Mucosal Barrier Research Articles

Management of Oral Mucositis in Pediatric Patients: APractical Overview of Available Treatment.

Oral mucositis (OM) is an inflammatory condition associated with breakdown of the protective mucosal barrier. Clinically, it can range from mucosal erythema to painful ulcerations that can lead to malnutrition, secondary infection, and increased medical costs due to hospitalizations. Existing literature regarding OM primarily investigates antineoplastic-induced OM in the adult population; however, many non-oncologic disease processes can present with OM, including autoimmune and infectious conditions such as pemphigus vulgaris, recurrent aphthous stomatitis, oral lichen planus, and reactive infectious mucocutaneous eruption. Management of OM is largely palliative and can be grouped into four domains: pain control, oral decontamination, nutritional support, and palliation of dry mouth. This review aims to articulate the current topical management strategies for symptom relief and treatment of OM in children secondary to non-oncologic disease processes. Future studies are needed to strengthen the evidence base for interventions in children with refractory OM that is not caused by oncotherapy.

Characterization of the intestinal microorganism in patients with congenital intestinal atresia: the preliminary exploration for establishment and influence of initial intestinal flora in newborns

PurposeThis study aimed to analyze the differences in microbial composition between the proximal and distal intestinal segments of newborns with intestinal atresia, speculating about the mechanism underlying the initial establishment of neonatal intestinal flora. Additionally, differential metabolic pathways were explored to predict their potential effects on gravidas and fetuses.MethodsThe microbial characteristics of intestinal flora were assessed using 16SrRNA sequencing. The alpha and beta-diversity indices were calculated to compare the microbial composition among three groups. Principal Coordinates Analysis (PCoA) was employed to identify and quantify differences in microbial communities. Furthermore, PICRUSt software was utilized to predict the possible functional impacts of differential metabolic pathways by comparing them with public databases.ResultsSamples were collected from 23 neonates with intestinal atresia (proximal and distal segments) and 25 healthy neonates (first meconium) based on predefined selection criteria. No significant differences in baseline characteristics were observed between the control and intestinal atresia groups (P > 0.05). Alpha-Diversity analysis revealed that the distal intestinal group exhibited greater microbial species richness. Beta-Diversity analysis indicated significant differences in bacterial composition between the control group and the distal intestinal group (P < 0.05), with the distal group showing a more pronounced divergence compared to the proximal group. Functional prediction analysis suggested that the differential metabolic pathways might protect the intestinal mucosal barrier. However, they could also negatively impact blood glucose regulation and lipid transport in gravidas and fetuses, potentially contributing to adverse emotional states in pregnant women.ConclusionThe distinct microbial profiles observed among the three groups suggest that the establishment of neonatal intestinal flora may result from a combination of placental transmission and digestive tract colonization. Functional pathway analysis suggested these microbial metabolic differences may exert pleiotropic effects, demonstrating both protective roles in intestinal barrier function and potentially detrimental impacts on emotional modulation and glucose/lipid dysregulation.

Intraepithelial lymphocytes in human oral diseases

ObjectiveAs a distinctive subset of T cells, intraepithelial lymphocytes (IELs) are found in the epithelium of mucosal barrier and serve as the primary defenders of the intestinal mucosal immune system. IELs exhibit phenotypic and functional diversity with high expression of activated marker molecules, tissue-homing integrins, NK cell receptors, cytotoxic T cell-related molecules, and cytokines. Meanwhile, IELs demonstrate differentiation plasticity, antigen recognition diversity, self-reactivity, and rapid “memory” effect, which enable them to play a crucial role in regulating responses, maintaining mucosal barriers, promoting immune tolerance, and providing resistance to infections. In addition, IELs have been explored in autoimmune diseases, inflammatory diseases, and cancers. However, the specific involvement and underlying mechanisms of IELs in oral diseases have not been systematically discussed.MethodsA systematic literature review was conducted using the PubMed/MEDLINE databases to identify and analyze relevant literatures on the roles of IELs in oral diseases.ResultsThe literature review revealed the characteristics of IELs and emphasized the potential roles of IELs in the pathogenesis of oral lichen planus, oral cancers, periodontal diseases, graft-versus-host disease, and primary Sjogren’s syndrome.ConclusionThis review mainly focuses on the involvement of IELs in oral diseases, with a particular emphasis on the main functions and underlying mechanisms by which IELs influence the pathogenesis and progression of these conditions.

Glycemic control and vaccine response: the role of mucosal immunity after vaccination in diabetic patients

This review explores the critical interplay between glycemic control, mucosal immunity, and vaccine response in diabetic patients. Diabetes mellitus, characterized by impaired glucose regulation, significantly impacts immune function, particularly at mucosal surfaces. Poor glycemic control diminishes vaccine-induced antibody responses and compromises mucosal defenses, such as secretory IgA production, increasing susceptibility to infections. We synthesize evidence highlighting the importance of optimizing glycemic management prior to vaccination to enhance immunogenicity. Furthermore, we examine the potential of personalized vaccination strategies, tailored to individual glycemic status, age, BMI, and kidney function, to improve vaccine efficacy in this vulnerable population. Additionally, we discuss the role of adjunct therapies, including probiotics, nutritional interventions, and lifestyle modifications, in modulating the gut microbiota and reinforcing mucosal barrier integrity. This review underscores the necessity for an interdisciplinary approach, integrating metabolic management with innovative vaccine designs, to maximize protection against infectious diseases in diabetic patients. Future research should prioritize longitudinal studies assessing both systemic and mucosal immunity and refine personalized vaccination strategies to ensure robust and durable protection.

Tranilast Reduces Intestinal Ischemia Reperfusion Injury in Rats Through the Upregulation of Heme-Oxygenase (HO)-1

Background: Intestinal ischemia reperfusion injury (IRI) is a harmful process that occurs during intestinal infarction and intestinal transplantation (ITx). It is characterized by severe inflammation which disrupts the mucosal barrier, causing bacterial translocation and sepsis. Tranilast (N-[3,4-dimethoxycinnamoyl]-anthranilic acid) (TL) is a synthetic compound with powerful anti-inflammatory properties. Objective: To investigate the effect of pretreatment with TL in a validated rat model of intestinal IRI (60 min of ischemia). Methods: TL (650 mg/kg) was administered by oral gavage 24 and 2 h before the onset of ischemia. Experiment 1 examined 7-day survival in 3 study groups (sham, vehicle+IRI and TL+IRI, n = 10/group). In Experiment 2, the effects on the intestinal wall integrity and inflammation were studied after 60 min of reperfusion using 3 groups (sham, IRI and TL+IRI, n = 6/group). The following end-points were studied: L-lactate, intestinal fatty acid-binding protein (I-FABP), histology, intestinal permeability, endotoxin translocation, pro- and anti-inflammatory cytokines and heme oxygenase-1 (HO-1) levels. Experiment 3 examined the role of HO-1 upregulation in TL pretreatment, by blocking its expression using Zinc protoporphyrin (ZnPP) at 20 mg/kg vs. placebo (n = 6/group). Results: Intestinal IRI resulted in severe damage of the intestinal wall and a 10% 7-day survival. These alterations led to endotoxin translocation and upregulation of pro-inflammatory cytokines. TL pretreatment improved survival up to 50%, significantly reduced inflammation and protected the intestinal barrier. The HO-1 inhibitor ZnPP, abolished the protective effect of TL. Conclusions: TL pretreatment improves survival by protecting the intestinal barrier function, decreasing inflammation and endotoxin translocation, through upregulation of HO-1.This rat study of severe intestinal ischemia reperfusion injury demonstrates a novel role for Tranilast as a potential therapy. Administration of Tranilast led to a marked reduction in mortality, inflammation and intestinal permeability and damage. The study proved that Tranilast functions through upregulation of heme oxygenase-1.

Non-antibiotic therapies for multidrug-resistant gastrointestinal infections: an overview of the use of probiotics, natural compounds, and bacteriophages

The worldwide increasing frequency and severity of multidrug-resistant gastrointestinal (MDR-GI) infections not only raises awareness of the debilities of conventional antibiotic treatments but also highlights the demand for alternative interventions. One of these alternatives is probiotics, harmless bacteria that compete with pathogenic species, which have been considered beneficial due to their therapeutic potential since they strengthen the mucosal barrier and modulate the host immune response. Other natural compounds (e.g., polyphenols, flavonoids, and essential oils) present diverse antimicrobial mechanisms, which are promising alternatives to mitigate resistant pathogens. Finally, bacteriophages, viruses that target specific bacteria, constitute a precise approach in which MDR bacteria are lysed or disrupted by the biofilms formed during colonization without compromising the normal gut microbiome. Therefore, the present manuscript provides an integrated perspective on alternative non-antibiotic therapies to manage MDR-GI infections; for this purpose, it covers aspects such as their action mechanisms, current clinical applications, and the challenges that limit their broader application in clinical practice. The potential of combining these approaches or personalizing infection treatments adjusted to patients’ microbiome profiles is also discussed, aiming to enhance efficacy and reduce resistance risks. Finally, the importance of continued research and development to optimize these alternatives is also debated, addressing aspects such as the need to surpass regulatory barriers and conducting large-scale clinical trials to establish the safety and efficacy of these non-antibiotic alternatives. This overview of the current knowledge contributes to the ongoing efforts to develop sustainable strategies to combat MDR-GI infections and reduce the global burden of antibiotic resistance.

Ingestion of Artemisia argyit essential oil combats Salmonella pullorum infections by altering gut microbiota composition in chicks

Pullorum disease, caused by Salmonella pullorum (S. pullorum), is a highly contagious illness affecting the poultry industry. Emerging evidence suggests that Artemisia argyit essential oil can influence the composition of gut microbes in the host, thereby promoting overall health. However, the specific mechanisms by which Artemisia argyit essential oil modulates gut microbiota to combat S. pullorum infection remains unclear. This study explored the effectiveness of various doses of Artemisia argyit essential oil in preventing S. pullorum infection in chicks. Our findings indicate that consuming this essential oil can mitigate the intestinal mucosal barrier damage and excessive inflammatory response caused by S. pullorum, as well as reverse the weight loss seen in infected chicks. Additionally, chicks that received faecal microbiota transplantation (FMT) from the gut microbiota of Artemisia argyit essential oil donors exhibited notable recovery from S. pullorum infections. This suggests that the observed protection may be linked to the modulation of gut microbiota. Furthermore, 16S rRNA sequencing revealed an increased abundance of Lactobacillus reuteri (L. reuteri), which along with the activation of Wnt/β-catenin pathways, played critical roles in the enhanced health of S. pullorum-infected chicks treated with Artemisia argyit essential oil. In summary, these findings highlight that the dietary inclusion of Artemisia argyit essential oil promotes the intestinal enrichment of L. reuteri, offering a promising strategy for the treatment and prevention of pullorum disease in chicks.

Impairment of Esophageal Barrier Integrity: New Insights into Esophageal Symptoms in Post-COVID-19.

The COVID-19 pandemic, caused by SARS-CoV-2, has unveiled a range of symptoms beyond the respiratory system, including significant gastrointestinal manifestations. This study explores the prevalence and intensity of gastroesophageal symptoms in post-COVID-19 patients and the integrity of the esophageal epithelial barrier. We conducted a prospective longitudinal cohort study with 55 patients hospitalized due to COVID-19 at a University Hospital. Patients were evaluated during hospitalization and between 3 and 6months post-discharge, using validated questionnaires for gastrointestinal and gastroesophageal reflux symptoms. Additionally, 25 of these patients underwent upper digestive endoscopy, with esophageal mucosal biopsies analyzed for transepithelial electrical resistance (TER), permeability, and expression of inflammatory cytokines and cell junction proteins. Data expressed as mean EPM, inference bytwo-way ANOVA. Results were considered statistically significant at p < 0.05. There were significant increases in heartburn and acid reflux symptoms in post-COVID-19 patients, as measured by the GSRS questionnaire. Biopsies from post-COVID patients revealed increased esophageal permeability when compared to non-COVID patients in acidic media (pH 2: non-COVID-19: 717.8 ± 168.2 vs. post-COVID-19: 1377.6 ± 316.4), suggesting compromised mucosal barrier. Furthermore, IL-8 levels and expression of Claudin-2 were elevated in these patients. The data suggested that COVID-19 infection may cause lasting damage to the esophageal epithelial barrier, increasing its permeability and provoking an exacerbated inflammatory response. These changes may explain the prevalence of post-infection gastroesophageal symptoms. Our findings underscored the importance of continuous monitoring and the development of therapeutic strategies to mitigate gastroesophageal effects in patients recovering from COVID-19.

Effects of Dietary Clostridium butyricum on Growth and Intestinal Mucosal Barrier Functions of Juvenile Channel Catfish (Ictalurus punctatus)

An 8-week feeding trial was conducted to investigate the effects of dietary Clostridium butyricum on the growth and intestinal mucosal barrier functions of juvenile channel catfish (Ictalurus punctatus). The diets included the control group feed (CD group) and the treatment group feed (containing 1 × 108 CFU/g C. butyricum; CB group). The CB group showed a rising trend in the growth performance. The CB group had significantly higher digestive and antioxidant enzyme activities, and significantly lower malondialdehyde and superoxide anion contents of the intestine. In terms of intestinal mechanical barrier, the CB group showed significantly higher gene expression of intestinal tight junction proteins. With regard to intestinal immune barrier, the CB group displayed significantly lower gene expression of pro-inflammatory factors. Regarding intestinal chemical barrier, the CB group had significantly higher gene expression of mucin-4, β-galactoside-binding lectin, lysozyme-c, and NK-lysin type 1. Dietary C. butyricum significantly increased the abundance of some beneficial bacteria and increased the levels of some beneficial metabolites in the intestine. Collectively, dietary C. butyricum could increase growth, enhance intestinal digestion and antioxidant capacity, strengthen intestinal mucosal barrier, and improve the intestinal metabolism of juvenile channel catfish.

Dietary isobutyric acid supplementation improves intestinal mucosal barrier function and meat quality by regulating cecal microbiota and serum metabolites in weaned piglets

This study aimed to provide evidence for the effects of isobutyric acid on the intestinal mucosal barrier and gut microbiota in weaned piglets. In this study, 30 piglets were divided into two groups: one group was fed a standard diet (CON group), and the other group was fed a diet supplemented with 0.5% isobutyric acid (IB group) for 21 days. The results showed that isobutyric acid significantly increased (p &amp;lt; 0.05) serum immunity and antioxidant capacity in weaned piglets. In small intestine of piglets, the ratio of villus height to crypt depth was significantly increased (p &amp;lt; 0.05). Administration of isobutyric acid also increased (p &amp;lt; 0.05) the expression of genes related to intestinal mucosal barrier function. Cecal microbiota analysis revealed that isobutyric acid significantly increased (p &amp;lt; 0.05) the abundance of the Eubacterium coprostanoligenes group. Untargeted serum metabolomics analysis indicated that the top three categories of metabolites were lipids and lipid-like molecules, organic acids and derivatives, and organic heterocyclic compounds. Additionally, in longissimus thoracis muscle, isobutyric acid significantly increased (p &amp;lt; 0 0.05) intramuscular fat and triglyceride content compared with the CON group. Overall, isobutyric acid can improve small intestinal mucosal barrier function, and may influence the fat deposition through the regulation of serum metabolites in weaned piglets.

Immune modulation for the patterns of epithelial cell death in inflammatory bowel disease.

Immune modulation for the patterns of epithelial cell death in inflammatory bowel disease.

An intranasal subunit vaccine induces protective systemic and mucosal antibody immunity against respiratory viruses in mouse models

Although vaccines are usually given intramuscularly, the intranasal delivery route may lead to better mucosal protection and limit the spread of respiratory virus while easing administration and improving vaccine acceptance. The challenge, however, is to achieve delivery across the selective epithelial cell barrier. Here we report on a subunit vaccine platform, in which the antigen is genetically fused to albumin to facilitate FcRn-mediated transport across the mucosal barrier in the presence of adjuvant. Intranasal delivery in conventional and transgenic mouse models induces both systemic and mucosal antigen-specific antibody responses that protect against challenge with SARS-CoV-2 or influenza A. When benchmarked against an intramuscularly administered mRNA vaccine or an intranasally administered antigen fused to an alternative carrier of similar size, only the albumin-based intranasal vaccine yields robust mucosal IgA antibody responses. Our results thus suggest that this needle-free, albumin-based vaccine platform may be suited for vaccination against respiratory pathogens.

Mucosal immune responses to SARS-CoV-2 infection and COVID-19 vaccination.

To determine whether SARS-CoV-2 infection or vaccination elicits specific neutralising antibodies in saliva, and to assess the longevity of protection. Initially, 111 COVID-19 convalescent participants were recruited, 11-369days after diagnosis. Saliva and blood samples were assayed for antibodies specific for Spike protein, Receptor Binding Domain and Nucleoprotein. In a second cohort, 123 participants were recruited. Saliva and serum antibodies to the same antigens were assayed before and after their first and second COVID-19 vaccinations, with 150day follow up. Natural infection induces and boosts IgA and IgG in oral fluid and serum; vaccination does not induce or boost specific saliva IgA; IgG can be found in saliva after vaccination, but only when serum IgG concentrations are high; IgA is important for SARS-CoV-2 neutralisation activity by oral fluid, but there can also be contributions from serum IgG and other factors. New COVID-19 vaccines should target both systemic and mucosal immunity, to establish a first line of immune defence at the mucosal barrier. This would benefit vulnerable patient populations and may help to eradicate SARS-CoV-2 circulation.

Lentinan mitigates ulcerative colitis via the IL-22 pathway to repair the compromised mucosal barrier and enhance antimicrobial defense.

Lentinan mitigates ulcerative colitis via the IL-22 pathway to repair the compromised mucosal barrier and enhance antimicrobial defense.

Neonatal Fc receptor participates in endocytosis of Fc fusion protein in vivo and in vitro.

Neonatal Fc receptor participates in endocytosis of Fc fusion protein in vivo and in vitro.

Administration of EPA improves lipopolysaccharide-induced intestinal dysfunction in turbot (Scophthalmus maximus L.) through modulation of TORC1 signaling.

Administration of EPA improves lipopolysaccharide-induced intestinal dysfunction in turbot (Scophthalmus maximus L.) through modulation of TORC1 signaling.

Gut Microbiota Dysbiosis: Pathogenesis, Diseases, Prevention, and Therapy.

Dysbiosis refers to the disruption of the gut microbiota balance and is the pathological basis of various diseases. The main pathogenic mechanisms include impaired intestinal mucosal barrier function, inflammation activation, immune dysregulation, and metabolic abnormalities. These mechanisms involve dysfunctions in the gut-brain axis, gut-liver axis, and others to cause broader effects. Although the association between diseases caused by dysbiosis has been extensively studied, many questions remain regarding the specific pathogenic mechanisms and treatment strategies. This review begins by examining the causes of gut microbiota dysbiosis and summarizes the potential mechanisms of representative diseases caused by microbiota imbalance. It integrates clinical evidence to explore preventive and therapeutic strategies targeting gut microbiota dysregulation, emphasizing the importance of understanding gut microbiota dysbiosis. Finally, we summarized the development of artificial intelligence (AI) in the gut microbiota research and suggested that it will play a critical role in future studies on gut dysbiosis. The research combining multiomics technologies and AI will further uncover the complex mechanisms of gut microbiota dysbiosis. It will drive the development of personalized treatment strategies.

MiR-483 targeting integrin β4 regulates the stability of intestinal barrier in turbot (Scophthalmus maximus) during pathogen infection.

MiR-483 targeting integrin β4 regulates the stability of intestinal barrier in turbot (Scophthalmus maximus) during pathogen infection.

Angelicin ameliorated ulcerative colitis through activating HDAC1-derived HIF-1α acetylation.

Angelicin ameliorated ulcerative colitis through activating HDAC1-derived HIF-1α acetylation.

NUDT1 aggravates intestinal epithelial barrier injury through oxidative stress in ulcerative colitis.

NUDT1 aggravates intestinal epithelial barrier injury through oxidative stress in ulcerative colitis.