Mucosal Barrier Function Research Articles

The Impact of Physical Activity on the Course of Inflammatory Bowel Diseases

Inflammatory bowel diseases (IBD) including Crohn's disease (CD) and ulcerative colitis (UC), are chronic, immune-mediated conditions with increasing global prevalence. While the etiology of IBD is multifactorial—encompassing genetic, environmental, microbial, and immunological components—emerging evidence highlights the role of lifestyle factors, such as physical activity (PA), in modulating disease mechanisms and outcomes. This review explores the multifaceted impact of PA on IBD, focusing on gut microbiota composition, intestinal barrier integrity, and immune function. Moderate, regular exercise has been shown to beneficially influence gut microbial diversity, promote the production of anti-inflammatory metabolites, and support mucosal barrier function. Additionally, PA modulates systemic and intestinal immune responses, potentially reducing pro-inflammatory cytokine activity. In CD, visceral adiposity and adipokine dysregulation further complicate disease progression, suggesting a specific relevance of PA in this patient group. While observational and interventional studies indicate that PA may reduce anxiety and improve quality of life in IBD patients, the evidence regarding its effects on somatic symptoms and disease course remains inconclusive. Future randomized controlled trials are essential to establish standardized exercise protocols and clarify the therapeutic potential of PA in IBD management. Nonetheless, current data support PA as a safe, promising adjunct to conventional therapies, with potential benefits for both physical and psychological health in IBD patients.

Hydrogel derived from decellularized pig small intestine submucosa boosted the therapeutic effect of FGF-20 on TNBS-induced colitis in rats via restoring gut mucosal integrity.

Hydrogel derived from decellularized pig small intestine submucosa boosted the therapeutic effect of FGF-20 on TNBS-induced colitis in rats via restoring gut mucosal integrity.

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.

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.

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

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

Mushroom Polysaccharides as Natural Modulators of IL-17: Implications for Gut Microbiota, Autoimmune Diseases and Cancer Therapy

Interleukin-17 (IL-17, also known as IL-17A) is a member of the pro-inflammatory cytokine family that plays a pivotal role in immune defense, inflammatory responses, and tissue homeostasis. It contributes to host protection, autoimmune diseases, and cancer progression. Recent studies have highlighted the critical role of gut microbiota in immune regulation and tumor progression. Alterations in its composition can disrupt protective mechanisms, increase infection risk, and elevate the likelihood of metabolic and immune-related diseases. Mushroom polysaccharides are biological macromolecules extracted from the fruiting bodies, mycelia, or fermentation broth of mushrooms. These compounds achieve anti-tumor, anti-inflammatory, anti-oxidative, and immune-regulatory effects by modulating gut microbiota, increasing short-chain fatty acid production, enhancing intestinal mucosal barrier function, regulating lipid metabolism, and activating specific signaling pathways. Mushroom polysaccharides have been shown to regulate IL-17 both directly through key signaling pathways and indirectly by modulating gut microbiota, thereby influencing immune-related diseases and tumor progression. Therefore, mushroom polysaccharides, acting as natural regulators of IL-17, possess extensive application potentials in cancer therapy and immune disease management.

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.

Exploring the mechanism of Sinisan in the treatment of ulcerative colitis with depression based on UPLC-Q-Orbitrap-MS combined with network pharmacology, molecular docking, and experimental validation.

Exploring the mechanism of Sinisan in the treatment of ulcerative colitis with depression based on UPLC-Q-Orbitrap-MS combined with network pharmacology, molecular docking, and experimental validation.

Podophyllotoxin Alleviates DSS-Induced Ulcerative Colitis via PI3K/AKT Pathway Activation.

This study systematically evaluated the therapeutic effects of podophyllotoxin in a DSS-induced mouse model of ulcerative colitis. A total of 374 podophyllotoxin-related targets were identified through database screening, and by intersecting them with 1,741 UC-related targets, 120 potential therapeutic targets were obtained. Subsequent GO and KEGG enrichment analyses revealed that these targets are primarily involved in biological processes such as the positive regulation of protein kinase B signaling, cellular response to lipopolysaccharide, and inflammatory responses, with significant enrichment in key pathways like the PI3K-Akt signaling pathway. Molecular docking results indicated that podophyllotoxin has strong binding activity with several targets related to inflammation and signal transduction. Animal experiments further validated the significant therapeutic effects of podophyllotoxin in the DSS-induced ulcerative colitis mouse model. Particularly at high doses, podophyllotoxin effectively alleviated ulcerative colitis symptoms, reduced pathological damage to colonic tissues, and enhanced intestinal barrier function. Additionally, podophyllotoxin significantly lowered the levels of inflammatory cytokines (TNF-?, IL-1?, IL-6) in the serum and colonic tissues of ulcerative colitis model mice and improved oxidative stress status. More importantly, podophyllotoxin effectively restored the impaired intestinal mucosal barrier function by enhancing the expression of tight junction proteins such as ZO-1 and occludin. Finally, the study revealed that podophyllotoxin may alleviate ulcerative colitis symptoms and promote colonic tissue repair by activating the PI3K/AKT signaling pathway. These findings provide strong experimental evidence for the potential use of podophyllotoxin as a therapeutic agent for ulcerative colitis and offer valuable insights for the future development of ulcerative colitis treatment strategies targeting the PI3K/AKT pathway. Key words: Podophyllotoxin, Ulcerative Colitis, Inflammation, PI3K/AKT.

Dietary supplementation with Nopalea cochenillifera enhances fecal mucin production and modulates serum immunoglobulin levels in a dose- and time-dependent manner in BALB/c mice.

The aim of this study was to determine the time-dependent effects of the prickly pear (Nopalea cochenillifera) on the intestinal environment and immune function in BALB/c mice, which exhibit a predominant T helper 2 immune response. Five-week-old female BALB/c mice were divided into a control group and groups fed diets supplemented with 5% or 10% N. cochenillifera powder (NCP). Blood and feces were collected every 7 days. On day 28, in addition to blood and feces, the small intestine, cecum, and large intestine were collected. The cecum content weight, cecum content pH, and fecal mucin were examined. Serum antibody levels (total Immunoglobulin (Ig)M) were lower on days 14 and 21 in the 10% NCP group than in the control and 5% NCP groups. Total serum IgG levels were higher at all time points and total IgA levels were higher on days 7, 14, 21 and 28 in the 5% NCP and 10% NCP groups than in the control group. Total fecal IgA levels were lower in the 5% NCP and 10% NCP groups than in the control group from 14 days. Fecal mucin contents were higher in the 10% NCP group than in the control group from 7 days. These results suggest that N. cochenillifera supplementation exerts time-dependent effects on serum antibodies and the intestinal environment in BALB/c mice. In particular, NCP at 10% may enhance the intestinal mucosal barrier function and promote systemic immune responses. Further mechanistic studies are needed to determine the effects on immune responses.

Association of intestinal mucosal barrier function with intestinal microbiota in Spleen-Kidney Yang Deficiency IBS-D mice.

To establish and evaluate an IBS-D mouse model with Spleen-Kidney Yang Deficiency, explore the microecological mechanisms of IBS-D, and provide experimental evidence for the clinical diagnosis and treatment of IBS-D with Spleen-Kidney Yang Deficiency. SPF-grade female Kunming mice were used to establish an IBS-D model with Spleen-Kidney Yang Deficiency through Folium senna-adenine administration combined with restraint-clamping tail. (1) Clinical symptoms and signs were assessed using diagnostic criteria. (2) The small intestine structure was examined via Alcian blue staining, and intestinal barrier markers like D-LA (D-lactate) and DAO (diamine oxidase) were measured by ELISA to assess pathophysiological changes. (3) 16S rRNA gene sequencing was performed to analyze the intestinal microbiota. (I) The model mice exhibited symptoms of IBS-D with Spleen-Kidney Yang Deficiency. (II) ELISA and alcian blue staining revealed elevated levels of D-LA and DAO activity in the model group, indicating damage to the intestinal mucosal barrier structure. (III) Analysis of the intestinal mucosal microbiota in the model group revealed differences in dominant and characteristic bacteria at various taxonomic levels compared with those in the normal group, reflecting an imbalance in the intestinal mucosal microbiota. (IV) Lactobacillus and Lentilactobacillus are associated with mucosal barrier damage in mice modeled by Folium senna-adenine administration combined with restraint-clamping tail. The combination of Folium senna-adenine administration with restraint-clamping tail can be used to successfully establish an IBS-D mouse model with Spleen-Kidney Yang Deficiency. This model leads to damage to the intestinal mucosal structure. Streptococcus, Serratia, Helicobacter, Phocaeicola, and Desulfomicrobium may serve as potential biological markers for the intestinal mucosal microbiota.

Therapeutic Effects and Molecular Mechanism of Banxia Xiexin Decoction on Intestinal Mucosal Barrier Function in Sepsis.

This study aims to investigate therapeutic effects and involved molecular mechanisms of Banxia Xiexin Decoction (BXD) in reducing gastrointestinal complications associated with sepsis. Sepsis is a common critical illness that threatens patient survival and costs society a lot. This syndrome is a prominent cause of death in ICUs due to its high mortality rate, which exceeds 30% after 28 days and 35.5% after 90 days. Sepsis remains a major medical challenge despite a 20%-30% drop in fatality rates due to a better understanding of its physiological and pathological features and better therapeutic techniques. There is no pharmacological treatment for sepsis, highlighting the need for more study. We explored the protecting effects of BXD on intestinal functionality in sepsis by investigating its roles in the regulation of mitochondrial autophagy and mitochondrial functioning in small intestinal epithelial cells, primarily via the PINK1/Parkin signaling pathway. We established a cell model of Human Intestinal Epithelial Cell (HIEC) injury induced by lipopolysaccharide (LPS) and a cecal ligation and perforation (CLP) sepsis model in Sprague Dawley (SD) rats. The cell model and animal model of sepsis were divided into control groups and different treatment groups that received different doses of BXD. We utilized HIECs with PINK1 knockdown to assess BXD's protective effects on the sepsis intestinal barrier and its regulatory mechanism both on the PINK1/Parkin signaling pathway, exploring both its facilitative and inhibitory effects. ELISA method was used to measure inflammatory markers IL-6, IL-1β, and intestinal injury-related molecules IFABP and DAO. Pathological assessments were performed with H&E staining, and tight junction proteins ZO-1 and Occludin were detected using immunohistochemical staining. Mitochondrial membrane protein TOM20 was detected through immunofluorescence staining. Mitochondrial membrane potential and autophagy were assessed via flow cytometry. The expression levels of PINK1, Park, LC3, and p62 proteins and mRNA, integral to the PINK1/Parkin autophagy pathway, were evaluated using Western Blot and RT-PCR. Compared to the control group, BXD therapy significantly lowered serum DAO, IFABP, and DA. The BXD therapy group showed a more significant and sustained drop in IL-6 and IL-1β levels than the control group. The BXD therapy reduced intestinal mucosa damage by lowering DAO and IFABP. BXD also restored tight junction proteins ZO-1 and Occludin, improving intestinal mucosal barrier function. In septic rats, BXD therapy lowered serum IL-6 and IL-1β levels, avoiding inflammation and reducing intestinal damage. BXD enhanced TOM20, which protected intestinal epithelial cell mitochondria against decreasing mitochondrial membrane potential. BXD increased the PINK1/Parkin mitochondrial autophagy pathway at the molecular level. Mitochondrial autophagy can repair mitochondria, reduce oxidative stress, maintain mitochondrial homeostasis, and help intestinal epithelial cells survive and function. BXD could improve intestinal mucosal damage and systemic inflammation caused by sepsis. BXD mainly promotes the PINK1/Parkin mitophagy pathway by upregulating PINK1 protein.

Control observation of different digestive tract reconstruction methods in total gastrectomy for gastric cancer

BACKGROUND For patients with advanced gastric cancer, surgical resection remains the main treatment option. Total gastrectomy combined with radical resection of gastric cancer lesions and sentinel lymph nodes can significantly prolong the survival of patients. Digestive tract reconstruction after total gastrectomy is essential to maintain gastrointestinal function and optimize postoperative recovery. Therefore, it is very important to choose a suitable reconstruction method to improve the quality of life of total gastrectomy patients. AIM To evaluate the effects of different digestive tract reconstruction methods in gastric cancer patients undergoing total gastrectomy. METHODS This retrospective study included 172 patients who underwent total gastrectomy for gastric cancer at The First Hospital of Hebei Medical University for analysis. The patients were categorized into two groups: Group A, consisting of 90 patients who underwent modified Roux-en-Y gastrojejunostomy, and group B, consisting of 82 patients who underwent uncut Roux-en-Y gastrojejunostomy. The general patient characteristics, perioperative indicators, postoperative gastrointestinal mucosal barrier function, nutritional status, immunological markers, and occurrence of complications were compared between the two groups. RESULTS Group A showed shorter digestive tract reconstruction time than group B (P < 0.05). On the first postoperative day, group A showed lower serum levels of D-lactate, diamine oxidase, and endotoxin than group B (P < 0.05). One month postoperatively, group A showed higher prognostic nutritional index, serum albumin, total protein, and body weight than group B (P < 0.05). One month postoperatively, the levels of cluster of differentiation (CD) 3 +, CD4 +, and CD8 + cells were not significantly different between two groups (P > 0.05). The complication rates were 10.00% in group A and 24.39% in group B; group A had a significantly lower complication rate than group B (P < 0.05). CONCLUSION Using modified Roux-en-Y gastrojejunostomy during total gastrectomy shortens the time required for gastrointestinal anastomosis, reduces surgery-induced gastrointestinal mucosal damage, and mitigates postoperative declines in nutritional status.

Evidence for a Modulatory Effect of a 12-Week Pomegranate Juice Intervention on the Transcriptional Response in Inflammatory Bowel Disease Patients Reducing Fecal Calprotectin Levels: Findings From a Proof-of-Principle Study.

This study aimed at investigating the effects of pomegranate juice (POMJ) consumption on inflammatory biomarkers and gene expression in patients with inflammatory bowel disease (IBD) in clinical remission. In this randomized, placebo-controlled trial, 16 subjects with IBD in remission consumed POMJ or placebo for 12 weeks. POMJ consumption significantly reduced fecal calprotectin (FC) and plasma endotoxin levels. Transcriptomic analysis of peripheral blood mononuclear cells revealed upregulation of genes involved in mucosal immunity, including aryl hydrocarbon receptor (AHR), neutrophil cytosolic factor 4 (NCF4), and nuclear factor, interleukin 3 regulated (NFIL3). Urolithin metabotypes were predominantly of the B type, associated with intestinal dysbiosis. No significant changes were observed in serum inflammatory markers or colonic mucosal cytokine expression. POMJ consumption reduced markers of intestinal inflammation and modulated gene expression related to mucosal immunity and barrier function in patients with IBD. These findings suggest the potential of POMJ as a beneficial dietary intervention for maintaining remission in IBD, highlighting the promise of targeted nutritional strategies in managing chronic inflammatory conditions. Further research is needed to elucidate the long-term clinical implications of these molecular changes. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT03000101.

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.

Effects of Ficus carica L. polysaccharide on the intestinal immune function and microbiota of broilers.

Ficus carica L. polysaccharides (FLPs) are groups of biologically active compounds extracted from Ficus carica L. In this study, we analyzed the structure of FLPs, predicted their immune enhancement pathway, and detected the impact of FLPs on the growth performance, immune function, and intestinal microflora of broiler chickens. The results showed that FLPs are comprised of monosaccharides including rhamnose, arabinose, mannose, glucose, and galactose. Feeding with FLPs significantly promoted the growth performance, slaughtering performance, and immune organs index of chickens compared to the control group (p < 0.05). Moreover, the FLP-h and FLP-m groups had increased levels of sIgA, IgG, IL-4, IL-5, IL-12, and IFN-g; improved immunity and barrier function; and a higher percentage of spleen CD4+ and CD8+ T cell differentiation compared to the control group (p < 0.05). Additionally, the FLP-h group had increased levels of various SCFAs, and increased beneficial bacteria such as Firmicutes at the phylum level and Faecalibacterium, Blautia, Phascolarctobacterium, and Alistipes at the genus level. The results of network pharmacology and KEGG pathway prediction indicate that FLPs may change the structure and metabolism of intestinal microbiota by enhancing carbon fixation pathways in prokaryotes, and promote intestinal immune barrier function through the joint action of bisphenol degradation, retinol metabolism, NODlike signaling pathways, toll-like receptor signaling pathways, and the MAPK signaling pathway. These results suggest that FLP-h supplementation effectively promotes growth performance and enhances the intestinal mucosal immune barrier function in chickens.

Butyrate alleviates food allergy by improving intestinal barrier integrity through suppressing oxidative stress-mediated Notch signaling.

Food allergy (FA) has received increased attention in recent years. Multiple studies have highlighted the crucial role of short-chain fatty acids (SCFAs) in the development of IgE-mediated FA. Here, a case-control approach was employed to analyze SCFAs profiles in children with FA, while an ovalbumin (OVA)-sensitized mouse model was utilized to explore the underlying mechanism by which SCFAs mitigate FA. Children with food-sensitized tolerance (FST) (n = 20) or FA (n = 20), and healthy controls (HC) (n = 20) were recruited to analyze SCFAs profiles. The HC group exhibited higher SCFAs levels in fecal samples than the FST, FA, and FST + FA groups. Data from an OVA-sensitized mouse model showed that butyrate exhibited a more significant effect on reducing allergic reactions compared to other SCFAs. Compared to the negative control group, OVA-induced oxidative stress (OS) triggered excessive Notch signaling activation, which subsequently impaired both tight junctions integrity and mucosal barrier function in murine intestinal epithelial cells (IECs). Gut dysbiosis induced mucus layer erosion, thereby elevating IECs exposure to food antigens and OS, which potentiated Notch signaling activation. However, butyrate counteracted this loop by restoring microbiota structure and suppressing reactive oxygen species (ROS)/Notch cascades. Strikingly, low-dose butyrate (0.25-1 mM) protected rat small intestine crypt epithelial cells (IEC-6) by inhibiting ROS, whereas high-dose (2-5 mM) exacerbated oxidative injury and triggered activation of Notch signaling. Our study revealed the potential molecular mechanisms through which butyrate alleviates food allergy, providing a potential therapeutic strategy for its management.

Importance of rectal over colon status in ulcerative colitis remission: the role of microinflammation and mucosal barrier dysfunction in relapse.

Ulcerative colitis (UC) is a refractory inflammatory disease that affects the rectum and colon, with pivotal involvement of the rectal environment in relapse initiation. This study was conducted in two phases to examine the differences in gene expression between the rectum and colon and to identify relapse factors. In ***Study 1, RNA sequencing was performed on biopsies from the colon and rectum of patients with active UC, those with remission UC, and controls. In Study 2, the mucosal impedance (MI) values reflecting mucosal barrier function and the mRNA expression of tight junction proteins and inflammatory cytokines were examined in 32 patients with remission UC and 22 controls. Relapse was monitored prospectively. In Study 1, comprehensive genetic analysis using RNA sequencing revealed distinct gene profiles in the rectum and sigmoid colon of patients with remission UC. The rectum of these patients exhibited an enriched immune response and apical junction phenotype with persistent upregulation of CLDN2 gene expression. In Study 2, even in patients with remission UC, the MI values in the rectum, but not in the sigmoid colon, were significantly decreased, whereas they were negatively correlated with CLDN2, IL-1β, and IL-6 expressions. The status of the rectum in patients with remission UC differs from that of the colon, with microinflammation and impaired mucosal barrier function, which are associated with the upregulation of CLDN2, playing a role in relapse.

Nasal transcriptome differences preceding recurrent wheezing in infancy.

Nasal transcriptome differences preceding recurrent wheezing in infancy.

Escin Ia ameliorates DSS-induced chronic colitis in mice by inhibiting inflammation and oxidative stress via the LOXL2/MMP-9 pathway.

Escin Ia ameliorates DSS-induced chronic colitis in mice by inhibiting inflammation and oxidative stress via the LOXL2/MMP-9 pathway.