Gastrointestinal Diseases: Molecular Mechanism, Clinical Research, and Therapeutics

A special issue of Life (ISSN 2075-1729). This special issue belongs to the section "Medical Research".

Deadline for manuscript submissions: closed (30 November 2023) | Viewed by 7629

Special Issue Editors


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Guest Editor
Instituto de Investigación Biomédica de Málaga (IBIMA-BIONAND), Hospital Regional Universitario de Málaga, 29010 Málaga, Spain
Interests: gastrointestinal diseases; innate immunity; Immunology; B cells; allergy; rhinitis; food allergy; IgE

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Guest Editor
Department of Medicine 1, Universitätsklinikum Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg, 91054 Erlangen, Germany
Interests: gastrointestinal diseases; liver diseases; macrophage; acute pancreatitis; alkaline phosphatase; colon cancer

Special Issue Information

Dear Colleagues,

The gut is a complex organ involved in multiple critical processes, including food and water absorption, waste excretion and barrier regulation. The latter includes dealing with different environmental challenges such as microbial antigens and food allergens. Hence, intestinal homeostasis is maintained by an orchestrated interaction between host immunity and intestinal microbiota. Alterations in this equilibrium lead to different pathologies, which pose a substantial challenge to clinical care. Gastrointestinal (GI) diseases refer to a wide range of conditions that affect the digestive system, including the esophagus, stomach, small intestine, colon, and rectum. The molecular mechanisms underlying these diseases vary, but they usually involve genetic factors, abnormal immune responses, infections, and changes in the gut microbiome. Clinical research in this field is focused on understanding the causes and mechanisms of GI diseases, as well as finding new and more effective treatments. These treatments include medications, lifestyle changes, surgery, and other interventions aimed at improving symptoms and patients´ quality of life.

GI Diseases include acid reflux, inflammatory bowel disease (IBD), irritable bowel syndrome (IBS), peptic ulcer disease, gastrointestinal cancers, food allergies and eosinophilic esophagitis (EoE).

Irritable bowel syndrome is a common chronic gastrointestinal condition characterized by abdominal pain and alterations in bowel habits. Diet, genetic predisposition and more importantly, stress exposure, are acknowledged factors in the pathophysiology of this disorder. IBS is not a life-threatening condition; however, it has an enormous influence on the quality of life. 

Inflammatory bowel disease includes two conditions, Ulcerative colitis and Crohn's disease. Both are characterised by chronic inflammation and a dysregulated immune response. Although the aetiology of IBD remains largely unknown; genetic, environmental and microbiota-derived factors are key components in the pathogenesis.

Gastric cancer, esophageal cancer and colorectal cancer are the most common types of gastrointestinal cancer. Although most cases appear to arise sporadically, the hereditary component is present in a low percentage of the cases. GI cancers account for 26% of the global cancer incidence and 35% of cancer-related deaths. GI tract cancers are caused by the accumulation of mutations in genes that control differentiation, growth, or DNA repair.

Food allergies (FA) are defined as immune-mediated, adverse health effects that occur after exposure to food. These effects are usually reproducible and to a certain specific food. They can be broadly classified into IgE-mediated, non-IgE-dependent, or a combination of both. IgE-mediated food allergy occurs when the adverse immune response to food proteins takes place with the production of high-affinity IgE antibodies. FA can lead to symptoms such as abdominal pain, nausea, vomiting, diarrhea, and skin rashes. In some cases, food allergies can lead to more serious reactions, such as anaphylaxis, a severe and potentially life-threatening reaction.

EoE is a chronic inflammatory condition that affects the esophagus, the muscular tube that connects the mouth to the stomach. The main characteristic of EoE is an excessive accumulation of eosinophils, a type of white blood cell, in the esophageal tissue. This inflammation can lead to symptoms such as difficulty swallowing (dysphagia), food impaction, heartburn, chest pain, and nausea. The exact causes of EoE are not fully understood, but it is thought to involve a combination of genetic, environmental, and immunological factors. In some cases, surgical interventions may be necessary to treat severe cases of EoE.

This Special Issue welcomes submissions of original research articles and reviews on novel studies performed in Gastrointestinal Diseases. Specific subject areas of interest include but are not limited to:

  • Molecular mechanisms of the pathophysiology of IBD, IBS, gastrointestinal cancer, FA and EoE.
  • Current clinical practices and new perspectives on GI disease treatment.
  • Novel desensitization strategies in food allergy.
  • Specific mechanisms of allergen immunotherapy (cellular and molecular).
  • Research in novel brain-gut axis mechanisms involving GI diseases.

Dr. Carlos J. Aranda
Dr. Reyes Gamez-Belmonte
Guest Editors

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Keywords

  • IBD
  • food allergy
  • eosinophilic esophagitis
  • gastrointestinal cancer
  • immunotherapy

Published Papers (6 papers)

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Research

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13 pages, 1823 KiB  
Article
Correlation between Psychosomatic Assessment, Heart Rate Variability, and Refractory GERD: A Prospective Study in Patients with Acid Reflux Esophagitis
by Hsin-Ming Wang, Pao-Yuan Huang, Shih-Cheng Yang, Ming-Kung Wu, Wei-Chen Tai, Chih-Hung Chen, Chih-Chien Yao, Lung-Sheng Lu, Seng-Kee Chuah, Yu-Chi Lee and Chih-Ming Liang
Life 2023, 13(9), 1862; https://doi.org/10.3390/life13091862 - 03 Sep 2023
Viewed by 1406
Abstract
Background: Gastroesophageal reflux disease (GERD) affects a significant proportion of individuals, with life stress being a contributing factor. This study aimed to investigate the correlation between psychosomatic evaluations, heart rate variability (HRV), and GERD in a cohort of individuals. Additionally, the study aimed [...] Read more.
Background: Gastroesophageal reflux disease (GERD) affects a significant proportion of individuals, with life stress being a contributing factor. This study aimed to investigate the correlation between psychosomatic evaluations, heart rate variability (HRV), and GERD in a cohort of individuals. Additionally, the study aimed to analyze the sequencing changes following proton pump inhibitor (PPI) treatment and identify predictive factors associated with refractory GERD. Methods: A prospective cohort of 105 individuals with reflux esophagitis and a control group of 50 participants without acid reflux symptoms were enrolled. Psychosomatic evaluations, including GERDQ, GERDQLQ, RSI, BAI, BDI, and SSS-8, were assessed at baseline and during treatment. HRV parameters were also evaluated. Multivariate analysis was used to identify predictive factors for refractory GERD. PPIs were administered regularly for the initial 2 months and then used on-demand. Refractory GERD was defined as less than 50% improvement in symptom relief or GERDQLQ score ≥ 20 after 8 weeks of PPI treatment. Results: The GERD group had higher scores in all psychosomatic evaluations compared to the control group (all p-values < 0.001). There were no significant changes in any parameters of HRV before and after treatment in the GERD group. Strong and consistent correlations were observed between GERD symptoms and psychological scores (BAI, BDI, and SSS-8) across all time points (W0, W4, and W8). Sequential reductions in GERD symptom scores and psychosomatic evaluations were observed during the initial eight weeks of treatment. Higher GERDQ (≥10) and SSS-8 (≥12) scores were predictive of refractory GERD (p = 0.004 and p = 0.009, respectively). Conclusions: This study emphasizes the importance of considering physiological and psychological factors in the management of GERD. Psychosomatic evaluations provide valuable insights for assessing and treating GERD patients. Integrating stress management and comprehensive assessments into personalized treatment strategies is crucial. Full article
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13 pages, 964 KiB  
Article
Decreased HDL-C Levels as a Predictor of Organ Failure in Acute Pancreatitis in the Emergency Department
by Ana Rocío Venegas-Tamayo, Olga Mariel Peña-Veites, Martha Alicia Hernández-González and Cornelio Barrientos-Alvarado
Life 2023, 13(7), 1602; https://doi.org/10.3390/life13071602 - 21 Jul 2023
Cited by 2 | Viewed by 1014
Abstract
High-density lipoprotein cholesterol (HDL-C) is reported as a biomarker of systemic inflammation and multi-organ failure (MOF), which has been rarely investigated in acute pancreatitis (AP), a frequent condition in the emergency department (ED). The objective was to study the predictive capacity of the [...] Read more.
High-density lipoprotein cholesterol (HDL-C) is reported as a biomarker of systemic inflammation and multi-organ failure (MOF), which has been rarely investigated in acute pancreatitis (AP), a frequent condition in the emergency department (ED). The objective was to study the predictive capacity of the decrease in HDL-C to the progression of MOF in AP in the ED; analyzing 114 patients with AP for one year in a longitudinal and prospective study, AP severity was obtained by the Atlanta classification, in relation to modified Marshall and Bedside Index for Severity in Acute Pancreatitis (BISAP) scores, and clinical and laboratory parameters in a 48 h hospital stay. The area under the receiver operating characteristic (ROC) curve was used to estimate the validity of the predictor and define optimal cut-off points. It was found that AP was classified as severe in 24.5%, mainly for biliary etiology (78.9%) and female sex (73.6%). As a biomarker, HDL-C decreased from 31.6 to 29.5 mg/dL in a 48 h stay (p < 0.001), correlating negatively with the increase in severity index > 2 and the modified Marshall (p < 0.032) and BISAP (p < 0.009) scores, finding an area under the ROC curve with a predictive capacity of 0.756 (95% CI, 0.614–0.898; p < 0.004) and a cut-off point of 28.5 mg/dL (sensitivity: 79%, specificity: 78%), demonstrating that the decrease in HDL-C levels serves as a useful indicator with a predictive capacity for MOF in mild to severe AP, during a 48 h hospital stay in the ED. Full article
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15 pages, 5396 KiB  
Article
Circulating Epithelial Cells in Patients with Intraductal Papillary Mucinous Neoplasm of the Pancreas
by Jasmina Kuvendjiska, Felix Müller, Peter Bronsert, Sylvia Timme-Bronsert, Stefan Fichtner-Feigl and Birte Kulemann
Life 2023, 13(7), 1570; https://doi.org/10.3390/life13071570 - 15 Jul 2023
Cited by 3 | Viewed by 1007
Abstract
Intraductal papillary mucinous neoplasm (IPMN) is the most common pancreatic cyst and a precursor of pancreatic cancer (PDAC). Since PDAC has a devastatingly high mortality rate, the early diagnosis and treatment of any precursor lesion are rational. The safety of the existing guidelines [...] Read more.
Intraductal papillary mucinous neoplasm (IPMN) is the most common pancreatic cyst and a precursor of pancreatic cancer (PDAC). Since PDAC has a devastatingly high mortality rate, the early diagnosis and treatment of any precursor lesion are rational. The safety of the existing guidelines on the clinical management of IPMN has been criticized due to unsatisfactory sensitivity and specificity, showing the need for further markers. Blood obtained from patients with IPMN was therefore subjected to size-based isolation of circulating epithelial cells (CECs). We isolated CECs and evaluated their cytological characteristics. Additionally, we compared Kirsten rat sarcoma viral oncogene homolog (KRAS) mutations in CECs and the primary IPMN tissue, since KRAS mutations are very typical for PDAC. Samples from 27 IPMN patients were analyzed. In 10 (37%) patients, CECs were isolated and showed a hybrid pattern of surface markers involving both epithelial and mesenchymal markers, suggesting a possible EMT process of the cells. Especially, patients with high-grade dysplasia in the main specimen were all CEC-positive. KRAS mutations were also present in CECs but less common than in IPMN tissue. The existence of CEC in IPMN patients offers additional blood-based research possibilities for IMPN biology. Full article
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Review

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20 pages, 314 KiB  
Review
Chronic Nonbacterial Osteomyelitis in Inflammatory Bowel Disease
by Ariadni Tzaneti, Elli Athanasopoulou, Smaragdi Fessatou and Lampros Fotis
Life 2023, 13(12), 2347; https://doi.org/10.3390/life13122347 - 15 Dec 2023
Viewed by 1174
Abstract
Chronic nonbacterial osteomyelitis (CNO), also known as chronic recurrent multifocal osteomyelitis (CRMO), is a rare autoinflammatory bone disease primarily affecting children and adolescents. This review presents a comprehensive analysis of the intricate relationship between CNO and inflammatory bowel disease (IBD), shedding light on [...] Read more.
Chronic nonbacterial osteomyelitis (CNO), also known as chronic recurrent multifocal osteomyelitis (CRMO), is a rare autoinflammatory bone disease primarily affecting children and adolescents. This review presents a comprehensive analysis of the intricate relationship between CNO and inflammatory bowel disease (IBD), shedding light on shared pathophysiological mechanisms and clinical management. A thorough literature review was conducted, encompassing 24 case reports involving 40 patients. The demographic distribution of patients revealed a near-equal gender ratio, with a median age of diagnosis at 12 years. The diagnosis patterns showed a higher proportion of CNO as the initial diagnosis, while Crohn’s disease was more prevalent than ulcerative colitis. The time interval between the clinical presentations varied, ranging from simultaneous detection to a substantial 15-year gap. Treatment modalities included nonsteroidal anti-inflammatory drugs (NSAIDs), steroids, aminosalicylates, and biologic agents, such as infliximab, often overlapping in their use and suggesting shared pathophysiological pathways. Both conditions displayed systemic manifestations, and patients often responded well to immunosuppressive medications. The pathophysiology of CNO involves a genetic predisposition, cytokine dysregulation, and osteoclast activation. Dysregulated innate immunity results in immune cell infiltration into bones, causing sterile bone lesions. Notably, emerging evidence hints at a potential link between the microbiome and CNO. In contrast, IBD results from imbalanced mucosal immune responses to the intestinal microbiota. Polymorphisms in the promotor region of IL-10, common cytokines, immune cells, and genetic markers indicate shared immunological and genetic factors between CNO and IBD. Both conditions also involve extraintestinal symptoms. This analysis underscores the need for clinical awareness of the co-occurrence of CNO and IBD, especially among pediatric patients. A deepened understanding of the connections between these seemingly distinct diseases could lead to more effective management and improved patient outcomes. Full article
19 pages, 8324 KiB  
Review
Imaging of Strictures in Crohn’s Disease
by Laura Maria Minordi, Luigi Larosa, Antonio Bevere, Francesca Bice D’Angelo, Antonio Pierro, Savino Cilla, Annemilia Del Ciello, Franco Scaldaferri and Brunella Barbaro
Life 2023, 13(12), 2283; https://doi.org/10.3390/life13122283 - 29 Nov 2023
Viewed by 1044
Abstract
Crohn’s disease (CD) is a chronic inflammation of the digestive tract, and it frequently affects young patients. It can involve any intestinal segment, even though it frequently affects the distal ileum. Up to 80% of patients with CD present with inflammatory behavior, and [...] Read more.
Crohn’s disease (CD) is a chronic inflammation of the digestive tract, and it frequently affects young patients. It can involve any intestinal segment, even though it frequently affects the distal ileum. Up to 80% of patients with CD present with inflammatory behavior, and 5% to 28% develop stricturing disease. Based on the predominant mechanism causing them, strictures can be categorized as inflammatory, fibrotic, or mixed. Determining the relative amounts of inflammation and fibrosis in a stricture can influence treatment decisions. Imaging is an extremely useful tool in patients with small bowel stricturing CD to confirm the diagnosis and to evaluate disease characteristics, usually using CT or MRI. The aim of this paper is to describe how imaging can evaluate a patient with small bowel CD stricture. Full article
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21 pages, 1476 KiB  
Review
Metabolic and Bariatric Endoscopy: A Mini-Review
by Benjamin Charles Norton, Andrea Telese, Apostolis Papaefthymiou, Nasar Aslam, Janine Makaronidis, Charles Murray and Rehan Haidry
Life 2023, 13(9), 1905; https://doi.org/10.3390/life13091905 - 13 Sep 2023
Cited by 1 | Viewed by 1259
Abstract
We are currently in a worldwide obesity pandemic, which is one of the most significant health problems of the 21st century. As the prevalence of obesity continues to rise, new and innovate treatments are becoming available. Metabolic and bariatric endoscopic procedures are exciting [...] Read more.
We are currently in a worldwide obesity pandemic, which is one of the most significant health problems of the 21st century. As the prevalence of obesity continues to rise, new and innovate treatments are becoming available. Metabolic and bariatric endoscopic procedures are exciting new areas of gastroenterology that have been developed as a direct response to the obesity crisis. These novel interventions offer a potentially reversible, less invasive, safer, and more cost-effective method of tackling obesity compared to traditional bariatric surgery. Minimally invasive endoscopic treatments are not entirely novel, but as technology has rapidly improved, many of the procedures have been proven to be extremely effective for weight loss and metabolic health, based on high-quality clinical trial data. This mini-review examines the existing evidence for the most prominent metabolic and bariatric procedures, followed by a discussion on the future trajectory of this emerging subspecialty. Full article
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