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Molecular Mechanisms of Gastrointestinal Immune System and Its Role in Gut Homeostasis and Pathologies

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Immunology".

Deadline for manuscript submissions: closed (31 August 2024) | Viewed by 24921

Special Issue Editors

Dr. Jose E. Mesonero

E-Mail Website
Guest Editor
Instituto de Investigacion Sanitaria de Aragon (IIS Aragon), 50009 Zaragoza, Spain
Interests: gastroenterology; gastrointestinal disorders; endocrinology; intestinal transport; PRRs; serotonin
Special Issues, Collections and Topics in MDPI journals
Dr. Eva Latorre

E-Mail Website
Guest Editor
Instituto de Investigacion Sanitaria de Aragon (IIS Aragon), 50009 Zaragoza, Spain
Interests: microbiota; PRRs; gut–brain axis; innate immunity
Special Issues, Collections and Topics in MDPI journals
Dr. Elena Layunta

E-Mail Website
Guest Editor
Department of Medical Biochemistry and Cell Biology, Institute of Biomedicine, University of Gothenburg, Medicinaregatan 9C, 41390 Gothenburg, Sweden
Interests: intestinal defenses; mucins; microbiota; intestinal development; gut–brain axis; PRRs; serotonin

Special Issue Information

Dear Colleagues,

Gastrointestinal homeostasis requires stringent regulation of immune responses against various environmental conditions, dietary antigens, commensal bacteria, and pathogens. Yet, homeostasis can be disrupted due to either failure or defects in the immunological mechanisms, or because the disrupting agents are new or excessive, a pathology is established. In this sense, the incidence of gastrointestinal diseases has increased dramatically, leading to an increase in the morbidity and mortality rate worldwide. Over the last decade, the immune responses in the gut have been extensively described and defined as a critical key to maintain the homeostasis in the gastrointestinal tract. However, the involvement of the immune response in gastrointestinal pathologies remains unexplored, representing the next challenge for the scientific community.

The aim of this Special Issue is to cover different gastrointestinal diseases focusing on recent improvements in the immunological aspects of the gastrointestinal tract. Furthermore, the innate immunity of the gut, the pathophysiology features of gastrointestinal diseases, and novel immunotherapies are reviewed also in this Special Issue. We welcome research or review articles focusing on these topics.

Dr. Jose E. Mesonero
Dr. Eva Latorre
Dr. Elena Layunta
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. International Journal of Molecular Sciences is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. There is an Article Processing Charge (APC) for publication in this open access journal. For details about the APC please see here. Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • gastrointestinal immune system
  • inflammation
  • intestinal infections
  • host–microbe interactions
  • pattern recognition receptors
  • gut microbiota
  • gut dysbiosis
  • IgA
  • inflammatory bowel disease
  • inflammatory bowel syndrome
  • coeliac disease
  • colorectal cancer
  • food allergy

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Published Papers (6 papers)

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Editorial

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4 pages, 183 KiB  
Editorial
Guardians at the Gate: Immune System in Gastrointestinal Diseases
by Elena Layunta, Jose Emilio Mesonero and Eva Latorre
Int. J. Mol. Sci. 2024, 25(11), 5933; https://doi.org/10.3390/ijms25115933 - 29 May 2024
Viewed by 1267
Abstract
The immune system plays a key role in gastrointestinal (GI) pathologies, being responsible for protecting the body against infection, maintaining homeostasis, and regulating the inflammatory response in the GI tract [...] Full article
(This article belongs to the Special Issue Molecular Mechanisms of Gastrointestinal Immune System and Its Role in Gut Homeostasis and Pathologies)

Research

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14 pages, 7088 KiB  
Communication
The Relationships between Intestinal Permeability and Target Antibodies for a Spectrum of Autoimmune Diseases
by Datis Kharrazian, Martha Herbert and Jama Lambert
Int. J. Mol. Sci. 2023, 24(22), 16352; https://doi.org/10.3390/ijms242216352 - 15 Nov 2023
Cited by 5 | Viewed by 12765
Abstract
The worldwide prevalence of autoimmune diseases that have limited treatment options and preventive strategies is rapidly rising. There is growing evidence that the microbiota and the integrity of the intestinal barrier play a role in autoimmune diseases. The potential to evaluate intestinal barrier [...] Read more.
The worldwide prevalence of autoimmune diseases that have limited treatment options and preventive strategies is rapidly rising. There is growing evidence that the microbiota and the integrity of the intestinal barrier play a role in autoimmune diseases. The potential to evaluate intestinal barrier integrity for susceptible individuals and to determine whether restoring intestinal junction integrity impacts autoimmune diseases is an important area of research that requires further attention. In the intestinal permeability model of autoimmune diseases, the breakdown of the intestinal tight junction proteins (zonulin/occludin) allows bacteria, toxins, undigested dietary proteins, and other antigens to pass into the lumen, thereby increasing the number of inflammatory reactions and the activation of immune cells throughout the body. In this study, we investigate the relationship between zonulin/occludin antibodies, which are used to determine intestinal permeability, with autoantibodies used to diagnose autoimmunity. Our investigation may identify significant levels of circulating autoantibodies in human subjects with intestinal permeability compared to those without intestinal permeability. Furthermore, we identified that significant positive linear correlations between serum occludin/zonulin antibodies and circulating autoantibodies could be used to determine autoimmune diseases. Full article
(This article belongs to the Special Issue Molecular Mechanisms of Gastrointestinal Immune System and Its Role in Gut Homeostasis and Pathologies)
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16 pages, 3669 KiB  
Article
Route of Arsenic Exposure Differentially Impacts the Expression of Genes Involved in Gut-Mucosa-Associated Immune Responses and Gastrointestinal Permeability
by Kuppan Gokulan, Aakriti Mathur, Amit Kumar, Michelle M. Vanlandingham and Sangeeta Khare
Int. J. Mol. Sci. 2023, 24(7), 6352; https://doi.org/10.3390/ijms24076352 - 28 Mar 2023
Cited by 4 | Viewed by 1773
Abstract
First-pass metabolism alters arsenic biotransformation and its immunomodulatory activities. This study aims to determine the mRNA expression of intestinal-immunity- and permeability-associated genes, levels of cytokine/chemokines and levels of immunoglobulin isotypes when CD-1 mice were exposed to a single dose of intravenous (IV) sodium [...] Read more.
First-pass metabolism alters arsenic biotransformation and its immunomodulatory activities. This study aims to determine the mRNA expression of intestinal-immunity- and permeability-associated genes, levels of cytokine/chemokines and levels of immunoglobulin isotypes when CD-1 mice were exposed to a single dose of intravenous (IV) sodium arsenite (50 µg/kg body weight (BW)) and to compare these responses to exposure via oral gavage (OG) (50 µg/kg BW). Samples were collected at 1, 4, 24 and 48 h post IV exposure and 24 and 48 h post OG. Sodium arsenite IV exposure led to a transient modulation of mRNA expression and protein levels of immunity-related genes involved in inflammation/apoptotic pathways and production of cytokines/chemokines, whereas it also led to downregulated expression of genes encoding tight junction, focal adhesion, and gap junction proteins, which are responsible for maintaining cell permeability. Oral exposure perturbed fewer cell-permeability-related genes at 24 and 48 h post exposure. At 24 h post exposure, OG decreased IgA and IgG2b levels; however, IV exposure significantly increased IgG2b, IgG3 and IgA in ileal tissue. Earlier, we showed significant downregulation of mRNA expression of genes involved in the immune-related pathways during OG in the intestinal mucosa of the same animals. Cumulatively, these results provide evidence that the exposure route of a xenobiotic can differentially impact the intestinal responses due to the impact of first-pass metabolism. Full article
(This article belongs to the Special Issue Molecular Mechanisms of Gastrointestinal Immune System and Its Role in Gut Homeostasis and Pathologies)
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Review

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17 pages, 742 KiB  
Review
Systematic Review: Urine Biomarker Discovery for Inflammatory Bowel Disease Diagnosis
by Montse Baldan-Martin, María Chaparro and Javier P. Gisbert
Int. J. Mol. Sci. 2023, 24(12), 10159; https://doi.org/10.3390/ijms241210159 - 15 Jun 2023
Cited by 7 | Viewed by 3164
Abstract
Inflammatory bowel diseases (IBDs) are chronic, heterogeneous, and inflammatory conditions mainly affecting the gastrointestinal tract. Currently, endoscopy is the gold standard test for assessing mucosal activity and healing in clinical practice; however, it is a costly, time-consuming, invasive, and uncomfortable procedure for the [...] Read more.
Inflammatory bowel diseases (IBDs) are chronic, heterogeneous, and inflammatory conditions mainly affecting the gastrointestinal tract. Currently, endoscopy is the gold standard test for assessing mucosal activity and healing in clinical practice; however, it is a costly, time-consuming, invasive, and uncomfortable procedure for the patients. Therefore, there is an urgent need for sensitive, specific, fast and non-invasive biomarkers for the diagnosis of IBD in medical research. Urine is an excellent biofluid for discovering biomarkers because it is non-invasive to sample. In this review, we aimed to summarize proteomics and metabolomics studies performed in both animal models of IBD and humans that identify urinary biomarkers for IBD diagnosis. Future large-scale multi-omics studies should be conducted in collaboration with clinicians, researchers, and industry to make progress toward the development of sensitive and specific diagnostic biomarkers, thereby making personalized medicine possible. Full article
(This article belongs to the Special Issue Molecular Mechanisms of Gastrointestinal Immune System and Its Role in Gut Homeostasis and Pathologies)
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12 pages, 1708 KiB  
Review
Do Colonic Mucosal Tumor Necrosis Factor Alpha Levels Play a Role in Diverticular Disease? A Systematic Review and Meta-Analysis
by Cristina Maria Sabo, Mohamed Ismaiel, Abdulrahman Ismaiel, Daniel-Corneliu Leucuta, Stefan-Lucian Popa, Simona Grad and Dan L. Dumitrascu
Int. J. Mol. Sci. 2023, 24(12), 9934; https://doi.org/10.3390/ijms24129934 - 9 Jun 2023
Cited by 6 | Viewed by 1696
Abstract
Diverticular disease (DD) is the most frequent condition in the Western world that affects the colon. Although chronic mild inflammatory processes have recently been proposed as a central factor in DD, limited information is currently available regarding the role of inflammatory cytokines, such [...] Read more.
Diverticular disease (DD) is the most frequent condition in the Western world that affects the colon. Although chronic mild inflammatory processes have recently been proposed as a central factor in DD, limited information is currently available regarding the role of inflammatory cytokines, such as tumor necrosis factor-alpha (TNF-α). Therefore, we conducted a systematic review and meta-analysis aiming to assess the mucosal TNF-α levels in DD. We conducted a systematic literature search using PubMed, Embase, and Scopus to identify observational studies assessing the TNF-α levels in DD. Full-text articles that satisfied our inclusion and exclusion criteria were included, and a quality assessment was performed using the Newcastle–Ottawa Scale (NOS). The principal summary outcome was the mean difference (MD). The results were reported as MD (95% confidence interval (CI)). A total of 12 articles involving 883 subjects were included in the qualitative synthesis, out of which 6 studies were included in our quantitative synthesis. We did not observe statistical significance related to the mucosal TNF-α levels in symptomatic uncomplicated diverticular disease (SUDD) vs. the controls (0.517 (95% CI −1.148–2.182)), and symptomatic vs. asymptomatic DD patients (0.657 (95% CI −0.883–2.196)). However, the TNF-α levels were found to be significantly increased in DD compared to irritable bowel disease (IBS) patients (27.368 (95% CI 23.744–30.992)), and segmental colitis associated with diverticulosis (SCAD) vs. IBS patients (25.303 (95% CI 19.823–30.784)). Between SUDD and the controls, as well as symptomatic and asymptomatic DD, there were no significant differences in the mucosal TNF-α levels. However, the TNF-α levels were considerably higher in DD and SCAD patients than IBS patients. Our findings suggest that TNF-α may play a key role in the pathogenesis of DD in specific subgroups and could potentially be a target for future therapies. Full article
(This article belongs to the Special Issue Molecular Mechanisms of Gastrointestinal Immune System and Its Role in Gut Homeostasis and Pathologies)
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20 pages, 2240 KiB  
Review
Dimethyl Fumarate and Intestine: From Main Suspect to Potential Ally against Gut Disorders
by Federico Manai, Lisa Zanoletti, Davide Arfini, Simone Giorgio De Micco, Arolda Gjyzeli, Sergio Comincini and Marialaura Amadio
Int. J. Mol. Sci. 2023, 24(12), 9912; https://doi.org/10.3390/ijms24129912 - 8 Jun 2023
Cited by 6 | Viewed by 2913
Abstract
Dimethyl fumarate (DMF) is a well-characterized molecule that exhibits immuno-modulatory, anti-inflammatory, and antioxidant properties and that is currently approved for the treatment of psoriasis and multiple sclerosis. Due to its Nrf2-dependent and independent mechanisms of action, DMF has a therapeutic potential much broader [...] Read more.
Dimethyl fumarate (DMF) is a well-characterized molecule that exhibits immuno-modulatory, anti-inflammatory, and antioxidant properties and that is currently approved for the treatment of psoriasis and multiple sclerosis. Due to its Nrf2-dependent and independent mechanisms of action, DMF has a therapeutic potential much broader than expected. In this comprehensive review, we discuss the state-of-the-art and future perspectives regarding the potential repurposing of DMF in the context of chronic inflammatory diseases of the intestine, such as inflammatory bowel disorders (i.e., Crohn’s disease and ulcerative colitis) and celiac disease. DMF’s mechanisms of action, as well as an exhaustive analysis of the in vitro/in vivo evidence of its beneficial effects on the intestine and the gut microbiota, together with observational studies on multiple sclerosis patients, are here reported. Based on the collected evidence, we highlight the new potential applications of this molecule in the context of inflammatory and immune-mediated intestinal diseases. Full article
(This article belongs to the Special Issue Molecular Mechanisms of Gastrointestinal Immune System and Its Role in Gut Homeostasis and Pathologies)
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