Search Results (4,141)

Alcohol consumption has been increasingly associated with alterations in the gut microbiota and its metabolic activity; however, evidence regarding microbiota-derived metabolites remains fragmented. This systematic review aimed to synthesize current evidence on the effects of alcohol consumption on gut microbiota-derived metabolites in humans and non-human primates. The review was conducted according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines and included studies published between 2012 and 2026. Searches were performed in PubMed, Web of Science, Scopus, and ScienceDirect. Study quality was assessed using the Newcastle–Ottawa Scale for human studies and the Systematic Review Centre for Laboratory Animal Experimentation (SYRCLE) Risk of Bias tool for non-human primate studies. Twelve studies met the inclusion criteria, comprising four non-human primate studies and eight human studies. Alcohol exposure was consistently associated with metabolomic alterations across multiple biological matrices. Recurrent findings included reductions in short-chain fatty acids, alterations in tryptophan-derived metabolites, changes in phenolic and aromatic amino acid-related compounds such as hippuric acid, and disturbances in bile acid and purine metabolism. Findings regarding microbial diversity and taxonomic composition were more heterogeneous, with several studies reporting reduced abundances of Faecalibacterium and related butyrate-producing taxa. Studies evaluating abstinence suggested partial recovery of both microbial and metabolomic alterations. Overall, the available evidence suggests that alcohol consumption is associated with alterations across several microbiota-related metabolic pathways, highlighting candidate metabolites that may contribute to alcohol-related pathophysiology and serve as potential translational biomarkers. Full article

Background/Objectives: Persistent inflammation and impaired tissue regeneration delay mucosal and cutaneous wound healing. Potato (Solanum tuberosum L.) preparations contain bioactive metabolites with anti-inflammatory and regenerative potential, yet their wound-healing mechanisms have not been systematically mapped. This scoping review aimed to map potato-derived bioactive metabolites and their roles in modulating inflammation and promoting tissue regeneration during wound healing. Methods: A scoping review was conducted in accordance with the PRISMA-ScR guidelines. Articles published between 2015 and 2025 were retrieved from the Scopus, PubMed, EBSCO, and ScienceDirect databases combined with hand searching. Eligible studies included in vivo animal models; mechanistically relevant in vitro studies; and limited clinical or human skin safety studies investigating potato-derived extracts, fractions, or defined preparation effects in wound, ulcer, and burn healing. Results: Among the 583 records identified, only 15 met the inclusion criteria. These studies reported five major bioactive metabolite classes—flavonoids/anthocyanins, polyphenols, alkaloids, polysaccharides, and peptides—together with potato-derived exosomal vesicles as an extracellular vesicle/delivery system (not a metabolite class). Potato-derived preparations have been associated with accelerated wound closure, enhanced fibroblast proliferation, collagen deposition, and the attenuation of inflammatory mediators. Molecular evidence, which was included in only six studies, supported the modulation of NF-κB, STAT1/3, COX-2, iNOS, cytokines, and MMP-9. In addition, five priority gaps were identified: lack of standardization, fragmented biomarker profiling, limited compound-specific validation, scarce clinical translation, and absence of omics-based and complex wound models. Conclusions: Potato-derived bioactive metabolites show multi-target preclinical associations with wound healing and warrant further development as potential adjunctive therapies for mucosal and cutaneous wounds after standardization and clinical validation. Full article

Finger lime (Citrus australasica) is an emerging high-value fruit species, yet the chemical profiles of Mediterranean-cultivated varieties remain underexplored. This study presents the first chemical characterization of two finger lime varieties, Pink Ice and Green Crystal, grown in Greece, providing the first report on the volatile and non-volatile composition of Green Crystal. Peel essential oils were extracted and analyzed through GC-MS across two harvesting periods (H1 and H2), while methanolic extracts were assessed for their total phenolic content (TPC) and DPPH radical scavenging activity. Non-volatile untargeted profiling was performed on stage H1 extracts using UHPLC-MS/MS. The results revealed a significant chemical divergence between the varieties. Green Crystal exhibited an unprecedented p-cymene/β-phellandrene/citronellal/citronellol volatile chemotype, while Pink Ice displayed a limonene/p-cymene/sabinene/terpinen-4-ol chemotype. Maturity of the fruit significantly influenced monoterpene distribution, with an increase in monoterpene hydrocarbons at the expense of oxygenated derivatives. TPC peaked at stage H1, showing a significant maturity-dependent decline in both varieties, whereas DPPH radical scavenging capacity remained stable across both harvests. UHPLC-MS/MS analysis annotated 58 metabolites, including several compounds reported for the first time in the species. Variety-specific tendencies were observed, with Pink Ice exhibiting greater diversity in flavanones, flavonols, and simple coumarins, whereas Green Crystal exhibited greater diversity in flavones, furanocoumarins, and HMG (hydroxy-3-methylglutaric acid)-flavonoid conjugates. These findings demonstrate that variety selection and harvesting timing are critical parameters for optimizing the commercial and bioactive value of Mediterranean-grown finger lime, highlighting the significant potential for expanded cultivation in the region. Full article

The chemical composition of donkey and sheep milk showed significant differences, with donkey milk containing less fat and protein and a higher level of lactose, while sheep milk had more dry matter and a higher proportion of casein and saturated, unsaturated, monounsaturated, and polyunsaturated fatty acids. This study investigated the biological effects of in vitro-digested donkey and sheep milk, and their blends at different ratios, on differentiated human intestinal Caco-2 cells. Gene expression analysis showed that treatment with digested donkey milk (100%) significantly altered the expression of the autophagy-related gene (SQSTM1), tight junction (CLDN4), and innate defense genes (DEFB1, MUC2, and MUC5), showing a non-cytotoxic response and a profile consistent with a barrier-related transcriptional response. In contrast, sheep milk (100%) and certain milk blends (70% and 50% sheep’s milk) down-regulated genes involved in the autophagy process (ULK1, AMBRA, BECN1, ATG5, GABARAP, and SQSTM1), tight junction genes (OCLN and CDH1), and innate defense genes (DEFB1 and MUC2), suggesting a distinct epithelial response that warrants further confirmation. Metabolomic profiling revealed clear compositional and functional distinctions among the digested milks, identifying 166 metabolites that were differentially regulated (136 compounds were down-regulated and 30 up-regulated). Donkey milk digestion yielded a metabolite profile enriched in polar peptides and compounds with reported antioxidant associations, whereas sheep milk digestion showed a different pattern dominated by hydrophobic peptides and lipid-related metabolites. These findings indicate that, under the tested in vitro conditions, donkey milk digestion is associated with gene expression and metabolomic patterns consistent with epithelial barrier support. Full article

Lobostemon fruticosus (L.) H. Buek is an indigenous South African medicinal plant valued for its traditional therapeutic uses; however, information on its phytochemical variation and pyrrolizidine alkaloid (PA) content across geographical populations remains limited. This study investigated the secondary metabolite composition and PA accumulation in nine biological samples (three geographical locations × three biological replicates) of L. fruticosus collected from Rhodes Memorial, Doringrivier, and Grootnek Fontein in the Western Cape Province between January and March 2025 using untargeted UPLC-QTOF-MS and targeted LC-MS/MS, with values presented as mean ± standard deviation (SD). A total of 15 secondary metabolites of different classes were putatively annotated. Seven compounds, including kaempferol, jaceidin 7-rhamnoside, schizotenuin F, senburiside III, cosmosporaside B, lirioresinol A, and (−)-steganacin, are reported for the first time in L. fruticosus. Significant geographical variation (p < 0.05) was observed, with Doringrivier containing the highest relative abundances of rutin (4815.60 ± 18.96 mg CE g⁻¹ DW), rosmarinic acid (3846.89 ± 285.78 mg CE g⁻¹ DW), and rabdosiin (5142.10 ± 651.00 mg CE g⁻¹ DW). Six of the ten targeted PAs were detected, with lycopsamine N-oxide being the predominant alkaloid (3.89 mg kg⁻¹ in Grootnek Fontein). Principal component analysis explained 97.2% of the total metabolomic variation (PC1 = 72.6%; PC2 = 24.6%) and clearly separated the three geographical populations. The OPLS-DA model showed strong discrimination among populations (R²X = 0.725, R²Y = 0.998, and Q² = 0.994), supporting the presence of location-specific chemotypic differences. The observed chemotypic differences may be associated with variation in soil properties, climatic conditions, water availability, altitude, and nutrient status among the study sites. Collectively, the results provide a foundation for chemotype selection, quality control, conservation, and the safe medicinal utilization of this species. Full article

Antarctic marine-derived fungi represent an underexplored reservoir of bioactive secondary metabolites shaped by extreme environmental pressures. In this study, nine fungal isolates obtained from Antarctic macroalgae, lichens, sponge tissue, and sediments were evaluated for their antimicrobial, anticancer, antibiofilm, and metabolomic profiles. Untargeted LC–MS/MS molecular networking (GNPS) revealed a chemically rich metabolome, dominated by alkaloids, followed by polyketides, meroterpenoids, and diketopiperazines, with Penicillium crustosum (A15A) emerging as a major biosynthetic contributor. The annotation of structurally diverse metabolites, including roquefortines, viridicatin derivatives, andrastins, and multiple diketopiperazines, highlights the metabolic plasticity of Antarctic fungi. Anticancer evaluation indicated cytotoxicity, with Aspergillus awamori (A30), Alternaria malorum (A36), and Cladosporium malorum (A38) displaying activity toward HCT 116 colorectal cancer cells at IC₅₀ ≥ 30 µg/mL. Extracts were screened against methicillin-resistant Staphylococcus aureus (MRSA, COL), methicillin-susceptible S. aureus (MSSA, NCTC8325 4), and Escherichia coli K12, revealing low to no activity against these pathogens. Six of the nine isolates exhibited strong antibiofilm activity without inhibiting planktonic bacterial growth, indicating selective biofilm inhibition against MSSA and meeting the criteria for clinical developmental “hits”. Biofilm inhibition ranged from 81.10% to 98.50%, with A15A showing the highest activity (98.50% at 250 µg/mL), followed by A36 (91.16% at 31.35 µg/mL). Botrytis sp. (A22A), P. chrysogenum (A7), Ulocladium microsporum (A24B), and A30 also demonstrated strong antibiofilm activity (81.10–85.89%). To our knowledge, this is the first report describing antibiofilm activity of Antarctic fungal extracts. Full article

Cannabidiol (CBD) is a bioactive phytocannabinoid with considerable pharmacological potential. However, its limited aqueous solubility and high lipophilicity remain significant barriers to its broader pharmaceutical application. In this study, the enzymatic potential of selected filamentous fungi was investigated as a whole-cell biocatalytic platform for the regioselective functionalization of CBD. Sixteen fungal strains were screened, and thirteen microorganisms successfully transformed CBD into more polar derivatives. Four strains showing distinct and promising chromatographic profiles were selected for scale-up biotransformation and product isolation: Mucor hiemalis KCh W2, M. hiemalis AM 450, Isaria fumosorosea KCh J2, and Metarhizium robertsii MU4. Eight CBD derivatives were isolated and identified by UHPLC-DAD, NMR spectroscopy, and HRESI-MS, including hydroxylated, glycosylated, and methylglycosylated products. Among them, two metabolites, 2′-O-(4‴-O-methyl-β-D-glucopyranosyl)-cannabidiol and 2′-O-(4‴-O-methyl-β-D-glucopyranosyl)-5″-hydroxycannabidiol, are reported here as previously undescribed CBD derivatives. I. fumosorosea KCh J2 and M. robertsii MU4 demonstrated the ability to catalyse 4-O-methylglycosylation. An additional experiment using 2′-O-(β-D-glucopyranosyl)-cannabidiol as an intermediate supported a sequential pathway involving initial phenolic O-glycosylation followed by methylation of the sugar moiety. In silico analysis predicted reduced lipophilicity for the newly obtained derivatives compared with CBD; however, these computational results require experimental verification and should not be interpreted as evidence of improved aqueous solubility, bioavailability, or biological activity. These findings demonstrate that filamentous fungi are useful whole-cell biocatalysts for generating structurally diverse CBD derivatives with increased polarity and provide new compounds for future physicochemical and biological evaluation. Full article

The rapid emergence and dissemination of antimicrobial resistance (AMR) among bacterial pathogens, particularly the ESKAPE group (Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter spp.), represents one of the most pressing global public health challenges, contributing to increased morbidity, mortality, and healthcare costs. The limited development of new antibiotic classes over the past two decades has intensified the search for structurally novel antimicrobial agents and adjuvants capable of overcoming multidrug resistance. Natural products continue to serve as an invaluable source of anti-infective drug leads owing to their remarkable structural diversity and broad spectrum of biological activities. Mangrove ecosystems, located at the interface of terrestrial and marine environments, harbor highly diverse microbial communities, including fungi that have evolved under extreme environmental conditions and produce a wide range of unique secondary metabolites. Beyond their ecological significance, mangrove-associated fungi have emerged as prolific producers of bioactive compounds with promising antibacterial activity against multidrug-resistant pathogens. This review comprehensively summarizes recent advances (2018–2026) in the discovery of antibacterial metabolites from mangrove-associated fungi active against ESKAPE pathogens, which discusses their structural diversity, reported antimicrobial activities, and emerging strategies for accelerating natural product discovery, including genome mining, metabolomics, OSMAC, adaptive laboratory evolution, and artificial intelligence-assisted approaches. A total of 139 chemically distinct metabolites (Compounds 1–139) isolated from mangrove-associated fungi are critically reviewed, highlighting their potential as promising leads for the development of next-generation antimicrobial agents against ESKAPE pathogens. Full article

Examining the relationship between an animal’s diet and physiology is crucial to understanding their responses to environmental change. Dietary-induced physiological variation can influence key life history processes, including growth and reproduction, ultimately affecting individual fitness. Reported here are the plasma biochemical parameters related to energy storage, use and nutritional condition in juvenile white sharks (Carcharodon carcharias) in Eastern Australia. Specifically, we used plasma metabolites (triglyceride, cholesterol and β-hydroxybutyrate), thyroid hormone thyroxine and fatty acid profiles from 50 juvenile white sharks (152–340 cm total length) captured on SMART drumlines in Eastern Australia to examine blood biochemistry and nutritional ecology. Concentrations of triglycerides and β-hydroxybutyrate indicated high energy expenditure likely associated with the broad-scale migration of white sharks along the Australian coast, highlighting the importance of β-hydroxybutyrate as an energy source. Seasonal variation in the triglyceride/cholesterol and ω3/ω6 fatty acid ratio, in conjunction with lower docosahexaenoic acid, suggests that lower-quality prey is consumed during winter months, thereby influencing the nutritional condition of these sharks. Additionally, the positive correlation between thyroxine concentrations and water temperature suggests reduced metabolic activity during cooler months. Such fluxes in food quality and nutritional condition may affect juvenile white sharks’ growth and development rate and future reproductive success. Full article

Marine organisms from deep-sea environments have attracted considerable attention in drug discovery because they produce structurally diverse natural products. However, Norwegian deep-sea ecosystems remain largely unexplored in terms of natural product chemistry and bioactivity. In this study, a deep-sea sponge belonging to the genus Phakellia was selectively collected using a low-impact, remotely operated vehicle approach from the Mohn’s Treasure area in the Norwegian Sea at a depth of 2858 m, representing one of the deepest sponge samples investigated in Norwegian waters to date. Chemical investigation of this specimen resulted in the isolation of three new glycosylated fatty acid amides, phakelliosides A–C (1–3), together with two known compounds, 11-(S)-myxillin B (4) and 11-(S)-myxillin C (5), which were isolated as pure individual compounds from natural sources for the first time, with their absolute configurations unambiguously established. These compounds were isolated using a combination of chromatographic techniques, and the structures of the isolated compounds were elucidated by comprehensive spectroscopic analyses, including 1D and 2D NMR and UHPLC–HRMS data. The absolute configurations were determined by optical rotation analysis following acid hydrolysis. Compounds 1–5 were subjected to preliminary antibacterial screening against Enterococcus faecalis, Staphylococcus aureus, Streptococcus agalactiae, Escherichia coli, and Pseudomonas aeruginosa at 100 µg/mL. Under the screening conditions, compound 3 produced the lowest OD₆₀₀ value against E. faecalis (OD₆₀₀ = 0.154), whereas generally higher OD₆₀₀ values were observed against the Gram-negative strains. To the best of our knowledge, this is the first report describing the preliminary antibacterial screening of glycosylated fatty acid amides isolated from Norwegian deep-sea organisms. These findings expand current knowledge of the chemical diversity of natural products associated with Norwegian deep-sea sponges. The biosynthetic origin of these metabolites remains unresolved and warrants further investigation. Full article

Atopic dermatitis (AD) is a chronic inflammatory skin disease characterized by epidermal barrier dysfunction, immune dysregulation, and marked clinical heterogeneity. Growing evidence implicates the gut microbiome in AD-related pathways through microbial metabolites, intestinal barrier function, and systemic immune signaling. This narrative review synthesizes current evidence on gut microbial alterations in AD, with particular attention to short-chain fatty acids, tryptophan-derived aryl hydrocarbon receptor ligands, intestinal permeability, gut–skin microbiome interactions, and microbiota-targeted interventions. Human studies have reported associations between AD and altered abundance of selected microbial taxa, metabolite profiles, and markers of intestinal barrier dysfunction, whereas animal and in vitro studies provide complementary mechanistic evidence. However, findings remain heterogeneous across age groups, disease phenotypes, geographic populations, analytical platforms, and treatment exposures, and causality is incompletely established. Probiotic and synbiotic interventions have shown strain-specific and context-dependent effects, while postbiotics, fecal microbiota transplantation, washed microbiota transplantation, and metabolite-directed approaches remain investigational. AI-assisted multi-omics methods may improve biological stratification and hypothesis generation, but current applications are limited by small sample sizes, cohort heterogeneity, overfitting, insufficient external validation, and limited clinical implementation. Current evidence therefore supports the gut microbiome as a mechanistically plausible contributor, potential biomarker, and therapeutic target in AD while underscoring the need for longitudinal, phenotype-aware, and externally validated studies before routine clinical translation. Full article

Rare actinomycetes have emerged as important yet underexplored reservoirs for the discovery of novel bioactive compounds. Microbispora, a genus of rare actinomycetes, is widely distributed across diverse ecological niches, including terrestrial soils, marine-associated environments, plant-associated ecosystems, and insect-derived environments. To date, 81 secondary metabolites have been reported from this genus, encompassing quinones, chromones and chromanones, macrolides, other polyketides, alkaloids, peptides and diketopiperazines, and miscellaneous structural classes. These metabolites display antimicrobial, anticancer, neuroprotective, antiviral, plant growth-promoting, and enzyme inhibitory activities. Beyond systematically cataloging these compounds, this review provides an integrated analysis of their structure–activity relationships (SAR), biosynthetic origins, and biological significance. In addition, the biosynthetic potential of Microbispora is discussed based on reported genomic studies, highlighting the presence of numerous predicted and poorly characterized biosynthetic gene clusters. This review provides an integrative perspective on Microbispora as an underexplored but promising source of structurally diverse and bioactive natural products for drug discovery. Full article

Metabolic syndrome (MetS) is a complex cluster of interconnected metabolic abnormalities, including central obesity, insulin resistance, dyslipidemia, hypertension, chronic inflammation, and impaired glucose metabolism, which collectively increase the risk of type 2 diabetes and cardiovascular diseases. Although current therapeutic strategies, including lifestyle interventions and pharmacological treatments, can be effective in managing specific MetS components, the multifactorial nature of this condition continues to encourage the search for complementary approaches and novel bioactive compounds. Salt-tolerant plants (STPs), particularly halophytes, survive under adverse saline and oxidative stress conditions through specialized physiological and biochemical adaptations, including the production of diverse secondary metabolites such as phenolic acids, flavonoids, sterols, terpenoids and polysaccharides. Several of these compounds have been associated with health-promoting properties, including antioxidant, anti-inflammatory, antidiabetic, antihypertensive, lipid-modulating and cardioprotective effects. This review provides an integrated and critical overview of the ethnomedicinal uses, phytochemistry and bioactivities of STPs with potential relevance to MetS and its associated conditions, namely chronic inflammation, diabetes, hypertension, cardiovascular disorders, dyslipidemia and obesity. The review first introduces the main features of MetS and the relevance of STPs as bioresources, followed by a synthesis of ethnomedicinal uses related to MetS-associated disorders. It then discusses in vitro and in vivo evidence for selected species, extracts and compounds, including reported bioactive metabolites and proposed mechanisms of action when available. Finally, the most promising species, extracts and metabolites are highlighted, together with current limitations and future research needs regarding efficacy, safety, bioavailability, standardization and clinical relevance. Full article

Background/Objectives: Antimicrobial resistance (AMR) poses a major global health challenge, particularly in opportunistic pathogens such as Pseudomonas aeruginosa. This study aimed to identify metabolic adaptations associated with antibiotic resistance by integrating transcriptomic data from drug-resistant clinical isolates with a genome-scale metabolic model (GEM) of P. aeruginosa under four antibiotic treatments: ceftazidime (CAZ), ciprofloxacin (CIP), meropenem (MEM), and tobramycin (TOB). Methods: Transcriptomic data from 414 clinical isolates were integrated with the iPau21 genome-scale metabolic model (GEM) of P. aeruginosa. Differential gene expression analysis was performed using DESeq2, and differentially expressed genes (DEGs) were identified using a false discovery rate (FDR)-adjusted p-value < 0.05 and a fold-change threshold of ≥2 or ≤0.5. Reporter metabolites (RMs) were identified using the Reporter Metabolite algorithm with an FDR-adjusted p-value < 0.05. Pathway enrichment analysis was performed to characterize condition-specific metabolic alterations, and pathway significance was determined using the Benjamini–Hochberg procedure with an adjusted p-value < 0.05. Results: The analysis revealed predominantly antibiotic-specific transcriptional responses, with limited overlap in DEGs across treatment conditions. Reporter metabolite and pathway enrichment analyses identified distinct metabolic adaptations associated with biofilm formation, virulence, and stress response pathways. Several metabolites, including propionic acid, acetic acid, L-inositol, glutamine, glutarate, fumarate, and melatonin, were computationally prioritized candidate metabolites for future metabolite-based adjuvant strategies aimed at enhancing antibiotic efficacy. Conclusions: This systems biology approach provides a comprehensive framework for identifying metabolic vulnerabilities associated with AMR in P. aeruginosa. The identified metabolites represent candidate antibiotic adjuvant molecules generated through computational prioritization and should be regarded as hypotheses for future experimental validation rather than validated therapeutic interventions. These findings provide a foundation for future studies exploring metabolism-based strategies to improve antibiotic efficacy and combat antimicrobial resistance. Full article

Patient-reported outcomes (PROs) are often regarded in clinical practice as less reliable than biomarkers because they are patient-dependent and not objectively measurable in the same way as circulating molecules or imaging findings. This view may be reductive. Biomarkers are frequently considered reliable because they are easily quantifiable, yet biological meaning does not depend solely on measurement. In precision and personalized medicine, the absolute level of a circulating hormone, cytokine, or metabolite is often insufficient unless interpreted in relation to how a given patient, at a given time, responds to that molecular signal. If biomarkers are considered less absolute and more context-dependent, the relevance of PROs becomes clearer. Standardized PROs capture the subjective impact of disease on the patient system in a reproducible and clinically interpretable manner. This is particularly relevant in Long COVID, where no validated diagnostic biomarker is currently available, and severity stratification cannot rely exclusively on objective biological measures. Among available tools, the Fatigue Assessment Scale (FAS) may be particularly useful for quantifying the fatigue burden in Long COVID, including both physical and mental components. Moreover, FAS scores have been shown to correlate with the number of symptoms reported by patients, suggesting that this scale may help stratify patients not only according to fatigue severity but also according to overall symptom burden. Greater standardization of clinical characterization through instruments such as the FAS may improve comparability across cohorts and facilitate interpretation of data from different clinical trials. Full article