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Rahaman MM, Wangchuk P, Sarker S. A systematic review on the role of gut microbiome in inflammatory bowel disease: Spotlight on virome and plant metabolites. Microb Pathog 2025; 205:107608. [PMID: 40250496 DOI: 10.1016/j.micpath.2025.107608] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/02/2024] [Revised: 04/14/2025] [Accepted: 04/16/2025] [Indexed: 04/20/2025]
Abstract
Inflammatory bowel diseases (IBD), including ulcerative colitis and Crohn's disease, arise from various factors such as dietary, genetic, immunological, and microbiological influences. The gut microbiota plays a crucial role in the development and treatment of IBD, though the exact mechanisms remain uncertain. Current research has yet to definitively establish the beneficial effects of the microbiome on IBD. Bacteria and viruses (both prokaryotic and eukaryotic) are key components of the microbiome uniquely related to IBD. Numerous studies suggest that dysbiosis of the microbiota, including bacteria, viruses, and bacteriophages, contributes to IBD pathogenesis. Conversely, some research indicates that bacteria and bacteriophages may positively impact IBD outcomes. Additionally, plant metabolites play a crucial role in alleviating IBD due to their anti-inflammatory and microbiome-modulating properties. This systematic review discusses the role of the microbiome in IBD pathogenesis and evaluates the potential connection between plant metabolites and the microbiome in the context of IBD pathophysiology.
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Affiliation(s)
- Md Mizanur Rahaman
- Biomedical Sciences and Molecular Biology, College of Medicine and Dentistry, James Cook University, Townsville, QLD, 4811, Australia; Australian Institute of Tropical Health and Medicine, James Cook University, Townsville, QLD, 4811, Australia
| | - Phurpa Wangchuk
- College of Science and Engineering, James Cook University, Nguma Bada campus, McGregor Rd, Smithfield, Cairns, QLD 4878, Australia; Australian Institute of Tropical Health and Medicine, James Cook University, Nguma Bada campus, McGregor Rd, Smithfield, Cairns, QLD, 4878, Australia
| | - Subir Sarker
- Biomedical Sciences and Molecular Biology, College of Medicine and Dentistry, James Cook University, Townsville, QLD, 4811, Australia; Australian Institute of Tropical Health and Medicine, James Cook University, Townsville, QLD, 4811, Australia.
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2
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Shawky A, Saber S, Abd El-Kader EM, El-Kashef HA. Verapamil inhibits TXNIP-dependent NLRP3 Inflammasome activation in an ulcerative colitis rat model: A new evolving role of the calcium channel blocker. Int Immunopharmacol 2025; 158:114751. [PMID: 40359884 DOI: 10.1016/j.intimp.2025.114751] [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: 02/27/2025] [Revised: 04/23/2025] [Accepted: 04/25/2025] [Indexed: 05/15/2025]
Abstract
Ulcerative colitis (UC) is a long-term inflammatory bowel disease (IBD) associated with significant morbidity. It is marked by inflammation and damage to the colon's mucosal lining. Studies have shown that NLRP3 inflammasome activation, apoptosis, and impaired autophagy are critical in its pathogenesis. Verapamil, a calcium channel blocker, has been found to inhibit NLRP3 inflammasome activation in various preclinical models. However, the potential influence of verapamil on the TXNIP in UC remains unexplored. This study investigates the effects of verapamil on an UC rat model induced chemically by acetic acid. Verapamil effectively inhibited the TXNIP-NLRP3-caspase-1 axis, reducing inflammasome activation and the release of IL-1β and IL-18. Additionally, verapamil suppressed NFκB, the priming step of NLRP3 activation. The drug enhanced autophagic activity, as indicated by increased expression of LC3-II and Beclin-1, along with reduced LC3-I and mTOR expression. Moreover, it demonstrated anti-apoptotic effects mediated by regulating Bax and cleaved caspase-3. These molecular changes contributed to mucosal healing and improved microscopic and macroscopic outcomes in the colitis model. Furthermore, verapamil improved the colon weight-to-length ratio and disease activity scores and mitigated oxidative stress. As verapamil has been safely used in clinics to treat hypertension, our findings suggest it may be a safe therapeutic option for ameliorating inflammation and apoptosis and activating autophagy in UC pathology. Since hypertension demonstrates a strong association with UC, the use of verapamil merits particular attention in hypertensive patients fighting against IBD.
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Affiliation(s)
- Ahmed Shawky
- Department of Pharmacology, Faculty of Pharmacy, Delta University for Science and Technology, Gamasa, 11152, Egypt
| | - Sameh Saber
- Department of Pharmacology, Faculty of Pharmacy, Delta University for Science and Technology, Gamasa, 11152, Egypt.
| | - Eman M Abd El-Kader
- Department of Pharmacology, Faculty of Pharmacy, Delta University for Science and Technology, Gamasa, 11152, Egypt.
| | - Hassan A El-Kashef
- Department of Pharmacology, Faculty of Pharmacy, Delta University for Science and Technology, Gamasa, 11152, Egypt; Department of Pharmacology and Toxicology, Faculty of Pharmacy, Mansoura University, Mansoura 35516, Egypt.
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3
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Qi J, Chen J, von Stillfried S, Kozcera P, Shi Y, Rix A, Kiessling F. Molecular Ultrasound Imaging With Clinically Translatable cRGD-Coated Microbubbles to Assess α v β 3 -Integrin Expression in Inflammatory Bowel Disease. Invest Radiol 2025; 60:407-413. [PMID: 39609095 DOI: 10.1097/rli.0000000000001143] [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: 11/30/2024]
Abstract
OBJECTIVES Inflammatory bowel disease (IBD) subdivides into Crohn disease (CD) and ulcerative colitis (UC), and is characterized by unpredictable periods of inflammation and results in significant patient suffering and even death. Conventional diagnostic methods, for example, colonoscopy, computed tomography, or magnetic resonance imaging, have limitations such as invasiveness, patient discomfort, and limited sensitivity and accuracy. Therefore, we propose ultrasound molecular imaging (USMI) to detect and characterize IBD. First, we evaluated integrin-α v β 3 as a biomarker of IBD in human samples and then used clinically translatable cyclic Arg-Gly-Asp-D-Phe-Lys (cRGDfK)-coupled poly(butyl)cyanoacrylate microbubbles (cRGD-MB) to assess IBD in mice. MATERIALS AND METHODS Vascular integrin-α v β 3 expression in human colon tissue samples (healthy, CD and UC, n = 10 per group) was analyzed by immunofluorescence staining. In mice, acute colitis was induced by administration of 4% dextran sodium sulfate in drinking water for 5 days. On day 7, USMI with cRGD-MB was performed in colitis (n = 6) and healthy (n = 5) mice. The signal of bound cRGD-MB was assessed by the destruction-replenishment method. Ex vivo analysis of mouse colon tissue was performed to assess the degree of colitis by hematoxylin-eosin staining and the vascular expression of integrin-α v by immunofluorescence. RESULTS Human samples showed a significantly higher vascular integrin-α v β 3 expression in CD and UC tissue, when compared with healthy samples ( P < 0.005). In mice, a higher binding of cRGD-MB to inflamed colon was detected by USMI compared with healthy controls ( P < 0.005). Immunofluorescence staining confirmed these findings, showing stronger integrin-α v expression in acute colitis, with a good correlation between USMI signal intensity and integrin-α v expression ( r = 0.8, P = 0.0016). CONCLUSIONS Integrin-α v β 3 on vessels is a suitable marker for IBD. USMI using cRGD-MB accurately detects this marker and correlates well with histology. These encouraging results support clinical translation of this imaging method as a noninvasive and cost-effective monitoring tool.
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Affiliation(s)
- Jinwei Qi
- From the Institute for Experimental Molecular Imaging, Medical Faculty, RWTH Aachen University, Aachen, Germany (J.Q., J.C., P.K., Y.S., A.R., F.K.); and Institute of Pathology, Medical Faculty, RWTH Aachen University, Aachen, Germany (S.V.)
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Magier SJ, Morley TS, Kelly CR. Optimizing Therapeutic Potential of Fecal Transplant in Inflammatory Bowel Disease. Gastroenterol Clin North Am 2025; 54:277-293. [PMID: 40348488 DOI: 10.1016/j.gtc.2024.12.002] [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: 05/14/2025]
Abstract
Inflammatory bowel disease (IBD) is a chronic inflammatory condition of the gastrointestinal tract influenced by genetic, environmental, immune, and microbial factors. Reduced gut microbial diversity and elevated proinflammatory bacteria levels in IBD disrupt mucosal immunity, barrier function, and inflammatory pathways. Fecal microbiota transplantation (FMT) is a potential therapy to restore microbial balance. Studies suggest that FMT may induce remission in mild-to-moderate ulcerative colitis but show limited efficacy in Crohn's disease and pouchitis. Donor microbiota colonization correlates with remission, but varied study designs challenge findings. Further research is required to standardize FMT protocols, optimize donor selection, and ensure long-term safety.
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Affiliation(s)
- Samantha J Magier
- Department of Medicine, Division of Gastroenterology, Brigham and Women's Hospital, Boston, MA, USA; Harvard Medical School, Boston, MA, USA
| | - Thomas S Morley
- Department of Medicine, Division of Gastroenterology, Brigham and Women's Hospital, Boston, MA, USA; Harvard Medical School, Boston, MA, USA
| | - Colleen R Kelly
- Department of Medicine, Division of Gastroenterology, Brigham and Women's Hospital, Boston, MA, USA; Harvard Medical School, Boston, MA, USA.
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Langeraert J, Gasthuys E, Vermeulen A. Small molecule drug absorption in inflammatory bowel disease and current implementation in physiologically- based pharmacokinetic models. Eur J Pharm Sci 2025; 209:107095. [PMID: 40187540 DOI: 10.1016/j.ejps.2025.107095] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/12/2024] [Revised: 02/09/2025] [Accepted: 04/03/2025] [Indexed: 04/07/2025]
Abstract
Inflammatory bowel disease (IBD) is characterized by a chronic inflammation of the intestinal mucosa, with predominant localization in the colon in ulcerative colitis (UC) or affecting the entire length of the gastrointestinal tract in Crohn's disease (CD). Recent advances in the drug development space have been marked by a return to orally administered small molecules with novel mechanisms of action such as Janus kinase inhibitors. Additionally, the prevalence of certain chronic conditions is higher in IBD patients, many of which are treated with orally administered drugs. Given the pathophysiology and localization of IBD, altered drug absorption from the gastrointestinal tract can be expected. This review discusses several physiological differences between the small and large intestine with the potential to influence drug absorption including pathophysiology related alterations associated with IBD. The main physiological parameters which are identified include luminal fluid volume, luminal pH, transit time, bile salt concentration, microbiome, absorptive surface area, permeability and metabolizing enzymes and transporters. Literature regarding these factors in IBD patients is marked with high heterogeneity in reporting of disease severity and location leading to difficulties in interpreting data across different studies. While the influence of most of these factors has been directly assessed in healthy volunteers, this is rarely the case for IBD patients. Furthermore, studies which used PBPK modelling to describe the PK of an orally administered drug in an IBD population and were able to verify their findings using clinical data are critically examined. These models were able to incorporate the pathophysiological changes associated with IBD and partly succeeded in adequately predicting drug absorption in this population. Given the limited amount of PBPK studies performed on a limited number of drugs, the developed models are most likely not suitable to be used as a general PBPK model for the IBD population.
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Affiliation(s)
- Jonas Langeraert
- Laboratory of Medicinal Biochemistry and Clinical Analysis, Department of Bioanalysis, Ghent University, Ottergemsesteenweg 460, 9000 Ghent, Belgium.
| | - Elke Gasthuys
- Laboratory of Medicinal Biochemistry and Clinical Analysis, Department of Bioanalysis, Ghent University, Ottergemsesteenweg 460, 9000 Ghent, Belgium
| | - An Vermeulen
- Laboratory of Medicinal Biochemistry and Clinical Analysis, Department of Bioanalysis, Ghent University, Ottergemsesteenweg 460, 9000 Ghent, Belgium
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Loh L, Orlicky DJ, Spengler A, Domenico J, Klarquist J, Levens C, Celli S, Kofonow JM, Robertson CE, Lantz O, Legoux F, Frank DN, Matsuda J, Norman PJ, Kuhn KA, Onyiah J, Gapin L. MAIT cells exacerbate colonic inflammation in a genetically diverse murine model of spontaneous colitis. Mucosal Immunol 2025:S1933-0219(25)00053-4. [PMID: 40425090 DOI: 10.1016/j.mucimm.2025.05.006] [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: 09/07/2024] [Revised: 05/01/2025] [Accepted: 05/21/2025] [Indexed: 05/29/2025]
Abstract
IL-17-producing lymphocytes are involved in both tissue repair and the propagation of inflammation, with their effects highly context-dependent. Mucosal-Associated-Invariant-T-cells (MAIT), a subset of innate-like T cells with features of both Th1 and Th17 lineages, are increasingly recognized for their roles in mucosal immunity. Here, we identified the Collaborative-Cross CC011/Unc strain, which spontaneously develops chronic colitis, as being enriched for MAIT cells. This expansion coincides with an age-related loss of intestinal barrier permeability and colonic inflammation. Microbiota from CC011 mice activated MAIT cells in an MR1-dependent manner and selectively promoted the accumulation of MAIT17 cells in peripheral tissues. Single-cell transcriptomic analyses revealed colon MAIT cells from colitic CC011 mice expressed a pathogenic Th17-like signature, characterized by IL-1 and IL-23 signaling, IL-17A and IFNγ co-expression, and upregulation of IL-23R, features that correlated with inflammatory Ly6Chi monocyte abundance. Genetic deletion of Traj33, essential for MAIT development, significantly reduced colonic inflammation in this model. These findings demonstrate that MAIT cells integrate microbial and cytokine cues to adopt a pathogenic effector phenotype that exacerbates chronic intestinal inflammation.
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Affiliation(s)
- Liyen Loh
- Department of Immunology and Microbiology, University of Colorado School of Medicine, Aurora, CO, USA.
| | - David J Orlicky
- Department of Pathology, University of Colorado School of Medicine, Aurora, CO, USA
| | - Andrea Spengler
- Department of Immunology and Microbiology, University of Colorado School of Medicine, Aurora, CO, USA
| | - Joanne Domenico
- Department of Immunology and Microbiology, University of Colorado School of Medicine, Aurora, CO, USA
| | - Jared Klarquist
- Department of Immunology and Microbiology, University of Colorado School of Medicine, Aurora, CO, USA
| | - Cassandra Levens
- Division of Rheumatology, Department of Medicine, University of Colorado School of Medicine, Aurora, CO, USA
| | - Sofia Celli
- Department of Biomedical Informatics, University of Colorado School of Medicine, Aurora, CO, USA
| | - Jennifer M Kofonow
- Division of Infectious Diseases, Department of Medicine, University of Colorado School of Medicine, Aurora, CO, USA
| | - Charles E Robertson
- Division of Infectious Diseases, Department of Medicine, University of Colorado School of Medicine, Aurora, CO, USA
| | - Olivier Lantz
- Institut Curie, Paris Sciences et Lettres University, Inserm U932, Immunity and Cancer, Paris, France
| | - Francois Legoux
- INSERM ERL 1305, CNRS UMR6290, Université de Rennes, Institut de Génétique & Développement de Rennes, France
| | - Daniel N Frank
- Division of Infectious Diseases, Department of Medicine, University of Colorado School of Medicine, Aurora, CO, USA
| | - Jennifer Matsuda
- Department of Immunology and Microbiology, University of Colorado School of Medicine, Aurora, CO, USA; Mouse Genetics Core, National Jewish Health, Denver, CO, USA
| | - Paul J Norman
- Department of Immunology and Microbiology, University of Colorado School of Medicine, Aurora, CO, USA; Department of Biomedical Informatics, University of Colorado School of Medicine, Aurora, CO, USA
| | - Kristine A Kuhn
- Division of Rheumatology, Department of Medicine, University of Colorado School of Medicine, Aurora, CO, USA
| | - Joseph Onyiah
- Division of Gastroenterology and Hepatology, Department of Medicine, University of Colorado School of Medicine, Aurora, CO, USA; Rocky Mountain Regional VA Medical Center, Aurora, CO, USA
| | - Laurent Gapin
- Department of Immunology and Microbiology, University of Colorado School of Medicine, Aurora, CO, USA.
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Zhou P, Tang T, Zhao P, Wang Q, Hu X, Si J, Yang T, Zhou S, An W, Jiang Y. Unveiling the hidden dance: SPP1 + macrophages identified in ulcerative colitis reveal crosstalk with CHI3L1 + fibroblasts. J Transl Med 2025; 23:567. [PMID: 40399882 PMCID: PMC12093798 DOI: 10.1186/s12967-025-06565-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/21/2024] [Accepted: 04/30/2025] [Indexed: 05/23/2025] Open
Abstract
BACKGROUND Ulcerative colitis (UC) is a chronic inflammatory bowel disease characterized by persistent inflammation of the colon. The specific cause of UC is still not fully understood, but this condition is believed to arise from a combination of environmental, genetic, microbial, and immune factors. This study aimed to explore the specific roles of macrophages and fibroblasts in UC pathogenesis, focusing on their interactions and contributions to disease progression. METHODS We utilized single-cell RNA sequencing (scRNA-seq) to analyze macrophages and fibroblasts in peripheral blood and colon biopsy samples from UC patients. Bulk RNA sequencing and spatial transcriptomic data from the Gene Expression Omnibus (GEO) database and flow cytometry and multiplex immunohistochemistry (mIHC) data were used for validation. Statistical analyses were performed to assess the correlation between cell abundance and disease severity. RESULTS Macrophages and fibroblasts were identified as key communication hubs in UC; specifically, SPP1 + macrophages and CHI3L1 + fibroblasts were significantly enriched at the sites of inflammation. These cells are strongly correlated with disease severity and orchestrate inflammatory responses within the intestinal immune microenvironment, contributing to UC-associated colorectal cancer. CONCLUSIONS Our study identified SPP1 + macrophages and CHI3L1 + fibroblasts as key contributors to UC pathogenesis. These cells are enriched in inflammatory sites, are correlated with disease severity, and play a role in UC-associated colorectal cancer, providing new insights into UC mechanisms.
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Affiliation(s)
- Peiwen Zhou
- Genetic Diagnosis Center, The First Hospital of Jilin University, Changchun, 130021, China
| | - Tongyu Tang
- Department of Gastroenterology, The First Hospital of Jilin University, Changchun, 130021, China
| | - Pingwei Zhao
- Department of Gastrointestinal Surgery, General Surgery Center, The First Hospital of Jilin University, Changchun, 130021, China
| | - Quan Wang
- Department of Gastrointestinal Surgery, General Surgery Center, The First Hospital of Jilin University, Changchun, 130021, China
| | - Xintong Hu
- Genetic Diagnosis Center, The First Hospital of Jilin University, Changchun, 130021, China
| | - Junzhuo Si
- Genetic Diagnosis Center, The First Hospital of Jilin University, Changchun, 130021, China
| | - Tianshi Yang
- Genetic Diagnosis Center, The First Hospital of Jilin University, Changchun, 130021, China
| | - Shuai Zhou
- Genetic Diagnosis Center, The First Hospital of Jilin University, Changchun, 130021, China
| | - Wenyan An
- Genetic Diagnosis Center, The First Hospital of Jilin University, Changchun, 130021, China
| | - Yanfang Jiang
- Genetic Diagnosis Center, The First Hospital of Jilin University, Changchun, 130021, China.
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Gong T, Zeng Z, Huang Z, Luo Y, Cao X, Li H, Zhao Y, Han D, Li D, Zhong M. Downregulation of METTL3 enhances TRADD-mediated apoptosis in inflammatory bowel disease. SCIENCE CHINA. LIFE SCIENCES 2025:10.1007/s11427-024-2799-6. [PMID: 40347213 DOI: 10.1007/s11427-024-2799-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 10/09/2024] [Accepted: 11/07/2024] [Indexed: 05/12/2025]
Abstract
Dysregulation of RNA N6-methyladenosine (m6A) modification in intestinal epithelial cells (IECs) compromises intestinal homeostasis, which is critical for maintaining gastrointestinal functions, immunity, and barrier integrity in inflammatory bowel disease (IBD). Here we explored the role of m6A modification, particularly through methyltransferase like 3 (METTL3), in IBD pathology and the apoptosis of intestinal stem cells (ISCs). Reduced m6A RNA methylation and METTL3 expression were detected in IBD tissues, which correlated with increased ISC apoptosis and spontaneous enteritis in METTL3-deficient models; mechanistically, Mettl3 depletion increased TRADD expression in a m6A-dependent manner, thereby augmenting the TNF-induced apoptosis pathway, whereas pharmacological inhibition of TRADD ameliorated the apoptotic phenotype in METTL3-deficient models and improved survival rates in the enteritis mouse model, suggesting a novel therapeutic avenue for IBD management. Collectively, METTL3-mediated m6A RNA methylation plays a pivotal role in maintaining intestinal homeostasis and is activated in ISCs to mitigate the hyperactivity of endogenous inflammatory signals; by modulating TRADD transcript metabolism, METTL3 limits excessive ISC apoptosis, providing insights into IBD pathogenesis and treatment strategies.
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Affiliation(s)
- Tingyue Gong
- Department of Gastrointestinal Surgery, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200127, China
| | - Zhiyang Zeng
- Department of Central Laboratory, Fengxian Central Hospital Affiliated to Southern Medical University, Shanghai, 201499, China
- Shanghai Key Laboratory of Regulatory Biology, Joint Research Center for Translational Medicine, ECNU-Fengxian Hospital, Institute of Biomedical Sciences and School of Life Sciences, East China Normal University, Shanghai, 200241, China
| | - Zurui Huang
- Key Laboratory of Genomic and Precision Medicine, Beijing Institute of Genomics, Chinese Academy of Sciences, Beijing, 100101, China
- College of Future Technology, Sino-Danish College, University of Chinese Academy of Sciences, Beijing, 100049, China
| | - Yang Luo
- Department of Gastrointestinal Surgery, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200127, China
| | - Xiya Cao
- Shanghai Key Laboratory of Regulatory Biology, Joint Research Center for Translational Medicine, ECNU-Fengxian Hospital, Institute of Biomedical Sciences and School of Life Sciences, East China Normal University, Shanghai, 200241, China
| | - Hao Li
- Department of Gastrointestinal Surgery, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200127, China
| | - Yongheng Zhao
- Department of Gastrointestinal Surgery, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200127, China
| | - Dali Han
- Key Laboratory of Genomic and Precision Medicine, Beijing Institute of Genomics, Chinese Academy of Sciences, Beijing, 100101, China.
- College of Future Technology, Sino-Danish College, University of Chinese Academy of Sciences, Beijing, 100049, China.
- Institute for Stem Cell and Regeneration, Chinese Academy of Sciences, Beijing, 100101, China.
- China National Center for Bioinformation, Beijing, 100101, China.
| | - Dali Li
- Shanghai Key Laboratory of Regulatory Biology, Joint Research Center for Translational Medicine, ECNU-Fengxian Hospital, Institute of Biomedical Sciences and School of Life Sciences, East China Normal University, Shanghai, 200241, China.
| | - Ming Zhong
- Department of Gastrointestinal Surgery, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200127, China.
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Gu JM, Zhao M, Zhu J, Tao HW, Shao XP, Qin LQ, Ge YY, Chen GC. Dietary inflammatory potential, genetic predisposition, and incidence of Crohn's disease and ulcerative colitis. Nutr Metab (Lond) 2025; 22:35. [PMID: 40312362 PMCID: PMC12044715 DOI: 10.1186/s12986-025-00934-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/09/2024] [Accepted: 04/23/2025] [Indexed: 05/03/2025] Open
Abstract
BACKGROUND Evidence for a potential link between dietary inflammatory potential and inflammatory bowel disease is limited, and the moderating role of genetic susceptibility remains to be assessed. OBJECTIVE To evaluate energy-adjusted dietary inflammatory index (E-DII) for the associations with incident Crohn's disease (CD) and ulcerative colitis (UC) and the role of genetic susceptibility. METHODS A total of 205,706 UK Biobank participants who were aged 39-72 years and had no known CD or UC at baseline (2006-2010) were included. The E-DII score was calculated based on energy-adjusted average intakes of 33 food or nutrient items derived from up to five 24-hour dietary recalls. Multivariable Cox regression models were used estimate hazard ratios (HRs) with 95% confidence interval (CI) for incident CD and UC. RESULTS During a median 12.3 years of follow-up, 382 incident CD and 798 incident UC cases were ascertained. A higher E-DII score was not associated with risk of CD (HR Q4 VS. Q1 = 1.28, 95% CI: 0.94-1.74; P-trend = 0.09) or UC (HR Q4 VS. Q1 = 1.10, 95% CI: 0.90-1.36; P-trend = 0.17). There was an interaction between the E-DII and the polygenic risk score (PRS) for CD on incident CD (P-interaction = 0.023), with an association only among participants with a high PRS (HR Q4 VS. Q1 = 1.64, 95% CI: 1.03-2.61) (P-interaction = 0.023). As compared with the participants with a low PRS for CD and a low E-DII score, participants with high levels of both scores had a particularly higher risk of CD (HR = 3.12; 95% CI: 1.74-5.60). CONCLUSIONS The association of dietary inflammatory potential with incident CD appears to be amplified by high genetic susceptibility to CD.
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Affiliation(s)
- Ji-Mei Gu
- Department of Nutrition and Food Hygiene, School of Public Health, The Fourth Affiliated Hospital, Suzhou Medical College of Soochow University, 199 Ren'ai Road, Suzhou, 215123, China
| | - Miao Zhao
- Department of Nutrition and Food Hygiene, School of Public Health, The Fourth Affiliated Hospital, Suzhou Medical College of Soochow University, 199 Ren'ai Road, Suzhou, 215123, China
| | - Jie Zhu
- Department of Nutrition and Food Hygiene, School of Public Health, The Fourth Affiliated Hospital, Suzhou Medical College of Soochow University, 199 Ren'ai Road, Suzhou, 215123, China
| | - Hao-Wei Tao
- Department of Nutrition and Food Hygiene, School of Public Health, The Fourth Affiliated Hospital, Suzhou Medical College of Soochow University, 199 Ren'ai Road, Suzhou, 215123, China
| | - Xiao-Ping Shao
- Department of Nutrition and Food Hygiene, School of Public Health, The Fourth Affiliated Hospital, Suzhou Medical College of Soochow University, 199 Ren'ai Road, Suzhou, 215123, China
| | - Li-Qiang Qin
- Department of Nutrition and Food Hygiene, School of Public Health, The Fourth Affiliated Hospital, Suzhou Medical College of Soochow University, 199 Ren'ai Road, Suzhou, 215123, China
| | - Yang-Yang Ge
- Department of Radiation Oncology, The Affiliated Tumor Hospital of Nantong University, Nantong Tumor Hospital, 30 Tongyang North Road, Nantong, 226361, China.
| | - Guo-Chong Chen
- Department of Nutrition and Food Hygiene, School of Public Health, The Fourth Affiliated Hospital, Suzhou Medical College of Soochow University, 199 Ren'ai Road, Suzhou, 215123, China.
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10
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Turpin W, Lee SH, Croitoru K. Gut Microbiome Signature in Predisease Phase of Inflammatory Bowel Disease: Prediction to Pathogenesis to Prevention. Gastroenterology 2025; 168:902-913. [PMID: 39914464 DOI: 10.1053/j.gastro.2025.01.004] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/05/2024] [Revised: 01/02/2025] [Accepted: 01/08/2025] [Indexed: 03/23/2025]
Abstract
Advances in understanding the pathogenesis of inflammatory bowel disease (IBD) point toward a key role of the gut microbiome. We review the data describing the changes in the gut microbiome from IBD case-control studies and compare these findings with emerging data from studies of the preclinical phase of IBD. What is apparent is that assessing changes in the composition and function of the gut microbiome during the preclinical phase helps address confounding factors, such as disease activity and drug therapy, which can directly influence the gut microbiome. Understanding these changes in the predisease phase provides a means of predicting IBD in high-risk populations and offers insights into possible mechanisms involved in disease pathogenesis. Finally, we discuss strategies to use this information to design interventions aimed at modulating the microbiome as a means of preventing or delaying the onset of IBD.
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Affiliation(s)
- Williams Turpin
- Division of Gastroenterology & Hepatology, Temerty Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada; Zane Cohen Centre for Digestive Diseases, Lunenfeld Tanenbaum Research Institute, Mount Sinai Hospital, Toronto, Ontario, Canada
| | - Sun-Ho Lee
- Division of Gastroenterology & Hepatology, Temerty Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada; Zane Cohen Centre for Digestive Diseases, Lunenfeld Tanenbaum Research Institute, Mount Sinai Hospital, Toronto, Ontario, Canada
| | - Kenneth Croitoru
- Division of Gastroenterology & Hepatology, Temerty Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada; Zane Cohen Centre for Digestive Diseases, Lunenfeld Tanenbaum Research Institute, Mount Sinai Hospital, Toronto, Ontario, Canada.
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Gan L, Yu CY, Chen J, Zou B, Xiao Z, Jiang W, Li D, Sun Q, Wang Z, Li C, Liu Y, Chu Y, Tang J, Fu M, Li X, Munford R, Lu M. Acyloxyacyl Hydrolase Prevents Colitis and Colitis-Associated Colorectal Cancer by Inactivating Stimulatory LPS in the Intestine. FASEB J 2025; 39:e70566. [PMID: 40277184 DOI: 10.1096/fj.202500310r] [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: 02/05/2025] [Revised: 03/22/2025] [Accepted: 04/14/2025] [Indexed: 04/26/2025]
Abstract
Ulcerative colitis (UC) is believed to be triggered by a dysregulated inflammatory response to the intestinal microbiota. Acyloxyacyl hydrolase (AOAH) is a unique host lipase that inactivates Gram-negative bacterial lipopolysaccharides (LPS). After finding that AOAH produced in the intestine decreases stimulatory LPS levels in colon contents, we used the dextran sodium sulfate (DSS) model to test the enzyme's ability to prevent colitis in mice. We found that AOAH played a protective role by decreasing colonic inflammation, tissue injury, and barrier permeability. Increasing or decreasing intestinal LPS abundance exacerbated or alleviated colitis, respectively, suggesting that AOAH prevents colitis by reducing stimulatory intestinal LPS levels. AOAH also mitigated colitis-associated colorectal cancer. This highly conserved enzyme may exert its protective effects by preventing LPS-induced injury to the epithelial cell mitochondria that are important for restoring the mucosal epithelial barrier after injury. By decreasing intestinal levels of stimulatory LPS, AOAH prevents colitis and colorectal cancer.
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Affiliation(s)
- Lu Gan
- Department of Immunology, School of Basic Medical Sciences, Fudan University, Shanghai, China
- Department of Trauma-Emergency & Critical Care Medicine, Shanghai Fifth People's Hospital, Fudan University, Shanghai, China
| | - Cheng-Yun Yu
- Department of Immunology, School of Basic Medical Sciences, Fudan University, Shanghai, China
- Department of Trauma-Emergency & Critical Care Medicine, Shanghai Fifth People's Hospital, Fudan University, Shanghai, China
| | - Jiayi Chen
- Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Fudan University, Shanghai, China
| | - Benkun Zou
- BeiGene Institute, BeiGene (Shanghai) Research & Development Co., Ltd, Shanghai, China
| | - Zeling Xiao
- Department of Immunology, School of Basic Medical Sciences, Fudan University, Shanghai, China
- Department of Trauma-Emergency & Critical Care Medicine, Shanghai Fifth People's Hospital, Fudan University, Shanghai, China
| | - Wei Jiang
- Department of Rheumatology and Immunology, The Affiliated Hospital of Guizhou Medical University, Guiyang, Guizhou, China
| | - Dantong Li
- Shanghai Medical College, Fudan University, Shanghai, China
| | - Qingyang Sun
- Department of Immunology, School of Basic Medical Sciences, Fudan University, Shanghai, China
- Department of Trauma-Emergency & Critical Care Medicine, Shanghai Fifth People's Hospital, Fudan University, Shanghai, China
| | - Zhiyan Wang
- Department of Immunology, School of Basic Medical Sciences, Fudan University, Shanghai, China
- Department of Trauma-Emergency & Critical Care Medicine, Shanghai Fifth People's Hospital, Fudan University, Shanghai, China
| | - Changshun Li
- Department of Immunology, School of Basic Medical Sciences, Fudan University, Shanghai, China
- Department of Trauma-Emergency & Critical Care Medicine, Shanghai Fifth People's Hospital, Fudan University, Shanghai, China
| | - Yiling Liu
- Department of Immunology, School of Basic Medical Sciences, Fudan University, Shanghai, China
- Department of Trauma-Emergency & Critical Care Medicine, Shanghai Fifth People's Hospital, Fudan University, Shanghai, China
| | - Yiwei Chu
- Department of Immunology, School of Basic Medical Sciences, Fudan University, Shanghai, China
- Department of Trauma-Emergency & Critical Care Medicine, Shanghai Fifth People's Hospital, Fudan University, Shanghai, China
| | - Jianguo Tang
- Department of Trauma-Emergency & Critical Care Medicine, Shanghai Fifth People's Hospital, Fudan University, Shanghai, China
| | - Mingsheng Fu
- Department of Gastroenterology, Shanghai Fifth People's Hospital, Fudan University, Shanghai, China
| | - Xiaobo Li
- Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Fudan University, Shanghai, China
| | - Robert Munford
- Antibacterial Host Defense Unit, Laboratory of Clinical Immunology and Microbiology, National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), Bethesda, Maryland, USA
| | - Mingfang Lu
- Department of Immunology, School of Basic Medical Sciences, Fudan University, Shanghai, China
- Department of Trauma-Emergency & Critical Care Medicine, Shanghai Fifth People's Hospital, Fudan University, Shanghai, China
- MOE Innovative Center for New Drug Development of Immune Inflammatory Diseases, Fudan University, Shanghai, China
- Shanghai Sci-Tech Inno Center for Infection & Immunity, Shanghai, China
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12
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Bahirwani J, Elmer J, Eskarous H, Jai Kumar Ahuja S, Changela M, Dahiya DS, Stoltzfus J, Schneider Y. Frailty Prevalence and Evaluation of the FRAIL Scale Questionnaire in Patients with Inflammatory Bowel Disease. Dig Dis Sci 2025:10.1007/s10620-025-09073-0. [PMID: 40299292 DOI: 10.1007/s10620-025-09073-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/13/2025] [Accepted: 04/17/2025] [Indexed: 04/30/2025]
Abstract
BACKGROUND Inflammatory bowel disease (IBD) predisposes individuals to frailty, linked with adverse outcomes. While the Fried Frailty Index (FFI) is a well-established phenotypic tool to assess frailty, its administration is cumbersome. The FRAIL scale, simpler but not widely used in patients with IBD, presents an alternative. We aimed to assess the prevalence of frailty and compare the FRAIL scale with the FFI. METHODS A cohort of patients with IBD underwent assessment using both the FFI and the FRAIL scale. Patients were categorized as non-frail, pre-frail, or frail. The primary outcome was frailty prevalence, while secondary outcomes included comparison of FFI and FRAIL scale and associations between frailty and disease-related factors. Statistical analyses included chi-square tests, ANOVA, Kruskal-Wallis tests, and ROC curve analysis using SPSS v27, with p < 0.05 indicating significance. RESULTS Among participants (53.5% female, median age 44), 37% were non-frail, 50% pre-frail, and 13% frail. The FRAIL scale exhibited strong correlation with the FFI for all three categories. Age showed no significant association with frailty. Frail individuals displayed higher inflammatory markers and more severe clinical disease, with frailty more prevalent in patients with UC than CD. Frail individuals also exhibited lower hemoglobin, creatinine, and albumin levels. CONCLUSION Frailty and pre-frailty are prevalent in patients with IBD and not necessarily linked with older age. The FRAIL scale demonstrated excellent correlation with the FFI, offering a practical tool for identifying frailty in IBD without physical measurements. Future studies should explore multivariable models incorporating frailty risk factors and interventions to mitigate adverse outcomes in patients with IBD.
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Affiliation(s)
- Janak Bahirwani
- Department of Gastroenterology, Kadlec Regional Medical Center, 1270 Lee Blvd, Richland, WA, 99352, USA.
| | - Joshua Elmer
- Department of Internal Medicine, Mayo Clinic, Rochester, MN, USA
| | - Hany Eskarous
- Department of Gastroenterology, The Wright Center, Scranton, PA, USA
| | | | - Madhav Changela
- Department of Internal Medicine, One Brooklyn Health System, Brooklyn, NY, USA
| | - Dushyant Singh Dahiya
- Department of Gastroenterology, Hepatology and Motility, School of Medicine, University of Kansas, Kansas City, KS, USA
| | - Jill Stoltzfus
- Department of Research, St Luke's University Health Network, Bethlehem, PA, USA
| | - Yecheskel Schneider
- Director of Inflammatory Bowel Disease and Nutrition, Department of Gastroenterology, St Luke's University Health Network, Bethlehem, PA, USA
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13
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Alotaibi AD, Al-Abdulwahab AA, Ismail MH, AlElyani JM, Alamri TA, Alsulaiman RM, Alhafid IA, Alzahrani IM, AlSulaiman RS, Althubaity A, Buhulaigah SH, AlQurain AA, Alrezuk AM. Prevalence of H. Pylori in inflammatory bowel disease patients and its association with severity. BMC Gastroenterol 2025; 25:317. [PMID: 40301738 PMCID: PMC12042615 DOI: 10.1186/s12876-025-03892-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/12/2025] [Accepted: 04/14/2025] [Indexed: 05/01/2025] Open
Abstract
INTRODUCTION One key area of interest in gastroenterology research is the relationship between Helicobacter pylori (H. pylori) and Inflammatory bowel disease (IBD). Several studies have shown varying results regarding the prevalence of H. pylori in IBD patients and its impact on disease progression, severity, and overall outcome. METHOD This is a prospective cohort study conducted at King Fahad University Hospital in Al Khobar, Saudi Arabia from November 2023 to May 2024 to determine the prevalence of H. pylori in IBD patients and its association with severity. The study included 2 arms for comparison which are IBD patients and control group, IBD will be further classified to CD and UC. Prevalence of H. pylori infection and severity of the disease was compared between these groups. RESULTS A total of 360 patients were included in the study which were divided equally into IBD group and control group. The IBD was subdivided into CD with 91 cases and UC with 89 cases. H. Pylori was significantly higher in control group (23.3%) compared with UC cases (13.2%) p value: 0.048. H. pylori infection was significantly high in smokers p value = < 0.0001. The presence of autoimmune disease was significantly associated with H. Pylori infection (16.4%) p value: 0.023. CONCLUSION H. pylori infection was significantly higher in the control group in comparison to IBD group. In addition, smoking and autoimmune disease were significantly associated with H. pylori infection. Finally, the overall association between severity of CD, UC and medication use with H. Pylori were insignificant.
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Affiliation(s)
- Abdullah D Alotaibi
- Department of Internal Medicine, College of Medicine, Imam Abdulrahman Bin Faisal university, Dammam, Eastern Province, Saudi Arabia.
- King Fahad University Hospital, Shura Street, Al Aqrabiyah, Al Khobar, 34445, Saudi Arabia.
| | - Abdullah A Al-Abdulwahab
- Department of Internal Medicine, College of Medicine, Imam Abdulrahman Bin Faisal university, Dammam, Eastern Province, Saudi Arabia
- King Fahad University Hospital, Shura Street, Al Aqrabiyah, Al Khobar, 34445, Saudi Arabia
| | - Mona H Ismail
- Department of Internal Medicine, College of Medicine, Imam Abdulrahman Bin Faisal university, Dammam, Eastern Province, Saudi Arabia
- King Fahad University Hospital, Shura Street, Al Aqrabiyah, Al Khobar, 34445, Saudi Arabia
| | - Jaber M AlElyani
- Department of Internal Medicine, College of Medicine, Imam Abdulrahman Bin Faisal university, Dammam, Eastern Province, Saudi Arabia
- King Fahad University Hospital, Shura Street, Al Aqrabiyah, Al Khobar, 34445, Saudi Arabia
| | - Turki A Alamri
- Department of Internal Medicine, College of Medicine, Imam Abdulrahman Bin Faisal university, Dammam, Eastern Province, Saudi Arabia
- King Fahad University Hospital, Shura Street, Al Aqrabiyah, Al Khobar, 34445, Saudi Arabia
| | - Raed M Alsulaiman
- Department of Internal Medicine, College of Medicine, Imam Abdulrahman Bin Faisal university, Dammam, Eastern Province, Saudi Arabia
- King Fahad University Hospital, Shura Street, Al Aqrabiyah, Al Khobar, 34445, Saudi Arabia
| | - Ibrahim A Alhafid
- Department of Internal Medicine, College of Medicine, Imam Abdulrahman Bin Faisal university, Dammam, Eastern Province, Saudi Arabia
- King Fahad University Hospital, Shura Street, Al Aqrabiyah, Al Khobar, 34445, Saudi Arabia
| | - Ibrahim M Alzahrani
- Department of Internal Medicine, College of Medicine, Imam Abdulrahman Bin Faisal university, Dammam, Eastern Province, Saudi Arabia
- King Fahad University Hospital, Shura Street, Al Aqrabiyah, Al Khobar, 34445, Saudi Arabia
| | - Reem S AlSulaiman
- Department of Internal Medicine, College of Medicine, Imam Abdulrahman Bin Faisal university, Dammam, Eastern Province, Saudi Arabia.
- King Fahad University Hospital, Shura Street, Al Aqrabiyah, Al Khobar, 34445, Saudi Arabia.
| | - Arwa Althubaity
- Department of Internal Medicine, College of Medicine, Imam Abdulrahman Bin Faisal university, Dammam, Eastern Province, Saudi Arabia
- King Fahad University Hospital, Shura Street, Al Aqrabiyah, Al Khobar, 34445, Saudi Arabia
| | - Sarah H Buhulaigah
- Department of Internal Medicine, College of Medicine, Imam Abdulrahman Bin Faisal university, Dammam, Eastern Province, Saudi Arabia
- King Fahad University Hospital, Shura Street, Al Aqrabiyah, Al Khobar, 34445, Saudi Arabia
| | - Abdulaziz A AlQurain
- Department of Internal Medicine, College of Medicine, Imam Abdulrahman Bin Faisal university, Dammam, Eastern Province, Saudi Arabia
- King Fahad University Hospital, Shura Street, Al Aqrabiyah, Al Khobar, 34445, Saudi Arabia
| | - Abdulaziz M Alrezuk
- Department of Internal Medicine, College of Medicine, Imam Abdulrahman Bin Faisal university, Dammam, Eastern Province, Saudi Arabia
- King Fahad University Hospital, Shura Street, Al Aqrabiyah, Al Khobar, 34445, Saudi Arabia
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14
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Thapa HB, Passegger CA, Fleischhacker D, Kohl P, Chen YC, Kalawong R, Tam-Amersdorfer C, Gerstorfer MR, Strahlhofer J, Schild-Prüfert K, Zechner EL, Blesl A, Binder L, Busslinger GA, Eberl L, Gorkiewicz G, Strobl H, Högenauer C, Schild S. Enrichment of human IgA-coated bacterial vesicles in ulcerative colitis as a driver of inflammation. Nat Commun 2025; 16:3995. [PMID: 40301356 PMCID: PMC12041585 DOI: 10.1038/s41467-025-59354-5] [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: 03/01/2024] [Accepted: 04/21/2025] [Indexed: 05/01/2025] Open
Abstract
The gut microbiome contributes to chronic inflammatory responses in ulcerative colitis (UC), but molecular mechanisms and disease-relevant effectors remain unclear. Here we analyze the pro-inflammatory properties of colonic fluid obtained during colonoscopy from UC and control patients. In patients with UC, we find that the pelletable effector fraction is composed mostly of bacterial extracellular vesicles (BEVs) that exhibit high IgA-levels and incite strong pro-inflammatory responses in IgA receptor-positive (CD89+) immune cells. Biopsy analyses reveal higher infiltration of CD89+ immune cells in the colonic mucosa from patients with UC than control individuals. Further studies show that IgA-coated BEVs, but not host-derived vesicles nor soluble IgA, are potent activators of pro-inflammatory responses in CD89+ cells. IgA-coated BEVs also exacerbate intestinal inflammation in a dextran sodium sulfate colitis model using transgenic mice expressing human CD89. Our data thus implicate a link between IgA-coated BEVs and intestinal inflammation via CD89+ immune cells, and also hint a potential new therapeutic target for UC.
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Affiliation(s)
- Himadri B Thapa
- Institute of Molecular Biosciences, University of Graz, Graz, Austria
| | - Christina A Passegger
- Division of Immunology, Otto Loewi Research Center for Vascular Biology, Immunology and Inflammation, Medical University of Graz, Graz, Austria
| | | | - Paul Kohl
- Institute of Molecular Biosciences, University of Graz, Graz, Austria
| | - Yi-Chi Chen
- Department of Plant and Microbial Biology, University of Zurich, Zurich, Switzerland
| | - Ratchara Kalawong
- Department of Plant and Microbial Biology, University of Zurich, Zurich, Switzerland
| | - Carmen Tam-Amersdorfer
- Division of Immunology, Otto Loewi Research Center for Vascular Biology, Immunology and Inflammation, Medical University of Graz, Graz, Austria
| | - Michael R Gerstorfer
- Research Center for Molecular Medicine (CeMM) of the Austrian Academy of Sciences, Vienna, Austria
| | - Jana Strahlhofer
- Institute of Molecular Biosciences, University of Graz, Graz, Austria
| | | | - Ellen L Zechner
- Institute of Molecular Biosciences, University of Graz, Graz, Austria
- BioTechMed, Graz, Austria
- Field of Excellence Biohealth - University of Graz, Graz, Austria
| | - Andreas Blesl
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Medical University of Graz, Graz, Austria
| | - Lukas Binder
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Medical University of Graz, Graz, Austria
| | - Georg A Busslinger
- Research Center for Molecular Medicine (CeMM) of the Austrian Academy of Sciences, Vienna, Austria
| | - Leo Eberl
- Department of Plant and Microbial Biology, University of Zurich, Zurich, Switzerland
| | - Gregor Gorkiewicz
- BioTechMed, Graz, Austria
- Diagnostic and Research Institute of Pathology, Medical University of Graz, Graz, Austria
| | - Herbert Strobl
- Division of Immunology, Otto Loewi Research Center for Vascular Biology, Immunology and Inflammation, Medical University of Graz, Graz, Austria
- BioTechMed, Graz, Austria
| | - Christoph Högenauer
- BioTechMed, Graz, Austria.
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Medical University of Graz, Graz, Austria.
| | - Stefan Schild
- Institute of Molecular Biosciences, University of Graz, Graz, Austria.
- BioTechMed, Graz, Austria.
- Field of Excellence Biohealth - University of Graz, Graz, Austria.
- Austrian Agency for Health and Food Safety (AGES), Institute for Medical Microbiology and Hygiene, Graz, Austria.
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15
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Li D, Ye ZD, Li MX, Luo YY, Zhou CK, Mei QH, Xia CL, Huang S, Su JY. Maslinic Acid Ameliorates DSS-Induced Experimental Colitis by Suppressing Th Cell-Mediated Inflammation via AICD Induction. Phytother Res 2025. [PMID: 40242940 DOI: 10.1002/ptr.8479] [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: 10/31/2023] [Revised: 04/04/2024] [Accepted: 04/24/2024] [Indexed: 04/18/2025]
Abstract
Ulcerative colitis (UC) is a nonspecific chronic inflammatory disease that occurs in the gastrointestinal tract and is characterized by the breakdown of mucosal immunity. T helper (Th) cells paradigm disequilibrium is a critical for pathogenesis. Maslinic acid (MA), a naturally occurring pentacyclic triterpene isolated from olive pomace and Fructus crataegi, has a variety of applications in both medicine and food. This study investigated the molecular mechanism of the anti-inflammatory potential of MA in a colitis model and activated Th cells. A dextran sulfate sodium-induced experimental colitis model was established. Clinical symptoms were evaluated, and biological samples were collected to examine intestinal mucosal function, inflammation levels, and Th cell-mediated immune responses. The mechanism of the activation-induced cell death (AICD) effect regulated by MA was investigated in the anti-CD3ε/CD28-stimulated Th cell activation model using molecular biotechnology and transcriptome analysis. Key results:MA treatment protected intestinal mucosa, which manifested as reduced inflammatory cytokines, Th cell infiltration, and subset differentiation. Additionally, it was found to suppress Th cell proliferation and differentiation of subsets, regulate cell cycle distribution, and promote AICD by regulating the mitochondria-mediated intrinsic pathway in vitro. JAK-STAT and FcεRI pathways were probable essential pathways, and MAF might be a crucial potential targeting molecule in activated Th cells with MA treatment. This finding demonstrated that MA induced remission of the colitis-related inflammation, which may depend on the resolution of acute inflammation by reducing Th cell-mediated inflammation via AICD induction, emphasizing its promising potential in the treatment of UC.
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Affiliation(s)
- Dan Li
- Department of Pharmacy, The Affiliated Guangdong Second Provincial General Hospital of Jinan University, Guangzhou, People's Republic of China
- School of Pharmaceutical Sciences, Guangzhou University of Chinese Medicine, Guangzhou, People's Republic of China
| | - Zhan-Dong Ye
- School of Pharmaceutical Sciences, Guangzhou University of Chinese Medicine, Guangzhou, People's Republic of China
| | - Mu-Xia Li
- Shenzhen Key Laboratory of Hospital Chinese Medicine Preparation, Shenzhen Traditional Chinese Medicine Hospital, The Fourth Clinical Medical College of Guangzhou University of Chinese Medicine, Shenzhen, People's Republic of China
| | - Ying-Yi Luo
- Stomatological Hospital, Southern Medical University, Guangzhou, People's Republic of China
| | - Can-Kun Zhou
- Affiliated Foshan Maternity and Child Healthcare Hospital, Southern Medical University, Foshan, People's Republic of China
| | - Qing-Hua Mei
- Department of Pharmacy, The Affiliated Guangdong Second Provincial General Hospital of Jinan University, Guangzhou, People's Republic of China
| | - Cheng-Lai Xia
- Foshan Maternity & Child Healthcare Hospital, Foshan, People's Republic of China
- School of Pharmaceutical Sciences, Southern Medical University, Guangzhou, People's Republic of China
| | - Song Huang
- School of Pharmaceutical Sciences, Guangzhou University of Chinese Medicine, Guangzhou, People's Republic of China
| | - Ji-Yan Su
- Foshan Maternity & Child Healthcare Hospital, Foshan, People's Republic of China
- School of Pharmaceutical Sciences, Southern Medical University, Guangzhou, People's Republic of China
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16
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Wei J, Kurumi H, Isomoto H, Ogihara R, Matsushima K, Machida H, Ishida T, Hirayama T, Yamaguchi N, Yoshida Y, Tsukamoto K. Toll-like Receptor Gene Polymorphisms as Predictive Biomarkers for Response to Infliximab in Japanese Patients with Crohn's Disease. Diagnostics (Basel) 2025; 15:971. [PMID: 40310362 PMCID: PMC12026024 DOI: 10.3390/diagnostics15080971] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/27/2025] [Revised: 04/03/2025] [Accepted: 04/07/2025] [Indexed: 05/02/2025] Open
Abstract
Objectives: To explore the possible relationship between Toll-like receptor (TLR) gene encoding and a predictive outcome for the loss of response (LOR) to IFX treatment among Japanese patients with Crohn's disease (CD). Methods: An association analysis that involved 25 single-nucleotide polymorphisms (SNPs) across the TLR1, TLR2, TLR4, TLR6, TLR9, and TLR10 genes was performed on a cohort of 127 Japanese patients with CD. The therapeutic responses were evaluated at 10 weeks, 1 year, and 2 years using three different inheritance models. Results: The CD patients with a G/G genotype of rs5743565 in TLR1 were significantly less likely in the responders at 10 weeks compared with the non-responders (p = 0.023, OR = 0.206). The frequencies of the C/T or T/T genotypes of rs5743604 in the TLR1, G/A, or A/A genotypes of rs13105517 in TLR2, both in the minor allele dominant model, were significantly higher in the responders at 10 weeks as compared with those in the non-responders (p = 0.035, OR = 4.401; p = 0.017, OR = 5.473). The patients with an A/A genotype of rs13105517 in TLR2 in the minor allele recessive model were significantly less likely in the responders at one year of IFX treatment compared with those in the non-responders (p = 0.004, OR = 0.195). Conclusions: The polymorphisms of TLR1 and TLR2 can be useful as biomarkers for predicting initial and secondary LOR to IFX in Japanese CD patients. The IFX response in genetic testing may target molecules for new drugs to overcome the non-response and LOR to IFX.
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Affiliation(s)
- Jingjing Wei
- Department of Endoscopy, The First Affiliated Hospital of Fujian Medical University, Fuzhou 350004, China;
- Department of Endoscopy, National Regional Medical Center, Binhai Campus of the First Affiliated Hospital of Fujian Medical University, Fuzhou 350212, China
- Division of Gastroenterology and Nephrology, Department of Multidisciplinary Internal Medicine, School of Medicine, Faculty of Medicine, Tottori University, Yonago 683-8504, Japan; (H.K.); (H.I.); (R.O.); (Y.Y.)
| | - Hiroki Kurumi
- Division of Gastroenterology and Nephrology, Department of Multidisciplinary Internal Medicine, School of Medicine, Faculty of Medicine, Tottori University, Yonago 683-8504, Japan; (H.K.); (H.I.); (R.O.); (Y.Y.)
| | - Hajime Isomoto
- Division of Gastroenterology and Nephrology, Department of Multidisciplinary Internal Medicine, School of Medicine, Faculty of Medicine, Tottori University, Yonago 683-8504, Japan; (H.K.); (H.I.); (R.O.); (Y.Y.)
| | - Ryohei Ogihara
- Division of Gastroenterology and Nephrology, Department of Multidisciplinary Internal Medicine, School of Medicine, Faculty of Medicine, Tottori University, Yonago 683-8504, Japan; (H.K.); (H.I.); (R.O.); (Y.Y.)
| | - Kayoko Matsushima
- Department of Gastroenterology and Hepatology, Nagasaki University Hospital, 1-7-1 Sakamoto, Nagasaki 852-8501, Japan; (K.M.); (H.M.)
| | - Haruhisa Machida
- Department of Gastroenterology and Hepatology, Nagasaki University Hospital, 1-7-1 Sakamoto, Nagasaki 852-8501, Japan; (K.M.); (H.M.)
| | - Tetsuya Ishida
- Department of Gastroenterology, Oita Red Cross Hospital, 3-2-27 Chiyo-machi, Oita 870-0033, Japan;
| | - Tatsuro Hirayama
- Department of Pharmacotherapeutics, Nagasaki University Graduate School of Biomedical Sciences, 1-7-1 Sakamoto, Nagasaki 852-8501, Japan;
| | - Naoyuki Yamaguchi
- Department of Endoscopy, Nagasaki University Hospital, 1-7-1 Sakamoto, Nagasaki 852-8501, Japan;
| | - Yukina Yoshida
- Division of Gastroenterology and Nephrology, Department of Multidisciplinary Internal Medicine, School of Medicine, Faculty of Medicine, Tottori University, Yonago 683-8504, Japan; (H.K.); (H.I.); (R.O.); (Y.Y.)
| | - Kazuhiro Tsukamoto
- Department of Pharmacotherapeutics, Nagasaki University Graduate School of Biomedical Sciences, 1-7-1 Sakamoto, Nagasaki 852-8501, Japan;
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17
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Koppelman LJM, Stevens CL, Barth I, Jacobs RJ, Dijkstra G, van der Meulen-de Jong AE, Campmans-Kuijpers MJE. Can Diet Quality Be Associated with Disease Activity in a Prospective Dutch Inflammatory Bowel Disease Cohort? Nutrients 2025; 17:1298. [PMID: 40284163 PMCID: PMC12029865 DOI: 10.3390/nu17081298] [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: 03/10/2025] [Revised: 04/04/2025] [Accepted: 04/07/2025] [Indexed: 04/29/2025] Open
Abstract
Background/Objectives: Inflammatory bowel disease (IBD) is characterized by a relapsing-remitting disease course, influenced by dietary factors. This study aims to examine diet quality in IBD patients and investigate its association with disease activity. Methods: In total, 477 participants from a prospective IBD cohort study at two Dutch hospitals were approached to complete a population-specific food frequency questionnaire (GINQ-FFQ) at baseline and after one year. Disease characteristics were assessed at multiple time points. Food-related Quality of Life (FrQoL) was assessed at baseline. Diet quality was measured via the Dietary Inflammatory Index (DII), Mediterranean Diet Score (MDS), Healthy Diet Indicator score (HDI), ultra-processed food intake, and Principal Component Analysis (PCA) to identify dietary patterns. The outcomes were compared to the general Dutch population. Results: In total, 191 participants completed the GINQ-FFQ at baseline, of whom 53 had active disease. Patients in remission had higher FrQoL than patients with active disease (p = 0.020). Diet quality and adherence to specific dietary patterns were not associated with disease activity. However, logistic regression showed a trend toward increased odds of increase in disease activity with an animal protein-rich pattern (OR: 1.479, p = 0.088) and a potential association between the Convenience diet and decreased disease activity (OR: 1.396, p = 0.060). Both the Dutch population and the patient cohort scored poor on all diet quality scores. Conclusions: The current study shows no conclusive evidence of an association between disease activity and both diet quality and dietary patterns in patients with IBD. However, the findings do suggest a possible association between animal protein-rich diets with more disease activity and Convenience-like diets with less disease activity. Furthermore, a similar diet quality was observed in IBD patients and the general Dutch population. Nevertheless, diet quality was generally poor and can be improved.
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Affiliation(s)
- Lola J. M. Koppelman
- Department of Gastroenterology and Hepatology, Leiden University Medical Centre, Albinusdreef 2, 2333 ZG Leiden, The Netherlands;
| | - Corien L. Stevens
- Department of Gastroenterology and Hepatology, University Medical Centre Groningen, University of Groningen, Hanzeplein 1, 9713 GZ Groningen, The Netherlands; (I.B.); (G.D.); (M.J.E.C.-K.)
| | - Iris Barth
- Department of Gastroenterology and Hepatology, University Medical Centre Groningen, University of Groningen, Hanzeplein 1, 9713 GZ Groningen, The Netherlands; (I.B.); (G.D.); (M.J.E.C.-K.)
| | - Rutger J. Jacobs
- Department of Gastroenterology and Hepatology, Alrijne Hospital, Houtlaan 55, 2334 CK Leiden, The Netherlands;
| | - Gerard Dijkstra
- Department of Gastroenterology and Hepatology, University Medical Centre Groningen, University of Groningen, Hanzeplein 1, 9713 GZ Groningen, The Netherlands; (I.B.); (G.D.); (M.J.E.C.-K.)
| | - Andrea E. van der Meulen-de Jong
- Department of Gastroenterology and Hepatology, Leiden University Medical Centre, Albinusdreef 2, 2333 ZG Leiden, The Netherlands;
| | - Marjo J. E. Campmans-Kuijpers
- Department of Gastroenterology and Hepatology, University Medical Centre Groningen, University of Groningen, Hanzeplein 1, 9713 GZ Groningen, The Netherlands; (I.B.); (G.D.); (M.J.E.C.-K.)
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18
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Fu Q, Remes PM, Lee J, Jacob C, Li D, Vegesna M, Raedschelders K, Haghani A, Mengesha E, Debbas P, Hoedt E, Joung S, Cheng S, Peterman S, Fert-Bober J, Melmed GY, McGovern DPB, Murray CI, Van Eyk JE. Development and Clinical Evaluation of a Multiplexed Health Surveillance Panel Using Ultra High-Throughput PRM-MS in an Inflammatory Bowel Disease Cohort. BIORXIV : THE PREPRINT SERVER FOR BIOLOGY 2025:2025.04.02.646850. [PMID: 40236053 PMCID: PMC11996553 DOI: 10.1101/2025.04.02.646850] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 04/17/2025]
Abstract
Despite advances in clinical proteomics, translating protein biomarker discoveries into clinical use remains challenging due to the technical complexity of the validation process. Targeted MS-based proteomics approaches such as parallel reaction monitoring (PRM) offer sensitive and specific assays for biomarker translation. In this study, we developed a multiplex PRM assay using the Stellar mass spectrometry platform to quantify 57 plasma proteins, including 21 FDA-approved proteins. Loading curves (11-points) were performed at 4 sample throughputs (100, 144, 180, and 300 samples per day) using independent, optimized, and scheduled PRM methods. Following optimization, an inflammatory bowel disease (IBD) cohort of plasma samples (493 IBD, 509 matched controls) was analyzed at a throughput of 180 SPD. To monitor system performance, the study also included 1,000 additional injections for system suitability tests, low-, middle-, and high-quality controls, washes, and blanks. Using this approach, we observed high quantifiability (linearity, sensitivity, reproducibility) in the PRM assay and consistent in data acquisition across a large cohort. We also validated the candidate IBD markers, C-reactive protein and orosomucoid protein, identified in a recent discovery experiment.
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Nishioka K, Ogino H, Ihara E, Chinen T, Kimura Y, Esaki M, Bai X, Minoda Y, Tanaka Y, Wada M, Hata Y, Ambrosini YM, Ogawa Y. Importance of rectal over colon status in ulcerative colitis remission: the role of microinflammation and mucosal barrier dysfunction in relapse. J Gastroenterol 2025; 60:416-429. [PMID: 39672976 DOI: 10.1007/s00535-024-02199-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/03/2024] [Accepted: 12/03/2024] [Indexed: 12/15/2024]
Abstract
BACKGROUND Ulcerative colitis (UC) is a refractory inflammatory disease that affects the rectum and colon, with pivotal involvement of the rectal environment in relapse initiation. This study was conducted in two phases to examine the differences in gene expression between the rectum and colon and to identify relapse factors. METHODS In ***Study 1, RNA sequencing was performed on biopsies from the colon and rectum of patients with active UC, those with remission UC, and controls. In Study 2, the mucosal impedance (MI) values reflecting mucosal barrier function and the mRNA expression of tight junction proteins and inflammatory cytokines were examined in 32 patients with remission UC and 22 controls. Relapse was monitored prospectively. RESULTS In Study 1, comprehensive genetic analysis using RNA sequencing revealed distinct gene profiles in the rectum and sigmoid colon of patients with remission UC. The rectum of these patients exhibited an enriched immune response and apical junction phenotype with persistent upregulation of CLDN2 gene expression. In Study 2, even in patients with remission UC, the MI values in the rectum, but not in the sigmoid colon, were significantly decreased, whereas they were negatively correlated with CLDN2, IL-1β, and IL-6 expressions. CONCLUSION The status of the rectum in patients with remission UC differs from that of the colon, with microinflammation and impaired mucosal barrier function, which are associated with the upregulation of CLDN2, playing a role in relapse.
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Affiliation(s)
- Kei Nishioka
- Department of Gastroenterology, Saiseikai Futsukaichi Hospital, Chikushino, Japan
- Department of Medicine and Bioregulatory Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
| | - Haruei Ogino
- Department of Medicine and Bioregulatory Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
- Department of Gastroenterology and Metabolism, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
| | - Eikichi Ihara
- Department of Medicine and Bioregulatory Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
| | - Takatoshi Chinen
- Department of Medicine and Bioregulatory Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
| | - Yusuke Kimura
- Department of Medicine and Bioregulatory Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
| | - Mitsuru Esaki
- Department of Medicine and Bioregulatory Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
- Division of Gastroenterology and Hepatology, Mayo Clinic, Scottsdale, USA
| | - Xiaopeng Bai
- Department of Medicine and Bioregulatory Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
| | - Yosuke Minoda
- Department of Medicine and Bioregulatory Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
| | - Yoshimasa Tanaka
- Department of Medicine and Bioregulatory Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
| | - Masafumi Wada
- Department of Medicine and Bioregulatory Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
| | - Yoshitaka Hata
- Department of Medicine and Bioregulatory Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
| | - Yoko M Ambrosini
- Department of Veterinary Clinical Sciences, College of Veterinary Medicine, Washington State University, Pullman, USA
| | - Yoshihiro Ogawa
- Department of Medicine and Bioregulatory Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
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20
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Liu JF, Jiang QX, Liu J, Liu AL, Wang YH. Investigation and Analysis of Frailty and Nutritional Status in Patients With Inflammatory Bowel Disease. CROHN'S & COLITIS 360 2025; 7:otaf010. [PMID: 40230499 PMCID: PMC11995394 DOI: 10.1093/crocol/otaf010] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/16/2024] [Indexed: 04/16/2025] Open
Abstract
Background To analyze the current status of frailty and the primary factors influencing frailty in patients with inflammatory bowel disease (IBD). Methods We conducted a study using a fixed-point consecutive sampling method to investigate hospitalized patients with IBD aged 18 years or older in the Gastroenterology Department of a general hospital in Anhui, China, from July 2022 to July 2023. We also assessed the prevalence of frailty and malnutrition using the frailty phenotype scale (trial of fatigue, grip strength, physical activity, walking speed, and weight loss) and the Global Leadership Initiative on Malnutrition criteria to analyze the factors influencing frailty. Results A total of 300 patients with IBD were included. Of them, 21.67% were classified as frail, 46.67% were prefrail, 31.6% were nonfrail, 35% showed nutritional risk, and 33% were malnourished. The results of bivariate correlation analysis showed that frailty scores were correlated with age, white blood cell count, faecal calprotectin, and C-reactive protein levels and were negatively correlated with body mass index (BMI), hemoglobin, albumin (ALB), and pre-albumin (PALB) levels (r = -0.35, -0.45, -0.55, -0.44, P <.01). The results of multiple linear regression analysis showed that BMI scores, nutritional status, disease state, and ALB levels were important factors influencing frailty (P <.05). Conclusions The patients with IBD were frail and prefrail, with a high prevalence of malnutrition. Lower BMI scores, a poor nutritional status, a worse disease state, and lower ALB levels were risk factors for frailty. A cyclical relationship was identified between frailty and malnutrition, with each condition exacerbating the other.
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Affiliation(s)
- Jin-Feng Liu
- Department of Gastroenterology, The First Affiliated Hospital of USTC (Anhui Provincial Hospital), 17 Lujiang Road, Hefei, Anhui, China
| | - Qiu-Xia Jiang
- Department of Gastroenterology, The First Affiliated Hospital of USTC (Anhui Provincial Hospital), 17 Lujiang Road, Hefei, Anhui, China
| | - Juan Liu
- Department of Gastroenterology, The First Affiliated Hospital of USTC (Anhui Provincial Hospital), 17 Lujiang Road, Hefei, Anhui, China
| | - A-Lan Liu
- Department of Gastroenterology, The First Affiliated Hospital of USTC (Anhui Provincial Hospital), 17 Lujiang Road, Hefei, Anhui, China
| | - Yu-Han Wang
- Department of Gastroenterology, The First Affiliated Hospital of USTC (Anhui Provincial Hospital), 17 Lujiang Road, Hefei, Anhui, China
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21
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Ngew E, Kollipara R, Bessissow T, Karboune S, George S. Nanoencapsulation enhanced the performance of β-carotene for ameliorating inflammation in patient-derived organoids. Nanomedicine (Lond) 2025; 20:663-675. [PMID: 39943855 PMCID: PMC11970773 DOI: 10.1080/17435889.2025.2465247] [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: 10/22/2024] [Accepted: 02/07/2025] [Indexed: 04/02/2025] Open
Abstract
AIM This study aims to develop a nanocarrier system for the oral delivery of β-Carotene (BC) (as a model therapeutic agent) and to test its efficacy in ameliorating inflammation in an ulcerative colitis (UC) patient-derived organoid. MATERIALS & METHODS BC was encapsulated in a zein protein nano-cage surface-functionalized with pectin and polyethyleneglycol (PEG). The nanoencapsulated BC (nBC) was characterized for physicochemical properties (size, charge, surface chemistry) and functional properties (radical scavenging, mucoadhesion and penetration, release in simulated digestive fluids). Further, we evaluated the performance of nBC in ameliorating inflammation in Caco-2 and UC patient-derived organoid models. RESULTS nBC achieved 75% encapsulation efficiency with improved stability and functional properties when compared to free BC. The nanocarrier was non-cytotoxic and improved mucoadhesion, mucopenetration, and the anti-inflammatory potential of BC. In UC organoids, nBC suppressed dextran sulfate sodium (DSS)-induced TNF-α and IL-8 production by approximately 70% and 31%, respectively, which was significantly higher than free BC at comparable concentrations. CONCLUSIONS The protein-polymer nanoencapsulation strategy showed promise in protecting BC and overcoming intestinal mucus barriers for an improved anti-inflammatory effect in the organoid model. Further studies using animal models are warranted for establishing pharmacokinetics, tissue distribution, and therapeutic index of orally delivered nBC.
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Affiliation(s)
- Estee Ngew
- Department of Food Science and Agricultural Chemistry, McGill University, Québec, Canada
| | - Revathi Kollipara
- Department of Food Science and Agricultural Chemistry, McGill University, Québec, Canada
| | - Talat Bessissow
- Division of Gastroenterology, McGill University Health Centre, Quebec, Canada
| | - Salwa Karboune
- Department of Food Science and Agricultural Chemistry, McGill University, Québec, Canada
| | - Saji George
- Department of Food Science and Agricultural Chemistry, McGill University, Québec, Canada
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22
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Hou S, Yu J, Li Y, Zhao D, Zhang Z. Advances in Fecal Microbiota Transplantation for Gut Dysbiosis-Related Diseases. ADVANCED SCIENCE (WEINHEIM, BADEN-WURTTEMBERG, GERMANY) 2025; 12:e2413197. [PMID: 40013938 PMCID: PMC11967859 DOI: 10.1002/advs.202413197] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 10/18/2024] [Revised: 01/22/2025] [Indexed: 02/28/2025]
Abstract
This article provides an overview of the advancements in the application of fecal microbiota transplantation (FMT) in treating diseases related to intestinal dysbiosis. FMT involves the transfer of healthy donor fecal microbiota into the patient's body, aiming to restore the balance of intestinal microbiota and thereby treat a variety of intestinal diseases such as recurrent Clostridioides difficile infection (rCDI), inflammatory bowel disease (IBD), constipation, short bowel syndrome (SBS), and irritable bowel syndrome (IBS). While FMT has shown high efficacy in the treatment of rCDI, further research is needed for its application in other chronic conditions. This article elaborates on the application of FMT in intestinal diseases and the mechanisms of intestinal dysbiosis, as well as discusses key factors influencing the effectiveness of FMT, including donor selection, recipient characteristics, treatment protocols, and methods for assessing microbiota. Additionally, it emphasizes the key to successful FMT. Future research should focus on optimizing the FMT process to ensure long-term safety and explore the potential application of FMT in a broader range of medical conditions.
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Affiliation(s)
- Shuna Hou
- Department of OrthopedicsThe Fourth Affiliated Hospital of China Medical UniversityChina Medical UniversityLiao NingShen Yang110032P. R. China
- Department of general surgeryThe Fourth Affiliated Hospital of China Medical UniversityChina Medical UniversityLiao NingShen Yang110032P. R. China
| | - Jiachen Yu
- Department of OrthopedicsThe Fourth Affiliated Hospital of China Medical UniversityChina Medical UniversityLiao NingShen Yang110032P. R. China
| | - Yongshuang Li
- Department of general surgeryThe Fourth Affiliated Hospital of China Medical UniversityChina Medical UniversityLiao NingShen Yang110032P. R. China
| | - Duoyi Zhao
- Department of OrthopedicsThe Fourth Affiliated Hospital of China Medical UniversityChina Medical UniversityLiao NingShen Yang110032P. R. China
| | - Zhiyu Zhang
- Department of OrthopedicsThe Fourth Affiliated Hospital of China Medical UniversityChina Medical UniversityLiao NingShen Yang110032P. R. China
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Wespi N, Vavricka S, Brand S, Aepli P, Burri E, Misselwitz B, Seibold F, Hruz P, Peyrin‐Biroulet L, Schoepfer A, Biedermann L, Sokollik C, Rogler G, Greuter T. Fecal urgency and incontinence in inflammatory bowel disease perceived by physician and patient: Results from the Swiss fecal urgency survey. United European Gastroenterol J 2025; 13:392-401. [PMID: 39246002 PMCID: PMC11999039 DOI: 10.1002/ueg2.12657] [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: 05/09/2024] [Accepted: 08/06/2024] [Indexed: 09/10/2024] Open
Abstract
INTRODUCTION Although increasingly appreciated, little is known about the prevalence of fecal urgency, fecal incontinence and differences between patients' and physicians' perception in inflammatory bowel disease (IBD). METHODS We performed an online patient and physician survey to evaluate the assessment, prevalence and impact of fecal urgency and incontinence in IBD. RESULTS A total of 593 patients (44.0% ulcerative colitis (UC), 53.5% Crohn's disease (CD), 2.2% indeterminate colitis, 2 not specified) completed the survey (65.8% females, mean age 47.1 years). Fecal urgency was often reported (UC: 98.5%, CD: 96.2%) and was prevalent even during remission (UC: 65.9%, CD: 68.5%). Fecal urgency considerably impacted daily activities (visual analog scale [VAS] 5, IQR 3-8). Yet, 22.8% of patients have never discussed fecal urgency with their physicians. Fecal incontinence was experienced by 44.7% of patients and 7.9% on a weekly basis. Diapers/pads were required at least once a month in 20.4% of patients. However, 29.7% of patients never talked with their physician about fecal incontinence. UC was an independent predictor for the presence of moderate-severe fecal urgency (OR 1.65, 95% CI 1.13-2.41) and fecal incontinence (OR 1.77, 95% CI 1.22-2.59). All physicians claimed to regularly inquire about fecal urgency and incontinence. However, the impact of these symptoms on daily activities was overestimated compared with the patient feedback (median VAS 8 vs. 5, p = 0.0113, and 9 vs. 5, p = 0.0187). CONCLUSIONS Fecal urgency and incontinence are burdensome symptoms in IBD, with a similar prevalence in UC and CD. A mismatch was found between the physician and patient perception. These symptoms should be addressed during outpatient visits.
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Affiliation(s)
- Nadia Wespi
- Department of Gastroenterology and HepatologyUniversity Hospital Zurich and University of ZurichZurichSwitzerland
| | - Stephan Vavricka
- Department of Gastroenterology and HepatologyUniversity Hospital Zurich and University of ZurichZurichSwitzerland
| | - Stephan Brand
- Division of Gastroenterology and HepatologyCantonal Hospital St. GallenSt. GallenSwitzerland
| | - Patrick Aepli
- Division of Gastroenterology and HepatologyCantonal Hospital LucerneLucerneSwitzerland
| | - Emanuel Burri
- Division of Gastroenterology and HepatologyUniversity Medical ClinicCantonal Hospital BasellandLiestalSwitzerland
| | - Benjamin Misselwitz
- Department of Visceral Surgery and MedicineBern University HospitalUniversity of BernBernSwitzerland
| | | | - Petr Hruz
- Division of Gastroenterology and HepatologyClarunisUniversity Hospital BaselBaselSwitzerland
| | - Laurent Peyrin‐Biroulet
- Department of GastroenterologyINFINY InstituteFHU‐CUREINSERM NGERENancy University HospitalVandœuvre‐lès‐NancyFrance
- Groupe Hospitalier privé Ambroise Paré ‐ HartmannParis IBD CenterNeuilly‐sur‐SeineFrance
- Division of Gastroenterology and HepatologyMcGill University Health CentreMontrealQuebecCanada
| | - Alain Schoepfer
- Division of Gastroenterology and HepatologyCHUV University Hospital Lausanne and University of Lausanne UNILLausanneSwitzerland
| | - Luc Biedermann
- Department of Gastroenterology and HepatologyUniversity Hospital Zurich and University of ZurichZurichSwitzerland
| | - Christiane Sokollik
- Pediatric Gastroenterology, Hepatology and NutritionChildren's HospitalBern University HospitalUniversity of BernBernSwitzerland
| | - Gerhard Rogler
- Department of Gastroenterology and HepatologyUniversity Hospital Zurich and University of ZurichZurichSwitzerland
| | - Thomas Greuter
- Department of Gastroenterology and HepatologyUniversity Hospital Zurich and University of ZurichZurichSwitzerland
- Division of Gastroenterology and HepatologyCHUV University Hospital Lausanne and University of Lausanne UNILLausanneSwitzerland
- Division of Gastroenterology and HepatologyGZO—Zurich Regional Health CenterWetzikonSwitzerland
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24
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Bharambe MV, Doshi PR, Lakhe RR, Kulkarni PS, Bharadwaj RP. Role of Novel Target Molecules (β-Catenin and Retinoblastoma Protein) in the Spectrum of Inflammatory Bowel Disease. Cureus 2025; 17:e83162. [PMID: 40443602 PMCID: PMC12120537 DOI: 10.7759/cureus.83162] [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: 02/27/2025] [Accepted: 04/27/2025] [Indexed: 06/02/2025] Open
Abstract
Background Inflammatory bowel disease (IBD) has been a worldwide health care challenge with a continually increasing incidence in India. Spectrum of IBD mainly includes ulcerative colitis (UC) and Crohn's disease (CD). Pharmacological and surgical treatments differ widely in CD and UC; hence, establishment of a correct diagnosis is of paramount importance as it critically influences the disease outcome. Aim The aim of this study was to assess the utility and diagnostic accuracy of immunohistochemical profile of β-catenin and retinoblastoma protein in IBD as potential biomarkers. Study design This is a cross-sectional observational study. Material and methods Data of 61 cases of IBD with UC and CD were retrieved from the Department of Pathology. Immunohistochemical markers β-catenin and retinoblastoma protein were applied on the paraffin blocks of these cases, and their results were interpreted. Results Of the 61 cases, 49 cases of UC showed positivity for β-catenin with 100% sensitivity and 75% specificity and nine cases of CD showed positivity for retinoblastoma protein with 75% sensitivity and 95.92% specificity. Three cases were IBD unclassified. Overall, accuracy of β-catenin in UC was found to be 95.08% and that of retinoblastoma protein in CD was 91.80%. Conclusion Our study provides insights into the expressions of these specific immunohistochemistry markers and their significance in the differentiation of IBD into UC and CD.
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Affiliation(s)
- Manali V Bharambe
- Pathology, Bharati Vidyapeeth (Deemed to be University) Medical College, Pune, Pune, IND
| | - Preeti R Doshi
- Pathology, Bharati Vidyapeeth (Deemed to be University) Medical College, Pune, Pune, IND
| | - Rachana R Lakhe
- Pathology, Bharati Vidyapeeth (Deemed to be University) Medical College, Pune, Pune, IND
| | - Purva S Kulkarni
- Pathology, Bharati Vidyapeeth (Deemed to be University) Medical College, Pune, Pune, IND
| | - Reena P Bharadwaj
- Pathology, Bharati Vidyapeeth (Deemed to be University) Medical College, Pune, Pune, IND
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25
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Stevens CL, Adriaans GMC, Spooren CEGM, Peters V, Pierik MJ, Weersma RK, van Dullemen HM, Festen EAM, Visschedijk MC, Hendrix EMB, Perenboom CWM, Feskens EJM, Dijkstra G, Almeida RJ, Jonkers DMAE, Campmans-Kuijpers MJE. Exploring diet categorizations and their influence on flare prediction in inflammatory bowel disease, using the Sparse Grouped Least Absolute Shrinkage and Selection Operator method. Clin Nutr 2025; 47:212-226. [PMID: 40048994 DOI: 10.1016/j.clnu.2025.02.027] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/25/2024] [Revised: 02/11/2025] [Accepted: 02/20/2025] [Indexed: 03/23/2025]
Abstract
BACKGROUND & AIMS Diet is an important environmental factor in inflammatory bowel disease (IBD) onset and disease course, but analyses are hindered by its complexity. We aim to explore the Sparse Grouped Least Absolute Shrinkage and Selection Operator (Sparse Grouped LASSO or SGL) method to study whether different food categorizations, representing different dietary patterns, can predict flares in IBD. METHODS Baseline data on habitual dietary intake and longitudinal data on disease course were collected over a 24 month-period in two distinct cohorts. Food items were classified into 22 food groups. These were further classified into three diet categorizations: 1. Plant vs animal vs mixed; 2. Potentially healthy vs potentially unhealthy vs neutral; 3. Ultra-processed vs not ultra-processed. The SGL parameter 'lambda' identifies important groups using a-priori group information, while allowing for only a subset of variables within a group to be important predictors. RESULTS Of 724 eligible patients, 427 were in remission at baseline and were included in the SGL analyses. 106 (24.8 %) included patients developed a flare within 11.2 ± 6.6 months (65.1 % female, 34 % ulcerative colitis, mean age 43.3 ± 14.7 years). They had a higher crude food intake of red meat (p = 0.028) and vegetables (p = 0.027) than those who stayed in remission. Prediction models for flare development were moderate with AUC varying between 0.425 and 0.542 for model 1, 0.512 and 0.562 for model 2 and 0.451 and 0.612 for model 3. All models showed red meat, legumes and vegetables as the first selected predicting variables. However, female sex and energy intake had the highest predictive values in all 3 models. CONCLUSION Categorization of the same food groups in different ways influences the predictive value of the SGL method. The current exploration of the SGL method shows that food might not be the most important predictor of flares in IBD.
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Affiliation(s)
- Corien L Stevens
- Department of Gastroenterology and Hepatology, University Medical Centre Groningen, University of Groningen, Groningen, the Netherlands.
| | - Greetje M C Adriaans
- Department Gastroenterology-Hepatology, Maastricht University Medical Centre+, Maastricht, the Netherlands; Research Institute for Nutrition and Translational Research in Metabolism (NUTRIM), Maastricht University, Maastricht, the Netherlands
| | - Corinne E G M Spooren
- Department Gastroenterology-Hepatology, Maastricht University Medical Centre+, Maastricht, the Netherlands; Research Institute for Nutrition and Translational Research in Metabolism (NUTRIM), Maastricht University, Maastricht, the Netherlands
| | - Vera Peters
- Department of Gastroenterology and Hepatology, University Medical Centre Groningen, University of Groningen, Groningen, the Netherlands
| | - Marie J Pierik
- Department Gastroenterology-Hepatology, Maastricht University Medical Centre+, Maastricht, the Netherlands; Research Institute for Nutrition and Translational Research in Metabolism (NUTRIM), Maastricht University, Maastricht, the Netherlands
| | - Rinse K Weersma
- Department of Gastroenterology and Hepatology, University Medical Centre Groningen, University of Groningen, Groningen, the Netherlands
| | - Hendrik M van Dullemen
- Department of Gastroenterology and Hepatology, University Medical Centre Groningen, University of Groningen, Groningen, the Netherlands
| | - Eleonora A M Festen
- Department of Gastroenterology and Hepatology, University Medical Centre Groningen, University of Groningen, Groningen, the Netherlands
| | - Marijn C Visschedijk
- Department of Gastroenterology and Hepatology, University Medical Centre Groningen, University of Groningen, Groningen, the Netherlands
| | - Evelien M B Hendrix
- Department Gastroenterology-Hepatology, Maastricht University Medical Centre+, Maastricht, the Netherlands; Research Institute for Nutrition and Translational Research in Metabolism (NUTRIM), Maastricht University, Maastricht, the Netherlands
| | - Corine W M Perenboom
- Division of Human Nutrition and Health, Wageningen University & Research, Wageningen, the Netherlands
| | - Edith J M Feskens
- Division of Human Nutrition and Health, Wageningen University & Research, Wageningen, the Netherlands
| | - Gerard Dijkstra
- Department of Gastroenterology and Hepatology, University Medical Centre Groningen, University of Groningen, Groningen, the Netherlands
| | - Rui J Almeida
- Department of Quantitative Economics, School of Business and Economics, Maastricht University, Maastricht, the Netherlands; Department of Data Analytics and Digitalization, Maastricht University, Maastricht, the Netherlands
| | - Daisy M A E Jonkers
- Department Gastroenterology-Hepatology, Maastricht University Medical Centre+, Maastricht, the Netherlands; Research Institute for Nutrition and Translational Research in Metabolism (NUTRIM), Maastricht University, Maastricht, the Netherlands
| | - Marjo J E Campmans-Kuijpers
- Department of Gastroenterology and Hepatology, University Medical Centre Groningen, University of Groningen, Groningen, the Netherlands
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Koppelman LJM, Oyugi AA, Maljaars PWJ, van der Meulen-de Jong AE. Modifiable Factors Influencing Disease Flares in Inflammatory Bowel Disease: A Literature Overview of Lifestyle, Psychological, and Environmental Risk Factors. J Clin Med 2025; 14:2296. [PMID: 40217745 PMCID: PMC11989426 DOI: 10.3390/jcm14072296] [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: 01/29/2025] [Revised: 03/21/2025] [Accepted: 03/24/2025] [Indexed: 04/14/2025] Open
Abstract
Background: A significant concern for patients with Inflammatory Bowel Disease (IBD) is predicting and managing disease flares. While healthcare providers rely on biomarkers, providing conclusive patient advice remains challenging. This review explores the role of lifestyle, psychological health, and environmental exposures in the prediction and management of IBD flares. Methods: This review followed PRISMA guidelines (2020). A structured search was conducted in PubMed for articles published between 2012 and 2024, using free and Medical Subject Heading (MeSH) terms for predicting factors in IBD. Inclusion criteria included studies reporting primary data on modifiable clinical or environmental predictors of IBD relapse, excluding studies on post-operative investigations, treatment cessation, and pediatric or pregnant populations. The Mixed Method Appraisal Tool (MMAT) was used to assess the quality of the studies. Results: Out of 2287 identified citations, 58 articles were included. Several modifiable factors influencing disease flares were identified, including psychological stress, sleep disturbances, smoking, and nutrition. Poor sleep quality and mental health were linked to increased flare risks, while smoking was associated with higher relapse rates in Crohn's disease. Environmental exposures, such as heat waves and high-altitude regions, also contributed. Predictive models integrating clinical, lifestyle, and psychological factors showed promising accuracy but require further refinement. Limitations of this review include the potential for publication bias, variability in flare definitions, and limited sample sizes Conclusions: Key predictors of IBD flares include dietary factors, psychological stress, poor sleep quality, and pharmacological influences. Personalized approaches integrating these predictors can optimize disease control and improve patient outcomes.
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Affiliation(s)
- Lola J. M. Koppelman
- Department of Gastroenterology and Hepatology, Leiden University Medical Centre, 2333 ZA Leiden, The Netherlands
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Metwally H. STAT Signature Dish: Serving Immunity with a Side of Dietary Control. Biomolecules 2025; 15:487. [PMID: 40305224 PMCID: PMC12024614 DOI: 10.3390/biom15040487] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/17/2025] [Revised: 03/10/2025] [Accepted: 03/25/2025] [Indexed: 05/02/2025] Open
Abstract
Immunity is a fundamental aspect of animal biology, defined as the host's ability to detect and defend against harmful pathogens and toxic substances to preserve homeostasis. However, immune defenses are metabolically demanding, requiring the efficient allocation of limited resources to balance immune function with other physiological and developmental needs. To achieve this balance, organisms have evolved sophisticated signaling networks that enable precise, context-specific responses to internal and external cues. These networks are essential for survival and adaptation in multicellular systems. Central to this regulatory architecture is the STAT (signal transducer and activator of Transcription) family, a group of versatile signaling molecules that govern a wide array of biological processes across eukaryotes. STAT signaling demonstrates remarkable plasticity, from orchestrating host defense mechanisms to regulating dietary metabolism. Despite its critical role, the cell-specific and context-dependent nuances of STAT signaling remain incompletely understood, highlighting a significant gap in our understanding. This review delves into emerging perspectives on immunity, presenting dynamic frameworks to explore the complexity and adaptability of STAT signaling and the underlying logic driving cellular decision-making. It emphasizes how STAT pathways integrate diverse physiological processes, from immune responses to dietary regulation, ultimately supporting organismal balance and homeostasis.
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Affiliation(s)
- Hozaifa Metwally
- Laboratory of Immune Regulation, The World Premier International Research Center Initiative (WPI) Immunology Frontier Research Center, Osaka University, Osaka 565-0871, Japan
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28
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Miljković R, Marinković E, Prodić I, Kovačević A, Protić-Rosić I, Vasić M, Lukić I, Gavrović-Jankulović M, Stojanović M. Ameliorative Effect of Banana Lectin in TNBS-Induced Colitis in C57BL/6 Mice Relies on the Promotion of Antioxidative Mechanisms in the Colon. Biomolecules 2025; 15:476. [PMID: 40305159 PMCID: PMC12024995 DOI: 10.3390/biom15040476] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/14/2025] [Revised: 02/22/2025] [Accepted: 03/05/2025] [Indexed: 05/02/2025] Open
Abstract
Background: The global burden of inflammatory bowel diseases (IBDs), including ulcerative colitis and Crohn's disease, is constantly rising. As IBDs significantly reduce patients' quality of life, prevention and efficient treatment of IBDs are of paramount importance. Although the molecular mechanisms underlying IBD pathogenesis are still not completely understood, numerous studies indicate the essential role of oxidative stress in the progression of the diseases. Objective: The aim of this study was to investigate whether prophylactic administration of recombinant banana lectin (rBanLec) could positively affect antioxidative mechanisms in the colon and thus prevent or alleviate the severity of experimental colitis induced in C57BL/6 mice. Methods: The prophylactic potential of rBanLec, a mannose-binding lectin with immunomodulatory properties, was investigated in a model of 2,4,6-trinitrobenzene sulfonic acid (TNBS)-induced colitis in C57BL/6 mice. Mice received rBanLec at various doses (0.1, 1 and 10 μg/mL) before the induction of colitis. The severity of the disease was assessed by weight loss and reduction in colon length, and correlated with histopathological findings, cytokine milieu, and oxidative stress markers in the colon. Results: The obtained results revealed that pretreatment with a low dose of rBanLec (0.1 μg/mL) significantly reduced the severity of TNBS-induced colitis, as indicated by reduced weight loss, less severe histopathological damage, and a favorable anti-inflammatory cytokine milieu (increased IL-10 and TGFβ). In addition, rBanLec pretreatment improved the activity of antioxidant enzymes (SOD, CAT, and GST) and reduced markers of oxidative stress such as nitric oxide levels at the peak of the disease. In contrast, higher doses of rBanLec exacerbated inflammatory responses. Conclusions: Our findings indicate that at low doses rBanLec can alleviate the severity of colitis by modulating oxidative stress and promoting anti-inflammatory cytokine responses, positioning rBanLec as a potential candidate for treating IBDs.
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Grants
- 451-03-66/2024-03/200177 Ministry of Science, Technological Development and Innovation, Serbia
- 451-03-66/2024-03/200007 Ministry of Science, Technological Development and Innovation, Serbia
- 451-03-66/2024-03/200168 Ministry of Science, Technological Development and Innovation, Serbia
- 451-03-136/2025-03/ 200177 Ministry of Science, Technological Development and Innovation, Serbia
- 451-03-136/2025-03/ 200007 Ministry of Science, Technological Development and Innovation, Serbia
- 451-03-136/2025-03/ 200168 Ministry of Science, Technological Development and Innovation, Serbia
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Affiliation(s)
- Radmila Miljković
- Department of Research and Development, Institute of Virology, Vaccines and Sera “Torlak”, 11221 Belgrade, Serbia; (R.M.); (I.P.); (A.K.); (M.V.); (I.L.)
| | - Emilija Marinković
- Institute for Immunology, University Hospital Heidelberg, 69120 Heidelberg, Germany;
| | - Ivana Prodić
- Department of Research and Development, Institute of Virology, Vaccines and Sera “Torlak”, 11221 Belgrade, Serbia; (R.M.); (I.P.); (A.K.); (M.V.); (I.L.)
| | - Ana Kovačević
- Department of Research and Development, Institute of Virology, Vaccines and Sera “Torlak”, 11221 Belgrade, Serbia; (R.M.); (I.P.); (A.K.); (M.V.); (I.L.)
| | - Isidora Protić-Rosić
- Department of Biochemistry, Faculty of Chemistry, University of Belgrade, 11158 Belgrade, Serbia; (I.P.-R.); (M.G.-J.)
- Institute of Immunology, Center for Pathophysiology, Infectiology and Immunology, Medical University of Vienna, 1090 Vienna, Austria
| | - Marko Vasić
- Department of Research and Development, Institute of Virology, Vaccines and Sera “Torlak”, 11221 Belgrade, Serbia; (R.M.); (I.P.); (A.K.); (M.V.); (I.L.)
| | - Ivana Lukić
- Department of Research and Development, Institute of Virology, Vaccines and Sera “Torlak”, 11221 Belgrade, Serbia; (R.M.); (I.P.); (A.K.); (M.V.); (I.L.)
| | - Marija Gavrović-Jankulović
- Department of Biochemistry, Faculty of Chemistry, University of Belgrade, 11158 Belgrade, Serbia; (I.P.-R.); (M.G.-J.)
| | - Marijana Stojanović
- Department of Molecular Biology, Institute for Biological Research “Siniša Stanković”—National Institute of the Republic of Serbia, University of Belgrade, 11108 Belgrade, Serbia
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29
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Sharma B, Agriantonis G, Twelker K, Ebelle D, Kiernan S, Siddiqui M, Soni A, Cheerasarn S, Simon W, Jiang W, Cardona A, Chapelet J, Agathis AZ, Gamboa A, Dave J, Mestre J, Bhatia ND, Shaefee Z, Whittington J. Gut Microbiota Serves as a Crucial Independent Biomarker in Inflammatory Bowel Disease (IBD). Int J Mol Sci 2025; 26:2503. [PMID: 40141145 PMCID: PMC11942158 DOI: 10.3390/ijms26062503] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/17/2025] [Revised: 03/03/2025] [Accepted: 03/06/2025] [Indexed: 03/28/2025] Open
Abstract
Inflammatory bowel disease (IBD), encompassing Crohn's disease (CD), ulcerative colitis (UC), and IBD unclassified (IBD-U), is a complex intestinal disorder influenced by genetic, environmental, and microbial factors. Recent evidence highlights the gut microbiota as a pivotal biomarker and modulator in IBD pathogenesis. Dysbiosis, characterized by reduced microbial diversity and altered composition, is a hallmark of IBD. A consistent decrease in anti-inflammatory bacteria, such as Faecalibacterium prausnitzii, and an increase in pro-inflammatory species, including Escherichia coli, have been observed. Metabolomic studies reveal decreased short-chain fatty acids (SCFAs) and secondary bile acids, critical for gut homeostasis, alongside elevated pro-inflammatory metabolites. The gut microbiota interacts with host immune pathways, influencing morphogens, glycosylation, and podoplanin (PDPN) expression. The disruption of glycosylation impairs mucosal barriers, while aberrant PDPN activity exacerbates inflammation. Additionally, microbial alterations contribute to oxidative stress, further destabilizing intestinal barriers. These molecular and cellular disruptions underscore the role of the microbiome in IBD pathophysiology. Emerging therapeutic strategies, including probiotics, prebiotics, and dietary interventions, aim to restore microbial balance and mitigate inflammation. Advanced studies on microbiota-targeted therapies reveal their potential to reduce disease severity and improve patient outcomes. Nevertheless, further research is needed to elucidate the bidirectional interactions between the gut microbiome and host immune responses and to translate these insights into clinical applications. This review consolidates current findings on the gut microbiota's role in IBD, emphasizing its diagnostic and therapeutic implications, and advocates for the continued exploration of microbiome-based interventions to combat this debilitating disease.
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Affiliation(s)
- Bharti Sharma
- Department of Surgery, NYC Health and Hospitals—Elmhurst, New York, NY 11373, USA; (B.S.); (G.A.); (S.K.); (S.C.); (A.C.); (J.D.); (J.M.); (N.D.B.); (Z.S.)
- Department of Surgery, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA; (W.J.); (A.Z.A.)
| | - George Agriantonis
- Department of Surgery, NYC Health and Hospitals—Elmhurst, New York, NY 11373, USA; (B.S.); (G.A.); (S.K.); (S.C.); (A.C.); (J.D.); (J.M.); (N.D.B.); (Z.S.)
- Department of Surgery, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA; (W.J.); (A.Z.A.)
| | - Kate Twelker
- Department of Surgery, NYC Health and Hospitals—Elmhurst, New York, NY 11373, USA; (B.S.); (G.A.); (S.K.); (S.C.); (A.C.); (J.D.); (J.M.); (N.D.B.); (Z.S.)
- Department of Surgery, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA; (W.J.); (A.Z.A.)
| | - Danielle Ebelle
- Department of Medicine, St. George’s University, Grenada FZ818, West Indies; (D.E.); (M.S.); (W.S.); (J.C.)
| | - Samantha Kiernan
- Department of Surgery, NYC Health and Hospitals—Elmhurst, New York, NY 11373, USA; (B.S.); (G.A.); (S.K.); (S.C.); (A.C.); (J.D.); (J.M.); (N.D.B.); (Z.S.)
| | - Maham Siddiqui
- Department of Medicine, St. George’s University, Grenada FZ818, West Indies; (D.E.); (M.S.); (W.S.); (J.C.)
| | - Aditi Soni
- Department of Medicine, St. George’s University, Grenada FZ818, West Indies; (D.E.); (M.S.); (W.S.); (J.C.)
| | - Sittha Cheerasarn
- Department of Surgery, NYC Health and Hospitals—Elmhurst, New York, NY 11373, USA; (B.S.); (G.A.); (S.K.); (S.C.); (A.C.); (J.D.); (J.M.); (N.D.B.); (Z.S.)
| | - Whenzdjyny Simon
- Department of Medicine, St. George’s University, Grenada FZ818, West Indies; (D.E.); (M.S.); (W.S.); (J.C.)
| | - Winston Jiang
- Department of Surgery, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA; (W.J.); (A.Z.A.)
| | - Angie Cardona
- Department of Surgery, NYC Health and Hospitals—Elmhurst, New York, NY 11373, USA; (B.S.); (G.A.); (S.K.); (S.C.); (A.C.); (J.D.); (J.M.); (N.D.B.); (Z.S.)
| | - Jessica Chapelet
- Department of Medicine, St. George’s University, Grenada FZ818, West Indies; (D.E.); (M.S.); (W.S.); (J.C.)
| | - Alexandra Z. Agathis
- Department of Surgery, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA; (W.J.); (A.Z.A.)
| | - Alejandro Gamboa
- Department of Medicine, Medical University of the Americas, Devens, MA 01434, USA;
| | - Jasmine Dave
- Department of Surgery, NYC Health and Hospitals—Elmhurst, New York, NY 11373, USA; (B.S.); (G.A.); (S.K.); (S.C.); (A.C.); (J.D.); (J.M.); (N.D.B.); (Z.S.)
- Department of Surgery, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA; (W.J.); (A.Z.A.)
| | - Juan Mestre
- Department of Surgery, NYC Health and Hospitals—Elmhurst, New York, NY 11373, USA; (B.S.); (G.A.); (S.K.); (S.C.); (A.C.); (J.D.); (J.M.); (N.D.B.); (Z.S.)
- Department of Surgery, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA; (W.J.); (A.Z.A.)
| | - Navin D. Bhatia
- Department of Surgery, NYC Health and Hospitals—Elmhurst, New York, NY 11373, USA; (B.S.); (G.A.); (S.K.); (S.C.); (A.C.); (J.D.); (J.M.); (N.D.B.); (Z.S.)
- Department of Surgery, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA; (W.J.); (A.Z.A.)
| | - Zahra Shaefee
- Department of Surgery, NYC Health and Hospitals—Elmhurst, New York, NY 11373, USA; (B.S.); (G.A.); (S.K.); (S.C.); (A.C.); (J.D.); (J.M.); (N.D.B.); (Z.S.)
- Department of Surgery, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA; (W.J.); (A.Z.A.)
| | - Jennifer Whittington
- Department of Surgery, NYC Health and Hospitals—Elmhurst, New York, NY 11373, USA; (B.S.); (G.A.); (S.K.); (S.C.); (A.C.); (J.D.); (J.M.); (N.D.B.); (Z.S.)
- Department of Surgery, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA; (W.J.); (A.Z.A.)
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30
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Soundararajan R, Maurin MM, Rodriguez-Silva J, Upadhyay G, Alden AJ, Gowda SGB, Schell MJ, Yang M, Levine NJ, Gowda D, Sundaraswamy PM, Hui SP, Pflieger L, Wang H, Marcet J, Martinez C, Bennett RD, Chudzinski A, Karachristos A, Nywening TM, Cavallaro PM, Anderson ML, Coffey RJ, Nebozhyn MV, Loboda A, Coppola D, Pledger WJ, Halade GV, Yeatman TJ. Integration of lipidomics with targeted, single cell, and spatial transcriptomics defines an unresolved pro-inflammatory state in colon cancer. Gut 2025; 74:586-602. [PMID: 39658263 PMCID: PMC11885055 DOI: 10.1136/gutjnl-2024-332535] [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: 03/28/2024] [Accepted: 10/09/2024] [Indexed: 12/12/2024]
Abstract
BACKGROUND Over a century ago, Virchow proposed that cancer represents a chronically inflamed, poorly healing wound. Normal wound healing is represented by a transitory phase of inflammation, followed by a pro-resolution phase, with prostaglandin (PGE2/PGD2)-induced 'lipid class switching' producing inflammation-quenching lipoxins (LXA4, LXB4). OBJECTIVE We explored if lipid dysregulation in colorectal cancers (CRCs) is driven by a failure to resolve inflammation. DESIGN We performed liquid chromatography and tandem mass spectrometry (LC-MS/MS) untargeted analysis of 40 human CRC and normal paired samples and targeted, quantitative analysis of 81 human CRC and normal paired samples. We integrated analysis of lipidomics, quantitative reverse transcription-PCR, large scale gene expression, and spatial transcriptomics with public scRNASEQ data to characterize pattern, expression and cellular localisation of genes that produce and modify lipid mediators. RESULTS Targeted, quantitative LC-MS/MS demonstrated a marked imbalance of pro-inflammatory mediators, with a dearth of resolving lipid mediators. In tumours, we observed prominent over-expression of arachidonic acid derivatives, the genes encoding their synthetic enzymes and receptors, but poor expression of genes producing pro-resolving synthetic enzymes and resultant lipoxins (LXA4, LXB4) and associated receptors. These results indicate that CRC is the product of defective lipid class switching likely related to inadequate or ineffective levels of PGE2/PGD2. CONCLUSION We show that the lipidomic profile of CRC tumours exhibits a distinct pro-inflammatory bias with a deficiency of endogenous resolving mediators secondary to defective lipid class switching. These observations pave the way for 'resolution medicine', a novel therapeutic approach for inducing or providing resolvins to mitigate the chronic inflammation driving cancer growth and progression.
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Affiliation(s)
| | - Michelle M Maurin
- Department of Surgery, University of South Florida Health, Tampa, Florida, USA
| | | | - Gunjan Upadhyay
- Department of Internal Medicine, University of South Florida Health, Tampa, Florida, USA
| | - Ashley J Alden
- Department of Surgery, University of South Florida Health, Tampa, Florida, USA
| | | | - Michael J Schell
- Biostatistics and Bioinformatics Department, Moffitt Cancer Center, Tampa, Florida, USA
| | - Mingli Yang
- Department of Surgery, University of South Florida Health, Tampa, Florida, USA
| | - Noah Jhad Levine
- Center for Phenom Health, Buck Institute for Research on Aging, Novato, California, USA
| | - Divyavani Gowda
- Faculty of Health Sciences, Hokkaido University, Kita-12, Nishi-5, Kita-ku, Sappora, Japan
| | - Punith M Sundaraswamy
- Graduate School of Global Food Resources, Hokkaido University, Kita-9, Nishi-9, Kita-ku, Sapporo, Japan
| | - Shu-Ping Hui
- Faculty of Health Sciences, Hokkaido University, Kita-12, Nishi-5, Kita-ku, Sappora, Japan
| | - Lance Pflieger
- Center for Phenom Health, Buck Institute for Research on Aging, Novato, California, USA
| | - Heiman Wang
- Department of Surgery, University of South Florida Health, Tampa, Florida, USA
| | - Jorge Marcet
- Department of Surgery, Tampa General Hospital, Tampa, Florida, USA
| | | | | | - Allen Chudzinski
- Department of Surgery, Tampa General Hospital, Tampa, Florida, USA
| | | | - Timothy M Nywening
- Division of Surgical Oncology, Department of Surgery, Tampa General Hospital, Tampa, Florida, USA
| | - Paul M Cavallaro
- Department of Surgery, Tampa General Hospital, Tampa, Florida, USA
| | | | - Robert J Coffey
- Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee, USA
| | | | - Andrey Loboda
- Merck Research Laboratories Boston, Boston, Massachusetts, USA
| | - Domenico Coppola
- Department of Pathology, Florida Digestive Health Specialists LLP, Bradenton, Florida, USA
| | - Warren Jackson Pledger
- Tampa General Hospital, Tampa, Florida, USA
- Department of Molecular Medicine, University of South Florida Health, Tampa, Florida, USA
| | - Ganesh V Halade
- Department of Internal Medicine, University of South Florida Health, Tampa, Florida, USA
| | - Timothy J Yeatman
- Department of Surgery, University of South Florida Health, Tampa, Florida, USA
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31
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Wang J, Guay H, Chang D. Crohn's Disease and Ulcerative Colitis Share 2 Molecular Subtypes With Different Mechanisms and Drug Responses. J Crohns Colitis 2025; 19:jjae152. [PMID: 39361323 DOI: 10.1093/ecco-jcc/jjae152] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/03/2024] [Revised: 09/04/2024] [Accepted: 10/02/2024] [Indexed: 03/29/2025]
Abstract
BACKGROUND AND AIMS Several therapies have been approved to treat Crohn's disease (CD) and ulcerative colitis (UC), indicating that both diseases may share the same molecular subtypes. The aim of this study is to identify shared patient subtypes with common molecular drivers of disease. METHODS Five public datasets with 406 CD and 421 UC samples were integrated to identify molecular subtypes. Then, the patient labels from 6 independent datasets and 8 treatment datasets were predicted for validating subtypes and identifying the relationship with response status of corticosteroids, infliximab, vedolizumab, and ustekinumab. RESULTS Two molecular subtypes were identified from the training datasets, in which CD and UC patients were relatively evenly represented in each subtype. We found 6 S1-specific gene modules related to innate/adaptive immune responses and tissue remodeling and 9 S1-specific cell types (cycling T cells, Tregs, CD8+ lamina propria, follicular B cells, cycling B cells, plasma cells, inflammatory monocytes, inflammatory fibroblasts, and postcapillary venules). Subtype S2 was associated with 3 modules related to metabolism functions and 4 cell types (immature enterocytes, transit amplifying cells, immature goblet cells, and WNT5B+ cells). The subtypes can be replicated in 6 independent datasets based on a 20-gene classifier. Furthermore, response rates to 4 treatments in subtype S2 were significantly higher than those in subtype S1. CONCLUSIONS This study discovered and validated a robust transcriptome-based molecular classification shared by CD and UC and built a 20-gene classifier. Because 2 subtypes have different molecular mechanisms and drug response, our classification may aid interpretation of heterogeneous molecular and clinical information in inflammatory bowel disease patients.
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Affiliation(s)
- Jing Wang
- Genomic Research Center, AbbVie Inc., Cambridge, MA, USA
| | - Heath Guay
- AbbVie Bioresearch Center, Worcester, MA, USA
| | - Dan Chang
- Genomic Research Center, AbbVie Inc., Cambridge, MA, USA
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32
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Yang YJ, Jeon SR. Metabolic musculoskeletal disorders in patients with inflammatory bowel disease. Korean J Intern Med 2025; 40:181-195. [PMID: 40102707 PMCID: PMC11938716 DOI: 10.3904/kjim.2024.359] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/21/2024] [Revised: 11/13/2024] [Accepted: 11/14/2024] [Indexed: 03/20/2025] Open
Abstract
Inflammatory bowel disease (IBD), which includes Crohn's disease and ulcerative colitis, is a chronic inflammatory disorder that affects not only the gastrointestinal tract but also extraintestinal organs, leading to various extraintestinal manifestations and complications. Among these, musculoskeletal disorders such as osteoporosis, sarcopenia, and axial and peripheral spondyloarthritis are the most commonly observed. These conditions arise from complex mechanisms, including chronic inflammation, malnutrition, gut dysbiosis, and glucocorticoid use, all of which contribute to reduced bone density, muscle loss, and joint inflammation. Osteoporosis and sarcopenia may co-occur as osteosarcopenia, a condition that heightens the risk of fractures, impairs physical performance, and diminishes quality of life, particularly in elderly patients with IBD. Holistic management strategies, including lifestyle modifications, calcium, and vitamin D supplementation, resistance training, and pharmacological interventions, are essential for mitigating the impact of these conditions. Spondyloarthritis, which affects both axial and peripheral joints, further complicates disease management and significantly compromises joint health. Timely diagnosis and appropriate medical interventions, such as administration of nonsteroidal anti-inflammatory drugs and biologics, are critical for preventing chronic joint damage and disability. Moreover, a multidisciplinary approach that addresses both metabolic and inflammatory aspects is essential for optimizing physical function and improving treatment outcomes in patients who have IBD with musculoskeletal involvement.
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Affiliation(s)
- Young Joo Yang
- Department of Internal Medicine, Hallym University College of Medicine, Chuncheon,
Korea
- Institute for Liver and Digestive Diseases, Hallym University, Chuncheon,
Korea
| | - Seong Ran Jeon
- Digestive Disease Center, Institute for Digestive Research, Soonchunhyang University College of Medicine, Seoul,
Korea
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33
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Shim JV, Rehberg M, Wagenhuber B, van der Graaf PH, Chung DW. Combining mechanistic modeling with machine learning as a strategy to predict inflammatory bowel disease clinical scores. Front Pharmacol 2025; 16:1479666. [PMID: 40070575 PMCID: PMC11893853 DOI: 10.3389/fphar.2025.1479666] [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: 08/12/2024] [Accepted: 01/27/2025] [Indexed: 03/14/2025] Open
Abstract
Disease activity scores are efficacy endpoints in clinical trials of inflammatory bowel disease (IBD) therapies. Crohn's disease activity index (CDAI), Mayo endoscopic score (MES) and Mayo score are frequently used in clinical trials. They rely on either the physician's observation of the inflammatory state of the patient's gastrointestinal tissue alone or combined with the patient's subjective evaluation of general wellbeing. Given the importance of these scores in evaluating the efficacy of drug treatment and disease severity, there has been interest in developing a computational approach to reliably predict these scores. A promising approach is using mechanistic models such as quantitative systems pharmacology (QSP) which simulate the mechanisms of the disease and its modulation by the drug pharmacology. However, extending QSP model simulations to clinical score predictions has been challenging due to the limited availability of gut biopsy measurements and the subjective nature of some of the evaluation criteria for these scores that cannot be described using mechanistic relationships. In this perspective, we examine details of IBD disease activity scores and current progress in building predictive models for these scores (such as biomarkers for disease activity). Then, we propose a method to leverage simulated markers of inflammation from a QSP model to predict IBD clinical scores using a machine learning algorithm. We will demonstrate how this combined approach can be used to (1) explore mechanistic insights underlying clinical observations; and (2) simulate novel therapeutic strategies that could potentially improve clinical outcomes.
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Affiliation(s)
- Jaehee V. Shim
- Certara Applied BioSimulation, Sheffield, United Kingdom
| | - Markus Rehberg
- Sanofi R&D, Translational Disease Modeling, Frankfurt amMain, Germany
| | - Britta Wagenhuber
- Sanofi R&D, Translational Disease Modeling, Frankfurt amMain, Germany
| | - Piet H. van der Graaf
- Certara Applied BioSimulation, Sheffield, United Kingdom
- Division of Systems Pharmacology and Pharmacy, Leiden Academic Centre for Drug Research, Leiden University, Leiden, Netherlands
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34
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Zhang Y, Zhang X, Lv L, Gao S, Li X, Wang R, Wang P, Shi F, She J, Wang Y. Versatile inulin/trans-ferulic acid/silk sericin nanoparticles-nourished probiotic complex with prolonged intestinal retention for synergistic therapy of inflammatory bowel disease. Carbohydr Polym 2025; 350:123063. [PMID: 39647933 DOI: 10.1016/j.carbpol.2024.123063] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/12/2024] [Revised: 10/31/2024] [Accepted: 11/23/2024] [Indexed: 12/10/2024]
Abstract
To achieve effective long-term synergistic treatment of inflammatory bowel disease (IBD) with probiotics, we developed a versatile inulin/trans-ferulic acid/silk sericin nanoparticles-nourished probiotic complex. Inulin/TFA/SS nanoparticles were fabricated by inulin, trans-ferulic acid (TFA), and silk sericin (SS), and then loaded onto the surface of poly-l-lysine (PLL) and poly-glutamic acid (PGA)-coated Bifidobacterium longum (BL) to obtain BL@PLL-PGA-Inulin/TFA/SS NPs (BL@PP-NPs). This design simultaneously endowed the complex with excellent gastrointestinal resistance, antioxidant, and anti-inflammation abilities. Moreover, the inulin in the nanoparticles acts as a prebiotic, promoting the Bifidobacterium's rapid proliferation to exert effects within a short period. Compared with uncoated BL, BL@PP-NPs exhibited excellent gastric acid tolerance and up to 31.32-fold colonic colonization, and the ROS scavenging and proliferative capacity were increased by 5.61- and 1.39-fold, respectively. In a mouse model of dextran sulfate sodium (DSS)- and trinitrobenzene sulfonic acid (TNBS)-induced colitis, the components of Inulin/TFA/SS NPs synergized with probiotics to efficiently treat IBD by attenuating oxidative stress, decreasing inflammation, repairing intestinal barrier, and promoting the rapid proliferation of probiotics to reverse gut microbial disorders. Collectively, food-grade BL@PP-NPs represent a novel approach to probiotic modification that offers an effective, safe, and synergistic therapy for IBD.
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Affiliation(s)
- Yujie Zhang
- Department of General Surgery, The First Affiliated Hospital of Xi'an Jiaotong University, 710061 Xi'an, Shaanxi, PR China
| | - Xiaojiang Zhang
- Department of General Surgery, The First Affiliated Hospital of Xi'an Jiaotong University, 710061 Xi'an, Shaanxi, PR China
| | - Lianxi Lv
- Health Science Center, Xi'an Jiaotong University, 710061 Xi'an, Shaanxi, PR China
| | - Sheng Gao
- Health Science Center, Xi'an Jiaotong University, 710061 Xi'an, Shaanxi, PR China
| | - Xiang Li
- Center for Gut Microbiome Research, Med-X Institute, The First Affiliated Hospital of Xi'an Jiaotong University, 710061 Xi'an, Shaanxi, PR China; Department of Otorhinolaryngology-Head and Neck Surgery, The First Affiliated Hospital of Xi'an Jiaotong University, 710061 Xi'an, Shaanxi, PR China
| | - Ruochen Wang
- Center for Gut Microbiome Research, Med-X Institute, The First Affiliated Hospital of Xi'an Jiaotong University, 710061 Xi'an, Shaanxi, PR China
| | - Pengqian Wang
- Department of Chemical Engineering, School of Water and Environment, Chang'an University, 710064 Xi'an, Shaanxi, PR China.
| | - Feiyu Shi
- Department of General Surgery, The First Affiliated Hospital of Xi'an Jiaotong University, 710061 Xi'an, Shaanxi, PR China.
| | - Junjun She
- Department of General Surgery, The First Affiliated Hospital of Xi'an Jiaotong University, 710061 Xi'an, Shaanxi, PR China; Center for Gut Microbiome Research, Med-X Institute, The First Affiliated Hospital of Xi'an Jiaotong University, 710061 Xi'an, Shaanxi, PR China; Department of High Talent, The First Affiliated Hospital of Xi'an Jiaotong University, 710061 Xi'an, Shaanxi, PR China.
| | - Ya Wang
- Center for Gut Microbiome Research, Med-X Institute, The First Affiliated Hospital of Xi'an Jiaotong University, 710061 Xi'an, Shaanxi, PR China.
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Holt BM, Stine JM, Beardslee LA, Ayansola H, Jin Y, Pasricha PJ, Ghodssi R. An ingestible bioimpedance sensing device for wireless monitoring of epithelial barriers. MICROSYSTEMS & NANOENGINEERING 2025; 11:24. [PMID: 39915452 PMCID: PMC11802857 DOI: 10.1038/s41378-025-00877-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 10/02/2024] [Revised: 12/03/2024] [Accepted: 01/04/2025] [Indexed: 02/09/2025]
Abstract
Existing gastrointestinal (GI) diagnostic tools are unable to non-invasively monitor mucosal tight junction integrity in vivo beyond the esophagus. In the GI tract, local inflammatory processes induce alterations in tight junction proteins, enhancing paracellular ion permeability. Although transepithelial electrical resistance (TEER) may be used in the laboratory to assess mucosal barrier integrity, there are no existing methodologies for characterizing tight junction dilation in vivo. Addressing this technology gap, intraluminal bioimpedance sensing may be employed as a localized, non-invasive surrogate to TEER electrodes used in cell cultures. Thus far, bioimpedance has only been implemented in esophagogastroduodenoscopy (EGD) due to the need for external electronics connections. In this work, we develop a novel, noise-resilient Bluetooth-enabled ingestible device for the continuous, non-invasive measurement of intestinal mucosal "leakiness." As a proof-of-concept, we validate wireless impedance readout on excised porcine tissues in motion. Through an animal study, we demonstrate how the device exhibits altered impedance response to tight junction dilation induced on mice colonic tissue through calcium-chelator exposure. Device measurements are validated using standard benchtop methods for assessing mucosal permeability.
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Affiliation(s)
- Brian M Holt
- Department of Electrical and Computer Engineering, University of Maryland, College Park, MD, 20742, USA
- Institute for Systems Research, University of Maryland, College Park, MD, 20742, USA
- Robert E. Fischell Institute for Biomedical Devices, University of Maryland, College Park, MD, 20742, USA
| | - Justin M Stine
- Matrix Lab at A. James Clark School of Engineering, University of Maryland, California, MD, 20619, USA
| | - Luke A Beardslee
- Institute for Systems Research, University of Maryland, College Park, MD, 20742, USA
| | - Hammed Ayansola
- Department of Animal & Avian Sciences, University of Maryland, College Park, MD, 20742, USA
| | - Younggeon Jin
- Department of Animal & Avian Sciences, University of Maryland, College Park, MD, 20742, USA
| | | | - Reza Ghodssi
- Department of Electrical and Computer Engineering, University of Maryland, College Park, MD, 20742, USA.
- Institute for Systems Research, University of Maryland, College Park, MD, 20742, USA.
- Robert E. Fischell Institute for Biomedical Devices, University of Maryland, College Park, MD, 20742, USA.
- Matrix Lab at A. James Clark School of Engineering, University of Maryland, California, MD, 20619, USA.
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Lin ZH, Li CP, Sun CK, Cho DY, Tsai FJ, Yip HT, Chang R, Hung YM. Increased Risk of Inflammatory Bowel Disease Among Patients With Nontyphoidal Salmonella Infections: A Population-Based Cohort Study. Inflamm Bowel Dis 2025; 31:351-361. [PMID: 38567440 DOI: 10.1093/ibd/izae053] [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: 09/06/2023] [Indexed: 04/04/2024]
Abstract
BACKGROUND Despite the known association between microorganisms and development of inflammatory bowel disease (IBD), the role of nontyphoidal Salmonella (NTS) in IBD is not adequately addressed. We aimed at elucidating the relationship between NTS infection and the risk of IBD. METHODS Based on the National Health Insurance Research Database in Taiwan, this retrospective cohort study enrolled patients with NTS infection (exposure group; n = 4651) and those without NTS infection (comparator group; n = 4651) who were propensity score matched (1:1) by demographic data, medications, comorbidities, and index date. All patients were followed until IBD onset, individual mortality, or December 31, 2018. Cox proportional hazards regression analysis was performed to determine the hazard ratios and 95% confidence intervals (CIs). Sensitivity analyses were used for cross-validation. RESULTS The NTS group demonstrated an increased risk of IBD compared with the non-NTS groups (adjusted hazard ratio [aHR], 2.12; 95% CI, 1.62-2.78) with a higher risk of developing ulcerative colitis in the former (aHR, 2.27; 95% CI, 1.69-3.04). Nevertheless, the small sample size may contribute to lack of significant difference in Crohn's disease. Consistent findings were noted after excluding IBD diagnosed within 6 months of NTS infection (aHR, 2.28; 95% CI, 1.71-3.03), excluding those with enteritis/colitis before index date (aHR, 1.85; 95% CI, 1.28-2.68), excluding those using antibiotics for 1 month in the year before IBD onset (aHR, 1.81; 95% CI, 1.34-2.45), inverse probability of treatment weighting (aHR, 1.64; 95% CI, 1.31-2.04), and inclusion of individuals regardless of age (n = 10 431; aHR, 1.83; 95% CI, 1.53-2.19). CONCLUSIONS Patients with NTS were associated with an increased risk of developing IBD, especially ulcerative colitis.
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Affiliation(s)
- Zong-Han Lin
- Department of Medical Education and Research, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan
| | - Chung-Pin Li
- Division of Gastroenterology and Hepatology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan
- Division of Clinical Skills Training, Department of Medical Education, Taipei Veterans General Hospital, Taipei, Taiwan
- School of Medicine, College of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan
- Therapeutic and Research Center of Pancreatic Cancer, Taipei Veterans General Hospital, Taipei, Taiwan
| | - Cheuk-Kwan Sun
- Department of Emergency Medicine, E-Da Dachang Hospital, I-Shou University, Kaohsiung, Taiwan
- School of Medicine for International Students, College of Medicine, I-Shou University, Kaohsiung, Taiwan
| | - Der-Yang Cho
- Translational Cell Therapy Center, Department of Medical Research, China Medical University Hospital, Taichung, Taiwan
- Department of Neurosurgery, China Medical University Hospital, Taichung, Taiwan
- Graduate Institute of Biomedical Sciences, China Medical University, Taichung, Taiwan
| | - Fuu-Jen Tsai
- School of Chinese Medicine, College of Chinese Medicine, China Medical University, Taichung, Taiwan
- Department of Medical Research, China Medical University Hospital, Taichung, Taiwan
- Division of Medical Genetics, China Medical University Children's Hospital, Taichung, Taiwan
- Department of Biotechnology and Bioinformatics, Asia University, Taichung, Taiwan
| | - Hei-Tung Yip
- Management Office for Health Data, China Medical University Hospital, Taichung, Taiwan
| | - Renin Chang
- Division of Medical Research, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan
- Department of Emergency Medicine, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan
| | - Yao-Min Hung
- Division of Nephrology, Department of Internal Medicine, Taipei Veterans General Hospital Taitung Branch, Taitung, Taiwan
- Master Program in Biomedicine, College of Science and Engineering, National Taitung University, Taitung, Taiwan
- College of Health and Nursing, Meiho University, Pingtung, Taiwan
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Yarur AJ, Dervieux T, Ungaro R, Spencer EA, Bruss A, Nunez L, Berens B, Vermeire S, Wang Z, Panetta JC, Dreesen E, Dubinsky MC. Ustekinumab Drug Clearance Is Better Associated with Disease Control than Serum Trough Concentrations in a Prospective Cohort of Inflammatory Bowel Disease. Pharmaceutics 2025; 17:187. [PMID: 40006554 PMCID: PMC11859385 DOI: 10.3390/pharmaceutics17020187] [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: 12/06/2024] [Revised: 01/27/2025] [Accepted: 01/30/2025] [Indexed: 02/27/2025] Open
Abstract
Background/Objectives: This study aimed to compare the association of ustekinumab (UST) drug clearance (CL) and trough drug concentrations with disease activity in patients with inflammatory bowel diseases (IBDs). Methods: A prospective cohort of 83 patients with IBD receiving maintenance therapy with 90 mg subcutaneous UST was analyzed using Bayesian PK modeling. UST concentrations and antibodies to UST (ATU) were collected at the trough and measured using a drug-tolerant homogenous mobility shift assay (HMSA). CL was estimated using Bayesian estimation methods with priors from a previous population pharmacokinetic study specifically reparametrized using HMSA. Outcomes were combined clinical and biochemical remission and endoscopic healing index (EHI) score, a validated marker of endoscopic active disease in IBD. Statistical analysis consisted of linear and nonlinear mixed effect models for repeated time-to-event analysis. Results: A total of 83 patients with IBD were enrolled (median age 42 years, 52% female) and evaluated across 312 dose cycles (median follow-up: 279 days, median of 3 cycles/patient). Median concentrations and CL were 5.0 µg/mL and 0.157 L/day, respectively. Most patients (89%) were exposed to other biologics before starting UST, which was associated with lower rates of clinical and biochemical remission (p = 0.01). Longitudinal changes in concentrations were not associated with remission (p = 0.53). Conversely, higher CL was associated with a lower likelihood of remission (p < 0.01). EHI > 50 points (endoscopic active disease, n = 303 cycles) was associated with higher UST CL (p < 0.01). Conclusions: UST CL was more strongly associated with clinical and biochemical outcomes than trough concentrations, highlighting its potential role in therapy optimization.
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Affiliation(s)
| | | | - Ryan Ungaro
- Mount Sinai Medical Center, New York, NY 10029, USA; (R.U.); (E.A.S.)
| | | | - Alexandra Bruss
- Medical College of Wisconsin, Milwaukee, WI 53226, USA; (A.B.); (L.N.); (B.B.)
| | - Lizbeth Nunez
- Medical College of Wisconsin, Milwaukee, WI 53226, USA; (A.B.); (L.N.); (B.B.)
| | - Brandon Berens
- Medical College of Wisconsin, Milwaukee, WI 53226, USA; (A.B.); (L.N.); (B.B.)
| | - Séverine Vermeire
- KU Leuven, Department of Gastroenterology, Pharmacometrics, 3000 Leuven, Belgium; (S.V.); (Z.W.); (E.D.)
| | - Zhigang Wang
- KU Leuven, Department of Gastroenterology, Pharmacometrics, 3000 Leuven, Belgium; (S.V.); (Z.W.); (E.D.)
| | - John C. Panetta
- St Jude Children’s Research Hospital, Memphis, TN 38016, USA;
| | - Erwin Dreesen
- KU Leuven, Department of Gastroenterology, Pharmacometrics, 3000 Leuven, Belgium; (S.V.); (Z.W.); (E.D.)
| | - Marla C. Dubinsky
- Mount Sinai Medical Center, New York, NY 10029, USA; (R.U.); (E.A.S.)
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Brunet-Mas E, Selva A, Bas-Cutrina F, Brujats A, Caballol B, Font R, Gómez B, Gonzalez-Muñosa C, Busquets D, Monfort D, Vera DP, Maristany E, Cirera G, Torres G, Castro-Poceiro J, Lopez J, Gonzalez-Gonzalez L, Màrquez-Mosquera L, Gallach M, Esteve M, Tremosa G, Torra S, Robles-Alonso V, Garcia-Iglesias P, Rodríguez-Lago I, Calvet X. Asymptomatic Inflammatory Bowel Disease Diagnosed During Colorectal Cancer Population Screening in Catalonia: Characteristics and Natural History. Clin Transl Gastroenterol 2025; 16:e00740. [PMID: 39729123 PMCID: PMC11845185 DOI: 10.14309/ctg.0000000000000740] [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: 02/16/2024] [Accepted: 06/21/2024] [Indexed: 12/28/2024] Open
Abstract
INTRODUCTION Inflammatory bowel disease (IBD) is usually diagnosed when symptomatic. Prognosis and evolution of preclinical IBD is largely unknown. However, colorectal cancer screening programs (CRCSP) detect a subset of patients with IBD with no symptoms. The aim of this study was to describe the natural history of asymptomatic IBD diagnosed through CRCSP. METHODS An observational, longitudinal, and retrospective study was performed at 22 centers in Catalonia between January 2010 and December 2019 including patients with asymptomatic IBD detected in the CRCSP. Demographic data and IBD characteristics, evolution, and treatment were recorded. Descriptive statistics and Kaplan-Meier analysis were used for the analysis. Data were given separately for IBD, Crohn's disease (CD), ulcerative colitis (UC), and IBD unclassified (IBDU). RESULTS One hundred eighty-eight patients were included: 103 UC (54.8%), 60 CD (31.9%), and 25 IBDU (13.3%). Sixty-six (35.1%) were women, and the average age was 59.9 ± 5.9 years. Sixty-four patients (34.0%) developed symptoms after a median follow-up of 35.6 months. Diarrhea was the most frequent symptom for CD and IBDU (25.4% and 11.5%, respectively) and blood in stools for UC (21.4%). The median time to first symptom was 11.6 months. Treatment was prescribed in 135 patients (72.2%); mesalazine was the most prescribed drug (123 patients; 65.4%). Thirteen patients (6.9%) required biological treatment. None underwent surgery. DISCUSSION Around one-third of asymptomatic patients with IBD developed symptoms after a medium follow-up of 3 years. Only 6.9% required biological treatment, and none required surgery. Overall, prognosis of asymptomatic IBD seems better.
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Affiliation(s)
- Eduard Brunet-Mas
- Gastroenterlogy Department, Parc Taulí Hospital Universitari, Institut d’Investigació i Innovació Parc Taulí (I3PT-CERCA), Sabadell, Spain
- Departament de Medicina, Universitat Autònoma de Barcelona, Barcelona, Spain
- CIBERehd, Instituto de Salud Carlos III, Madrid, Spain
| | - Anna Selva
- Clinical Epidemiology and Cancer Screening, Parc Taulí Hospital Universitari, Institut d’Investigació i Innovació Parc Taulí (I3PT_CERCA), Universitat Autònoma de Barcelona, Barcelona, Spain
- Department of Pediatrics, Obstetrics, Gynecology and Preventive Medicine, Universitat Autònoma de Barcelona, Barcelona, Spain
- CIBER de Epidemiología y Salud Pública, Instituto de Salud Carlos III, Madrid, Spain
| | | | - Anna Brujats
- Gastroenterology Department, Hospital de Berga - Salut Catalunya Central, Berga, Spain
- Gastroenterology Department, Hospital de la Santa Creu i Sant Pau de Barcelona, Barcelona, Spain
| | - Berta Caballol
- Gastroenterology Department, Hospital Clinic i Provincial, Institut d'Investigacions biomèdiques Pi Sunyer (IDIBAPS), CIBEREHD, Barcelona, Spain
| | - Rebeca Font
- Department of Health, Catalan Cancer Plan, Barcelona, Spain
- Bellvitge Biomedical Research Institute (IDIBELL), Barcelona, Spain
| | - Bàrbara Gómez
- Gastroenterology Department, Hospital de Mataró, Mataró, Spain
| | - Carlos Gonzalez-Muñosa
- Gastroenterology Department, Hospital de la Santa Creu i Sant Pau de Barcelona, Barcelona, Spain
| | - David Busquets
- Gastroenterology Department, Hospital Universitari de Girona Dr. J. Trueta, Girona, Spain
| | - David Monfort
- Gastroenterology Department, Consorci Sanitari de Terrassa, Terrassa, Spain
| | | | | | - Gemma Cirera
- Gastroenterology Department, Hospital Althaia, Manresa, Spain
| | - Gisela Torres
- Gastroenterology Department, Hospital Universitari Arnau de Vilanova, Lleida, Spain
| | - Jesús Castro-Poceiro
- Gastroenterology Department, Hospital Moisès Broggi Sant Joan Despí, Barcelona, Spain
| | - Joel Lopez
- Gastroenterology Department, Hospital Universitari Joan XXIII, Tarragona, Spain
| | | | | | - Marta Gallach
- Gastroenterology Department, Hospital Universitari de Vic, Vic, Spain
| | - Maria Esteve
- CIBERehd, Instituto de Salud Carlos III, Madrid, Spain
- Gastroenterology Department, Hospital Universitari Mutua Terrassa, Terrassa, Spain
| | - Gemma Tremosa
- Gastroenterology Department, Hospital Comarcal de l’Alt Penedès, Barcelona, Spain
| | - Sandra Torra
- Gastroenterology Department, Parc Sanitari Sant Joan de Déu, Barcelona, Spain
| | | | | | - Iago Rodríguez-Lago
- Gastroenterology Department, Hospital Universitario de Galdakao, Biobizkaia Health Research Institute, Universidad de Deusto, Galdakao, Spain
| | - Xavier Calvet
- Gastroenterlogy Department, Parc Taulí Hospital Universitari, Institut d’Investigació i Innovació Parc Taulí (I3PT-CERCA), Sabadell, Spain
- Departament de Medicina, Universitat Autònoma de Barcelona, Barcelona, Spain
- CIBERehd, Instituto de Salud Carlos III, Madrid, Spain
- Medicine Department, Universitat Autònoma de Barcelona, Bellaterra, Spain
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Khan A, Azzam MA. Inflammatory Bowel Disease and Stroke: Exploring Hidden Vascular Risks. Cureus 2025; 17:e79304. [PMID: 40125129 PMCID: PMC11927930 DOI: 10.7759/cureus.79304] [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: 02/19/2025] [Indexed: 03/25/2025] Open
Abstract
Inflammatory bowel disease (IBD), encompassing Crohn's disease and ulcerative colitis, is primarily known for its gastrointestinal manifestations. However, emerging evidence suggests a potential link between IBD and an increased risk of stroke, likely mediated by chronic systemic inflammation, endothelial dysfunction, and a prothrombotic state. Despite this growing recognition, the exact mechanisms and extent of this association remain unclear, highlighting a critical knowledge gap. This review aims to systematically analyze the association between IBD and stroke, exploring the underlying vascular mechanisms and identifying potential risk factors contributing to cerebrovascular events in IBD patients. A comprehensive literature search was conducted following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines across PubMed, Scopus, and Google Scholar using keywords such as "IBD," "Stroke," "Chronic inflammation," "Cerebrovascular risk," and "Gut-brain axis." After screening 150 studies and applying inclusion and exclusion criteria, six studies were included in the final synthesis. The findings suggest that chronic inflammation in IBD plays a key role in increasing stroke risk through endothelial dysfunction and a heightened prothrombotic state, with additional risk factors such as atrial fibrillation during active IBD flares further contributing to cerebrovascular events. While biologic therapies, including tumor necrosis factor (TNF)-alpha inhibitors, are effective in reducing systemic inflammation, their impact on mitigating stroke risk remains inconclusive. Given the potential role of IBD as an independent risk factor for stroke, a multidisciplinary approach to management is crucial. Addressing modifiable risk factors through pharmacologic interventions such as biologics, statins, and antiplatelet agents, alongside lifestyle modifications, could help reduce cerebrovascular complications in IBD patients. Further research is needed to explore personalized therapeutic strategies and establish clearer preventive guidelines for this at-risk population.
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Affiliation(s)
- Abdallah Khan
- Internal Medicine, RAK Medical and Health Sciences University, Ras Al Khaimah, ARE
| | - Maysoon A Azzam
- Internal Medicine, RAK Medical and Health Sciences University, Ras Al Khaimah, ARE
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Koureta E, Karatzas P, Kanellopoulos PN, Papapanagiotou A, Lekakis V, Bamias G, Karamanolis G, Vlachogiannakos J, Papavassiliou AG, Papatheodoridis GV. The importance of growth differentiation factor 15 and interleukin 6 serum levels in inflammatory bowel diseases. J Physiol Biochem 2025; 81:111-122. [PMID: 39560915 DOI: 10.1007/s13105-024-01057-4] [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: 09/27/2024] [Accepted: 10/22/2024] [Indexed: 11/20/2024]
Abstract
There are only scarce recent reports about the role of growth differentiation factor 15 (GDF-15) and some more data about interleukin-6 (IL-6) in inflammatory bowel diseases (IBD). We assessed GDF-15 and IL-6 serum levels in patients with IBD and associations with their characteristics. We included 122 and 71 stored samples from patients with Crohn's disease (CD) and ulcerative colitis (UC), respectively, and regular follow-up and 44 samples from healthy controls. Data regarding epidemiologic and disease characteristics were recorded. In CD, both GDF-15 and IL-6 levels were higher in active disease or all patients than controls (P ≤ 0.020) as well as patients with elevated CRP (P ≤ 0.008), endoscopically active disease (P ≤ 0.017), age ≥ 40 years (P ≤ 0.005) and active smokers (P ≤ 0.050) and were positively correlated with hospitalization numbers (P ≤ 0.019). GDF-15 levels were also positively correlated with flares within year-1 (P < 0.001). In UC, both GDF-15 and IL-6 levels were higher in clinically active or all patients than controls (P < 0.001), but they shared no other association with patient characteristics except for positive correlation with CRP. Only IL-6 levels were higher in active than inactive UC either clinically (P = 0.047) or endoscopically (P < 0.001) and were positively correlated with stool calprotectin (P = 0.021). GDF-15 was positively correlated to IL-6 levels only in UC (rs=0.591, P < 0.001) but not in CD. In conclusion, in CD, GDF-15 and IL-6 levels could constitute indexes of activity and even offer a prognostic index of disease progression. In UC, IL-6 could also represent an activity index, but the role of GDF-15 needs further evaluation.
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Affiliation(s)
- Evgenia Koureta
- Department of Gastroenterology, Medical School of National and Kapodistrian University of Athens, General Hospital of Athens "Laiko", 17 Agiou Thoma street, Athens, 11527, Greece
| | - Pantelis Karatzas
- Department of Gastroenterology, Medical School of National and Kapodistrian University of Athens, General Hospital of Athens "Laiko", 17 Agiou Thoma street, Athens, 11527, Greece
| | - Panagiotis N Kanellopoulos
- Department of Biological Chemistry, Medical School of National and Kapodistrian University of Athens, General Hospital of Athens "Laiko", Athens, Greece
| | - Angeliki Papapanagiotou
- Department of Biological Chemistry, Medical School of National and Kapodistrian University of Athens, General Hospital of Athens "Laiko", Athens, Greece
| | - Vasileios Lekakis
- Department of Gastroenterology, Medical School of National and Kapodistrian University of Athens, General Hospital of Athens "Laiko", 17 Agiou Thoma street, Athens, 11527, Greece
| | - Giorgos Bamias
- GastroenteroIogy Unit, 3rd Department of Internal Medicine, Medical School of National, Kapodistrian University of Athens, "Sotiria" Hospital, Athens, Greece
| | - George Karamanolis
- Department of Gastroenterology, Medical School of National and Kapodistrian University of Athens, General Hospital of Athens "Laiko", 17 Agiou Thoma street, Athens, 11527, Greece
| | - Jiannis Vlachogiannakos
- Department of Gastroenterology, Medical School of National and Kapodistrian University of Athens, General Hospital of Athens "Laiko", 17 Agiou Thoma street, Athens, 11527, Greece
| | - Athanasios G Papavassiliou
- Department of Biological Chemistry, Medical School of National and Kapodistrian University of Athens, General Hospital of Athens "Laiko", Athens, Greece
| | - George V Papatheodoridis
- Department of Gastroenterology, Medical School of National and Kapodistrian University of Athens, General Hospital of Athens "Laiko", 17 Agiou Thoma street, Athens, 11527, Greece.
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Bhati R, Yadav A, Mitrolia B, Saini V, Dadhich SK, Bhargava N. Real-World Experience With Tofacitinib in Steroid-Dependent Patients With Moderate-to-Severe Ulcerative Colitis on Immunomodulators. Cureus 2025; 17:e79456. [PMID: 40130137 PMCID: PMC11932056 DOI: 10.7759/cureus.79456] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 02/21/2025] [Indexed: 03/26/2025] Open
Abstract
INTRODUCTION Patients with moderate-to-severe ulcerative colitis (UC) who are steroid-dependent despite being on immunomodulators pose significant clinical challenges. Currently, biologics therapy is the only option apart from considering surgery. Tofacitinib is an oral Janus kinase inhibitor used as a second-line therapy for patients with UC following the failure of biologics therapy. There is a lack of Indian data on the use of tofacitinib in biologically naïve patients with moderate-to-severe UC. Our study aimed to evaluate the efficacy and safety of tofacitinib in steroid-dependent patients with moderate-to-severe UC who were already on immunomodulators. MATERIALS AND METHODS An open-label, single-arm, prospective observational study was conducted on steroid-dependent UC patients from January 2021 to June 2023. All eligible patients received tofacitinib according to standard guidelines. Clinical response and remission were assessed at eight and 24 weeks. RESULTS A total of 53 patients met the inclusion criteria, of whom 52.83% were male and 47.16% were female. The mean age was 40.35 years (SD ± 10.85 years). At eight weeks, 36 patients (67.92%) showed a clinical response, 19 (35.8%) achieved clinical remission, and 12 (22.64%) attained endoscopic remission. At 24 weeks, 35 patients (66.03%) achieved clinical remission (p<0.001), and 22 (41.50%) attained endoscopic remission (p=0.003). A total of 36 patients (68%) showed a clinical response, while 17 (32%) did not respond to tofacitinib at eight weeks. CRP and Mayo scores showed significant differences between responders and non-responders (p<0.001). Only two patients developed herpes zoster infection, both of whom were managed conservatively without requiring discontinuation of tofacitinib. No other adverse effects, such as thromboembolic events, were observed during the study period. CONCLUSION The oral small-molecule tofacitinib is an effective and safe treatment for moderate-to-severe UC that is steroid-dependent in patients already on immunomodulators.
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Affiliation(s)
- Rajendra Bhati
- Gastroenterology and Hepatology, All India Institute of Medical Sciences, Jodhpur, Jodhpur, IND
- Gastroenterology and Hepatology, Dr. Sampurnanand Medical College, Jodhpur, IND
| | - Abhishek Yadav
- Gastroenterology and Hepatology, Dr. Sampurnanand Medical College, Jodhpur, IND
| | - Bobby Mitrolia
- Gastroenterology and Hepatology, Dr. Sampurnanand Medical College, Jodhpur, IND
| | - Vivek Saini
- Gastroenterology and Hepatology, Dr. Sampurnanand Medical College, Jodhpur, IND
| | - Sunil K Dadhich
- Gastroenterology and Hepatology, Dr. Sampurnanand Medical College, Jodhpur, IND
| | - Narendra Bhargava
- Gastroenterology and Hepatology, Dr. Sampurnanand Medical College, Jodhpur, IND
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Liu X, Chen Y, Liu Y, Hu Y, Wang K, Huang L, Ke X, Peng L, Guo Z. Protective effects and mechanisms of extracts of Gleditsia sinensis Lam. Thorn on DSS-induced colitis in mice. JOURNAL OF ETHNOPHARMACOLOGY 2025; 340:119244. [PMID: 39722326 DOI: 10.1016/j.jep.2024.119244] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 11/07/2024] [Revised: 12/07/2024] [Accepted: 12/13/2024] [Indexed: 12/28/2024]
Abstract
ETHNOPHARMACOLOGICAL RELEVANCE Inflammatory Bowel Disease (IBD), encompassing Ulcerative Colitis (UC) and Crohn's Disease (CD), stems from a multifaceted interaction of hereditary, immunological, ecological, and microbial elements. Current treatments have limitations, necessitating new therapeutic approaches. AIM OF THE STUDY This study investigates the safeguarding impacts and fundamental processes of extracts of Gleditsia sinensis Lam. thorn (EGST) in a dextran sulfate sodium (DSS)-induced colitis model in mice. MATERIALS AND METHODS A total of 180g of dried EGST were prepared, and untargeted metabolomic profiling using high-resolution liquid chromatography electrospray ionization orbitrap mass spectrometry (HR-LC-ESI-Orbitrap-MS) identified 930 compounds. UC model mice were administered 3% DSS for 7 d, followed by EGST treatment. The analysis encompassed physiological and pathological evaluations, serum cytokine ELISA, gut microbiota (GM) metagenomic sequencing, GC-MS metabolomics, mRNA sequencing, and Western Blot. RESULTS EGST markedly mitigated colitis symptoms, evidenced by reduced weight loss, lower DAI scores, and less colon shortening. It also decreased levels of pro-inflammatory cytokines (TNF-α, IL-6, IL-1β) while boosting IL-10. Histological examination revealed diminished tissue damage, restoration of crypts, and reduced inflammation, with barrier integrity maintained via upregulation of occludin and ZO-1. Metagenomic sequencing demonstrated that EGST modulated the GM, enhancing the levels of Firmicutes and Bacteroidetes while reducing the levels of Proteobacteria and Verrucomicrobia. Metabolomic analysis indicated that EGST influenced critical pathways, including those involving D-amino acids, glutathione, cysteine, and methionine metabolism. Furthermore, mRNA sequencing identified 2625 differentially expressed genes (DEGs), comprising 1729 with increased and 896 with decreased expression, and highlighted EGST's impact on the PPARγ/AMPK/NF-κB pathway. CONCLUSION Overall, EGST mitigates DSS-induced colitis through modulation of GM, metabolic profiles, and gene expression, suggesting its promise as a naturally derived treatment for colitis.
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Affiliation(s)
- Xiaoming Liu
- Department of Gastroenterology, Huaihe Hospital of Henan University, 115 Ximen Street, Kaifeng, 475000, Henan, China
| | - Yujie Chen
- Department of Gastroenterology, Suzhou Hospital of Anhui Medical University (Suzhou Municipal Hospital of Anhui province), NO.616 Bianyangsan Road, Suzhou, 234000, Anhui, China
| | - Yong Liu
- Institute of Chemical Industry of Forest Products, CAF, National Engineering Laboratory for Biomass Chemical Utilization, Key and Open Laboratory on Forest Chemical Engineering, SFA, Key Laboratory of Biomass Energy and Material, Jiangsu Province, Nanjing, 210042, China
| | - Yang Hu
- Department of Gastroenterology, Suzhou Hospital of Anhui Medical University (Suzhou Municipal Hospital of Anhui province), NO.616 Bianyangsan Road, Suzhou, 234000, Anhui, China
| | - Keke Wang
- Department of Gastroenterology, Suzhou Hospital of Anhui Medical University (Suzhou Municipal Hospital of Anhui province), NO.616 Bianyangsan Road, Suzhou, 234000, Anhui, China
| | - Lixin Huang
- Institute of Chemical Industry of Forest Products, CAF, National Engineering Laboratory for Biomass Chemical Utilization, Key and Open Laboratory on Forest Chemical Engineering, SFA, Key Laboratory of Biomass Energy and Material, Jiangsu Province, Nanjing, 210042, China; Co-Innovation Center of Efficient Processing and Utilization of Forest Resources, Nanjing Forestry University, Nanjing, 210037, China.
| | - Xiquan Ke
- Department of Gastroenterology, The First Affiliated Hospital of Bengbu Medical University, No. 287 Changhuai Road, Bengbu, Anhui, 233004, China.
| | - Lei Peng
- Department of Biological and Food Engineering, Suzhou University, 1769 Xuefu Avenue, Suzhou city, Anhui, 234000, China.
| | - Zhiguo Guo
- Department of Gastroenterology, Suzhou Hospital of Anhui Medical University (Suzhou Municipal Hospital of Anhui province), NO.616 Bianyangsan Road, Suzhou, 234000, Anhui, China.
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Guo Y, Pabitra D, Pan L, Gong L, Li A, Liu S, Xiong J. Quantitative proteomic studies of the intestinal mucosa provide new insights into the molecular mechanism of ulcerative colitis. BMC Gastroenterol 2025; 25:48. [PMID: 39891110 PMCID: PMC11786489 DOI: 10.1186/s12876-025-03647-y] [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: 02/25/2024] [Accepted: 01/23/2025] [Indexed: 02/03/2025] Open
Abstract
BACKGROUND Differentiation between ulcerative colitis (UC) and other intestinal inflammatory diseases is difficult, and the precise etiology of UC is poorly understood. Thus, there is a need for novel diagnostic and prognostic biomarkers for UC. METHODS Intestinal mucosal biopsy tissue specimens of inflamed (ulcerative colitis-inflamed, UC-I) and non-inflamed (ulcerative colitis-noninflamed, UC-N) tissue were obtained simultaneously during colonoscopy from newly diagnosed UC patients prior to any treatments. Label-free liquid chromatography tandem mass spectrometry (LC-MS/MS) quantitative proteomics was used to detect proteomic differences between UC-I, UC-N, and normal control subjects (n = 5). Proteins with a fold-change > 1.5 and P < 0.05 between groups were considered to be differentially expressed (DEPs). Candidate biomarkers were further verified in 8 patients of each group by parallel reaction monitoring (PRM) (a prospective cohort, n = 8). Expression of TXNDC5 was quantified using immunohistochemistry (IHC). RESULTS A total of 4,788 proteins were identified. Multiple upregulated pathways, including leukocyte trans-endothelial migration and natural killer (NK) cell-mediated cytotoxicity, were identified. Network analysis showed that proteins were involved in 4 pathways in UC-I and 3 pathways in UC-N tissues, and participated in protein-protein interactions. Increased expression of 9 DEPs, including TXNDC5, EPX, and ITGAM were detected in UC patients compared to normal control subjects. Subsequent verification of the 9 DEPs by PRM confirmed the reliability of the mass spectrometry data. TXNDC5 expression was significantly increased in UC. CONCLUSIONS The pathways, networks, and proteins identified in this study may provide new insights into the molecular pathogenesis of UC. Further studies are required to determine if the proteins identified may help in the diagnosis and treatment of UC.
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Affiliation(s)
- Yandong Guo
- Department of Gastroenterology, Nanfang Hospital, Southern Medical University, Guangzhou, China
| | - Dahal Pabitra
- Department of Gastroenterology, Nanfang Hospital, Southern Medical University, Guangzhou, China
| | - Lei Pan
- Department of Gastroenterology, Nanfang Hospital, Southern Medical University, Guangzhou, China
| | - Lanbo Gong
- Department of Gastroenterology, Nanfang Hospital, Southern Medical University, Guangzhou, China
| | - Aimin Li
- Department of Gastroenterology, Nanfang Hospital, Southern Medical University, Guangzhou, China
| | - Side Liu
- Department of Gastroenterology, Nanfang Hospital, Southern Medical University, Guangzhou, China
| | - Jing Xiong
- Department of Gastroenterology, Nanfang Hospital, Southern Medical University, Guangzhou, China.
- Guangdong Provincial Key Laboratory of Gastroenterology, Department of Gastroenterology, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, Guangdong Province, China.
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Bencardino S, Matichecchia CS, Fanizza J, Peyrin-Biroulet L, Della-Torre E, Danese S, D'Amico F. IgG4 in the gut: Gastrointestinal IgG4-related disease or a new subtype of inflammatory bowel disease. Autoimmun Rev 2025; 24:103720. [PMID: 39653260 DOI: 10.1016/j.autrev.2024.103720] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/31/2024] [Revised: 11/27/2024] [Accepted: 12/06/2024] [Indexed: 12/13/2024]
Abstract
IgG4-related disease (IgG4-RD) is a chronic inflammatory condition characterized by tissue infiltration with IgG4-positive plasma cells, leading to fibrosis and organ dysfunction. While primarily affecting the pancreas, bile ducts, and salivary glands, IgG4-RD can also involve the gastrointestinal tract, raising questions about its relationship with inflammatory bowel disease (IBD). Recent studies suggest that patients with IBD may exhibit histological and serological features consistent with IgG4-RD, such as a dense lymphoplasmacytic infiltration, a storiform-type of fibrosis and a prominent IgG4 immune response. This overlap represents a diagnostic challenge, as differentiating between primary IBD and IgG4-RD involving the gut is crucial for appropriate treatment. Further research is essential to delineate the prevalence of tissue and serum IgG4 expression in patients with IBD. This approach could classify subtypes of IBD, enabling advancements in non-invasive diagnosis and monitoring as well as personalized therapies. The purpose of this review is to summarize the available evidence regarding intestinal involvement in IgG4-RD and the role of both serum and tissue IgG4 in inflammatory bowel diseases IBD.
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Affiliation(s)
- Sarah Bencardino
- Gastroenterology and Endoscopy, IRCCS San Raffaele Hospital and Vita-Salute San Raffaele University, Milan, Italy
| | - Cosimo Simone Matichecchia
- Gastroenterology and Endoscopy, IRCCS San Raffaele Hospital and Vita-Salute San Raffaele University, Milan, Italy
| | - Jacopo Fanizza
- Gastroenterology and Endoscopy, IRCCS San Raffaele Hospital and Vita-Salute San Raffaele University, Milan, Italy
| | - Laurent Peyrin-Biroulet
- Department of Gastroenterology, INFINY Institute, INSERM NGERE, CHRU Nancy, F-54500 Vandœuvre-lès-Nancy, France
| | - Emanuel Della-Torre
- Unit of Immunology, Rheumatology, Allergy and Rare Diseases, IRCCS San Raffaele Scientific Institute and Vita-Salute San Raffaele University, Milan, Italy
| | - Silvio Danese
- Gastroenterology and Endoscopy, IRCCS San Raffaele Hospital and Vita-Salute San Raffaele University, Milan, Italy
| | - Ferdinando D'Amico
- Gastroenterology and Endoscopy, IRCCS San Raffaele Hospital and Vita-Salute San Raffaele University, Milan, Italy.
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Wu T, Cheng H, Zhuang J, Liu X, Ouyang Z, Qian R. Risk factors for inflammatory bowel disease: an umbrella review. Front Cell Infect Microbiol 2025; 14:1410506. [PMID: 39926114 PMCID: PMC11802543 DOI: 10.3389/fcimb.2024.1410506] [Citation(s) in RCA: 1] [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: 04/01/2024] [Accepted: 11/21/2024] [Indexed: 02/11/2025] Open
Abstract
Introduction Inflammatory bowel disease (IBD) represents a cluster of chronic idiopathic inflammatory disorders situated at the nexus of intricate interplays. The primary aim of the present investigation is to perform an umbrella review of metaanalyses, systematically offering a comprehensive overview of the evidence concerning risk factors for IBD. Methods To achieve this, we searched reputable databases, including PubMed, Embase, Web of Science, and the Cochrane Database of Systematic Reviews, from inception through April 2023. Two authors independently assessed the methodological quality of each metaanalysis using the AMSTAR tool and adhered to evidence classification criteria. Results In total, we extracted 191 unique risk factors in meta-analyses, including 92 significantly associated risk factors. The top ten risk factors were human cytomegalovirus (HCMV) infection, IBD family history, periodontal disease, poliomyelitis, campylobacter species infection, hidradenitis suppurativa, psoriasis, use of proton pump inhibitors, chronic obstructive pulmonary disease, and western dietary pattern. Discussion In conclusion, this umbrella review extracted 62 risk factors and 30 protective factors, most of which were related to underlying diseases, personal lifestyle and environmental factors. The findings in this paper help to develop better prevention and treatment measures to reduce the incidence of IBD, delay its progression, and reduce the burden of IBD-related disease worldwide. Systematic review registration https://www.crd.york.ac.uk/PROSPERO/, identifier CRD42023417175.
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Affiliation(s)
- Tingping Wu
- Shenzhen Bao'an Chinese Medicine Hospital, The Seventh Clinical College of Guangzhou University of Chinese Medicine, Shenzhen, Guangdong, China
| | - Honghui Cheng
- Shenzhen Bao'an Chinese Medicine Hospital, The Seventh Clinical College of Guangzhou University of Chinese Medicine, Shenzhen, Guangdong, China
| | - Jiamei Zhuang
- The Fourth Clinical Medical College of Guangzhou University of Chinese Medicine, Shenzhen, Guangdong, China
| | - Xianhua Liu
- Shenzhen Bao'an Chinese Medicine Hospital, The Seventh Clinical College of Guangzhou University of Chinese Medicine, Shenzhen, Guangdong, China
| | - Zichen Ouyang
- Shenzhen Bao'an Chinese Medicine Hospital, The Seventh Clinical College of Guangzhou University of Chinese Medicine, Shenzhen, Guangdong, China
| | - Rui Qian
- Shenzhen Bao'an Chinese Medicine Hospital, The Seventh Clinical College of Guangzhou University of Chinese Medicine, Shenzhen, Guangdong, China
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Buoso E, Masi M, Limosani RV, Fagiani F, Oliviero C, Colombo G, Cari L, Gentili M, Lusenti E, Rosati L, Pisati F, Pasini A, Lenti MV, Di Sabatino A, Mobbs CL, Przyborski S, Ronchetti S, Travelli C, Racchi M. Disruption of Epithelial Barrier Integrity via Altered GILZ/c-Rel/RACK1 Signaling in Inflammatory Bowel Disease. J Crohns Colitis 2025; 19:jjae191. [PMID: 39693354 DOI: 10.1093/ecco-jcc/jjae191] [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: 07/12/2024] [Revised: 11/21/2024] [Accepted: 12/17/2024] [Indexed: 12/20/2024]
Abstract
BACKGROUND AND AIMS Given the role of Receptor for Activated C Kinase 1 (RACK1) in both immune cell activation and in the maintenance of the intestinal epithelial barrier integrity, we investigated whether it was involved in inflammatory bowel disease (IBD). METHODS RACK1 expression was analyzed in intestinal mucosal samples of healthy and IBD patients, in mice with chemically induced colitis, and in diseased in vitro 2D and 3D coculture models by luciferase assay, reverse transcription-quantitative PCR, Western blotting, immunofluorescence, and immunohistochemistry. Based on our finding that glucocorticoid-induced leucine zipper (GILZ or tsc22d3) positively correlates with RACK1 expression in IBD patients, GILZ knockout mice and cell silencing experiments were performed. RESULTS RACK1 was significantly decreased in IBD, especially in ulcerative colitis. This was associated with an NF-κB/c-Rel-related mechanism, correlating with decreased GILZ protein expression. GILZ depletion confirmed a decrease in RACK1 expression, which favored SRC activation and led to a significant reduction in E-cadherin, resulting in impaired epithelial barrier integrity. Finally, our data highlighted that this novel mechanism could be considered to develop new therapies since dexamethasone, the first line of treatment in IBD, restored RACK1 expression through the glucocorticoid receptor in a c-Rel/GILZ-independent manner. CONCLUSIONS We provide the first evidence that an alteration of RACK1/SRC/E-cadherin regulatory mechanism, correlating with decreased GILZ protein expression, is involved in epithelial barrier disruption. The clinical relevance is based on the fact that this mechanism involving GILZ/c-Rel-related RACK1 expression could be considered to improve IBD therapies, particularly in patients with low or no response to glucocorticoid treatment.
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Affiliation(s)
- Erica Buoso
- Department of Drug Sciences, University of Pavia, viale Taramelli 12/14, 27100 Pavia, Italy
- Department of Pharmacology, Physiology & Biophysics, Boston University Chobanian & Avedisian School of Medicine, 700 Albany St W302 Boston, MA 02215, USA
| | - Mirco Masi
- Department of Drug Sciences, University of Pavia, viale Taramelli 12/14, 27100 Pavia, Italy
- University School of Advanced Studies IUSS, Palazzo del Broletto, Piazza della Vittoria 15, 27100 Pavia, Italy
| | | | - Francesca Fagiani
- Translational Neuropathology Unit, Division of Neuroscience, IRCCS San Raffaele Scientific Institute, via Olgettina 60, 20132 Milan, Italy
| | - Chiara Oliviero
- Department of Drug Sciences, University of Pavia, viale Taramelli 12/14, 27100 Pavia, Italy
| | - Giorgia Colombo
- Department of Pharmaceutical Sciences, University of Eastern Piedmont, Largo Donegani 2/3, 28100 Novara, Italy
| | - Luigi Cari
- Pharmacology Division, Department of Medicine and Surgery, University of Perugia, Piazzale Gambuli 1, 06132 Perugia, Italy
| | - Marco Gentili
- Pharmacology Division, Department of Medicine and Surgery, University of Perugia, Piazzale Gambuli 1, 06132 Perugia, Italy
| | - Eleonora Lusenti
- Pharmacology Division, Department of Medicine and Surgery, University of Perugia, Piazzale Gambuli 1, 06132 Perugia, Italy
| | - Lucrezia Rosati
- Pharmacology Division, Department of Medicine and Surgery, University of Perugia, Piazzale Gambuli 1, 06132 Perugia, Italy
| | - Federica Pisati
- Cogentech Ltd. Benefit Corporation With a Sole Shareholder, via Adamello 16, 20139 Milan, Italy
| | - Alessandra Pasini
- Department of Internal Medicine and Medical Therapeutics, University of Pavia, Campus della Salute, presso Policlinico San Matteo, viale Camillo Golgi 19, 27100 Pavia, Italy
- Department of Internal Medicine, Fondazione IRCCS Policlinico San Matteo, viale Camillo Golgi 19, 27100 Pavia, Italy
| | - Marco Vincenzo Lenti
- Department of Internal Medicine and Medical Therapeutics, University of Pavia, Campus della Salute, presso Policlinico San Matteo, viale Camillo Golgi 19, 27100 Pavia, Italy
- Department of Internal Medicine, Fondazione IRCCS Policlinico San Matteo, viale Camillo Golgi 19, 27100 Pavia, Italy
| | - Antonio Di Sabatino
- Department of Internal Medicine and Medical Therapeutics, University of Pavia, Campus della Salute, presso Policlinico San Matteo, viale Camillo Golgi 19, 27100 Pavia, Italy
- Department of Internal Medicine, Fondazione IRCCS Policlinico San Matteo, viale Camillo Golgi 19, 27100 Pavia, Italy
| | | | - Stefan Przyborski
- Department of Biosciences, Durham University, South Rd, Durham DH1 3LE, UK
| | - Simona Ronchetti
- Pharmacology Division, Department of Medicine and Surgery, University of Perugia, Piazzale Gambuli 1, 06132 Perugia, Italy
| | - Cristina Travelli
- Department of Drug Sciences, University of Pavia, viale Taramelli 12/14, 27100 Pavia, Italy
| | - Marco Racchi
- Department of Drug Sciences, University of Pavia, viale Taramelli 12/14, 27100 Pavia, Italy
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Barth I, Stevens CL, Peters V, Lucassen DA, Feskens EJM, Dijkstra G, Campmans-Kuijpers MJE. Relative Validity of the Groningen IBD Nutritional Questionnaire (GINQ-FFQ): A Food Frequency Questionnaire Designed to Assess Nutritional Intake in Patients with Inflammatory Bowel Disease. Nutrients 2025; 17:239. [PMID: 39861369 PMCID: PMC11768067 DOI: 10.3390/nu17020239] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/23/2024] [Revised: 01/06/2025] [Accepted: 01/08/2025] [Indexed: 01/27/2025] Open
Abstract
Background and Objective: To assess nutritional intake of patients with inflammatory bowel disease (IBD), a disease-specific food frequency questionnaire (FFQ) was developed: the Groningen IBD Nutritional Questionnaire (GINQ-FFQ). Aim of this study was to assess the relative validity of the GINQ-FFQ. Methods: Between 2019 and 2022, participants of the 1000IBD cohort were included and filled out a 3-day food diary and the GINQ-FFQ. Nutritional intake of nutrients and food groups was calculated. Bland-Altman analysis was conducted for energy intake, while paired t-tests and Wilcoxon signed rank tests were used for nutrient and food group intake. Additionally, group-level bias, cross-classification, and correlation analysis were performed. Results: 142 patients (59.2% females, mean age of 49 ± 14 years) were included. Bland-Altman analysis showed a mean difference between the GINQ-FFQ and 3FD of -63.6 kcal (±638.4), with limits of agreement ranging from -1315 to 1188 kcal. Differences in energy intake was significantly associated with higher mean total energy intake (p < 0.001). When stratifying for sex, this association only was significant for males. Group-level bias showed that the GINQ-FFQ tends to result in lower intake reports for macro- and micronutrients. Ranking ability (cross-classification) of macro-, micronutrients and food groups was good. Correlation coefficients for nutrients and food groups were considered acceptable or good. Conclusions: Overall, the GINQ-FFQ is a valid food frequency questionnaire to assess nutritional intake specifically for patients with IBD. However, for males with high total energy intakes, dietary assessment could be less accurate.
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Affiliation(s)
- Iris Barth
- Department of Gastroenterology and Hepatology, University Medical Centre Groningen (UMCG), 9713 GZ Groningen, The Netherlands (G.D.); (M.J.E.C.-K.)
- Graduate School of Medical Sciences (GSMS), University of Groningen (RUG), 9700 AB Groningen, The Netherlands
| | - Corien L. Stevens
- Department of Gastroenterology and Hepatology, University Medical Centre Groningen (UMCG), 9713 GZ Groningen, The Netherlands (G.D.); (M.J.E.C.-K.)
- Graduate School of Medical Sciences (GSMS), University of Groningen (RUG), 9700 AB Groningen, The Netherlands
| | - Vera Peters
- Department of Gastroenterology and Hepatology, University Medical Centre Groningen (UMCG), 9713 GZ Groningen, The Netherlands (G.D.); (M.J.E.C.-K.)
- Graduate School of Medical Sciences (GSMS), University of Groningen (RUG), 9700 AB Groningen, The Netherlands
| | - Desiree A. Lucassen
- Division of Human Nutrition and Health, Wageningen University & Research, 6700 AB Wageningen, The Netherlands; (D.A.L.); (E.J.M.F.)
| | - Edith J. M. Feskens
- Division of Human Nutrition and Health, Wageningen University & Research, 6700 AB Wageningen, The Netherlands; (D.A.L.); (E.J.M.F.)
| | - Gerard Dijkstra
- Department of Gastroenterology and Hepatology, University Medical Centre Groningen (UMCG), 9713 GZ Groningen, The Netherlands (G.D.); (M.J.E.C.-K.)
- Graduate School of Medical Sciences (GSMS), University of Groningen (RUG), 9700 AB Groningen, The Netherlands
| | - Marjo J. E. Campmans-Kuijpers
- Department of Gastroenterology and Hepatology, University Medical Centre Groningen (UMCG), 9713 GZ Groningen, The Netherlands (G.D.); (M.J.E.C.-K.)
- Graduate School of Medical Sciences (GSMS), University of Groningen (RUG), 9700 AB Groningen, The Netherlands
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Sannaa W, Almasry M, Peedikayil M, Grimshaw AA, Attamimi M, AlMutairdi A, Al-Bawardy B. Effectiveness and safety of oral vancomycin for the treatment of inflammatory bowel disease associated with primary sclerosing cholangitis: a systematic review and pooled analysis. Therap Adv Gastroenterol 2025; 18:17562848241312766. [PMID: 39802627 PMCID: PMC11719443 DOI: 10.1177/17562848241312766] [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: 09/21/2024] [Accepted: 12/23/2024] [Indexed: 01/16/2025] Open
Abstract
Background Inflammatory bowel disease (IBD) occurs in up to 70%-80% of patients with primary sclerosing cholangitis (PSC). Oral vancomycin therapy (OVT) has been reported to be effective in the treatment of IBD associated with PSC (IBD-PSC). Objectives To examine the effectiveness and safety of OVT in the treatment of IBD-PSC by performing a systematic review and pooled analysis of the literature. Design We performed a systematic review and pooled analysis of studies reporting IBD clinical response to OVT in IBD-PSC. Data sources and methods A systematic search was conducted in Cochrane Library, Embase, Google Scholar, Medline, PubMed, Scopus, and Web of Science from database inception to June 3, 2024. We included adult and pediatric studies that reported on clinical response (defined as any improvement in IBD-related clinical symptoms) of IBD-PSC patients treated with OVT (including pre- and post-liver transplantation cohorts). Pooled analyses of OVT response and safety were performed. Results A total of 21 (open-label, non-controlled) studies including 290 patients with IBD-PSC treated with OVT were included. The median duration of OVT to treat IBD-PSC was 32.5 weeks (interquartile range (IQR): 19-83 weeks). The total daily dose of OVT ranged from 250 to 1500 mg. Concomitant treatment included the following: mesalamine in 14.5% (n = 42), advanced therapies in 10.7% (n = 31), and immunosuppressive agents in 14.1% (n = 41). Clinical response was noted in 47.6% (138/290) and clinical remission in 43.5% (100/230). The biochemical remission rate post-OVT was 68.8% (55/80) and endoscopic remission was 39.4% (80/203). Three studies (n = 11) reported no episodes of acute cholangitis while on OVT. Five studies (n = 69) reported an incidence rate of 8.7% of vancomycin-resistant enterococci post-OVT to treat IBD-PSC. Conclusion OVT was associated with clinical response/remission in almost half of patients with IBD-PSC with a favorable side effect profile. Further prospective randomized trials are needed to confirm the dosing, efficacy, treatment duration, and long-term safety of OVT for the treatment of IBD-PSC. Trial registration The study protocol was registered with PROSPERO a priori (no. CRD42023438341).
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Affiliation(s)
- Wassel Sannaa
- Department of Medicine, University at Buffalo-Catholic Health System, Buffalo, NY, USA
| | - Mazen Almasry
- Department of Medicine, University of Wisconsin School of Medicine & Public Health, Madison, WI, USA
| | - Mustafa Peedikayil
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, King Faisal Specialist Hospital, Riyadh, Saudi Arabia
| | - Alyssa A. Grimshaw
- Harvey Cushing/John Hay Whitney Medical Library, Yale University, New Haven, CT, USA
| | - Mashary Attamimi
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, King Faisal Specialist Hospital, Riyadh, Saudi Arabia
| | - Abdulelah AlMutairdi
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, King Faisal Specialist Hospital, Riyadh, Saudi Arabia
| | - Badr Al-Bawardy
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, King Faisal Specialist Hospital and Research Center, P. O. Box 3354, Riyadh 11121, Saudi Arabia
- Department of Internal Medicine, Section of Digestive Diseases, Yale School of Medicine, New Haven, CT, USA
- College of Medicine, Alfaisal University, Riyadh, Saudi Arabia
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Haedrich J, Huber R. Crohn's disease, irritable bowel syndrome, and chronic fatigue: the importance of communication and symptom management-a case report. J Med Case Rep 2025; 19:9. [PMID: 39789666 PMCID: PMC11721286 DOI: 10.1186/s13256-024-05010-3] [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: 09/17/2024] [Accepted: 12/12/2024] [Indexed: 01/12/2025] Open
Abstract
BACKGROUND Crohn's disease and irritable bowel syndrome may both cause abdominal pain and diarrhea. Irritable bowel syndrome not only is an important differential diagnosis for Crohn's disease but also occurs in one out of three patients with Crohn's disease in remission in parallel. If not adequately diagnosed and treated, additional functional symptoms such as fatigue and/or muscle pain may develop, indicating a more severe course. CASE PRESENTATION A 64-year-old Caucasian male with long-standing, widely inactive Crohn's disease presented with persistent diarrhea, bloating, abdominal pain, general fatigue, unexplained hip pain, and frequent shivering with cold extremities, which had worsened following a gastrointestinal infection and psychological stress. A plausible explanation of his symptoms, based on an understanding of mind-body interactions, the autonomic nervous system, and temperature regulation, combined with symptom relief, was associated with rapid and sustainable improvement. After 2.5 years of follow-up, the patient is almost symptom-free. CONCLUSIONS This case report exemplifies the interrelation between organic (Crohn's disease) and functional diseases (irritable bowel syndrome, chronic fatigue syndrome, and somatoform pain). It further demonstrates that these connections may be overlooked in daily practice and that providing a plausible explanation in combination with symptom relief may be important for patients with functional syndromes.
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Affiliation(s)
- Johannes Haedrich
- Center for Complementary Medicine, Department of Internal Medicine II, Faculty of Medicine, Medical Center - University of Freiburg, University of Freiburg, 79106, Freiburg, Germany
| | - Roman Huber
- Center for Complementary Medicine, Department of Internal Medicine II, Faculty of Medicine, Medical Center - University of Freiburg, University of Freiburg, 79106, Freiburg, Germany.
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Jiang HY, Shao B, Wang HD, Zhao WQ, Ren SH, Xu YN, Liu T, Sun CL, Xiao YY, Li YC, Chen Q, Zhao PY, Yang GM, Liu X, Ren YF, Wang H. Analysis of nanomedicine applications for inflammatory bowel disease: structural and temporal dynamics, research hotspots, and emerging trends. Front Pharmacol 2025; 15:1523052. [PMID: 39845796 PMCID: PMC11750799 DOI: 10.3389/fphar.2024.1523052] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/05/2024] [Accepted: 12/24/2024] [Indexed: 01/24/2025] Open
Abstract
Background The application of nanomedicine in inflammatory bowel disease (IBD) has gained significant attention in the recent years. As the field rapidly evolves, analyzing research trends and identifying research hotpots are essential for guiding future advancements, and a comprehensive bibliometric can provide valuable insights. Methods The current research focused on publications from 2001 to 2024, and was sourced from the Web of Science Core Collection (WoSCC). CiteSpace and VOSviewer were employed to visualize authors, institutions, countries, co-cited references, and keywords, thereby mapping the intellectual structure and identifying emerging trends in the field. Results The analysis covered 1,518 literature across 447 journals, authored by 9,334 researchers from 5,459 institutions and 287 countries/regions. The global publication numbers exhibited an upward trend, particularly in the last decade, with China leading as the top publishing country and the Chinese Academy of Sciences emerging as the foremost institution. Dr. Xiao Bo is the prominent figure in advanced drug delivery systems. This interdisciplinary field, which spans materials science, pharmacy, and medicine, has seen influential publications mainly concentrated on targeted nanoparticles treatment for IBD. Keyword analysis revealed that current research hotspots include drug delivery, immune cell regulation, antioxidant damage, intestinal microbiota homeostasis, and nanovesicles. Conclusion This study offers a comprehensive overview of global research landscape, emphasizing the rapid growth and increasing complexity of this field. It identifies key research hotspots and trends, including efforts to enhance the precision, efficacy, and safety of nanomedicine applications. Emerging directions are highlighted as crucial for further progress in this evolving area.
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Affiliation(s)
- Hong-Yu Jiang
- Department of General Surgery, Tianjin Medical University General Hospital, Tianjin, China
- Tianjin General Surgery Institute, Tianjin Medical University General Hospital, Tianjin, China
| | - Bo Shao
- Department of General Surgery, Tianjin Medical University General Hospital, Tianjin, China
- Tianjin General Surgery Institute, Tianjin Medical University General Hospital, Tianjin, China
| | - Hong-Da Wang
- Department of General Surgery, Tianjin Medical University General Hospital, Tianjin, China
- Tianjin General Surgery Institute, Tianjin Medical University General Hospital, Tianjin, China
| | - Wen-Qi Zhao
- Tianjin Key Laboratory of Precise Vascular Reconstruction and Organ Function Repair, Tianjin, China
| | - Shao-Hua Ren
- Department of General Surgery, Tianjin Medical University General Hospital, Tianjin, China
- Tianjin General Surgery Institute, Tianjin Medical University General Hospital, Tianjin, China
- Department of General Surgery, The Affiliated Hospital of Inner Mongolia Medical University, Hohhot, China
| | - Yi-Ni Xu
- Department of General Surgery, Tianjin Medical University General Hospital, Tianjin, China
- Tianjin General Surgery Institute, Tianjin Medical University General Hospital, Tianjin, China
| | - Tong Liu
- Department of General Surgery, Tianjin Medical University General Hospital, Tianjin, China
- Tianjin General Surgery Institute, Tianjin Medical University General Hospital, Tianjin, China
| | - Cheng-Lu Sun
- Department of General Surgery, Tianjin Medical University General Hospital, Tianjin, China
- Tianjin General Surgery Institute, Tianjin Medical University General Hospital, Tianjin, China
| | - Yi-Yi Xiao
- Department of General Surgery, Tianjin Medical University General Hospital, Tianjin, China
- Tianjin General Surgery Institute, Tianjin Medical University General Hospital, Tianjin, China
| | - Yi-Cheng Li
- Department of General Surgery, Tianjin Medical University General Hospital, Tianjin, China
- Tianjin General Surgery Institute, Tianjin Medical University General Hospital, Tianjin, China
| | - Qiang Chen
- Department of General Surgery, Tianjin Medical University General Hospital, Tianjin, China
- Tianjin General Surgery Institute, Tianjin Medical University General Hospital, Tianjin, China
| | - Peng-Yu Zhao
- Department of General Surgery, Tianjin Medical University General Hospital, Tianjin, China
- Tianjin General Surgery Institute, Tianjin Medical University General Hospital, Tianjin, China
| | - Guang-Mei Yang
- Department of General Surgery, Tianjin Medical University General Hospital, Tianjin, China
- Tianjin General Surgery Institute, Tianjin Medical University General Hospital, Tianjin, China
| | - Xu Liu
- Department of General Surgery, Tianjin Medical University General Hospital, Tianjin, China
- Tianjin General Surgery Institute, Tianjin Medical University General Hospital, Tianjin, China
| | - Yu-Fan Ren
- Department of General Surgery, Tianjin Medical University General Hospital, Tianjin, China
- Tianjin General Surgery Institute, Tianjin Medical University General Hospital, Tianjin, China
| | - Hao Wang
- Department of General Surgery, Tianjin Medical University General Hospital, Tianjin, China
- Tianjin General Surgery Institute, Tianjin Medical University General Hospital, Tianjin, China
- Tianjin Key Laboratory of Precise Vascular Reconstruction and Organ Function Repair, Tianjin, China
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