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Gastrointestinal Diseases: Molecular Mechanism, Diagnostics, and Novel Therapeutic Approaches

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: closed (15 May 2024) | Viewed by 12590

Special Issue Editor


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Guest Editor
Department of Internal Medicine, Kosin University College of Medicine, Busan 49267, Republic of Korea
Interests: colorectal cancer; gut microbiome; therapeutic intervention

Special Issue Information

Dear Colleagues,

We are pleased to announce the call for papers for a Special Issue on "Gastrointestinal Diseases: Molecular Mechanism, Diagnostics, and Novel Therapeutic Approaches". This Special Issue aims to bring together original research and review articles exploring the molecular aspects of gastrointestinal diseases, highlighting innovative approaches and advancements in diagnosing and treating gastrointestinal diseases.

Gastrointestinal diseases encompass a wide range of conditions affecting the digestive system, including gastroesophageal reflux syndrome, Barrett’s esophagus, H. pylori-related disorders, inflammatory bowel disease, irritable bowel syndrome, gastrointestinal cancer, and other related disorders. The aim of this Special Issue is to provide a platform for researchers and clinicians to share their latest findings and insights into the field, with a particular focus on new molecular diagnostic techniques and therapeutic strategies.

Recent advancements in molecular biology, genomics, and imaging technologies have revolutionized our understanding of gastrointestinal diseases. These breakthroughs have led to the identification of novel biomarkers, the development of innovative imaging modalities, and the emergence of targeted therapies. This Special Issue will showcase research that sheds light on the molecular mechanisms underlying gastrointestinal diseases, explores cutting-edge diagnostic tools, and evaluates the efficacy of novel therapeutic interventions.

We invite researchers from diverse disciplines, including but not limited to gastroenterology, oncology, pathology, radiology, and molecular biology, to submit their original research articles, reviews, and case studies. Topics of interest for this Special Issue include, but are not limited to:

  1. Molecular biomarkers for early detection and diagnosis of gastrointestinal diseases
  2. Novel molecular imaging techniques for assessing gastrointestinal pathology
  3. Unraveling the molecular interplay between gut microbiota and gastrointestinal health
  4. Molecular biomarkers for predicting the treatment response and prognosis
  5. Exploring molecular therapeutic approaches, including immunotherapy and gene therapy

We aim to provide a comprehensive overview of the current state-of-the-art gastrointestinal disease research field by bringing together a collection of high-quality articles in this Special Issue. We encourage both basic science and clinical researchers to contribute their work to foster collaborations and inspire further advancements in diagnosing and treating gastrointestinal diseases.

We look forward to receiving your submissions and sharing your valuable contributions with the scientific community.

Best regards,

Dr. Jae-hyun Kim
Guest Editor

Manuscript Submission Information

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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

  • gut microbiota
  • gut–brain axis
  • drug metabolism
  • drug delivery systems
  • drug resistance
  • gut barrier function
  • gut hormones
  • intestinal permeability
  • molecular diagnostics
  • biomarkers
  • molecular genetic profiling
  • molecular imaging modalities
  • molecular therapeutic targets
  • nanomedicine
  • molecular immunotherapy
  • molecular basis of immune response
  • molecular gene therapy
  • molecular mechanisms
  • genomics/epigenomics
  • next-generation sequencing
  • tumor microenvironment
  • DNA repair/methylation
  • animal models
  • signaling pathway

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Published Papers (7 papers)

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Research

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28 pages, 10222 KiB  
Article
Integrated Analysis of Microbiome and Metabolome Reveals Disease-Specific Profiles in Inflammatory Bowel Diseases and Intestinal Behçet’s Disease
by Yehyun Park, Jae Bum Ahn, Da Hye Kim, I Seul Park, Mijeong Son, Ji Hyung Kim, Hyun Woo Ma, Seung Won Kim and Jae Hee Cheon
Int. J. Mol. Sci. 2024, 25(12), 6697; https://doi.org/10.3390/ijms25126697 - 18 Jun 2024
Cited by 1 | Viewed by 1272
Abstract
The gut microbial and metabolic characteristics of intestinal Behçet’s disease (BD), a condition sharing many clinical similarities with ulcerative colitis (UC) and Crohn’s disease (CD), are largely unexplored. This study investigated the gut microbial and metabolic characteristics of intestinal BD as well as [...] Read more.
The gut microbial and metabolic characteristics of intestinal Behçet’s disease (BD), a condition sharing many clinical similarities with ulcerative colitis (UC) and Crohn’s disease (CD), are largely unexplored. This study investigated the gut microbial and metabolic characteristics of intestinal BD as well as potential biomarkers, comparing them with those in UC, CD, and healthy controls. Colon tissue and stool samples from 100 patients (35 UC, 30 CD, and 35 intestinal BD) and 41 healthy volunteers were analyzed using 16S ribosomal RNA sequencing to assess microbial diversity, taxonomic composition, and functional profiling. Plasma metabolomic analyses were performed using gas chromatography and ultra-performance liquid chromatography-mass spectrometry. Results indicated reduced microbial diversity in CD but not in intestinal BD, with intestinal BD showing fewer changes compared to controls yet distinct taxonomic features from UC, CD, and controls. Common alterations across all diseases included a reduction in beneficial bacteria producing short-chain fatty acids. Intestinal BD-specific changes featured a decreased abundance of Bacteroides fragilis. Metabolomic profiles in intestinal BD were similar to those in CD but distinct from those in UC, displaying significant changes in energy metabolism and genetic information processing. This integrative analysis revealed both shared and unique profiles in intestinal BD compared with UC, CD, and controls, advancing our understanding of the distinctive features of these diseases. Full article
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16 pages, 2619 KiB  
Article
Sterile Fecal Microbiota Transplantation Boosts Anti-Inflammatory T-Cell Response in Ulcerative Colitis Patients
by Anton Chechushkov, Pavel Desyukevich, Timir Yakovlev, Lina Al Allaf, Evgeniya Shrainer, Vitalyi Morozov and Nina Tikunova
Int. J. Mol. Sci. 2024, 25(3), 1886; https://doi.org/10.3390/ijms25031886 - 4 Feb 2024
Cited by 2 | Viewed by 1417
Abstract
Ulcerative colitis is a chronic immune-mediated disease of unclear etiology, affecting people of different ages and significantly reducing the quality of life. Modern methods of therapy are mainly represented by anti-inflammatory drugs and are not aimed at a specific pathogenetic factor. In this [...] Read more.
Ulcerative colitis is a chronic immune-mediated disease of unclear etiology, affecting people of different ages and significantly reducing the quality of life. Modern methods of therapy are mainly represented by anti-inflammatory drugs and are not aimed at a specific pathogenetic factor. In this study, we investigated the effect of transplantation of sterile stool filtrate from healthy donors on the induction of anti-inflammatory immune mechanisms. It was shown that performing such a procedure in patients with ulcerative colitis caused the appearance of T helper cells in the blood, which reacted to the content of sterile stool filtrates in an antigen-specific manner and produced IL-10. At the same time, cells of the same patients before therapy in response to the addition of sterile stool filtrates were less reactive and predominantly produced IL-4, indicating its pro-inflammatory skewing. The obtained data demonstrated the effect of an anti-inflammatory shift in the T-helper response after transplantation of sterile stool filtrate, which increased and persisted for at least three months after the procedure. Full article
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14 pages, 2775 KiB  
Article
Serum Amyloid A as a Potential Biomarker in Inflammatory Bowel Diseases, Especially in Patients with Low C-Reactive Protein
by Marie Stute, Martin Kreysing, Markus Zorn, Patrick Michl and Annika Gauss
Int. J. Mol. Sci. 2024, 25(2), 1177; https://doi.org/10.3390/ijms25021177 - 18 Jan 2024
Cited by 2 | Viewed by 1516
Abstract
The acute phase protein Serum Amyloid A (SAA) is synthesised by the liver in response to inflammatory stimuli. Previous studies have revealed that SAA may be a better biomarker of disease activity in inflammatory bowel disease (IBD) compared to C-reactive protein (CRP). This [...] Read more.
The acute phase protein Serum Amyloid A (SAA) is synthesised by the liver in response to inflammatory stimuli. Previous studies have revealed that SAA may be a better biomarker of disease activity in inflammatory bowel disease (IBD) compared to C-reactive protein (CRP). This retrospective monocentric study evaluated whether SAA correlates with biomarkers like faecal calprotectin (FC), CRP, the Neutrophil to Lymphocyte ratio (NLR), the platelet count and clinical disease activity of IBD patients. Serum samples from the IBD outpatient clinic of the University Hospital Heidelberg were analysed for SAA concentrations if an FC concentration measurement was available from ±14 days to collection of the serum sample. Three hundred and six serum samples from 265 patients (166 with Crohn’s disease, 91 with ulcerative colitis and 8 with IBD unclassified) met the inclusion criteria. There was a significant positive correlation between SAA and FC, CRP, NLR, platelet count and the Simple Clinical Colitis Activity Index (SCCAI). The cut-off for SAA serum concentration at 4.55 mg/L achieved a sensitivity of 57.5% and a specificity of 69.7% for the detection of active inflammation in IBD. SAA may be used as an additional biomarker in the disease monitoring strategy of IBD patients, especially in patients with low CRP concentrations. Full article
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14 pages, 2765 KiB  
Article
Potential Molecular Markers Related to Lymph Node Metastasis and Stalk Resection Margins in Pedunculated T1 Colorectal Cancers Using Digital Spatial Profiling: A Pilot Study with a Small Case Series
by Mi Jung Kwon, Ha Young Park, Hyun Lim, Il Tae Son, Min-Jeong Kim, Nan Young Kim, Min Jeong Kim, Eun Sook Nam, Seong Jin Cho, Woo Jin Bang and Ho Suk Kang
Int. J. Mol. Sci. 2024, 25(2), 1103; https://doi.org/10.3390/ijms25021103 - 16 Jan 2024
Viewed by 1504
Abstract
There is a debate regarding the prediction of lymph node metastasis (LNM) in pedunculated T1 colorectal cancer (CRC). In this study with four cases of pedunculated T1 CRCs, we aimed to investigate gene expression variations based on the distance from the Haggitt line [...] Read more.
There is a debate regarding the prediction of lymph node metastasis (LNM) in pedunculated T1 colorectal cancer (CRC). In this study with four cases of pedunculated T1 CRCs, we aimed to investigate gene expression variations based on the distance from the Haggitt line (HL) and identify potential molecular risk factors for LNM. By leveraging the Cancer Transcriptome Atlas and digital spatial profiling technology, we meticulously analyzed discrete regions, including the head, HL, proximal stalk region (300–1000 μm from HL), and distal stalk region (1500–2000 μm from HL) to identify spatially sequential molecular changes. Our findings showed significant overall gene expression variations among the head, proximal stalk, and distal stalk regions of pedunculated T1 CRCs compared to the control adenoma. Compared to LNM-negative T1 CRCs, LNM-positive T1 CRC showed that the expression of genes involved in immune-related pathways such as B2M, HLA-B, and HLA-E were significantly downregulated in the distal stalk region compared to the proximal stalk region. In summary, our results may tentatively suggest considering endoscopic resection of the stalk with a minimum 2000 μm margin from the HL, taking into account the gene expression alterations related to immune-related pathways. However, we acknowledge the limitations of this pilot study, notably the small case series, which may restrict the depth of interpretation. Further validation is imperative to substantiate these findings. Full article
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18 pages, 2720 KiB  
Article
Slowed Intestinal Transit Induced by Less Mucus in Intestinal Goblet Cell Piezo1-Deficient Mice through Impaired Epithelial Homeostasis
by Feifei Fang, Ying Liu, Yilin Xiong, Xueyan Li, Gangping Li, Yudong Jiang, Xiaohua Hou and Jun Song
Int. J. Mol. Sci. 2023, 24(18), 14377; https://doi.org/10.3390/ijms241814377 - 21 Sep 2023
Cited by 3 | Viewed by 1653
Abstract
Mucus secreted by goblet cells (GCs) may play an important role in intestinal transit function. Our previous study found that Piezo1 protein is essential for GC function; however, the effect of GC Piezo1 on intestinal transit function is unclear. Our study aimed to [...] Read more.
Mucus secreted by goblet cells (GCs) may play an important role in intestinal transit function. Our previous study found that Piezo1 protein is essential for GC function; however, the effect of GC Piezo1 on intestinal transit function is unclear. Our study aimed to investigate the effect of Piezo1 in GCs on intestinal transit and the potential mechanism. We compared intestinal mucus, fecal form, intestinal transit time, intestinal epithelial cell composition, and stem cell function in WT and GC-specific Piezo1-deficient (Piezo1ΔGC) mice. Our results revealed a correlation between mucus and intestinal transit: the less mucus there was, the slower the intestinal transit. Piezo1 deficiency in GCs led to decreased mucus synthesis and also disrupted the ecological niche of colon stem cells (CSCs). Through organoid culture, we found that the capacity of proliferation and differentiation in Piezo1ΔGC mouse CSCs was significantly decreased, which also led to a reduced source of GCs. Further studies found that the reduced Wnt and Notch signals in colon crypts might be the potential mechanism. These results indicated the importance of GC Piezo1 in intestinal transit function, which acts by maintaining the homeostasis of intestinal epithelial cells and mucus. Full article
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9 pages, 3523 KiB  
Article
Single-Cell Network-Based Drug Repositioning for Discovery of Therapies against Anti-Tumour Necrosis Factor-Resistant Crohn’s Disease
by Min Seob Kwak, Chang-Il Hwang, Jae Myung Cha, Jung Won Jeon, Jin Young Yoon and Su Bee Park
Int. J. Mol. Sci. 2023, 24(18), 14099; https://doi.org/10.3390/ijms241814099 - 14 Sep 2023
Cited by 2 | Viewed by 1760
Abstract
Primary and secondary non-response affects approximately 50% of patients with Crohn’s disease treated with anti-tumour necrosis factor (TNF) monoclonal antibodies. To date, very little single cell research exists regarding drug repurposing in Crohn’s disease. We aimed to elucidate the cellular phenomena underlying resistance [...] Read more.
Primary and secondary non-response affects approximately 50% of patients with Crohn’s disease treated with anti-tumour necrosis factor (TNF) monoclonal antibodies. To date, very little single cell research exists regarding drug repurposing in Crohn’s disease. We aimed to elucidate the cellular phenomena underlying resistance to anti-TNF therapy in patients with Crohn’s disease and to identify potential drug candidates for these patients. Single-cell transcriptome analyses were performed using data (GSE134809) from the Gene Expression Omnibus and Library of Integrated Network-Based Cellular Signatures L1000 Project. Data aligned to the Genome Reference Consortium Human Build 38 reference genome using the Cell Ranger software were processed using the Seurat package. To capture significant functional terms, gene ontology functional enrichment analysis was performed on the marker genes. For biological analysis, 93,893 cells were retained (median 20,163 genes). Through marker genes, seven major cell lineages were identified: B-cells, T-cells, natural killer cells, monocytes, endothelial cells, epithelial cells, and tissue stem cells. In the anti-TNF-resistant samples, the top 10 differentially expressed genes were HLA-DQB-1, IGHG1, RPS23, RPL7A, ARID5B, LTB, STAT1, NAMPT, COTL1, ISG20, IGHA1, IGKC, and JCHAIN, which were robustly distributed in all cell lineages, mainly in B-cells. Through molecular function analyses, we found that the biological functions of both monocyte and T-cell groups mainly involved immune-mediated functions. According to multi-cluster drug repurposing prediction, vorinostat is the top drug candidate for patients with anti-TNF-refractory Crohn’s disease. Differences in cell populations and immune-related activity within tissues may influence the responsiveness of Crohn’s disease to anti-TNF agents. Vorinostat may serve as a promising novel therapy for anti-TNF-resistant Crohn’s disease. Full article
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Review

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23 pages, 1881 KiB  
Review
The Effect of Dexlansoprazole on Gastroesophageal Reflux Disease: A Systematic Review and Meta-Analysis
by Gabriel Pereira Nunes, Thayná Cerqueira Silveira, João Vítor Silveira Marciano, Alexandre Henrique dos Reis-Prado, Tulio Morandin Ferrisse, Evandro Barbosa dos Anjos and Maria Helena Fernandes
Int. J. Mol. Sci. 2024, 25(2), 1247; https://doi.org/10.3390/ijms25021247 - 19 Jan 2024
Cited by 1 | Viewed by 2706
Abstract
This systematic review and meta-analysis evaluated the efficacy of dexlansoprazole (a proton pump inhibitor—PPI) in resolving heartburn, reflux, and other symptoms and complications resulting from gastroesophageal reflux disease (GERD). The study followed PRISMA 2020 and was registered in PROSPERO (CRD42020206513). The search strategy [...] Read more.
This systematic review and meta-analysis evaluated the efficacy of dexlansoprazole (a proton pump inhibitor—PPI) in resolving heartburn, reflux, and other symptoms and complications resulting from gastroesophageal reflux disease (GERD). The study followed PRISMA 2020 and was registered in PROSPERO (CRD42020206513). The search strategy used MeSH and free terms appropriately adapted for each database. Only randomized clinical trials (RCTs) were included. The Cochrane tool (RoB 2.0) was used to assess the risk of bias, and the certainty of evidence was rated using GRADE. Ten RCTs were included. Dexlansoprazole outperformed the placebo and other PPIs in the resolution of heartburn and reflux symptoms in patients with GERD, with benefits during and after treatment, especially in those with moderate and severe symptoms. The meta-analyses indicated that dexlansoprazole at doses of 30 and 60 mg had more 24 h heartburn-free days and nights compared to the placebo medications; no difference was reported between dexlansoprazole at doses of 30 and 60 mg in heartburn-free nights. A low bias risk and a moderate certainty of evidence were observed. This review confirms the therapeutic effect of dexlansoprazole (placebo-controlled) and its improvements in GERD symptoms compared to another PPI. However, the interpretation of the results should be carried out cautiously due to the small number of included studies and other reported limitations. Full article
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