Search Results (1,367)

Schizophrenia (SCZ) is a complex psychiatric disorder with heterogeneous molecular underpinnings that remain poorly resolved by conventional single-omics approaches, limiting biomarker discovery and mechanistic insights. To address this gap, we applied an artificial intelligence (AI)-driven multi-omics framework to an open access dataset comprising plasma proteomics, post-translational modifications (PTMs), and metabolomics to systematically dissect SCZ pathophysiology. In a cohort of 104 individuals, comparative analysis of 17 machine learning models revealed that multi-omics integration significantly enhanced classification performance, reaching a maximum AUC of 0.9727 (95% CI: 0.8889–1.000) using LightGBMXT, compared to 0.9636 (95% CI: 0.8636–1.0000) with CNNBiLSTM for proteomics alone. Interpretable feature prioritization identified carbamylation at immunoglobulin-constant region sites IGKC_K20 and IGHG1_K8, alongside oxidation of coagulation factor F10 at residue M8, as key discriminative molecular events. Functional analyses identified significantly enriched pathways including complement activation, platelet signaling, and gut microbiota-associated metabolism. Protein interaction networks further implicated coagulation factors F2, F10, and PLG, as well as complement regulators CFI and C9, as central molecular hubs. The clustering of these molecules highlights a potential axis linking immune activation, blood coagulation, and tissue homeostasis, biological domains increasingly recognized in psychiatric disorders. These results implicate immune–thrombotic dysregulation as a critical component of SCZ pathology, with PTMs of immune proteins serving as quantifiable disease indicators. Our work delineates a robust computational strategy for multi-omics integration into psychiatric research, offering biomarker candidates that warrant further validation for diagnostic and therapeutic applications. Full article

Premature ovarian insufficiency (POI) is an important factor in female infertility and is often associated with oxidative stress. Alginate oligosaccharides (AOSs), derived from the degradation of alginate, have been demonstrated to have protective effects against various oxidative stress-related diseases. However, the impact of AOSs on POI has not been previously explored. The current study explored the effects of AOSs on ovarian dysfunction in a mouse model of POI induced by D-galactose (D-gal). Female C57BL/6 mice were randomly divided into five groups: the control (CON), POI model (D-gal), and low-, medium-, and high-dose AOS groups (AOS-L, 100 mg/kg/day; AOS-M, 150 mg/kg/day; AOS-H, 200 mg/kg/day). For 42 consecutive days, mice in the D-gal, AOS-L, AOS-M, and AOS-H groups received daily intraperitoneal injections of D-gal (200 mg/kg/day), whereas those in the CON group received equivalent volumes of sterile saline. Following D-gal injection, AOSs were administered via gavage at the specified doses; mice in the CON and D-gal groups received sterile saline instead. AOS treatment markedly improved estrous cycle irregularities, normalized serum hormone levels, reduced granulosa cell apoptosis, and increased follicle counts in POI mice. Moreover, AOSs significantly reduced ovarian oxidative stress and senescence in POI mice, as indicated by lower levels of malondialdehyde (MDA), higher activities of catalase (CAT) and superoxide dismutase (SOD), and decreased protein expression of 4-hydroxynonenal (4-HNE), nitrotyrosine (NTY), 8-hydroxydeoxyguanosine (8-OHdG), and p16 in ovarian tissue. Analysis of the gut microbiota through 16S rRNA gene sequencing and short-chain fatty acid (SCFA) analysis revealed significant differences in gut microbiota composition and SCFA levels (acetic acid and total SCFAs) between control and D-gal-induced POI mice. These differences were largely alleviated by AOS treatment. AOSs changed the gut microbiota by increasing the abundance of Ligilactobacillus and decreasing the abundance of Clostridiales, Clostridiaceae, Marinifilaceae, and Clostridium_T. Additionally, AOSs mitigated the decline in acetic acid and total SCFA levels observed in POI mice. Notably, the total SCFA level was significantly correlated with the abundance of Ligilactobacillus, Marinifilaceae, and Clostridium_T. In conclusion, AOS intervention effectively mitigates ovarian oxidative stress, restores gut microbiota homeostasis, and regulates the microbiota–SCFA axis, collectively improving D-gal-induced POI. Therefore, AOSs represent a promising therapeutic strategy for POI management. Full article

Background/Objectives: Senecio scandens Buch.-Ham. is a flavonoid-rich traditional medicinal plant with established immunomodulatory properties. However, the mechanisms underlying the immunoregulatory and intestinal protective effects of its flavonoid extract (Senecio scandens flavonoids—SSF) remain unclear. This study characterized SSF’s bioactive components and evaluated its efficacy against cyclophosphamide (CTX)-induced immunosuppression and intestinal injury. Methods: The constituents of SSF were identified using UHPLC/Q-Orbitrap/HRMS. Mice with CTX-induced immunosuppression were treated with SSF (80, 160, 320 mg/kg) for seven days. Immune parameters (organ indices, lymphocyte proliferation, cytokine, and immunoglobulin levels) and gut barrier integrity markers (ZO-1, Occludin, Claudin-1 protein expression; sIgA secretion; microbiota composition) were assessed. Network pharmacology combined with functional assays elucidated the underlying regulatory mechanisms. Results: Twenty flavonoids were identified in SSF, with six prototype compounds detectable in the blood. The SSF treatment significantly ameliorated CTX-induced weight loss and atrophy of the thymus and spleen. It enhanced splenic T- and B-lymphocyte proliferation by 43.6% and 29.7%, respectively; normalized the CD4⁺/CD8⁺ ratio (1.57-fold increase); and elevated levels of IL-2, IL-6, IL-10, TNF-α, IFN-γ, IgM, and IgG. Moreover, SSF reinforced the intestinal barrier by upregulating tight junction protein expression and sIgA levels while modulating the gut microbiota, enriching beneficial taxa (e.g., the Lachnospiraceae_NK4A136_group, Akkermansia) and suppressing pathogenic Alistipes. Mechanistically, SSF activated the TLR/MyD88/NF-κB pathway, with isoquercitrin identified as a pivotal bioactive constituent. Conclusions: SSF effectively mitigates CTX-induced immunosuppression and intestinal damage. These findings highlight SSF’s potential as a dual-functional natural agent for immunomodulation and intestinal protection. Subsequent research should validate isoquercitrin’s molecular targets and assess SSF’s clinical efficacy. Full article

Plant-sourced Dietary Fibers (PDFs) have garnered significant attention due to their multifaceted health benefits, particularly in glycemic control, lipid metabolism regulation, and gut microbiota modulation. This review systematically investigates advanced modification strategies, including physical, chemical, bioengineering, and hybrid approaches, to improve the physicochemical properties and bioactivity of PDFs from legumes, cereals, and other sources. Key modifications such as steam explosion, enzymatic hydrolysis, and carboxymethylation significantly improve solubility, porosity, and functional group exposure, thereby optimizing the health-promoting effects of legume-sourced dietary fiber. The review further elucidates critical structure–function relationships, highlighting PDF’s prebiotic potential, synergistic interactions with polyphenols and proteins, and responsive designs for targeted nutrient delivery. In functional food applications, cereal-sourced dietary fibers serve as a versatile functional ingredient in engineered foods including 3D-printed gels and low-glycemic energy bars, addressing specific metabolic disorders and personalized dietary requirements. By integrating state-of-the-art modification techniques with innovative applications, this review provides comprehensive insights into PDF’s transformative role in advancing functional foods and personalized nutrition solutions. Full article

Background: Ulcerative colitis (UC), characterized by chronic intestinal inflammation, epithelial barrier dysfunction, and immune imbalance demands novel ameliorative strategies beyond conventional approaches. Methods: In this study, the probiotic properties of Lactobacillus paracaseiL21 (L. paracaseiL21) and its ability to ameliorate colitis were evaluated using an in vitro lipopolysaccharide (LPS)-induced intestinal crypt epithelial cell (IEC-6) model and an in vivo dextran sulfate sodium (DSS)-induced UC mouse model. Results: In vitro, L. paracaseiL21 decreased levels of pro-inflammatory cytokines (TNF-α, IL-1β, IL-8) while increasing anti-inflammatory IL-10 levels (p < 0.05) in LPS-induced IEC-6 cells, significantly enhancing the expression of tight junction proteins (ZO-1, occludin, claudin-1), thereby restoring the intestinal barrier. In vivo, both viable L. paracaseiL21 and its heat-inactivated postbiotic (H-L21) mitigated weight loss, colon shortening, and disease activity indices, concurrently reducing serum LPS and proinflammatory mediators. Interventions inhibited NF-κB signaling while activating HIF1α/AhR pathways, increasing IL-22 and mucin MUC2 to restore goblet cell populations. Gut microbiota analysis showed that both interventions increased the abundance of beneficial gut bacteria (Lactobacillus, Dubococcus, and Akkermansia) and improved faecal propanoic acid and butyric acid levels. H-L21 uniquely exerted an anti-inflammatory effect, marked by the regulation of Dubosiella, while L. paracaseiL21 marked by the Akkermansia. Conclusions: These results highlight the potential of L. paracaseiL21 as a candidate for the development of both probiotic and postbiotic formulations. It is expected to provide a theoretical basis for the management of UC and to drive the development of the next generation of UC therapies. Full article

In recent years, edible insects have gained significant attention as a sustainable and innovative source of feed for animal nutrition due to their excellent content of protein, fats, vitamins, and chitin. Among these, chitin is the least studied nutritional component, despite its promising properties and potential benefits. Chitin, an important polysaccharide found in the exoskeleton of arthropods, including insects, presents both negative and positive aspects in animal nutrition. As is known, the main drawback is its digestibility, which varies among livestock animal species depending on their ability to produce chitinase. However, chitin also exhibits benefits, including the enhancement of gut microbiota and immune response, together with the reduction in cholesterol and pathogen levels in animals. This review aims to summarise the current knowledge on the effects of chitin derived from edible insects on animal nutrition by analysing both the negative aspects and benefits for the different farmed animals for which insect feeding is legally permitted (fish, poultry, and pigs), while proposing future research directions. Full article

Zearalenone (ZEN), a mycotoxin commonly found in cereal crops and foods, induces testicular damage and disrupts gut microbial composition. Curcumin (CUR), a bioactive compound derived from turmeric, is known to enhance intestinal microbial balance and exhibit anti-inflammatory properties. This study aimed to investigate the mechanism by which CUR alleviates ZEN-induced reductions in sperm quality through the modulation of the gut microbiota–testis axis. Forty-eight 6-week-old Balb/c male mice were randomly assigned to four treatment groups: control (CON), CUR (200 mg/kg body weight CUR), ZEN (40 mg/kg body weight ZEN), and ZEN + CUR (200 mg/kg CUR + 40 mg/kg ZEN). The degree of sperm damage was quantified by assessing both the survival rate and the morphological integrity of the spermatozoa. CUR was found to mitigate ZEN-induced reductions in the testosterone levels, testicular structural damage, and disrupted spermatogenesis. Exposure to ZEN markedly perturbed the gut microbiota, characterized by increased relative abundances of Prevotella and Bacteroides and a concomitant reduction in Lactobacillus. These alterations were accompanied by pronounced activation of the IL-17A–TNF-α signaling axis, as demonstrated by elevated transcriptional and translational expression of pathway-associated genes and proteins. Co-administration of CUR effectively reinstated microbial homeostasis and mitigated ZEN-induced IL-17A pathway activation. In conclusion, ZEN induces testicular inflammation and reduced sperm quality by lowering testosterone levels and disrupting gut microbial balance, which drives the testicular IL-17A signaling pathway. CUR alleviates ZEN-induced testicular inflammation and sperm quality reduction by restoring beneficial gut microbes and testosterone levels. Full article

Lymphoma continues to pose a serious challenge to global health, underscoring the urgent need for new therapeutic strategies. Recently, the gut microbiome has been shown to play a potential role in regulating immune responses and influencing cancer progression. However, its molecular mechanisms of action in lymphoma remain poorly understood. This study investigates the antiproliferative and apoptotic activities of gut microbiota-derived metabolites, specifically nisin (N) and urolithin B (UB), individually and in combination 7:3 (5750 μM), against the human lymphoma cell line HKB-11. Comprehensive evaluations were performed using Alamar Blue viability assays, combination index (CI) analyses, reactive oxygen species (ROS) quantification, flow cytometry for apoptosis detection, and advanced bottom-up proteomics analyses. N and UB exhibited potent antiproliferative activity, with the 7:3 combination demonstrating strong synergistic effects (CI < 1), significantly enhancing apoptosis (p < 0.01) and ROS production (p < 0.0001) compared to the untreated control. Proteomics analyses revealed substantial alterations in proteins crucial to ribosomal biogenesis, mitochondrial function, cell cycle control, and apoptosis regulation, including a marked downregulation of ribosomal proteins (RPS27; Log₂FC = −3.47) and UBE2N (Log₂FC = −0.60). These findings highlight the potential of N and UB combinations as a novel and practical therapeutic approach for lymphoma treatment, warranting further in vivo exploration and clinical validation. Full article

Suckling is crucial for piglet intestinal development and gut health, as it improves resilience during the challenging weaning phase and promotes subsequent growth. IPS, comprising Na⁺/K⁺ ions, whey protein, and glucose, has been shown to have positive effects on animal growth and intestinal health. The objectives of this study were to assess the impact of IPS consumption on the growth performance, immunity, intestinal growth and development, and microbiota structure of suckling piglets. A total of 160 newborn piglets were randomly divided into control and IPS groups, with IPS supplementation starting from 2 to 8 days after birth and continuing until 3 days before weaning. The findings revealed that IPS boosted the body weight at 24 days by 3.6% (p < 0.05) and improved the body weight gain from 16 to 24 days by 15.7% (p < 0.05). Additionally, the jejunal villus height and villus height to crypt depth ratio in the IPS group were notably increased to 1.08 and 1.31 times (p < 0.05), respectively, compared to the control group. Furthermore, IPS elevated the plasma levels of IgA and IgM, reduced the plasma levels of blood urea nitrogen (BUN), and enhanced the content of secretory immunoglobulin A (SIgA) in the jejunal mucosa of suckling piglets. Furthermore, IPS upregulated the mRNA expression of tight junction proteins GLP-2, ZO-1, and Claudin-1 in jejunal tissue, while downregulating the regulatory genes in the Toll-like pathway, including MyD88 and TLR-4 (p < 0.05). The analysis of gut microbiota indicated that IPS altered the relative abundance of gut microbes, with an increase in beneficial bacteria like Alloprevotella and Bacteroides. In conclusion, this study demonstrates that IPS supplementation enhances weaning weight, growth performance, immune function, and intestinal development in piglets, supporting the integration of IPS supplementation in the management of pre-weaning piglets. Full article

Recent findings highlight that Reelin, a glycoprotein involved in neural development, synaptic plasticity, and neuroinflammation, plays some specific roles in neurodegenerative disorders associated with aging, such as age-related macular degeneration (AMD) and Alzheimer’s disease (AD). Reelin modulates synaptic function and guarantees homeostasis in neuronal-associated organs/tissues (brain and retina). The expression of Reelin is dysregulated in these neurological disorders, showing common pathways depending on chronic neurogenic inflammation and/or dysregulation of the extracellular matrix in which Reelin plays outstanding roles. Recently, the relationship between AMD and AD has gained increasing attention as they share many common risk factors (aging, genetic/epigenetic background, smoking, and malnutrition) and histopathological lesions, supporting certain pathophysiological crosstalk between these two diseases, especially regarding neuroinflammation, oxidative stress, and vascular complications. Outside the nervous system, Reelin is largely produced at the gastrointestinal epithelial level, in close association with innervated regions. The expression of Reelin receptors inside the gut suggests interesting aspects in the field of the gut–brain–eye axis, as dysregulation of the intestinal microbiota has been frequently described in neurodegenerative and behavioral disorders (AD, autism, and anxiety and/or depression), most probably linked to inflammatory, neurogenic mediators, including Reelin. Herein we examined previous and recent findings on Reelin and neurodegenerative disorders, offering findings on Reelin’s potential relation with the gut–brain and gut–brain–eye axes and providing novel attractive hypotheses on the gut–brain–eye link through neuromodulator and microbiota interplay. Neurodegenerative disorders will represent the ground for a future starting point for linking the common neurodegenerative biomarkers (β-amyloid and tau) and the new proteins probably engaged in counteracting neurodegeneration and synaptic loss. Full article

Sourdough fermentation, driven by the biochemical activity of lactic acid bacteria (LAB), presents a scientifically promising approach to addressing nutritional limitations in cereal-based staples. This review critically examines both the underlying mechanisms by which LAB enhance the nutritional profile of sourdough and the translational challenges in realizing these benefits. Key improvements explored include enhanced mineral bioavailability (e.g., up to 90% phytate reduction), improved protein digestibility, an attenuated glycemic response (GI ≈ 54 vs. ≈75 for conventional bread), and the generation of bioactive compounds. While in vitro and animal studies extensively demonstrate LAB’s potential to reshape nutrient profiles (e.g., phytate hydrolysis improving iron absorption, proteolysis releasing bioactive peptides), translating these effects into consistent human health outcomes proves complex. Significant challenges hinder this transition from laboratory to diet, including the limited bioavailability of LAB-derived metabolites, high strain variability, and sensitivity to fermentation conditions. Furthermore, interactions with the food matrix and host-specific factors, such as gut microbiota composition, contribute to inconsistent findings. This review highlights methodological gaps, particularly reliance on in vitro or animal models, and the lack of long-term, effective human trials. Although LAB hold significant promise for nutritional improvements in sourdough, translating these findings to validated human benefits necessitates continued efforts in mechanism-driven strain optimization, the standardization of fermentation processes, and rigorous human studies. Full article

Postbiotics, defined as metabolites produced by probiotics, encompass both bacterial cells and their metabolic byproducts, and offer significant health benefits to the host. However, there are relatively few reports on their effects on intestinal microbiota. In this study, we investigated the components, total antioxidant capacity of Lactobacillus helveticus postbiotics (LHPs) and their impact on intestinal flora using the Simulator for Human Intestinal Microecology Simulation (SHIME). The results indicate that the primary components of postbiotics include polysaccharides, proteins, and organic acids. Furthermore, LHPs have a strong ability to inhibit the growth of harmful bacteria while promoting the growth of probiotics. Additionally, LHPs significantly increased the total antioxidant capacity in the intestine and regulated the balance of intestinal microbiota. Notably, there was also a significant increase in the content of short-chain fatty acids (SCFAs) in the intestine. Overall, LHPs have the potential to aid in the prevention and treatment of diseases by enhancing gut microbiology. Full article

During commercial pig production, weaning is a major stressor that disrupts the gut microbiome, compromises intestinal barrier integrity, and increases the susceptibility of piglets to pathogens. This often results in post-weaning diarrhoea (PWD), leading to growth retardation, morbidity, and economic loss. This study investigated the effects of dietary xylo-oligosaccharide (XOS) supplementation on the growth performance and gut health of 216 piglets with naturally occurring PWD. Piglets received either 0 (CON), 50 (XOS-50), or 500 (XOS-500) mg XOS/kg feed from weaning at 28 days of age (d1) for 54 days. XOS-500 significantly improved body weight at d22 and d54, but had no effect on average daily gain, daily feed intake (DFI), or feed conversion ratio. The intestinal microbiota alpha-diversity was unaffected by XOS, though jejunal beta diversity differed between CON and XOS-500 groups at d22. Jejunal Chao richness correlated positively with d54 body weight, while ileal Chao richness correlated negatively with DFI. Salmonella was present in all diet groups but did not differ in abundance; however, the levels were negatively correlated with alpha diversity. XOSs increased Lactobacillus (d22, d54) and Clostridium_XI (d22), while reducing Veillonellaceae spp. (d22). XOSs reduced jejunal goblet cell (GC) density at d22 but increased duodenal and jejunal GCs and reduced duodenal crypt depth at d54. XOSs upregulated the genes for the tight junction proteins CLDN2, CLDN3, ALPI, and ZO-1, while downregulating the cytokine IL-8. These findings highlight XOSs’ potential to improve growth and gut health in weaning piglets with naturally occurring PWD, to maintain productivity and enhance welfare. Full article

The objective of this study was to investigate alterations in nutrient utilization, standardized ileal digestibility of amino acids (SIDAA), and intestinal health in response to heat stress (HS) in Pekin ducks. A total of 240 healthy 28-day-old male Pekin ducks were randomly allocated to three groups: a normal control (NC) group, an HS group, and a pair-fed (PF; provided an amount of feed equal to that consumed by the HS group to eliminate the effects of feed intake) group, each with eight replicate cages of ten birds. The results showed that HS significantly reduced the apparent utilization of dietary energy, ether extract, and crude protein compared to both the NC and PF groups (p < 0.05), but yielded comparable SIDAA to the PF group. The HS group exhibited reduced mRNA levels of EAAT3 and PepT1, along with elevated mRNA levels of CAT1, GLUT5, and FATP6 in the jejunum compared to the NC or PF groups, respectively (p < 0.05). Furthermore, HS resulted in a significant deterioration of jejunal morphology and goblet cell count compared to the NC and PF groups (p < 0.05). Serum fluorescein isothiocyanate-dextran levels were significantly higher in HS ducks than in NC ducks (p < 0.05), but did not differ from PF ducks. At order-level classification of ileal mucosal microbiota, HS markedly increased the relative abundance of Bacillales, Deferribacterales, and Actinomycetales versus NC (p < 0.05), while significantly decreasing Bifidobacteriales abundance relative to PF (p < 0.05). Collectively, HS induces a leaky gut and microbiota dysbiosis that compromises gut health, thereby reducing dietary nutrient utilization in Pekin ducks. The observed reduction in feed intake constitutes a primary driver of intestinal health deterioration in heat-stressed Pekin ducks. Full article

The objective of this experiment was to investigate the effects of tartary buckwheat flavonoids (TBF) and 25-hydroxyvitamin D₃ (25-OHD) on fatty liver syndrome (FLS) in laying hens. A total of 450 35-wk-old Lohmann laying hens were selected and randomly divided into five groups, with six replicates per treatment and 15 laying hens in each replicate. The control group was fed a corn-soybean meal basal diet. The FLS group was fed a high- energy–low-protein (HELP) diet, and the other three experimental groups were fed HELP diets supplemented with 60 mg/kg TBF, 69 μg/kg 25-OHD, and 60 mg/kg TBF plus 69 μg/kg 25-OHD, respectively. The experiment lasted 8 weeks. The results demonstrated that feeding laying hens with a HELP diet led to a significant accumulation of fat in their livers, liver enlargement and yellowing, as well as a decline in liver antioxidant capacity and an aggravation of inflammation. TBF alone, 25-OHD alone, and their combination had no effect on the laying performance of laying hens fed with a HELP diet. However, 25-OHD significantly enhanced the albumin content, eggshell strength, and eggshell thickness of eggs (p < 0.05). Compared with the HELP group, TBF, 25-OHD, or their combination reduced serum LDL-C and TG (p < 0.05). The combined treatment further lowered serum NEFA and MDA, enhanced liver SOD activity (p < 0.05), and unlike TBF alone (which reduced hepatic TG) or 25-OHD alone (which decreased liver index), reduced both liver index and hepatic TG (p < 0.05). Liver gene expression analysis showed that combined TBF and 25-OHD significantly inhibited the expression of fat synthesis-related genes (ACC, FAS, GPAT1, ChREBP1, LXRα, SREBP-1C, SREBP-2, FABP) as well as inflammation-related genes (IL-6, TNF-α, NF-κB, TLR4) (p < 0.05). At the phylum level of the cecal microbiota, TBF increased the abundance of Bacteroidota (p < 0.05), and combined TBF and 25-OHD tended to increase the abundance of Firmicutes_D. At the genus level, TBF increased the abundance of Phocaeicola_A (p < 0.05). Furthermore, TBF, 25-OHD, or their combination reduced the abundance of Faecalibacterium (p < 0.05). These findings suggest that combined TBF and 25-OHD mitigates FLS in laying hens potentially through remodeling gut microbiota and maintaining lipid metabolic homeostasis. Full article