Search Results (1,603)

Objectives: Disruption of gut–liver axis homeostasis is a hallmark of metabolic and toxic stress. This study aimed to evaluate the combined effects of high-fat diet (HFD), aflatoxin B1 (AFB1), and exogenous isoleucine supplementation on immunometabolic function under nutritional and toxic stress. Methods: Two-phase murine experiments assessed: (1) HFD and AFB1 effects individually and combined; and (2) dose-dependent isoleucine responses (25/50/100 mg/kg) across control, HFD, and HFD + AFB1 backgrounds. Results: HFD significantly impaired liver function, promoted Th17-mediated inflammation, and induced gut dysbiosis, while AFB1 alone exerted minimal effects. Their combination synergistically exacerbated hepatic steatosis, intestinal barrier disruption, and inflammatory responses. Fecal metabolomics identified elevated isoleucine as a potential inflammatory biomarker. Under HFD, isoleucine (50 mg/kg) amplified inflammation and oxidative stress. Remarkably, under HFD + AFB1, moderate/high-dose isoleucine reduced hepatic lipid deposition and triglycerides despite persistent intestinal damage, demonstrating context-dependent effects. Conclusions: HFD and AFB1 synergistically disrupt gut–liver axis integrity through immunometabolic mechanisms. Isoleucine supplementation exhibits dual-modulatory effects, exacerbating damage under nutritional stress while partially mitigating hepatic lipid accumulation under combined toxic-nutritional stress, highlighting the critical importance of environmental context in amino acid interventions. Full article

Background/Objectives: Ulcerative colitis (UC) incidence has risen alarmingly worldwide, posing significant clinical challenges due to limitations of therapeutic efficacy and side effects of current drugs. While Polygonatum kingianum polysaccharides (PKPs) exhibit anti-inflammatory and antioxidant properties, their anti-colitis potential remains unexplored. This study aimed to validate the protective effects of PKPs against dextran sulfate sodium (DSS)-induced colitis and elucidate its mechanisms. Methods: Acute UC was induced in C57BL/6J mice by 3% DSS. PKPs (125 mg/kg) were administered via gavage for 10 days. Integrated approaches included histopathology, tight junction protein (ZO-1/Occludin/Claudin-1) immunohistochemistry, inflammatory/oxidative markers (ELISA), Nrf2 pathway proteins (Western blot), 16S rRNA gut microbiota sequencing, fecal untargeted metabolomics (UHPLC-MS), short-chain fatty acids (SCFAs) analysis and combined analysis. Results: PKPs significantly alleviated colitis phenotypes: reduced weight loss, lowered disease activity index (DAI), and attenuated colon shortening. They restored intestinal barrier integrity by upregulating tight junction proteins and reducing plasma Diamine Oxidase (DAO)/D-lactate (D-Lac)/Endotoxin (ET). PKPs suppressed pro-inflammatory cytokines (TNF-α/IL-1β/IL-6) while elevating IL-10, activated the Nrf2/HO-1/NQO1 antioxidant pathway, and reduced oxidative stress (MDA decreased, SOD/GSH increased). Multi-omics revealed PKPs enriched beneficial bacteria (Blautia, Odoribacter, Rikenellaceae_RC9_gut_group), restored SCFAs (acetate/propionate/butyrate), and modulated metabolic pathways (sphingolipid/linoleic acid metabolism). Conclusions: PKPs ameliorate DSS-induced colitis through multi-target mechanisms: (1) preserving intestinal barrier function, (2) suppressing inflammation and oxidative stress via Nrf2 activation, (3) restoring gut microbiota balance and SCFA production, and (4) regulating host-microbiota metabolic interactions. These findings support PKPs as a promising dietary supplement for UC management. Full article

Technological advancements in computational power and algorithm design have enabled artificial intelligence to become a transformative force in microbiome research. This paper presents a concise overview of recent applications of this computational paradigm in human and animal health, with a particular emphasis on aquaculture. International projects focused on the intestinal microbiome have allowed human research to consistently dominate in terms of application cases, offering insights into various pathological conditions. In contrast, animal research has leveraged artificial intelligence in microbiome analysis to promote sustainable productivity, addressing environmental and public health concerns linked to livestock husbandry. In aquaculture, on the other hand, artificial intelligence has mainly supported management practices, improving rearing conditions and feeding strategies. When considering microbiome manipulation, however, fish farms have often relied on traditional methods, without harnessing the immense potential of artificial intelligence, whose recent applications include biomonitoring and modeling interactions between microbial communities and environmental factors in farming systems. Given the paradigm shift currently underway in both human health and animal husbandry, we advocate for a transition in the aquaculture industry toward smart farming, whose interconnected infrastructure will allow to fully leverage artificial intelligence to seamlessly integrate both biological measurements and rearing parameters. Full article

Lacticaseibacillus rhamnosus (Lbs. rhamnosus) is renowned for its tolerance to gastric acid and adaptability to bile and alkaline conditions, and is crucial for intestinal health and immune regulation. In this study, integrated transcriptomic and proteomic analyses were employed to elucidate the response mechanisms of Lbs. rhamnosus under osmotic stress, induced by exposure to 0.6 M sodium lactate, which elevates environmental osmotic pressure. It was shown that 792 differentially expressed genes and 138 differentially expressed proteins were detected in Lbs. rhamnosus ATCC 53103 treated with osmotic stress. The differential regulation of these genes/proteins mainly includes the inhibition of fatty acid metabolism with membrane structural remodeling (downregulation of the acetyl coenzyme A carboxylase family and fatty acid binding protein family expression), dynamic homeostasis of amino acid metabolism (restriction of the synthesis of histidine, cysteine, leucine, etc., and enhancement of the catabolism of lysine, tryptophan, etc.), and survival-oriented reconfiguration of carbohydrate metabolism (gene expression related to the glycolytic pathway increases, while gene expression related to the pentose phosphate pathway decreases). These synergistic alterations in metabolic regulation may facilitate the adaptive response of Lbs. rhamnosus ATCC 53103 to osmotic stress. Overall, our findings deepen the current understanding of the stress response mechanisms in lactic acid bacteria and offer novel insights into the survival strategies employed by Lbs. rhamnosus ATCC 53103 under hyperosmotic conditions. Full article

Bacterial disease infections pose a major challenge to the healthy growth of crucian carp. Hawthorn polysaccharide (HP) is a natural active ingredient in hawthorn and has a wide range of pharmacological effects. However, the mechanism of HP against Aeromonas hydrophila infection in crucian carp cultures is unknown. In this study, it was found that 0.4% HP could significantly reduce the mortality of crucian carp, significantly increase the activities of T-AOC, SOD, CAT, and GSH-PX of crucian carp infected with A. hydrophila (p < 0.05), decrease the activity of MDA, and decrease the expression levels of TGF-β, TNF-α, IFN-γ, and IL-8 genes. Increased IL-10 gene expression levels (p < 0.05) significantly improved the disease resistance of crucian carp. HP could relieve intestinal inflammation caused by A. hydrophila infection, restoring intestinal structural integrity. At the same time, HP increased the diversity and improved the structure of intestinal microbiota. At the phylum level, the abundance of Proteobacteria and Firmicutes increased, while that of Bacteroidota and Fusobacteriota decreased. At the genus level, the abundance of Aeromonas increased, while the abundance of Cetobacterium decreased. Non-targeted metabolomics analysis of crucian carp LC-MS revealed 147 different metabolites, 62 of which were up-regulated and 85 of which were down-regulated, and Linoleic acid metabolism and Glycerophospholipids were one of the most important metabolic pathways. In conclusion, the supplementation of HP in feed can promote the healthy breeding of crucian carp, and the effect of resisting A. hydrophila is better. Full article

Irritable Bowel Syndrome (IBS) and Metabolic dysfunction-associated fatty liver disease (MAFLD) have traditionally been viewed as disorders of distinct organ systems. IBS is a gut–brain axis disorder characterized by abdominal pain, altered bowel habits, and psychological comorbidities. MAFLD, recently redefined to emphasize its metabolic underpinnings, is the hepatic manifestation of systemic metabolic dysfunction. Growing evidence suggests that these conditions share overlapping pathophysiological mechanisms linked through disruption of the gut–liver–brain axis (GLBA), including psychological stress, gut dysbiosis, impaired intestinal permeability, systemic inflammation, and altered neuroendocrine signaling. Neuroimaging studies further reveal functional alterations in brain regions responsible for interoception, emotional regulation, and stress responsiveness in both disorders. This narrative review explores how psychological distress influences the onset and progression of IBS and MAFLD via GLBA dysfunction and stress-induced epigenetic reprogramming. A targeted literature search of major biomedical databases, supplemented by manual screening, identified relevant observational, clinical, neuroimaging, and molecular studies. Findings indicate that chronic psychological distress activates the hypothalamic–pituitary–adrenal (HPA) axis, elevates cortisol, disrupts gut microbiota, and reduces vagal tone; amplifying intestinal permeability and microbial translocation. These changes promote hepatic inflammation and gastrointestinal symptoms. Stress-related epigenetic modifications further impair GLBA communication, while psychological and lifestyle interventions may reverse some of these molecular imprints. Recognizing the shared neuromodulation and epigenetic mechanisms that link IBS and MAFLD opens promising avenues for integrated therapeutic strategies targeting the GLBA to improve outcomes across both conditions. Full article

The prevalence of hyperuricemia with elevated serum uric acid is increasing worldwide. However, the effects of high uric acid on diabetic patients with dyslipidemia and the mechanisms underlying these effects remain unexplored. This study aimed to develop a novel diabetic model of hyperuricemia and dyslipidemia in male hamsters to evaluate the effects of high uric acid on glucolipid metabolism, renal injury and the gut microbiota. Twelve healthy hamsters were randomly divided into two groups and fed with a normal diet and high-fat/cholesterol diet (HFCD), respectively. Twenty-four diabetic hamsters were randomly divided into four groups receiving a normal diet; HFCD; potassium oxonate (PO) treatment (intragastric PO at doses of 350 mg/kg and adenine at doses of 150 mg/kg with 5% fructose water); and PO treatment with HFCD, respectively. After 4 weeks, all animals were dissected for determining serum biochemical indicators, tissue antioxidant parameters, renal pathological changes, target gene expressions, fecal short-chain fatty acids content, and the gut microbiota composition. The results showed that a hamster model with hyperuricemia and dyslipidemia was successively established by the combination of PO treatment and HFCD, in which serum uric acid, glucose, triglyceride and total cholesterol levels reached 499.5 ± 61.96 μmol/L, 16.88 ± 2.81 mmol/L, 119.88 ± 27.14 mmol/L and 72.92 ± 16.62 mmol/L, respectively. PO treatment and HFCD had synergistic effects on increasing uric acid, urea nitrogen, creatinine levels, liver xanthine oxidase activity, plasminogen activator inhibitor-1 and transforming growth factor-β expressions, and the relative abundance of Lleibacterium (p < 0.05); in addition, they caused glomerular mesangial cells and matrix proliferation, protein casts and urate deposition. High uric acid was closely related to decreased antioxidant capacity; decreased renal vascular endothelial growth factor expression; increased acetic acid content; decreased butyric, propanoic, and isobutyric acid levels; decreased Firmicutes to Bacteroidetes ratios (p < 0.05); and altered epithelial integrity and structure of the gut microbiota in diabetic hamsters. The findings indicate that high uric acid affects the glucolipid metabolism, accelerates renal damage, and disrupts the balance of intestinal flora in diabetic animals, which provides a scientific basis for metabolic syndrome prevention and control in diabetes. Full article

Resveratrol (RES), a natural polyphenol with lipid metabolism-regulating properties, also demonstrates remarkable efficacy in strengthening intestinal barrier integrity. In order to elucidate the mechanism by which RES ameliorates intestinal damage and lipid metabolism disturbances in Megalobrama amblycephala under a high-fat (HF) diet, a conventional diet (CON), an HF diet (HF), or an HF diet supplemented with 0.6, 3, or 6 g/kg RES (HF + 0.06%, 0.3%, or 0.6% RES) was fed to fish. After 8 weeks, RES supplementation in the HF diet significantly improved the growth performance and alleviated hepatic lipid deposition. Microbiota profiling revealed RES improved intestinal barrier function by reducing α-diversity, Actinobacteria and Bosea abundances, and enriching Firmicutes abundance. RES also maintained the integrity of the intestinal physical barrier and inhibited the inflammatory response. MeRIP-seq analysis indicated that RES modulated intestinal mRNA m⁶A methylation by upregulating methyltransferase-like 3 (mettl3) and downregulating fat mass and obesity-associated gene (fto) and Alk B homolog 5 (alkbh5). Combined RNA-seq and MeRIP-seq data revealed that RES alleviated endoplasmic reticulum stress (ERS) by upregulating the m⁶A methylation and gene level of heat shock protein 70 (hsp70). Correlation analyses identified significant associations between intestinal microbiota composition and ERS, tight junction, and inflammation. In summary, RES ameliorates lipid dysregulation via a synergistic mechanism involving intestinal microbiota, m⁶A modification, ERS, barrier function, and inflammatory response. Full article

Liver-expressed antimicrobial peptide 2 (LEAP2) is a cationic peptide that is integral to the innate immune system. However, its regulatory function in the immunity of fish against pathogens remains largely unexplored. This study identifies a LEAP2 homolog (AoLEAP2) in clownfish, Amphiprion ocellaris. Our phylogenetic analysis places AoLEAP2 within the fish LEAP2 cluster, closely related to Tachinotus anak LEAP2. AoLEAP2 mRNA is present across various tissues, with the highest expression in the spleen. Following Vibrio harveyi infection, the AoLEAP2 mRNA levels significantly increased in the liver, spleen, gills, and intestine. The chemically synthesized AoLEAP2 mature peptide exhibits broad-spectrum antibacterial activity without displaying toxicity to FHM cells in vitro. The intraperitoneal injection of AoLEAP2 significantly suppresses the mRNA expression of the pro-inflammatory factors IL1β and TNFα induced by V. harveyi infection, demonstrating its anti-inflammatory and immune-regulatory role. Full article

Achieving precise drug release in the colon remains a key objective in therapies for inflammatory bowel disease (IBD). Natural polysaccharides, including high-amylose starch (HAS) and pectin, offer relevant characteristics for localized drug delivery due to their biocompatibility, biodegradability, and adaptability. In this work, high-esterified pectin (HEP) was incorporated during the retrogradation of HAS to further form cohesive films without the need for organic solvents or high temperatures. The resulting matrices showed improved mucoadhesive performance, particularly under colonic conditions, where hydrophobic ester groups in HEP enhanced tissue adherence. This feature is critical for prolonged residence time in inflamed mucosa. Variations in HEP content directly influenced matrix density, fluid interaction, and mechanical resistance, without compromising film integrity. The high degree of esterification limited pH-dependent swelling and promoted alternative release mechanisms potentially related to enzymatic degradation. Such behavior contrasts with traditional low-esterified pectin (LEP) systems, suggesting that HEP may act as a structural modifier rather than a neutral excipient. Despite its widespread use in food systems, HEP remains underexplored in pharmaceutical matrices, especially in combination with retrograded starch (RS). The physicochemical and biointerfacial properties observed here underscore their applicability for the rational design of colonic delivery systems and provide a foundation for formulation strategies tailored to chronic intestinal disorders. Full article

A novel diamine oxidase (DAO) was discovered in the bacterium Glutamicibacter halophytocola (DAO-GH). The gene of DAO-GH was integrated into the genome of the yeast Komagataella phaffii and recombinantly produced under control of the methanol-inducible AOX1 promoter in a bioreactor cultivation. A high DAO activity of 70.2 ± 5.2 µkat/L_culture (5.25 ± 0.22 µkat/g_protein) was yielded after 90 h of cultivation. The DAO-GH was partially purified by the polyethyleneimine precipitation of nucleic acids, fractionated ammonium sulfate precipitation and hydrophobic interaction chromatography, resulting in a specific DAO activity of 19.7 µkat/g_Protein. The DAO-GH was then biochemically investigated regarding its potential for histamine and tyramine degradation in fermented foods and the human small intestine. Interestingly, the DAO-GH showed activity even at a low pH of 5 and low temperature of 6 °C. Both histamine and tyramine were effectively degraded and DAO-GH showed especially very high affinity towards tyramine (K_m of 0.009 mM). The DAO-GH was shown to be capable of degrading around 20% of the initially applied histamine in tuna paste (pH 5.6) at 5 °C within 24 h and completely degraded the histamine in a simulated intestinal fluid within 1.5 h in bioconversion experiments. The DAO-GH was spray-dried for the production of a storable enzyme preparation. Only around 17% of activity were lost in this process and the DAO-GH remained stable at room temperature for at least 3 months. The discovery of this DAO with its very advantageous biochemical properties allows the preparation of histamine-reduced or -free fermented foods by a simple enzymatic treatment or the treatment of histamine intolerance symptoms as a dietary supplement or medicine. Full article

Neuroinflammation plays a central role in the pathogenesis of Alzheimer’s disease (AD), with amyloid-β (Aβ) deposition and neurofibrillary tangles driving both central and peripheral inflammatory responses. This study investigated the neuroprotective and anti-inflammatory effects of Vitex trifolia (VT), Plantago major (PM), Apocyni Veneti Folium (AVF), and Eucommiae folium (EF) using network pharmacology and a co-culture model of PC12 neuronal and Caco-2 intestinal epithelial cells. Bioactive compounds were identified via high-performance liquid chromatography (HPLC) and screened with network pharmacology analysis, yielding 27 for VT, 10 for PM, 6 for AVF, and 3 for EF. Molecular docking confirmed strong binding affinities between the key bioactive compounds and AD-related targets. A co-culture system of PC12 neuronal and Caco-2 intestinal epithelial cells was established to evaluate the effects of VT, PM, AVF, and EF extracts (at concentrations of 10 µg/mL, 20 µg/mL, and 50 µg/mL) and donepezil hydrochloride (positive-control) on Aβ_25–35-induced neurotoxicity and lipopolysaccharide (LPS)-induced intestinal inflammation, to assess cell viability, and effects on oxidative stress, mitochondrial function, and inflammatory markers. The VT, PM, AVF, and EF extracts activated phosphoinositide 3-kinase (PI3K)-Akt-glycogen synthase kinase-3β (GSK-3β) signaling, enhanced phosphorylation of AMP kinase, suggesting inhibition of Aβ accumulation and tau hyperphosphorylation (p < 0.05). However, donepezil hydrochloride only enhanced AMPK phosphorylation. The extracts reduced lipid peroxidation and acetylcholinesterase by about 5-fold. JC-1 staining confirmed preserved mitochondrial membrane potential, while hematoxylin and eosin staining indicated improved intestinal barrier integrity (p < 0.05). PM and AVF reduced the number of mast cells (p < 0.05). In conclusion, these findings highlight the multi-target potential of VT, PM, AVF, and EF in mitigating both neuronal and intestinal inflammation. Their dual regulatory effects on the gut–brain axis suggest promising therapeutic applications in AD through the modulation of central and peripheral immune responses. Full article

Cellulose nanofibers and pectin are promising candidates for polysaccharide-based gel carriers. However, their integration into a structurally modified hybrid gel system has not been extensively investigated. In this study, hybrid cryogels with a pH-responsive release profile favoring small intestinal delivery were prepared by freeze-drying various ratios of anionic nanofibrillar cellulose (aNFC) and amidated pectin (AP). Under acidic conditions, carboxylate protonation reduced intermolecular electrostatic repulsion, promoting the formation of the aNFC/AP hybrid gel network. Increasing the AP content enhanced the mechanical strength of the hydrogels and resulted in larger pore sizes after freeze-drying. The hybrid cryogels prolonged the release of a model drug for up to 20–30 min at pH 3.0, while exhibiting rapid release within 1–2 min when the pH exceeded 6.5, due to gel network collapse. The release behavior was governed by both the porous morphology and the crosslinking density of the cryogel scaffolds. These findings demonstrate that aNFC/AP hybrid cryogels possess a well-defined pH-responsive functional window (pH 6.5–7.0) and hold strong potential as oral drug delivery systems targeting the small intestine. Full article

Vitamin D is increasingly recognized as a key regulator of epithelial barrier integrity and mucosal immune homeostasis, with implications extending far beyond skeletal health. Through the vitamin D receptor (VDR), vitamin D regulates epithelial cohesion, innate immune responses, and tight-junction gene expression. This review explores the multifactorial role of vitamin D in modulating inflammation and preserving tissue barriers, with particular emphasis on its effects on tight junction (TJ) regulation and disease states characterized by barrier dysfunction, namely atopic dermatitis, psoriasis, inflammatory bowel disease (IBD), and celiac disease. In these settings, vitamin D/VDR signaling exerts protective actions by enhancing barrier structure, suppressing Th1/Th17-driven inflammation, modulating the gut and skin microbiome, and promoting epithelial repair. Animal studies and clinical data suggest that vitamin D supplementation can restore TJ expression, reduce disease activity, and improve clinical outcomes in both intestinal and dermatologic diseases. In the cardiovascular system, the role of vitamin D remains complex. While vitamin D influences endothelial function, insulin sensitivity, and systemic inflammation, supplementation trials yield mixed results, indicating a need for individualized approaches. Overall, this review synthesizes mechanistic, translational, and clinical data supporting vitamin D as a crucial modulator of barrier integrity and inflammation. These findings highlight its therapeutic relevance in chronic diseases characterized by immune dysregulation and epithelial disruption. Full article

Glutamine (Gln) supplementation during the weaning period can alleviate stress in piglets. However, free Gln has poor stability and low absorption in the small intestine. Glycyl-glutamine (Gly-Gln), a stable dipeptide form of Gln, has been evaluated as a potential alternative in pig nutrition. This study investigated the effects of Gly-Gln at 0, 0.125%, 0.25%, 0.375%, and 0.50%, as well as a Gly + Gln positive control, on growth performance, intestinal morphology, immunity, antioxidant status, and nutrient apparent digestibility in weaned piglets. The results showed that dietary supplementation with 0.25%, 0.375%, or 0.50% Gly-Gln significantly increased average daily gain, average daily feed intake, and final weight (p < 0.05). Linear and quadratic effects (p < 0.05) were observed for growth performance indicators, suggesting that moderate supplementation levels yielded optimal benefits. Dietary Gly-Gln supplementation with 0.25%, 0.375%, or 0.50% Gly-Gln significantly increased serum immunoglobulin (IgG, IgA, and IgM), insulin, insulin growth factor 1, growth hormone, and T4 and T3 contents, and decreased IFN-γ and IL-1β contents (p < 0.05). Diets supplemented with 0.25, 0.375, or 0.50% Gly-Gln increased total antioxidant capacity and superoxide dismutase content in serum and liver, and decreased MDA content (p < 0.05). Compared with the negative control group, dietary supplementation of 0.25%, 0.375%, or 0.50% Gly-Gln significantly increased the mRNA expression of ZO-1, Occludin, and Claudin-1 in the jejunum (p < 0.05). Furthermore, crude protein digestibility was significantly improved in piglets receiving 0.375% and 0.5% Gly-Gln (p < 0.05), with a significant linear relationship between Gly-Gln level and digestibility. In conclusion, 0.25% is the minimum effective dose of Gly-Gln for improving weaning outcomes. Gly-Gln is more effective than equivalent doses of free glycine and glutamine in enhancing growth performance, gut barrier integrity, and nutrient utilization in weaned piglets. Full article