Article
Multidisciplinary Sciences
Dicky L. Tahapary, Atikah I. Fatya, Farid Kurniawan, Cicilia Marcella, Ikhwan Rinaldi, Tri J. E. Tarigan, Dante S. Harbuwono, Em Yunir, Pradana Soewondo, Dyah Purnamasari
Summary: This study aimed to investigate the association of intestinal permeability, measured by levels of intestinal fatty acid-binding protein (I-FABP), with obesity-related type 2 diabetes mellitus (T2DM) in Indonesia. The results showed that the level of I-FABP was higher in the T2DM group compared to the non-T2DM group, and this association was independent of age. The linear regression model indicated a positive correlation between I-FABP and T2DM.
Article
Nutrition & Dietetics
Noah Joseph Murr, Tyler B. Olender, Margaret R. Smith, Amari S. Smith, Jennifer Pilotos, Lyndsay B. Richard, Chishimba Nathan Mowa, Michael Makokha Opata
Summary: The study revealed that moderately malnourished mice infected with malaria had lower parasite burden at the peak of infection, but showed damaged mucosal epithelial cells, increased intestinal permeability, shortened small intestine, and decreased number of innate immune cells in the large intestine. Despite lower numbers, macrophages in the moderately malnourished mice were highly activated in the small intestine, indicating exacerbation of some abnormalities in the gut induced by the moderate malnutrition.
Article
Immunology
Mia Ogaard Monsted, Nora Dakini Falck, Kristina Pedersen, Karsten Buschard, Laurits Juulskov Holm, Martin Haupt-Jorgensen
Summary: Research on patients with T1D and animal models of T1D indicates a link between increased intestinal permeability and disease development, highlighting the importance of careful selection of research methods and experimental setups.
JOURNAL OF AUTOIMMUNITY
(2021)
Article
Medicine, General & Internal
Olof Karlson, Henrik Arnell, Audur H. Gudjonsdottir, Daniel Agardh, Asa Torinsson Naluai
Summary: This study found significantly lower expression of intestinal gluconeogenesis (IGN) related genes in duodenal biopsies from children with untreated celiac disease, which may be associated with long-term effects on metabolic control and development of NAFLD. Further research is needed to determine whether this decreased expression is a result of intestinal inflammation or impaired metabolic pathways shared with other chronic metabolic diseases. Impaired IGN could potentially explain the increased risk of NAFLD in celiac disease patients.
Editorial Material
Gastroenterology & Hepatology
Saurabh Mehandru, Jean-Frederic Colombel
Summary: Key studies in 2020 highlight that impaired intestinal barrier function precedes the clinical diagnosis of inflammatory bowel disease by years and could serve as a potential therapeutic target in the future.
NATURE REVIEWS GASTROENTEROLOGY & HEPATOLOGY
(2021)
Article
Endocrinology & Metabolism
Matthew Snelson, Cassandra de Pasquale, Elif I. Ekinci, Melinda T. Coughlan
Summary: Changes in gut microbiota in diabetes can lead to decreased intestinal barrier function, affecting systemic inflammation and worsening microvascular diabetes complications. Prebiotics offer a dietary approach to increase beneficial short chain fatty acids produced by gut microbiota and improve intestinal permeability in diabetes.
BEST PRACTICE & RESEARCH CLINICAL ENDOCRINOLOGY & METABOLISM
(2021)
Review
Biochemistry & Molecular Biology
Yonatan Shneor Patt, Adi Lahat, Paula David, Chen Patt, Rowand Eyade, Kassem Sharif
Summary: Celiac disease is a complex immune-mediated disease with various pathological manifestations that extend beyond gastrointestinal symptoms. The existing main treatment, a gluten-free diet, presents challenges and alternative therapies are being developed.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Review
Biochemistry & Molecular Biology
Tasuku Tamai, Kenji Ihara
Summary: Celiac disease is an autoimmune disease caused by gluten ingestion that primarily affects the small intestine. It is prevalent worldwide, but often goes undiagnosed, especially in Asian countries like Japan. This paper provides an overview of the epidemiology, diagnosis, and treatment of celiac disease, as well as summarizing reported Japanese cases.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Letter
Medicine, General & Internal
Claude Matuchansky
Summary: The study reports the preliminary trial of the transglutaminase 2 inhibitor ZED1227 in adults with celiac disease, showing that the drug attenuated gluten-induced duodenal mucosal damage. The authors suggest that their findings support the role of transglutaminase 2 in celiac disease pathogenesis, but do not discuss other possible mechanisms of action of ZED1227.
NEW ENGLAND JOURNAL OF MEDICINE
(2021)
Article
Microbiology
M. Kristina R. Hamilton, Elena Wall, Catherine R. Robinson, Karen Guillemin, Judith R. Eisen
Summary: The enteric nervous system (ENS) plays an important role in regulating intestinal homeostasis, including luminal pH, permeability, and transit. ENS deficiency leads to intestinal inflammation and dysbiosis, independent of microbial induction. Treatment with omeprazole, a proton pump inhibitor, corrects the acidic luminal pH and prevents Vibrio overabundance and inflammation. Conversely, acetazolamide, a carbonic anhydrase inhibitor, increases luminal acidity, leading to increased Vibrio abundance and intestinal inflammation. In conclusion, the primary function of the ENS is to regulate luminal pH, shaping the microbial community and promoting intestinal health.
Review
Endocrinology & Metabolism
Pamela Houeiss, Sandrine Luce, Christian Boitard
Summary: Environmental factors play a significant role in the development of type 1 diabetes. Current prediction is mainly based on autoantibody detection and further research is needed to establish causality between different environmental risk factors and disease development.
FRONTIERS IN ENDOCRINOLOGY
(2022)
Article
Pediatrics
Juan-juan Zhang, Jun-qi Wang, Xu Xu, Li-dan Zhang, Cai-ping Zhang, Wen-li Lu, Wei-qiong Gu, Zhi-ya Dong, Yuan Xiao, Zhen-wei Xia
Summary: This study found a high frequency of celiac disease autoantibodies (CDAbs) in Chinese children with type 1 diabetes (T1D). The expression profile of circRNAs in T1D children with CDAbs was different from that of general T1D patients. Hsa_circ_0004564 and its parental gene RAPH1 may be new targets for studying immune mechanisms in children with T1D and celiac disease (CD).
FRONTIERS IN PEDIATRICS
(2022)
Review
Immunology
Meng Sun, Jingyi Ju, Hongzhen Xu, Yufang Wang
Summary: The human gastrointestinal tract contains trillions of commensal microorganisms, and a possible link between intestinal fungal dysbiosis and antifungal mucosal immunity in inflammatory bowel disease, particularly Crohn's disease, has been suggested. Secretory immunoglobulin A (SIgA) functions as a protective factor for the gut mucosa by preventing bacterial invasion and maintaining a healthy microbiota community. Recent studies have shown the important role of antifungal SIgA antibodies in mucosal immunity, including their regulation of intestinal immunity and binding to hyphae-associated virulence factors. This review summarizes the current knowledge on intestinal fungal dysbiosis and antifungal mucosal immunity in healthy individuals and patients with Crohn's disease, discusses factors governing antifungal SIgA responses in the intestinal mucosa of the latter group, and highlights the potential of antifungal vaccines targeting SIgA to prevent Crohn's disease.
FRONTIERS IN IMMUNOLOGY
(2023)
Article
Computer Science, Interdisciplinary Applications
Oliver Faust, Simona De Michele, Joel E. W. Koh, V Jahmunah, Oh Shu Lih, Aditya P. Kamath, Prabal Datta Barua, Edward J. Ciaccio, Suzanne K. Lewis, Peter H. Green, Govind Bhagat, U. Rajendra Acharya
Summary: This study aimed to utilize AI models to distinguish between normal individuals, individuals with celiac disease (CD), and individuals with non-celiac duodenitis (NCD) based on characteristics of the small intestinal lamina propria. By preprocessing high magnification biopsy images, the study found that AI models can effectively differentiate between different types of intestinal disorders and can potentially be applied in clinical settings.
COMPUTER METHODS AND PROGRAMS IN BIOMEDICINE
(2023)
Article
Pharmacology & Pharmacy
Serena Vitale, Mariantonia Maglio, Stefania Picascia, Ilaria Mottola, Erasmo Miele, Riccardo Troncone, Renata Auricchio, Carmen Gianfrani
Summary: Celiac disease is a chronic intestinal inflammation caused by gluten ingestion in genetically predisposed individuals. Overt-CD and potential-CD are two main forms with varying degrees of intestinal mucosa lesion and clinical management. Patients with overt-CD require a gluten-free diet, while dietary therapy is recommended for potential-CD only in symptomatic subjects.
Article
Immunology
Simone J. C. F. M. Moorlag, Vasiliki Matzaraki, Jelmer H. van Puffelen, Charlotte van der Heijden, Sam Keating, Laszlo Groh, Rutger Jan Roring, Olivier B. Bakker, Valerie A. C. M. Koeken, L. Charlotte J. de Bree, Sanne P. Smeekens, Marije Oosting, Raul Aguirre Gamboa, Niels P. Riksen, Ramnik J. Xavier, Cisca Wijmenga, Vinod Kumar, Reinout van Crevel, Boris Novakovic, Leo A. B. Joosten, Yang Li, Mihai G. Netea
Summary: Innate immune cells can develop memory characteristics through trained immunity. Host factors that affect the intensity of individual trained immunity responses are still largely unknown. This study identified key genes that influence trained immunity responses and highlighted the important roles of metabolic and epigenetic processes in regulating these responses.
EUROPEAN JOURNAL OF IMMUNOLOGY
(2022)
Article
Genetics & Heredity
Esteban A. Lopera-Maya, Alexander Kurilshikov, Adriaan van der Graaf, Shixian Hu, Sergio Andreu-Sanchez, Lianmin Chen, Arnau Vich Vila, Ranko Gacesa, Trishla Sinha, Valerie Collij, Marjiolein A. Y. Klaassen, Laura A. Bolte, Milla F. Brandao Gois, Pieter B. T. Neerincx, Morris A. Swertz, Hermie J. M. Harmsen, Cisca Wijmenga, Jingyuan Fu, Rinse K. Weersma, Alexandra Zhernakova, Serena Sanna
Summary: Host genetics influence the gut microbiome, with the LCT and ABO genes showing significant associations with microbial composition and function. The associations at the LCT locus are modulated by lactose intake, while those at ABO can be explained by participant secretor status determined by their FUT2 genotype. Further loci also show potential associations with microbial taxa and pathways. Larger sample sizes are needed to fully understand the effects of host genetics on the gut microbiome.
Article
Hematology
Astrid G. S. van Halteren, Jessica S. Suwandi, Sander Tuit, Jelske Borst, Sandra Laban, Roula Tsonaka, Ada Struijk, Anna-Sophia Wiekmeijer, Melissa van Pel, Bart O. Roep, Jaap Jan Zwaginga, Arjan C. Lankester, Koen Schepers, Maarten J. D. van Tol, Willem E. Fibbe
Summary: Acute graft-versus-host disease (aGVHD) is a potentially fatal complication of stem cell transplantation. This study used mass cytometry to analyze the immune cells in children with severe aGVHD and compared the results with control groups. The onset of aGVHD was associated with the appearance of specific myeloid and lymphoid cells in the blood and affected organs such as the skin and gastrointestinal tract. The findings highlight the importance of immune cell profiling for evaluating clinical response and managing severe aGVHD.
Article
Multidisciplinary Sciences
Rene O. van Tienhoven, Anh Nguyet Vu, John Kaddis, Bart Roep
Summary: Type 1 diabetes patients carrying a protective insulin gene variant have reduced risk of proliferative diabetic retinopathy (PDR) and diabetic kidney disease (DKD) as long-term complications. The presence of this variant is associated with superior glycemic control and improved beta cell function. Intensive insulin therapy combined with this protective variant further decreases the risk of these complications.
Review
Genetics & Heredity
Victoria E. J. M. Palasantzas, Isabel Tamargo-Rubio, Kieu Le, Jelle Slager, Cisca Wijmenga, Iris H. Jonkers, Vinod Kumar, Jingyuan Fu, Sebo Withoff
Summary: Genome-wide association studies (GWAS) have identified numerous genetic variants associated with complex genetic diseases and drug efficacy. However, functional characterization of these variants is challenging due to the lack of human model systems. Organ-on-a-chip (OoC) platforms, enabled by advances in molecular and nanotechnology, provide personalized platforms for studying the impact of genetics and environment on organ physiology. This review highlights the technology and showcases the potential of OoCs in disease modeling and pharmacogenetic research.
TRENDS IN GENETICS
(2023)
Article
Immunology
Bart O. Roep
Summary: The current standard of care for type 1 diabetes patients focuses on managing symptoms rather than addressing the underlying cause. Understanding the immunological aspects of the disease is crucial in order to develop effective treatments and personalize patient care. Immune monitoring provides valuable insights into disease progression, patient heterogeneity, and therapeutic responses, despite the associated challenges and costs. This perspective highlights the importance of immune monitoring in future trials and patient selection.
FRONTIERS IN IMMUNOLOGY
(2023)
Article
Endocrinology & Metabolism
Sarah C. Shuck, Peter Achenbach, Bart O. Roep, John S. Termini, Carlos Hernandez-Castillo, Christiane Winkler, Andreas Weiss, Anette-Gabriele Ziegler
Summary: The study found that serum levels of MG-AGEs were associated with the rate of progression to stage 3 type 1 diabetes, with lower levels increasing the risk of progression. This provides a potential new clinical biomarker for determining the rate of disease progression and points to contributing metabolic pathways.
FRONTIERS IN ENDOCRINOLOGY
(2023)
Article
Endocrinology & Metabolism
Neslihan Erdem, Kuan-Tsen Chen, Meirigeng Qi, Yuqi Zhao, Xiwei Wu, Isaac Garcia, Hsun Teresa Ku, Enrique Montero, Ismail H. Al-Abdullah, Fouad Kandeel, Bart O. Roep, Jeffrey S. Isenberg
Summary: TSP1 is a secreted protein that is increased in disease and age. It binds to the cell receptor CD47 and creates a checkpoint for immune activation. Human islets express CD47 and secrete TSP1, but lack SIRPa. These findings are important for the use of CD47 and SIRPa blocking molecules in cancer patients.
AMERICAN JOURNAL OF PHYSIOLOGY-ENDOCRINOLOGY AND METABOLISM
(2023)
Article
Endocrinology & Metabolism
Rene van Tienhoven, Maria J. L. Kracht, Arno R. van der Slik, Sofia Thomaidou, Anouk H. G. Wolters, Ben N. G. Giepmans, Juan Pablo Romero Riojas, Michael S. Nelson, Francoise Carlotti, Eelco J. P. de Koning, Rob C. Hoeben, Arnaud Zaldumbide, Bart O. Roep
Summary: Transcriptome analysis identified insulin-gene-derived transcripts in non-beta endocrine islet cells. Researchers studied alternative splicing of human INS mRNA in pancreatic islets and found an alternatively spliced INS product that is expressed in delta cells but not in beta cells. This variant encodes the complete insulin signal peptide and B chain, and its presence in delta cells may play a role in islet autoimmunity and pathology.
Article
Medicine, General & Internal
Tomi Suomi, Inna Starskaia, Ubaid Ullah Kalim, Omid Rasool, Maria K. Jaakkola, Toni Gronroos, Tommi Valikangas, Caroline Brorsson, Gianluca Mazzoni, Sylvaine Bruggraber, Lut Overbergh, David Dunger, Mark Peakman, Piotr Chmura, Seren Brunak, Anke M. Schulte, Chantal Mathieu, Mikael Knip, Riitta Lahesmaa, Laura L. Elo
Summary: This study aimed to identify transcriptional changes associated with disease progression in patients with recent-onset type 1 diabetes. They found that genes and pathways related to innate immunity were downregulated during the first year after diagnosis. Associations between gene expression changes and ZnT8A autoantibody positivity were also observed. Additionally, changes in the expression of 16 genes were found to predict the decline in C-peptide at 24 months, and increased B cell levels and decreased neutrophil levels were associated with rapid progression, consistent with previous reports.
Review
Health Care Sciences & Services
Yuxin Teng, Amrit Sandhu, Edith J. J. Liemburg, Elnaz Naderi, Behrooz Z. Z. Alizadeh
Summary: This study reports the evidence for associations between pharmacogenetic variants and antipsychotics outcomes in patients with schizophrenia spectrum disorders. The findings suggest potential effects of certain genetic variants on antipsychotic response, weight gain, metabolic syndrome, prolactin levels, tardive dyskinesia, agranulocytosis, and drug concentration levels. However, further well-designed studies are needed to validate these findings.
JOURNAL OF PERSONALIZED MEDICINE
(2023)
Article
Health Care Sciences & Services
Tesfa Dejenie Habtewold, Jiasi Hao, Edith J. Liemburg, Nalan Basturk, Richard Bruggeman, Behrooz Z. Alizadeh
Summary: Heterogeneity poses a major challenge in the traditional classification of mental disorders, including schizophrenia spectrum disorders (SSD), due to the lack of objective diagnostic criteria. This article presents findings from the GROUP cohort study on the deep clinical phenotyping of SSD, focusing on positive and negative symptoms, cognitive impairments, and psychosocial functioning. Several latent subtypes of symptoms and cognitive impairments were identified in patients, siblings, and controls, while subtypes of psychosocial function were identified in patients. These findings are valuable for identifying high-risk groups and informing intervention selection in precision psychiatry.
JOURNAL OF PERSONALIZED MEDICINE
(2023)
Article
Health Care Sciences & Services
Amrit K. Sandhu, Elnaz Naderi, Morenika J. Wijninga, Edith J. Liemburg, Danielle Cath, Richard Bruggeman, Behrooz Z. Alizadeh
Summary: This study aimed to investigate the association between genetic variation and long-term clinical outcomes in patients with schizophrenia spectrum disorders. The study found no association between PGx polygenic risk scores and clinical outcomes, but did find an association with CYP2D6 activity scores. These findings highlight the need to test PGx efficacy with different symptom domains.
JOURNAL OF PERSONALIZED MEDICINE
(2023)
Meeting Abstract
Gastroenterology & Hepatology
Shixian Hu, J. Casper Swarte, Yanni Li, Johannes Bjork, Ranko Gacesa, Arnau Vich Vila, Rianne Douwes, Valerie Collij, Alexander Kurilshikov, Aadrian Post, Marjolein A. Y. Klaassen, Michele F. Eisenga, Antonio W. Gomes-Neto, Daan Kremer, Bernadien H. Jansen, Tim J. Knobbe, Stefan P. Berger, Jan-Stephan F. Sanders, M. Rebecca Heiner-Fokkema, Robert J. Porte, Frans J. C. Cuperus, Vincent E. Demeijer, Cisca Wijmenga, Eleonora A. M. Festen, Alexandra Zhernakova, Jingyuan Fu, Hermie J. M. Harmsen, Hans Blokzijl, Stephan J. L. Bakker, Rinse Weersma
JOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY
(2023)
