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Precision Medicine in Inflammatory Bowel Diseases: Epigenetics, Gut Microbiome, Sex Differences and Beyond

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

Deadline for manuscript submissions: closed (10 April 2023) | Viewed by 10434

Special Issue Editor

Dr. Alessandra Soriano

E-Mail Website
Guest Editor
1. Department of Pathology, Case Western Reserve University, Cleveland, OH 44106-1712, USA
2. IBD Center, Gastroenterology Division, Department of Internal Medicine, Arcispedale S. Maria Nuova – IRCCS, 42121 Reggio Emilia, Italy
Interests: gastro-intestinal pathology; inflammatory bowel diseases; chronic inflammation; autoimmunity; innate immunity; gut microbiome; gender medicine; sex differences; epigenetics; epigenomics; precision medicine
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Inflammatory bowel diseases (IBD) constitute a spectrum of multifactorial chronic inflammatory and immune-mediated gastrointestinal disorders, mainly represented by Crohn’s disease and ulcerative colitis, whose etiopathogenesis remains unknown. The interplay between host genome, epigenetics, mucosal and systemic immunity, and gut microbiome in the pathogenesis of IBD is a matter of deep interest, both at basic and translational research level. The gut microbiome is able to shape both the intestinal and the systemic immune response. Inappropriate mucosal immunity/gut microbiome interaction can become detrimental and play a central role in driving the development and/or the worsening of IBD. Evidence in both preclinical and clinical models also suggests a gut microbiome contribution to sex-based differences in IBD. Additionally, in recent years, carcinogenesis pathways related to chronic inflammation as targets of epigenetic modification—and their plausible correlation with IBD pathogenesis—have become clear. Studies using candidate gene strategies have described new differentially methylated genes mostly involved in innate immunity, while epigenome-wide association studies (EWAS) have shown how methylation profiles might contribute to a better characterization of IBD phenotypes.

In an era moving toward precision medicine, a personalized and sex-based approach to treat IBD patients is strongly warranted. This Special Issue aims to discuss state-of-the art research on the human gut microbiome’s role in the pathogenesis of IBD, and also as a potential contributor to sexual dimorphism in IBD. We will include epigenetics studies, such as those focused on circulating IBD methylome, as well as studies analyzing other ‘omics’ data (i.e., transcriptomics, metabolomics, proteomics).

Dr. Alessandra Soriano
Guest Editor

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

  • Inflammatory bowel diseases (IBD)
  • Crohn’s disease
  • Ulcerative colitis
  • Microbiome
  • Sex differences
  • Precision medicine
  • Epigenetics
  • DNA methylation
  • Epigenomics
  • Transcriptomics
  • Single-cell RNA sequencing

Published Papers (4 papers)

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Research

13 pages, 1153 KiB  
Article
Proof-of-Concept Human Organ-on-Chip Study: First Step of Platform to Assess Neuro-Immunological Communication Involved in Inflammatory Bowel Diseases
by Tristan Gabriel-Segard, Jessica Rontard, Louise Miny, Louise Dubuisson, Aurélie Batut, Delphine Debis, Mélanie Gleyzes, Fabien François, Florian Larramendy, Alessandra Soriano, Thibault Honegger and Stéphane Paul
Int. J. Mol. Sci. 2023, 24(13), 10568; https://doi.org/10.3390/ijms241310568 - 24 Jun 2023
Cited by 4 | Viewed by 1545
Abstract
Inflammatory bowel diseases (IBD) are complex chronic inflammatory disorders of the gastrointestinal (GI) tract. Recent evidence suggests that the gut-brain axis may be pivotal in gastrointestinal and neurological diseases, especially IBD. Here, we present the first proof of concept for a microfluidic technology [...] Read more.
Inflammatory bowel diseases (IBD) are complex chronic inflammatory disorders of the gastrointestinal (GI) tract. Recent evidence suggests that the gut-brain axis may be pivotal in gastrointestinal and neurological diseases, especially IBD. Here, we present the first proof of concept for a microfluidic technology to model bilateral neuro-immunological communication. We designed a device composed of three compartments with an asymmetric channel that allows the isolation of soma and neurites thanks to microchannels and creates an in vitro synaptic compartment. Human-induced pluripotent stem cell-derived cortical glutamatergic neurons were maintained in soma compartments for up to 21 days. We performed a localized addition of dendritic cells (MoDCs) to either the soma or synaptic compartment. The microfluidic device was coupled with microelectrode arrays (MEAs) to assess the impact on the electrophysiological activity of neurons while adding dendritic cells. Our data highlight that an electrophysiologic signal is transmitted between two compartments of glutamatergic neurons linked by synapses in a bottom-up way when soma is exposed to primed dendritic cells. In conclusion, our study authenticates communication between dendritic cells and neurons in inflammatory conditions such as IBD. This platform opens the way to complexification with gut components to reach a device for pharmacological compound screening by blocking the gut-brain axis at a mucosal level and may help patients. Full article
(This article belongs to the Special Issue Precision Medicine in Inflammatory Bowel Diseases: Epigenetics, Gut Microbiome, Sex Differences and Beyond)
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24 pages, 25226 KiB  
Article
Weighted Gene Co-Expression Network Analysis Identifies a Functional Guild and Metabolite Cluster Mediating the Relationship between Mucosal Inflammation and Adherence to the Mediterranean Diet in Ulcerative Colitis
by Jaclyn C. Strauss, Natasha Haskey, Hena R. Ramay, Tarini Shankar Ghosh, Lorian M. Taylor, Munazza Yousuf, Christina Ohland, Kathy D. McCoy, Richard J. M. Ingram, Subrata Ghosh, Remo Panaccione and Maitreyi Raman
Int. J. Mol. Sci. 2023, 24(8), 7323; https://doi.org/10.3390/ijms24087323 - 15 Apr 2023
Cited by 3 | Viewed by 2379
Abstract
Diet influences the pathogenesis and clinical course of inflammatory bowel disease (IBD). The Mediterranean diet (MD) is linked to reductions in inflammatory biomarkers and alterations in microbial taxa and metabolites associated with health. We aimed to identify features of the gut microbiome that [...] Read more.
Diet influences the pathogenesis and clinical course of inflammatory bowel disease (IBD). The Mediterranean diet (MD) is linked to reductions in inflammatory biomarkers and alterations in microbial taxa and metabolites associated with health. We aimed to identify features of the gut microbiome that mediate the relationship between the MD and fecal calprotectin (FCP) in ulcerative colitis (UC). Weighted gene co-expression network analysis (WGCNA) was used to identify modules of co-abundant microbial taxa and metabolites correlated with the MD and FCP. The features considered were gut microbial taxa, serum metabolites, dietary components, short-chain fatty acid and bile acid profiles in participants that experienced an increase (n = 13) or decrease in FCP (n = 16) over eight weeks. WGCNA revealed ten modules containing sixteen key features that acted as key mediators between the MD and FCP. Three taxa (Faecalibacterium prausnitzii, Dorea longicatena, Roseburia inulinivorans) and a cluster of four metabolites (benzyl alcohol, 3-hydroxyphenylacetate, 3-4-hydroxyphenylacetate and phenylacetate) demonstrated a strong mediating effect (ACME: −1.23, p = 0.004). This study identified a novel association between diet, inflammation and the gut microbiome, providing new insights into the underlying mechanisms of how a MD may influence IBD. See clinicaltrials.gov (NCT04474561). Full article
(This article belongs to the Special Issue Precision Medicine in Inflammatory Bowel Diseases: Epigenetics, Gut Microbiome, Sex Differences and Beyond)
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12 pages, 834 KiB  
Article
Validation Study of a New Random-Access Chemiluminescence Immunoassay Analyzer i-TRACK10® to Monitor Infliximab and Adalimumab Serum trough Levels and Anti-Drug Antibodies
by Anne Emmanuelle Berger, Aude Gleizes, Louis Waeckel, Xavier Roblin, Roman Krzysiek, Salima Hacein-Bey-Abina, Alessandra Soriano and Stephane Paul
Int. J. Mol. Sci. 2022, 23(17), 9561; https://doi.org/10.3390/ijms23179561 - 24 Aug 2022
Cited by 5 | Viewed by 1729
Abstract
Background. Monitoring of biological TNF inhibitors is a very important tool to guide clinical decisions using specialized algorithms, especially in gastroenterology. A new chemiluminescent instrument (i-TRACK10® from Theradiag) could replace ELISA techniques to calculate the dosage of drugs and anti-drug antibodies. [...] Read more.
Background. Monitoring of biological TNF inhibitors is a very important tool to guide clinical decisions using specialized algorithms, especially in gastroenterology. A new chemiluminescent instrument (i-TRACK10® from Theradiag) could replace ELISA techniques to calculate the dosage of drugs and anti-drug antibodies. In this bi-centric study, we explored the analytical performances of i-TRACK10® using manual or automated (DS2®) ELISA Lisa-Tracker® assays, and compared the results. Patients and methods. Intra- and inter-run performances were evaluated with i-TRACK10® in two different laboratories and for two different ranges of values for infliximab, adalimumab, and their respective antibodies. Patients’ samples were used in the labs to compare the results obtained between the new instrument and either the manual Lisa-Tracker® or the automated DS2. Results. Intra- and inter-run performances were satisfactory, with values between 1.8% and 16.1% (for inter-run imprecision at low/medium values of infliximab). Results were generally comparable between assays. with the lowest value of correlation at 0.59 (anti-adalimumab dosage between i-TRACK10® and manual ELISA). Most often, values of drugs and anti-drug antibodies were higher with i-TRACK10® than with manual ELISA assay, and correlation values were better with automated ELISA. Agreements were globally acceptable, and the lowest coefficients of 0.7 was obtained for adalimumab values between i-TRACK10® and the two ELISA methods, and for anti-adalimumab values between i-TRACK10® and manual ELISA. The type of assay can potentially induce a change in the class of patients and lead to divergent therapeutic decisions. Conclusions. The new random-access instrument i-TRACK10® presents many advantages in a routine laboratory: rapidity, the possibility of standardization, usability, and expansion of the measurement range. Despite the relatively good agreement of results, it is preferable to use the same assay in longitudinal follow-up of a patient, because quantitative results were not completely equivalent especially for anti-drug antibodies. Full article
(This article belongs to the Special Issue Precision Medicine in Inflammatory Bowel Diseases: Epigenetics, Gut Microbiome, Sex Differences and Beyond)
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25 pages, 5746 KiB  
Article
Dietary Interventions Ameliorate Infectious Colitis by Restoring the Microbiome and Promoting Stem Cell Proliferation in Mice
by Ishfaq Ahmed, Kafayat Yusuf, Badal C. Roy, Jason Stubbs, Shrikant Anant, Thomas M. Attard, Venkatesh Sampath and Shahid Umar
Int. J. Mol. Sci. 2022, 23(1), 339; https://doi.org/10.3390/ijms23010339 - 29 Dec 2021
Cited by 8 | Viewed by 3568
Abstract
Decreases in short-chain-fatty-acids (SCFAs) are linked to inflammatory bowel disease (IBD). Yet, the mechanisms through which SCFAs promote wound healing, orchestrated by intestinal stem cells, are poorly understood. We discovered that, in mice with Citrobacter rodentium (CR)-induced infectious colitis, treatment with Pectin and [...] Read more.
Decreases in short-chain-fatty-acids (SCFAs) are linked to inflammatory bowel disease (IBD). Yet, the mechanisms through which SCFAs promote wound healing, orchestrated by intestinal stem cells, are poorly understood. We discovered that, in mice with Citrobacter rodentium (CR)-induced infectious colitis, treatment with Pectin and Tributyrin diets reduced the severity of colitis by restoring Firmicutes and Bacteroidetes and by increasing mucus production. RNA-seq in young adult mouse colon (YAMC) cells identified higher expression of Lgr4, Lgr6, DCLK1, Muc2, and SIGGIR after Butyrate treatment. Lineage tracing in CR-infected Lgr5-EGFP-IRES-CreERT2/ROSA26-LacZ (Lgr5-R) mice also revealed an expansion of LacZ-labeled Lgr5(+) stem cells in the colons of both Pectin and Tributyrin-treated mice compared to control. Interestingly, gut microbiota was required for Pectin but not Tributyrin-induced Lgr5(+) stem cell expansion. YAMC cells treated with sodium butyrate exhibited increased Lgr5 promoter reporter activity due to direct Butyrate binding with Lgr5 at −4.0 Kcal/mol, leading to thermal stabilization. Upon ChIP-seq, H3K4me3 increased near Lgr5 transcription start site that contained the consensus binding motif for a transcriptional activator of Lgr5 (SPIB). Thus, a multitude of effects on gut microbiome, differential gene expression, and/or expansion of Lgr5(+) stem cells seem to underlie amelioration of colitis following dietary intervention. Full article
(This article belongs to the Special Issue Precision Medicine in Inflammatory Bowel Diseases: Epigenetics, Gut Microbiome, Sex Differences and Beyond)
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