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Inflammatory Bowel Disease’s Journey: From Metabolism and Immunity to New Therapeutic Horizons

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Pathology, Diagnostics, and Therapeutics".

Deadline for manuscript submissions: 15 June 2024 | Viewed by 2962

Special Issue Editors

Dr. Rocco Spagnuolo

E-Mail Website
Guest Editor
Experimental and Clinical Medicine Department, Magna Graecia University, 88100 Catanzaro, Italy
Interests: inflammatory bowel disease; non alcoholic fatty liver disease; patient reported outcomes; anti-TF-alpha therapy; liver disease; irritable bowel syndrome
Special Issues, Collections and Topics in MDPI journals
Dr. Daniela Pugliese

E-Mail Website
Guest Editor
1. IBD UNIT, CEMAD Centro Malattie dell'Apparato Digerente, Medicina Interna e Gastroenterologia, Fondazione Policlinico Universitario Gemelli IRCCS, Roma, Italy
2. Dipartimento di Medicina e Chirurgia Traslazionale, Università Cattolica del Sacro Cuore, Roma, Italy
Interests: inflammatory bowel disease
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Inflammatory bowel diseases (IBD) encompassing two major forms, Crohn's disease (CD) and ulcerative colitis (UC), are immune-mediated disorders with a complex genetic background and involve constantly changing endogenous and environmental factors.

The comprehension of molecular actors, and the implementation of multi-omics technologies, as well as the pivotal role of the gut microbiome, are compelling the research community to reevaluate the knowledge and molecular processes. As our comprehension of the pathogenic mechanisms of inflammatory bowel disease (IBD) increases, the therapeutic armamentarium for its treatment can expand, and novel target therapies join the treatment pipeline.

In the present Research Topic, we encourage experienced colleagues to submit original research articles, case studies, and review articles regarding molecular and/or metabolic features in order to identify novel biomarkers, and novel diagnostic tools for detection and monitoring, to improve the medical treatment of UC and CD, to manage concomitant extra-intestinal manifestations and to identify novel therapeutics approaches.

Dr. Rocco Spagnuolo
Dr. Daniela Pugliese
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

  • intestinal barrier function
  • gut microbiota
  • inflammation
  • bacterial metabolites
  • immunological pathways
  • biomarkers and predictors
  • nutrients
  • cytokines

Published Papers (4 papers)

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Research

15 pages, 4954 KiB  
Article
Colonic Epithelial Permeability to Ions Is Restored after Vedolizumab Treatment and May Predict Clinical Response in Inflammatory Bowel Disease Patients
by Michele Cicala, Manuele Gori, Paola Balestrieri, Annamaria Altomare, Alessandro Tullio, Simone Di Cola, Sander Dejongh, Maria Giovanna Graziani, Cristiano Pagnini, Simone Carotti, Giuseppe Perrone, Mentore Ribolsi, Marcello Fiorani, Michele P. L. Guarino and Ricard Farré
Int. J. Mol. Sci. 2024, 25(11), 5817; https://doi.org/10.3390/ijms25115817 - 27 May 2024
Viewed by 245
Abstract
Vedolizumab (VDZ) is used for treating inflammatory bowel disease (IBD) patients. A study investigating colonic epithelial barrier function ex vivo following VDZ is lacking. This work aims to evaluate ex vivo the colonic epithelial barrier function in IBD patients at baseline and during [...] Read more.
Vedolizumab (VDZ) is used for treating inflammatory bowel disease (IBD) patients. A study investigating colonic epithelial barrier function ex vivo following VDZ is lacking. This work aims to evaluate ex vivo the colonic epithelial barrier function in IBD patients at baseline and during VDZ treatment, and to investigate the relationships between barrier function and clinical parameters. Colonic specimens were obtained from 23 IBD patients before, and at 24 and 52 weeks after VDZ treatment, and from 26 healthy volunteers (HV). Transepithelial electrical resistance (TEER, permeability to ions) and paracellular permeability were measured in Ussing chambers. IBD patients showed increased epithelial permeability to ions (TEER, 13.80 ± 1.04 Ω × cm2 vs. HV 20.70 ± 1.52 Ω × cm2, p < 0.001) without changes in paracellular permeability of a 4 kDa probe. VDZ increased TEER (18.09 ± 1.44 Ω × cm2, p < 0.001) after 52 weeks. A clinical response was observed in 58% and 25% of patients at week 24, and in 62% and 50% at week 52, in ulcerative colitis and Crohn’s disease, respectively. Clinical and endoscopic scores were strongly associated with TEER. TEER < 14.65 Ω × cm2 predicted response to VDZ (OR 11; CI 2–59). VDZ reduces the increased permeability to ions observed in the colonic epithelium of IBD patients before treatment, in parallel to a clinical, histological (inflammatory infiltrate), and endoscopic improvement. A low TEER predicts clinical response to VDZ therapy. Full article
(This article belongs to the Special Issue Inflammatory Bowel Disease’s Journey: From Metabolism and Immunity to New Therapeutic Horizons)
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15 pages, 1713 KiB  
Article
Gut Microbiota Profile Changes in Patients with Inflammatory Bowel Disease and Non-Alcoholic Fatty Liver Disease: A Metagenomic Study
by Carmen De Caro, Rocco Spagnuolo, Angela Quirino, Elisa Mazza, Federico Carrabetta, Samantha Maurotti, Cristina Cosco, Francesco Bennardo, Roberta Roberti, Emilio Russo, Amerigo Giudice, Arturo Pujia, Patrizia Doldo, Giovanni Matera and Nadia Marascio
Int. J. Mol. Sci. 2024, 25(10), 5453; https://doi.org/10.3390/ijms25105453 - 17 May 2024
Viewed by 450
Abstract
Gut microbiota imbalances have a significant role in the pathogenesis of Inflammatory Bowel Disease (IBD) and Non-Alcoholic Fatty Liver Disease (NAFLD). Herein, we compared gut microbial composition in patients diagnosed with either IBD or NAFLD or a combination of both. Seventy-four participants were [...] Read more.
Gut microbiota imbalances have a significant role in the pathogenesis of Inflammatory Bowel Disease (IBD) and Non-Alcoholic Fatty Liver Disease (NAFLD). Herein, we compared gut microbial composition in patients diagnosed with either IBD or NAFLD or a combination of both. Seventy-four participants were stratified into four groups: IBD-NAFLD, IBD-only, NAFLD-only patients, and healthy controls (CTRLs). The 16S rRNA was sequenced by Next-Generation Sequencing. Bioinformatics and statistical analysis were performed. Bacterial α-diversity showed a significant lower value when the IBD-only group was compared to the other groups and particularly against the IBD-NAFLD group. β-diversity also showed a significant difference among groups. The higher Bacteroidetes/Firmicutes ratio was found only when comparing IBD groups and CTRLs. Comparing the IBD-only group with the IBD-NAFLD group, a decrease in differential abundance of Subdoligranulum, Parabacteroides, and Fusicatenibacter was found. Comparing the NAFLD-only with the IBD-NAFLD groups, there was a higher abundance of Alistipes, Odoribacter, Sutterella, and Lachnospira. An inverse relationship in the comparison between the IBD-only group and the other groups was shown. For the first time, the singularity of the gut microbial composition in IBD and NAFLD patients has been shown, implying a potential microbial signature mainly influenced by gut inflammation. Full article
(This article belongs to the Special Issue Inflammatory Bowel Disease’s Journey: From Metabolism and Immunity to New Therapeutic Horizons)
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21 pages, 4439 KiB  
Article
Modulation of Serotonin-Related Genes by Extracellular Vesicles of the Probiotic Escherichia coli Nissle 1917 in the Interleukin-1β-Induced Inflammation Model of Intestinal Epithelial Cells
by Yenifer Olivo-Martínez, Sergio Martínez-Ruiz, Cecilia Cordero-Alday, Manel Bosch, Josefa Badia and Laura Baldoma
Int. J. Mol. Sci. 2024, 25(10), 5338; https://doi.org/10.3390/ijms25105338 - 14 May 2024
Viewed by 675
Abstract
Inflammatory bowel disease (IBD) is a chronic inflammatory condition involving dysregulated immune responses and imbalances in the gut microbiota in genetically susceptible individuals. Current therapies for IBD often have significant side-effects and limited success, prompting the search for novel therapeutic strategies. Microbiome-based approaches [...] Read more.
Inflammatory bowel disease (IBD) is a chronic inflammatory condition involving dysregulated immune responses and imbalances in the gut microbiota in genetically susceptible individuals. Current therapies for IBD often have significant side-effects and limited success, prompting the search for novel therapeutic strategies. Microbiome-based approaches aim to restore the gut microbiota balance towards anti-inflammatory and mucosa-healing profiles. Extracellular vesicles (EVs) from beneficial gut microbes are emerging as potential postbiotics. Serotonin plays a crucial role in intestinal homeostasis, and its dysregulation is associated with IBD severity. Our study investigated the impact of EVs from the probiotic Nissle 1917 (EcN) and commensal E. coli on intestinal serotonin metabolism under inflammatory conditions using an IL-1β-induced inflammation model in Caco-2 cells. We found strain-specific effects. Specifically, EcN EVs reduced free serotonin levels by upregulating SERT expression through the downregulation of miR-24, miR-200a, TLR4, and NOD1. Additionally, EcN EVs mitigated IL-1β-induced changes in tight junction proteins and oxidative stress markers. These findings underscore the potential of postbiotic interventions as a therapeutic approach for IBD and related pathologies, with EcN EVs exhibiting promise in modulating serotonin metabolism and preserving intestinal barrier integrity. This study is the first to demonstrate the regulation of miR-24 and miR-200a by probiotic-derived EVs. Full article
(This article belongs to the Special Issue Inflammatory Bowel Disease’s Journey: From Metabolism and Immunity to New Therapeutic Horizons)
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18 pages, 6844 KiB  
Article
Intrarectal Administration of Adelmidrol plus Hyaluronic Acid Gel Ameliorates Experimental Colitis in Mice and Inhibits Pro-Inflammatory Response in Ex Vivo Cultured Biopsies Derived from Ulcerative Colitis-Affected Patients
by Irene Palenca, Luisa Seguella, Aurora Zilli, Silvia Basili Franzin, Alessandro Del Re, Federico Pepi, Anna Troiani, Marcella Pesce, Sara Rurgo, Fatima Domenica Elisa De Palma, Gaetano Luglio, Francesca Paola Tropeano, Giovanni Sarnelli and Giuseppe Esposito
Int. J. Mol. Sci. 2024, 25(1), 165; https://doi.org/10.3390/ijms25010165 - 21 Dec 2023
Viewed by 1145
Abstract
Improving clinical outcomes and delaying disease recrudescence in Ulcerative Colitis (UC) patients is crucial for clinicians. In addition to traditional and new pharmacological therapies that utilize biological drugs, the development of medical devices that can ameliorate UC and facilitate the remission phase should [...] Read more.
Improving clinical outcomes and delaying disease recrudescence in Ulcerative Colitis (UC) patients is crucial for clinicians. In addition to traditional and new pharmacological therapies that utilize biological drugs, the development of medical devices that can ameliorate UC and facilitate the remission phase should not be overlooked. Drug-based therapy requires time to be personalized and to evaluate the benefit/risk ratio. However, the increasing number of diagnosed UC cases worldwide necessitates the exploration of new strategies to enhance clinical outcomes. By incorporating medical devices alongside pharmacological treatments, clinicians can provide additional support to UC patients, potentially improving their condition and slowing down the recurrence of symptoms. Chemically identified as an azelaic acid derivative and palmitoylethanolamide (PEA) analog, adelmidrol is a potent anti-inflammatory and antioxidant compound. In this study, we aimed to evaluate the effect of an intrarectal administration of 2% adelmidrol (Ade) and 0.1% hyaluronic acid (HA) gel formulation in both the acute and resolution phase of a mouse model of colitis induced via DNBS enema. We also investigated its activity in cultured human colon biopsies isolated from UC patients in the remission phase at follow-up when exposed in vitro to a cytomix challenge. Simultaneously, with its capacity to effectively alleviate chronic painful inflammatory cystitis when administered intravesically to urological patients such as Vessilen, the intrarectal administration of Ade/HA gel has shown remarkable potential in improving the course of colitis. This treatment approach has demonstrated a reduction in the histological damage score and an increase in the expression of ZO-1 and occludin tight junctions in both in vivo studies and human specimens. By acting independently on endogenous PEA levels and without any noticeable systemic absorption, the effectiveness of Ade/HA gel is reliant on a local antioxidant mechanism that functions as a “barrier effect” in the inflamed gut. Building on the findings of this preliminary study, we are confident that the Ade/HA gel medical device holds promise as a valuable adjunct in supporting traditional anti-UC therapies. Full article
(This article belongs to the Special Issue Inflammatory Bowel Disease’s Journey: From Metabolism and Immunity to New Therapeutic Horizons)
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