Search Results (1,219)

Background: Rheumatoid arthritis (RA) is influenced by environmental exposures. High humidity has been clinically associated with worsened joint symptoms, but the microbial and metabolic mechanisms remain unclear. We investigated whether a gut microbiota–metabolism axis contributes to humidity-associated aggravation of collagen-induced arthritis (CIA). Methods: CIA mice were maintained under normal or high relative humidity. We integrated 16S rRNA and metagenomic sequencing, liquid chromatography–tandem mass spectrometry metabolomics, and intestinal barrier assessments. Fecal microbiota transplantation (FMT) was performed to evaluate microbiota dependency. Based on multi-omics findings, we quantified chondroitin sulfate (CS) and conducted functional experiments involving Prevotella stercorea (P. stercorea) supplementation, CS administration, and in vitro degradation assays. Results: High humidity aggravated arthritis severity and systemic inflammation, including increased interleukin-6, interleukin-17A, and granulocyte colony-stimulating factor, and was accompanied by impaired intestinal barrier integrity. FMT supported a microbiota-dependent contribution. Metagenomic analysis identified enrichment of P. stercorea and glycosaminoglycan degradation pathways under high humidity. CS abundance was reduced in articular cartilage, P. stercorea degraded CS in vitro and was associated with cartilage CS loss in vivo, and CS supplementation attenuated arthritis under high humidity and reduced the arthritis-promoting effects associated with P. stercorea. Conclusions: High humidity is associated with microbiota-dependent functional remodeling, enhanced CS degradation, and aggravated arthritis in CIA mice. These findings suggest that humidity-associated alterations in microbial CS metabolism may link environmental exposure to cartilage disruption and joint inflammation. Full article

DNA methylation plays a fundamental role in maintaining intestinal homeostasis, immune tolerance, and inflammatory balance. Active DNA demethylation, mediated by the ten-eleven translocation family of dioxygenases (TET1, TET2, and TET3), has emerged as an important epigenetic mechanism linking environmental and metabolic cues to gene regulatory programs in the gut. In the intestinal epithelium, TET-dependent DNA hydroxymethylation contributes to intestinal stem cell maintenance, epithelial differentiation, regeneration, and barrier integrity. Perturbations in TET activity are associated with epithelial dysfunction, chronic inflammation, and increased susceptibility to colorectal tumorigenesis. Within the immune compartment, TET-mediated demethylation is required for the epigenetic stabilization of gut-associated immune cells. Altered TET function has been implicated in immune imbalance in inflammatory bowel disease, Hirschsprung’s disease, and colitis-associated colorectal cancer. Emerging evidence further indicates that intestinal microbiota-derived metabolites, including short-chain fatty acids and aryl hydrocarbon receptor ligands, modulate TET activity, positioning TET enzymes as epigenetic sensors of microbial and metabolic signals. In turn, TET-dependent programs shape immune responses to commensal microbes and pathogens, establishing a bidirectional microbiota–epigenetic axis that influences both intestinal and systemic immunity. In this review, we summarize and critically evaluate current evidence on the roles of TET enzymes in intestinal epithelial biology, immune cell regulation, and host–microbiota interactions in colorectal inflammation and disease. Full article

Low-molecular-weight collagen peptides from food processing byproducts offer a sustainable approach to mitigating intestinal inflammation, yet their mechanistic roles remain incompletely understood. We evaluated red fish scale collagen peptides-I (LSCP-I), a <3 kDa collagen peptide fraction derived from Lutjanus erythropterus scales, in cellular and murine models of colitis. In Caco-2 cells subjected to macrophage-mediated inflammatory injury, LSCP-I (50 µg/mL) increased proliferation by 35%, enhanced migration by 40%, preserved barrier integrity, reduced reactive oxygen species (ROS) by 45%, decreased lipid peroxidation by 30%, and restored glutathione (GSH) and superoxide dismutase (SOD) activity. In mice with dextran sulfate sodium (DSS)-induced colitis, oral administration of LSCP-I at 200, 400 and 800 mg/kg/day attenuated weight loss and diarrhea, lowered intestinal permeability by 38%, enhanced colon histology, and restored the balance between pro- and anti-inflammatory cytokines. Mechanistically, LSCP-I activated the Nrf2 antioxidant pathway and partially restored gut microbiota composition. These results demonstrate that LSCP-I reinforces intestinal barrier function, restores redox homeostasis, and modulates host–microbiota interactions, establishing its potential as a functional food ingredient for the prevention and management of inflammatory bowel disease. Full article

Nanoplastics (NPs; ≤1 µm) have been detected in human placenta, blood, lung, atherosclerotic plaque, testis, semen, olfactory bulb, and brain, shifting the field from environmental description toward mechanistic interrogation of barrier crossing. This review synthesises current evidence on NP translocation across the intestinal epithelium, the blood–brain barrier (BBB) and the placental syncytiotrophoblast. We distinguish four evidence categories throughout the review: detection, association, mechanism, and causality. We also apply model-system labels (in silico, in vitro, ex vivo, animal, and human) to every mechanistic claim, so that the strength of each statement can be read off directly. Most current studies use pristine polystyrene nanoplastics at concentrations 3–6 orders of magnitude above plausible human exposure, so the mechanistic conclusions below are hypothesis-generating for human disease rather than definitive. We propose a working conceptual framework—corona-driven barrier selectivity (CDBS)—in which the particle–corona–surface complex, rather than the bare polymer, is hypothesised to dictate which receptor and transport machinery (TfR1, LRP1, FcRn, P-gp/BCRP, caveolae) each barrier engages. CDBS is offered as a hypothesis-stage organising tool requiring experimental validation, not as an established mechanism. We outline reported transport modes, including clathrin- and caveolin-mediated endocytosis, paracellular leakage via ROS-induced tight-junction disassembly, receptor-mediated transcytosis, and the candidate olfactory route. We emphasise that pristine polystyrene-bead doses commonly exceed plausible human exposure by 3–6 orders of magnitude, that detection methods underestimate sub-micrometre particles, and that causal links between NPs and human disease remain hypothesis-generating. A research agenda built on weathered reference materials, microphysiological systems, and integrative human biomarker science is proposed. Full article

The reproductive efficiency of modern breeding sows is commonly restricted by a mismatch between high genetic reproductive potential and insufficient voluntary feed intake during critical physiological periods. This review comprehensively examines the physiological, nutritional, and management mechanisms regulating feed intake in sows and their implications for reproductive performance, synthesizing recent advances across neuroendocrine regulation, metabolic signaling, immune-related pathways, and precision feeding strategies. We construct an integrated framework involving three core dimensions: (1) Physiological regulation: the hypothalamic–pituitary–adrenal, hypothalamic–pituitary–gonadal, and hypothalamic–pituitary–spleen axes functionally interact via shared neuroimmune pathways within the hypothalamic–pituitary–immune axis, coordinately regulating feeding patterns and reproductive cyclicity through core hormonal and inflammatory signaling molecules. Perinatal stress induces pro-inflammatory cytokine secretion, activates the intestinal JAK-STAT3 pathway, and upregulates intestinal hepcidin expression, impairing intestinal barrier integrity and triggering persistent inflammation. These peripheral inflammatory signals modulate hypothalamic neuropeptide Y and Proopiomelanocortin expression, forming a negative feedback loop that suppresses feeding behavior. (2) Nutritional regulation: dietary nutrients and specific flavor compounds reshape intestinal satiety signaling, improving piglet growth performance and survival rates, while optimized dietary composition and functional additive supplementation enhance sow feed intake capacity. (3) Management strategies: standardized feeding regimes and optimal rearing environments regulate nutrient digestion and gut hormone secretion. Major knowledge gaps include the translational potential of precision nutrition approaches, biomarker validation for feed intake monitoring, and the scalability of integrated interventions under commercial production conditions. This review provides a multidimensional framework integrating physiological, nutritional, and management strategies to enhance sow feed intake, offering theoretical insights and practical guidance for sustainable pig production. Full article

This study aimed to investigate the therapeutic effects of camel milk (CM) on chronic fatigue syndrome (CFS) and elucidate the mechanisms underlying the microbiota–gut–brain axis. Using a murine model of CFS induced by chronic restraint and forced swimming stress, we administered lyophilized CM (1500 mg/kg/day, equivalent to approximately 121.5 mg/kg/day in humans based on body surface area conversion using the standard allometric scaling formula) orally. CM supplementation was significantly associated with ameliorated fatigue-like behaviors, as evidenced by prolonged swimming endurance and reduced immobility time. Metagenomic analysis revealed that CM was associated with reshaping of the small intestinal microbiota, including enrichment of beneficial Lactococcus lactis and suppression of pathobionts (H. hepaticus and H. typhlonius). These microbial shifts correlated with increased luminal lactic acid, improved intestinal barrier integrity (increased villus height, reduced crypt depth), and attenuated local inflammation (reduced TNF-α and IL-6, elevated IL-10). Consequently, CM was associated with reduced bacterial translocation and systemic inflammation, and normalization of hypothalamic–pituitary–adrenal (HPA) axis hyperactivity. We conclude that CM is associated with prevention of CFS-like symptoms through modulation of the gut ecosystem and strengthening of the intestinal barrier, potentially breaking the vicious cycle of gut inflammation and HPA axis dysfunction, although causality remains to be established through fecal microbiota transplantation or similar mechanistic studies. Full article

Emerging evidence links gut microbiota (GM) dysbiosis to hyperuricemia (HUA). The GM plays a critical role in regulating host health and homeostasis by producing a diverse array of metabolites, including short-chain fatty acids, bile acids and uremic toxins. Dysregulation of the microbial metabolite profile has been implicated in the pathogenesis of HUA. Given the urgent need for green and safe urate-lowering therapies for HUA, recent years have seen an increasing focus on interpreting the ability of natural products to modulate these microbial metabolites. Such interventions enhance beneficial metabolites and suppress uremic toxins, thereby alleviating HUA through coordinated regulation of urate transporters, restoration of intestinal barrier integrity, reprogramming of systemic metabolic disturbances, and inhibition of inflammation via Toll-like receptor 4 (TLR4)/ nuclear factor kappa B (NF-κB), Janus kinase (JAK)/ signal transducer and activator of transcription (STAT), and Phosphatidylinositol-3-kinase (PI3K)/ protein kinase B (AKT) pathways. Furthermore, a comprehensive translational roadmap has been proposed, grounded in a critical appraisal of current trial limitations. Overall, this review consolidates evidence for the protective effects of natural products against HUA and related comorbidities, with an emphasis on GM-derived metabolites, aiming to expand clinical applications and provide insights for future studies. Full article

Obesity is a major global health problem and is closely associated with a broad range of metabolic disorders, including metabolic syndrome (MetS), dyslipidemia, hypertension, atherosclerosis, type 2 diabetes mellitus, and cardiovascular disease. The gut microbiota plays a central role in maintaining intestinal epithelial integrity, regulating glucose and lipid metabolism, and modulating immune function. Through the gut–brain axis, it also contributes to appetite regulation and energy homeostasis by influencing the release of anorexigenic hormones. Dysbiosis, including alterations in the relative abundance of major bacterial phyla such as Firmicutes and Bacteroidetes, has been associated with increased intestinal permeability, metabolic endotoxemia, and chronic low-grade inflammation, all of which may contribute to the development of obesity and insulin resistance. Diets rich in plant-derived fiber can beneficially shape gut microbiota composition. Bacterial fermentation of dietary fiber produces short-chain fatty acids (SCFAs), including butyrate, acetate, and propionate, which contribute to intestinal barrier integrity, inflammatory regulation, immune regulation, and metabolic homeostasis. Overall, the interaction between gut microbiota, diet, and host metabolic pathways represents a promising field for therapeutic and nutritional interventions aimed at preventing and managing MetS and metabolic diseases. Full article

Chronic inflammation and the associated dysbiosis of the gut microbiota are increasingly recognized as key factors contributing to the development of inflammatory bowel disease (IBD) and colorectal cancer (CRC). The diet–gut microbiota–immune system–cancer axis is considered a key regulator of these processes. Among the bioactive compounds found in the diet, ellagitannins have garnered significant scientific interest due to their conversion by the gut microbiota into biologically active metabolites known as urolithins. Urolithin A (UroA), one of the best characterized compounds, exhibits broad anti-inflammatory, antioxidant, immunomodulatory, and anticancer properties. It modulates signaling pathways associated with inflammation, oxidative stress, mitochondrial dysfunction, and cell proliferation. Furthermore, UroA has been shown to improve intestinal barrier integrity, regulate immune cell activity, and induce mitophagy, thereby contributing to the restoration of mitochondrial and cellular homeostasis. A growing body of evidence also suggests that UroA may inhibit cancer cell proliferation, induce apoptosis, and disrupt the molecular pathways involved in colorectal carcinogenesis. This review summarizes the current state of knowledge regarding the biosynthesis and bioavailability of UroA, its molecular mechanisms of action in IBD, and its potential role in the prevention and treatment of CRC. Furthermore, the limitations of UroA-based therapies and future research directions are discussed. Although further, well-designed clinical trials are necessary, current findings suggest that UroA may represent a promising microflora-targeted therapeutic strategy in chronic inflammatory and CRC diseases. Full article

Olive oil, particularly virgin (VOO) and extra-virgin olive oil (EVOO), is a central component of the Mediterranean diet and has been associated with cardiometabolic, anti-inflammatory, and intestinal health benefits. Increasing evidence suggests that these effects may involve interactions with the gut microbiota, intestinal barrier, and host inflammatory pathways. This narrative review summarizes current evidence on the impact of olive oil, olive-derived phenolics, and olive oil-rich dietary patterns on gut microbiota modulation, barrier function, inflammatory bowel diseases, and related systemic outcomes. The available literature indicates that olive oil may interact with the gut ecosystem through both its oleic acid-rich lipid matrix and its minor phenolic fraction. VOO and EVOO appear more consistently associated than refined oils with microbial or microbial metabolite profiles related to saccharolytic metabolism, short-chain fatty acid production, mucus-layer dynamics, and anti-inflammatory intestinal environments. Olive-derived phenolics, including hydroxytyrosol, tyrosol, oleuropein derivatives, and oleocanthal, can undergo microbial biotransformation and may influence bile acid metabolism, epithelial barrier integrity, and inflammatory signaling. Whole EVOO evidence is strongest in experimental colitis models, whereas human evidence mainly supports effects on postprandial endotoxemia, lipid oxidation, and selected inflammatory markers. However, findings remain heterogeneous and depend on oil quality, phenolic composition, comparator fat, dietary context, and host condition. Well-controlled human studies directly comparing EVOO, VOO, refined olive oil, and oleic acid-rich controls are needed to clarify reproducible microbiota-mediated effects and their relevance to intestinal and systemic health. Full article

Background: Alcohol use is a major global health burden and is causally linked to several wholly alcohol-attributed conditions, including alcohol use disorder (AUD) and alcohol-associated liver disease (ALD). Current therapeutic options remain limited. Dihydromyricetin (DHM), a plant-derived flavonoid with antioxidant and anti-inflammatory properties, has emerged as a potential candidate for mitigating alcohol-induced toxicity. This systematic review aimed to comprehensively evaluate the therapeutic effects of DHM across alcohol-related conditions. Methods: A systematic literature search was conducted in PubMed from inception through December 2025 for studies investigating the effects of DHM or DHM-containing extracts on alcohol-related outcomes. Both preclinical (in vitro and in vivo) and clinical studies were considered. Study quality was assessed qualitatively due to heterogeneity precluding use of a standardized risk-of-bias tool. Results were synthesized narratively by outcome category; meta-analysis was not performed. This review was unregistered with no prior protocol. Results: A total of 22 studies were included, comprising 8 in vitro, 17 in vivo, and 2 clinical studies, with some studies contributing data to more than one category. Across models, DHM consistently attenuated ethanol-induced cytotoxicity, oxidative stress, inflammation, and hepatic steatosis. DHM improved liver injury biomarkers (e.g., AST and ALT), enhanced antioxidant defenses, and modulated key signaling pathways including Nrf2 and AMPK. Additionally, DHM supported mitochondrial function and intestinal barrier integrity. However, findings related to ethanol metabolism and neurobehavioral outcomes were inconsistent. Clinical evidence was limited to two small trials using Hovenia dulcis extracts, which demonstrated reductions in hangover severity and selected inflammatory markers but did not directly evaluate isolated DHM. Conclusions: DHM demonstrates robust preclinical efficacy in mitigating alcohol-induced injury, particularly in hepatic outcomes. Despite promising mechanistic and experimental evidence, clinical data remain limited. The certainty of evidence is constrained by preclinical study heterogeneity, the absence of formal risk-of-bias assessment, and the lack of clinical trials using isolated DHM. Well-designed clinical trials using standardized DHM formulations are needed to establish its complete therapeutic potential in alcohol-related disorders. Full article

Inflammatory bowel disease, including ulcerative colitis (UC) and Crohn’s disease (CD), is associated with reduced vagus nerve activity and impaired barrier function. Transcutaneous auricular vagus nerve stimulation (taVNS) shows preventive effects in acute colitis, but its impact on intestinal barrier integrity remains unclear. To assess this, C57BL/6 male mice received taVNS (10 V, 20 Hz, 500 µs, 10 min) prior to colitis induction. UC-like colitis was induced using 5% dextran sulfate sodium (DSS) for 120 h with daily taVNS, while CD-like colitis was induced by intrarectal dinitrobenzene sulfonic acid (DNBS, 4 mg) in 30% ethanol with taVNS during induction and for 48 h. TaVNS reduced colonic proliferation in non-colitic mice in a homeostatic manner, as well as in DNBS-colitic mice, and enhanced differentiation. It decreased enteroendocrine cells in non-colitic conditions but not in DSS-colitic mice, and reduced tuft cells in DSS and DNBS groups. TaVNS increased MUC2 in DSS colitis and decreased TFF3 in DNBS controls. It decreased Lgr5⁺ stem cells in DSS controls but maintained them during DSS colitis, while HOPX⁺ stem cells decreased in non-colitic DSS conditions, and fetal-like stem cells remained unchanged. Disease activity index negatively correlated with chromogranin A. TaVNS prevented increased paracellular permeability in the distal colon of DSS-colitic mice, increased TEER in distal DSS controls and proximal colitic colon, and enhanced ion transport in the proximal colon under non-colitic DSS conditions. Overall, taVNS effects on epithelial composition and barrier function are context- and model-dependent. Full article

NLRP6 is a member of the NOD-like receptor family that was initially characterized as an inflammasome-forming sensor in the intestine. However, accumulating evidence over the past decade has revealed that the functions of NLRP6 extend far beyond this canonical role. NLRP6 operates in a wide range of tissues, including the intestine, liver, lung, and immune system, where it exerts context-dependent effects that can be either protective or detrimental. In the intestine, NLRP6 is most consistently associated with host protection, contributing to antiviral defense, epithelial barrier integrity, and the maintenance of microbial and metabolic homeostasis through both inflammasome-dependent and -independent mechanisms. In contrast, in systemic infection models and in certain inflammatory settings, NLRP6 can also promote pathology by suppressing NF-κB signaling; inducing IL-18–mediated lymphocyte death, or enhancing inflammatory cell death pathways. Moreover, studies using both conventional and tissue-specific knockout models have highlighted the importance of the gut–organ axis; particularly the gut–liver axis, in shaping NLRP6-dependent disease outcomes. Here, we summarize recent advances in understanding the upstream regulation, downstream signaling, and tissue-specific functions of NLRP6. Full article

Non-steroidal anti-inflammatory drugs (NSAIDs) are widely prescribed worldwide for their analgesic, antipyretic, and anti-inflammatory properties. However, their long-term use is associated with substantial gastrointestinal (GI) toxicity. Although upper GI injury has traditionally received greater attention, NSAID-induced enteropathy is now increasingly recognized as a common yet underdiagnosed condition. Advances in small-bowel imaging, particularly capsule endoscopy, have demonstrated that mucosal injury of the small intestine occurs in up to 70–80% of chronic NSAID users and may also develop after short-term exposure in otherwise healthy individuals, often without overt clinical symptoms. When symptoms do occur, NSAID-induced enteropathy is characterized by non-specific clinical manifestations and may lead to severe complications in approximately 1% of cases. The pathogenesis of NSAID-induced enteropathy is multifactorial and more complex than that underlying upper GI damage. It involves prostaglandin depletion, increased intestinal permeability, bile acid-mediated toxicity, enterohepatic recirculation of NSAIDs, and, importantly, interactions with the gut microbiota. Concomitant therapies, particularly proton pump inhibitors, may further aggravate small-bowel injury by promoting intestinal dysbiosis. Growing evidence supports a relevant contributory role for the gut microbiota as both a mediator and a modulator of NSAID-induced toxicity, affecting epithelial barrier function, oxidative stress, immune responses, and bile acid metabolism. This review provides an overview of current knowledge of NSAID-induced enteropathy, with a particular emphasis on the microbiota-driven mechanisms underlying mucosal injury. By integrating emerging microbiota-targeted therapeutic approaches, we propose a management algorithm that may help modify disease progression in a condition that remains frequently overlooked in clinical practice. Full article

The protective effect of Compound terminalia chebula extract (HL) against colonic injury induced by Porcine epidemic diarrhea virus (PEDV) infection in neonatal piglets remains unclear. This study aimed to evaluate the mitigating effects of HL on PEDV-induced colonic injury and elucidate the underlying mechanisms. Eighteen 7-day-old Duroc × Landrace × Large White piglets (2.58 ± 0.05 kg) were randomly assigned to three groups (n = 6/group): CON (blank control), PEDV (infected), and HL + PEDV (HL-supplemented + infected). The 11-day trial included 3 days of acclimatization (days 0–3) and an 8-day experimental period (days 4–11). HL (10 mg/kg BW) was orally administered daily to the HL + PEDV group. On day 8, PEDV and HL + PEDV groups were challenged with 3 mL PEDV (3 × 10⁶ TCID₅₀/mL), while CON received Dulbecco’s Modified Eagle Medium (DMEM). All piglets were euthanized on day 11 for colonic tissue collection. Results indicated that PEDV infection induced colonic injury, manifested by a significant increase in crypt depth and disruption of intestinal homeostasis. This was evidenced by impaired barrier integrity (upregulation of matrix metalloproteinase-7 gene [MMP7] and matrix metalloproteinase 13 gene [MMP13], mucus disorganization (elevation of mucin 5AC gene [MUC5AC]), oxidative stress (reduced catalase [CAT] activity and increased malondialdehyde [MDA] levels in serum and colon), and inflammation (upregulation of regenerative islet-derived protein 3γ gene [REG3G], S100 calcium-binding protein A8/A9 gene [S100A8/A9], and interleukin-1β gene [IL-1β]). Additionally, PEDV impaired colonic ion transport by downregulating calcium channel genes (Transient Receptor Potential Cation Channel Subfamily V Member 6 gene [TRPV6], Transient Receptor Potential Cation Channel Subfamily M Member 6 gene [TRPM6]). Notably, HL supplementation effectively reversed these adverse effects. HL restored colonic morphology, increased CAT activity, reduced MDA accumulation, and suppressed inflammatory gene expression. Furthermore, HL modulated the expression of genes involved in water and ion transport upregulating Aquaporin 7 gene (AQP7), Chloride Channel Accessory 4 gene (CLCA4), Sodium-Hydrogen Exchanger 3 gene (NHE3), Transient Receptor Potential Vanilloid 6 (TRPV6), and Transient Receptor Potential Melastatin 6 gene (TRPM6) and significantly inhibited PEDV replication, as indicated by the downregulation of the transcription levels of PEDV membranegene (M), nucleocapsid gene (N), and spike gene (S). Taken together, HL alleviates PEDV-triggered colonic tissue damage in suckling piglets via improving colonic antioxidant capacity, mitigating inflammatory response, partially regulating intestinal barrier and ion/water transport-related genes, and downregulating the transcription of PEDV structural genes at molecular and histological levels. Full article