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Gastroenterol. Insights, Volume 15, Issue 3 (September 2024) – 5 articles

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14 pages, 4016 KiB

Open AccessArticle

Mitigative Effect of Graphene Oxide Nanoparticles in Maintaining Gut–Liver Homeostasis against Alcohol Injury

by Hiral Aghara, Prashsti Chadha and Palash Mandal

Gastroenterol. Insights 2024, 15(3), 574-587; https://doi.org/10.3390/gastroent15030042 (registering DOI) - 2 Jul 2024

Viewed by 157

Abstract

Alcoholic liver disease (ALD) develops when the immunotolerant environment of the liver is compromised due to excessive alcohol consumption. ALD progression involves variations in the expressions of multiple genes, resulting in liver inflammation and the development of a leaky gut. It is still unclear which molecular mechanism is involved in ALD progression, and due to that, there are currently no FDA-approved drugs available for its treatment. In this study, the protective effects of graphene oxide (GO) nanoparticles were investigated against ethanol-induced damage in the gut–liver axis in in vitro. GO was synthesized using a modified Hummer’s method, and characterization was performed. Given the general concerns regarding nanoparticle toxicity, assessments of cell viability, lipid accumulation, DNA damage, cell death, and the generation of reactive oxygen species (ROS) were conducted using various techniques. Furthermore, the gene expressions of pro- and anti-inflammatory cytokines were determined using RT-qPCR. The findings reveal that GO promoted cell viability even against ethanol treatment. Additionally, lipid accumulation significantly decreased when cells were treated with GO alongside ethanol compared to ethanol treatment alone, with similar trends observed for other assays. A gene expression analysis indicated that GO treatment reduced the expression of proinflammatory cytokines while enhancing the expression of antioxidant genes. Moreover, GO treatment led to improvements in gut integrity and a reduction in proinflammatory cytokines in colon cells damaged by ethanol. These findings suggest that GO holds promise as a drug carrier, exhibiting no observed toxic effects. By shedding light on the protective effects of GO against ethanol-induced damage, this study contributes to the burgeoning field of nanoparticle-mediated therapy for ALD. Full article

(This article belongs to the Section Liver)

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19 pages, 2672 KiB

Open AccessReview

Exploring Gut–Brain Interaction Disorders: Mechanisms and Translational Therapies Crossing Neurology to Gastroenterology

by Georgi V. Vasilev, Dimitrina Miteva, Milena Gulinac, Lyubomir Chervenkov, Meglena Kitanova and Tsvetelina Velikova

Gastroenterol. Insights 2024, 15(3), 555-573; https://doi.org/10.3390/gastroent15030041 (registering DOI) - 2 Jul 2024

Viewed by 151

Abstract

The bidirectional communication network between the gut and the brain, known as the gut–brain axis, plays a crucial role in health and disease. This review explores the mechanisms underlying gut–brain interaction disorders and highlights translational therapies bridging neurology and gastroenterology. Mechanisms encompass anatomical, endocrine, humoral, metabolic, and immune pathways, with the gut microbiota exerting profound influence. Clinical evidence links gut microbiota fluctuations to mood disorders, GI disruptions, and neurodevelopmental conditions, emphasizing the microbiome’s pivotal role in sha** brain–gut interactions. Pharmacological therapies such as amitriptyline and selective serotonin reuptake inhibitors modulate neurotransmitter activity, offering relief in functional gastrointestinal disorders like irritable bowel syndrome (IBS). Non-pharmacological interventions like cognitive–behavioral therapy and hypnotherapy address maladaptive thoughts and induce relaxation, alleviating gastrointestinal symptoms exacerbated by stress. Emerging therapies include gut microbiota modulation, dietary interventions, vagus nerve stimulation, and intestinal barrier modulation, offering novel approaches to manage neurological disorders via the gastrointestinal tract. Understanding and harnessing the gut–brain axis holds promise for personalized therapeutic strategies in neurogastroenterology. Full article

(This article belongs to the Section Gastrointestinal Disease)

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14 pages, 7521 KiB

Open AccessArticle

Evaluation of Immunological Response to TLR2 and α-SMA in Crohn’s Disease and Ulcerative Colitis

by Anthea Miller, Giorgia Pia Lombardo, Giuseppina Rizzo, Magdalena Kotanska, Giuseppinella Melita, Socrate Pallio, Alba Migliorato, Giuseppina Cutroneo and Simona Pergolizzi

Gastroenterol. Insights 2024, 15(3), 541-554; https://doi.org/10.3390/gastroent15030040 - 28 Jun 2024

Viewed by 259

Abstract

Inflammatory bowel diseases (IBDs) represent multifactorial chronic inflammatory conditions of the gastrointestinal tract. The main IBDs are Crohn’s disease (CD) and ulcerative colitis (UC). CD may cause perforation, stricture or transmural inflammation, which can occur discontinuously in the entire gastrointestinal tract (GIT). UC leads to mucosal inflammation as well as mucosal atrophy in the rectum and the colon. Innate immunity is considered the first line of defense against microbial invasion; among Toll-like receptors, TLR2 is the most important for defense against mycobacterial infection. TLR2 has been reported to have a lot of functions in infectious diseases and in other pathologies, such as chronic and acute inflammatory diseases. Alfa-Smooth Muscle Actin (α-SMA) is an important biomarker in IBDs. All myofibroblasts express α-SMA, which has been found to be upregulated in CD and UC. Paraformaldehyde-fixed intestinal tissues, from patients with CD and patients with UC, were analyzed by immunostaining for TLR2 and α-SMA. Our results showed that, in the samples obtained from UC patients with inflamed mucosa, TLR2-positive epithelial cells concentrated on the mucosal surface and scattered immune cells in the connective tissue; furthermore, numerous α-SMA-positive cells (subepithelial myofibroblasts) were detected in the lamina propria and around glands, while some myofibroblasts co-localizing with α-SMA and TLR2 could be inflammatory macrophages. In CD patients, TLR2-positive enterocytes and α-SMA-positive myofibroblasts in the lamina propria of the villus have been observed. In control samples, a low positivity to α-SMA and TLR2 was observed in subepithelial myofibroblasts and scattered immune cells of the lamina propria. These data showed the recall of α-SMA-positive myofibroblasts during the inflammatory state; in addition, TLR2 expression has been observed to change in the intestinal epithelium in IBDs, demonstrating that alterations in the innate system response may contribute to the pathogenesis of these diseases. Full article

(This article belongs to the Section Gastrointestinal Disease)

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11 pages, 1609 KiB

Open AccessArticle

The Severity of Gastrointestinal Disorders and Autistic-Like Behaviors Could Be Associated with a Selective Humoral Response to Bovine Milk Caseins: A Case Series

by Ángel F. Valenzuela-Zamora, Rocío Campos-Vega, José A. López-Diaz and Abraham Wall-Medrano

Gastroenterol. Insights 2024, 15(3), 530-540; https://doi.org/10.3390/gastroent15030039 - 26 Jun 2024

Viewed by 613

Abstract

Severe gastrointestinal symptoms (GIS) and food hypersensitivity are tightly associated in young individuals with autism spectrum disorders (ASD). Here, we explored the relationship of GIS (gastrointestinal severity index, ROMA IV criteria, Bristol scale), ASD-like behaviors (Childhood Autism Rating Scale), and certain sociodemographic/clinical traits (epidemiological survey) with serum immunoreactivity (IgG, IgA, IgE titers) towards bovine milk caseins (BMC; by ELISA) and subfractions (by immunoblotting) in thirty-one pediatric patients (~3–15 y, 77% male) with mild-to-severe GIS and ASD-like behaviors. In total, 42%, 25%, and 23% of all participants exhibited no (IgG−/IgA−), mono (IgG+/IgA−), or dual (IgG+/IgA+) immunoreactivity to BMC, respectively; the trend was significantly associated with the severity of the GIS and ASD-like behaviors, regurgitations, and self-reported allergies (OR: 1 → (1.9–3.1) → 13.5–16.0)]. No IgE+ response to BMC was found. Dual responders were α > κ > β-casein, though nonspecific reactivity to other protein fractions was also observed. The IgA+ > IgG+ but not IgE+ response to BMC (mainly α-casein) seems to be related to the severity of GIS and ASD-like behaviors, although a larger number of ASD patients are needed to draw a causal association. Full article

(This article belongs to the Special Issue Recent Advances in the Management of Gastrointestinal Disorders)

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11 pages, 874 KiB

Open AccessArticle

Repeated Previous Transarterial Treatments Negatively Affect Survival in Patients with Hepatocellular Carcinoma Receiving Sorafenib

by Bernardo Stefanini, Luca Ielasi, Andrea Casadei-Gardini, Michele Piscopo, Raffaella Tortora, Lorenzo Lani, Tiziana Pressiani, Vito Sansone, Rodolfo Sacco, Giulia Magini, Matteo Renzulli, Francesco Giuseppe Foschi, Fabio Piscaglia, Francesco Tovoli and Alessandro Granito

Gastroenterol. Insights 2024, 15(3), 519-529; https://doi.org/10.3390/gastroent15030038 - 22 Jun 2024

Viewed by 209

Abstract

Background: Transarterial chemoembolisation (TACE) and radioembolisation (TARE) can lead to the deterioration of liver function, especially in cases of a high tumour burden, potentially lessening the benefits of subsequent systemic treatments. We aimed to verify whether a high number of previous transarterial treatments modified the outcomes of patients who received sorafenib as a frontline systemic treatment. Methods: A retrospective analysis of a large multicenter dataset containing prospectively collected data of sorafenib-treated patients was conducted. Results: Data from 696 patients were analysed, with 139 patients having received >two transarterial procedures before starting sorafenib. A propensity score matched 139 identified pairs of patients. Having received >two locoregional treatments was independently associated with a shorter survival (hazard ratio 1.325, 95% confidence interval 1.018–1.725, p = 0.039). This pattern was confirmed amongst responders to sorafenib, but not in progressors. A trend toward a higher rate of the permanent discontinuation of sorafenib due to liver failure (18.7 vs. 10.8%, p = 0.089) and a lower rate of eligibility for second-line treatments (24.5 vs. 17.3%, p = 0.184) was observed in patients who had received >two transarterial procedures. Conclusions: Repeated endovascular treatments negatively impacted the survival of HCC patients, especially sorafenib-responders. An early switch to systemic therapies should be considered in cases that are unlikely to respond. Full article

(This article belongs to the Section Liver)

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