Search Results (777)

Background: Eleutherococcus senticosus (Rupr. et Maxim.) Maxim., widely used in Russian and Chinese traditional medicine for its anti-inflammatory activity, contains bioactive compounds capable of stabilizing epithelial function and reducing inflammation. Despite prior research on its effects in the colon, the impact and mechanism of action of E. senticosus fruit extract on epithelial tissues of the upper digestive and respiratory tract remains unexplored. Objectives: This study aimed to evaluate the influence of E. senticosus fruit extract on the transepithelial electrical potential and resistance in the tracheal and small intestinal epithelium of rabbits. In addition, the chemical composition of the extract was also profiled by the means of UHPLC-DAD-MS. Methods: Tissue segments from the trachea and small intestine of New Zealand white male rabbits were examined using the Ussing chamber technique. Three concentrations of E. senticosus fruit extract (0.001, 0.1, 10 mg/100 mL) were applied, and changes in transepithelial electrical potential (dPD) and resistance (R) were recorded. Chemical analysis of the extract was conducted using UHPLC-DAD-MS. Results: For the first time, we have discovered that the E. senticosus extract increased membrane resistance in tracheal tissue, suggesting enhanced barrier integrity. In contrast, a slight decrease in resistance was observed in small intestinal tissue. UHPLC-DAD-MS confirmed the presence of chlorogenic acid, dicaffeoylquinic acids, quercetin derivatives, and myo-inositol, compounds known for their antioxidant, anti-inflammatory, and membrane-stabilizing effects. Conclusions: The differential response of respiratory and intestinal epithelium to the E. senticosus extract highlights its tissue-specific action and supports its traditional use in the prevention and treatment of diseases characterized by epithelial barrier dysfunction, such as asthma, COPD, and Crohn’s disease. Full article

Schizochytrium is often added to feed to enhance the growth and health of farmed animals, yet research on its effects on amphibians remains relatively scarce. Here, this study investigated the effects of dietary Schizochytrium meal on growth, metamorphosis, intermediate metabolism, and intestinal health of bullfrogs. Six compound feeds (S0–S5) containing different gradients of Schizochytrium meal (0.00, 2.00, 5.00, 10.00, 15.00, and 20.00 g/kg diets) were formulated. After 90 days, the S4 group (15.00 g/kg) exhibited significantly superior growth performance, with the weight gain rate (WGR) increasing by up to 23.78% compared to the control (S0). Metamorphosis rate (MR) peaked at 23.33% in the S4 group. The enzyme activities of digestion (amylase (AMS), lipase (LPS), protease), brush border membrane (Na⁺, K⁺-ATPase, alkaline phosphatase (AKP), γ-glutamyl transferase (γ-GT), creatine kinase (CK), and antioxidation (superoxide dismutase (SOD), catalase (CAT)), as well as microvilli length and mucosal epithelial cell height in the intestine were the highest in the S4 group. Intestinal microbial diversity (Ace index) significantly increased by 41.28% in the S4 group, which also promoted beneficial bacteria. Key genes related to the GH-IGF-1 axis, metabolism, and intestinal barrier function were significantly upregulated with increasing Schizochytrium levels up to 15.00 g/kg, whereas pro-inflammatory genes showed an opposite trend. Overall, dietary supplementation with Schizochytrium meal at 15.00 g/kg promotes growth, metamorphosis, and intestinal health in bullfrog tadpoles by modulating the GH-IGF-1 axis, enhancing digestion and absorption, and improving intestinal integrity. Optimal Schizochytrium meal levels were identified as 13.27 g/kg. Full article

Microphysiological systems (MPSs) have emerged as alternatives to animal testing in drug development, following the FDA Modernization Act 2.0. Double-layer channel-type MPS chips with porous membranes are widely used for modeling various organs, including the intestines, blood–brain barrier, renal tubules, and lungs. However, these chips faced challenges owing to optical interference caused by light scattering from the porous membrane, which hinders cell observation. Trans-epithelial electrical resistance (TEER) measurement offers a non-invasive method for assessing barrier integrity in these chips. However, existing electrode-integrated MPS chips for TEER measurement have non-uniform current densities, leading to compromised measurement accuracy. Additionally, chips made from polydimethylsiloxane have been associated with drug absorption issues. This study developed an electrode-integrated MPS chip for TEER measurement with a uniform current distribution and minimal drug absorption. Through a finite element method simulation, electrode patterns were optimized and incorporated into a polyethylene terephthalate (PET)-based chip. The device was fabricated by laminating PET films, porous membranes, and patterned gold electrodes. The chip’s performance was evaluated using a perfused Caco-2 intestinal model. TEER levels increased and peaked on day 5 when cells formed a monolayer, and then they decreased with the development of villi-like structures. Concurrently, capacitance increased, indicating microvilli formation. Exposure to staurosporine resulted in a dose-dependent reduction in TEER, which was validated by immunostaining, indicating a disruption of the tight junction. This study presents a TEER measurement MPS platform with a uniform current density and reduced drug absorption, thereby enhancing TEER measurement reliability. This system effectively monitors barrier integrity and drug responses, demonstrating its potential for non-animal drug-testing applications. Full article

Irritable Bowel Syndrome (IBS) is a common gastrointestinal disorder, characterized by abdominal pain, altered bowel habits (diarrhea and/or constipation) and a dysbiosis of the gut microbiome. This dysbiosis is difficult to restore via fiber supplementation, which typically promotes gas production, potentially worsening IBS symptoms. We therefore studied how two novel products, triacetin (TA; REBiome™) and a mushroom blend (MB; Hōlistiq™), modulate the microbiome of IBS subjects (n = 8) using the ex vivo SIFR^® (Systemic Intestinal Fermentation Research) technology combined with a co-culture of epithelial/immune (Caco-2/THP-1) cells. First, the IBS microbiomes revealed large interpersonal variability and an IBS-associated dysbiosis. TA increased the beneficial metabolites acetate and butyrate (~Anaerobutyricum soehngenii, Mediterraneibacter_A butyricigenes, Faecalibacterium prausnitzii). Moreover, MB stimulated a wide range of gut microbes and additionally promoted propionate. Despite more strongly increasing total short-chain fatty acid (SCFA) levels, TA induced significantly less gas production than MB. Mechanistically, acetate with TA was derived from hydrolysis, a process that indeed does not induce gas production. Notably, both TA and MB enhanced gut barrier integrity (transepithelial electrical TEER), which is related to lower symptom severity in IBS patients. Overall, our findings highlight the product-specific microbiome modulation and potential of MB, TA or combinations thereof as dietary interventions for managing IBS symptom severity. Full article

Ulcerative colitis (UC) is a chronic inflammatory bowel disease marked by disruption of the intestinal barrier and gut microbiota imbalance, leading to significant impairment in patient quality of life. This study investigated the therapeutic efficacy of a synbiotic formulation composed of purified fucoidan from bloom-forming Sargassum horneri and the probiotic Lactobacillus plantarum in a dextran sulfate sodium (DSS)-induced zebrafish model of UC. Polysaccharides from S. horneri were extracted using Celluclast-assisted extraction and fractionated via DEAE anion-exchange chromatography, resulting in six fucoidan fractions. The sixth fraction (SH-F), with a molecular weight of 254 kDa, showed the highest fucose, sulfate contents, and demonstrated the highest effect on promoting L. plantarum growth. Structural analysis revealed that SH-F contained α-L-Fucp-(1→3), α-L-Fucp-(1→4), β-D-Galp-(1→2,3,4), α-L-Fucp-(1→3,4), and terminal α-L-Fucp residues where Fuc₁(SO₃)₁, Gal1Fuc₁(SO₃)₁, and Fuc₂(SO₃)₂ were the most common glycans. Synbiotic administration significantly attenuated DSS-induced colonic shrinkage, inhibited pro-inflammatory cytokines (IL-6, TNF-ɑ, and IL-1β), restored tight junction proteins (ZO-1, occludin), and downregulated the iNOS, COX2, and NF-κB signaling pathway in adult zebrafish. 16S rRNA gene sequencing revealed restoration of gut microbial diversity and increased abundance of beneficial bacterial taxa to improve DSS-induced UC. These findings highlight the potential synergistic effects of SH-F and L. plantarum as a combinatorial strategy to regulate gut inflammation and enhance epithelial barrier function, potentially offering new insights and therapeutic opportunities for UC intervention. Full article

Despite growing recognition of the role of the gut microbiome in host health and in modulating pathogen activity, the dynamic and reciprocal relationship between enteric viruses and the gut microbial ecosystem remains insufficiently defined and requires further exploration. This comprehensive review examines the bidirectional interplay between the gut microbiome and enteric viral infections by addressing (i) viruses associated with gastrointestinal alterations, (ii) how enteric viral infections alter the composition and function of the gut microbiome, (iii) how the gut microbiome modulates viral infectivity and host susceptibility, and (iv) current microbial-based approaches for preventing or treating enteric viral infections. Gastrointestinal viral infections induce gut microbiome dysbiosis, marked by reductions in beneficial bacteria and increases in potentially pathogenic populations. Specific gut microorganisms can modulate host susceptibility, with certain bacterial genera increasing or decreasing infection risk and disease severity. Pattern recognition receptors in the intestinal epithelium detect microbial signals and trigger antimicrobial peptides, mucus, and interferon responses to control viral replication while maintaining tolerance to commensal bacteria. The gut microbiome can indirectly facilitate viral infections by creating a tolerogenic environment, suppressing antiviral antibody responses, and modulating interferon signaling, or directly enhance viral replication by stabilizing virions, promoting host cell attachment, and facilitating coinfection and viral recombination. In turn, commensal gut bacteria can inhibit viral entry, enhance host antiviral responses, and strengthen mucosal barrier function, contributing to protection against gastrointestinal viral infections. Probiotics and fecal microbiota transplantation constitute potential microbial-based therapeutics that support antiviral defenses, preserve epithelial integrity, and restore microbial balance. In conclusion, the role of the gut microbiome in modulating enteric viral infections represents a promising area of future investigation. Therefore, integrating microbiome insights with virology and immunology could enable predictive and personalized strategies for prevention and treatment. Full article

Neuropeptides and their corresponding receptors have been observed to play a significant role in modulating immune cell functions and epithelial barrier functions. In teleost, Neuropeptide Y (NPY) is identified to be involved in the immune regulation of intestinal tissues during bacterial infections. However, the mechanism of NPY on infected gastrointestinal tissue remains unclear, as does whether other members of the NPY family, like ligand PYYb and some receptors Y7 and Y8b, also contribute to this immunoregulatory process. Herein, the responses of PYYb and receptors Y7 and Y8b were explored after pathogen challenging, as well as the effect of NPY on the gastrointestinal tissues of Nile tilapia (Oreochromis niloticus). Using a NPY and S. agalactiae co-injection model, we measured the expression of pyyb, y7, and y8b and the inflammatory and oxidative stress responses in gastrointestinal tissues. S. agalactiae infection significantly upregulated pyyb expression, while co-treatment with NPY further amplified its expression. Infection caused an imbalance between y7 and y8b and was alleviated by NPY. Moreover, NPY contributed to immune protection. NPY co-treatment reduced inflammatory cytokine expression in the gastrointestinal tissues and alleviated tissue damage inflicted by S. agalactiae. Additionally, NPY mitigated immune and oxidative stress by enhancing lysozyme, AKP and ACP activities, normalizing glucose and albumin levels, and reducing lipid peroxidation (MDA). These findings demonstrated that PYYb and receptors Y7 and Y8b were involved in the immune response caused by S. agalactiae. NPY not only enhanced their reactions but also reduced inflammation and oxidative stress induced by the pathogen, indicating its potential as a therapeutic intervention for S. agalactiae infections in fish. Full article

The undesirable properties of bioactive substances (such as poor solubility and low stability) and various barriers in the gastrointestinal tract (gastric acid, digestive enzymes, mucus and intestinal epithelial cells) hinder their absorption and utilisation by the human body. Nanodelivery systems have been proven to effectively address the above problems, particularly targeted nanodelivery systems, which have more advantages in improving the bioavailability of bioactive substances. However, many studies have not included all barriers. Furthermore, given that the small intestine is the main site for the absorption of bioactive substances in the human body, this review primarily discusses targeted nanodelivery systems designed for the gastrointestinal barrier and summarises how to construct a nanodelivery system that can resist the adverse effects of the gastrointestinal tract and target the small intestine for the absorption of bioactive substances. This paper proposes that the ideal system is the active targeted nanodelivery system that targets enterocytes and its future development trend is discussed. This review aims to provide new insights for the rational design of nanodelivery platforms that efficiently target the small intestine and promote the absorption of bioactive substances, as well as promote the development of fields such as personalised nutrition and nutritional intervention. Full article

Microphysiological systems (MPSs), such as organ-on-a-chip platforms, are promising alternatives to animal testing for drug development and physiological research. The BioStellar™ Plate is a commercial MPS platform featuring an open-top culture chamber design with on-chip stirrer pumps that circulate culture medium through six independent, dual microchannel-connected chamber multiorgan units. Although this design enables a circular flow, the open-top culture chamber format prevents the application of fluidic shear stress, a force that cells experience in vivo, which affects their behavior and function. To address this, we developed two fluidic shear stress attachments for the BioStellar™ Plate. These attachment channel fluids provide controlled mechanical stimulation to cultured cells. The flow dynamics were simulated using COMSOL Multiphysics to estimate shear stress levels. The attachments were fabricated and validated through fluorescent bead tracking and biological assays. The FSSA-D is designed for flat-bottom standard cell cultures, while the FSSA-I is designed for epithelial monolayers, enabling the application of fluidic shear stress across the basal membrane. Experiments with intestinal epithelial cells (Caco-2) demonstrated that both attachments enhanced cell barrier function under a fluidic environment, as indicated by higher transepithelial electrical resistance (TEER). These findings demonstrate that the attachments are practical tools for mechanobiology research with MPS platforms. Full article

The human microbiome plays a central role in modulating the immune system and maintaining immunophysiological homeostasis, contributing to the prevention of immune-mediated diseases. In particular, the gut microbiota is a key ecosystem for immune system maturation, especially in early life. This review aimed to analyze the molecular and cellular mechanisms linking the microbiome to immune and neuronal functions, as well as the impact of dysbiosis and emerging therapeutic strategies targeting the microbiome. The analysis was based on scientific databases, prioritizing studies published since 2000, with special emphasis on the past decade. The microbiome influences immune signaling through microorganism-associated molecular patterns (MAMPs) and pattern recognition receptors (PRRs), including Toll-like receptors (TLRs). Additionally, microbial metabolites—such as short-chain fatty acids (SCFAs), tryptophan derivatives, and secondary bile acids—exert significant immunomodulatory effects. The intestinal epithelial barrier is also described as an active immunological interface contributing to systemic regulation. The literature highlights innovative therapies, including fecal microbiota transplantation (FMT), probiotics, and microbiome editing with CRISPR-Cas technologies. These strategies aim to restore microbial balance and improve immune outcomes. The growing body of evidence positions the microbiome as a valuable clinical and diagnostic target, with significant potential for application in personalized medicine. Full article

In the context of thermal injury, local tissue integrity and systemic homeostasis are compromised, often resulting in delayed healing, infections, and disturbances of the skin and intestinal microbial balance. Despite several reviews addressing probiotics in wound healing, none has specifically focused on their role in thermal injuries and burn-associated pathophysiology. This review uniquely integrates evidence on the gut–skin axis, postbiotic innovations, and regenerative perspectives tailored to burn care. We conducted a critical synthesis of recent preclinical and clinical trials evaluating the use of probiotics and their derivatives to promote tissue regeneration following burn injury. Previous reviews have addressed probiotics in general wound repair, but the present synthesis advances the field by bridging mechanistic insights (immune modulation, angiogenesis, microbiome restoration) with translational evidence in burn patients, offering a framework for personalized regenerative approaches. Based on a structured review of the literature—including in vitro models, animal experiments, and randomized trials with topical, enteral, and systemic administration of probiotic—we identified four main mechanisms of action: modulation of the immune response by balancing cytokines and polarization of T lymphocytes; stimulation of tissue repair by increasing the proliferation of keratinocytes and fibroblasts, increased collagen synthesis, and induction of angiogenesis; direct antimicrobial activity against biofilms and multiresistant pathogens; and the restoration of eubiosis with the improvement of the function of epithelial barriers. While these findings endorse the adjunctive use of probiotics in burn management, large multicenter trials are required to standardize strains, dosages, and formulations before their routine clinical adoption. Full article

Gut barrier dysfunction and increased intestinal permeability are closely linked to the pathogenesis of type 1 diabetes and its complications. Streptozotocin (STZ)-induced diabetic mice, which mimic β-cell destruction and insulin deficiency, provide a widely used model for studying type 1 diabetes-associated intestinal barrier impairment. However, the cellular pathways mediating this dysfunction, particularly the role of goblet cells, remain incompletely elucidated. This study aimed to investigate the association between the gut barrier function and diabetes. Using real-time intravital multiphoton microscopy, we investigated intestinal barrier integrity in STZ-induced type 1 diabetic mice. Three groups were analysed: the control, STZ-diabetic, and STZ-diabetic mice treated with fructooligosaccharide (FOS) for 1 week. Intestinal permeability was assessed by measuring fluorescein isothiocyanate (FITC)-dextran concentrations in the portal vein and visualising translocation into villi. Epithelial morphology was examined, focusing on goblet cell density and leakage pathways. STZ-diabetic mice demonstrated a significant increase in intestinal permeability, evidenced by elevated FITC-dextran levels in the portal vein and villi. Multiphoton imaging revealed a notable rise in the goblet cell-to-enterocyte ratio in diabetic mice, while the gap density remained unchanged. The predominant route of macromolecular leakage in STZ-diabetic mice was via goblet cells rather than by paracellular gaps. One-week FOS supplementation significantly reduced goblet cell density and partially restored barrier function without altering the distribution of leakage pathways. These findings highlight goblet cell-mediated transcellular leakage as a major mechanism of gut barrier dysfunction in type 1 diabetic mice. Short-term FOS treatment partially reverses these alterations. Targeting goblet cell function may offer a promising therapeutic strategy to restore gut barrier integrity in diabetes. Full article

The objective of our study was to verify the intervention effect of Bacillus amyloliquefaciens SC06 on NE by constructing a C. perfringens-induced intestinal damage mouse model. A total of 40 mice were randomly assigned to four treatments: CON (basal diet), CP (basal diet + C. perfringens), SC06 + CP (basal diet + SC06 + C. perfringens) and SC06 (basal diet + SC06). Our findings indicated that SC06 supplementation was effective in maintaining the integrity of the intestinal barrier, enhancing the antioxidant capacity of the intestine, reducing the generation of an inflammatory response, and suppressing enterocyte apoptosis in the presence of C. perfringens. Furthermore, SC06 supplementation enhanced the prefoliation of intestinal stem cells (ISC) and prompted their differentiation into goblet cells and Paneth cells. Moreover, our findings indicate that SC06 promotes the proliferation of C. perfringens-induced jejunum organoids and the expression of genes and proteins associated with ISC differentiation and regeneration. The mechanism by which SC06 modulates ISCs has been validated, and the results align with those obtained in vivo. In conclusion, the findings demonstrated that SC06 stimulates the proliferation and differentiation of ISCs through the activation of the Wnt/β-catenin signaling pathway, thereby accelerating epithelial regeneration and repair. Full article

Mutations in the CFTR genes causing cystic fibrosis (CF) are associated with the presence of thick, viscous mucus and the formation of biofilms in the gastrointestinal tract (GI) that impair intestinal homeostasis, triggering chronic inflammation, epithelial barrier dysfunction, and changes in the composition and activity of the gut microbiota. CFTR protein modulators represent a promising approach to enhancing lower GI function in patients with CF. The aim of the review is to present the complex relationships between the presence of CFTR gene mutations and the gut microbiota dysbiosis in patients with cystic fibrosis. Mutations in the CFTR gene, the molecular basis of cystic fibrosis (CF), disrupt epithelial ion transport and profoundly alter the gastrointestinal environment. Defective chloride and bicarbonate secretion leads to dehydration of the mucosal layer, increased mucus viscosity, and the formation of biofilms that favour microbial persistence, which together promote gut microbiota dysbiosis. This dysbiotic state contributes to impaired epithelial barrier function, chronic intestinal inflammation, and abnormal immune activation, thereby reinforcing disease progression. The interplay between CFTR dysfunction and microbial imbalance appears to be bidirectional, as dysbiosis may further exacerbate epithelial stress and inflammatory signalling. Therapeutic interventions with CFTR protein modulators offer the potential to partially restore epithelial physiology, improve mucus hydration, and foster a microbial milieu more consistent with intestinal homeostasis. The aim of this review is to elucidate the complex relationships between CFTR gene mutations and gut microbiota dysbiosis in patients with cystic fibrosis, with a particular emphasis on the clinical implications of these interactions and their potential to inform novel therapeutic strategies. Full article

Intestinal disorders such as inflammatory bowel diseases (IBDs), Crohn’s disease, malabsorption syndromes, and gastrointestinal fistulae (GIFs) are often characterized by chronic inflammation, epithelial barrier disruption, impaired stromal remodeling, and defective angiogenesis. These multifactorial alterations hinder tissue repair and contribute to poor clinical outcomes, with limited efficacy from current therapeutic options. Despite recent advances in surgical and endoscopic techniques, current treatment options remain limited and are frequently accompanied by high morbidity and costs. In this context, regenerative medicine offers a promising avenue to support tissue repair and improve patient care Regenerative medicine offers a promising avenue to restore intestinal homeostasis using advanced biomaterials and cell-based therapies. In this study, we developed a 3D-bioprinted model based on patient-derived stromal vascular fraction (SVF) embedded in a GelMA hydrogel, designed to promote intestinal tissue regeneration. To identify the most suitable hydrogel for bioprinting, we initially evaluated the mechanical properties and biocompatibility of four distinct matrices using bone marrow-derived mesenchymal stromal cells (BM-MSCs). Among the tested formulations, GelMA demonstrated optimal support for cell viability, low oxidative stress, and structural stability in physiologically relevant conditions. Based on these results, GelMA was selected for subsequent bioprinting of freshly isolated SVF. The resulting bioprinted constructs enhanced key regenerative processes across multiple compartments. The SVF-laden constructs significantly enhanced intestinal epithelial cell viability and tight junction formation, as shown by increased trans-epithelial electrical resistance (TEER). Co-culture with fibroblasts accelerated wound closure, while endothelial cells exhibited increased tube formation in the presence of SVF. Together with VEGF secretion, indicating strong paracrine and angiogenic effects. By supporting epithelial, stromal, and vascular regeneration, this approach provides a versatile and translational platform for treating a broad spectrum of intestinal pathologies. Full article