The TLR9 Agonist Cobitolimod Induces IL10-Producing Wound Healing Macrophages and Regulatory T Cells in Ulcerative Colitis - Peeref (2024)

Article Pharmacology & Pharmacy

Lactobacillus acidophilus and HKL Suspension Alleviates Ulcerative Colitis in Rats by Regulating Gut Microbiota, Suppressing TLR9, and Promoting Metabolism

Kasimujiang Aximujiang, Kuerbannaimu Kaheman, Xilinguli Wushouer, Guixia Wu, Abulaiti Ahemaiti, Kurexi Yunusi

Summary: The combination therapy of probiotics and traditional Chinese medicine can alleviate inflammation in ulcerative colitis by modulating gut microbiota and metabolites, Toll-like receptors, and cytokines in different pathways.

Article Toxicology

Oxymatrine attenuates TNBS-induced colinutis in rats through TLR9/Myd88/NF-κB signal pathway

Shengwei Li, Guangqing Feng, Min Zhang, Xing Zhang, Jihong Lu, Chenyahui Feng, Fangshi Zhu

Summary: Oxymatrine (OMT) relieves ulcerative colitis by impacting tight junction proteins' TLR9/Myd88/NF-kappa B signal pathways and activity.

Article Gastroenterology & Hepatology

Interferon-Gamma-Producing CD8+ Tissue Resident Memory T Cells Are a Targetable Hallmark of Immune Checkpoint Inhibitor-Colitis

Sarah C. Sasson, Stephanie M. Slevin, Vincent T. F. Cheung, Isar Nassiri, Anna Olsson-Brown, Eve Fryer, Ricardo C. Ferreira, Dominik Trzupek, Tarun Gupta, Lulia Al-Hillawi, Mari-lenna Issaias, Alistair Easton, Leticia Campo, Michael E. B. FitzPatrick, Joss Adams, Meenali Chitnis, Andrew Protheroe, Mark Tuthill, Nicholas Coupe, Alison Simmons, Miranda Payne, Mark R. Middleton, Simon P. L. Travis, Benjamin P. Fairfax, Paul Klenerman, Oliver Brain

Summary: Our study demonstrates that CD8(+) tissue resident memory T (T-RM) cells are the main activated T cell subset in ICI colitis. The pattern of gastrointestinal immunopathology in ICI colitis is distinct from ulcerative colitis at both the immune and epithelial-signaling levels. Activation of CD8+ T-RM cells correlates with clinical and endoscopic severity of ICI colitis.

Review Pharmacology & Pharmacy

Ulcerative Colitis and Acute Severe Ulcerative Colitis Patients Are Overlooked in Infliximab Population Pharmaco*kinetic Models: Results from a Comprehensive Review

Alix Demaris, Ella S. K. Widigson, Johan F. K. F. Ilvemark, Casper Steenholdt, Jakob B. Seidelin, Wilhelm Huisinga, Robin Michelet, Linda B. S. Aulin, Charlotte Kloft

Summary: This review aims to analyze the population PK models of infliximab (IFX) in patients with ulcerative colitis (UC) and acute severe UC (ASUC), and assess the impact of disease activity on IFX PK. The results showed that there are still many gaps in the current research, such as a limited number of models specifically developed for UC patients, a lack of studies on severe UC patients, and a lack of evaluation of predictive performance for the models. Therefore, more comprehensive research and adequate reporting and evaluation of the models are needed for clinical application.

Article Multidisciplinary Sciences

Orange juice containing Pediococcus acidilactici CE51 modulates the intestinal microbiota and reduces induced inflammation in a murine model of colitis

Karolinny Cristiny de Oliveira Vieira, Ana Beatriz Batista da Silva, Suelen Aparecida Felicio, Fabio Santos Lira, Caique de Figueiredo, Eugenia Bezirtzoglou, Valeria Cataneli Pereira, Wilson Romero Nakagaki, Gisele Alborghetti Nai, Lizziane Kretli Winkelstroter

Summary: This study evaluated the effects of probiotic orange juice containing Pediococcus acidilactici CE51 in a mouse model of colitis. The probiotic treatment reduced inflammation and modulated the gut microbiota composition.

Review Gastroenterology & Hepatology

Efficacy of biological therapies and small molecules in moderate to severe ulcerative colitis: systematic review and network meta-analysis

Nicholas E. Burr, David J. Gracie, Christopher J. Black, Alexander C. Ford

Summary: In a network meta-analysis, upadacitinib 45 mg once daily ranked first for clinical remission in all patients, patients naive to anti-TNF-alpha drugs and patients previously exposed. Infliximab 10 mg/kg ranked first for endoscopic improvement. Most drugs were safe and well tolerated.

Article Biochemistry & Molecular Biology

Ginger polysaccharides relieve ulcerative colitis via maintaining intestinal barrier integrity and gut microbiota modulation

Wei Hao, Zhejie Chen, Qin Yuan, Meiling Ma, Caifang Gao, Yangyang Zhou, Hefeng Zhou, Xu Wu, Dingtao Wu, Mohamed A. Farag, Shengpeng Wang, Yitao Wang

Summary: Ginger polysaccharides (GP) have potential in alleviating ulcerative colitis (UC) by inhibiting inflammatory cytokines, repairing intestinal barrier, and regulating gut microbiota.

Article Medicine, Research & Experimental

Long noncoding RNA Gm31629 protects against mucosal damage in experimental colitis via YB-1/E2F pathway

Xu Feng, Ye Xiao, Jian He, Mi Yang, Qi Guo, Tian Su, Yan Huang, Jun Yi, Chang-Jun Li, Xiang-Hang Luo, Xiao-Wei Liu, Hai-Yan Zhou

Summary: A study found that the long noncoding RNA Gm31629 plays a crucial role in inflammatory bowel disease by promoting E2F pathways and cell proliferation, thus facilitating intestinal epithelial regeneration. Deficiency of Gm31629 may lead to worsened intestinal inflammation and delayed epithelial regeneration.

Article Immunology

Protective Effect of Qingchang Wenzhong Decoction on Colitis and Colitis-Related Carcinogenesis by Regulating Inflammation and Intestinal Fibrosis

Yuan Cheng, Junxiang Li, Xiaosi Zhang, Yalan Li, Xiaojun Shi, Rui Shi, Tangyou Mao, Fushun Kou, Lei Shi

Summary: This study explores and verifies the pharmacological mechanisms of Qingchang Wenzhong Decoction (QCWZD) in the treatment of ulcerative colitis (UC) and ulcerative colitis-associated carcinogenesis (UCAC) through microarray analysis, network pharmacology, and biological verification. The results demonstrate that QCWZD may treat UC and UCAC by activating the IL-17, NF-kB, and TLR4 signaling pathways to protect the intestinal mucosal barrier, regulate inflammation, and improve intestinal fibrosis.

Article Medicine, Research & Experimental

Epigenetic DNA methylation of Zbtb7b regulates the population of double-positive CD4+CD8+ T cells in ulcerative colitis

Hao-ming Xu, Jing Xu, Mei-feng Yang, Yu-jie Liang, Quan-zhou Peng, Yuan Zhang, Cheng-mei Tian, Yu-qiang Nie, Li-sheng Wang, Jun Yao, De-feng Li

Summary: Ulcerative colitis (UC) is a heterogeneous disorder with complex pathogenesis. This study aimed to evaluate genome-wide DNA methylation changes associated with the pathogenesis of UC. The results confirmed that Zbtb7b was demethylated in UC tissues and its expression was up-regulated in both UC patients and a colitis model. Over-expression of Zbtb7b activated the maturation of CD4(+)T cells and repressed the differentiation of DP CD4(+)CD8(+)T cells, resulting in the production of inflammatory cytokines in colonic tissue.

Article Gastroenterology & Hepatology

Tofacitinib in Ulcerative Colitis: Real-world Evidence From the ENEIDA Registry

Maria Chaparro, Ana Garre, Francisco Mesonero, Cristina Rodriguez, Manuel Barreiro-de Acosta, Jesus Martinez-Cadilla, Maria T. Arroyo, Noemi Mancenido, Monica Sierra-Ausin, Isabel Vera-Mendoza, Maria Jose Casanova, Pilar Nos, Carlos Gonzalez-Munoza, Teresa Martinez, Maia Bosca-Watts, Margalida Calafat, David Busquets, Eva Girona, Jordina Llao, Maria Dolores Martin-Arranz, Marta Piqueras, Laura Ramos, Gerard Suris, Fernando Bermejo, Ana Y. Carbajo, Diego Casas-Deza, Agnes Fernandez-Clotet, Maria J. Garcia, Daniel Ginard, Ana Gutierrez-Casbas, Luis Hernandez, Alfredo J. Lucendo, Lucia Marquez, Olga Merino-Ochoa, Francisco J. Rancel, Carlos Taxonera, Antonio Lopez Sanroman, Saioa Rubio, Eugeni Domenech, Javier P. Gisbert

Summary: The study findings indicate that tofacitinib is effective and safe in treating active ulcerative colitis. However, a significant proportion of patients discontinue the drug over time, mainly due to primary failure.

Article Surgery

The Impact of Surgeon Speciality Interest on Outcomes of Emergency Laparotomy in IBD

J. A. Bunce, B. Doleman, J. N. Lund, G. M. Tierney

Summary: This study investigated the impact of surgeon subspeciality on outcomes after emergency laparotomy for inflammatory bowel disease (IBD). It found that colorectal surgeons had significantly better outcomes in terms of mortality and length of stay for the least urgent category of IBD emergency laparotomies. However, this association was not seen in more urgent cases.

Review Medicine, Research & Experimental

CXCL8 chemokine in ulcerative colitis

Yunfei Zhu, Shihua Yang, Nan Zhao, Chuanguo Liu, Fayan Zhang, Yuting Guo, Huimin Liu

Summary: Ulcerative colitis is a type of inflammatory bowel disease characterized by diffuse inflammation of the colon and rectum mucosa. The pathogenesis of UC involves dysregulated expression of molecules involved in proinflammatory and anti-inflammatory processes, with the CXCL8-CXCR1/2 axis playing a key role through multiple signaling pathways. Additionally, specific non-coding RNA expression profiles in UC patients may contribute to inflammation development.

Article Biochemistry & Molecular Biology

Titanium Dioxide Presents a Different Profile in Dextran Sodium Sulphate-Induced Experimental Colitis in Mice Lacking the IBD Risk Gene Ptpn2 in Myeloid Cells

Javier Conde, Marlene Schwarzfischer, Egle Katkeviciute, Janine Hafliger, Anna Niechcial, Nathalie Brillant, Roberto Manzini, Katharina Babler, Kirstin Atrott, Silvia Lang, Michael Scharl

Summary: This study investigated the interaction between the food additive TiO2 and the IBD risk gene Ptpn2 in the development of intestinal inflammation. Results showed that TiO2 exacerbated intestinal inflammation in Ptpn2 deficient mice by impacting the differentiation of intestinal macrophages. Furthermore, TiO2 was found to induce the secretion of IL-1 beta and suppress the expression of IL-10 in macrophages through different signaling pathways.

Article Gastroenterology & Hepatology

Interleukin 1β Blockade Reduces Intestinal Inflammation in a Murine Model of Tumor Necrosis Factor-Independent Ulcerative Colitis

Marina Liso, Giulio Verna, Elisabetta Cavalcanti, Stefania De Santis, Raffaele Armentano, Angela Tafaro, Antonio Lippolis, Pietro Campiglia, Antonio Gasbarrini, Mauro Mastronardi, Theresa Torres Pizarro, Fabio Cominelli, Loris Riccardo Lopetuso, Marcello Chieppa

Summary: This study provides new insights and alternative approaches to treat ulcerative colitis (UC) patients. It suggests that anti-interleukin (IL)1 strategies, such as anakinra, may be a more effective therapeutic option for primary nonresponders to anti-tumor necrosis factor (TNF) therapy.

Review Gastroenterology & Hepatology

Is histological healing a feasible endpoint in ulcerative colitis?

Timo Rath, Raja Atreya, Markus F. Neurath

Summary: In ulcerative colitis treatment, achieving histologic healing is becoming increasingly recognized as an important goal, potentially outweighing the significance of clinical remission and mucosal healing. However, consensus definitions and more evidence are needed before histologic healing can be widely accepted as a superior treatment endpoint.

Editorial Material Gastroenterology & Hepatology

Missed lesions and artificial intelligence during colonoscopy: the tireless working expert in the room

Timo Rath

Article Gastroenterology & Hepatology

PICaSSO Histologic Remission Index (PHRI) in ulcerative colitis: development of a novel simplified histological score for monitoring mucosal healing and predicting clinical outcomes and its applicability in an artificial intelligence system

Xianyong Gui, Alina Bazarova, Rocio Del Amor, Michael Vieth, Gert de Hertogh, Vincenzo Villanacci, Davide Zardo, Tommaso Lorenzo Parigi, Elin Synnove Royset, Uday N. Shivaji, Melissa Anna Teresa Monica, Giulio Mandelli, Pradeep Bhandari, Silvio Danese, Jose G. Ferraz, Bu'Hussain Hayee, Mark Lazarev, Adolfo Parra-Blanco, Luca Pastorelli, Remo Panaccione, Timo Rath, Gian Eugenio Tontini, Ralf Kiesslich, Raf Bisschops, Enrico Grisan, Valery Naranjo, Subrata Ghosh, Marietta Iacucci

Summary: Histological remission is emerging as a key treatment target in UC, and the development of a simple histological index PHRI showed high correlation with endoscopic activity and clinical outcomes. A deep learning AI system based on PHRI accurately predicted histological remission and differentiated active from quiescent UC, with promising sensitivity, specificity, and accuracy results.

Article Gastroenterology & Hepatology

The outcome of patients with inflammatory bowel disease-associated colorectal cancer is not worse than that of patients with sporadic colorectal cancer-a matched-pair analysis of survival

Francesco Vitali, Axel Wein, Timo Rath, Markus Eckstein, Clemens Neufert, Juergen Siebler, Raja Atreya, Arndt Hartmann, Werner Hohenberger, Klaus Weber, Markus Friedrich Neurath, Robert Gruetzmann, Susanne Merkel

Summary: Patients with inflammatory bowel disease (IBD) have an increased risk for colorectal cancer (CRC), which requires close monitoring. Despite being younger and more likely to have right-sided carcinomas, IBD patients with CRC showed no significant survival difference compared to matched-pair sporadic CRC patients after curative resection.

Article Gastroenterology & Hepatology

Motorized spiral enteroscopy: results of an international multicenter prospective observational clinical study in patients with normal and altered gastrointestinal anatomy

Torsten Beyna, Tom Moreels, Marianna Arvanitakis, Mathieu Pioche, Jean-Christophe Saurin, Andrea May, Mate Knabe, Jorgen Steen Agnholt, Niels Christian Bjerregaard, Lauri Puustinen, Christoph Schlag, Lars Aabakken, Vemund Paulsen, Markus Schneider, Markus F. Neurath, Timo Rath, Jacques Deviere, Horst Neuhaus

Summary: This study conducted a prospective multicenter study to investigate the safety, efficacy, and learning curve associated with Motorized Spiral Enteroscopy (MSE) in a real-life scenario, including patients with altered anatomy and previous abdominal surgery. The results showed that MSE was feasible and safe after a short learning curve, with no increase in serious adverse event rate even in postsurgical patients.

Article Gastroenterology & Hepatology

Autologous regulatory T-cell transfer in refractory ulcerative colitis with concomitant primary sclerosing cholangitis

Caroline Voskens, Diane Stoica, Marita Rosenberg, Francesco Vitali, Sebastian Zundler, Marion Ganslmayer, Heike Knott, Manuel Wiesinger, Jutta Wunder, Mirko Kummer, Britta Siegmund, Elisabeth Schnoy, Timo Rath, Arndt Hartmann, Holger Hackstein, Beatrice Schuler-Thurner, Carola Berking, Gerold Schuler, Raja Atreya, Markus F. Neurath

Summary: This study reports a successful case of adoptive transfer of ex vivo expanded Tregs in a patient with refractory UC, showing positive responses. These findings suggest that adoptive Treg therapy might be effective in refractory UC.

Letter Ophthalmology

Beneficial Effect of Upadacitinib in an Adult Patient with Juvenile Idiopathic Arthritis-associated Uveitis after Unsatisfactory Response to Tofacitinib: A Case Report

Karoline Baquet-Walscheid, Carsten Heinz, Thomas Rath, Martin Scheel, Arnd Heiligenhaus

Summary: This case suggests that switching JAK-I might be a successful strategy in the treatment of JIAU, despite previously incomplete response to other preparations.

Article Gastroenterology & Hepatology

Endoscopic remission assessed with PICaSSO virtual electronic chromendoscopy accurately predicts clinical outcomes in ulcerative colitis

Olga Maria Nardone, Alina Bazarova, Pradeep Bhandari, Rosanna Cannatelli, Marco Daperno, Jose Ferraz, Martin Goetz, Xianyong Gui, Bu Hayee, Gert De Hertogh, Mark Lazarev, Ji Li, Adolfo Parra-Blanco, Luca Pastorelli, Remo Panaccione, Vincenzo Occhipinti, Timo Rath, Samuel C. L. Smith, Uday N. Shivaji, Gian Eugenio Tontini, Michael Vieth, Vincenzo Villanacci, Davide Zardo, Raf Bisschops, Ralf Kiesslich, Subrata Ghosh, Marietta Iacucci

Summary: This study investigated the importance of combined endoscopic-histologic remission in predicting clinical outcomes in ulcerative colitis patients. The results showed that at 12 months, there was no significant difference in predicting specified clinical outcomes between endoscopic remission alone and combined endoscopic-histologic remission, but UCEIS combined with histology showed a significant advantage. More studies with specific therapeutic interventions are needed to confirm these findings.

Article Oncology

Orchestrating Treatment Modalities in Metastatic Pancreatic Neuroendocrine Tumors-Need for a Conductor

Alexander R. Siebenhuener, Melanie Langheinrich, Juliane Friemel, Niklaus Schafer, Dilmurodjon Eshmuminov, Kuno Lehmann

Summary: This review provides an updated view on treatment options for metastatic pancreatic neuroendocrine tumors (pNETs) and emphasizes the importance of selecting the right timing for surgery in the context of multimodal treatment.

Editorial Material Gastroenterology & Hepatology

Barrett's Esophagus: Today's Mistakes and Tomorrow's Wisdom

Roos E. Pouw, Oliver Pech, Rehan Haidry, Raf Bisschops, Timo Rath, Suzanne Gisbertz

Article Computer Science, Interdisciplinary Applications

Constrained multiple instance learning for ulcerative colitis prediction using histological images

Rocio del Amor, Pablo Meseguer, Tommaso Lorenzo Parigi, Vincenzo Villanacci, Adrian Colomer, Laetitia Launet, Alina Bazarova, Gian Eugenio Tontini, Raf Bisschops, Gert de Hertogh, Jose G. Ferraz, Martin Goetz, Xianyong Gui, Bu'Hussain Hayee, Mark Lazarev, Remo Panaccione, Adolfo Parra-Blanco, Pradeep Bhandari, Luca Pastorelli, Timo Rath, Elin Synnove Royset, Michael Vieth, Davide Zardo, Enrico Grisan, Subrata Ghosh, Marietta Iacucci, Valery Naranjo

Summary: This study developed a novel approach based on multiple instance learning framework to detect ulcerative colitis using whole-slide images. The method introduced constraints and weighted embedding to improve accuracy of identification.

Article Gastroenterology & Hepatology

Endocytoscopy for assessing histologic inflammation in ulcerative colitis: development and prospective validation of the ELECT (ErLangen Endocytoscopy in ColiTis) score (with videos)

Francesco Vitali, Nadine Morgenstern, Markus Eckstein, Raja Atreya, Maximilian Waldner, Arndt Hartmann, Markus F. Neurath, Timo Rath

Summary: This study aimed to evaluate the use of endocytoscopy (EC) to accurately assess histologic inflammation and predict disease progression in ulcerative colitis (UC) patients. The results showed that EC assessment of inflammatory activity in UC was strongly correlated with histopathologic scoring and superior to white-light endoscopy. Therefore, EC can provide real-time histology in UC patients and better predict clinical outcomes.

Article Medicine, General & Internal

NCR, an Inflammation and Nutrition Related Blood-Based Marker in Colon Cancer Patients: A New Promising Biomarker to Predict Outcome

Melanie Langheinrich, Alexander Reinhard Siebenhuener, Justus Baecker, Maximilian Miragall, Felix Wiesmueller, Vera Schellerer, Susanne Merkel, Maximilian Brunner, Christian Krautz, Klaus Weber, Robert Gruetzmann, Stephan Kersting

Summary: This study aimed to evaluate the value of different blood-based markers and assess the significance of a newly developed inflammatory-nutrition-related biomarker (NCR = BMI x albumin/CRP) in colon cancer patients. Lower preoperative NCR levels were associated with worse prognosis, tumor sidedness, undifferentiated histology, nodal involvement, and advanced UICC stage. The NCR proved to be a reliable indicator of poor prognosis for colon cancer patients and could be used for risk stratification and treatment selection.

Article Biochemistry & Molecular Biology

Colon Cancer Microbiome Landscaping: Differences in Right- and Left-Sided Colon Cancer and a Tumor Microbiome-Ileal Microbiome Association

Barbara Kneis, Stefan Wirtz, Klaus Weber, Axel Denz, Matthias Gittler, Carol Geppert, Maximilian Brunner, Christian Krautz, Alexander Reinhard Siebenhuener, Robert Schierwagen, Olaf Tyc, Abbas Agaimy, Robert Gruetzmann, Jonel Trebicka, Stephan Kersting, Melanie Langheinrich

Summary: In the current era of precision oncology, it is recognized that colorectal cancer (CRC) is a heterogeneous disease. The tumor location is crucial in determining disease progression and prognosis. The microbiome has been identified as an important factor in CRC, but previous studies have shown inconsistent results due to the heterogeneous nature of microbiomes and the lack of separate analysis of colon cancer (CC) and rectal cancer (RC). Our prospective study aimed to map the colon cancer landscape using 16S rRNA amplicon sequencing, and we found distinct microbiomes in right- and left-sided colon cancers, as well as a significant increase in potentially pathogenic bacteria in stool samples after surgery.

Article Gastroenterology & Hepatology

Updated S2k guidelines for celiac disease from the German Society for Gastroenterology, Digestive and Metabolic Diseases (DGVS) December 2021-AWMF registration number: 021-021

Jorg Felber, Hendrik Blaker, Wolfgang Fischbach, Sibylle Koletzko, Martin Laass, Nils Lachmann, Pia Lorenz, Petra Lynen, Imke Reese, Katharina Scherf, Detlef Schuppan, Michael Schumann