Search Results (602)

Background: The early-life gut microbiota plays a critical role in programming intestinal barrier function and immune homeostasis, with profound implications for long-term host health. However, the effects of early-life compound probiotic intervention on the maturation of intestinal barrier function and the underlying molecular mechanisms remain incompletely understood, particularly in large-animal models relevant to human physiology. Methods: In this preclinical study, 3627 neonatal piglets—a well-established translational model for human infant gut development—were orally administered a novel compound probiotic formulation comprising Bifidobacterium longum subsp. infantis BZ, Lactobacillus plantarum LZ, and Pediococcus acidilactici PZ during early life. A total of 1512 fecal samples collected at seven time points from birth to day 180 were analyzed by 16S rRNA sequencing, and 525 samples from three developmental windows (days 10, 25, and 70) were subjected to LC-MS-based metabolomics. The candidate metabolite indole-3-lactic acid (ILA) was further mechanistically validated in a DSS-induced colitis mouse model and in IPEC-J2 cells. Results: Early-life probiotic intervention significantly enhanced intestinal barrier integrity, as evidenced by improved intestinal morphology and upregulated expression of tight junction proteins—zonula occludens-1 (ZO-1), occludin (OCLN), and Claudin-1 (CLDN1)—in the jejunum (p < 0.05). Notably, intervention at birth was more effective than post-weaning administration, and two administrations (birth + weaning) yielded superior outcomes compared with a single administration (p < 0.05). Microbiome analysis revealed enhanced microbial diversity and enrichment of beneficial genera during the juvenile-to-adult transition (p < 0.05). Metabolomic profiling identified ILA as a signature metabolite consistently elevated by probiotic supplementation. Conclusions: These findings provide evidence that early-life compound probiotic intervention is associated with improved intestinal barrier maturation, with ILA identified as a key candidate metabolite that may mediate this effect, as supported by functional validation in murine and cellular models. This provides a mechanistic rationale for probiotic-based strategies to support intestinal health in human infants during critical developmental windows. Full article

Metabolic syndrome (MetS) represents a growing global health burden characterized by obesity, insulin resistance, dyslipidemia, and hypertension. Increasing evidence suggests that gut microbiota-associated mediators may serve as signaling intermediates involved in host metabolic regulation. However, the mechanisms by which these mediators interact with host signaling pathways and influence metabolic responses remain incompletely understood. This review summarizes current advances in gut microbiota-associated mediators, focusing on short-chain fatty acids, bile acids, lipopolysaccharide, trimethylamine N-oxide, and branched-chain amino acids. We discuss their interactions with host metabolic and inflammatory pathways, including pathways implicated in FFAR2/3-mediated signaling, FXR/TGR5 signaling, TLR4/NF-κB-mediated inflammatory signaling, and mTORC1-associated nutrient-sensing. Furthermore, we propose a microbiota–mediator–host signaling network framework as an emerging conceptual model to integrate these molecular interactions and highlight the utility of multi-omics approaches in characterizing complex microbiota–host communication. Despite mechanistic advances, substantial challenges remain, including heterogeneous microbial signatures across populations, limited causal evidence, inter-individual variability in therapeutic responses, and barriers to clinical translation of microbiota-targeted interventions. A better understanding of microbiota-associated signaling networks may provide new insights into metabolic regulation and contribute to the rational development of microbiota-targeted strategies that complement established lifestyle interventions for MetS management. Full article

Non-IgE-mediated food allergy is characterized by delayed gastrointestinal manifestations and the absence of reliable non-invasive biomarkers. Increasing evidence suggests that gut microbiota may contribute to this disease pathogenesis. The aim of this study was to characterize the gut microbiome composition in thirty pediatric patients diagnosed with non-IgE-mediated food allergy, in comparison to fifteen healthy controls children, and to investigate its association with fecal calprotectin, eosinophil-derived neurotoxin (EDN) and IgA. Gut microbiota profiling was performed by 16S rRNA gene sequencing targeting the V3–V4 region. Compared with healthy controls, higher mean relative abundances of Bacteroides, Faecalibacterium, Alistipes, Parabacteroides, and Sutterella were observed in patients. Conversely, healthy children showed higher mean relative abundances of Pseudobutyrivibrio, Roseburia, Bifidobacterium, Collinsella, Clostridium, Eubacterium, Streptococcus, and Barnesiella. Several genera (Escherichia–Shigella, Agathobacter, and Enterococcus/Streptococcus) were detected only in the allergy cohort. Shannon diversity was higher in patients compared to controls and in the subgroups of patients with elevated fecal calprotectin (p = 0.028), previous antibiotic exposure (p = 0.015), and atopic dermatitis (p = 0.021). Stratification according to inflammatory biomarkers identified a distinct inflammatory microbiome endotype characterized by increased fecal calprotectin and EDN together with enrichment of Veillonellaceae and depletion of Bifidobacteriaceae and Lachnospiraceae. Correlation analyses further revealed positive associations between Veillonella abundance and both fecal calprotectin and EDN. These findings suggest that pediatric non-IgE-mediated food allergy is characterized by distinct microbiome–inflammation relationships rather than a single dysbiotic signature. Full article

The gut microbiota is a metabolically active ecosystem that influences host physiology through bioactive metabolites and interactions with host signaling pathways. Recent research has established a bidirectional gut–muscle axis in which microbial metabolites and muscle-derived factors (myokines) regulate muscle protein synthesis, degradation, regeneration, fiber-type specification, and overall muscle performance. Studies using germ-free, antibiotic-treated, probiotic-supplemented, and fecal microbiota transplantation models demonstrate that the gut microbiota is a critical determinant of skeletal muscle mass and function. Key mediators include short-chain fatty acids, bile acids, aromatic amino acid metabolites, microbial-associated molecular patterns, and methylamine metabolites. This review summarizes current mechanistic knowledge of gut–muscle communication and its relevance to livestock production. In monogastric livestock, particularly pigs and poultry, microbiota transplantation experiments and targeted probiotic interventions provide causal evidence that gut microbial communities influence muscle growth, muscle fiber composition, intramuscular fat deposition, carcass traits, and meat quality, including tenderness, marbling, water-holding capacity, and flavor. Several studies have also identified specific microbial taxa and metabolites capable of transferring desirable production phenotypes. In contrast, evidence in ruminants remains largely associative and originates mainly from multi-omics and dietary intervention studies. Future research should validate causal mechanisms, identify robust microbial biomarkers, and develop species-specific microbiome-based strategies for precision livestock production. Full article

Background/Objective: Maternal diet is an important determinant of gut microbiota composition in dams and offspring. This study investigated whether HDCA supplementation during maternal high-fat diet (HFD) exposure was associated with gut microbiota composition in dams and offspring and with selected obesity-related phenotypes. Methods: Nineteen C57BL/6J female mice were assigned to a control diet group (CON), a high-fat diet group (HFD), and a high-fat diet supplemented with 0.5% hyodeoxycholic acid group (HFD+HDCA). Fecal samples were collected from the dams before mating, following 8 weeks of dietary intervention, and from the offspring at weaning. All samples were analyzed using 5R 16S rRNA gene sequencing. Body weight was monitored in both dams and offspring, and liver histology was assessed by hematoxylin and eosin staining. Results: HFD exposure was associated with obesity-related phenotypes in dams and offspring, including increased maternal body weight and greater hepatic lipid accumulation and visceral adiposity in offspring. LEfSe and ANCOM-BC2 analyses identified concordant microbial changes between dams and offspring under corresponding dietary conditions. Lachnospiraceae_Unknown_genus3261 and Coprococcus increased with HFD exposure in both dams and offspring, whereas Bifidobacterium, Coprococcus, and Allobaculum decreased following HDCA supplementation. These findings indicate maternal–offspring concordance in microbiota responses to HFD and HDCA, without establishing direct vertical transmission. PICRUSt2 analysis suggested group association differences in predicted functional potential for pathways annotated to propionate, pyruvate, and β-alanine metabolism. Conclusions: HDCA supplementation during maternal HFD exposure was associated with differences in offspring gut microbiota at weaning and with attenuation of selected obesity-related phenotypes. These findings suggest a potential role of the gut microbiota–bile acid axis in mediating intergenerational dietary effects. However, the study does not establish direct microbial transmission, altered metabolic activity, or causality; these findings require confirmation in litter-aware and mechanistic studies. Full article

Insect protein farming offers sustainable advantages in land efficiency, emission reductions, and bioconversion, yet optimizing the nutrient composition remains a major challenge for cost-effective production. This study investigates the co-regulatory mechanism between alkali-soluble protein (SpA) and the gut microbiota in black soldier fly larvae (Hermetia illucens) and their effect on protein conversion efficiency. Feeding trials with varying alfalfa/SpA ratios identified a wheat middlings/alfalfa meal blend at a (5:0 ratio) as optimal for promoting larval protein accumulation. SDS-PAGE and 16S rRNA analyses revealed a strong positive correlation between SpA and larval crude protein (R² = 0.82). The network analysis and Pearson correlation heatmap further confirmed positive correlations among SpA, larval protein, Enterococcus, and Ignatzschineria (p < 0.05), suggesting that high SpA in the substrate was associated with the enrichment of these taxa, which synergistically enhanced proteolysis through alkaline protease secretion (R² = 0.85) and chitinase-mediated gut remodeling. Multi-linear regression modeling verified SpA as a superior predictor of the crude protein content compared with total nitrogen (TN), improving the model’s coefficient of determination (R²) from 0.40 to 0.82. These findings highlight SpA’s higher bioavailability and its direct role in metabolic utilization. By integrating the feed composition, microbiome function, and host metabolism, this study established a regulatory network driving larval protein biosynthesis. The targeted modulation of dietary SpA content may offer a promising approach to enhance beneficial microbial communities and improve protein conversion efficiency in BSFL-rearing systems. These findings provide a theoretical basis for optimizing feed formulations to support sustainable insect protein production from organic waste. Full article

Depression is a prevalent and complex neuropsychiatric disorder that substantially impairs quality of life worldwide. Current pharmacological and psychotherapeutic interventions are often limited by inadequate efficacy and restricted accessibility. Exercise has emerged as a potent non-pharmacological alternative, exhibiting antidepressant effects comparable to conventional treatments, with the microbiota–gut–brain (MGB) axis increasingly recognized as a key mediator. Despite growing interest, existing research articles largely describe associations without mapping the molecular pathways from exercise-altered microbes to neurobiological changes in depression. This review addresses these gaps by comprehensively dissecting the molecular cascades from microbial remodeling to synaptic and systemic adaptations, thereby providing a mechanistic roadmap absent in current syntheses. We first delineate how gut dysbiosis contributes to depression via endocrine, neural, and immune pathways. Subsequently, we highlight the ability of exercise to reverse these pathological states by restoring microbial diversity, reinforcing intestinal barrier function, and modulating the production of microbial metabolites. These exercise-driven changes collectively attenuate systemic and neuroinflammation, enhance brain-derived neurotrophic factor signaling, augment serotonin synthesis, and dampen hypothalamic–pituitary–adrenal axis hyperactivity. By reinstating intestinal homeostasis, exercise acts as a central regulator of the MGB axis and represents a promising therapeutic strategy. This integrative framework offers novel insights into depression pathogenesis and opens avenues for multifaceted intervention. Full article

Prebiotic-mediated gut microbiota modulation is a promising approach for obesity management. Red onions have been identified as a potential source of inulin and inulin neoseries oligosaccharides. This study evaluated the in vivo effects of short-chain inulin and inulin neoseries oligosaccharides (SCIINOs) on the fecal microbiota of obese rats and assessed their potential role in obesity attenuation. Male Wistar rats were fed a high-fat diet (HFD) for 16 weeks to induce obesity, while control rats received a normal diet (ND). From weeks 16 to 24, HFD-fed obese rats were randomly assigned to four groups: SCIINOs at 0.5 g/day, SCIINOs at 1 g/day, atorvastatin (10 mg/kg/day), or no intervention. Obesity status was confirmed by increased body weight, total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), and higher food and energy intakes. SCIINOs were enzymatically hydrolyzed and purified by yeast treatment and chromatographic methods. After 8 weeks of SCIINO administration (1 g/day), the fecal microbiota was markedly enriched in Bifidobacterium and Allobaculum, whereas Blautia abundance significantly decreased. SCIINOs also increased taxa negatively associated with obesity-related parameters, including Dubosiella, Rothia, Parabacteroides, Eubacterium, and Coriobacteriaceae UCG-002, which correlated with reductions in body weight, triglycerides, TC, LDL-C, and fasting blood glucose, along with increased high-density lipoprotein cholesterol (HDL-C). In parallel, SCIINOs increased fecal acetate and butyrate levels, which was consistent with the enrichment of Bifidobacterium and butyrate-producing bacteria. Overall, SCIINOs derived from red onions show promise as a prebiotic candidate for obesity attenuation through selective microbiota modulation and enhanced short-chain fatty acid production. Full article

Metabolic diseases, including obesity and type 2 diabetes mellitus, represent a major global health burden and are closely linked to the composition and function of the gut microbiota. Advances in molecular methods have enabled detailed characterization of microbial communities and their interactions with diet, medications, and host physiology, positioning the microbiome as an active metabolic organ. However, the field faces persistent challenges in distinguishing causal relationships from associations, largely owing to substantial biological, exposure-related, and methodological heterogeneity. This review systematizes the principal lines of evidence connecting the gut microbiome to metabolic disorders and critically examines the sources of variability that limit reproducibility and cross-cohort transferability of these findings. We discuss the taxonomic, functional, and metabolite-based levels of microbiome analysis, evaluate the strengths and limitations of cross-sectional, case–control, cohort, and interventional study designs, and consider approaches for establishing causality, including fecal microbiota transplantation, Mendelian randomization, mediation analysis, causal diagrams, and triangulation of evidence. We conclude that only a comprehensive, standardized, and causally informed approach will allow reliable discrimination between true microbiota-driven effects and methodological artifacts, thereby advancing the integration of microbiome science into the management of metabolic diseases and diabetes. Full article

Sulforaphane (SFN), an isothiocyanate produced from glucoraphanin in cruciferous vegetables, has been associated with the regulation of lipid storage, fatty acid oxidation, and autophagic lipid turnover. Therefore, in the current narrative review, AMPK-centered mechanisms were critically evaluated by distinguishing pathway association from experimentally demonstrated AMPK dependence. In cell and animal models, SFN treatment was associated with ACC phosphorylation, inhibition of mTORC1-SREBP signaling, CPT-1-related fatty acid oxidation, PGC-1α/PPAR-α transcriptional regulation, and ULK1-mediated lipophagy. However, most studies measured AMPK phosphorylation without pharmacological or genetic suppression, and one adipocyte study showed decreased AMPK phosphorylation during SFN-induced lipolysis. These findings indicate that SFN signaling can vary depending on the model, dose, and measured endpoint. Human studies have also shown highly variable SFN exposure and limited or inconsistent effects on lipid and glycemic outcomes, but AMPK-mediated lipid remodeling has not been directly demonstrated in target tissues. In addition, food matrix, myrosinase activity, dose, gut microbiota, and SFN-NIT formation can influence systemic exposure. Therefore, AMPK may be considered an important component of a broader SFN-responsive network rather than an exclusive mechanism. Further standardized human studies are required to evaluate quantified SFN exposure, lipid-related outcomes, tissue-relevant pathway biomarkers, and long-term safety. Full article

Chronic kidney disease (CKD) is common in older cats, and nutritional management remains the intervention with the strongest clinical evidence. Interest has expanded from conventional control of phosphorus and uremic signs to the gut–kidney axis, in which renal dysfunction may alter the intestinal environment while microbial metabolism generates solutes that accumulate as kidney function declines. This PRISMA-ScR-guided scoping review and critical narrative synthesis evaluates feline evidence on CKD-associated dysbiosis, gut-derived uremic solutes, bile acid metabolism, and microbiome-directed nutrition. The original search covered January 2021 to April 2026, with inclusion of earlier studies and targeted source verification through July 2026. Eligibility was organized into two evidence strata: core feline evidence and contextual evidence. The final revised evidence map comprised 49 unique sources (28 empirical feline sources and 21 contextual sources spanning comparative, methodological, guideline, regulatory, or safety evidence); non-feline evidence was used only for mechanistic, methodological, safety, or translational interpretation and was not pooled with feline clinical outcomes. Cats with CKD have shown lower fecal microbial richness and diversity and higher circulating indoxyl sulfate in small cross-sectional cohorts, but causality remains unproven. Recent work also identified altered secondary bile acids and lower fecal ursodeoxycholic acid; however, Peptacetobacter hiranonis is principally linked to bai-mediated 7α-dehydroxylation, whereas ursodeoxycholic acid formation requires distinct hydroxysteroid dehydrogenase reactions. Complete therapeutic renal diets improve clinical outcomes, but their benefits reflect multiple simultaneous modifications and cannot yet be decomposed into a microbiome-specific effect. Evidence for isolated prebiotics, probiotics, postbiotics, synbiotics, fecal microbiota transplantation, and precision nutrition algorithms is preliminary or absent in feline CKD. The field is constrained by small cohorts, confounding, reliance on 16S rRNA sequencing, compositional data, and limited interlaboratory reproducibility. Current clinical practice should therefore prioritize a palatable complete renal diet, adequate energy and protein intake, muscle condition monitoring, hydration, and constipation management, while microbiome-directed products remain adjunctive or investigational. Full article

Background/Objectives: Obesity is a major global health challenge characterized by adipose tissue dysfunction, insulin resistance, chronic low-grade inflammation, oxidative stress, mitochondrial dysfunction, and increased cardiometabolic risk. Despite substantial therapeutic advances, limitations related to cost, adverse effects, and long-term adherence have stimulated interest in complementary nutritional approaches. Sulforaphane, a bioactive isothiocyanate derived primarily from broccoli and other cruciferous vegetables, has attracted considerable attention because of its antioxidant, anti-inflammatory, and metabolic regulatory properties. This narrative review critically evaluates the current evidence regarding the role of sulforaphane and broccoli-derived preparations in obesity and obesity-associated metabolic dysfunction. Methods: A narrative review was conducted using PubMed/MEDLINE, Scopus, Web of Science, and Google Scholar. Eligible publications included in vitro, animal, clinical, observational, and relevant review studies investigating sulforaphane, glucoraphanin, or broccoli-derived preparations in relation to obesity, adiposity, insulin resistance, metabolic syndrome, inflammation, oxidative stress, energy metabolism, and related metabolic abnormalities. Results: In vitro studies consistently demonstrate inhibition of adipocyte differentiation and lipid accumulation, attenuation of oxidative stress and inflammatory signaling, and enhancement of cellular energy metabolism. Animal studies further report reductions in adiposity, insulin resistance, hepatic steatosis, oxidative stress, and chronic inflammation, together with improvements in energy expenditure, metabolic flexibility, and obesity-associated metabolic abnormalities. Mechanistic evidence indicates that sulforaphane exerts pleiotropic metabolic effects through activation of the Nrf2 and AMPK pathways, suppression of NF-κB-mediated inflammation, improvement of mitochondrial function, promotion of thermogenesis and adipose tissue browning, regulation of lipid metabolism, and modulation of gut microbiota composition. Human studies, although limited and heterogeneous, suggest possible improvements in glycemic control, insulin sensitivity, endothelial function, and other surrogate metabolic biomarkers associated with obesity. However, evidence demonstrating clinically meaningful reductions in body weight, adiposity, or body composition remains limited and inconsistent, and improvements in these surrogate biomarkers should not be interpreted as evidence of reduced obesity-related morbidity or clinically meaningful adiposity reduction. Bioavailability, myrosinase activity, food processing, gut microbiota composition, and interindividual variability remain important determinants of efficacy and key translational challenges. Conclusions: Current evidence provides strong mechanistic and preclinical support for sulforaphane as a promising candidate adjunctive nutritional intervention for improving obesity-associated metabolic dysfunction. Nevertheless, current human evidence suggests possible metabolic benefits but does not establish sulforaphane as an effective weight-loss intervention or an evidence-based treatment for obesity. Large, long-term randomized controlled trials employing standardized sulforaphane preparations and comprehensive assessments of body weight, adiposity, body composition, metabolic health, pharmacokinetics, and gut microbiota composition are required to establish its clinical efficacy and define its role within precision nutrition strategies for obesity and obesity-associated metabolic dysfunction. Full article

Background/Objectives: Microsatellite-stable colorectal cancer (MSS CRC) accounts for the vast majority of CRC cases and remains largely resistant to immune checkpoint inhibitors. Emerging evidence suggests that the gut microbiome is an important regulator of antitumor immunity and may contribute to immunotherapy resistance through multiple mechanisms involving the tumor microenvironment. This review aims to summarize current knowledge of the microbiome–immunity–therapy axis in MSS CRC and to explore microbiome-based strategies to enhance immunotherapy responsiveness. Methods: A narrative review of the recent literature was conducted, focusing on studies published within the last five years that investigated gut microbiota composition, microbial metabolites, tumor immune regulation, immunotherapy response, and microbiome-targeted therapeutic interventions in CRC. Evidence from mechanistic studies, translational research, clinical investigations, and multi-omics analyses was integrated. Results: Current evidence indicates that gut dysbiosis contributes to immune resistance in MSS CRC through immune exclusion, myeloid-driven immunosuppression, T-cell dysfunction, chronic inflammation, and altered microbial metabolite signaling. Specific microorganisms, including Fusobacterium nucleatum, enterotoxigenic Bacteroides fragilis, pks-positive Escherichia coli, and other CRC-associated pathobionts, have been implicated in tumor progression and modulation of antitumor immunity. Microbial metabolites such as short-chain fatty acids, tryptophan-derived compounds, bile acids, succinate, and inosine represent key functional mediators linking microbial communities to host immune responses. Emerging microbiome-targeted interventions, including fecal microbiota transplantation, next-generation probiotics, postbiotics, selective microbial depletion, and engineered bacterial therapeutics, have shown promising results in preclinical models and early translational or clinical studies, although robust clinical evidence remains limited. In parallel, advances in metagenomics, metabolomics, spatial transcriptomics, and artificial intelligence are facilitating the development of precision immuno-microbiome oncology approaches. Conclusions: The gut microbiome functions as a critical regulator of immune resistance in MSS CRC through coordinated effects on microbial composition, metabolite production, and tumor immune remodeling. Microbiome-targeted interventions, combined with multi-omics-based patient stratification, may provide new opportunities to overcome immunotherapy resistance and expand the clinical benefits of immune checkpoint blockade in this traditionally refractory disease. Full article

Cancer remains a leading global cause of morbidity and mortality, with oxidative stress playing a central role in its pathogenesis, progression, and response to therapy. Nutrition has emerged as a modifiable factor capable of influencing redox homeostasis, thereby contributing to both cancer prevention and therapeutic outcomes. This narrative review summarizes current evidence on dietary patterns, specific nutrients, and bioactive compounds that modulate oxidative stress and are associated with reduced cancer risk and improved response to treatment. A literature search was conducted using PubMed, Scopus, and Google Scholar, covering the period from 2002 to 2025 to capture contemporary dietary approaches and clinical evidence. Eligible studies addressed nutrient compounds, dietary strategies, obesity, gut microbiota, conventional cancer therapies, and clinical outcomes, with particular emphasis on mechanisms related to oxidative stress, inflammation, and immune modulation. Epidemiological evidence consistently supports the protective role of plant-based dietary patterns and reduced intake of red and processed meat, partly due to their antioxidant and anti-inflammatory properties. Nutrients such as dietary fiber, polyphenols, and omega-3 fatty acids are associated with decreased oxidative damage, improved immune responses, and enhanced therapeutic efficacy across multiple tumor types, including colorectal, breast, lung, and ovarian cancers, as well as glioblastoma. Emerging data also suggest that dietary interventions, including ketogenic diets and fasting, may influence tumor metabolism and redox balance, potentially increasing sensitivity to conventional therapies. The gut microbiota has been identified as a key mediator linking diet, oxidative stress, and cancer-related pathways. Although current evidence supports the role of nutritional strategies in targeting oxidative stress for cancer prevention and treatment, further large-scale randomized clinical trials are required to clarify their impact on survival and treatment efficacy. The integration of nutritional counseling into oncology practice represents a cost-effective, accessible, and patient-centered approach with the potential to modulate oxidative stress and improve clinical outcomes. Full article

Liposomes are among the most extensively studied delivery systems owing to their biocompatibility, structural versatility, and ability to improve the stability and bioavailability of bioactive compounds. Meanwhile, edible fungal polysaccharides (EFPs), particularly β-glucans and heteropolysaccharides, have attracted increasing interest because of their antioxidant, immunomodulatory, prebiotic, and health-promoting properties. The integration of EFPs with liposomal systems has emerged as a promising strategy for developing multifunctional nanocarriers with enhanced physicochemical stability and biological performance. However, current research remains fragmented, and the mechanisms by which EFP molecular structures influence liposome assembly, stability, gastrointestinal fate, and delivery efficiency are poorly understood. Moreover, existing reviews primarily focus on liposomes or fungal polysaccharides independently, without systematically addressing their interfacial interactions, structure-function relationships, and translational applications. This review provides a comprehensive and critical overview of EFP liposomes, highlighting the interactions between fungal polysaccharides and lipid bilayers, including hydrogen bonding, electrostatic interactions, hydrophobic association, and surface conjugation. The effects of EFPs on liposomal physicochemical properties, encapsulation performance, membrane stability, gastrointestinal protection, mucoadhesion, cellular uptake, and biological activity are further discussed. Emerging applications in targeted delivery, oral delivery, gut microbiota modulation, gut–brain axis regulation, and functional foods are also critically evaluated. Importantly, this review identifies key research gaps, including the lack of quantitative structure-function relationships, limited understanding of biological transport mechanisms, insufficient investigation of microbiota-mediated effects, and challenges in scalable manufacturing. By integrating glycobiology, nanotechnology, and food science, this review establishes a unified framework for the rational design and future development of EFP-based liposomal delivery systems. Full article