The study by Ruiz-Malagón et al marks a significant advancement in understanding the role of growth differentiation factor 15 (GDF15) in inflammatory bowel disease (IBD). Using both in vivo and in vitro models, the researchers detected elevated circulating GDF15 levels in patients with both ulcerative colitis (UC) and Crohn’s disease (CD), and its level correlates with markers of inflammation and intestinal permeability. Utilizing colonic organoids and T84 cells, they demonstrated that GDF15 increases intestinal permeability by reducing the expression of zonula occludens-1 (ZO-1) and claudin 1. They concluded that targeting GDF15 may offer a promising strategy to preserve intestinal barrier integrity and potentially reducing immune overactivation. However, results from a small-sample sized study (CD patients 21, UC patients 18, and healthy controls 23) signals interpretation with caution. Genetic approaches are needed to validate the findings that GDF15 alters the intestinal barrier and increases permeability by decreasing the levels of ZO-1 and claudin 1. GDF15 serves as a double-edged mediator with context-dependent protective or pathogenic roles, and clarifying this duality is a critical goal for translational research. Overall, the study represents a critical step in understanding the pathogenesis of IBD, highlighting both progresses made and the work still required for clinical translation.

Transient receptor potential vanilloid 6 (TRPV6) is a highly Ca2+-permeable cation channel predominantly expressed in the intestinal epithelium. It plays a crucial role in maintaining systemic calcium homeostasis by regulating Ca2+ absorption in the intestine. However, its local physiological and pathophysiological roles in the intestine remain unexplored. The exact cause of inflammatory bowel disease is not fully understood; however, disruption of the intestinal epithelial barrier is a key pathogenic mechanism. In this study, we aimed to elucidate the role of TRPV6 in the pathogenesis of colitis. Experimental colitis was induced in TRPV6-deficient (KO) and wild-type (WT) mice by administering 2% dextran sulfate sodium solution (DSS) in drinking water for 7 days. DSS treatment resulted in weight loss, diarrhea/bloody stool, histological colonic injury, and colon shortening. The systemic symptoms and colonic injury were significantly worse in TRPV6KO mice than in WT mice. DSS treatment increased tumor necrotic factor-α, interleukin-1β, interleukin-6 mRNA expressions, and myeloperoxidase activity, and these responses were significantly enhanced in TRPV6KO mice compared with WT mice. Under normal (no-DSS-treated) conditions, TRPV6KO mice exhibited increased intestinal permeability compared with WT mice. No difference was observed in the number of goblet cells between WT and TRPV6KO mice; however, the expression of intercellular junction proteins, including E-cadherin, claudin-3, and occludin, was significantly suppressed in TRPV6KO mice compared with WT mice. These findings suggest that TRPV6 protects against DSS-induced colitis, potentially by regulating epithelial barrier function through intracellular junction protein expressions.

Enteropathogenic bacteria are a major cause of morbidity and mortality globally. While mouse models have been indispensable in advancing our understanding of infectious enteric diseases, key differences in intestinal microbiota and immunobiology between mice and humans underscore the need for alternative mammalian models that better recapitulate human disease states. The naked mole rat (NMR), the longest-lived rodent and a model of healthy ageing, presents a unique opportunity. It possesses an exceptionally robust intestinal barrier, an abundance of goblet cells, a thicker mucin layer, and reduced gut permeability compared to mice. Additionally, the NMR gut microbiome exhibits compositional and functional features shared with human centenarians and traditional-lifestyle populations (e.g. Hadza hunter-gatherers), including an enrichment of health-associated taxa and metabolic pathways. Here, we leverage this model to show that systemic Citrobacter braakii infection is associated with colonic inflammation and epithelial injury that closely mimics human haemorrhagic colitis. Infected NMRs develop mucosal erosions, ulcerations, depletion of goblet cells, expansion of proliferative compartments, and active inflammation in the lamina propria. Without intervention, systemic inflammation associated with sepsis ensues and results in high mortality. Furthermore, we demonstrate the utility of this model for therapeutic testing by showing a strong effect of a probiotic cocktail comprising lactobacilli, bifidobacteria, streptococci, and enterococci. Treatment with this cocktail promoted mucosal healing, restored intestinal homeostasis, and exerted an anti-inflammatory effect. Taken together, we establish the NMR as a translatable model for investigating disease mechanisms in infectious colitis, including disruptions in mucosal barrier permeability, gut microbial ecology, and local and systemic immune regulation, as well as for testing functional probiotic strains as potential therapeutics. © 2026 The Author(s). The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.

Paracellular transport is the primary pathway for the intact absorption of the egg white-derived peptide QIGLF. This study aimed to explore the paracellular absorption process of QIGLF in Caco-2 cells using 4D-FastDIA proteomics. A total of 147 differentially expressed proteins (DEPs) were identified. Gene Ontology enrichment analysis revealed that key DEPs, including GRHL2, ECT2, and MARVELD2 involved in apical junction assembly and tight junctions, as well as ARHGEF18 and EphA2 in the plasma membrane, participate in regulating the paracellular absorption of QIGLF. KEGG pathway analysis further indicated that Toll-like receptors and nuclear factor-kappa B-signaling pathways, along with the phosphatidylinositol signaling system, were closely associated with this absorption process. Altogether, the findings of this study demonstrate that QIGLF may alter the expression or subcellular localization of tight junction proteins through these signaling pathways, thereby modulating intestinal tight junction permeability and facilitating its paracellular absorption.

Hyaluronic acid-ethylenediamine-cinnamic acid attenuates IBS-D via regulating 5-hydroxytryptamine signaling pathway, intestinal barrier and gut microbiota.

Background/Objectives: Whether saponins aid in whey protein supplementation remains unclear. We aimed to investigate the effects of Astragalus and Panax saponins (APS) on whey protein absorption, intestinal permeability, and muscle function in healthy adults across different age groups. Methods: A randomized, double-blind, placebo-controlled crossover trial was conducted with 30 healthy participants equally stratified into three age groups (18–25, 26–59, and 60–80 years), over two phases: a single-dose trial to measure immediate amino acid absorption from whey protein and a 4-week phase combining daily supplementation with resistance training to assess long-term effects on amino acid absorption kinetics, muscle function, and gut health. Results: Immediate APS supplementation resulted in a 6.67% higher area under the curve for valine, 3.62% for leucine, and 0.15% for isoleucine, compared with the placebo. After 4 weeks, APS supplementation significantly increased the absorption of valine (14.07%) and leucine (8.34%) and improved the absorption of isoleucine (6.33%). The effects were most pronounced in older adults (60–80 years), who showed a 12.74% increase in total essential amino acid absorption. APS also caused a substantially greater increase (APS: +5.20% vs. placebo: +2.44%) in grip strength, an increase (APS: +0.85% vs. placebo: +0.68%) in muscle mass, and a reduction in blood zonulin levels (APS: −13.01% vs. placebo: −0.9%), indicating improved muscle function and intestinal barrier integrity, without adverse effects on liver or kidney function. Conclusions: APS supplementation enhances amino acid absorption from whey proteins, muscle function and gut barrier integrity, especially in older adults. These findings highlight its synergistic role in improving protein supplementation efficacy for those with age-related muscle loss.

Objective: Systemic intoxication was analyzed from a cause-and-effect perspective to differentiate its endogenous and exogenous forms and to interpret its role as a relevant causal chain in the health–disease transition, going beyond the traditional focus on the clinical effect. Methodology: An exploratory sequential mixed-methods study was conducted. In this phase, the qualitative documentary component was prioritized, based on a literature review in PubMed, Google Scholar, Latindex, and meta-search engines. Additionally, an interpretive integration of applied clinical biosemiotics was carried out using the iterative metabolic assessment methodology of the technique application system for metabolic diagnosis (ATDM system). Capillaroscopy was used to identify microcirculatory and metabolic signals associated with toxic accumulation processes. Results: A classification framework was established that distinguished endogenous intoxication (due to deficient metabolite generation or clearance) from exogenous intoxication (resulting from exposure to environmental or occupational xenobiotics, consumption/abuse, or venoms), and illustrative capillaroscopic patterns linked to detoxification impairments, intestinal permeability, and exposure to external compounds were described; additionally, the literature review revealed that recent studies have predominantly addressed systemic intoxication from the perspective of its effects, identifying a gap in research focused on its interpretation as a primary cause of disease. Conclusions: It was concluded that the cause-and-effect approach, articulated thru Applied Clinical Biosemiotics and the ATDM System, enabled an integrative interpretation for the early identification of tissue and metabolic processes related to systemic intoxication, with potential preventive and personalized utility; it was proposed to continue with the experimental quantitative phase to evaluate diagnostic performance, reproducibility, and applicability across different exposure profiles.

Qizhiweitong granule alleviates diarrhea-predominant irritable bowel syndrome via inhibition of the IL-6/Src/STAT3 feedback loop.

Short-chain fatty acids alleviated fluoride-induced neuroinflammation via the gut-brain axis in rats.

Application of the protease-resistant antimicrobial peptide R7I, composed of natural amino acids, as a functional food ingredient for modulating intestinal health.

Design of biomimetic chylomicrons based on 1,3-diolein grafted hyaluronic acid to drive biomacromolecules across the intestinal mucosal barrier.

Intestinal barrier dysfunction is a key driver of obesity pathogenesis. This study aimed to elucidate the anti-obesity mechanism of mulberry leaf extract (MLE) by investigating its effects on the intestinal barrier, including the mechanical, immune, and microbial barriers. A high-fat diet (HFD)-induced obese mouse model was employed and treated with MLE. We systematically assessed obesity phenotypes, glucolipid metabolic parameters, systemic and intestinal inflammation, intestinal tight junction proteins and mucus secretion, and gut microbiota composition. The results showed that MLE significantly reduced body weight by over 5%, and ameliorated dyslipidemia, hepatic steatosis, and glucose intolerance. Concurrently, MLE activated PPARα/CPT-1 fatty acid β-oxidation and PI3K/AKT signaling while suppressing SREBP-1c lipogenesis. Mechanistically, MLE enhanced intestinal mechanical barriers, as evidenced by the upregulation of tight junction proteins, increased mucus secretion, and reduced serum levels of intestinal permeability markers (diamine oxidase and endotoxin). Furthermore, MLE suppressed systemic and intestinal inflammation (TNF-α, IL-1β, and IL-6). Furthermore, MLE improved gut microbiota dysbiosis, reducing the Firmicutes/Bacteroidota ratio by 61.39%, enriching beneficial Alloprevotella and Muribaculaceae_norank, and depleting Faecalibaculum and Lachnoclostridium. Correlation analysis revealed significant associations between MLE-modulated microbiota and improved metabolic and barrier parameters. Collectively, MLE alleviated obesity by synergistically modulating glucolipid metabolism, gut microbiota, intestinal mechanical barrier and inflammation.

Multiple sclerosis (MS) is a chronic autoimmune disease of the central nervous system characterized by progressive disability. Emerging evidence has implicated gut microbiome dysbiosis, characterized by decreased short-chain fatty acids (SCFAs)-producing taxa and increased pro-inflammatory species, in disturbed immune signaling, T-helper17/T-regulatory cells imbalance, disturbed tryptophan metabolism, and disrupted integrity of the blood-brain barrier. In this review, we summarize the mechanistic and therapeutic insights from studies that have explored the gut microbiome in MS. We performed a literature search in PubMed, Scopus, Web of Science, and ClinicalTrials.gov from database inception to January 2025; only English-language articles were included, comprising human MS cohorts and preclinical experimental autoimmune encephalomyelitis models. Of these, approximately 95 human and preclinical studies fulfilled the inclusion criteria. Evidence synthesis was narrative, without meta-analysis. There has been a consistent depletion of beneficial genera such as Faecalibacterium and Roseburia, expansion of Akkermansia muciniphila, and reduction in microbial metabolites such as butyrate, propionate, and neuroactive indole derivatives in MS patients across studies. These changes promote intestinal permeability, exaggerated pro-inflammatory cytokine responses, and microglial activation. The therapeutic approach of restoring microbial balance includes therapies such as probiotics, prebiotics, synbiotics, fecal microbiota transplantation, and dietary interventions. Early trials have shown modest improvements in relapse rates, fatigue, immune profiles, and microbiome composition. Results across randomized studies are heterogeneous, with no significant clinical benefit in several. Pilot trials report modest reductions in relapse rate (RR≈0.85) and fatigue (Cohen'sd≈0.3), but several double‑blind RCTs showed no significant benefit (p > 0.05) in up to 40% of participants, highlighting variable effect sizes. Interventions aimed at the microbiome are promising as adjunct approaches to the treatment of MS, acting principally through the restoration of SCFAs, immune modulation, and strengthening of the gut-brain axis. Larger, longer-term randomized trials are required to confirm clinical efficacy, define responder phenotypes, and inform personalized microbiome-based therapies.

Previous studies have shown that Aquamin ® , a multi-mineral extract from red marine algae, enhances barrier integrity proteins in the human colon. These findings prompted further investigation into Aquamin ® 's effects on gastrointestinal barrier function and permeability. Subjects with mild or in remission ulcerative colitis (UC) and healthy controls were enrolled in an open-label trial and received Aquamin ® capsules (800 mg calcium/day) for 90 days. Intestinal permeability was evaluated before and after the 90-day intervention by urinary mannitol excretion after ingestion of a 5 g mannitol solution, with collections across several time intervals (pre-drink, 0-2 h, 2-8 h, and 8-24 h). The primary outcome was the change in mannitol excretion. Serum samples were also collected to assess liver and renal function. In this pilot study ( NCT04855799 ), which included UC patients and healthy controls (n = 8 per group), baseline urine mannitol levels in the 0-2 h sample were 54% higher in UC patients compared to healthy subjects (p = 0.006). Following 90 days of Aquamin ® supplementation, urinary mannitol levels in UC patients decreased by 28%, 26%, and 41% at the 0-2 h, 2-8 h, and 8-24 h timepoints, respectively; the reduction at the 0-2 h interval reached statistical significance (p = 0.015). Overall, Aquamin ® supplementation reduced total post-intervention mannitol excretion by 29% (p = 0.024). Aquamin ® was well tolerated, with no serious adverse events reported. The serum metabolic panel revealed a modest but statistically significant reduction in alkaline phosphatase levels after 90 days of intervention. These results provide preliminary evidence that Aquamin ® supplementation beneficially modulates gut barrier function and supports epithelial integrity in UC patients. These findings support further investigation of Aquamin ® as a safe and promising adjunct to current UC management strategies, with potential utility as a barrier therapy in UC. Aquamin ® supplementation for 90 days reduced intestinal permeability in ulcerative colitis patients, as measured by urinary mannitol excretion. The intervention was well tolerated, suggesting Aquamin ® may be a safe, promising adjunct for enhancing gut barrier function in UC management.

Tuft cells in the gut limit cognitive disorders by regulating gut homeostasis.

ABSTRACT Background: Recent studies indicate that maintaining a healthy gut microbiota balance positively influences brain function through the microbiota-gut-brain (MGB) axis. Intestinal inflammation disrupts gut microbial homeostasis, exacerbates inflammatory and oxidative processes, and reduces beneficial microbial metabolites essential for brain health. These alterations may impair MGB axis signaling and increase intestinal and blood-brain barrier (BBB) permeability, facilitating the translocation of inflammatory mediators and potentially contributing to neurological dysfunction. Kefir has emerged as a fermented food with potential psychobiotic properties due to its ability to modulate gut microbiota and its metabolites. However, its effects on brain-related outcomes during intestinal inflammation remain poorly understood. Aim: To investigate the association between milk kefir consumption and selected brain biomarkers in IL-10−/− mice. Methods: Male C57BL/6 mice were allocated into four groups (n = 5/group): wild-type mice receiving water (WWT), wild-type mice receiving milk kefir (KWT), IL-10−/− mice receiving water (WKO), and IL-10−/− mice receiving milk kefir (KKO). Brain analyses included cytokine levels, antioxidant activity, tight junction protein expression, and short-chain fatty acids (SCFAs), while histological evaluation focused on the small intestine. Results: Kefir consumption was associated with improved intestinal morphology in IL-10−/− mice (p < 0.03), increased brain SCFA levels (p < 0.001), reduced malondialdehyde concentrations, and higher occludin expression in brain tissue. Conclusion: Overall, these findings suggest that milk kefir intake may influence specific brain biomarkers in IL-10−/− mice. These observations provide preliminary insights and support the need for further studies to elucidate the potential psychobiotic role of kefir in intestinal inflammation.

Mult omics reveal the mechanism of solid dispersion of genistein in alleviating fatty liver hemorrhagic syndrome in laying hens.

Our study explores interconnections between the occurrence of gastrointestinal (GI) symptoms with immunohistochemical analysis of colon biopsies, markers of intestinal permeability, and inflammation in individuals with type 1 diabetes. Twenty subjects with type 1 diabetes and seven healthy controls underwent colonoscopy. Colon biopsy materials were analyzed immunohistochemically for CD3+, CD20+, CD4+, CD8+, CD138+, and CD68+ cell counts. The levels of lipopolysaccharide (LPS), LPS-binding protein (LBP), and endogenous anti-endotoxin core antibodies (EndoCAb IgG and IgM) were measured in serum. Fecal calprotectin, immunoglobulin A (IgA), albumin, protein, and intestinal alkaline phosphatase (IAP) activity were analyzed in patient subgroups. Immune cell infiltration in lamina propria did not differ between type 1 diabetes and control subjects. In type 1 diabetes, the number of CD20+, CD8+, CD138+, and CD68+ cells correlated with several GI symptoms and usage of medications for diarrhea. Fecal calprotectin correlated positively with the number of CD20+ B cells, CD3+ Tcells, and CD138+ plasma cells. A negative correlation was found between CD20+ B-cell number and fecal IgA, while CD68+ macrophage number correlated positively with fecal albumin. Serum EndoCAb IgM correlated negatively with CD138+ plasma cells and CD4+ Tcells, and positively with CD68+ macrophages. Serum LBP correlated negatively with CD4+ Tcells, demonstrating links between gut mucosal inflammation and the systemic response to endotoxin. In type 1 diabetes, CD immune cell infiltration in the colon mucosa tended to correlate with fecal and systemic markers of inflammation and gastrointestinal symptoms. A key direction for future studies will be to elucidate the underlying pathogenic mechanisms.

This study aimed to investigate the effects of betaine supplementation in a high-carbohydrate diet on the intestinal health of juvenile largemouth bass ( Micropterus salmoides ). Six diets were formulated: a low-carbohydrate diet (8% corn starch), a high-carbohydrate diet (20% corn starch), and the HC diet supplemented with 0.5%, 1.0%, 1.5%, or 2.0% betaine (HCB1–HCB4). A total of 270 juvenile largemouth bass with an initial body weight of 4.34 ± 0.11 g were subjected to a 56-day feeding trial. The experimental results showed that 0.5% betaine significantly improved the weight gain rate (WGR) and specific growth rate (SGR) of juvenile largemouth bass. In terms of antioxidant capacity, the levels of total antioxidant capacity (T-AOC) and superoxide dismutase (SOD) in the intestine were markedly enhanced in the HCB groups, while 1.0% betaine significantly elevated intestinal glutathione (GSH) levels (P &lt; 0.05). Regarding intestinal histomorphology, betaine supplementation improved the intestinal histological structure, significantly upregulated the expression levels of zonula occludens-1 (ZO-1) and Occludin in the intestine, and notably augmented intestinal Claudin-1 expression in the 1% and 1.5% betaine groups (P &lt; 0.05). Furthermore, betaine reduced intestinal mucosal permeability, as evidenced by a significant decrease in serum diamine oxidase (DAO) levels (P &lt; 0.05). Additionally, betaine alleviated intestinal inflammation: specifically, 0.5% and 1% betaine markedly suppressed the expression of nuclear factor kappa-B (NF-κB), interleukin-8 (IL-8), and cyclooxygenase-2 (COX-2), while the expression level of interleukin-10 (IL-10) was significantly upregulated in the HCB groups (P &lt; 0.05). Concomitantly, supplementation with 0.5% betaine significantly boosted the relative abundance of Actinobacteria, whereas supplementation with 1% and 1.5% betaine significantly decreased the relative abundances of Proteobacteria and Enterobacteriaceae (P &lt; 0.05). In conclusion, dietary supplementation with 0.5%–1.5% betaine can significantly improve the intestinal health of juvenile largemouth bass.

The gut microbiota is one of the key elements responsible for maintaining the body’s homeostasis. Its diverse composition affects, among others, the digestive and immune systems and also the circulatory system. Imbalances within the microbial community, referred to as dysbiosis, may lead to increased intestinal barrier permeability, chronic inflammation, and abnormal immune responses, which can be associated with the development of numerous diseases. Gut dysbiosis results in disturbances in the production of short-chain fatty acids, which exert anti-inflammatory effects, regulate blood pressure, and inhibit cardiac fibrosis. At the same time, it promotes the increased synthesis of trimethylamine N-oxide, a metabolite linked to inflammation, endothelial dysfunction, a higher risk of thrombosis, and the occurrence of arrhythmias. Additionally, small intestinal bacterial overgrowth (SIBO) may increase inflammation and contribute to metabolic and cardiovascular diseases (CVDs). The gut microbiota also influences the immune system through the production of neurotransmitters and modulation of T-cell activity, which may play a role in the development of autoimmune diseases. Reduced microbial diversity and an increased abundance of pathogenic bacteria are observed in individuals with hypertension and CVD, underscoring the importance of the microbiota as both a preventive and therapeutic factor. These findings highlight the crucial role of the gut microbiota in maintaining cardiovascular health and emphasize the need for further research into its modulation in the treatment of chronic diseases.