID: 39062093 PMCID: PMC11274502 DOI: 10.3390/biomedicines12071520] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/31/2024] [Revised: 06/30/2024] [Accepted: 07/06/2024] [Indexed: 07/28/2024] Open
Abstract
Inflammatory bowel diseases (IBD) remain challenging in terms of understanding their causes and in terms of diagnosing, treating, and monitoring patients. Modern diagnosis combines biomarkers, imaging, and endoscopic methods. Common biomarkers like CRP and fecal calprotectin, while invaluable tools, have limitations and are not entirely specific to IBD. The limitations of existing markers and the invasiveness of endoscopic procedures highlight the need to discover and implement new markers. With an ideal biomarker, we could predict the risk of disease development, as well as the possibility of response to a particular therapy, which would be significant in elucidating the pathogenesis of the disease. Recent research in the fields of machine learning, proteomics, epigenetics, and gut microbiota provides further insight into the pathogenesis of the disease and is also revealing new biomarkers. New markers, such as BAFF, PGE-MUM, oncostatin M, microRNA panels, αvβ6 antibody, and S100A12 from stool, are increasingly being identified, with αvβ6 antibody and oncostatin M being potentially close to being presented into clinical practice. However, the specificity of certain markers still remains problematic. Furthermore, the use of expensive and less accessible technology for detecting new markers, such as microRNAs, represents a limitation for widespread use in clinical practice. Nevertheless, the need for non-invasive, comprehensive markers is becoming increasingly important regarding the complexity of treatment and overall management of IBD.
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Affiliation(s)
- Antonio Mestrovic
- Department of Gastroenterology, University Hospital of Split, Spinciceva 2, 21000 Split, Croatia; (A.M.); (N.P.); (D.B.)
| | - Nikola Perkovic
- Department of Gastroenterology, University Hospital of Split, Spinciceva 2, 21000 Split, Croatia; (A.M.); (N.P.); (D.B.)
| | - Dorotea Bozic
- Department of Gastroenterology, University Hospital of Split, Spinciceva 2, 21000 Split, Croatia; (A.M.); (N.P.); (D.B.)
| | - Marko Kumric
- Department of Pathophysiology, University of Split School of Medicine, Soltanska 2A, 21000 Split, Croatia;
- Laboratory for Cardiometabolic Research, University of Split School of Medicine, Soltanska 2A, 21000 Split, Croatia
| | - Marino Vilovic
- Department of Pathophysiology, University of Split School of Medicine, Soltanska 2A, 21000 Split, Croatia;
- Laboratory for Cardiometabolic Research, University of Split School of Medicine, Soltanska 2A, 21000 Split, Croatia
| | - Josko Bozic
- Department of Pathophysiology, University of Split School of Medicine, Soltanska 2A, 21000 Split, Croatia;
- Laboratory for Cardiometabolic Research, University of Split School of Medicine, Soltanska 2A, 21000 Split, Croatia
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Sanchez Cruz C, Rojas Huerta A, Lima Barrientos J, Rodriguez C, Devani A, Boosahda V, Rasagna Mareddy NS, Briceno Silva G, Del Castillo Miranda JC, Reyes Gochi KA, Reyes Gochi MD, Alvarez S, Ghattas Hasbun PE. Inflammatory Bowel Disease and Cardiovascular Disease: An Integrative Review With a Focus on the Gut Microbiome. Cureus 2024; 16:e65136. [PMID: 39170992 PMCID: PMC11338650 DOI: 10.7759/cureus.65136] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 07/22/2024] [Indexed: 08/23/2024] Open
Abstract
Inflammatory bowel disease (IBD), which includes Crohn's disease and ulcerative colitis, is a chronic inflammatory condition of the gastrointestinal tract. Recent research indicates a significant link between IBD and cardiovascular disease (CVD), the leading cause of global morbidity and mortality. This review examines the association between IBD and CVD, emphasizing the role of the gut microbiome in this relationship. IBD patients have a higher risk of cardiovascular events, such as coronary artery disease, heart failure, and cerebrovascular incidents, primarily due to chronic systemic inflammation, genetic factors, and gut microbiota imbalance (dysbiosis). Dysbiosis in IBD increases intestinal permeability, allowing bacterial products to enter the bloodstream, which promotes inflammation and endothelial dysfunction, contributing to CVD. Understanding the gut microbiome's role in IBD and CVD suggests new therapeutic interventions. Modulating the microbiome through diet, probiotics, and fecal microbiota transplantation (FMT) are promising research avenues. These interventions aim to restore a healthy gut microbiota balance, potentially reducing inflammation and improving cardiovascular outcomes. Additionally, the review emphasizes the importance of regular cardiovascular risk assessments and personalized preventive measures in managing IBD patients. Such measures include routine monitoring of cardiovascular health, tailored lifestyle modifications, and early intervention strategies to mitigate cardiovascular risk. By integrating current knowledge, this review aims to improve understanding and management of the interconnected pathophysiology of IBD and CVD. This approach will ultimately enhance patient outcomes and provide a foundation for future research and clinical practice guidelines in this area.
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Affiliation(s)
| | - Anahi Rojas Huerta
- General Practice, Benemérita Universidad Autónoma de Puebla, Puebla, MEX
| | | | - Cristina Rodriguez
- Internal Medicine, RWJBarnabas Health Community Medical Center, Toms River, USA
| | - Aarfa Devani
- General Practice, Malla Reddy Institute of Medical Sciences, Hyderabad, IND
| | - Vanessa Boosahda
- General Practice, Xavier University School of Medicine, Oranjestad, ABW
| | | | | | | | - Kevin A Reyes Gochi
- School of Medicine, Universidad Nacional Autonoma de Mexico, Mexico City, MEX
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Khrom M, Long M, Dube S, Robbins L, Botwin GJ, Yang S, Mengesha E, Li D, Naito T, Bonthala NN, Ha C, Melmed G, Rabizadeh S, Syal G, Vasiliauskas E, Ziring D, Brant SR, Cho J, Duerr RH, Rioux J, Schumm P, Silverberg M, Ananthakrishnan AN, Faubion WA, Jabri B, Lira SA, Newberry RD, Sandler RS, Xavier RJ, Kugathasan S, Hercules D, Targan SR, Sartor RB, Haritunians T, McGovern DPB. Comprehensive Association Analyses of Extraintestinal Manifestations in Inflammatory Bowel Disease. Gastroenterology 2024; 167:315-332. [PMID: 38490347 PMCID: PMC11193636 DOI: 10.1053/j.gastro.2024.02.026] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/16/2022] [Revised: 02/11/2024] [Accepted: 02/13/2024] [Indexed: 03/17/2024]
Abstract
BACKGROUND & AIMS Patients with inflammatory bowel disease (IBD) frequently develop extraintestinal manifestations (EIMs) that contribute substantially to morbidity. We assembled the largest multicohort data set to date to investigate the clinical, serologic, and genetic factors associated with EIM complications in IBD. METHODS Data were available in 12,083 unrelated European ancestry IBD cases with presence or absence of EIMs (eg, ankylosing spondylitis [ankylosing spondylitis and sacroiliitis], primary sclerosing cholangitis [PSC], peripheral arthritis, and skin and ocular manifestations) across 4 cohorts (Cedars-Sinai Medical Center, National Institute for Diabetes and Digestive and Kidney Diseases IBD Genetics Consortium, Sinai Helmsley Alliance for Research Excellence Consortium, and Risk Stratification and Identification of Immunogenetic and Microbial Markers of Rapid Disease Progression in Children with Crohn's Disease cohort). Clinical and serologic parameters were analyzed by means of univariable and multivariable regression analyses using a mixed-effects model. Within-case logistic regression was performed to assess genetic associations. RESULTS Most EIMs occurred more commonly in female subjects (overall EIM: P = 9.0E-05, odds ratio [OR], 1.2; 95% CI, 1.1-1.4), with CD (especially colonic disease location; P = 9.8E-09, OR, 1.7; 95% CI, 1.4-2.0), and in subjects who required surgery (both CD and UC; P = 3.6E-19, OR, 1.7; 95% CI, 1.5-1.9). Smoking increased risk of EIMs except for PSC, where there was a "protective" effect. Multiple serologic associations were observed, including with PSC (anti-nuclear cytoplasmic antibody; IgG and IgA, anti-Saccharomyces cerevisiae antibodies; and anti-flagellin) and any EIM (anti-nuclear cytoplasmic antibody; IgG and IgA, anti-Saccharomyces cerevisiae antibodies; and anti-Pseudomonas fluorescens-associated sequence). We identified genome-wide significant associations within major histocompatibility complex (ankylosing spondylitis and sacroiliitis, P = 1.4E-15; OR, 2.5; 95% CI, 2.0-3.1; PSC, P = 2.7E-10; OR, 2.8; 95% CI, 2.0-3.8; ocular, P = 2E-08, OR, 3.6; 95% CI, 2.3-5.6; and overall EIM, P = 8.4E-09; OR, 2.2; 95% CI, 1.7-2.9) and CPEB4 (skin, P = 2.7E-08; OR, 1.5; 95% CI, 1.3-1.8). Genetic associations implicated tumor necrosis factor, JAK-STAT, and IL6 as potential targets for EIMs. Contrary to previous reports, only 2% of our subjects had multiple EIMs and most co-occurrences were negatively correlated. CONCLUSIONS We have identified demographic, clinical, and genetic associations with EIMs that revealed underlying mechanisms and implicated novel and existing drug targets-important steps toward a more personalized approach to IBD management.
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MESH Headings
- Humans
- Female
- Male
- Adult
- Cholangitis, Sclerosing/immunology
- Cholangitis, Sclerosing/genetics
- Cholangitis, Sclerosing/diagnosis
- Cholangitis, Sclerosing/complications
- Middle Aged
- Colitis, Ulcerative/immunology
- Colitis, Ulcerative/genetics
- Colitis, Ulcerative/diagnosis
- Crohn Disease/immunology
- Crohn Disease/genetics
- Crohn Disease/diagnosis
- Adolescent
- Risk Factors
- Child
- Spondylitis, Ankylosing/genetics
- Spondylitis, Ankylosing/immunology
- Spondylitis, Ankylosing/diagnosis
- Spondylitis, Ankylosing/complications
- Genetic Predisposition to Disease
- Young Adult
- Sex Factors
- Skin Diseases/etiology
- Skin Diseases/immunology
- Skin Diseases/genetics
- Eye Diseases/etiology
- Eye Diseases/immunology
- Eye Diseases/diagnosis
- Eye Diseases/genetics
- Eye Diseases/epidemiology
- Phenotype
- Inflammatory Bowel Diseases/genetics
- Inflammatory Bowel Diseases/immunology
- Inflammatory Bowel Diseases/diagnosis
- Logistic Models
- Aged
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Affiliation(s)
- Michelle Khrom
- F. Widjaja Inflammatory Bowel Disease Institute, Cedars-Sinai Medical Center, Los Angeles, California
| | - Millie Long
- Center for Gastrointestinal Biology and Disease, University of North Carolina, Chapel Hill, North Carolina
| | - Shishir Dube
- F. Widjaja Inflammatory Bowel Disease Institute, Cedars-Sinai Medical Center, Los Angeles, California
| | - Lori Robbins
- Palmetto Digestive Health Specialists, Charleston, South Carolina
| | - Gregory J Botwin
- F. Widjaja Inflammatory Bowel Disease Institute, Cedars-Sinai Medical Center, Los Angeles, California
| | - Shaohong Yang
- F. Widjaja Inflammatory Bowel Disease Institute, Cedars-Sinai Medical Center, Los Angeles, California
| | - Emebet Mengesha
- F. Widjaja Inflammatory Bowel Disease Institute, Cedars-Sinai Medical Center, Los Angeles, California
| | - Dalin Li
- F. Widjaja Inflammatory Bowel Disease Institute, Cedars-Sinai Medical Center, Los Angeles, California
| | - Takeo Naito
- F. Widjaja Inflammatory Bowel Disease Institute, Cedars-Sinai Medical Center, Los Angeles, California
| | - Nirupama N Bonthala
- F. Widjaja Inflammatory Bowel Disease Institute, Cedars-Sinai Medical Center, Los Angeles, California
| | - Christina Ha
- Inflammatory Bowel Disease Center, Cedars-Sinai Medical Center, Los Angeles, California
| | - Gil Melmed
- Inflammatory Bowel Disease Center, Cedars-Sinai Medical Center, Los Angeles, California
| | - Shervin Rabizadeh
- Department of Pediatrics, Pediatric Inflammatory Bowel Disease Program, Cedars-Sinai Medical Center, Los Angeles, California
| | - Gaurav Syal
- Inflammatory Bowel Disease Center, Cedars-Sinai Medical Center, Los Angeles, California
| | - Eric Vasiliauskas
- Inflammatory Bowel Disease Center, Cedars-Sinai Medical Center, Los Angeles, California
| | - David Ziring
- Inflammatory Bowel Disease Center, Cedars-Sinai Medical Center, Los Angeles, California
| | - Steven R Brant
- Division of Gastroenterology and Hepatology, Department of Medicine, Rutgers Robert Wood Johnson Medical School, New Brunswick, New Jersey
| | - Judy Cho
- Icahn School of Medicine at Mount Sinai, Dr Henry D. Janowitz Division of Gastroenterology, New York, New York
| | - Richard H Duerr
- Division of Gastroenterology, Hepatology and Nutrition, Department of Medicine, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania
| | - John Rioux
- Department of Medicine, Université de Montréal and Research Center, Montreal Heart Institute, Montréal, Québec, Canada
| | - Phil Schumm
- Department of Public Health Sciences, University of Chicago, Chicago, Illinois
| | - Mark Silverberg
- University of Toronto, Samuel Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, Toronto, Ontario, Canada
| | | | | | - Bana Jabri
- University of Chicago, Pritzker School of Medicine, Chicago, Illinois
| | - Sergio A Lira
- Immunology Institute, Icahn School of Medicine at Mount Sinai, New York, New York
| | - Rodney D Newberry
- Department of Internal Medicine, Washington University School of Medicine, St. Louis, Missouri
| | - Robert S Sandler
- Center for Gastrointestinal Biology and Disease, University of North Carolina, Chapel Hill, North Carolina
| | - Ramnik J Xavier
- Broad Institute of MIT and Harvard, Cambridge, Massachusetts
| | - Subra Kugathasan
- Children's Healthcare of Atlanta Combined Center for Pediatric Inflammatory Bowel Disease, Atlanta, Georgia; Emory School of Medicine, Atlanta, Georgia
| | | | - Stephan R Targan
- F. Widjaja Inflammatory Bowel Disease Institute, Cedars-Sinai Medical Center, Los Angeles, California
| | - R Balfour Sartor
- Center for Gastrointestinal Biology and Disease, University of North Carolina, Chapel Hill, North Carolina
| | - Talin Haritunians
- F. Widjaja Inflammatory Bowel Disease Institute, Cedars-Sinai Medical Center, Los Angeles, California
| | - Dermot P B McGovern
- F. Widjaja Inflammatory Bowel Disease Institute, Cedars-Sinai Medical Center, Los Angeles, California.
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8
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Hong SM, Baek DH. Diagnostic Procedures for Inflammatory Bowel Disease: Laboratory, Endoscopy, Pathology, Imaging, and Beyond. Diagnostics (Basel) 2024; 14:1384. [PMID: 39001273 PMCID: PMC11241288 DOI: 10.3390/diagnostics14131384] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/17/2024] [Revised: 06/26/2024] [Accepted: 06/27/2024] [Indexed: 07/16/2024] Open
Abstract
Diagnosing inflammatory bowel disease (IBD) can often be challenging, and differentiating between Crohn's disease and ulcerative colitis can be particularly difficult. Diagnostic procedures for IBD include laboratory tests, endoscopy, pathological tests, and imaging tests. Serological and stool tests can be easily performed in an outpatient setting and provide critical diagnostic clues. Although endoscopy is an invasive procedure, it offers essential diagnostic information and allows for tissue biopsy and therapeutic procedures. Video capsule endoscopy and device-assisted enteroscopy are endoscopic procedures used to evaluate the small bowel. In addition to endoscopy, magnetic resonance imaging, computed tomography, and ultrasound (US) are valuable tools for small bowel assessment. Among these, US is noninvasive and easily utilized, making its use highly practical in daily clinical practice. Endoscopic biopsy aids in the diagnosis of IBD and is crucial for assessing the histological activity of the disease, facilitating a thorough evaluation of disease remission, and aiding in the development of treatment strategies. Recent advances in artificial intelligence hold promise for enhancing various aspects of IBD management, including diagnosis, monitoring, and precision medicine. This review compiles current procedures and promising future tools for the diagnosis of IBD, providing comprehensive insights.
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Affiliation(s)
- Seung Min Hong
- Department of Internal Medicine, Pusan National University School of Medicine and Biomedical Research Institute, Pusan National University Hospital, Busan 49241, Republic of Korea
| | - Dong Hoon Baek
- Department of Internal Medicine, Pusan National University School of Medicine and Biomedical Research Institute, Pusan National University Hospital, Busan 49241, Republic of Korea
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9
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Diez-Martin E, Hernandez-Suarez L, Muñoz-Villafranca C, Martin-Souto L, Astigarraga E, Ramirez-Garcia A, Barreda-Gómez G. Inflammatory Bowel Disease: A Comprehensive Analysis of Molecular Bases, Predictive Biomarkers, Diagnostic Methods, and Therapeutic Options. Int J Mol Sci 2024; 25:7062. [PMID: 39000169 PMCID: PMC11241012 DOI: 10.3390/ijms25137062] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/02/2024] [Revised: 06/15/2024] [Accepted: 06/25/2024] [Indexed: 07/16/2024] Open
Abstract
In inflammatory bowel diseases (IBDs), such as Crohn's disease (CD) and ulcerative colitis (UC), the immune system relentlessly attacks intestinal cells, causing recurrent tissue damage over the lifetime of patients. The etiology of IBD is complex and multifactorial, involving environmental, microbiota, genetic, and immunological factors that alter the molecular basis of the organism. Among these, the microbiota and immune cells play pivotal roles; the microbiota generates antigens recognized by immune cells and antibodies, while autoantibodies target and attack the intestinal membrane, exacerbating inflammation and tissue damage. Given the altered molecular framework, the analysis of multiple molecular biomarkers in patients proves exceedingly valuable for diagnosing and prognosing IBD, including markers like C reactive protein and fecal calprotectin. Upon detection and classification of patients, specific treatments are administered, ranging from conventional drugs to new biological therapies, such as antibodies to neutralize inflammatory molecules like tumor necrosis factor (TNF) and integrin. This review delves into the molecular basis and targets, biomarkers, treatment options, monitoring techniques, and, ultimately, current challenges in IBD management.
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Affiliation(s)
- Eguzkiñe Diez-Martin
- Research and Development Department, IMG Pharma Biotech S.L., 48170 Zamudio, Spain
- Department of Immunology, Microbiology and Parasitology, Faculty of Science and Technology, University of the Basque Country (UPV/EHU), 48940 Leioa, Spain
| | - Leidi Hernandez-Suarez
- Research and Development Department, IMG Pharma Biotech S.L., 48170 Zamudio, Spain
- Department of Immunology, Microbiology and Parasitology, Faculty of Science and Technology, University of the Basque Country (UPV/EHU), 48940 Leioa, Spain
| | - Carmen Muñoz-Villafranca
- Department of Gastroenterology, University Hospital of Basurto, Avda Montevideo 18, 48013 Bilbao, Spain
| | - Leire Martin-Souto
- Department of Immunology, Microbiology and Parasitology, Faculty of Science and Technology, University of the Basque Country (UPV/EHU), 48940 Leioa, Spain
| | - Egoitz Astigarraga
- Research and Development Department, IMG Pharma Biotech S.L., 48170 Zamudio, Spain
| | - Andoni Ramirez-Garcia
- Department of Immunology, Microbiology and Parasitology, Faculty of Science and Technology, University of the Basque Country (UPV/EHU), 48940 Leioa, Spain
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Alenzi M, Schildkraut T, Hartley I, Badiani S, Ding NS, Rao V, Segal JP. The aetiology of pouchitis in patients with inflammatory bowel disease. Therap Adv Gastroenterol 2024; 17:17562848241249449. [PMID: 38812704 PMCID: PMC11135114 DOI: 10.1177/17562848241249449] [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: 01/06/2024] [Accepted: 04/08/2024] [Indexed: 05/31/2024] Open
Abstract
Restorative proctocolectomy with ileal pouch-anal anastomosis is a treatment option for patients with refractory ulcerative colitis. Pouchitis is the most common complication, representing a spectrum of diseases ranging from acute antibiotic-responsive type to chronic antibiotic-refractory. Early accurate diagnosis using a combined assessment of symptoms, endoscopy and histology is important for both treatment and prognostication. Most patients respond well to antibiotic therapy; however, management of chronic antibiotic-refractory pouchitis remains a challenge, and treatment options are based on small studies. Pouchitis is thought to be driven by the interaction between genetics, the immune system and the environment but as yet a causal relationship has yet to be identified. Further longitudinal assessment of the pouch integrating new technologies may help us understand the factors driving pouchitis. This review outlines the currently understood risk factors and aetiology of pouchitis.
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Affiliation(s)
- Maram Alenzi
- Division of Gastroenterology, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA
| | - Tamar Schildkraut
- Department of Gastroenterology, St Vincent’s Hospital, Melbourne, VIC, Australia
| | - Imogen Hartley
- Department of Gastroenterology, St Vincent’s Hospital, Melbourne, VIC, Australia
- Department of Gastroenterology, Royal Melbourne Hospital, Parkville, VIC, Australia
| | - Sarit Badiani
- Department of Surgery, Royal North Shore Hospital, St Leonards, NSW, Australia
| | - Nik Sheng Ding
- Department of Gastroenterology, St Vincent’s Hospital, Melbourne, VIC, Australia
- Department of Gastroenterology, Royal Melbourne Hospital, Parkville, VIC, Australia
| | - Vikram Rao
- Department of General Medicine, Western Health, Footscray, VIC, Australia
| | - Jonathan P. Segal
- Department of Gastroenterology, Royal Melbourne Hospital, Parkville, VIC, Australia
- Department of Medicine, University of Melbourne, Parkville, VIC, Australia
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11
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Pyrillou K, Humphry M, Kitt LA, Rodgers A, Nus M, Bennett MR, Smith KG, Lyons PA, Mallat Z, Clarke MC. Loss of T follicular regulatory cell-derived IL-1R2 augments germinal center reactions via increased IL-1. JCI Insight 2024; 9:e174005. [PMID: 38329807 PMCID: PMC11143922 DOI: 10.1172/jci.insight.174005] [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: 07/18/2023] [Accepted: 01/31/2024] [Indexed: 02/10/2024] Open
Abstract
Inappropriate immune activity is key in the pathogenesis of multiple diseases, and it is typically driven by excess inflammation and/or autoimmunity. IL-1 is often the effector owing to its powerful role in both innate and adaptive immunity, and, thus, it is tightly controlled at multiple levels. IL-1R2 antagonizes IL-1, but effects of losing this regulation are unknown. We found that IL-1R2 resolves inflammation by rapidly scavenging free IL-1. Specific IL-1R2 loss in germinal center (GC) T follicular regulatory (Tfr) cells increased the GC response after a first, but not booster, immunization, with an increase in T follicular helper (Tfh) cells, GC B cells, and antigen-specific antibodies, which was reversed upon IL-1 blockade. However, IL-1 signaling is not obligate for GC reactions, as WT and Il1r1-/- mice showed equivalent phenotypes, suggesting that GC IL-1 is normally restrained by IL-1R2. Fascinatingly, germline Il1r2-/- mice did not show this phenotype, but conditional Il1r2 deletion in adulthood recapitulated it, implying that compensation during development counteracts IL-1R2 loss. Finally, patients with ulcerative colitis or Crohn's disease had lower serum IL-1R2. All together, we show that IL-1R2 controls important aspects of innate and adaptive immunity and that IL-1R2 level may contribute to human disease propensity and/or progression.
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Affiliation(s)
- Katerina Pyrillou
- Section of CardioRespiratory Medicine, Heart and Lung Research Institute, and
| | - Melanie Humphry
- Section of CardioRespiratory Medicine, Heart and Lung Research Institute, and
| | - Lauren A. Kitt
- Section of CardioRespiratory Medicine, Heart and Lung Research Institute, and
| | - Amanda Rodgers
- Section of CardioRespiratory Medicine, Heart and Lung Research Institute, and
| | - Meritxell Nus
- Section of CardioRespiratory Medicine, Heart and Lung Research Institute, and
| | - Martin R. Bennett
- Section of CardioRespiratory Medicine, Heart and Lung Research Institute, and
| | - Kenneth G.C. Smith
- Cambridge Institute of Therapeutic Immunology and Infectious Disease, Jeffrey Cheah Biomedical Centre, University of Cambridge, Cambridge Biomedical Campus, Cambridge, United Kingdom
| | - Paul A. Lyons
- Cambridge Institute of Therapeutic Immunology and Infectious Disease, Jeffrey Cheah Biomedical Centre, University of Cambridge, Cambridge Biomedical Campus, Cambridge, United Kingdom
| | - Ziad Mallat
- Section of CardioRespiratory Medicine, Heart and Lung Research Institute, and
| | - Murray C.H. Clarke
- Section of CardioRespiratory Medicine, Heart and Lung Research Institute, and
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Vălean D, Zaharie R, Țaulean R, Usatiuc L, Zaharie F. Recent Trends in Non-Invasive Methods of Diagnosis and Evaluation of Inflammatory Bowel Disease: A Short Review. Int J Mol Sci 2024; 25:2077. [PMID: 38396754 PMCID: PMC10889152 DOI: 10.3390/ijms25042077] [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: 01/16/2024] [Revised: 02/04/2024] [Accepted: 02/06/2024] [Indexed: 02/25/2024] Open
Abstract
Inflammatory bowel diseases are a conglomerate of disorders causing inflammation of the gastrointestinal tract, which have gained a significant increase in prevalence in the 21st century. As they present a challenge in the terms of diagnosis as well as treatment, IBDs can present an overwhelming impact on the individual and can take a toll on healthcare costs. Thus, a quick and precise diagnosis is required in order to prevent the high number of complications that can arise from a late diagnosis as well as a misdiagnosis. Although endoscopy remains the primary method of evaluation for IBD, recent trends have highlighted various non-invasive methods of diagnosis as well as reevaluating previous ones. This review focused on the current non-invasive methods in the diagnosis of IBD, exploring their possible implementation in the near future, with the goal of achieving earlier, feasible, and cheap methods of diagnosis as well as prognosis in IBD.
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Affiliation(s)
- Dan Vălean
- Regional Institute of Gastroenterology and Hepatology “Octavian Fodor”, 400162 Cluj-Napoca, Romania; (D.V.); (R.Ț.); (F.Z.)
- Department of General Surgery, University of Medicine and Pharmacy “Iuliu Hațieganu”, 400347 Cluj-Napoca, Romania
| | - Roxana Zaharie
- Regional Institute of Gastroenterology and Hepatology “Octavian Fodor”, 400162 Cluj-Napoca, Romania; (D.V.); (R.Ț.); (F.Z.)
- Department of Gastroenterology, University of Medicine and Pharmacy “Iuliu Hațieganu”, 400347 Cluj-Napoca, Romania
| | - Roman Țaulean
- Regional Institute of Gastroenterology and Hepatology “Octavian Fodor”, 400162 Cluj-Napoca, Romania; (D.V.); (R.Ț.); (F.Z.)
- Department of General Surgery, University of Medicine and Pharmacy “Iuliu Hațieganu”, 400347 Cluj-Napoca, Romania
| | - Lia Usatiuc
- Department of Patophysiology, University of Medicine and Pharmacy “Iuliu Hațieganu”, 400347 Cluj-Napoca, Romania;
| | - Florin Zaharie
- Regional Institute of Gastroenterology and Hepatology “Octavian Fodor”, 400162 Cluj-Napoca, Romania; (D.V.); (R.Ț.); (F.Z.)
- Department of General Surgery, University of Medicine and Pharmacy “Iuliu Hațieganu”, 400347 Cluj-Napoca, Romania
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Hernandez-Suarez L, Diez-Martin E, Egiguren-Ortiz J, Fernandez R, Etxebarria A, Astigarraga E, Miguelez C, Ramirez-Garcia A, Barreda-Gómez G. Serological Antibodies against Kidney, Liver, and Spleen Membrane Antigens as Potential Biomarkers in Patients with Immune Disorders. Int J Mol Sci 2024; 25:2025. [PMID: 38396703 PMCID: PMC10888476 DOI: 10.3390/ijms25042025] [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: 12/20/2023] [Revised: 01/30/2024] [Accepted: 02/05/2024] [Indexed: 02/25/2024] Open
Abstract
Immune disorders arise from complex genetic and environmental factors, which lead to dysregulation at the cellular and inflammatory levels and cause tissue damage. Recent research highlights the crucial role of reactive antibodies in autoimmune diseases and graft rejection, but their complex determination poses challenges for clinical use. Therefore, our study aimed to ascertain whether the presence of reactive antibodies against membrane antigens in tissues from both animal models and humans could serve as biomarkers in patients with autoimmune disorders. To address this issue, we examined the binding profile of serological antibodies against a diverse panel of cell membranes from the spleen, liver, and kidney tissues of monkeys, rats, and humans. After developing the cell membrane microarrays, human sera were immunologically assayed. The study was first conducted on sera from two groups, healthy subjects and patients with inflammatory and autoimmune disorders, and then optimized for kidney transplant patient sera. A significant increase in antibody reactivity against specific monkey kidney and spleen membranes was observed in the serum of patients with lupus nephritis, while kidney transplant patients showed a significant enhancement against human tissues and human embryonic kidney 293 cells. These results show the potential importance for clinical and basic research purposes of studying the presence of specific IgG against membrane antigens in patients' serum as potential biomarkers of immune disorders. However, it is important to note that these results need to be verified in further studies with a larger sample size to confirm their relevance.
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Affiliation(s)
- Leidi Hernandez-Suarez
- Department of Research and Development, IMG Pharma Biotech S.L., 48170 Zamudio, Spain; (L.H.-S.); (E.D.-M.); (J.E.-O.); (R.F.); (A.E.); (E.A.)
- Department of Immunology, Microbiology and Parasitology, Faculty of Science and Technology, University of the Basque Country (UPV/EHU), 48940 Leioa, Spain;
| | - Eguzkiñe Diez-Martin
- Department of Research and Development, IMG Pharma Biotech S.L., 48170 Zamudio, Spain; (L.H.-S.); (E.D.-M.); (J.E.-O.); (R.F.); (A.E.); (E.A.)
- Department of Immunology, Microbiology and Parasitology, Faculty of Science and Technology, University of the Basque Country (UPV/EHU), 48940 Leioa, Spain;
| | - June Egiguren-Ortiz
- Department of Research and Development, IMG Pharma Biotech S.L., 48170 Zamudio, Spain; (L.H.-S.); (E.D.-M.); (J.E.-O.); (R.F.); (A.E.); (E.A.)
- Department of Pharmacology, Faculty of Medicine and Nursing, University of the Basque Country (UPV/EHU), 48940 Leioa, Spain;
| | - Roberto Fernandez
- Department of Research and Development, IMG Pharma Biotech S.L., 48170 Zamudio, Spain; (L.H.-S.); (E.D.-M.); (J.E.-O.); (R.F.); (A.E.); (E.A.)
| | - Aitor Etxebarria
- Department of Research and Development, IMG Pharma Biotech S.L., 48170 Zamudio, Spain; (L.H.-S.); (E.D.-M.); (J.E.-O.); (R.F.); (A.E.); (E.A.)
| | - Egoitz Astigarraga
- Department of Research and Development, IMG Pharma Biotech S.L., 48170 Zamudio, Spain; (L.H.-S.); (E.D.-M.); (J.E.-O.); (R.F.); (A.E.); (E.A.)
| | - Cristina Miguelez
- Department of Pharmacology, Faculty of Medicine and Nursing, University of the Basque Country (UPV/EHU), 48940 Leioa, Spain;
- Neurodegenerative Diseases Group, BioBizkaia Health Research Institute, 48940 Barakaldo, Spain
| | - Andoni Ramirez-Garcia
- Department of Immunology, Microbiology and Parasitology, Faculty of Science and Technology, University of the Basque Country (UPV/EHU), 48940 Leioa, Spain;
| | - Gabriel Barreda-Gómez
- Department of Research and Development, IMG Pharma Biotech S.L., 48170 Zamudio, Spain; (L.H.-S.); (E.D.-M.); (J.E.-O.); (R.F.); (A.E.); (E.A.)
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14
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Ou CC, Wu YC, Chen JP, Huang WN, Chen YH, Chen YM. Association of atypical anti-neutrophil cytoplasmic antibody with comorbidities and outcome in a hospital-based population. Heliyon 2024; 10:e24105. [PMID: 38234907 PMCID: PMC10792567 DOI: 10.1016/j.heliyon.2024.e24105] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/23/2023] [Revised: 01/02/2024] [Accepted: 01/03/2024] [Indexed: 01/19/2024] Open
Abstract
Introduction Atypical anti-neutrophil cytoplasmic antibody (a-ANCA) is characterized by a positive fluorescence staining other than typical cytoplasmic or perinuclear ANCA. ANCA is associated with increased risk of dialysis and mortality in patients with ANCA vasculitis. However, comorbidities related to a-ANCA and whether a-ANCA exhibits an increased risk for renal failure and mortality remain unclear. This study aimed to explore the comorbidities and outcome associated with a-ANCA. Materials and methods This retrospective study enrolled 164 and 170 patients with typical ANCA and a-ANCA positivity, respectively, who visited Taichung Veterans General Hospital, Taiwan from January 2016 to March 2021. Logistic regression analysis was used to determine risk factors and the rheumatological diagnosis associated with a-ANCA. Cox proportional hazard regression and Kaplan-Meier curves were employed to identify variables associated with 5-year renal survival and mortality. Results Patients with a-ANCA had lower chance of ANCA-associated vasculitis (OR: 0.02, 95 % CI: 0.01-0.07 p < 0.001), and systemic lupus erythematosus (OR: 0.23, 95 % CI: 0.11-0.48, p < 0.001), but a higher risk of rheumatoid arthritis (OR: 2.99, 95 % CI: 1.15-7.83, p = 0.025) and ulcerative colitis (OR: 5.50, 95 % CI: 1.20-25.29, p = 0.028). Patients with a-ANCA had a better renal survival (OR: 0.14, 95 % CI: 0.08-0.24, p < 0.001) and lower mortality (OR: 0.31, 95 % CI: 0.16-0.60, p = 0.001) than patents in the typical ANCA group. The 5-year renal survival and mortality was 89.3 % and 8.8 %, respectively, in patients with a-ANCA. Conclusion Patients with a-ANCA had better renal survival and lower mortality rates compared to patients with typical ANCA. These real-world data provide evidence of the long-term outcome and shed light on avenues for the strategic management of patients with a-ANCA.
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Affiliation(s)
- Chiao-Chi Ou
- Division of Allergy, Immunology, and Rheumatology, Department of Internal Medicine, Taichung Veterans General Hospital, Taichung, Taiwan
- Department of Industrial Engineering and Enterprise Information, Tunghai University, Taichung, Taiwan
| | - Yen-Ching Wu
- Division of Allergy, Immunology, and Rheumatology, Department of Internal Medicine, Taichung Veterans General Hospital, Taichung, Taiwan
| | - Jun-Peng Chen
- Department of Medical Research, Taichung Veterans General Hospital, Taichung, Taiwan
| | - Wen-Nan Huang
- Division of Allergy, Immunology, and Rheumatology, Department of Internal Medicine, Taichung Veterans General Hospital, Taichung, Taiwan
- School of Medicine, College of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan
- College of Business and Management, Ling Tung University, Taichung, Taiwan
- Department of Post-Baccalaureate Medicine, College of Medicine, National Chung Hsing University, Taichung, Taiwan
| | - Yi-Hsing Chen
- Division of Allergy, Immunology, and Rheumatology, Department of Internal Medicine, Taichung Veterans General Hospital, Taichung, Taiwan
- School of Medicine, College of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan
- Department of Post-Baccalaureate Medicine, College of Medicine, National Chung Hsing University, Taichung, Taiwan
| | - Yi-Ming Chen
- Division of Allergy, Immunology, and Rheumatology, Department of Internal Medicine, Taichung Veterans General Hospital, Taichung, Taiwan
- Department of Medical Research, Taichung Veterans General Hospital, Taichung, Taiwan
- School of Medicine, College of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan
- Department of Post-Baccalaureate Medicine, College of Medicine, National Chung Hsing University, Taichung, Taiwan
- Institute of Biomedical Science and Rong Hsing Research Center for Translational Medicine, National Chung Hsing University, Taichung, Taiwan
- Precision Medicine Research Center, College of Medicine, National Chung Hsing University, Taichung, Taiwan
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Ondriš J, Husťak R, Ďurina J, Malicherová Jurková E, Bošák V. Serum Biomarkers in Diagnosis and Clinical Management of Inflammatory Bowel Disease: Anything New on the Horizon? Folia Biol (Praha) 2024; 70:248-261. [PMID: 39889217 DOI: 10.14712/fb2024070050248] [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] [Indexed: 02/02/2025]
Abstract
Persistent inflammation in inflammatory bowel disease (IBD) leads to progressive damage to the gastrointestinal tract, resulting in potentially severe sequelae. Diagnosis primarily relies on invasive endoscopy and monitoring of faecal calprotectin (FC), which has limitations, particularly regarding patient compliance. There is a pressing need for a new biomarker that is non-invasive, easily determinable, and possesses good diagnostic accuracy for both dia-gnosing and monitoring IBD. Our narrative review covers the latest developments in novel serum biomarkers, focusing on those with promising diagnostic accuracy and laboratory methods, and evaluates them in the context of established biomarkers such as FC and CRP. Serum calprotectin (SC) and leucine-rich alpha-2 glycoprotein (LRG) show the most extensive evidence and relatively good diagnostic accuracy but currently cannot replace FC due to insufficient evidence. Major limitations of the analysed studies include their monocentric nature, small sample sizes, lack of longitudinal monitoring and in some cases, missing assessments of endoscopic activity. ELISA holds a leading position among the laboratory methods; however, emerging evidence supports the potential use of point-of-care testing (POCT). Establishing these biomarkers for regular clinical application will require further validation through multicentric studies involving a larger number of patients with a longitudinal design, concurrent assessment of endoscopic activity and pro-active monitoring of the biomarker. However, based on the evidence accumulated so far, SC might potentially serve as a complementary biomarker and/or in assessing the activity of extraintestinal manifestations in IBD patients, while LRG appears to be effective in evaluating endoscopic activity, especially in small bowel CD.
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Affiliation(s)
- Juraj Ondriš
- AstraZeneca AB o.z., Bratislava, Slovakia.
- Department of Laboratory Medicine, Faculty of Health Care and Social Work, Trnava University, Trnava, Slovakia.
| | - Rastislav Husťak
- Department of Laboratory Medicine, Faculty of Health Care and Social Work, Trnava University, Trnava, Slovakia
- Gastroenterology Department, Clinic of Internal Medicine, University Hospital in Trnava, Slovakia
| | - Juraj Ďurina
- Gastroenterology and Hepatology Centre, University Hospital with Polyclinic in Nové Zámky, Slovakia
| | - Eva Malicherová Jurková
- Centre for Periodic Fever Syndromes, Department of Paediatrics, Jessenius Faculty of Medicine of Comenius University in Bratislava and University Hospital in Martin, Slovakia
| | - Vladimír Bošák
- Department of Laboratory Medicine, Faculty of Health Care and Social Work, Trnava University, Trnava, Slovakia
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Marafini I, Laudisi F, Salvatori S, Lavigna D, Venuto C, Giannarelli D, Monteleone G. Diagnostic value of anti-integrin αvβ6 antibodies in ulcerative colitis. Dig Liver Dis 2024; 56:55-60. [PMID: 37407314 DOI: 10.1016/j.dld.2023.06.024] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/11/2023] [Revised: 06/09/2023] [Accepted: 06/20/2023] [Indexed: 07/07/2023]
Abstract
Ulcerative colitis (UC)-related mucosal inflammation is characterized by the production of various autoantibodies with limited clinical relevance. Recent studies have shown that circulating levels of IgG against integrin αvβ6 are increased in UC patients as compared to Crohn's disease (CD) patients and healthy controls (HC). The present study assessed the diagnostic value of circulating IgG anti-αvβ6 in UC. Sera were prospectively collected from 108 outpatients with UC, 103 patients with CD, and 62 HC, and the levels of IgG anti-αvβ6 were measured using a commercially available ELISA kit. The cut-off for positive results was defined as the 95th percentile of the values of the autoantibodies in HC serum samples. Levels of IgG anti-αvβ6 were significantly higher in UC than in CD patients, including those with colonic localization, and HC. Fifty-six of the 108 (51.8%) UC patients had a positive test whereas only 17/103 (16.5%) patients with CD, and among these, 4/16 (25%) patients with colonic CD, were positive. In UC, there was no statistical difference between patients with IgG anti-αvβ6 positivity and those negative in terms of clinical disease activity, fecal calprotectin values, and disease extent. The sensitivity, specificity, predictive positive value, and predictive negative value of the test to differentiate between UC and CD were 51.9% (C.I.42.4-61.3), 83.5% (C.I. 76.3-90.7), 76.7% (C.I. 67.0-86.4), and 62.3% (C.I. 54.2-70.4) respectively. Our study confirms that anti-αvβ6 antibodies are demonstrable in the serum of the majority of UC patients and suggests the necessity of further research to understand if the anti-αvβ6 antibody determination could have a place in the clinical decision-making of IBD.
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Affiliation(s)
- Irene Marafini
- Gastroenterology Unit, Azienda Ospedaliera Policlinico Tor Vergata, Rome, Italy
| | - Federica Laudisi
- Department of Systems Medicine, University of Rome Tor Vergata, Rome, Italy
| | - Silvia Salvatori
- Department of Systems Medicine, University of Rome Tor Vergata, Rome, Italy
| | - Diletta Lavigna
- Department of Systems Medicine, University of Rome Tor Vergata, Rome, Italy
| | - Chiara Venuto
- Department of Systems Medicine, University of Rome Tor Vergata, Rome, Italy
| | - Diana Giannarelli
- Facility of Epidemiology and Biostatistics, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy
| | - Giovanni Monteleone
- Department of Systems Medicine, University of Rome Tor Vergata, Rome, Italy.
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Rintarhat P, Cho YJ, Koh H, Park S, Lee EJ, Lim H, Noh J, Lee DW, Jung WH. Assessment of DNA extraction methods for human gut mycobiome analysis. ROYAL SOCIETY OPEN SCIENCE 2024; 11:231129. [PMID: 38204788 PMCID: PMC10776226 DOI: 10.1098/rsos.231129] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 08/06/2023] [Accepted: 12/11/2023] [Indexed: 01/12/2024]
Abstract
The gut mycobiome plays an important role in the health and disease of the human gut, but its exact function is still under investigation. While there is a wealth of information available on the bacterial community of the human gut microbiome, research on the fungal community is still relatively limited. In particular, technical methodologies for mycobiome analysis, especially the DNA extraction method for human faecal samples, varied in different studies. In the current study, two commercial kits commonly used in DNA extraction, the QIAamp® Fast DNA Stool Mini Kit and DNeasy PowerSoil Pro Kit, and one manual method, the International Human Microbiome Standards Protocol Q, were compared. Furthermore, the effectiveness of two different bead-beating machines, the Mini-Beadbeater-16 and FastPrep-24TM 5G, was compared in parallel. A mock fungal community with a known composition of fungal strains was also generated and included to compare different DNA extraction methods. Our results suggested that the method using the DNeasy PowerSoil Pro Kit and Mini-Beadbeater-16 provides the best results to extract DNA from human faecal samples. Based on our data, we propose a standard operating procedure for DNA extraction from human faecal samples for mycobiome analysis.
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Affiliation(s)
- Piyapat Rintarhat
- Department of Systems Biotechnology, Chung-Ang University, Anseong 17546, Korea
| | - Yong-Joon Cho
- Department of Molecular Bioscience, Kangwon National University, Chuncheon 24341, Korea
| | - Hong Koh
- Division of Gastroenterology, Hepatology and Nutrition, Department of Pediatrics, Severance Hospital, Yonsei University College of Medicine, Seoul, Korea
| | - Sowon Park
- Division of Gastroenterology, Hepatology and Nutrition, Department of Pediatrics, Severance Hospital, Yonsei University College of Medicine, Seoul, Korea
| | - Eun Joo Lee
- Division of Gastroenterology, Hepatology and Nutrition, Department of Pediatrics, Severance Hospital, Yonsei University College of Medicine, Seoul, Korea
| | - Hyeji Lim
- Division of Gastroenterology, Hepatology and Nutrition, Department of Pediatrics, Severance Hospital, Yonsei University College of Medicine, Seoul, Korea
| | - Jihye Noh
- Division of Gastroenterology, Hepatology and Nutrition, Department of Pediatrics, Severance Hospital, Yonsei University College of Medicine, Seoul, Korea
| | - Dong-Woo Lee
- Department of Biotechnology, Yonsei University, Seoul, Korea
| | - Won Hee Jung
- Department of Systems Biotechnology, Chung-Ang University, Anseong 17546, Korea
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18
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Arora K, Gaudioso G, Solovyev P, Tuohy K, Di Cagno R, Gobbetti M, Fava F. In vitro faecal fermentation of Tritordeum breads and its effect on the human gut health. CURRENT RESEARCH IN MICROBIAL SCIENCES 2023; 6:100214. [PMID: 38116184 PMCID: PMC10727946 DOI: 10.1016/j.crmicr.2023.100214] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/21/2023] Open
Abstract
Spontaneous fermentation of Tritordeum flour enhances the nutritional potential of this hybrid cereal. However, the effect of consumption of Tritordeum sourdough bread (SDB) on gut health remains to be elucidated. This study investigated the effect of in vitro digestion and faecal fermentation of SDB compared to that of traditional baker's yeast (BYB) Tritordeum bread. After 24-h anaerobic faecal fermentation, both SDB and BYB (1% w/v) induced an increase in the relative abundances of Bifidobacterium, Megasphaera, Mitsuokella, and Phascolarctobacterium genera compared to baseline, while concentrations of acetate and butyrate were significantly higher at 24 h for SDB compared to those for BYB. Integrity of intestinal epithelium, as assessed through in vitro trans-epithelial electrical resistance (TEER) assay, was slightly increased after incubation with SDB fermentation supernatants, but not after incubation with BYB fermentation supernatants. The SDB stimulated in vitro mucosal immune response by inducing early secretion of inflammatory cytokines, IL-6 and TNF-α, followed by downregulation of the inflammatory trigger through induction of anti-inflammatory IL-10 expression. Overall, our findings suggest that Tritordeum sourdough can modulate gut microbiota fermentation activity and positively impact the gut health.
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Affiliation(s)
- Kashika Arora
- Faculty of Agricultural, Environmental and Food Sciences, Libera Università di Bolzano, Piazza Università, 5, Bolzano 39100, Italy
| | - Giulia Gaudioso
- Nutrition and Nutrigenomics Unit, Fondazione Edmund Mach di San Michele all'Adige Via E. Mach, 1 38098 S. Michele all'Adige, Italy
| | - Pavel Solovyev
- Traceability Unit, Fondazione Edmund Mach di San Michele all'Adige Via E. Mach, 1 38098 S. Michele all'Adige, Italy
| | - Kieran Tuohy
- Nutrition and Nutrigenomics Unit, Fondazione Edmund Mach di San Michele all'Adige Via E. Mach, 1 38098 S. Michele all'Adige, Italy
- School of Food Science & Nutrition, University of Leeds, Leeds LS2 9JT, UK
| | - Raffaella Di Cagno
- Faculty of Agricultural, Environmental and Food Sciences, Libera Università di Bolzano, Piazza Università, 5, Bolzano 39100, Italy
| | - Marco Gobbetti
- Faculty of Agricultural, Environmental and Food Sciences, Libera Università di Bolzano, Piazza Università, 5, Bolzano 39100, Italy
| | - Francesca Fava
- Nutrition and Nutrigenomics Unit, Fondazione Edmund Mach di San Michele all'Adige Via E. Mach, 1 38098 S. Michele all'Adige, Italy
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19
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Fetter K, Weigel M, Ott B, Fritzenwanker M, Stricker S, de Laffolie J, Hain T. The microbiome landscape in pediatric Crohn's disease and therapeutic implications. Gut Microbes 2023; 15:2247019. [PMID: 37614093 PMCID: PMC10453987 DOI: 10.1080/19490976.2023.2247019] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/31/2023] [Revised: 06/29/2023] [Accepted: 08/08/2023] [Indexed: 08/25/2023] Open
Abstract
Dysbiosis of the gut microbiome and a pathological immune response in intestinal tissues form the basis of Crohn's disease (CD), which is a debilitating disease with relevant morbidity and mortality. It is increasing in childhood and adolescents, due to western life-style and nutrition and a large set of predisposing genetic factors. Crohn's disease-associated genetic mutations play an essential role in killing pathogens, altering mucosal barrier function, and protecting the host microbiome, suggesting an important pathogenic link. The intestinal microbiome is highly variable and can be influenced by environmental factors. Changes in microbial composition and a reduction in species diversity have been shown to be central features of disease progression and are therefore the target of therapeutic approaches. In this review, we summarize the current literature on the role of the gut microbiome in childhood, adolescent, and adult CD, current therapeutic options, and their impact on the microbiome.
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Affiliation(s)
- Karin Fetter
- Institute of Medical Microbiology, Justus Liebig University Giessen, Giessen, Germany
- German Center for Infection Research (DZIF), Partner Site Giessen-Marburg-Langen, Justus Liebig University Giessen, Giessen, Germany
| | - Markus Weigel
- Institute of Medical Microbiology, Justus Liebig University Giessen, Giessen, Germany
| | - Benjamin Ott
- Institute of Medical Microbiology, Justus Liebig University Giessen, Giessen, Germany
| | - Moritz Fritzenwanker
- Institute of Medical Microbiology, Justus Liebig University Giessen, Giessen, Germany
| | - Sebastian Stricker
- Department of Pediatrics, Justus Liebig University Giessen, Giessen, Germany
| | - Jan de Laffolie
- Department of Pediatrics, Justus Liebig University Giessen, Giessen, Germany
| | - Torsten Hain
- Institute of Medical Microbiology, Justus Liebig University Giessen, Giessen, Germany
- German Center for Infection Research (DZIF), Partner Site Giessen-Marburg-Langen, Justus Liebig University Giessen, Giessen, Germany
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20
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Yan J, Deng F, Tan Y, Zhou B, Liu D. Systemic immune-inflammation index as a potential biomarker to monitor ulcerative colitis. Curr Med Res Opin 2023; 39:1321-1328. [PMID: 37691449 DOI: 10.1080/03007995.2023.2257599] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/24/2023] [Revised: 08/17/2023] [Accepted: 09/07/2023] [Indexed: 09/12/2023]
Abstract
OBJECTIVE The treat-to-target strategy is recommended by Selecting Therapeutic Targets in Inflammatory Bowel Disease II (STRIDE-II) for treating ulcerative colitis (UC), and monitoring remission status is crucial during this management. The systemic immune-inflammation index (SII), defined as platelet * neutrophil/lymphocyte, is a complete blood count-based index reflecting the balance of immune and inflammatory status. This study aims to investigate the feasibility of SII for diagnosing UC and monitoring UC disease activity. METHODS This study retrospectively analyzed patients with UC and controls. Relationships between SII and Mayo clinical score, Mayo Endoscopic Score (MES), and Nancy Histological Index (NHI) were evaluated. RESULTS 167 patients with UC and 106 controls were included. SII significantly increased in patients with UC and was closely correlated with the Mayo clinical score, MES, and NHI. SII diagnosed UC with a cut-off value of 619.1 × 109/L (area under the curve = 0.861, p < 0.0001, sensitivity 79.64%, specificity 77.36%), evaluated clinical remission status with a cut-off value of 1068 × 109/L (area under the curve = 0.691, p < 0.05, sensitivity 55.71%, specificity 81.48%), endoscopic improvement with a cut-off value of 981.3 × 109/L (area under the curve = 0.819, p < 0.0001, sensitivity 65.22%, specificity 89.66%), and histological healing with a cut-off value of 689.3 × 109/L (area under the curve = 0.898, p < 0.0001, sensitivity 88.89%, specificity 95.83%). CONCLUSION SII is a potential biomarker for diagnosing UC and monitoring UC disease severity, especially in evaluating mucosal and histological healing during the long-term management in treat-to-target strategy. However, further research is needed to confirm its usefulness and optimize its clinical application.
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Affiliation(s)
- Jin Yan
- Department of Gastroenterology, the Second Xiangya Hospital of Central South University, Changsha, Hunan, China
- Research Center of Digestive Disease, Central South University, Changsha, Hunan, China
| | - Feihong Deng
- Department of Gastroenterology, the Second Xiangya Hospital of Central South University, Changsha, Hunan, China
- Research Center of Digestive Disease, Central South University, Changsha, Hunan, China
| | - Yuyong Tan
- Department of Gastroenterology, the Second Xiangya Hospital of Central South University, Changsha, Hunan, China
- Research Center of Digestive Disease, Central South University, Changsha, Hunan, China
| | - Bingyi Zhou
- Department of Gastroenterology, the Second Xiangya Hospital of Central South University, Changsha, Hunan, China
- Research Center of Digestive Disease, Central South University, Changsha, Hunan, China
| | - Deliang Liu
- Department of Gastroenterology, the Second Xiangya Hospital of Central South University, Changsha, Hunan, China
- Research Center of Digestive Disease, Central South University, Changsha, Hunan, China
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21
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Choudhury A, Dhillon J, Sekar A, Gupta P, Singh H, Sharma V. Differentiating gastrointestinal tuberculosis and Crohn's disease- a comprehensive review. BMC Gastroenterol 2023; 23:246. [PMID: 37468869 DOI: 10.1186/s12876-023-02887-0] [Citation(s) in RCA: 12] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/27/2023] [Accepted: 07/13/2023] [Indexed: 07/21/2023] Open
Abstract
Gastrointestinal Tuberculosis (GITB) and Crohn's disease (CD) are both chronic granulomatous diseases with a predilection to involve primarily the terminal ileum. GITB is often considered a disease of the developing world, while CD and inflammatory bowel disease are considered a disease of the developed world. But in recent times, the epidemiology of both diseases has changed. Differentiating GITB from CD is of immense clinical importance as the management of both diseases differs. While GITB needs anti-tubercular therapy (ATT), CD needs immunosuppressive therapy. Misdiagnosis or a delay in diagnosis can lead to catastrophic consequences. Most of the clinical features, endoscopic findings, and imaging features are not pathognomonic for either of these two conditions. The definitive diagnosis of GITB can be clinched only in a fraction of cases with microbiological positivity (acid-fast bacilli, mycobacterial culture, or PCR-based tests). In most cases, the diagnosis is often based on consistent clinical, endoscopic, imaging, and histological findings. Similarly, no single finding can conclusively diagnose CD. Multiparametric-based predictive models incorporating clinical, endoscopy findings, histology, radiology, and serology have been used to differentiate GITB from CD with varied results. However, it is limited by the lack of validation studies for most such models. Many patients, especially in TB endemic regions, are initiated on a trial of ATT to see for an objective response to therapy. Early mucosal response assessed at two months is an objective marker of response to ATT. Prolonged ATT in CD is recognized to have a fibrotic effect. Therefore, early discrimination may be vital in preventing the delay in the diagnosis of CD and avoiding a complicated course.
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Affiliation(s)
| | | | - Aravind Sekar
- Postgraduate Institute of Medical Education and Research, Chandigarh, 160012, India
| | - Pankaj Gupta
- Postgraduate Institute of Medical Education and Research, Chandigarh, 160012, India
| | - Harjeet Singh
- Postgraduate Institute of Medical Education and Research, Chandigarh, 160012, India
| | - Vishal Sharma
- Postgraduate Institute of Medical Education and Research, Chandigarh, 160012, India.
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22
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Pyzik M, Kozicky LK, Gandhi AK, Blumberg RS. The therapeutic age of the neonatal Fc receptor. Nat Rev Immunol 2023; 23:415-432. [PMID: 36726033 PMCID: PMC9891766 DOI: 10.1038/s41577-022-00821-1] [Citation(s) in RCA: 84] [Impact Index Per Article: 42.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 11/29/2022] [Indexed: 02/03/2023]
Abstract
IgGs are essential soluble components of the adaptive immune response that evolved to protect the body from infection. Compared with other immunoglobulins, the role of IgGs is distinguished and enhanced by their high circulating levels, long half-life and ability to transfer from mother to offspring, properties that are conferred by interactions with neonatal Fc receptor (FcRn). FcRn binds to the Fc portion of IgGs in a pH-dependent manner and protects them from intracellular degradation. It also allows their transport across polarized cells that separate tissue compartments, such as the endothelium and epithelium. Further, it is becoming apparent that FcRn functions to potentiate cellular immune responses when IgGs, bound to their antigens, form IgG immune complexes. Besides the protective role of IgG, IgG autoantibodies are associated with numerous pathological conditions. As such, FcRn blockade is a novel and effective strategy to reduce circulating levels of pathogenic IgG autoantibodies and curtail IgG-mediated diseases, with several FcRn-blocking strategies on the path to therapeutic use. Here, we describe the current state of knowledge of FcRn-IgG immunobiology, with an emphasis on the functional and pathological aspects, and an overview of FcRn-targeted therapy development.
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Affiliation(s)
- Michal Pyzik
- Division of Gastroenterology, Hepatology and Endoscopy, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
| | - Lisa K Kozicky
- Division of Gastroenterology, Hepatology and Endoscopy, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA
| | - Amit K Gandhi
- Division of Gastroenterology, Hepatology and Endoscopy, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA
| | - Richard S Blumberg
- Division of Gastroenterology, Hepatology and Endoscopy, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
- Harvard Digestive Diseases Center, Boston, MA, USA.
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23
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Bourgonje AR, Andreu-Sánchez S, Vogl T, Hu S, Vich Vila A, Gacesa R, Leviatan S, Kurilshikov A, Klompus S, Kalka IN, van Dullemen HM, Weinberger A, Visschedijk MC, Festen EAM, Faber KN, Wijmenga C, Dijkstra G, Segal E, Fu J, Zhernakova A, Weersma RK. Phage-display immunoprecipitation sequencing of the antibody epitope repertoire in inflammatory bowel disease reveals distinct antibody signatures. Immunity 2023; 56:1393-1409.e6. [PMID: 37164015 DOI: 10.1016/j.immuni.2023.04.017] [Citation(s) in RCA: 22] [Impact Index Per Article: 11.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/07/2021] [Revised: 12/13/2022] [Accepted: 04/14/2023] [Indexed: 05/12/2023]
Abstract
Inflammatory bowel diseases (IBDs), e.g., Crohn's disease (CD) and ulcerative colitis (UC), are chronic immune-mediated inflammatory diseases. A comprehensive overview of an IBD-specific antibody epitope repertoire is, however, lacking. Using high-throughput phage-display immunoprecipitation sequencing (PhIP-Seq), we identified antibodies against 344,000 antimicrobial, immune, and food antigens in 497 individuals with IBD compared with 1,326 controls. IBD was characterized by 373 differentially abundant antibody responses (202 overrepresented and 171 underrepresented), with 17% shared by both IBDs, 55% unique to CD, and 28% unique to UC. Antibody reactivities against bacterial flagellins dominated in CD and were associated with ileal involvement, fibrostenotic disease, and anti-Saccharomyces cerevisiae antibody positivity, but not with fecal microbiome composition. Antibody epitope repertoires accurately discriminated CD from controls (area under the curve [AUC] = 0.89), and similar discrimination was achieved when using only ten antibodies (AUC = 0.87). Individuals with IBD thus show a distinct antibody repertoire against selected peptides, allowing clinical stratification and discovery of immunological targets.
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Affiliation(s)
- Arno R Bourgonje
- Department of Gastroenterology and Hepatology, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands
| | - Sergio Andreu-Sánchez
- Department of Genetics, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands; Department of Pediatrics, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands
| | - Thomas Vogl
- Department of Computer Science and Applied Mathematics, Weizmann Institute of Science, Rehovot, Israel; Department of Molecular Cell Biology, Weizmann Institute of Science, Rehovot, Israel; Diagnostic and Research Institute of Hygiene, Microbiology and Environmental Medicine, Medical University Graz, Graz, Austria; Center for Cancer Research, Medical University of Vienna, Wien, Austria
| | - Shixian Hu
- Department of Gastroenterology and Hepatology, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands; Department of Genetics, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands
| | - Arnau Vich Vila
- Department of Gastroenterology and Hepatology, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands; Department of Genetics, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands
| | - Ranko Gacesa
- Department of Gastroenterology and Hepatology, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands; Department of Genetics, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands
| | - Sigal Leviatan
- Department of Computer Science and Applied Mathematics, Weizmann Institute of Science, Rehovot, Israel; Department of Molecular Cell Biology, Weizmann Institute of Science, Rehovot, Israel
| | - Alexander Kurilshikov
- Department of Genetics, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands
| | - Shelley Klompus
- Department of Computer Science and Applied Mathematics, Weizmann Institute of Science, Rehovot, Israel; Department of Molecular Cell Biology, Weizmann Institute of Science, Rehovot, Israel
| | - Iris N Kalka
- Department of Computer Science and Applied Mathematics, Weizmann Institute of Science, Rehovot, Israel; Department of Molecular Cell Biology, Weizmann Institute of Science, Rehovot, Israel
| | - Hendrik M van Dullemen
- Department of Gastroenterology and Hepatology, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands
| | - Adina Weinberger
- Department of Computer Science and Applied Mathematics, Weizmann Institute of Science, Rehovot, Israel; Department of Molecular Cell Biology, Weizmann Institute of Science, Rehovot, Israel
| | - Marijn C Visschedijk
- Department of Gastroenterology and Hepatology, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands
| | - Eleonora A M Festen
- Department of Gastroenterology and Hepatology, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands
| | - Klaas Nico Faber
- Department of Gastroenterology and Hepatology, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands
| | - Cisca Wijmenga
- Department of Genetics, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands
| | - Gerard Dijkstra
- Department of Gastroenterology and Hepatology, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands
| | - Eran Segal
- Department of Computer Science and Applied Mathematics, Weizmann Institute of Science, Rehovot, Israel; Department of Molecular Cell Biology, Weizmann Institute of Science, Rehovot, Israel
| | - Jingyuan Fu
- Department of Genetics, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands; Department of Pediatrics, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands
| | - Alexandra Zhernakova
- Department of Genetics, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands
| | - Rinse K Weersma
- Department of Gastroenterology and Hepatology, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands.
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24
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Räisänen L, Agrawal N, Mathew B, Kääriäinen S, Kolho KL, Viljakainen H. Pre-Diagnostic Saliva Microbiota of School-Aged Children Who Developed Type 1 Diabetes or Inflammatory Bowel Diseases. Int J Mol Sci 2023; 24:ijms24098279. [PMID: 37175985 PMCID: PMC10179007 DOI: 10.3390/ijms24098279] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/09/2023] [Revised: 04/20/2023] [Accepted: 04/28/2023] [Indexed: 05/15/2023] Open
Abstract
Altered commensal microbiota composition has been associated with pediatric type 1 diabetes mellitus (T1D) and inflammatory bowel diseases (IBD), but the causal relationship is still unclear. To search for potential pre-diagnostic biomarkers for pediatric T1D or IBD, we compared microbiota in saliva samples in a nested case-control design comprising children developing T1D (nchildren = 52) or IBD (nchildren = 21) and controls with a similar age, sex, and residential area (nchildren = 79). The pre-diagnostic saliva microbiota alpha- and beta-diversity of children who would develop T1D (nsamples = 27) or IBD (nsamples = 14) minimally varied from that of controls. The relative abundances of Abiotrophia were higher, while those of Veillonella, Actinomyces, Megasphaera, Butyrivibrio, and Candidatus ancillula were lower in children who would develop T1D. Within 2 years before diagnosis, the metabolic PWY-5677 pathway (converting succinate into butyrate) was lower in pre-T1D samples than in controls (q = 0.034). No significant pre-IBD differences were found. In conclusion, saliva microbiota diversity or composition were not successful predictors for pediatric T1D nor IBD. Intriguingly, the succinate fermentation pathway was predicted to be lowered before the onset of T1D. Thus, investigating functional pathways might provide a better approach in searching for biomarkers for autoimmune disease in the future.
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Affiliation(s)
- Laura Räisänen
- Faculty of Medicine and Health Technology (MET), Tampere University, 33100 Tampere, Finland
- Department of Pediatrics, Tampere University Hospital, 33520 Tampere, Finland
- Folkhälsan Research Center, 00250 Helsinki, Finland
| | - Nitin Agrawal
- Folkhälsan Research Center, 00250 Helsinki, Finland
- Faculty of Medicine, University of Helsinki, 00014 Helsinki, Finland
| | - Binu Mathew
- Folkhälsan Research Center, 00250 Helsinki, Finland
| | - Sohvi Kääriäinen
- Finnish Institute for Health and Welfare, 00271 Helsinki, Finland
| | - Kaija-Leena Kolho
- Faculty of Medicine and Health Technology (MET), Tampere University, 33100 Tampere, Finland
- Faculty of Medicine, University of Helsinki, 00014 Helsinki, Finland
- Children's Hospital, University of Helsinki and Helsinki University Hospital (HUS), 00290 Helsinki, Finland
| | - Heli Viljakainen
- Folkhälsan Research Center, 00250 Helsinki, Finland
- Finnish Institute for Health and Welfare, 00271 Helsinki, Finland
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25
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Räisänen LK, Kääriäinen SE, Sund R, Engberg E, Viljakainen HT, Kolho KL. Antibiotic exposures and the development of pediatric autoimmune diseases: a register-based case-control study. Pediatr Res 2023; 93:1096-1104. [PMID: 35854091 PMCID: PMC10033398 DOI: 10.1038/s41390-022-02188-4] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/24/2022] [Revised: 05/27/2022] [Accepted: 06/22/2022] [Indexed: 11/09/2022]
Abstract
BACKGROUND Antibiotics have been associated with several individual autoimmune diseases (ADs). This study aims to discover whether pre-diagnostic antibiotics are associated with the onset of ADs in general. METHODS From a cohort of 11,407 children, 242 developed ADs (type 1 diabetes, autoimmune thyroiditis, juvenile idiopathic arthritis (JIA), or inflammatory bowel diseases) by a median age of 16 years. Antibiotic purchases from birth until the date of diagnosis (or respective date in the matched controls n = 708) were traced from national registers. RESULTS Total number of antibiotic purchases was not related to the onset of ADs when studied as a group. Of specific diagnoses, JIA was associated with the total number of antibiotics throughout the childhood and with broad-spectrum antibiotics before the age of 3 years. Intriguingly, recent and frequent antibiotic use (within 2 years before diagnosis and ≥3 purchases) was associated with the onset of ADs (OR 1.72, 95% CI 1.08-2.74). Regardless of frequent use in childhood (40% of all antibiotics), penicillin group antibiotics were not related to any ADs. CONCLUSIONS Use of antibiotics was relatively safe regarding the overall development of ADs. However, broad-spectrum antibiotics should be used considerately as they may associate with an increased likelihood of JIA. IMPACT Increasing numbers of antibiotic purchases before the age of 3 years or throughout childhood were not associated with the development of pediatric autoimmune diseases. Broad-spectrum antibiotics were related to the development of autoimmune diseases, especially juvenile idiopathic arthritis in children, while penicillin group antibiotics were not. The use of broad-spectrum antibiotics in children should be cautious as they may carry along a risk for autoimmune disease development.
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Affiliation(s)
- Laura K Räisänen
- Faculty of Medicine and Health Technology (MET), Tampere University, Tampere, Finland
- Folkhälsan Research Center, Helsinki, Finland
- Department of Pediatrics, Tampere University Hospital, Tampere, Finland
| | | | - Reijo Sund
- Institute of Clinical Medicine, School of Medicine, Faculty of Health Sciences, University of Eastern Finland, Kuopio, Finland
| | - Elina Engberg
- Folkhälsan Research Center, Helsinki, Finland
- Faculty of Medicine, University of Helsinki, Helsinki, Finland
| | - Heli T Viljakainen
- Folkhälsan Research Center, Helsinki, Finland
- Faculty of Medicine, University of Helsinki, Helsinki, Finland
| | - Kaija-Leena Kolho
- Faculty of Medicine and Health Technology (MET), Tampere University, Tampere, Finland.
- Faculty of Medicine, University of Helsinki, Helsinki, Finland.
- Children's Hospital, Helsinki University Hospital, Helsinki, Finland.
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26
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Mannon PJ. Immunologic Diseases of the Gastrointestinal Tract. Clin Immunol 2023. [DOI: 10.1016/b978-0-7020-8165-1.00075-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 04/09/2023]
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27
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Sakurai T, Saruta M. Positioning and Usefulness of Biomarkers in Inflammatory Bowel Disease. Digestion 2023; 104:30-41. [PMID: 36404714 PMCID: PMC9843547 DOI: 10.1159/000527846] [Citation(s) in RCA: 52] [Impact Index Per Article: 26.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/31/2022] [Accepted: 10/27/2022] [Indexed: 11/19/2022]
Abstract
BACKGROUND Mucosal healing (MH) was proposed to be an ideal treatment goal for patients with inflammatory bowel disease (IBD). Instead of endoscopy to confirm MH, biomarkers are frequently used and have become an indispensable modality for the clinical examination of patients with IBD. SUMMARY Common biomarkers of IBD include C-reactive protein (CRP), erythrocyte sedimentation rate, antineutrophil cytoplasmic antibodies, anti-Saccharomyces cerevisiae antibodies, leucine-rich α2 glycoprotein, fecal calprotectin (FCP), and the fecal immunochemical test. Biomarkers play five major roles in the management of IBD: (1) diagnosing and distinguishing between IBD and non-IBD or ulcerative colitis and Crohn's disease; (2) predicting treatment response, especially before administrating biologics; (3) monitoring and grasping endoscopic or histological disease activity; (4) replacing endoscopy for diagnosing MH, including endoscopic and histological remission; and (5) predicting recurrence before disease activity appears through symptoms. Many reports have demonstrated the usefulness of CRP and FCP for those five roles; however, they have limitations for diagnosing MH or predicting treatment response. In general, FCP has better ability in those positions than CRP; additionally, leucine-rich α2 glycoprotein can diagnose endoscopic disease activity better than CRP. The novel biomarker, prostaglandin E-major urinary metabolite, and anti-αvβ6 antibody are expected to be noninvasive and reliable biomarkers; however, more evidence is required for future studies. Oncostatin M and microRNA are also prospects, in addition to other familiar and novel biomarkers. KEY MESSAGES Each biomarker has a useful feature; therefore, we should consider their features and use appropriate biomarkers for the five roles to enable noninvasive and smooth management of IBD.
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28
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Räisänen L, Viljakainen H, Kolho KL. Exposure to proton pump inhibitors is associated with the development of pediatric autoimmune diseases. Front Pediatr 2023; 11:1157547. [PMID: 37051434 PMCID: PMC10083351 DOI: 10.3389/fped.2023.1157547] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/02/2023] [Accepted: 03/08/2023] [Indexed: 04/14/2023] Open
Abstract
Proton pump inhibitors (PPIs) have been associated with decreased gut microbiota diversity. Disrupted gut microbiota composition has been reported in several autoimmune diseases (ADs), such as type 1 diabetes mellitus (DM), autoimmune thyroiditis (AIT), juvenile idiopathic arthritis (JIA), and inflammatory bowel diseases (IBD). We investigated whether PPIs are associated with the development of ADs in children and concluded that PPI exposures could be related to the onset of ADs, especially IBD and potentially AIT as well.
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Affiliation(s)
- Laura Räisänen
- Department of Pediatrics, Tampere University Hospital, Tampere, Finland
- Correspondence: Laura Räisänen Kaija-Leena Kolho
| | - Heli Viljakainen
- Public Health Research Program, Folkhälsan Research Center, Helsinki, Finland
- Children’s Hospital, University of Helsinki and HUS, Helsinki, Finland
| | - Kaija-Leena Kolho
- Children’s Hospital, University of Helsinki and HUS, Helsinki, Finland
- Faculty of Medicine and Medical Technology, Tampere University, Tampere, Finland
- Correspondence: Laura Räisänen Kaija-Leena Kolho
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Ma H, Murphy C, Loscher CE, O’Kennedy R. Autoantibodies - enemies, and/or potential allies? Front Immunol 2022; 13:953726. [PMID: 36341384 PMCID: PMC9627499 DOI: 10.3389/fimmu.2022.953726] [Citation(s) in RCA: 16] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/26/2022] [Accepted: 08/24/2022] [Indexed: 08/13/2023] Open
Abstract
Autoantibodies are well known as potentially highly harmful antibodies which attack the host via binding to self-antigens, thus causing severe associated diseases and symptoms (e.g. autoimmune diseases). However, detection of autoantibodies to a range of disease-associated antigens has enabled their successful usage as important tools in disease diagnosis, prognosis and treatment. There are several advantages of using such autoantibodies. These include the capacity to measure their presence very early in disease development, their stability, which is often much better than their related antigen, and the capacity to use an array of such autoantibodies for enhanced diagnostics and to better predict prognosis. They may also possess capacity for utilization in therapy, in vivo. In this review both the positive and negative aspects of autoantibodies are critically assessed, including their role in autoimmune diseases, cancers and the global pandemic caused by COVID-19. Important issues related to their detection are also highlighted.
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Affiliation(s)
- Hui Ma
- School of Biotechnology, Dublin City University, Dublin, Ireland
| | - Caroline Murphy
- School of Biotechnology, Dublin City University, Dublin, Ireland
| | | | - Richard O’Kennedy
- School of Biotechnology, Dublin City University, Dublin, Ireland
- Research, Development and Innovation, Qatar Foundation, Doha, Qatar
- Hamad Bin Khalifa University, Doha, Qatar
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Pseudo-mercaptoethyl pyridine functionalized polyhedral oligomeric silsesquioxane-graphene composite via thiol-ene click reaction for highly selective purification of antibody. J Chromatogr B Analyt Technol Biomed Life Sci 2022; 1208:123408. [DOI: 10.1016/j.jchromb.2022.123408] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/24/2022] [Revised: 08/03/2022] [Accepted: 08/03/2022] [Indexed: 11/21/2022]
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Jena A, Dutta U, Shah J, Sharma V, Prasad KK, Shivaprakash RM, Mandavdhare HS, Samanta J, Sharma P, Popli P, Sharma AK, Sinha SK, Chakrabarti A, Kochhar R. Oral Fluconazole Therapy in Patients With Active Ulcerative Colitis Who Have Detectable Candida in the Stool : A Double-Blind Randomized Placebo-controlled Trial. J Clin Gastroenterol 2022; 56:705-711. [PMID: 34516459 DOI: 10.1097/mcg.0000000000001609] [Citation(s) in RCA: 11] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/19/2021] [Accepted: 07/24/2021] [Indexed: 01/20/2023]
Abstract
BACKGROUND There is an emerging role of fungal dysbiosis in the pathogenesis of inflammatory bowel disease. Prevalence of Candida in patients with active ulcerative colitis (UC) and the effect of fluconazole therapy in reducing disease activity of UC are not known. PATIENTS AND METHODS All consecutive consenting patients with active UC defined as Mayo score ≥3 were evaluated for presence of Candida by stool culture and predictors for presence of Candida were identified. Those who had evidence of Candida in the stool were randomized to receive oral fluconazole 200 mg daily or placebo for 3 weeks along with standard medical therapy. Patients were assessed by clinical, sigmoidoscopy, and laboratory parameters at baseline and at 4 weeks. The primary outcome was clinical and endoscopic response at 4 weeks defined by a 3-point reduction in Mayo score. Secondary outcomes were reduction in fecal calprotectin, histologic response, and adverse events. RESULTS Of the 242 patients with active UC, 68 (28%) patients had Candida in stool culture. Independent predictors for presence of Candida in patients with active UC were partial Mayo score of ≥3 and steroid exposure. Among those with Candida on stool culture (n=68), 61 patients fulfilled eligibility criteria and were randomized to receive fluconazole (n=31) or placebo (n=30). Three-point reduction in Mayo score though was numerically higher in the fluconazole group than the placebo group but was not statistically significant [5 (16.1%) vs. 1 (3.33%); P =0.19]. Postintervention median Mayo score was lower in fluconazole than placebo group [4 (3, 5) vs. 5 (4, 6); P =0.034]. Patients in fluconazole group had more often reduction in fecal calprotectin [26 (83.9%) vs. 11 (36.7%); P =0.001] and histologic scores [23 (74.1%) vs. 10 (33.3%); P =0.001] compared with placebo. All patients were compliant and did not report any serious adverse event. CONCLUSION Candida colonization is found in 28% of patients with UC. Steroid exposure and active disease were independent predictors for the presence of Candida . There was no statistically significant difference in the number of patients who achieved 3-point reduction in Mayo score between 2 groups. However, clinical, histologic, and calprotectin levels showed significant improvement in fluconazole group.
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Affiliation(s)
| | | | | | | | | | | | | | | | | | | | | | | | - Arunaloke Chakrabarti
- Microbiology, Postgraduate Institute of Medical Education and Research, Chandigarh, India
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Shome M, Song L, Williams S, Chung Y, Murugan V, Park JG, Faubion W, Pasha SF, Leighton JA, LaBaer J, Qiu J. Serological profiling of Crohn’s disease and ulcerative colitis patients reveals anti-microbial antibody signatures. World J Gastroenterol 2022; 28:4089-4101. [PMID: 36157118 PMCID: PMC9403437 DOI: 10.3748/wjg.v28.i30.4089] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/04/2022] [Revised: 06/16/2022] [Accepted: 07/11/2022] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND The healthcare burden of inflammatory bowel disease (IBD) is rising globally and there are limited non-invasive biomarkers for accurate and early diagnosis.
AIM To understand the important role that intestinal microbiota play in IBD pathogenesis and identify anti-microbial antibody signatures that benefit clinical management of IBD patients.
METHODS We performed serological profiling of 100 Crohn’s disease (CD) patients, 100 ulcerative colitis (UC) patients and 100 healthy controls against 1173 bacterial and 397 viral proteins from 50 bacteria and 33 viruses on protein microarrays. The study subjects were randomly divided into discovery (n = 150) and validation (n = 150) sets. Statistical analysis was performed using R packages.
RESULTS Anti-bacterial antibody responses showed greater differential prevalence among the three subject groups than anti-viral antibody responses. We identified novel antibodies against the antigens of Bacteroidetes vulgatus (BVU_0562) and Streptococcus pneumoniae (SP_1992) showing higher prevalence in CD patients relative to healthy controls. We also identified antibodies against the antigen of Streptococcus pyogenes (SPy_2009) showing higher prevalence in healthy controls relative to UC patients. Using these novel antibodies, we built biomarker panels with area under the curve (AUC) of 0.81, 0.87, and 0.82 distinguishing CD vs control, UC vs control, and CD vs UC, respectively. Subgroup analysis revealed that penetrating CD behavior, colonic CD location, CD patients with a history of surgery, and extensive UC exhibited highest antibody prevalence among all patients. We demonstrated that autoantibodies and anti-microbial antibodies in CD patients had minimal correlation.
CONCLUSION We have identified antibody signatures for CD and UC using a comprehensive analysis of anti-microbial antibody response in IBD. These antibodies and the source microorganisms of their target antigens improve our understanding of the role of specific microorganisms in IBD pathogenesis and, after future validation, should aid early and accurate diagnosis of IBD.
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Affiliation(s)
- Mahasish Shome
- Virginia G. Piper Center for Personalized Diagnostics, Biodesign Institute, Arizona State University, Tempe, AZ 85281, United States
| | - Lusheng Song
- Virginia G. Piper Center for Personalized Diagnostics, Biodesign Institute, Arizona State University, Tempe, AZ 85281, United States
| | - Stacy Williams
- Virginia G. Piper Center for Personalized Diagnostics, Biodesign Institute, Arizona State University, Tempe, AZ 85281, United States
| | - Yunro Chung
- Virginia G. Piper Center for Personalized Diagnostics, Biodesign Institute, Arizona State University, Tempe, AZ 85281, United States
| | - Vel Murugan
- Virginia G. Piper Center for Personalized Diagnostics, Biodesign Institute, Arizona State University, Tempe, AZ 85281, United States
| | - Jin G Park
- Virginia G. Piper Center for Personalized Diagnostics, Biodesign Institute, Arizona State University, Tempe, AZ 85281, United States
| | - William Faubion
- Department of Internal Medicine, Mayo Clinic, Rochester, MN 55902, United States
| | - Shabana F Pasha
- Department of Internal Medicine, Division of Gastroenterology and Hepatology, Mayo Clinic Arizona, Scottsdale, AZ 85259, United States
| | - Jonathan A Leighton
- Division of Gastroenterology, Mayo Clinic School of Medicine, Scottsdale, AZ 85259, United States
| | - Joshua LaBaer
- Virginia G. Piper Center for Personalized Diagnostics, Biodesign Institute, Arizona State University, Tempe, AZ 85281, United States
| | - Ji Qiu
- Virginia G. Piper Center for Personalized Diagnostics, Biodesign Institute, Arizona State University, Tempe, AZ 85281, United States
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Petersen AM. Gastrointestinal dysbiosis and Escherichia coli pathobionts in inflammatory bowel diseases. APMIS 2022; 130 Suppl 144:1-38. [PMID: 35899316 PMCID: PMC9546507 DOI: 10.1111/apm.13256] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/28/2022]
Affiliation(s)
- Andreas Munk Petersen
- Department of Gastroenterology and Department of Clinical Microbiology, Copenhagen University Hospital - Amager and Hvidovre, Copenhagen, Denmark
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Emeasoba EU, Ibeson CE, Kundal S, Biondi S, Nwosu I, Golfeyz S, Kantrowitz M, Khodorskiy D. A Rare Case of New-Onset Ulcerative Colitis in a Nonagenarian. Cureus 2022; 14:e26203. [PMID: 35891824 PMCID: PMC9307128 DOI: 10.7759/cureus.26203] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 06/20/2022] [Indexed: 11/05/2022] Open
Abstract
Ulcerative colitis (UC) is one of two major types of inflammatory bowel disease (IBD). It is defined as a chronic idiopathic inflammatory disease limited to the colorectal mucosal layer and characterized by relapsing and remitting episodes of inflammation. UC almost invariably involves the rectum and extends proximally in a continuous distribution to part or the entire colon. Development of disease after 75 years of age is uncommon, with new-onset over the age of 80 accounting only for 1% of all new diagnoses. We present a case of a new onset UC in a 90-year-old patient presenting with painless hematochezia.
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35
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Bourgonje AR, Vogl T, Segal E, Weersma RK. Antibody signatures in inflammatory bowel disease: current developments and future applications. Trends Mol Med 2022; 28:693-705. [DOI: 10.1016/j.molmed.2022.05.004] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/23/2022] [Revised: 05/01/2022] [Accepted: 05/03/2022] [Indexed: 11/25/2022]
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Bos A, van Egmond M, Mebius R. The role of retinoic acid in the production of immunoglobulin A. Mucosal Immunol 2022; 15:562-572. [PMID: 35418672 DOI: 10.1038/s41385-022-00509-8] [Citation(s) in RCA: 18] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/21/2021] [Revised: 03/09/2022] [Accepted: 03/26/2022] [Indexed: 02/04/2023]
Abstract
Vitamin A and its derivative retinoic acid (RA) play important roles in the regulation of mucosal immunity. The effect of vitamin A metabolism on T lymphocyte immunity has been well documented, but its role in mucosal B lymphocyte regulation is less well described. Intestinal immunoglobulin A (IgA) is key in orchestrating a balanced gut microbiota composition. Here, we describe the contribution of RA to IgA class switching in tissues including the lamina propria, mesenteric lymph nodes, Peyer's patches and isolated lymphoid follicles. RA can either indirectly skew T cells or directly affect B cell differentiation. IgA levels in healthy individuals are under the control of the metabolism of vitamin A, providing a steady supply of RA. However, IgA levels are altered in inflammatory bowel disease patients, making control of the metabolism of vitamin A a potential therapeutic target. Thus, dietary vitamin A is a key player in regulating IgA production within the intestine, acting via multiple immunological pathways.
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Affiliation(s)
- Amelie Bos
- Amsterdam UMC, Department of Molecular Cell Biology and Immunology, Research Institute of Amsterdam Institute for Infection and Immunity, Vrije Universiteit, Amsterdam, The Netherlands
| | - Marjolein van Egmond
- Amsterdam UMC, Department of Molecular Cell Biology and Immunology, Research Institute of Amsterdam Institute for Infection and Immunity, Vrije Universiteit, Amsterdam, The Netherlands.,Amsterdam UMC, Department of Surgery, Research Institute of Amsterdam Institute for Infection and Immunity, Vrije Universiteit, Amsterdam, The Netherlands
| | - Reina Mebius
- Amsterdam UMC, Department of Molecular Cell Biology and Immunology, Research Institute of Amsterdam Institute for Infection and Immunity, Vrije Universiteit, Amsterdam, The Netherlands.
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37
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Underhill DM, Braun J. Fungal microbiome in inflammatory bowel disease: a critical assessment. J Clin Invest 2022; 132:155786. [PMID: 35229726 PMCID: PMC8884899 DOI: 10.1172/jci155786] [Citation(s) in RCA: 37] [Impact Index Per Article: 12.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022] Open
Abstract
The gut microbiome is at the center of inflammatory bowel disease (IBD) pathogenesis and disease activity. While this has mainly been studied in the context of the bacterial microbiome, recent advances have provided tools for the study of host genetics and metagenomics of host-fungal interaction. Through these tools, strong evidence has emerged linking certain fungal taxa, such as Candida and Malassezia, with cellular and molecular pathways of IBD disease biology. Mouse models and human fecal microbial transplant also suggest that some disease-participatory bacteria and fungi may act not via the host directly, but via their fungal-bacterial ecologic interactions. We hope that these insights, and the study design and multi-omics strategies used to develop them, will facilitate the inclusion of the fungal community in basic and translational IBD research.
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Affiliation(s)
- David M Underhill
- F. Widjaja Inflammatory Bowel and Immunobiology Research Institute.,Division of Gastroenterology, Department of Medicine, and.,Research Division of Immunology, Department of Biomedical Sciences; Cedars-Sinai Medical Center, Los Angeles, California, USA
| | - Jonathan Braun
- F. Widjaja Inflammatory Bowel and Immunobiology Research Institute.,Division of Gastroenterology, Department of Medicine, and.,Research Division of Immunology, Department of Biomedical Sciences; Cedars-Sinai Medical Center, Los Angeles, California, USA
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Abstract
Inflammatory bowel disease, including ulcerative colitis and Crohn disease, is an idiopathic chronic inflammatory condition of the gastrointestinal tract. Since neither the clinical manifestations nor the morphologic features of inflammatory bowel disease are pathognomonic alone, the differential diagnosis to consider is relatively broad, and it relies on the synthesis of clinical, endoscopic, and microscopic features. Long-held histologic diagnostic principles include recognizing structural and inflammatory features of chronicity, that is, architectural distortion, basal plasmacytosis, and expansion of the lamina propria lymphoplasmacytic infiltrate. In addition, evaluation of the neutrophilic inflammation and related crypt and epithelial destruction is essential to gauge the activity of the disease. Nevertheless, these features can be difficult to confirm in special settings, including at the inception of the disease or in partially treated cases. This review will explore the classic morphologic features of ulcerative colitis and Crohn disease, followed by a detailed discussion of atypical and diagnostically challenging presentations and a brief review of the clinical aspects necessary for the daily practice of pathologists.
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Medical Treatment of Intestinal Crohn's disease. SEMINARS IN COLON AND RECTAL SURGERY 2022. [DOI: 10.1016/j.scrs.2022.100862] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/17/2022]
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40
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Estruch JJ, Johnson J, Ford S, Yoshimoto S, Mills T, Bergman P. Response to letter regarding "Utility of the combined use of 3 serologic markers in the diagnosis and monitoring of chronic enteropathies in dogs". J Vet Intern Med 2021; 35:2570-2571. [PMID: 34825415 PMCID: PMC8692223 DOI: 10.1111/jvim.16304] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/18/2021] [Accepted: 10/18/2021] [Indexed: 11/28/2022] Open
Affiliation(s)
| | | | - Sarah Ford
- Blue Pearl Specialty, Scottsdale, Arizona, USA
| | | | - Tracy Mills
- VCA Clinical Studies, Los Angeles, California, USA
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Buisson A, Vazeille E, Fumery M, Pariente B, Nancey S, Seksik P, Peyrin‐Biroulet L, Allez M, Ballet N, Filippi J, Yzet C, Nachury M, Boschetti G, Billard E, Dubois A, Rodriguez S, Chevarin C, Goutte M, Bommelaer G, Pereira B, Hebuterne X, Barnich N. Faster and less invasive tools to identify patients with ileal colonization by adherent-invasive E. coli in Crohn's disease. United European Gastroenterol J 2021; 9:1007-1018. [PMID: 34791806 PMCID: PMC8598958 DOI: 10.1002/ueg2.12161] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/25/2021] [Accepted: 07/27/2021] [Indexed: 01/17/2023] Open
Abstract
BACKGROUND AND AIMS The identification of Crohn's disease (CD)-associated adherent and invasive Escherichia coli (AIEC) is time-consuming and requires ileal biopsies. We aimed to identify a faster and less invasive methods to detect ileal colonization by AIEC in CD patients. METHODS CD patients requiring ileo-colonoscopy were consecutively enrolled in this prospective multicenter study. Samples from saliva, serum, stools, and ileal biopsies of CD patients were collected. RESULTS Among 102 CD patients, the prevalence of AIEC on ileal biopsies was 24.5%. The abundance and global invasive ability of ileal-associated total E. coli were respectively ten-fold (p = 0.0065) and two-fold (p = 0.0007) higher in AIEC-positive (vs. AIEC-negative), while abundance of total E. coli in the feces was not correlated with AIEC status in the ileum. The best threshold of ileal total E. coli was 60 cfu/biopsy to detect AIEC-positive patients, with high negative predictive value (NPV) (94.1%[80.3-99.3]), while the global invasive ability (>9000 internalized bacteria) was able to detect the presence of AIEC with high positive predictive value (80.0% [55.2-100.0]). Overall, 78.1% of the AIEC + patients were colonized by two or less different AIEC strains. The level of serum anti-total E. coli antibodies (AEcAb) was higher in AIEC-positive patients (p = 0.038) with a very high negative predictive value (96.6% [89.9-100.0]) (p = 0.038) for a cut-off value > 1.9 × 10-3 . CONCLUSIONS More than two thirds of AIEC-positive CD patients were colonized by two or less AIEC strains. While stools samples are not accurate to screen AIEC status, the AEcAb level appears to be an attractive, rapid and easier biomarker to identify patients with Crohn's disease harboring AIEC.
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Affiliation(s)
- Anthony Buisson
- Université Clermont Auvergne/Inserm U1071USC‐INRAe 2018Microbes, Intestin, Inflammation et Susceptibilité de l'Hôte (M2iSH)Clermont‐FerrandFrance
- Université Clermont AuvergneInserm3iHPCHU Clermont‐FerrandService d'Hépato‐Gastro EntérologieClermont‐FerrandFrance
| | - Emilie Vazeille
- Université Clermont Auvergne/Inserm U1071USC‐INRAe 2018Microbes, Intestin, Inflammation et Susceptibilité de l'Hôte (M2iSH)Clermont‐FerrandFrance
- Université Clermont AuvergneInserm3iHPCHU Clermont‐FerrandService d'Hépato‐Gastro EntérologieClermont‐FerrandFrance
| | - Mathurin Fumery
- Department of HepatogastroenterologyAmiens University Hospital, and PeriTox UMR‐I 01AmiensFrance
| | - Benjamin Pariente
- Department of GastroenterologyClaude Huriez HospitalUniversity of LilleLilleFrance
| | - Stéphane Nancey
- Department of GastroenterologyLyon Sud HospitalHospices Civils de Lyonand INSERM U‐1111CIRILyonFrance
| | - Philippe Seksik
- GastroenterologySorbonne UniversitésAP‐HPHospital Saint‐AntoineParisFrance
| | - Laurent Peyrin‐Biroulet
- Department of GastroenterologyNancy University HospitalNancyFrance
- Inserm U1256 NGERELorraine UniversityNancyFrance
| | - Matthieu Allez
- Inserm UMR 1160AP‐HP Gastroenterology Hôpital Saint LouisUniversité ParisDiderotFrance
| | | | - Jérôme Filippi
- Gastroenterology and Clinical NutritionCHU of Nice and University Côte d'Azur NiceFrance
| | - Clara Yzet
- Department of HepatogastroenterologyAmiens University Hospital, and PeriTox UMR‐I 01AmiensFrance
| | - Maria Nachury
- Department of GastroenterologyClaude Huriez HospitalUniversity of LilleLilleFrance
| | - Gilles Boschetti
- Department of GastroenterologyLyon Sud HospitalHospices Civils de Lyonand INSERM U‐1111CIRILyonFrance
| | - Elisabeth Billard
- Université Clermont Auvergne/Inserm U1071USC‐INRAe 2018Microbes, Intestin, Inflammation et Susceptibilité de l'Hôte (M2iSH)Clermont‐FerrandFrance
| | - Anaëlle Dubois
- Université Clermont Auvergne/Inserm U1071USC‐INRAe 2018Microbes, Intestin, Inflammation et Susceptibilité de l'Hôte (M2iSH)Clermont‐FerrandFrance
| | - Stéphanie Rodriguez
- Université Clermont Auvergne/Inserm U1071USC‐INRAe 2018Microbes, Intestin, Inflammation et Susceptibilité de l'Hôte (M2iSH)Clermont‐FerrandFrance
| | - Caroline Chevarin
- Université Clermont Auvergne/Inserm U1071USC‐INRAe 2018Microbes, Intestin, Inflammation et Susceptibilité de l'Hôte (M2iSH)Clermont‐FerrandFrance
| | - Marion Goutte
- Université Clermont Auvergne/Inserm U1071USC‐INRAe 2018Microbes, Intestin, Inflammation et Susceptibilité de l'Hôte (M2iSH)Clermont‐FerrandFrance
- Université Clermont AuvergneInserm3iHPCHU Clermont‐FerrandService d'Hépato‐Gastro EntérologieClermont‐FerrandFrance
| | - Gilles Bommelaer
- Université Clermont Auvergne/Inserm U1071USC‐INRAe 2018Microbes, Intestin, Inflammation et Susceptibilité de l'Hôte (M2iSH)Clermont‐FerrandFrance
- Université Clermont AuvergneInserm3iHPCHU Clermont‐FerrandService d'Hépato‐Gastro EntérologieClermont‐FerrandFrance
| | - Bruno Pereira
- Université Clermont AuvergneCHU Clermont‐FerrandDRCIUnité de BiostatistiquesClermont‐FerrandFrance
- Université Clermont AuvergneCHU Clermont‐FerrandCNRSSIGMA ClermontInstitut PascalClermont‐FerrandFrance
| | - Xavier Hebuterne
- Gastroenterology and Clinical NutritionCHU of Nice and University Côte d'Azur NiceFrance
| | - Nicolas Barnich
- Université Clermont Auvergne/Inserm U1071USC‐INRAe 2018Microbes, Intestin, Inflammation et Susceptibilité de l'Hôte (M2iSH)Clermont‐FerrandFrance
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Klag KA, Round JL. Microbiota-Immune Interactions Regulate Metabolic Disease. JOURNAL OF IMMUNOLOGY (BALTIMORE, MD. : 1950) 2021; 207:1719-1724. [PMID: 34544814 PMCID: PMC9105212 DOI: 10.4049/jimmunol.2100419] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Received: 05/04/2021] [Accepted: 06/18/2021] [Indexed: 12/13/2022]
Abstract
Metabolic diseases are common worldwide and include diseases of overnutrition, such as obesity, or undernutrition, such as kwashiorkor. Both the immune system and the microbiota contribute to a variety of metabolic diseases; however, these two processes have largely been studied independently of one another in this context. The gastrointestinal system houses the greatest density of microbes but also houses one of the largest collections of immune molecules, especially Abs. The IgA isotype dominates the Ab landscape at mucosal sites, and a number of studies have demonstrated the importance of this Ab to the stability of the microbiota. In this article, we review the literature that demonstrates how homeostatic Ab responses control microbiota composition and function to influence metabolic disease. We propose that many metabolic diseases may arise from disruptions to homeostatic immune control of gut commensals and that further understanding this interaction can offer a novel opportunity for therapeutic interventions.
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Affiliation(s)
- Kendra A Klag
- Division of Microbiology and Immunology, Department of Pathology, University of Utah School of Medicine, Salt Lake City, UT; and
| | - June L Round
- Division of Microbiology and Immunology, Department of Pathology, University of Utah School of Medicine, Salt Lake City, UT; and .,Huntsman Cancer Institute, University of Utah, Salt Lake City, UT
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Majidova K, Handfield J, Kafi K, Martin RD, Kubinski R. Role of Digital Health and Artificial Intelligence in Inflammatory Bowel Disease: A Scoping Review. Genes (Basel) 2021; 12:1465. [PMID: 34680860 PMCID: PMC8535572 DOI: 10.3390/genes12101465] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/26/2021] [Accepted: 09/14/2021] [Indexed: 12/12/2022] Open
Abstract
Inflammatory bowel diseases (IBD), subdivided into Crohn's disease (CD) and ulcerative colitis (UC), are chronic diseases that are characterized by relapsing and remitting periods of inflammation in the gastrointestinal tract. In recent years, the amount of research surrounding digital health (DH) and artificial intelligence (AI) has increased. The purpose of this scoping review is to explore this growing field of research to summarize the role of DH and AI in the diagnosis, treatment, monitoring and prognosis of IBD. A review of 21 articles revealed the impact of both AI algorithms and DH technologies; AI algorithms can improve diagnostic accuracy, assess disease activity, and predict treatment response based on data modalities such as endoscopic imaging and genetic data. In terms of DH, patients utilizing DH platforms experienced improvements in quality of life, disease literacy, treatment adherence, and medication management. In addition, DH methods can reduce the need for in-person appointments, decreasing the use of healthcare resources without compromising the standard of care. These articles demonstrate preliminary evidence of the potential of DH and AI for improving the management of IBD. However, the majority of these studies were performed in a regulated clinical environment. Therefore, further validation of these results in a real-world environment is required to assess the efficacy of these methods in the general IBD population.
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Affiliation(s)
| | | | | | | | - Ryszard Kubinski
- Phyla Technologies Inc., Montréal, QC H3C 4J9, Canada; (K.M.); (J.H.); (K.K.); (R.D.M.)
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Antibodies Against Glycoprotein 2 Are Specific Biomarkers for Pediatric Crohn's Disease. Dig Dis Sci 2021; 66:2619-2626. [PMID: 32886311 DOI: 10.1007/s10620-020-06589-5] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/30/2020] [Accepted: 08/26/2020] [Indexed: 12/09/2022]
Abstract
BACKGROUND Serological markers can assist in accurate differentiation between Crohn's disease (CD) and ulcerative colitis (UC). One such marker is anti-glycoprotein 2 (anti-GP2) which was shown to be a specific marker for CD in adult patients. The aim of our study was to assess the utility of anti-GP2 and GP2 as biomarkers for pediatric CD, and determine whether they correlate with disease activity. METHODS Serum samples were tested by ELISA for anti-GP2 isoform 4 IgG and IgA, and also for GP2. Results were correlated with demographic and clinical data. RESULTS The cohort consisted of 53 pediatric patients with CD, 42 with UC, and 53 controls. Levels of anti-GP2 were significantly increased in pediatric patients with CD in comparison with patients with UC, and control subjects, with high positive predictive value for both IgG and IgA (97.9% and 82.6%, respectively). While specificity of anti-GP2 IgG and IgA was very high (98.7% and 90.0%, respectively), sensitivity was low (42.0% and 35.5% for IgG and IgA, respectively). In CD, anti-GP2 correlated with disease activity, and decreased in treatment-naïve patients following successful induction therapy. A higher IgA anti-GP2 was also demonstrated in patients with ileo-colonic involvement, and was associated with a younger age. Finally, positive GP2 level was identified in only 1/211 serum samples. CONCLUSIONS A positive anti-GP2 level is highly associated with CD, while a negative result does not exclude CD. Additional studies are required to determine whether these markers can be used in pediatric patients with CD for risk stratification.
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Mizuochi T, Arai K, Kudo T, Nambu R, Tajiri H, Aomatsu T, Abe N, Kakiuchi T, Hashimoto K, Sogo T, Takahashi M, Etani Y, Takaki Y, Konishi KI, Ishihara J, Obara H, Kakuma T, Kurei S, Yamashita Y, Mitsuyama K. Diagnostic accuracy of serum proteinase 3 antineutrophil cytoplasmic antibodies in children with ulcerative colitis. J Gastroenterol Hepatol 2021; 36:1538-1544. [PMID: 33047817 DOI: 10.1111/jgh.15296] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/17/2020] [Revised: 09/15/2020] [Accepted: 10/07/2020] [Indexed: 12/13/2022]
Abstract
BACKGROUND AND AIM Serologic markers such as myeloperoxidase (MPO) antineutrophil cytoplasmic antibodies (ANCA) (MPO-ANCA) have been used to screen patients for ulcerative colitis (UC). However, MPO-ANCA shows limited accuracy in Asians. Proteinase 3 ANCA (PR3-ANCA) has performed better at UC diagnosis in Japanese adults than MPO-ANCA. The present study aimed to evaluate usefulness of PR3-ANCA for diagnosis of UC in Japanese pediatric practice. METHODS Patients under 17 years old undergoing assessment at 12 Japanese pediatric centers between November 2016 and February 2018 were prospectively enrolled and divided into groups with UC, Crohn's disease (CD), intestinal disease control (IC), and healthy control (HC). Serum PR3-ANCA and MPO-ANCA were analyzed using chemiluminescence enzyme immunoassay kits. RESULTS Sera from 367 patients (148 with UC at a median age of 12 years; 120 with CD, 13 years; 56 with IC, 10.5 years; and 43 with HC, 10 years) were examined. Median PR3-ANCA values in UC (1.6 U/mL) were greater than in CD (0.2; P < 0.001), IC (0.15; P < 0.001), and HC (0.1; P < 0.001). In receiver operating characteristic curve analyses, the area under the curve for PR3-ANCA was 0.79, significantly greater than for MPO-ANCA (0.58; P < 0.001). Using a cut-off value of 0.8 U/mL determined from the receiver operating characteristic analyses, PR3-ANCA showed significantly greater sensitivity (64.9%) than MPO-ANCA (cut-off, 0.2 U/mL; sensitivity, 19.6%; P < 0.001) and good specificity (83.6%). CONCLUSIONS In Japanese children and adolescents, PR3-ANCA performed better as a serologic marker for diagnosis of UC than MPO-ANCA. To our knowledge, this is the first report of such a comparison.
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Affiliation(s)
- Tatsuki Mizuochi
- Department of Pediatrics and Child Health, Kurume University School of Medicine, Kurume, Japan
| | - Katsuhiro Arai
- Division of Gastroenterology, National Center for Child Health and Development, Tokyo, Japan
| | - Takahiro Kudo
- Department of Pediatrics, Juntendo University Faculty of Medicine, Tokyo, Japan
| | - Ryusuke Nambu
- Division of Gastroenterology and Hepatology, Saitama Children's Medical Center, Saitama, Japan
| | - Hitoshi Tajiri
- Department of Pediatrics, Osaka General Medical Center, Osaka, Japan
| | - Tomoki Aomatsu
- Department of Pediatrics, Osaka Medical College, Osaka, Japan
| | - Naoki Abe
- Department of Infection and Immunology, Aichi Children's Health and Medical Center, Obu, Japan
| | - Toshihiko Kakiuchi
- Department of Pediatrics, Faculty of Medicine, Saga University, Saga, Japan
| | - Kunio Hashimoto
- Department of Pediatrics, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan
| | - Tsuyoshi Sogo
- Department of Pediatric Hepatology and Gastroenterology, Saiseikai Yokohamashi Tobu Hospital, Yokohama, Japan
| | - Michiko Takahashi
- Department of Pediatrics, Sapporo Kosei General Hospital, Sapporo, Japan
| | - Yuri Etani
- Department of Gastroenterology and Endocrinology, Osaka Women's and Children's Hospital, Osaka, Japan
| | - Yugo Takaki
- Department of Pediatrics and Child Health, Kurume University School of Medicine, Kurume, Japan
| | - Ken-Ichiro Konishi
- Department of Pediatrics and Child Health, Kurume University School of Medicine, Kurume, Japan
| | - Jun Ishihara
- Department of Pediatrics and Child Health, Kurume University School of Medicine, Kurume, Japan
| | - Hitoshi Obara
- Biostatistics Center, Kurume University School of Medicine, Kurume, Japan
| | - Tatsuyuki Kakuma
- Biostatistics Center, Kurume University School of Medicine, Kurume, Japan
| | | | - Yushiro Yamashita
- Department of Pediatrics and Child Health, Kurume University School of Medicine, Kurume, Japan
| | - Keiichi Mitsuyama
- Division of Gastroenterology, Department of Medicine, Kurume University School of Medicine, Kurume, Japan
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Aldars-García L, Chaparro M, Gisbert JP. Systematic Review: The Gut Microbiome and Its Potential Clinical Application in Inflammatory Bowel Disease. Microorganisms 2021; 9:microorganisms9050977. [PMID: 33946482 PMCID: PMC8147118 DOI: 10.3390/microorganisms9050977] [Citation(s) in RCA: 96] [Impact Index Per Article: 24.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/05/2021] [Revised: 04/22/2021] [Accepted: 04/29/2021] [Indexed: 02/07/2023] Open
Abstract
Inflammatory bowel disease (IBD) is a chronic relapsing-remitting systemic disease of the gastrointestinal tract. It is well established that the gut microbiome has a profound impact on IBD pathogenesis. Our aim was to systematically review the literature on the IBD gut microbiome and its usefulness to provide microbiome-based biomarkers. A systematic search of the online bibliographic database PubMed from inception to August 2020 with screening in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines was conducted. One-hundred and forty-four papers were eligible for inclusion. There was a wide heterogeneity in microbiome analysis methods or experimental design. The IBD intestinal microbiome was generally characterized by reduced species richness and diversity, and lower temporal stability, while changes in the gut microbiome seemed to play a pivotal role in determining the onset of IBD. Multiple studies have identified certain microbial taxa that are enriched or depleted in IBD, including bacteria, fungi, viruses, and archaea. The two main features in this sense are the decrease in beneficial bacteria and the increase in pathogenic bacteria. Significant differences were also present between remission and relapse IBD status. Shifts in gut microbial community composition and abundance have proven to be valuable as diagnostic biomarkers. The gut microbiome plays a major role in IBD, yet studies need to go from casualty to causality. Longitudinal designs including newly diagnosed treatment-naïve patients are needed to provide insights into the role of microbes in the onset of intestinal inflammation. A better understanding of the human gut microbiome could provide innovative targets for diagnosis, prognosis, treatment and even cure of this relevant disease.
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Affiliation(s)
- Laila Aldars-García
- Hospital Universitario de La Princesa, Instituto de Investigación Sanitaria Princesa (IIS-IP), Universidad Autónoma de Madrid, 28006 Madrid, Spain; (L.A.-G.); (M.C.)
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), 28006 Madrid, Spain
| | - María Chaparro
- Hospital Universitario de La Princesa, Instituto de Investigación Sanitaria Princesa (IIS-IP), Universidad Autónoma de Madrid, 28006 Madrid, Spain; (L.A.-G.); (M.C.)
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), 28006 Madrid, Spain
| | - Javier P. Gisbert
- Hospital Universitario de La Princesa, Instituto de Investigación Sanitaria Princesa (IIS-IP), Universidad Autónoma de Madrid, 28006 Madrid, Spain; (L.A.-G.); (M.C.)
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), 28006 Madrid, Spain
- Correspondence: ; Tel.: +34-913-093-911; Fax: +34-915-204-013
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Treatments of inflammatory bowel disease toward personalized medicine. Arch Pharm Res 2021; 44:293-309. [PMID: 33763844 DOI: 10.1007/s12272-021-01318-6] [Citation(s) in RCA: 14] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/03/2021] [Accepted: 03/06/2021] [Indexed: 12/12/2022]
Abstract
Inflammatory bowel disease (IBD), including ulcerative colitis (UC) and Crohn's disease (CD), is a chronic inflammatory disease characterized by intestinal inflammation and epithelial injury. For the treatment of IBD, 5-aminosalicylic acids, corticosteroids, immunomodulators, and biologic agents targeting tumor necrosis factor (TNF)-α, α4β7-integrin, and interleukin (IL)-12/23 have been widely used. Especially, anti-TNF-α antibodies are the first biologic agents that presently remain at the forefront. However, 10-30% of patients resist biologic agents, including anti-TNF-α agents (primary non-responder; PNR), and 20-50% of primary responders develop treatment resistance within one year (secondary loss of response; SLR). Nonetheless, the etiologies of PNR and SLR are not clearly understood, and predictors of response to biologic agents are also not defined yet. Numerous studies are being performed to discover prediction markers of the response to biologic agents, and this review will introduce currently available therapeutic options for IBD, biologics under investigation, and recent studies exploring various predictive factors related to PNR and SLR.
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Edwards SJ, Barton S, Bacelar M, Karner C, Cain P, Wakefield V, Marceniuk G. Prognostic tools for identification of high risk in people with Crohn's disease: systematic review and cost-effectiveness study. Health Technol Assess 2021; 25:1-138. [PMID: 33783345 PMCID: PMC8040347 DOI: 10.3310/hta25230] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/24/2022] Open
Abstract
BACKGROUND Crohn's disease is a lifelong condition that can affect any segment of the gastrointestinal tract. Some people with Crohn's disease may be at higher risk of following a severe course of disease than others and being able to identify the level of risk a patient has could lead to personalised management. OBJECTIVE To assess the prognostic test accuracy, clinical impact and cost-effectiveness of two tools for the stratification of people with a diagnosis of Crohn's disease by risk of following a severe course of disease. DATA SOURCES The data sources MEDLINE, EMBASE, the Cochrane Database of Systematic Reviews and the Cochrane Central Register of Controlled Trials were searched to inform the systematic reviews on prognostic accuracy, clinical impact of the prognostic tools, and economic evaluations. Additional data sources to inform the review of economic evaluations were NHS Economic Evaluation Database, Database of Abstracts of Reviews of Effects and the Health Technology Assessment Database. REVIEW METHODS Systematic reviews of electronic databases were carried out from inception to June 2019 for studies assessing the prognostic accuracy and clinical impact of the IBDX® (Crohn's disease Prognosis Test; Glycominds Ltd, Lod, Israel) biomarker stratification tool and the PredictSURE-IBD™ (PredictImmune Ltd, Cambridge, UK) tool. Systematic reviews of studies reporting on the cost-effectiveness of treatments for Crohn's disease were run from inception to July 2019. Two reviewers independently agreed on studies for inclusion, assessed the quality of included studies and validated the data extracted from studies. Clinical and methodological heterogeneity across studies precluded the synthesis of data for prognostic accuracy. A de novo economic model was developed to compare the costs and consequences of two treatment approaches - the 'top-down' and 'step-up' strategies, with step-up considered standard care - in people at high risk of following a severe course of Crohn's disease. The model comprised a decision tree and a Markov cohort model. RESULTS Sixteen publications, including eight original studies (n = 1478), were deemed relevant to the review of prognostic accuracy. Documents supplied by the companies marketing the prognostic tools were also reviewed. No study meeting the eligibility criteria reported on the sensitivity or specificity of the IBDX biomarker stratification tool, whereas one study provided estimates of sensitivity, specificity and negative predictive value for the PredictSURE-IBD tool. All identified studies were observational and were considered to provide weak evidence on the effectiveness of the tools. Owing to the paucity of data on the two tools, in the base-case analysis the accuracy of PredictSURE-IBD was assumed to be 100%. Accuracy of IBDX was assumed to be 100% in a scenario analysis, with the cost of the tests being the only difference between the analyses. The incremental analysis of cost-effectiveness demonstrated that top-down (via the use of PredictSURE-IBD in the model) is more expensive and generates fewer quality-adjusted life-years than step-up (via the standard care arm of the model). LIMITATIONS Despite extensive systematic searches of the literature, no robust evidence was identified of the prognostic accuracy of the biomarker stratification tools IBDX and PredictSURE-IBD. CONCLUSIONS Although the model indicates that standard care dominates the tests, the lack of evidence of prognostic accuracy of the two tests and the uncertainty around the benefits of the top-down and step-up treatment approaches mean that the results should be interpreted as indicative rather than definitive. STUDY REGISTRATION This study is registered as PROSPERO CRD42019138737. FUNDING This project was funded by the National Institute for Health Research (NIHR) Evidence Synthesis programme and will be published in full in Health Technology Assessment; Vol. 25, No. 23. See the NIHR Journals Library website for further project information.
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Mager R, Roda G, Shalaby MK, Vetrano S. Fibrotic Strictures in Crohn's Disease: Mechanisms and Predictive Factors. Curr Drug Targets 2021; 22:241-251. [PMID: 33081672 DOI: 10.2174/1389450121666201020160803] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/08/2020] [Revised: 08/13/2020] [Accepted: 08/27/2020] [Indexed: 11/22/2022]
Abstract
Fibrotic strictures are one of the most severe complications of Crohn's Disease (CD). They occur in about 50% of patients at five years and in 70% at ten years of the diagnosis. The only treatment available for symptomatic fibrotic strictures is surgical resection and endoscopic dilation. Both strategies are associated with a high rate of recurrence, and with multiple surgical resections, which pose the threat of surgical morbidity and short bowel syndrome. Therefore, it is crucial to identify, early, the patients more prone to develop intestinal fibrosis to intensify follow-ups, switch to more aggressive treatments, and suggest lifestyle modifications. Scarce data are available concerning biomarkers and genetic determinants to predict which patient will develop intestinal fibrosis. Biologic or clinical markers would be useful to determine this subgroup of CD patients and to predict the onset of intestinal fibrosis and, ideally, its severity. Furthermore, the identification of environmental risk factors may suggest lifestyle changes aimed at modifying the natural course, thus decreasing the risk of complicated CD. In this review, we will critically revise clinical, environmental, genetic, and serologic factors that have been associated with a complicated CD course with a particular focus on the fibrostenosing phenotype and their possible implications as predictive factors of intestinal fibrosis.
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Affiliation(s)
- Riccardo Mager
- Department of Biomedical Sciences, Humanitas University, Pieve Emanuele, 20090, Milan, Italy
| | - Giulia Roda
- IBD Center, Laboratory of Gastrointestinal Immunopathology, Humanitas Clinical and Research Center-IRCCS, Rozzano, Milan, Italy
| | - Mohammad Khaled Shalaby
- IBD Center, Laboratory of Gastrointestinal Immunopathology, Humanitas Clinical and Research Center-IRCCS, Rozzano, Milan, Italy
| | - Stefania Vetrano
- Department of Biomedical Sciences, Humanitas University, Pieve Emanuele, 20090, Milan, Italy
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Aleksandrova EN, Novikov AA, Lukina GV, Parfenov AI. [Clinical value of antibodies in inflammatory bowel diseases]. TERAPEVT ARKH 2021; 93:228-235. [PMID: 36286642 DOI: 10.26442/00403660.2021.02.200610] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/05/2021] [Accepted: 04/05/2021] [Indexed: 11/22/2022]
Abstract
Inflammatory bowel disease IBD (Crohns disease CD, ulcerative colitis UC) immune-mediated diseases of the digestive tract of unknown etiology. The basis of the pathogenesis of IBD is a violation of the protective mechanisms of the intestinal barrier as a result of a complex interaction of environmental factors, a genetic predisposition and defects in the activation of the immune response in the lymphoid tissue of the intestinal mucosa. Three groups of antibodies are detected in the sera of IBD patients: autoantibodies, antimicrobial antibodies and antibodies to peptide antigens. In CD, the most useful diagnostic markers are ASCA; in UC patients pANCA. Antibodies are not among the diagnostic criteria for CD and UC, the diagnosis of which is traditionally made on the basis of a complex of clinical, radiological, endoscopic and histological signs, but can be used as useful additional non-invasive markers for early diagnosis, assessment of clinical phenotypes, prognosis and effectiveness of treatment of these diseases.
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Affiliation(s)
| | - A A Novikov
- Loginov Moscow Clinical Research and Practical Center
| | - G V Lukina
- Loginov Moscow Clinical Research and Practical Center
| | - A I Parfenov
- Loginov Moscow Clinical Research and Practical Center
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