{"title":"Unmasking the Steroid Curtain: Reevaluating Corticosteroid Use in IBD Clinical Trials.","authors":"Jeffrey A Berinstein, Nurulamin M Noor","doi":"10.1093/ibd/izae245","DOIUrl":"10.1093/ibd/izae245","url":null,"abstract":"","PeriodicalId":13623,"journal":{"name":"Inflammatory Bowel Diseases","volume":" ","pages":"893-894"},"PeriodicalIF":4.5,"publicationDate":"2025-03-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142464342","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Charlène Brochard, Laurent Siproudhis, Nadia Fathallah, Philippe Zerbib, Charles Sabbagh, Dominique Bouchard, Isabelle Etienney, Eddy Cotte
{"title":"Allogenic Stem Cells in Anal Fistulas of Crohn's Disease: From Promising Premises to Real Life Experience.","authors":"Charlène Brochard, Laurent Siproudhis, Nadia Fathallah, Philippe Zerbib, Charles Sabbagh, Dominique Bouchard, Isabelle Etienney, Eddy Cotte","doi":"10.1093/ibd/izae065","DOIUrl":"10.1093/ibd/izae065","url":null,"abstract":"<p><strong>Background: </strong>Allogenic adipocyte stem cells represent an unprecedented opportunity for regenerative therapy to treat Crohn anal fistulas. Apart from the results of one 8-year-old trial, scientific evidence remains scarce.</p><p><strong>Methods: </strong>Data from consecutive patients treated with darvadstrocel for Crohn anal fistulas were reviewed at 6 first tertiary reference centers. The judgment criteria combined asymptomatic status plus clinical occlusion of the fistula tract and MRI-confirmed healing of the tract (no inflammation and/or disappearance of the tract). Both clinical and MRI-confirmed healing of the tract defined a deep remission. Clinical remission was defined by an absence of complaint, occlusion of all external openings, and no fistula discharge.</p><p><strong>Results: </strong>A total of 116 patients were extracted (median follow-up after cell stem injection: 11 [6-14] months). No severe adverse events were reported after surgery except for subsequent anal surgery in 29 (25%) patients. Fifty-one (44%) patients had clinical remission defined by the absence of complaints, the occlusion of all external openings, and the presence of no fistula discharge. Deep remission was observed in 23 (29%) patients. Patients with clinical remission more often received combined therapy (immunosuppressant antitumor necrosis factors) than those with no improvement (31 of 51 [61%] vs 23 of 65 [35%]; P = .007). Regression analysis showed that high fistulas (odds ratio, 3.8 [1.1-12.5]; P = .03) and younger age (<38 years, odds ratio, 2.3 [1.0-58;4]; P = .02) were associated with a better outcome.</p><p><strong>Conclusions: </strong>Allogeneic stem cell treatment of Crohn's anal fistulas results in complete remission in less than half of patients, with a significant reintervention rate.</p>","PeriodicalId":13623,"journal":{"name":"Inflammatory Bowel Diseases","volume":" ","pages":"671-676"},"PeriodicalIF":4.5,"publicationDate":"2025-03-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141305884","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Maia Kayal, Elizabeth A Spencer, Matthew Smyth, Laura Raffals, Taha Qazi, Parakkal Deepak, Poonam Beniwal-Patel, Shannon Chang, Peter Higgins, Raymond K Cross, Chelsea Anderson, Millie Long, Hans H Herfarth, Marla C Dubinsky, Edward L Barnes
{"title":"Risankizumab Is Effective for The Management of Crohn's Disease of the Pouch.","authors":"Maia Kayal, Elizabeth A Spencer, Matthew Smyth, Laura Raffals, Taha Qazi, Parakkal Deepak, Poonam Beniwal-Patel, Shannon Chang, Peter Higgins, Raymond K Cross, Chelsea Anderson, Millie Long, Hans H Herfarth, Marla C Dubinsky, Edward L Barnes","doi":"10.1093/ibd/izae164","DOIUrl":"10.1093/ibd/izae164","url":null,"abstract":"","PeriodicalId":13623,"journal":{"name":"Inflammatory Bowel Diseases","volume":" ","pages":"878-881"},"PeriodicalIF":4.5,"publicationDate":"2025-03-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11879156/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141748132","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Jonathan Golob, Krishna Rao, Jeffrey A Berinstein, Prashant Singh, William D Chey, Chung Owyang, Nobuhiko Kamada, Peter D R Higgins, Vincent Young, Shrinivas Bishu, Allen A Lee
{"title":"Why Symptoms Linger in Quiescent Crohn's Disease: Investigating the Impact of Sulfidogenic Microbes and Sulfur Metabolic Pathways.","authors":"Jonathan Golob, Krishna Rao, Jeffrey A Berinstein, Prashant Singh, William D Chey, Chung Owyang, Nobuhiko Kamada, Peter D R Higgins, Vincent Young, Shrinivas Bishu, Allen A Lee","doi":"10.1093/ibd/izae238","DOIUrl":"10.1093/ibd/izae238","url":null,"abstract":"<p><strong>Introduction: </strong>Even in the absence of inflammation, persistent symptoms in patients with Crohn's disease (CD) are prevalent and worsen quality of life. We previously demonstrated enrichment in sulfidogenic microbes in quiescent Crohn's disease patients with (qCD + S) vs without persistent GI symptoms (qCD-S). Thus, we hypothesized that sulfur metabolic pathways would be enriched in stool while differentially abundant microbes would be associated with important sulfur metabolic pathways in qCD + S.</p><p><strong>Methods: </strong>We performed a multicenter observational study nested within SPARC IBD. Quiescent inflammation was defined by fecal calprotectin level < 150 mcg/g. Persistent symptoms were defined by CD-PRO2. Active CD (aCD) and non-IBD diarrhea-predominant irritable bowel syndrome (IBS-D) were included as controls.</p><p><strong>Results: </strong>Thirty-nine patients with qCD + S, 274 qCD-S, 21 aCD, and 40 IBS-D underwent paired shotgun metagenomic sequencing and untargeted metabolomic profiling. The fecal metabolome in qCD + S was significantly different relative to qCD-S and IBS-D but not aCD. Patients with qCD + S were enriched in sulfur-containing amino acid pathways, including cysteine and methionine, as well as serine, glycine, and threonine. Glutathione and nicotinate/nicotinamide pathways were also enriched in qCD + S relative to qCD-S, suggestive of mitochondrial dysfunction, a downstream target of H2S signaling. Multi-omic integration demonstrated that enriched microbes in qCD + S were associated with important sulfur metabolic pathways. Bacterial sulfur metabolic genes, including CTH, isfD, sarD, and asrC, were dysregulated in qCD + S. Finally, sulfur metabolites with and without sulfidogenic microbes showed good accuracy in predicting the presence of qCD + S.</p><p><strong>Discussion: </strong>Microbial-derived sulfur pathways and downstream mitochondrial function are perturbed in qCD + S, which implicate H2S signaling in the pathogenesis of this condition. Future studies will determine whether targeting H2S pathways results in improved quality of life in qCD + S.</p>","PeriodicalId":13623,"journal":{"name":"Inflammatory Bowel Diseases","volume":" ","pages":"763-776"},"PeriodicalIF":4.5,"publicationDate":"2025-03-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11879174/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142619708","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Comment on: \"The Burden of Psychiatric Manifestations in Inflammatory Bowel Diseases: A Systematic Review With Meta-analysis\".","authors":"Ganesh Bushi, Muhammed Shabil, Sanjit Sah","doi":"10.1093/ibd/izae260","DOIUrl":"10.1093/ibd/izae260","url":null,"abstract":"","PeriodicalId":13623,"journal":{"name":"Inflammatory Bowel Diseases","volume":" ","pages":"895-896"},"PeriodicalIF":4.5,"publicationDate":"2025-03-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142619549","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Sarah Shahub, Ruchita Mahesh Kumar, Kai-Chun Lin, Ivneet Banga, Natalie K Choi, Nicole M Garcia, Sriram Muthukumar, David T Rubin, Shalini Prasad
{"title":"Continuous Monitoring of CRP, IL-6, and Calprotectin in Inflammatory Bowel Disease Using a Perspiration-Based Wearable Device.","authors":"Sarah Shahub, Ruchita Mahesh Kumar, Kai-Chun Lin, Ivneet Banga, Natalie K Choi, Nicole M Garcia, Sriram Muthukumar, David T Rubin, Shalini Prasad","doi":"10.1093/ibd/izae054","DOIUrl":"10.1093/ibd/izae054","url":null,"abstract":"<p><strong>Background: </strong>Wearable sensor devices represent a noninvasive technology to continuously track biomarkers linked to inflammatory bowel disease (IBD). We assessed the inflammatory markers associated with IBD in human perspiration.</p><p><strong>Methods: </strong>Participants with IBD were monitored for 40 to 130 minutes with a proprietary wearable sensor device used to measure C-reactive protein, interleukin-6, and calprotectin. Sensor response using electrochemical impedance spectroscopy and serum samples were measured on the same day. The Mann-Whitney test was used to analyze the relationship between active and remission IBD in serum and perspiration, classified according to endoscopic reports and serum biomarker levels. Asynchronously collected fecal calprotectin from a subset of the population was similarly analyzed.</p><p><strong>Results: </strong>A total of 33 subjects were enrolled. Expression of calprotectin was significantly elevated in the active cohort compared with the remission cohort in perspiration (P < .05; median = 906.69 ng/mL; active 95% confidence interval [CI], 466.0-1833 ng/mL; remission 95% CI, 328.4-950.8 ng/mL), serum (median = 1860.82 ng/mL; active 95% CI, 1705-2985 ng/mL; remission 95% CI, 870.2-1786 ng/mL), and stool (P < .05; median = 126.74 µg/g; active 95% CI, 77.08-347.1 µg/g; remission 95% CI, 5.038-190.4 µg/g). Expression of CRP in perspiration and serum was comparable between the active and remission cohorts (perspiration: P > .05; median = 970.83 pg/mL; active 95% CI, 908.7-992 pg/mL; remission 95% CI, 903.3-991.9 pg/mL; serum: median = 2.34 µg/mL; active 95% CI, 1.267-4.492 µg/mL; remission 95% CI, 1.648-4.287 µg/mL). Expression of interleukin-6 in perspiration was nonsignificant in the active cohort compared with the remission cohort and was significantly elevated in serum (perspiration: P < .05; median = 2.13 pg/mL; active 95% CI, 2.124-2.44 pg/mL; remission 95% CI, 1.661-2.451 pg/mL; serum: median = 1.15 pg/mL; active 95% CI, 1.549-3.964 pg/mL; remission 95% CI, 0.4301-1.257 pg/mL). Analysis of the linear relationship between perspiration and serum calprotectin (R2 = 0.7195), C-reactive protein (R2 = 0.615), and interleukin-6 (R2 = 0.5411) demonstrated a strong to moderate relationship across mediums.</p><p><strong>Conclusions: </strong>We demonstrate the clinical utility of perspiration as a noninvasive medium for continuous measurement of inflammatory markers in IBD and find that the measures correlate with serum and stool markers across a range of disease activity.</p>","PeriodicalId":13623,"journal":{"name":"Inflammatory Bowel Diseases","volume":" ","pages":"647-654"},"PeriodicalIF":4.5,"publicationDate":"2025-03-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140193695","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Unraveling Twisted Pouch Syndrome: A Narrative Review of Classification, Diagnosis, Treatment, and Prevention.","authors":"Stefan D Holubar","doi":"10.1093/ibd/izae161","DOIUrl":"10.1093/ibd/izae161","url":null,"abstract":"<p><strong>Background: </strong>We recently described a cluster of symptoms known as twisted pouch syndrome that rarely affects patients with ileoanal pouches. Herein, we present a narrative review in which we describe the diagnosis, treatment, and prevention of twisted pouch syndrome, with a focus on a simple classification schema.</p><p><strong>Methods: </strong>Diagnostic signs from endoscopic and radiological examinations, treatment, and prevention strategies are presented.</p><p><strong>Results: </strong>Patients with twisted pouch syndrome suffer from a triad of obstructive symptoms, erratic bowel habits, and pain which may be severe, debilitating visceral pain, all in the setting of a mechanical pouch abnormality. Diagnostic modalities include imaging, careful pouchoscopy, functional testing, diagnostic laparoscopy or laparotomy, and recently 3-dimensional pouchography. Classification of twisted pouch syndrome is based on the location and degree of rotation of the pouch and its mesentery. Outlet twists may result when the distal pouch rotates >90° to 360° clockwise inadvertently during anastomosis; when only the distal most pouch is twisted, it results in an iris-like deformity of the pouch outlet, or when the distal half of the pouch is twisted, a mid-pouch stenosis and an hourglass-shaped pouch may result. Inlet twists are either a full 360° (mesentery posterior), unintentional 180° (mesentery anterior), or 90° counterclockwise twists. Both inlet and outlet twists are fixed deformities and may only be reduced by disconnecting the entire pouch from the anus. If they result in twisted pouch syndrome, a redo pouch procedure or pouch excision is required to reduce the twist; 90° counterclockwise twists may undergo pouch inlet transposition. Adhesive twists result when the pouch becomes fixed in the pelvis in an abnormal configuration, such as when the efferent limb becomes twisted underneath the afferent limb secondary to an occult tip of the J leak, and may be reduced by pelvic adhesiolysis with or without pouch revision.</p><p><strong>Conclusions: </strong>Pouches may rarely be inadvertently twisted during construction or twisted owing to adhesive disease or leaks. A high index of suspicion is needed to establish the diagnosis. We present a simple classification of twisted pouch syndrome that may aid in the prevention and recognition of these often difficult to diagnose postoperative complications.</p>","PeriodicalId":13623,"journal":{"name":"Inflammatory Bowel Diseases","volume":" ","pages":"850-856"},"PeriodicalIF":4.5,"publicationDate":"2025-03-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141889083","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Ohad Atia, Rachel Buchuk, Rona Lujan, Shira Greenfeld, Revital Kariv, Yiska Loewenberg Weisband, Natan Lederman, Eran Matz, Oren Ledder, Eran Zittan, Henit Yanai, Doron Shwartz, Moti Freiman, Iris Dotan, Daniel Nevo, Dan Turner
{"title":"Predictors of Complicated Disease Course in Children and Adults With Ulcerative Colitis: A Nationwide Study From the epi-IIRN.","authors":"Ohad Atia, Rachel Buchuk, Rona Lujan, Shira Greenfeld, Revital Kariv, Yiska Loewenberg Weisband, Natan Lederman, Eran Matz, Oren Ledder, Eran Zittan, Henit Yanai, Doron Shwartz, Moti Freiman, Iris Dotan, Daniel Nevo, Dan Turner","doi":"10.1093/ibd/izae094","DOIUrl":"10.1093/ibd/izae094","url":null,"abstract":"<p><strong>Background: </strong>Data on predictors of complicated ulcerative colitis (UC) course from unselected populations cohorts are scarce. We aimed to utilize a nationwide cohort to explore predictors at diagnosis of disease course in children and adults with UC.</p><p><strong>Methods: </strong>Data of patients diagnosed with UC since 2005 were retrieved from the nationwide epi-IIRN cohort. Complicated disease course was defined as colectomy, steroid-dependency, or the need for biologic drugs. Hierarchical clustering categorized disease severity at diagnosis based on complete blood count, albumin, C-reactive protein and erythrocyte sedimentation rate (ESR), analyzed together.</p><p><strong>Results: </strong>A total of 13 471 patients with UC (1427 [11%] pediatric-onset) including 103 212 person-years of follow-up were included. Complicated disease course was recorded in 2829 (21%) patients: 1052 (7.9%) escalated to biologics, 1357 (10%) experienced steroid-dependency, and 420 (3.1%) underwent colectomy. Probabilities of complicated disease course at 1 and 5 years from diagnosis were higher in pediatric-onset (11% and 32%, respectively) than adult-onset disease (4% and 16%; P < .001). In a Cox multivariate model, complicated course was predicted by induction therapy with steroids (hazard ratio [HR], 1.5; 95% CI, 1.2-2.0), extraintestinal manifestations (HR, 1.3; 95% CI, 1.03-1.5) and the disease severity clusters of blood tests (HR, 1.8; 95% CI, 1.01-3.1), while induction therapy with enemas (HR, 0.6; 95% CI, 0.5-0.7) and older age (HR, 0.99; 95% CI, 0.98-0.99) were associated with noncomplicated course.</p><p><strong>Conclusion: </strong>In this nationwide cohort, the probability of complicated disease course during the first 5 years from diagnosis was 32% in pediatric-onset and 16% in adults with UC and was associated with more severe clusters of routinely collected laboratory tests, younger age at diagnosis, extraintestinal manifestations, and type of induction therapy.</p>","PeriodicalId":13623,"journal":{"name":"Inflammatory Bowel Diseases","volume":" ","pages":"655-664"},"PeriodicalIF":4.5,"publicationDate":"2025-03-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141071004","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Anna L Silverman, Balu Bhasuran, Arman Mosenia, Fatema Yasini, Gokul Ramasamy, Imon Banerjee, Saransh Gupta, Taline Mardirossian, Rohan Narain, Justin Sewell, Atul J Butte, Vivek A Rudrapatna
{"title":"Accurate, Robust, and Scalable Machine Abstraction of Mayo Endoscopic Subscores From Colonoscopy Reports.","authors":"Anna L Silverman, Balu Bhasuran, Arman Mosenia, Fatema Yasini, Gokul Ramasamy, Imon Banerjee, Saransh Gupta, Taline Mardirossian, Rohan Narain, Justin Sewell, Atul J Butte, Vivek A Rudrapatna","doi":"10.1093/ibd/izae068","DOIUrl":"10.1093/ibd/izae068","url":null,"abstract":"<p><strong>Background: </strong>The Mayo endoscopic subscore (MES) is an important quantitative measure of disease activity in ulcerative colitis. Colonoscopy reports in routine clinical care usually characterize ulcerative colitis disease activity using free text description, limiting their utility for clinical research and quality improvement. We sought to develop algorithms to classify colonoscopy reports according to their MES.</p><p><strong>Methods: </strong>We annotated 500 colonoscopy reports from 2 health systems. We trained and evaluated 4 classes of algorithms. Our primary outcome was accuracy in identifying scorable reports (binary) and assigning an MES (ordinal). Secondary outcomes included learning efficiency, generalizability, and fairness.</p><p><strong>Results: </strong>Automated machine learning models achieved 98% and 97% accuracy on the binary and ordinal prediction tasks, outperforming other models. Binary models trained on the University of California, San Francisco data alone maintained accuracy (96%) on validation data from Zuckerberg San Francisco General. When using 80% of the training data, models remained accurate for the binary task (97% [n = 320]) but lost accuracy on the ordinal task (67% [n = 194]). We found no evidence of bias by gender (P = .65) or area deprivation index (P = .80).</p><p><strong>Conclusions: </strong>We derived a highly accurate pair of models capable of classifying reports by their MES and recognizing when to abstain from prediction. Our models were generalizable on outside institution validation. There was no evidence of algorithmic bias. Our methods have the potential to enable retrospective studies of treatment effectiveness, prospective identification of patients meeting study criteria, and quality improvement efforts in inflammatory bowel diseases.</p>","PeriodicalId":13623,"journal":{"name":"Inflammatory Bowel Diseases","volume":" ","pages":"665-670"},"PeriodicalIF":4.5,"publicationDate":"2025-03-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11879245/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140293462","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Anoop Kumar, Nazim Husain, Arivarasu N Anbazhagan, Dulari Jayawardena, Shubha Priyamvada, Megha Singhal, Charu Jain, Prabhdeep Kaur, Grace Guzman, Seema Saksena, Pradeep K Dudeja
{"title":"Dexamethasone Upregulates the Expression of the Human SLC26A3 (DRA, Down-Regulated in Adenoma) Transporter (an IBD Susceptibility Gene) in Intestinal Epithelial Cells and Attenuates Gut Inflammation.","authors":"Anoop Kumar, Nazim Husain, Arivarasu N Anbazhagan, Dulari Jayawardena, Shubha Priyamvada, Megha Singhal, Charu Jain, Prabhdeep Kaur, Grace Guzman, Seema Saksena, Pradeep K Dudeja","doi":"10.1093/ibd/izae271","DOIUrl":"10.1093/ibd/izae271","url":null,"abstract":"<p><strong>Background: </strong>Down-Regulated in Adenoma (DRA) plays a critical role in intestinal chloride absorption and a decrease in its expression is a key event in diarrheal disorders. Recently, DRA has emerged as an Inflammatory Bowel Disease (IBD) susceptibility gene. Therefore, the strategies to upregulate DRA expression are potentially novel approaches to not only treat IBD-associated diarrhea but also gut inflammation. In this study, the effect of dexamethasone (DEX), an anti-inflammatory corticosteroid on DRA expression was investigated.</p><p><strong>Methods: </strong>GR (glucocorticoid receptor) overexpressed Caco-2 cells and C57BL/6/J mice and anti-αIL-10R mAb model of IBD were used. Protein expression was assessed by immunoblotting and immunofluorescence. Transcript levels were assessed by quantative-real-time polymerase chain reaction (qRT-PCR) and promoter activity was measured by luciferase assays.</p><p><strong>Results: </strong>Our results showed that DEX significantly increased DRA mRNA and protein expression in GR overexpressing Caco-2 cells. DEX-induced upregulation of DRA was GR dependent and appeared at least in part to occur via a transcriptional mechanism, as promoter activity of the DRA construct (-1183/+114 bp) was significantly increased in response to DEX. The increase in DRA mRNA was abrogated in the presence of MKP-1 inhibitor, triptolide. Administration of DEX (2 mg/kg body weight) to mice for 24 and 48 hours significantly increased the DRA expression in mouse colon. DEX treatment to mice for 7 days in the αIL-10R mAb model of colitis was able to significantly attenuate the gut inflammation and associated decrease in DRA expression.</p><p><strong>Conclusions: </strong>We demonstrate that DEX stimulates DRA expression via transcriptional mechanisms and suggest that upregulation of DRA may contribute to both anti-inflammatory and pro-absorptive effects of DEX.</p>","PeriodicalId":13623,"journal":{"name":"Inflammatory Bowel Diseases","volume":" ","pages":"625-635"},"PeriodicalIF":4.5,"publicationDate":"2025-03-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142828444","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}