Search Results (42)

Background: We previously demonstrated recapitulation of the relative hypogonadotropic hypogonadism of obesity, the Reprometabolic Syndrome (RMS), in women of normal BMI with a one-month high-fat, eucaloric diet (HFD). Objective: Assess effects of HFD on sleep, body composition and lifestyle and metabolic secondary outcomes and correlate insulin sensitivity changes with the RMS. Methods: A total of 18 normally cycling women aged 18–38 with BMI 18–24 kg/m² were enrolled for a four-month study including a eucaloric HFD (48% calories from fat) for one menstrual cycle. Activity, sleep, body composition, and the lipidome were measured in all participants. Fecal microbiome was analyzed in the last nine participants, and insulin sensitivity by two-stage hyperinsulinemic euglycemic clamp was measured before and after HFD in 15 participants. Results: Relative to the pre-diet period, BMI, activity and sleep measures did not change, except for waking after sleep onset (WASO), which appeared to decrease during and post HFD. DXA revealed statistically significant decreases in total percent fat, total fat mass, visceral fat volume, and trunk fat volume. Whole-body insulin sensitivity decreased with the HFD while adipocyte insulin sensitivity was unaffected. Insulin sensitivity changes did not correlate with change in gonadotropins or response to gonadotropin releasing hormone (GnRH). Multiple significant changes in plasma lipids were observed, including increased ceramides and glucosylceramides. Microbiome analysis revealed increased microbial diversity. Conclusions: A one-month eucaloric HFD that induced RMS in normal-weight, reproductive-aged women also induced whole-body insulin resistance (IR) and multiple lipidomics changes potentially associated with IR. These changes in IR occurred despite overall stable activity, BMI and sleep, but did not correlate with the HPO axis defects. The unexpected decrease in body fat and increase in microbial diversity may be related to specific dietary elements of the HFD. Full article

The growing global population and increasing pressure on conventional food systems have intensified the search for sustainable and nutrient-rich protein sources. Blue foods derived from marine and freshwater organisms offer significant nutritional advantages and lower environmental footprints compared with many terrestrial animal proteins. However, challenges related to resource sustainability, processing, preservation, and product traceability limit their full potential. This review provides a broad overview of emerging technologies shaping the future of blue food systems, covering innovative production strategies, advanced processing techniques, and omics-based analytical approaches. Key developments in cellular aquaculture and cellular mariculture are discussed as promising alternatives to traditional fisheries and aquaculture, enabling the production of blue food through controlled cell cultivation. Additionally, alternative protein platforms including plant-based, fermentation-derived, and cultivated blue food analogues are assessed for their potential to enhance sustainability and diversify aquatic protein sources. Advanced structuring technologies such as extrusion, electrospinning, wet spinning, and 3D printing are highlighted for their roles in developing blue food analogues with improved texture and sensory attributes. Furthermore, non-thermal preservation techniques, including cold plasma (CP), high-pressure processing (HPP), pulsed electric fields (PEFs), and ultraviolet-based treatments, are reviewed for their effectiveness in improving microbial safety and extending shelf life while maintaining nutritional quality. The integration of omics technologies (proteomics, metabolomics, and lipidomics) provides deeper molecular insights into product quality, authenticity, and traceability within blue food supply chains. Collectively, these interdisciplinary advancements demonstrate strong potential to transform blue food production into a more resilient, sustainable, and technology-driven sector. Future progress will depend on overcoming challenges related to scalability, regulatory frameworks, and consumer acceptance to enable the successful commercialization of next-generation blue food products. Full article

Background: The SARS-CoV-2 3CLpro is essential for viral replication and an attractive target for antiviral intervention. While most strategies target the catalytic site, recent studies suggest that the dimerization interface and cryptic allosteric pockets offer alternative mechanisms for inhibition. Objective: This study investigated lipid metabolites from the marine sediment-derived Streptomyces sp. DSD454^T as potential multi-site 3CLpro inhibitors. Methods: Metabolites were extracted from cultured biomass and characterized using LCMS-QTOF, MS/MS (LCMS-TQ), and ¹H NMR, with identities confirmed against authentic standards. 3CLpro inhibition was assessed using a FRET-based assay, and ligand–protein interactions were evaluated through molecular docking and MM/GBSA calculations. Lipid content and comparative lipidomic signatures were examined across bioactive Streptomyces strains through LCMS-TQ and BODIPY^TM 493/503 staining. Results: Palmitoleic and linoleic acids were identified as major constituents and inhibited SARS-CoV-2 3CLpro with IC₅₀ values of 1.59 µg/mL (6.25 µM) and 5.29 µg/mL (18.88 µM). Molecular docking predicted that both fatty acids bind not only to the catalytic site but also to the dimerization interface and cryptic allosteric pocket. Additional lipids, including 9-heptadecenoic acid, linolenic acid, 9-HODE, and monoacylglycerols such as aggrecerides A–C and glyceryl-based lipids, showed similarly favorable multi-site binding profiles. Streptomyces sp. DSD454^T also exhibited substantial lipid accumulation (~63% of crude extract). Across bioactive Streptomyces strains, a conserved lipid signature correlated strongly with 3CLpro inhibition. Conclusions: This study highlights the potential of microbial lipids as promising scaffolds for developing catalytic and allosteric SARS-CoV-2 3CLpro inhibitors and underscore marine Streptomyces as a valuable source of structurally simple yet mechanistically versatile antiviral metabolites. Full article

Acne vulgaris is a prevalent chronic inflammatory dermatosis primarily affecting the pilosebaceous units. Current therapeutic approaches often exhibit limited efficacy and high recurrence rates. To investigate the microbiome-related mechanisms of acne vulgaris, facial skin samples from 19 patients with moderate acne and 20 healthy individuals were analyzed using an integrated metagenomic and lipidomic profiling strategy. Metagenomic analysis revealed a significant reduction in microbial diversity (Chao index) in acne-affected skin compared to healthy controls (p < 0.001). The relative abundance of Staphylococcus, particularly Staphylococcus epidermidis, was significantly elevated in acne group (p < 0.05), while Cutibacterium acnes levels remained unchanged. Carbon metabolism pathways were enriched in the acne group (p < 0.05), predominantly driven by Cutibacterium, whereas other enriched metabolic pathways, such as ABC transporters and glycine, serine, and threonine metabolism (p < 0.05), showed a greater contribution from Staphylococcus. Virulence factors enriched in acne samples were primarily offensive in nature and largely attributed to Staphylococcus. Moreover, acne-associated microbiome exhibited a significantly higher prevalence of resistance genes against fluoroquinolones, fosfomycin, and triclosan (p < 0.05). Untargeted lipidomic analysis demonstrated significantly elevated total serum and triglyceride levels, along with a reduction in fatty acid chain length and a higher degree of saturation compared to the healthy group (p < 0.01). Specific triglycerides significantly enriched in the acne group, such as TG (15:0_14:0_16:0) + NH₄, exhibited a significant positive correlation with Staphylococcus. This correlation is associated with elevated clinical erythema and melanin indices, suggesting that Staphylococcus is implicated in the development of acne-related inflammation. Additionally, Thermus exhibits negative correlations with acne-associated lipids and inflammatory parameters, potentially exerting a protective role. These findings suggest that Cutibacterium and Staphylococcus play differential yet synergistic roles in acne pathogenesis. The observed skin microbiome dysbiosis and lipid metabolic alterations provide novel insights into the pathophysiology of acne vulgaris, which may inform the development of targeted therapeutic strategies. Full article

Recurrent Clostridioides difficile infection (rCDI) remains a major therapeutic challenge. Although faecal microbiota transplantation (FMT) is highly effective and thought to restore microbial composition and metabolic function, the mechanisms underlying its success are not fully understood. In particular, the contribution of non-bacterial components such as soluble metabolites remains unclear. Therefore, further investigation is needed to identify the mechanistic drivers of FMT efficacy and clarify how non-bacterial factors contribute to therapeutic outcomes. Here, we applied untargeted three-dimensional Orbitrap secondary ion mass spectrometry (3D OrbiSIMS) to profile faecal metabolic reprogramming in rCDI patients pre- and post-FMT, alongside C. difficile cultures exposed to sterile faecal filtrates. FMT induced extensive metabolic shifts, restoring glyoxylate/dicarboxylate and glycerophosphoinositol pathways and normalising disrupted bile acid and amino acid profiles. Faecal filtrate exposure caused strain-specific metabolic disruption in C. difficile, depleting proline, fumarate and succinate while enriching tryptophan. While multiple metabolite classes were profiled, the most significant functional changes were observed in lipids. Lipidomics identified >3.8-fold enrichment of phosphatidylinositol (PI) species, which localised to bacterial membranes and conferred cytoprotection against C. difficile toxins and other epithelial insults. Spatial metabolomics imaging revealed, for the first time, metabolite compartmentalisation within C. difficile, with proline and succinate broadly distributed across the cell surface and fumarate confined to distinct microdomains, highlighting functional heterogeneity in pathogen metabolism. Collectively, these findings demonstrate that soluble metabolites within faecal filtrates mediate pathogen suppression and epithelial barrier protection, establishing metabolite-driven mechanisms underlying FMT efficacy and identifying PI lipids as candidate post-biotic therapeutics for rCDI. Full article

Modern biomedicine frequently contextualizes disease around isolated molecular or organ-specific mechanisms, but numerous chronic diseases, including Alzheimer’s disease, multiple sclerosis, depression, diabetes, and sepsis, share common trajectories of systemic destabilization. An increasing body of evidence indicates that health is not a property of single organs but the emergent property of interdependent feedback networks linking the microbiome, endocannabinoidome, neuroimmune system, and metabolic regulators. We propose the Endocannabinoid–Microbiota–Neuroimmune Super-System (EMN-S) as an evolutionarily conserved conceptual model that describes how these fields of influence reciprocally interact through feedback control. The microbial communities constituting the EMN-S encode environmental and dietary inputs, endocannabinoid signaling serves as an integrative regulator that synchronizes neural and immune activity, and neuroimmune circuits effectuate adaptive behaviors that alter microbiotal and lipid ecosystems. This review formalizes the EMN-S, contending that it is a unitary and cohesive model of physiological resilience, as well as offering a framework for precision feedback therapeutics. We describe how three mechanisms—encoder drift, integrator detuning, and executor overutilization—convert stabilizing negative feedback into runaway feedback cascades that underlie chronic, recurrent, and multisystemic disease. We then specify the EMN-S signature—integrated microbiome, lipidomic, and immune readouts—as an early indicator of resilience collapse and prospective preclinical state. Finally, we recapitulate the potential of AI-driven digital twins to illuminate feedback collapse, predict tipping points, and direct closed-loop intervention and treatments to restore dynamic equilibrium. By anchoring complexity in concrete and measurable feedback principles, the EMN-S shifts focus to investigate pathophysiology as opposed to reductionist lesion models of systemic derangements and embraces a systemic, empirically testable theory of stability. Full article

Debaryomyces hansenii has the potential to enhance the flavor profile of traditional fermented meat products. This study investigates the impact of the D. hansenii LY090 strain on the microbial community, lipidome, flavor profiles, and sensory properties of Sichuan bacon. Inoculation with LY090 significantly inhibited the relative abundance of other yeasts, except for Debaryomyces, and altered bacterial community composition. The presence of LY090 led to a notable reduction (p < 0.05) in the levels of ceramide and phosphatidylcholine, resulting in an excessive inhibition of lipid degradation. This further affected the development of flavor and color in Sichuan bacon. However, the concentrations of aldehydes (249.80 μg/kg), ethyl 3-methylbutyrate (81.01 μg/kg), and acetoin (223.91 μg/kg) were all found to be abundant, and the bacon achieved the highest overall acceptance scores when inoculated with both LY090 and commercial starter culture FAST301. Correlation analysis indicated that the differential metabolites exhibited a stronger association with the yeast community, which plays a vital role in the flavor development of Sichuan bacon. These detailed investigations provide meaningful implications for D. hansenii LY090 implementation strategies in the Sichuan bacon industry. Full article

Fermented dairy products such as yogurt, kefir, and traditional cheeses are increasingly consumed worldwide for their nutritional and probiotic properties. Lipidomic profiling provides valuable insights into microbial-driven biochemical changes during fermentation. In this study, we performed a comprehensive untargeted lipidomic analysis of sheep milk and Gioddu, a traditional Sardinian fermented dairy product. Using UHPLC-QTOF-MS platform, we observed that fermentation significantly reshaped the lipidome. Gioddu samples showed higher levels of phosphatidylethanolamines (PE) and lysophosphatidylethanolamines (LPE), together with a pronounced reduction in sphingolipids (glucosylceramides, ceramides, sphingomyelins) and glycerophospholipids (phosphatidylinositols, phosphatidylserines, phosphatidylcholines) compared to sheep milk. These findings align with known enzymatic activities of lactic acid bacteria (LAB), including phospholipases A1 and A2, phosphatidylinositol-specific phospholipase C (PI-PLC), and sphingomyelinase. Fermentation also affected triglycerides, with reduced levels of FA 18:1-containing species, suggesting the selective lipolysis of monounsaturated fatty acids by microbial lipases. Complementary metabolomic profiling revealed reduced levels of simple sugars such as galactose and inositol in Gioddu samples, consistent with their use as primary carbon sources during early fermentation. Conversely, a marked accumulation of carboxylic acids (succinic, malic, hydroxyisovaleric, hydroxyglutaric, glyceric) was revealed, reflecting enhanced microbial fermentative activity. Increased levels of amino acids, including alanine, serine, proline, and ethanolamine, further highlighted active proteolysis and membrane remodeling driven by LAB metabolism. These findings show that LAB enzymes play a key role in modifying the lipidome of fermented dairy products, highlighting their metabolic flexibility and potential impact on nutritional and health properties. This integrated approach sheds new light on the metabolic plasticity of fermentative processes and underscores the value of omics-based tools in understanding traditional food systems. Full article

Lean metabolic dysfunction-associated steatotic liver disease (lean MASLD) challenges longstanding views that link hepatic steatosis primarily to obesity. Emerging as a distinct and under-recognized clinical entity, lean MASLD affects individuals with a normal body mass index (BMI), yet carries risks of cardiovascular disease, hepatocellular carcinoma, and liver-related mortality comparable to obesity-associated MASLD. The absence of overt metabolic dysfunction complicates diagnosis, revealing critical limitations in current screening frameworks centered on BMI. This review synthesizes evolving clinical insights and epidemiological trends in lean MASLD, and delineates its unique pathophysiological mechanisms. Recent advances in metabolomics have uncovered disease-specific disruptions in lipid and amino acid metabolism, bile acid signaling, and gut microbiota-derived metabolites. By integrating evidence from metabolic, genetic, and epigenetic domains, we identified promising biomarkers, and therapeutic targets that may support earlier detection and precision-guided treatment strategies. Full article

The global obesity epidemic and associated metabolic disorders present urgent public health challenges. This study employed a multi-omics approach (lipidomics, metabolomics, and gut microbiome analysis) to investigate how Bletilla striata polysaccharides (BSPs) and composite polysaccharides modulate liver lipid metabolism and gut microbiota in high-fat diet (HFD)-induced obese mice. HFD elevated hepatic phosphatidylcholines, cholesteryl esters (CEs), and acylcarnitines (CARs), alongside increased cecal choline and trimethylamine. BSP interventions reduced hepatic CEs, free fatty acids (FAs), CARs, and cecal sarcosine while restoring gut microbial diversity. Notably, BSP enriched beneficial genera, including Jeotgalicoccus and Atopostipes, and the network analysis revealed negative correlations between these genera and hepatic triglycerides (TGs), implicating the gut–liver axis in lipid metabolism regulation. These findings elucidate the anti-obesity mechanisms of polysaccharides through gut microbiota remodeling and cross-tissue metabolic interactions, providing a foundation for leveraging plant polysaccharides in developing safer, effective obesity therapies. Full article

Background/Objectives: Strawberries (Fragaria × ananassa) are among the most commonly consumed fruits due to their taste and nutritional benefits. However, their high rate of spoilage poses a major problem during the period from harvest and transport to further processing or marketing. The aim of this study was, therefore, to investigate the effects of passive modified atmosphere packaging on the metabolome and shelf life of strawberries as a more sustainable alternative compared to standard market storage conditions. Methods: A total of 99 strawberry samples were analyzed for microbial viable counts, water content, and metabolomic changes using non-targeted low-resolution near-infrared spectroscopy, high-resolution mass spectrometry, and microbial culture-based methods. Results: Using near-infrared spectroscopy as a rapid screening method, the linear regression model indicated that strawberries stored under modified atmosphere packaging conditions had a longer shelf life. Furthermore, lipidomic analysis using mass spectrometry showed that the levels of spoilage biomarkers, such as oxidized phosphatidylcholines and lysophosphatidylcholines, were increased under common market storage conditions without a controlled atmosphere. In contrast, the levels of these metabolites were reduced when strawberries were stored in modified atmosphere packaging. Moreover, the strawberries stored under modified atmosphere packaging had a lower number of bacteria, yeasts, and molds as well as a lower water loss throughout the entire storage period. Conclusions: Overall, the study highlights the potential of passive modified atmosphere packaging films to extend the shelf life and thus maintain the edibility of strawberries over a longer period. Full article

Streptococcus mutans (S. mutans) plays an important role in dental caries through acid production and biofilm formation. The membrane vesicles (MVs) of S. mutans are essential for microbial physiology, biofilm activity, and acid adaptation. The OpuB transporter regulates osmotic pressure in Bacillus subtilis; however, its role in S. mutans and its MVs remains unexplored. This study investigated the effects of the opuB pathway on MV biogenesis, as well as the proteomic and lipidomic profiles under neutral (pH 7.5) and acidic (pH 5.5) conditions. Nanoflow cytometry showed that the opuB-deficient strain (Smu_opuB) produced significantly more and smaller MVs than UA159 at pH 7.5, while the difference was not significant at pH 5.5. Lipidomic analysis revealed that opuB affected the lipid composition and concentration of S. mutans MVs. Proteomic analysis identified the differential enrichment of key metabolic processes associated with stress, including DNA repair. These findings highlight that opuB is an important regulator of MV biosynthesis and composition and may affect the environmental adaptability of S. mutans by regulating MVs. Full article

Background: Peripheral neuropathy (PN), a complication of diabetes and obesity, progresses through a complex pathophysiology. Lifestyle interventions to manage systemic metabolism are recommended to prevent or slow PN, given the multifactorial risks of diabetes and obesity. A high-fat diet rich in saturated fatty acids (SFAs) induces PN, which a diet rich in monounsaturated fatty acids (MUFAs) rescues, independent of weight loss, suggesting factors beyond systemic metabolism impact nerve health. Interest has grown in gut microbiome mechanisms in PN, which is characterized by a distinct microbiota signature that correlates with sciatic nerve lipidome. Methods: Herein, we postulated that SFA- versus MUFA-rich diet would impact gut microbiome composition and correlate with PN development. To assess causality, we performed fecal microbiota transplantation (FMT) from donor mice fed SFA- versus MUFA-rich diet to lean recipient mice and assessed metabolic and PN phenotypes. Results: We found that the SFA-rich diet altered the microbiome community structure, which the MUFA-rich diet partially reversed. PN metrics correlated with several microbial families, some containing genera with feasible mechanisms of action for microbiome-mediated effects on PN. SFA and MUFA FMT did not impact metabolic phenotypes in recipient mice although SFA FMT marginally induced motor PN. Conclusions: The involvement of diet-mediated changes in the microbiome on PN and gut–nerve axis may warrant further study. Full article

Traditionally, research on the adaptive immune system has focused on protein antigens, but emerging evidence has underscored the essential role of lipid antigens in immune modulation. Lipid antigens are presented by CD1 molecules and activate invariant natural killer T (iNKT) cells and group 1 CD1-restricted T cells, whereby they impact immune responses to pathogens and tumors. Recent advances in mass spectrometry, imaging techniques, and lipidomics have revolutionized the identification and characterization of lipid antigens and enhanced our understanding of their structural diversity and functional significance. These advancements have paved the way for lipid-based vaccines and immunotherapies through the application of nanoparticles and synthetic lipid antigens designed to boost immune responses against cancers and infectious diseases. Lipid trafficking, CD1 molecule interactions, and the immune system’s response to lipid antigens are yet to be completely understood, particularly in the context of autoimmunity and microbial infections. In the years to come, continued research efforts are needed to uncover its underlying biological mechanisms and to exploit the full potential of therapies directed against lipid antigens. Full article

This study investigated the fatty acids (FA) profile of 54 actinomycete strains isolated from marine sediments collected off the Portugal continental coast, specifically from the Estremadura Spur pockmarks field, by GC/MS. Fatty acid methyl esters (FAMEs) were prepared from the ethyl acetate lipidic extracts of these strains and analyzed by gas chromatography–mass spectrometry (GC/MS), with FA identification performed using the NIST library. The identified FAs varied from C12:0 to C20:0, where 32 distinct FAs were identified, including 7 branched-chain fatty acids (BCFAs), 9 odd-chain fatty acids (OCFAs), 8 monounsaturated fatty acids (MUFAs), 6 saturated fatty acids (SFAs), 1 polyunsaturated fatty acid (PUFA), and 1 cyclic chain fatty acid (CCFA). The average expressed content was BCFA (47.54%), MUFA (28.49%), OCFA (26.93%), and SFA (22.16%), of which i-C16:0, C18:1ω9, and C16:0 were predominant, while PUFA (3.58%) and CCFA (0.41%) were identified as minor components. The identified BCFA were i-C16:0, a-C15:0, i-C15:0, i-C15:1ω6, a-C16:0, a-C14:0, and i-C17:0, which include combined branching and unsaturation and branching and odd. SFAs were present in all species, with C16:0 and C18:0 being the most representative. Rare OCFAs C19:1ω9, C17:1ω7, C15:0, and C17:0 were expressed. PUFA C18:1ω9 was detected; within this class, omega families ω9, ω7, ω6, and ω5 were identified, and no ω3 was detected. The only CCFA was benzene-butanoic acid (benzene-C4:0). These findings highlight the metabolic versatility of actinomycetes, providing valuable insights into microbial chemotaxonomy and offering promising biochemical leads for the development of biofuel, nutraceutical, and antifungal agents. Furthermore, these results underline the diversity and biotechnological potential of FAs in actinomycetes, uncovering their potential to be used as microbial cell factories, and paving the way for innovations in biofuels, pharmaceuticals, and eco-friendly industrial products. Full article