Search Results (8,737)

Autoimmune and immune-mediated inflammatory diseases (IMIDs) develop when genetically and environmentally susceptible hosts lose stable immune tolerance. The gut ecosystem is increasingly recognized as a biologically active interface in this process. Its bacterial, fungal, and viral components may shape mucosal and systemic immunity through antigenic stimulation, barrier regulation, and metabolite-dependent signaling, although the strength of evidence is uneven: bacteriome data are currently the most mature, whereas mycobiome, virome, and phageome findings remain more disease-specific and emerging. Dysbiosis may influence autoimmunity through overlapping routes, including epithelial barrier failure, altered short-chain fatty acid, bile acid, and tryptophan metabolism, molecular mimicry, and cross-kingdom microbial interactions. Nutrition is central to this network because dietary substrates determine microbial growth, metabolic output, epithelial integrity, and immune-cell differentiation. In this narrative review, we integrate evidence on disease-associated bacteriome, mycobiome, and virome patterns in systemic autoimmune diseases, with emphasis on rheumatoid arthritis, systemic lupus erythematosus, Sjögren’s syndrome, systemic sclerosis, spondyloarthritis, vasculitides, and idiopathic inflammatory myopathies. COVID-19 is considered not as a proven causal driver of autoimmunity, but as an example of an environmental and infectious insult capable of perturbing microbiome–barrier–immune communication. Finally, we discuss diet-based and microbiome-targeted approaches, including probiotics, prebiotics, synbiotics, and postbiotics, as adjunctive strategies that may help restore microbial resilience and immune balance. A better understanding of the diet–microbiome–host immunity axis may support more personalized preventive and therapeutic concepts in autoimmune disease. Full article

Atopic dermatitis (AD) is a chronic immune-mediated inflammatory skin disease characterized by a complex and dynamic interplay between immune dysregulation and epidermal barrier dysfunction. Emerging evidence supports an integrated pathogenic model in which immune activation and barrier impairment form a bidirectional and self-reinforcing axis rather than representing separate processes. This review synthesizes current knowledge on the role of IL-4/IL-13-dependent signaling in regulating keratinocyte lipid metabolism and its impact on epidermal barrier integrity. IL-4/IL-13 signaling via the JAK-STAT pathway, particularly STAT6, contributes to keratinocyte dysfunction, resulting in impaired differentiation and coordinated alterations in lipid metabolism, including fatty acid elongation and ceramide synthesis. These cytokine-driven processes disrupt the organization of the stratum corneum lipid matrix, resulting in increased transepidermal water loss, enhanced skin permeability, and susceptibility to microbial colonization, thereby promoting chronic inflammation. Collectively, these findings support the concept that IL-4/IL-13-mediated dysregulation of keratinocyte lipid metabolism may represent an important immunometabolic mechanism linking type 2 inflammation with secondary barrier dysfunction in atopic dermatitis, thereby contributing to disease persistence. Targeting both immune pathways and epidermal lipid homeostasis may represent an effective strategy to restore barrier function and improve clinical outcomes. Full article

Persistent high-risk human papillomavirus infection is a critical prerequisite for cervical intraepithelial neoplasia and cervical cancer, yet viral factors alone do not fully explain why most infections clear while a subset persists and progresses. Emerging longitudinal, multi-omics, and mechanistic evidence supports a plausible model in which the cervicovaginal microbiota is not a passive bystander but a functional determinant of mucosal immunity, epithelial barrier integrity, and local metabolic tone. Lactobacillus-dominant community states, particularly those enriched in Lactobacillus crispatus, are generally associated with lower pH, regulated inflammatory signaling, stronger barrier function, and a higher likelihood of HPV clearance. In contrast, anaerobe-enriched dysbiosis is linked to elevated pro-inflammatory cytokines, altered antigen presentation, immune checkpoint signatures consistent with T-cell dysfunction, and metabolic shifts involving lactate depletion and accumulation of short-chain fatty acids and other metabolites that can influence epithelial and immune-cell programs. Importantly, the interaction is bidirectional: hrHPV can remodel the microenvironment by suppressing host defense peptides and perturbing mucosal barriers, thereby reducing Lactobacillus fitness and reinforcing dysbiosis in a feed-forward loop that favors persistence and oncogenic progression. This review integrates functional ecology, longitudinal clinical evidence, immunological and metabolic mechanisms, and translational implications, highlighting opportunities for microbiome-informed risk stratification and adjunctive interventions, as well as key gaps requiring standardized longitudinal multi-omics and rigorously designed clinical trials. Full article

Metformin, widely prescribed for type 2 diabetes mellitus (T2D), has emerged as a systemic immunomodulator with effects that extend far beyond glycemic control. Recent advances in immunometabolism reveal that metformin modulates innate immune responses through coordinated cellular metabolic reprogramming and epigenetic modification, which collectively modulate the functional phenotype of innate immune cells. This narrative review summarizes current evidence regarding the immunomodulatory effects of metformin on the innate immune system, with a focus on immunometabolism and epigenetic regulation. It explores how metformin modulates innate immunity by altering cellular energy sensing, mitochondrial function, and nutrient utilization. Such metabolic changes and alterations further reshape chromatin structure and architecture, as well as transcriptional profiles and programs. Through the regulation of glycolysis, fatty acid oxidation, and histone modification landscapes, metformin regulates the phenotypes of innate immune cells, which can be pro-inflammatory, tolerogenic, or homeostatic. This conceptual framework presents a new understanding of metformin. As well as acting as an anti-inflammatory agent, it may regulate immune memory. Full article

This study evaluated the effects of dietary inclusion of free and protected acid protease on productive performance, milk composition, metabolic profile, nutrient digestibility, and ruminal environment in lactating Jersey cows. Fifteen multiparous cows (67 ± 7.5 days in milk; 27.5 ± 3.5 kg/day) were assigned to a 3 × 3 Latin square (5 squares) design with 21-day periods. Treatments consisted of: control (no enzyme), free protease (4.4 g/day), and protected protease (4.4 g/day). The protected form was developed using alginate-based encapsulation to enhance enzyme stability under ruminal conditions. Protease inclusion did not affect dry matter intake, milk yield, or feed efficiency (p > 0.05). However, free protease increased lactation persistency (p = 0.05) and improved fat-corrected and energy-corrected milk yields (p ≤ 0.02), with intermediate responses observed for protected protease. Milk fat and protein contents were higher in enzyme-fed cows (p ≤ 0.05), while other compositional parameters remained unchanged. Apparent crude protein digestibility was greater in cows receiving free protease (p = 0.037), with no effects on dry matter or fiber digestibility. Protease intake increased total volatile fatty acid concentrations and major fermentation products (acetate, propionate, and butyrate; p ≤ 0.01), indicating enhanced ruminal fermentation. Blood metabolites showed increased total protein and globulin levels in cows fed free protease (p ≤ 0.05), suggesting improved protein metabolism. Microbiota analysis revealed no differences in alpha or beta diversity; however, specific microbial taxa and predicted metabolic pathways were modulated by treatments, particularly in post-ruminal compartments. In conclusion, exogenous protease, especially in free form, improved protein utilization and corrected milk production without disrupting microbial stability. These findings highlight the potential of protease as a nutritional strategy to enhance efficiency in dairy systems through targeted modulation of ruminal function and nutrient metabolism. Full article

White adipose tissue (WAT) is essential for maintaining energy homeostasis during hibernation by supplying lipolysis-derived fatty acids as a major fuel source. In raccoon dogs (Nyctereutes procyonoides), the activity of brown adipose tissue is diminished, providing a unique model to investigate how WAT supports metabolic homeostasis in a largely non-thermogenic state. Here, we integrated physiological, histological, transcriptomic, and molecular analyses of back-fat and tail-fat depots during autumn fattening and winter sleep. Despite reduced food intake, body weight loss, and mild hypothermia, raccoon dogs maintained systemic glucose and lipid homeostasis. Both WAT depots exhibited adipocyte atrophy and the coordinated suppression of core metabolic and biosynthetic pathways, indicating a shared program of metabolic depression. However, the two depots adopted distinct remodeling strategies. Back-fat showed collagen densification and vascular-associated remodeling, suggesting a structural adaptation that may preserve tissue integrity during winter sleep. In contrast, tail-fat displayed enhanced innate immune signaling and M2 macrophage enrichment, indicating immune niche remodeling that may support tissue protection during prolonged lipid mobilization. Together, these findings reveal that raccoon dogs maintain metabolic homeostasis during shallow hibernation through a non-thermogenic, WAT-centered strategy characterized by shared metabolic depression and depot-specific structural and immunometabolic remodeling. Full article

Bile acids are important for lipid digestion and metabolic regulation, but the roles of individual bile acids in crustaceans remain unclear. This study evaluated the effects of six dietary monomeric bile acids on growth and lipid metabolism in juvenile Pacific white shrimp. Juvenile shrimp (2.5 g) were fed a basal diet or the same diet supplemented with 0.04% bile acid (cholic acid, hyodeoxycholic acid, chenodeoxycholic acid, deoxycholic acid, ursodeoxycholic acid, or hyocholic acid) for 8 weeks. Each treatment was assigned to three replicate 100-L tanks, with 30 shrimp per tank. Dietary monomeric bile acids did not significantly affect growth performance, body composition, or muscle fatty acid composition. Compared with the control group, chenodeoxycholic acid, deoxycholic acid, and hyocholic acid significantly reduced the hemolymph triglyceride levels, while cholic acid, chenodeoxycholic acid, and hyocholic acid lowered the hepatopancreatic lipid levels. All bile acid treatments reduced the hepatopancreatic malondialdehyde content compared with the control group. Expression of genes related to bile acid transport, sterol metabolism, and lipid catabolism was generally upregulated by bile acids, indicating enhanced bile acid circulation and lipid turnover. In conclusion, monomeric bile acids mainly regulate lipid metabolism and oxidative status rather than directly promoting growth under the present dietary condition, with chenodeoxycholic acid, cholic acid, and deoxycholic acid showing relatively stronger effects. Full article

Diarrhea significantly impacts livestock and poultry health, causing growth delays and higher mortality rates. Macleaya cordata extract (MCE) demonstrates strong antioxidant, antibacterial, and anti-inflammatory properties, indicating its potential as a therapeutic agent for diarrhea. This research investigated whether MCE alleviates lipopolysaccharide (LPS)-induced diarrhea in mice through modulation of the gut microbiota. Here, changes in short-chain fatty acids (SCFAs) and gut bacterial structure were analyzed using gas chromatography–mass spectrometry (GC-MS) and 16S rRNA gene sequencing, respectively. The effects of MCE administration (40 mg/kg) on intestinal injury and inflammatory responses were assessed in mice induced with LPS. These results show that MCE-treated mice exhibited significantly lower diarrhea indices, attenuated duodenal villus shortening, and decreased crypt depth compared with LPS-induced mice. MCE treatment substantially reduced the mRNA expression of IL-6, IL-1β and NF-κB in the duodenum, as well as the serum levels of TNF-α and IL-8. Furthermore, MCE significantly increased SCFA levels, particularly acetic acid, and reshaped the gut microbiota composition by increasing the abundance of Lachnospiraceae. Given the close interaction between gut microbiota, microbial metabolites, and host inflammatory responses, these microbial and metabolic alterations are closely associated with the attenuation of intestinal and systemic inflammation. In conclusion, the protective effects of MCE against LPS-induced diarrhea in mice are closely associated with the modulation of gut microbiota structure, suppression of inflammatory responses, and enhancement of acetic acid production. This study provides a mechanistic basis for MCE as a natural alternative to antibiotics for treating inflammatory diarrhea in livestock and poultry. Full article

This study evaluated the effects of monolaurin intake per finishing feedlot cattle on growth performance, metabolic status, ruminal environment, and meat fatty acid profile. Twenty-four castrated Holstein males (379 ± 8.5 kg; 12 months old) were randomly assigned to two treatments: basal diet (control) or basal diet with α-monolaurin (treated: 0.762 g/kg dry matter intake; ≈6.63 g/animal/day) for 79 days. Feed intake, body weight, and feed efficiency were recorded, and blood and ruminal samples were collected during the trial. Ruminal fermentation parameters, protozoa counts, hematological and biochemical variables, oxidative status biomarkers, ruminal microbiota composition (16S rRNA sequencing), and Longissimus dorsi fatty acid profile were analyzed. Monolaurin feed did not affect dry matter intake or final body weight, but increased total weight gain, average daily gain, and feed efficiency (p ≤ 0.05), indicating improved nutrient utilization. Hematological and serum biochemical variables were largely unchanged, although total leukocyte counts were lower in treated cattle. Animals receiving monolaurin showed reduced reactive oxygen species and lower superoxide dismutase activity, suggesting improved oxidative balance without changes in lipid peroxidation. During the adaptation phase (day 14), treated cattle exhibited lower acetate, propionate, valerate, and total volatile fatty acid concentrations and higher protozoa counts, but these differences disappeared by day 79, indicating ruminal adaptation. Microbiota diversity was not altered overall, although specific genera differed in relative abundance between treatments. In meat, monolaurin increased lauric, linoleic, and arachidonic acids, reduced palmitic and heptadecanoic acids, decreased total saturated fatty acids, and increased polyunsaturated fatty acids (p ≤ 0.05). Overall, dietary monolaurin improved feed efficiency, modulated oxidative status, induced transient ruminal microbial adjustments, and enhanced the nutritional quality of beef lipids without compromising metabolic health. Full article

The prevention and treatment of cardiovascular disease (CVD) are undergoing a paradigm shift from a lipid-centric approach to a holistic metabolic perspective. Central to this evolution is the gut–fat–heart axis, a sophisticated three-dimensional communication network that integrates neural, endocrine, and immunometabolic signaling to regulate systemic lipid homeostasis. This manuscript systematically explores how the gut microbiota acts as a “metabolic organ” to remotely control host health through the production of bioactive metabolites and the modulation of molecular communication networks. At the physiological level, microbial products such as short-chain fatty acids (SCFAs) and modified bile acids regulate energy balance and lipid synthesis via the FXR-FGF15/19 axis and G protein-coupled receptors. Furthermore, gut hormones like GLP-1 and neuro-reflex pathways involving the vagus nerve provide rapid control over postprandial lipid clearance and feeding behavior. Conversely, pathological dysbiosis triggers the accumulation of harmful metabolites, such as trimethylamine N-oxide (TMAO) and lipopolysaccharides (LPS), which drive lipotoxicity, vascular inflammation, and “dysfunctional HDL” formation. These processes accelerate the progression of atherosclerosis, heart failure, and metabolic syndrome. Finally, the article outlines promising clinical translation strategies, including the development of TMA lyase inhibitors, next-generation probiotics, and the use of phytochemicals to reshape the microbial landscape. By decoding the molecular dialogues within the gut–fat–heart axis, this research provides a novel strategic vantage point for the integrated management of cardiovascular–kidney–metabolic (CKM) syndrome. Full article

A ketogenic diet (KD) is a low-carbohydrate, high-fat dietary approach. Beyond treating neurologic disorders, KDs have attracted significant media attention for their potential to improve obesity and diabetes. The diet induces a metabolic shift from glucose toward fatty acid oxidation and ketone body production. This shift leads to ketosis, which may reduce hunger, partly through the anorexigenic effects of ketone bodies, thereby contributing to weight loss and improved metabolic parameters, including glycaemic control and insulin sensitivity. In particular, the positive effects of KDs lower insulin demand and may thereby improve β-cell function. However, the long-term efficacy, safety, and sustainability of KDs, especially for diabetes, remain debated. This review offers current insights into the effects of ketogenesis and ketosis, as well as the potential mechanisms underlying them. We explore the metabolic effects of KDs in obesity and diabetes, drawing on preclinical and clinical studies, and suggest that combining KDs with antidiabetic agents may provide synergistic benefits. However, combining KDs with these pharmacotherapies, particularly SGLT-2 inhibitors, requires careful clinical supervision because of potential risks, including euglycaemic diabetic ketoacidosis. We explore how a KD alters the composition of the gut microbiota, thereby affecting host health. We conclude by highlighting challenges and future directions for optimising KD-based therapies and by outlining the limitations of the current review. Full article

Background: Sarcopenia and frailty are highly prevalent extrapulmonary manifestations of chronic obstructive pulmonary disease (COPD) and are strongly associated with reduced exercise tolerance, exacerbation risk, hospitalizations, and mortality. Beyond inflammation, oxidative stress, and physical inactivity, emerging evidence highlights nutrition as a major modifiable driver of muscle deterioration in COPD. Nutritional deficits impair anabolic signaling, exacerbate proteolysis, worsen mitochondrial dysfunction, and contribute to frailty progression. Methods: This narrative review synthesizes evidence from PubMed, Embase, Scopus, and Web of Science up to 2025, integrating mechanistic, metabolic, nutritional, and biomarker-related pathways underlying muscle dysfunction in COPD. Studies examining inflammation, hypoxemia, oxidative stress, hormonal imbalance, nutrition, and emerging biomarkers were included. Results: COPD-related sarcopenia results from converging inflammatory (TNF-α, IL-6), catabolic (FOXO, UPS), metabolic, and vascular mechanisms, compounded by energy deficiency, protein insufficiency, and micronutrient deficits. Inadequate intake of protein, vitamin D, antioxidants, and omega-3 fatty acids increase anabolic resistance, enhance muscle catabolism, and worsen frailty. Nutritional interventions, particularly high-protein supplementation, leucine-enriched formulas, vitamin D repletion, omega-3 fatty acids, and multimodal nutrition–exercise programs, demonstrate benefits in muscle mass, strength, and physical performance. Biomarkers such as GDF-15, CAF22, and specific microRNAs reflect nutritional status and correlate with muscle health in COPD. Conclusions: Sarcopenia and frailty in COPD arise from a complex interplay of inflammatory, metabolic, nutritional, and lifestyle-related factors. Integrating nutritional assessment and targeted dietary interventions with exercise and pulmonary rehabilitation is essential to counteract anabolic resistance and improve functional outcomes. Advances in biomarker research may support earlier diagnosis and personalized nutrition-based therapeutic strategies. Full article

Heart failure (HF) continues to be a major global health burden, with persistent morbidity and mortality despite guideline-directed and device-based therapies. Evidence suggests the gut–heart axis is a critical and underrecognized contributor to HF progression. Alterations in cardiac output and systemic venous congestion in HF lead to intestinal hypoperfusion, mucosal edema, and loss of barrier integrity, increasing intestinal permeability, gut dysbiosis, and translocation of microbial products. This systemic translocation is associated with chronic low-grade inflammation that activates innate immune pathways that correlate with endothelial dysfunction, oxidative stress, fibroblast activation, and adverse cardiac remodeling. Gut-derived metabolites derived by microbial metabolism modulate cardiovascular health by altering the metabolic profiles. Dysbiosis results in loss of protective short-chain fatty acid (SCFA)-producing bacteria and enriches pro-inflammatory taxa such as trimethylamine N-oxide (TMAO)-producing bacteria. Elevated TMAO is associated with increased mortality and hospitalization in HF, whereas SCFAs enhance barrier integrity and immune tolerance. Secondary bile acids and uremic toxins such as indoxyl sulfate and p-cresyl sulfate further link dysbiosis to fibrosis and vascular stiffness. Circulating markers such as TMAO, lipopolysaccharide-binding protein (LBP), and soluble CD14 carry prognostic value beyond traditional cardiac biomarkers. This review highlights current experimental, translational, and clinical evidence describing gut dysbiosis and its molecular links to HF progression. Targeting the gut–heart axis represents a novel therapeutic approach in HF. Dietary modulation, probiotics/prebiotics, fecal microbiota transplantation, and inhibitors of microbial metabolic pathways show promise. Future research should emphasize microbiota-based interventions in HF management. Full article

This study evaluated the effects of maternal overfeeding during mid-to-late gestation on maternal productivity, metabolic status, reproductive recovery, and calf performance in Hanwoo cattle using conventional statistics and machine learning (ML) approaches. A total of 243 pregnant cows were assigned to either a control group or an overfeeding group from gestation day 90 to parturition. The overfeeding treatment increased nutrient supply to approximately 140–145% of the control level. Maternal body weight (BW), body condition score (BCS), serum metabolites, and reproductive traits were evaluated throughout gestation and postpartum, while calf growth, morphometrics, and metabolic traits were assessed at birth and weaning. Calves were further classified into growth- or meat-quality-oriented genotypes using SNP-based profiling. Overfeeding increased maternal BW gain and BCS during gestation and reduced circulating non-esterified fatty acid concentrations, indicating improved maternal energy status. However, overfed cows showed a longer interval to postpartum estrus return. Calf birth weight was not significantly affected by maternal overfeeding, whereas calf growth and morphometric traits at weaning were more strongly influenced by parity, sex, and genotype. Machine learning models identified gestational BW, metabolic indicators, calf feed intake, and genotype as major predictors of maternal and calf outcomes, with random forest and XGBoost showing superior predictive performance compared with linear models. These findings suggest that parity- and genotype-informed nutritional management combined with ML-based prediction may support precision feeding strategies in beef cattle production systems. Full article

Background: Retinoid signaling is implicated in regulating membrane-bound polyunsaturated fatty acids (PUFAs), which serve as substrates for oxylipin biosynthesis. Dysregulated vitamin A status and altered oxylipin profiles have both been associated with the development of metabolic diseases. However, whether early-life vitamin A deficiency (VAD) causally influences oxylipin metabolism and liver health remains unclear. Methods: C57BL/6J mouse pups were exposed to either a vitamin A-deficient (VD) or vitamin A-replete (VR) AIN-93G-based diet during the fetal and suckling periods, and they weremaintained on the same diet from weaning (3 weeks of age) to 9 weeks of age. Oxylipin composition in plasma, liver and cerebral tissues was analyzed by liquid chromatography–mass spectrometry. Hepatic and cerebral expressions of genes involved in inflammation, phospholipid and PUFA catabolism, and oxylipin synthesis were analyzed using RT-qPCR. Results: Dietary deprivation induced severe VAD, which significantly altered 21 oxylipins in the liver and 34 oxylipins in the cerebrum, but did not affect the plasma oxylipin profile. In the liver, all altered oxylipins were elevated by VAD, the majority being ω-6-derived species with pro-inflammatory properties. In contrast, 27 altered oxylipins were lower in the VD cerebrum, including more ω-3-derived species. Multivariate analysis identified 11,12-EpETrE, 8,9-EpETrE, and 20-HETE as key hepatic oxylipins distinguishing VAD. VAD also altered hepatic expression of genes involved in membrane phospholipid remodeling (PNPLA8, PLA2G6, LPCAT3), and oxylipin metabolism (ALOX5, EPHX2), and it upregulated inflammatory signaling in the liver only, while fibrosis markers (TGFB1, COL1A1) remained unchanged. Conclusions: These findings demonstrate that early-life VAD is associated with tissue-specific alterations in oxylipin metabolism and hepatic inflammatory responses. Full article