Search Results (9,060)

Multiple acyl-CoA dehydrogenase deficiency (MADD) is considered an autosomal recessive disorder; yet, recent findings suggest up to 10% of cases may result from heterozygous electron transfer flavoprotein dehydrogenase (ETFDH) variants exhibiting dominant or dominant-like effects. Here, a novel heterozygous ETFDH variant (c.1798A>C, p.Asn600His) was identified within a three-generation family. The grandfather presented with muscular weakness at age 35, and the father developed similar symptoms at 19 following a tonsillectomy. Both were diagnosed with MADD based on muscle biopsies revealing neutral lipid accumulation and acylcarnitine profiles and responded fully to riboflavin therapy (150 mg/day). The two siblings, aged 8 and 10, carry the same mutation and show increased acyl-carnitine levels but remain asymptomatic due to early riboflavin treatment. Skin fibroblasts from affected individuals were immortalized and subjected to normal and reduced riboflavin levels. Gene expression analysis demonstrated unchanged ETFDH RNA but reduced protein levels in mutant cells, particularly under low riboflavin. Structural modelling suggested the Asn600His substitution destabilizes the protein, diminishing its mitochondrial function. Proximity ligation assays indicated a decreased interaction with mitochondrial complex III, while oxygen consumption via fatty acid oxidation was impaired, especially at reduced riboflavin. The novel ETFDH variant found in this family gives a possible dominant pattern of inheritance for MADD, where a single mutant allele impairs the mitochondrial metabolism, particularly under riboflavin-deficient conditions, and highlights the importance of early riboflavin supplementation in preventing clinical symptoms. Full article

Cider is a low-alcohol fruit wine produced by partial or complete fermentation of apple juice. In recent years, its consumption has grown significantly, especially in Asia. Its distinctive flavor profile reflects a complex interplay of aroma and non-volatile components. The composition of cider is mainly influenced by three factors: raw materials, starter cultures, and production process. This review begins by outlining the composition of cider, covering both its aromatic compounds and non-volatile components. The primary aroma profile is defined by higher alcohols, esters, fatty acids, and carbonyl compounds, while sugars, organic acids, and polyphenols are the key determinants of its taste. Subsequently, it provides a detailed analysis of how the raw material, the choice of starter cultures, and the applied production processes collectively shape the cider’s flavor. Research shows that apple variety and maturity influence the levels of sugars, organic acids, and polyphenols, shaping the flavor foundation of cider. To enhance flavor diversity, inoculation strategies have shifted from single-strain fermentation with Saccharomyces cerevisiae to mixed fermentations using non-Saccharomyces yeasts and lactic acid bacteria, either simultaneously or sequentially. Currently, screening non-Saccharomyces strains has become a key strategy to increase cider flavor complexity. Precise micro-oxygenation and nutrient supply regulate microbial metabolism, thereby controlling the fermentation process and the production of specific flavor compounds. In the future, given the untapped diversity of non-Saccharomyces yeasts and lactic acid bacteria in winemaking traits, research in this direction may be key to improving cider quality. In addition, selecting apple cultivars tailored to specific cider styles and exploring pre-fermentation treatments such as cold maceration and enzymolysis may also contribute to enhancing the flavor diversity of cider. Full article

Persistent racial and ethnic disparities in type 2 diabetes mellitus (T2DM) are incompletely explained by genetic susceptibility, obesity, lifestyle, and socioeconomic factors, suggesting that additional biological mechanisms may link environmental exposures to metabolic disease risk. Increasing evidence indicates that the exposome, encompassing environmental exposures across the life course, may influence long-term metabolic health through molecular mechanisms that integrate environmental signals with host biology. This Review synthesizes epidemiological, experimental, and mechanistic evidence on the gut microbiota–host epigenetic axis and its potential role in linking environmental exposures to population differences in T2DM susceptibility. Gut microbial dysbiosis alters the production and metabolism of short-chain fatty acids, bile acids, and tryptophan-derived metabolites. These microbial metabolites can modulate host signaling and epigenetic processes, including DNA methylation, histone modifications, and non-coding RNA activity, which may influence the expression of genes involved in glucose homeostasis, inflammation, and insulin sensitivity. Conversely, host epigenetic programs may influence intestinal barrier integrity and immune responses, thereby potentially affecting the gut microbial ecosystem, highlighting the reciprocal nature of host–microbiota interactions. We further examine how diet, psychosocial stress, environmental pollutants, and socioeconomic conditions may shape the microbiota–epigenetic axis across diverse populations, providing a framework for understanding differences in metabolic susceptibility without attributing disparities to intrinsic biological variation. However, direct human evidence linking the gut microbiota–host epigenetic axis to racial and ethnic disparities in T2DM risk remains limited, and much of the current framework is based on mechanistic studies, animal models, and associative human data rather than direct causal evidence. Further research in diverse human populations is needed to validate these pathways and establish their contribution to T2DM disparities. This framework may inform biomarker discovery, stratification, precision nutrition, and microbiome-targeted interventions and generate hypotheses for equitable prevention and personalized management of T2DM across diverse populations. Full article

Ruminal acidosis, particularly subacute ruminal acidosis, remains a major metabolic disorder that compromises animal health, production efficiency, and the sustainability of intensive ruminant systems. Although traditionally defined by reduced ruminal pH, it is increasingly recognized as a multidimensional disorder involving microbial ecological destabilization, disrupted metabolic cross-feeding, impaired epithelial barrier function, and dysregulated host inflammatory responses. This review synthesizes current knowledge of the microbial and metabolic mechanisms underlying acute and subacute ruminal acidosis and highlights processes that extend beyond pH depression alone. High-concentrate feeding shifts the balance among amylolytic and lactate-producing microorganisms, lactate-utilizing populations, and fibrolytic guilds, thereby promoting organic acid accumulation, reducing functional redundancy, and weakening microbial resilience. Concurrent increases in volatile fatty acids, lactate, lipopolysaccharide, histamine, and other microbially derived bioactive compounds increase epithelial acid load, disrupt tight-junction integrity, and facilitate inflammatory signaling. The principal novelty of this review is the integration of microbial functional guilds, metabolic cross-feeding, ecological resilience, epithelial barrier dysfunction, and host inflammation into a unified microbiota–metabolism–barrier–inflammation framework linking dietary perturbation with microbial dysfunction and host pathology. We further critically evaluate nutritional regulation, buffering agents, probiotics, yeast-derived products, postbiotics, and plant bioactive compounds according to their capacity to restore microbial function rather than merely correct ruminal pH. Additionally, this review may support multidimensional risk assessment, guide targeted intervention, and facilitate the integration of continuous ruminal monitoring with precision nutrition for earlier prediction and individualized prevention of ruminal acidosis. Full article

Intermittent fasting (IF) has gained increasing attention as a dietary strategy to improve metabolic health and prevent cardiometabolic disorders. Accumulating evidence suggests that modulation of the gut microbiota may represent one of the mechanisms underlying the physiological benefits of IF. This review summarizes the current knowledge on the mechanisms by which IF modulates gut microbial ecology and how these changes influence host metabolic and immune functions. We examine the effects of IF on gut microbiota diversity and composition, highlighting shifts in key microbial taxa associated with metabolic regulation. In addition, we discuss how fasting-induced microbial remodeling affects microbiota-derived metabolites, including short-chain fatty acids and bile acids, which play central roles in energy homeostasis, intestinal barrier integrity, and inflammatory signaling. Increasing evidence indicates that IF interacts with circadian rhythms, influencing both microbial oscillations and host metabolic pathways that coordinate nutrient sensing and energy metabolism. Furthermore, we explore the bidirectional crosstalk between the gut microbiota and the intestinal immune system, emphasizing that fasting-driven microbial changes may modulate inflammatory responses, epithelial barrier function, and immune cell activity. Finally, we discuss nutritional strategies that may enhance the beneficial effects of IF, including the incorporation of prebiotics, dietary fiber, and probiotic supplementation, to promote microbial diversity and functional resilience. Collectively, these findings support a model in which IF acts as a key modulator of the gut microbiota–immune–metabolic axis. Future integrative studies combining gut microbiome, metabolomic, and immunological approaches are needed to better understand these interactions and optimize microbiota-targeted dietary interventions. Full article

Diets high in fat and refined carbohydrates reliably mimic key features of metabolic dysfunction-associated fatty liver disease (MAFLD), including hepatic lipid accumulation, oxidative stress, and ongoing liver injury. This study evaluated the long-term, low-dose administration of Callistemon citrinus ethanolic leaf extract and its primary bioactive compounds: d-limonene, ellagic acid, gallic acid, and p-coumaric acid to prevent lipotoxicity in rats fed a high-fat–sucrose diet (HFSD). Sixty male Wistar rats were randomly divided into 10 groups: normal control group, an untreated HFSD group, and eight HFSD groups treated for 23 weeks with metformin, C. citrinus extract, the individual bioactive compounds, or a mixture of these compounds. We assessed body and organ weights, liver macroscopic features, serum markers of liver injury, oxidative stress biomarkers, histopathological changes, and hepatic fatty acid profiles. HFSD feeding induced significant body weight gain, hepatomegaly, severe tissue damage, elevated serum levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT), gamma-glutamyl transferase (GGT), glucose and triglycerides, alongside heightened hepatic oxidative stress, and altered saturated fatty acid profiles. Conversely, treatment with metformin and the natural compounds attenuated HFSD-induced liver injury to varying degrees. Improvements in histopathological severity and serum liver enzymes correlated with decreased oxidative stress biomarkers. Notably, ellagic acid, gallic acid, d-limonene, and the bioactive mixture, significantly improved hepatic fatty acid profiles, whereas p-coumaric acid exhibited more modest effects. These results demonstrate that long-term administration of low-dose treatment can successfully improve all evaluated metabolic, biochemical, and histological parameter, suggesting that modulating oxidative stress and liver lipid composition is strongly linked to the mitigation of liver injury in this experimental MAFLD model. Full article

Hemodialysis (HD) is the most widely used renal replacement therapy for patients with end-stage renal disease (ESRD) and is frequently accompanied by long-term complications that impair quality of life, including metabolic and inflammatory disturbances. Growing evidence suggests that these complications may be linked to alterations in the gut microbiota; however, microbial composition and interaction patterns in HD patients remain incompletely characterized. In this exploratory, cross-sectional study, high throughput 16S rRNA gene sequencing was used to profile the fecal microbiota of patients undergoing hemodialysis and of healthy controls. The objective was to characterize associations between hemodialysis and gut microbial composition, ecological network organization, and predicted functional potential. Comparative analyses revealed significant differences in bacterial community structure and microbial networks in the HD cohort. Both gender and dialysis vintage were associated with variation in specific taxa, including increased detection of the Synergistetes phylum, particularly among male patients and those undergoing long-term HD. Associations were also observed between clinical and demographic factors and the relative abundance of several short-chain fatty acid-associated taxa, including members of the Lachnospiraceae and Ruminococcaceae families and the genus Bifidobacterium. Predicted functional potential (PICRUSt2) indicated distinct microbial metabolic profiles in HD patients compared with controls, particularly in pathways related to carbohydrate, nucleotide, and amino acid metabolism, with additional variation according to dialysis vintage. Overall, these findings provide an exploratory characterization of structural, compositional, and predicted functional alterations of the gut microbiota associated with hemodialysis. Although the modest cohort size precludes definitive conclusions, the results support the rationale for larger, longitudinal studies investigating microbiota-derived biomarkers and host–microbiome interactions in ESRD. Full article

The growing demand for sustainable and nutritionally optimized protein sources has positioned edible insects as promising platforms for next-generation food and feed systems. Although insect composition varies with diet, the deliberate engineering of their nutritional profiles through controlled dietary and microbiome modulation remains insufficiently characterized. This review proposes an integrative framework in which edible insects are conceptualized as programmable biological systems whose biochemical composition can be tailored through diet–microbiome interactions. Current evidence is critically synthesized to elucidate how dietary inputs, including agro-industrial by-products and algal biomass, reshape gut microbial communities and metabolic pathways in key species such as Hermetia illucens, Tenebrio molitor, and Acheta domesticus. Emphasis is placed on engineering lipid metabolism and fatty acid composition because of their relevance to human nutrition, animal nutrition, and the development of functional food and feed products. By integrating insights from insect physiology, microbiology, and nutritional biochemistry, this work outlines strategies for precision feeding and microbiome-guided interventions aimed at optimizing insect-derived biomass. Key knowledge gaps and technical limitations are also identified, highlighting the need to transition from empirical approaches toward predictive, systems-based nutritional engineering. Collectively, this review highlights the transition from empirical feeding strategies toward predictive, systems-based approaches for designing customized insect biomass within sustainable circular bioeconomy frameworks. Full article

Breast cancer is a highly heterogeneous malignancy in which fatty acid metabolism plays a critical yet insufficiently characterized role in tumor progression, immune evasion, and treatment resistance. To address this gap, we performed a comprehensive re-analysis of single-cell transcriptomic data from 62 breast cancer patients using the Non-negative Matrix Factorization (NMF) algorithm to delineate tumor cell subpopulations at single-cell resolution. Through Gene Set Enrichment Analysis (GSEA), we identified the tumor cell subgroup most significantly associated with fatty acid metabolism. Subsequent Slingshot trajectory analysis revealed STARD10 as a key regulatory gene in fatty acid metabolic reprogramming along tumor cell differentiation trajectories. In vitro functional experiments further validated that STARD10 plays a functional role in modulating fatty acid metabolism in breast cancer cells. These findings establish STARD10 as a novel molecular marker and potential therapeutic target in breast cancer, offering new insights into the metabolic mechanisms underlying tumor heterogeneity and disease progression. Full article

Precision nutrigenomics requires a diet–microbiome–host perspective because microorganisms can transform feed substrates, generate bioactive metabolites, compete with pathogens, and modify intestinal and systemic gene regulation. This structured narrative review synthesizes representative controlled feeding trials, transcriptomic and targeted gene-expression studies, microbiome analyses, and complementary multi-omic evidence concerning dietary regulations in cultured finfish. The available evidence is concentrated particularly on soybean-derived proteins, lipid-source replacements, selected amino acids and micronutrients, functional additives, probiotics, and fermented ingredients in a limited range of cultured finfish species; therefore, the synthesis is not intended to provide exhaustive coverage of every dietary intervention or finfish taxon. Recurrent host responses involve intestinal inflammation and barrier integrity, nutrient transport, lipid and bile-acid metabolism, long-chain polyunsaturated fatty-acid biosynthesis, targets of rapamycin/insulin-like growth factor (TOR/IGF) signaling, and nuclear factor erythroid 2-related factor 2/Kelch-like ECH-associated protein 1 (Nrf2/Keap1) antioxidant defense. The expanded microorganism-centered synthesis shows that dietary effects depend on microbial niche, substrate availability, community succession, metabolite production, and strain-specific probiotic or pathobiont activity. Lactic-acid bacteria, Bacillus-associated interventions, butyrate-generating strategies, fermented ingredients, and microbial biomass may support digestion, immune balance, and disease resistance, but taxonomic shifts alone do not demonstrate functional benefit. Current evidence is limited by extensive reliance on 16S ribosomal RNA (16S rRNA) relative-abundance data, inconsistent digesta-versus-mucosa sampling, inadequate feed and water controls, and weak causal validation. Future precision aquafeed studies should combine host transcriptomics with absolute microbial quantification, shotgun metagenomics, metatranscriptomics, metabolomics, culturomics, histology, and pathogen challenge. Integrating microbial function with host phenotype can improve sustainable feed design, intestinal health, and resilience. Full article

Biotic stresses (pest feeding, pathogenic fungal/bacterial/viral infection) and diverse abiotic stresses (extreme temperature, drought, waterlogging, saline–alkali soil, heavy metal pollution, nutrient deficiency, UV-B, ozone) severely restrict crop growth and global agricultural yield. Lipids act as core membrane structural constituents and vital secondary signaling messengers, executing multi-layered adaptive balancing functions during cell-type interactive stress acclimation, rather than uniform whole-plant lipid responses. They sustain membrane structural integrity across distinct cell populations, serve as synthetic precursors of bioactive signaling molecules, and trigger cascaded transcriptional and metabolic reprogramming upon environmental stimuli to rebalance physiological status among different cell types. This review systematically summarizes cell-type interactive lipid-mediated plant defense and acclimation balance mechanisms across biotic and abiotic stress contexts. We elaborate the biological functions of fatty acids, phospholipids, galactolipids, sphingolipids and their derivatives (jasmonate, salicylic acid, phosphatidic acid, oxylipin) in stress signal transduction and antioxidant defense and strictly distinguish two categories of lipid changes under all stress types: active adaptive lipid remodeling and passive stress-induced lipid oxidative damage. Key contents include stress-triggered cell-type-specific membrane lipid remodeling, the hierarchical transcriptional regulatory network mediated by WRI1, LEC1, PHR, MADS and other transcription factors governing oil metabolism, as well as crosstalk between lipid metabolism and compartmentalized reactive oxygen species (reactive oxygen species (ROS)) signaling. We further compare conserved lipid-regulatory modules and species-specific divergent responses across model plants and economic oilseed crops, integrating state-of-the-art targeted/untargeted lipidomics, single-cell spatial lipidomics and multi-omics joint breeding strategies to improve multi-stress tolerance in oilseed crops. By consolidating global research progress up to 2025, including the two latest 2026 cross-species meta-analysis reviews, this review provides systematic theoretical support and operable multi-level technical frameworks for genetic engineering targeting conserved lipid pathways to breed stress-resilient high-oil crop germplasm, and highlights reliable lipid stress biomarker screening as a promising translational research direction. Full article

The lipid and fatty acid composition of the little Baikal oilfish (Comephorus dybowskii Korotneff, 1905) was studied to identify the features of its biochemical adaptation to the environmental conditions of Lake Baikal. Multivariate analysis of lipid classes and FA profiles revealed reproducible clustering patterns in both muscle tissue and whole-body samples, indicating the presence of distinct physiological states differing in membrane organization and lipid metabolism. Lipid-class variability was primarily associated with sphingomyelin, cholesterol esters, phosphatidylinositol, and lysophosphatidylcholine, suggesting the coordinated regulation of membrane structure. The fatty-acid profiles were mainly presented by variations in saturated, monounsaturated, and long-chain polyunsaturated fatty acids, with muscle tissues characterized by a relatively longer carbon chain (ACL = 19 vs. 18 I whole body) and unsaturation (UI = 1.98–2.76 vs. 1.64–2.53 in whole body). At the same time, comparative analysis demonstrated low correspondence between lipid and FA profiles, indicating partially independent adaptive mechanisms. The experimental transfer of fish from their natural habitat to controlled conditions resulted in the significant remodeling of both lipid and FA compositions, including increases in acylglycerols, membrane phospholipids, and monounsaturated fatty acids, together with a decline in long-chain n-3 polyunsaturated fatty acids. The results suggest that lipid classes and fatty acids represent complementary but functionally distinct levels of biochemical adaptation contributing to the maintenance of membrane organization and metabolic homeostasis in C. dybowskii, revealing a previously undescribed multi-level organization of lipid-related adaptive responses in this endemic deep-water fish. Full article

Background/Objectives: Omega-3 and omega-9 fatty acid supplementation has shown metabolic and immunomodulatory benefits, but evidence in pediatric insulin resistance is limited, and the persistence of effects after treatment discontinuation remains uncharacterized. This study evaluated the independent and combined effects of omega-3 and omega-9 supplementation on the metabolic and inflammatory profile of children with obesity and insulin resistance, during and after active treatment. Methods: This prespecified secondary analysis of a multicenter, randomized, triple-blind, three-arm parallel trial (NCT05488223) included 97 children (8–17 years) with overweight/obesity and baseline insulin resistance (HOMA-IR > 3.0). Participants received 1.8 g/day of omega-3 (n = 32), omega-9 (n = 34), or combined supplementation (n = 31) for 3 months, followed by a 2-month post-intervention follow-up. Metabolic and inflammatory markers were assessed at baseline (T1), end of treatment (T2), and follow-up (T3). The primary outcome was the change in HOMA-IR from T1 to T2. Results: Active supplementation significantly reduced fasting insulin and HOMA-IR in the Combined (p < 0.001) and Omega-9 (p = 0.010 and p = 0.006) groups; at month 5, only the Combined group maintained significant reductions in both. IL-6 and leptin decreased across all groups during intervention and remained reduced at follow-up. Multivariable regression (n = 96) showed the metabolic response was most strongly associated with baseline metabolic status and concurrent BMI reduction rather than intervention group, which was not an independent predictor of metabolic response, nor consistently of inflammatory outcomes (one exception: a smaller IL-4 increase with omega-9, p = 0.043, unconfirmed in GEE). Conclusions: Within-group reductions in HOMA-IR and fasting insulin persisted after discontinuation only in the Combined group, but without significant between-group differences at any timepoint, consistent with response magnitude reflecting baseline status and adiposity reduction rather than treatment group per se. This positions combined supplementation as a potential metabolic adjuvant—not a standalone therapy—for HOMA-IR-defined insulin resistance in pediatric obesity, assessed here via anthropometric and biochemical rather than imaging-based measures. Full article

High-fat diets may improve energy supply in laying hens, but they can also increase fat deposition in the liver and contribute to fatty liver hemorrhagic syndrome (FLHS), a metabolic disorder that impairs hen health and egg production. Bile acids (BAs), which are natural compounds produced in the liver to support fat digestion and metabolic regulation, may help reduce these negative effects. This study evaluated the effects of dietary BA supplementation on production performance, selected egg quality traits, lipid-related indices, liver histology, and cecal microbiota in late-phase laying hens fed a high-fat diet (HFD). A total of 150 Hy-Line Brown laying hens at 50 weeks of age were allocated either a normal diet (ND), a HFD, or a HFD supplemented with 300 mg/kg BAs (HFD + BAs) for 5 weeks. Compared with the HFD group, BA supplementation affected average daily feed intake (ADFI) and increased the Haugh unit (HU) (p < 0.05), whereas laying rate (LR), average egg weight (AEW), feed conversion ratio (FCR), and most other egg quality traits were not significantly changed. BA supplementation was also associated with differences in selected serum and hepatic lipid-related indices. Histological observations indicated differences in hepatic lipid deposition among treatments. Cecal microbiota analysis showed treatment-associated differences in microbial composition, and correlation analysis identified associations between selected taxa and lipid-related indices. These results indicate that, under the present HFD conditions, dietary BAs were associated with changes in selected egg quality traits, hepatic lipid-related indices, and cecal microbial composition. These findings indicate that dietary BAs may improve selected egg quality traits and liver health in late-phase laying hens by regulating lipid metabolism and intestinal microbiota. Full article

Obesity is a heterogeneous chronic disease for which safe, scalable adjuncts to lifestyle and clinical care remain needed. Tea derived from Camellia sinensis contains catechins, caffeine, theaflavins, thearubigins, theabrownins, polysaccharides, and other constituents whose abundance is shaped by withering, fixation, partial oxidation, full oxidation, and post-fermentation. This review integrates processing-dependent composition with molecular mechanisms, gut–liver signaling, human evidence, safety, and real-world preparation. Evidence is strongest for modest effects of green-tea catechin–caffeine preparations on energy metabolism and selected anthropometric or lipid outcomes, whereas inhibition of adipogenesis, activation of AMP-activated protein kinase, browning of white adipose tissue, and many appetite-related pathways remain supported mainly by cell and rodent studies. A recent meta-analysis in women with overweight or obesity estimated mean reductions of −1.23 kg in body weight and −3.46 cm in waist circumference, with intervention durations across the included trials typically ranging from 4 to 24 weeks, though most of the evidence derives from short- to medium-term interventions (generally ≤12 weeks); heterogeneity was moderate to high and the average weight effect remained below conventional clinical thresholds. Partially oxidized oolong tea and fully oxidized or post-fermented teas provide distinct profiles of caffeine, oxidized polyphenols, and microbial metabolites; their metabolic effects are promising but are less consistently tested in adequately powered human trials. Across tea types, convergent mechanisms include reduced digestive-enzyme activity, increased fatty-acid oxidation, modulation of thermogenesis, reinforcement of the intestinal barrier, and microbiota-dependent production of short-chain fatty acids and bile-acid signals. Translation is constrained by low systemic polyphenol exposure (i.e., limited bioavailability of intact catechins and their metabolites in circulation due to poor intestinal absorption, extensive phase-II metabolism, and rapid clearance), non-standardized doses and products, short intervention periods, interindividual variability, and limited direct comparisons among tea types. Available clinical data do not support tea as a primary treatment for obesity; rather, unsweetened tea or standardized preparations may serve as adjuncts to evidence-based dietary, physical activity, behavioral, and medical management. Priority areas include physiologically relevant dosing, standardized reporting of brewed-tea composition, long-term trials, and microbiome-informed personalization. Full article