PubMed

Physiol Genomics. 2025 Jan 7. doi: 10.1152/physiolgenomics.00106.2024. Online ahead of print.ABSTRACTPreeclampsia (PE) is a life-threatening hypertensive disorder of pregnancy with an incidence rate of up to 8% worldwide. However, the complete pathogenesis is still unknown. Obesity increases the risk of developing PE three-fold. To better understand the relationship of maternal risk factors, the BPH/5 mouse was described as a model of superimposed PE. Previous research demonstrated that adult BPH/5 female mice have an adverse cardiometabolic phenotype characterized by hypertension, obesity with increased white adipose tissue and dyslipidemia, exaggerated by pregnancy. We hypothesize that BPH/5 mice have gut dysbiosis characterized by changes in alpha and beta diversity of bacterial community structure as well as perturbed short chain fatty acids (SCFA) compared to controls in pregnancy. Fecal samples were used for Illumina sequencing of 16S v4 rRNA amplicons. Microbial community composition of the pregnant BPH/5 compared to C57 controls was different using PERMANOVA with Bray-Curtis dissimilarity. Alpha diversity was increased in pregnant BPH/5 dams compared to controls. Alistipes and Helicobacter were increased while Bacteroides, Lactobacillus, Parasulterrella, and Parabacteroides were decreased compared to controls. Fecal SCFAs were not different between groups, but BPH/5 serum acetic and butyric acid were decreased while isobutyric and isovaleric acid were increased specifically in pregnancy. BPH/5 pregnant colons had decreased expression of free fatty acid receptor, GPR41. In conclusion, the BPH/5 maternal fecal microbiome demonstrates microbial dysbiosis characterized by community structure and diversity changes before and after the onset of pregnancy. Gut dysbiosis may be a key mechanism linking SCFA signaling and obesity to the BPH/5 PE-like phenotype.PMID:39773069 | DOI:10.1152/physiolgenomics.00106.2024

Microbiol Spectr. 2025 Jan 8:e0190124. doi: 10.1128/spectrum.01901-24. Online ahead of print.ABSTRACTLimnospira can colonize a wide variety of environments (e.g., freshwater, brackish, alkaline, or alkaline-saline water) and develop dominant and even permanent blooms that overshadow and limit the diversity of adjacent phototrophs, especially in alkaline and saline environments. Previous phylogenomic analysis of Limnospira allowed us to distinguish two major phylogenetic clades (I and II) but failed to clearly segregate strains according to their respective habitats in terms of salinity or biogeography. In the present work, we attempted to determine whether Limnospira displays metabolic signatures specific to its different habitats, particularly brackish and alkaline-saline ecosystems. The impact of accessory gene repertoires on respective chemical adaptations was also determined. In complement of our previous phylogenomic investigation of Limnospira (Roussel et al., 2023), we develop a specific analysis of the metabolomic diversity of 93 strains of Limnospira, grown under standardized lab culture conditions. Overall, this original work showed distinct chemical fingerprints that were correlated with the respective biogeographic origins of the strains. The molecules that most distinguished the different Limnospira geographic groups were sugars, lipids, peptides, photosynthetic pigments, and antioxidants. Interestingly, these molecular enrichments might represent consequent adaptations to conditions of salinity, light, and oxidative stress in their respective sampling environments. Although the genes specifically involved in the production of these components remain unknown, we hypothesized that within extreme environments, such as those colonized by Limnospira, a large set of flexible genes could support the production of peculiar metabolite sets providing remarkable adaptations to specific local environmental conditions.IMPORTANCE: Limnospira are ubiquitous cyanobacteria with remarkable adaptive strategies allowing them to colonize and dominate a wide range of alkaline-saline environments worldwide. Phylogenomic analysis of Limnospira revealed two distinct major phylogenetic clades but failed to clearly segregate strains according to their habitats in terms of salinity or biogeography. We hypothesized that the genes found within this variable portion of the genome of these clades could be involved in the adaptation of Limnospira to local environmental conditions. In the present paper, we attempted to determine whether Limnospira displayed metabolic signatures specific to its different habitats. We also sought to understand the impact of the accessory gene repertoire on respective chemical adaptations.PMID:39772964 | DOI:10.1128/spectrum.01901-24

J Proteome Res. 2025 Jan 8. doi: 10.1021/acs.jproteome.4c00939. Online ahead of print.ABSTRACTSkeletal muscle aging poses a major threat to the health and quality of life of elderly individuals. Fisetin, a natural polyphenolic compound, exhibits various biological activities; however, its role in preventing skeletal muscle cell aging is still unclear. This study aimed to elucidate the effects of fisetin on skeletal muscle aging using a d-galactose-induced C2C12 myoblast senescence model. Fisetin treatment effectively ameliorated d-galactose-induced aging damage and restored cellular functionality by improving cell viability, reducing the accumulation of the senescence marker enzyme SA-β-gal, and decreasing the expression of key aging marker proteins, p16 and p53. NMR-based metabolomics and RNA-seq transcriptomics analyses revealed that fisetin regulates several critical metabolic pathways, including glutathione metabolism, glycine, serine and threonine metabolism, as well as taurine and hypotaurine metabolism. This regulation led to the restoration of amino acid metabolism, stabilization of cellular energy homeostasis, and the preservation of membrane integrity. In addition, fisetin inhibited calcium signaling and JAK-STAT pathways, reduced cellular stress responses and reversed senescence-induced cell cycle arrest. Together, these findings highlight the potential of fisetin as a therapeutic agent to combat skeletal muscle aging and restore cellular homeostasis, offering a promising avenue for the development of antiaging treatments for skeletal muscle degeneration.PMID:39772754 | DOI:10.1021/acs.jproteome.4c00939

mSystems. 2025 Jan 7:e0003824. doi: 10.1128/msystems.00038-24. Online ahead of print.ABSTRACTInfectious disease treatment success requires symptom resolution (clinical treatment success), which often but not always involves pathogen clearance. Both of these treatment goals face disease-specific and general challenges. In this review, we summarize the current state of knowledge in mechanisms of clinical and parasitological treatment failure in the context of Chagas disease, a neglected tropical disease causing cardiac and gastrointestinal symptoms. Parasite drug resistance and persistence, drug pharmacokinetics and dynamics, as well as persistently altered host immune responses and tissue damage are the most common reasons for Chagas disease treatment failure. We discuss the therapeutics that failed before regulatory approval, limitations of current therapeutic options and new treatment strategies to overcome persistent parasites, inflammatory responses, and metabolic alterations. Large-scale omics analyses were critical in generating these insights and will continue to play a prominent role in addressing the challenges still facing Chagas disease drug treatment.PMID:39772644 | DOI:10.1128/msystems.00038-24

Anal Chem. 2025 Jan 7. doi: 10.1021/acs.analchem.4c04421. Online ahead of print.ABSTRACTThe integrative multiomics characterization of minute amounts of clinical tissue specimens has become increasingly important. Here, we present an approach called Integral-Omics, which enables sequential extraction of metabolites, lipids, genomic DNA, total RNA, proteins, and phosphopeptides from a single biopsy-level tissue specimen. We benchmarked this method with various samples, applied the workflow to perform multiomics profiling of tissues from six patients with colorectal cancer, and found that tumor tissues exhibited suppressed ferroptosis pathways at multiomics levels. Together, this study presents a methodology that enables sequential extraction and profiling of metabolomics, lipidomics, genomics, transcriptomics, proteomics, and phosphoproteomics using biopsy tissue specimens.PMID:39772508 | DOI:10.1021/acs.analchem.4c04421

Chem Res Toxicol. 2025 Jan 8. doi: 10.1021/acs.chemrestox.4c00449. Online ahead of print.ABSTRACTDeficiency of the V-domain immunoglobulin suppressor of T-cell activation (VISTA) accelerates disease progression in lupus-prone mice, and activation of VISTA shows therapeutic effects in mouse models of a lupus-like disease. Metabolic reprogramming of T cells in systemic lupus erythematosus (SLE) patients is important in regulating T-cell function and disease progression. However, the mechanism by which VISTA affects the immunometabolism in SLE remains unclear. Here, we demonstrated that the deficiency of VISTA promoted the synthesis of the metabolite lysophosphatidylcholine (LPC) using untargeted metabolomics and increased the protein expression of the CD40 ligand (CD40L). Furthermore, baloxavir marboxil (BXM), a small molecule agonist of VISTA, significantly ameliorated autoantibody production, renal damage, and imbalance of immune cell subpopulations in the models of a lupus-like disease in mice (chronic graft-versus-host disease and MRL/MpJ-Faslpr/J mice) possibly by inhibiting LPC synthesis to downregulate CD40L protein expression and inhibiting aberrant activation of noncanonical nuclear factor-κB pathway. Our results indicated that BXM targeting VISTA ameliorated lupus-like symptoms by altering lipid metabolism and CD40L expression, which offers novel mechanisms and a promising therapy for SLE.PMID:39772456 | DOI:10.1021/acs.chemrestox.4c00449

ACS Appl Mater Interfaces. 2025 Jan 8. doi: 10.1021/acsami.4c20503. Online ahead of print.ABSTRACTThyroid nodules are a very common entity. The overall prevalence in the populace is estimated to be around 65-68%, among which a small portion (less than 5%) is malignant (cancerous). Therefore, it is important to discriminate benign thyroid nodules from malignant thyroid nodules. In this study, an equal number of participants with benign and malignant thyroid nodules (N = 10/group) were recruited. Saliva samples were collected from each participant, and SERS spectra were acquired, followed by validation using a metabolomics approach. An additional equal number of patients (N = 40/group) were recruited to construct diagnostic models. The performance of various machine learning (ML) algorithms was assessed using multiple evaluation metrics. Finally, the reliability of the optimal model was tested using blind test data (N = 10/group for benign and malignant thyroid nodules). The results showed a consistent trend between the SERS metabolic profile and the metabolites identified through MS analysis. The Multi-ResNet algorithm was optimal, achieving a 95% accuracy in sample discrimination. Additionally, blind test data sets yielded an overall accuracy of 83%. In summary, the deep-learning-guided SERS technique holds great potential in the accurate discrimination of benign and malignant thyroid nodules via human saliva samples, which facilitates the noninvasive diagnosis of malignant thyroid nodules in clinical settings.PMID:39772412 | DOI:10.1021/acsami.4c20503

Vaccines (Basel). 2024 Dec 17;12(12):1421. doi: 10.3390/vaccines12121421.ABSTRACTFollowing the publication of paper [...].PMID:39772114 | DOI:10.3390/vaccines12121421

Plants (Basel). 2024 Dec 19;13(24):3554. doi: 10.3390/plants13243554.ABSTRACTRice sheath blight (RSB), caused by the pathogenic fungus Rhizoctonia solani, poses a significant threat to global food security. The defense mechanisms employed by rice against RSB are not well understood. In our study, we analyzed the interactions between rice and R. solani by comparing the phenotypic changes, ROS content, and metabolite variations in both tolerant and susceptible rice varieties during the early stages of fungal infection. Notably, there were distinct phenotypic differences in the response to R. solani between the tolerant cultivar Zhengdao22 (ZD) and the susceptible cultivar Xinzhi No.1 (XZ). We observed that the activities of five defense-related enzymes in both tolerant and susceptible cultivars changed dynamically from 0 to 72 h post-infection with R. solani. In particular, the activities of superoxide dismutase and peroxidase were closely associated with resistance to RSB. Metabolomic analysis revealed 825 differentially accumulated metabolites (DAMs) between the tolerant and susceptible varieties, with 493 DAMs responding to R. solani infection. Among these, lipids and lipid-like molecules, organic oxygen compounds, phenylpropanoids and polyketides, organoheterocyclic compounds, and organic acids and their derivatives were the most significantly enriched. One DAM, P-coumaraldehyde, which responded to R. solani infection, was found to effectively inhibit the growth of R. solani, Magnaporthe grisea, and Ustilaginoidea virens. Additionally, multiple metabolic pathways, including amino acid metabolism, carbohydrate metabolism, metabolism of cofactors and vitamins, and metabolism of terpenoids and polyketides, are likely involved in RSB resistance. Our research provides valuable insights into the molecular mechanisms underlying the interaction between rice and R. solani.PMID:39771252 | DOI:10.3390/plants13243554

Plants (Basel). 2024 Dec 17;13(24):3528. doi: 10.3390/plants13243528.ABSTRACTBlueberry plants are among the most important fruit-bearing shrubs, but they have shallow, hairless roots that are not conducive to water and nutrient uptake, especially under drought conditions. Therefore, the mechanism underlying blueberry root drought tolerance should be clarified. Hence, we established a yeast expression library comprising blueberry genes associated with root responses to drought stress. High-throughput sequencing technology enabled the identification of 1475 genes potentially related to drought tolerance. A subsequent KEGG enrichment analysis revealed 77 key genes associated with six pathways: carbon and energy metabolism, biosynthesis of secondary metabolites, nucleotide and amino acid metabolism, genetic information processing, signal transduction, and material transport and catabolism. Metabolomic profiling of drought-tolerant yeast strains under drought conditions detected 1749 differentially abundant metabolites (DAMs), including several up-regulated metabolites (organic acids, amino acids and derivatives, alkaloids, and phenylpropanoids). An integrative analysis indicated that genes encoding several enzymes, including GALM, PK, PGLS, and PIP5K, modulate key carbon metabolism-related metabolites, including D-glucose 6-phosphate and β-D-fructose 6-phosphate. Additionally, genes encoding FDPS and CCR were implicated in terpenoid and phenylalanine biosynthesis, which affected metabolite contents (e.g., farnesylcysteine and tyrosine). Furthermore, genes for GST and GLT1, along with eight DAMs, including L-γ-glutamylcysteine and L-ornithine, contributed to amino acid metabolism, while genes encoding NDPK and APRT were linked to purine metabolism, thereby affecting certain metabolites (e.g., inosine and 3',5'-cyclic GMP). Overall, the yeast functional screening system used in this study effectively identified genes and metabolites influencing blueberry root drought tolerance, offering new insights into the associated molecular mechanisms.PMID:39771226 | DOI:10.3390/plants13243528

Plants (Basel). 2024 Dec 14;13(24):3495. doi: 10.3390/plants13243495.ABSTRACTTo investigate the effects of different light qualities on the growth, photosynthesis, transcriptome, and metabolome of mint, three treatments were designed: (1) 7R3B (70% red light and 30% blue light, CK); (2) 7R3B+ far-red light (FR); (3) 7R3B+ ultraviolet light A (UVA). The results showed that supplemental FR significantly promoted the growth and photosynthesis of mint, as evidenced by the increase in plant height, plant width, biomass, effective quantum yield of PSII photochemistry (Fv'/Fm'), maximal quantum yield of PSII (Fv/Fm), and performance index (PI). UVA and CK exhibited minimal differences. Transcriptomic and metabolomic analysis indicated that a total of 788 differentially expressed genes (DEGs) and 2291 differential accumulated metabolites (DAMs) were identified under FR treatment, mainly related to plant hormone signal transduction, phenylpropanoid biosynthesis, and flavonoid biosynthesis. FR also promoted the accumulation of phenylalanine, sinapyl alcohol, methylchavicol, and anethole in the phenylpropanoid biosynthesis pathway, and increased the levels of luteolin and leucocyanidin in the flavonoid biosynthesis pathway, which may perhaps be applied in practical production to promote the natural antibacterial and antioxidant properties of mint. An appropriate increase in FR radiation might alter transcript reprogramming and redirect metabolic flux in mint, subsequently regulating its growth and secondary metabolism. Our study uncovered the regulation of FR and UVA treatments on mint in terms of growth, physiology, transcriptome, and metabolome, providing reference for the cultivation of mint and other horticultural plants.PMID:39771193 | DOI:10.3390/plants13243495

Plants (Basel). 2024 Dec 10;13(24):3459. doi: 10.3390/plants13243459.ABSTRACTThis study aims to reveal the interannual and seasonal variations in functional components in Polygonatum cyrtonema Hua. rhizomes and evaluate whether the variations significantly affect the quality of rhizomes as a traditional Chinese herbal medicine. The interannual and seasonal variations in total flavonoid content and total saponin content were analyzed. The global dynamic variation in secondary metabolites in the rhizomes during a five-year growth period and in two traditional harvesting seasons were investigated based on metabolomics method. Results clearly showed that the functional components in P. cyrtonema rhizomes exhibited a significant increase in accumulation during the one- to four-year growth period and a significant decrease in accumulation during the four- to five-year growth period. The most active accumulation occurred during the three- to four-year growth period. Drastic variations in functional components occurred from spring to autumn. The significant interannual variation and drastic seasonal variation were strongly associated with the enrichment in some pathways related to the biosynthesis of secondary metabolites and the metabolisms of amino acids. The interannual and seasonal variations in functional components significantly affected the quality of P. cyrtonema rhizomes. The four-year-old rhizomes had the most superior quality due to their higher content of functional components and much more newly formed components. The rhizomes harvested in spring or autumn had unequal quality because of their significant differences in composition and content of functional components. Specifically, the rhizomes from spring contained more flavonoids, alkaloids, and phenolic acids, while those from autumn comprised more steroids. In conclusion, this study reveals that the interannual and seasonal variations in functional components can significantly affect the quality of P. cyrtonema rhizomes as a traditional Chinese herbal medicine. This study provides foundational insights and theoretical guidance for determining an optimal cultivation period to obtain medicinal rhizomes with superior quality. It also offers a strategy for harvesting medicinal rhizomes in two different seasons to achieve unequal quality.PMID:39771157 | DOI:10.3390/plants13243459

Nutrients. 2024 Dec 17;16(24):4358. doi: 10.3390/nu16244358.ABSTRACTBACKGROUND/OBJECTIVES: Thus far, no studies have examined the relationship between fruit and vegetable (F and V) intake, urinary metabolite quantities, and weight change. Therefore, the aim of the current study was to explore changes in urinary metabolomic profiles during and after a 10-week weight loss intervention where participants were prescribed a high F and V diet (7 servings daily).METHODS: Adults with overweight and obesity (n = 34) received medical nutrition therapy counselling to increase their F and V intakes to national targets (7 servings a day). Data collection included weight, dietary intake, and urine samples at baseline at week 2 and week 10. Urinary metabolite profiles were quantified using 1H NMR spectroscopy. Machine learning statistical approaches were employed to identify novel urine-based metabolite biomarkers associated with high F and V diet patterns at weeks 2 and 10. Metabolic changes appearing in urine in response to diet were quantified using Metabolite Set Enrichment Analysis (MSEA).RESULTS: Energy intake was significantly lower (p = 0.02) at week 10 compared with baseline. Total F and V intake was significantly higher at week 2 and week 10 (p < 0.05). In total, 123 urinary metabolites were quantified. At week 10, 21 metabolites showed significant changes relative to baseline. Of these, 11 metabolites also significantly changed at week 2. These overlapping metabolites were acetic acid, dimethylamine, choline, fumaric acid, glutamic acid, L-tyrosine, histidine, succinic acid, uracil, histamine, and 2-hydroxyglutarate. Ridge Classifier and Linear Discriminant Analysis provided best prediction accuracy values of 0.96 when metabolite level of baseline was compared to week 10.CONCLUSIONS: Urinary metabolites quantified represent potential candidate biomarkers of high F and V intake, associated with a reduction in energy intake. Further studies are needed to validate these findings in larger population studies.PMID:39770979 | DOI:10.3390/nu16244358

Nutrients. 2024 Dec 13;16(24):4311. doi: 10.3390/nu16244311.ABSTRACTBACKGROUND: Caryopteris mongolica Bunge (CM) shows promising potential for managing rheumatoid arthritis (RA) and digestive disorders, attributed to its rich content of bioactive compounds such as polyphenols and flavonoids. Despite its common use in herbal tea, the specific mechanisms underlying CM's anti-inflammatory and joint-protective effects remain unclear, limiting its development as a functional food. This study investigated the effects of aqueous CM extract on RA in collagen-induced arthritis (CIA) rats and explored the underlying mechanisms.METHODS: Forty-eight female Sprague-Dawley rats were randomly assigned to six groups (n = 8): normal control, CIA model, methotrexate (MTX), and CM high-, middle-, and low-dose groups. Anti-inflammatory and joint-protective effects were evaluated using biochemical and histological analyses. To elucidate the mechanisms, we applied metabolomics, network pharmacology, and transcriptomics approaches.RESULTS: The results demonstrated that CM extract effectively suppressed synovial inflammation in CIA rats, reducing joint degradation. CM's anti-inflammatory effects were mediated through the TNF signaling pathway, modulating glycerophospholipid and amino acid metabolism, including reduced levels of tryptophan, LysoPC, and asparagine. Molecular docking identified scutellarin and apigenin as key bioactive compounds. Additionally, immunofluorescence analysis revealed CM's therapeutic effects via TNF signaling inhibition and suppression of M1 macrophage polarization.CONCLUSIONS: These findings highlight the therapeutic potential of CM for RA and support its development as a functional food or pharmaceutical product.PMID:39770932 | DOI:10.3390/nu16244311

Nutrients. 2024 Dec 12;16(24):4297. doi: 10.3390/nu16244297.ABSTRACTIMPORTANCE: Although prolonged fasting has become increasingly popular, the favourable biological adaptations and possible adverse effects in humans have yet to be fully elucidated.OBJECTIVE: To investigate the effects of a three-day water-only fasting, with or without exercise-induced glycogen depletion, on autophagy activation and the molecular pathways involved in cellular damage accumulation and repair in healthy humans.DESIGN: A randomised, single-centre, two-period, two-sequence crossover trial. The primary outcome is autophagic activity, assessed as flux in peripheral blood mononuclear cells (PBMCs) measured in the context of whole blood. Secondary outcomes include changes in body composition, heart rate variability, endothelial function, and genomic, epigenomic, metabolomic, proteomic, and metagenomic adaptations to fasting in plasma, platelets, urine, stools, and PBMCs. Detailed profiling of circulating immune cell populations and their functional states will be assessed by flow cytometry.SETTING: All clinical investigations will be undertaken at the Charles Perkins Centre Royal Prince Alfred Hospital clinic, University of Sydney, Australia.PARTICIPANTS: Twenty-four individuals aged 18 to 70 years, with a BMI of 20-40 kg/m2, free of major health conditions other than obesity.DISCUSSION: While autophagic flux induction through fasting has garnered interest, there is a notable lack of human studies on this topic. This trial aims to provide the most detailed and integrated analysis of how three days of prolonged water-only fasting, combined with glycogen-depleting exercise, affects autophagy activation and other crucial metabolic and molecular pathways linked to cellular, metabolic, and immune health. Insights from this study may pave the way for safe and effective strategies to induce autophagy, offering potential preventive interventions for a range of chronic conditions.PMID:39770918 | DOI:10.3390/nu16244297

Nutrients. 2024 Dec 11;16(24):4267. doi: 10.3390/nu16244267.ABSTRACTThe literature on the postprandial metabolic changes in individuals with Metabolic Syndrome (MetS) remains limited, despite the fact that postprandial states represent the most common physiological condition in Western societies.BACKGROUND/OBJECTIVES: The objective of this study was to investigate the plasma metabolomics profile in both fasting and postprandial states following a high-fat challenge in individuals with MetS who consumed diets with varying quantities and qualities of dietary fat over 12 weeks.METHODS: Seventy-five patients with MetS (28 males and 47 females) from the Spanish LIPGENE cohort were included in the study. MetS patients were randomly stratified to follow one of four dietary interventions (isoenergetic diets) for a 12-week long-term study. The four diets were high in saturated fatty acids and high in monounsaturated fatty acids (HSFA and HMUFA), low-fat high-complex carbohydrates (LFHCC), and LFHCC supplemented with n-3. The metabolomics analysis of plasma samples was carried out using Liquid Chromatography Time-of-Flight Mass Spectrometry (LC-TOF/MS).RESULTS: We observed a decrease in inflammation biomarkers, including acetylcarnitine and L-carnitine during the fasting state and hexanoyl-L-carnitine and isobutyryl-L-carnitine during the postprandial period, mediated by the replacement of HSFA with HMUFA. Additionally, antioxidant compounds such as 4-hydroxybenzaldehyde and L-valine were expressed at higher levels after consumption of the HMUFA diet compared to the HSFA diet. HSFA also presented altered levels of phosphatidylcholine, a metabolite previously linked with insulin resistance.CONCLUSIONS: These findings suggest that replacing HSFA with HMUFA may reduce inflammation and improve antioxidant profiles, supporting the potential for tailored dietary interventions in individuals with MetS.PMID:39770889 | DOI:10.3390/nu16244267

Microorganisms. 2024 Dec 4;12(12):2499. doi: 10.3390/microorganisms12122499.ABSTRACTLaboratory mice are instrumental for preclinical research but there are serious concerns that the use of a clean standardized environment for specific-pathogen-free (SPF) mice results in poor bench-to-bedside translation due to their immature immune system. The aim of the present study was to test the importance of the gut microbiota in wild vs. SPF mice for evaluating host immune responses in a house-dust-mite-induced allergic airway inflammation model without the influence of pathogens. The wild mouse microbiome reduced histopathological changes and TNF-α in the lungs and serum when transplanted to microbiota-depleted mice compared to mice transplanted with the microbiome from SPF mice. Moreover, the colonic gene expression of Gata3 was significantly lower in the wild microbiome-associated mice, whereas Muc1 was more highly expressed in both the ileum and colon. Intestinal microbiome and metabolomic analyses revealed distinct profiles associated with the wild-derived microbiome. The wild-mouse microbiome thus partly reduced sensitivity to house-dust-mite-induced allergic airway inflammation compared to the SPF mouse microbiome, and preclinical studies using this model should consider using both 'dirty' rewilded and SPF mice for testing new therapeutic compounds due to the significant effects of their respective microbiomes and derived metabolites on host immune responses.PMID:39770703 | DOI:10.3390/microorganisms12122499

Microorganisms. 2024 Dec 2;12(12):2483. doi: 10.3390/microorganisms12122483.ABSTRACTPreeclampsia (PE) is a serious complication of pregnancy linked to endothelial dysfunction and an imbalance in the gut microbiota. While Akkermansia muciniphila (AKK) has shown promise in alleviating PE symptoms, the use of live bacteria raises safety concerns. This study explored the potential of pasteurized A. muciniphila (pAKK) as a safer alternative for treating PE, focusing on its effects on endothelial function and metabolic regulation. A PE mouse model was induced via the nitric oxide synthase inhibitor L-NAME, followed by treatment with either pAKK or live AKK. Fecal metabolomic profiling was performed via liquid chromatography-tandem mass spectrometry (LC-MS/MS), and in vivo and in vitro experiments were used to assess the effects of pAKK on endothelial function and metabolic pathways. pAKK exhibited therapeutic effects comparable to those of live AKK in improving L-NAME-induced PE-like phenotypes in mice, including enhanced gut barrier function and reduced endotoxemia. pAKK also promoted placental angiogenesis by restoring endothelial nitric oxide synthase (eNOS) activity and nitric oxide (NO) production. The in vitro experiments further confirmed that pAKK alleviated L-NAME-induced NO reduction and endothelial dysfunction in human umbilical vein endothelial cells (HUVECs). Metabolomic analysis revealed that both pAKK and live AKK reversed metabolic disturbances in PE by modulating key metabolites and pathways related to unsaturated fatty acid biosynthesis, folate, and linoleic acid metabolism. As a postbiotic, pAKK may support existing treatments for preeclampsia by improving gut barrier function, restoring endothelial function, and regulating metabolic dysregulation, offering a safer alternative to live bacteria. These findings highlight the potential clinical value of pAKK as an adjunctive therapy in managing PE.PMID:39770686 | DOI:10.3390/microorganisms12122483

Microorganisms. 2024 Nov 25;12(12):2413. doi: 10.3390/microorganisms12122413.ABSTRACTAntimicrobial resistance is becoming a critical issue due to the widespread and indiscriminate use of antibiotics and antifungals to treat common infections, leading to a growing shortage of effective drugs. Moreover, the increase in antimicrobial resistance is enhancing the pathogenicity and virulence of various pathogens. Microorganisms are key sources of chemically diverse specialized metabolites, which are produced in the final stages of their growth cycle. These metabolites hold significant value in chemical, pharmaceutical, and agrochemical industries. One of the major challenges researchers face in this field is the frequent isolation of already-known substances when classical protocols are used. To address this, several innovative strategies have been developed. The co-culture approach is a powerful tool for activating silent biosynthetic gene clusters, as it simulates natural microbial environments by creating artificial microbial communities. This method has shown promising results, with new compounds being isolated and the yields of target substances being improved. In this context, this review provides examples of antimicrobial compounds obtained from co-cultures of endophytic fungi, conducted in both liquid and solid media. Additionally, the review discusses the advantages and challenges of the co-culture technique. Significance and Impact of the Study: Microbial co-culture is a valuable strategy for discovering new natural products with antimicrobial activity, as well as for scaling up the production of target substances. This review aims to summarize important examples of endophyte co-cultures and highlights the potential of endophytic fungi co-culture for pharmacological applications.PMID:39770616 | DOI:10.3390/microorganisms12122413

Microorganisms. 2024 Nov 22;12(12):2396. doi: 10.3390/microorganisms12122396.ABSTRACTRotavirus (RV) is a significant contributor to diarrhea in both young children and animals, especially in piglets, resulting in considerable economic impacts on the global pig industry. Isoleucine (Ile), a branched-chain amino acid, is crucial for regulating nutrient metabolism and has been found to help mitigate diarrhea. This study aimed to assess the impact of isoleucine supplementation in feed on colonic barrier function, colonic microbiota, and metabolism in RV-infected weanling piglets. A total of thirty-two weaned piglets, aged 21 days, were randomly assigned to two dietary groups (each further divided into two subgroups, with eight replicates in each subgroup), receiving diets with either 0% or 1% isoleucine for a duration of 14 days. One group from each treatment was then challenged with RV, and the experimental period lasted for 19 days. The results showed that dietary Ile significantly increased the secretion of IL-4, IL-10, and sIgA in the colon of RV-infected weanling piglets (p < 0.05). In addition, Ile supplementation notably increased the expression of tight junction proteins, including Claudin-3, Occludin, and ZO-1 (p < 0.01), as well as the mucin protein MUC-1 in the colon of RV-infected weanling piglets (p < 0.05). Gut microbiota analysis revealed that dietary Ile increased the relative abundance of Prevotella and decreased the relative abundance of Rikenellaceae in the colons of RV-infected weanling piglets. Compared with the RV+CON, metabolic pathways in the RV+ILE group were significantly enriched in vitamin digestion and absorption, steroid biosynthesis, purine metabolism, pantothenate and CoA biosynthesis, cutin, suberine, and wax biosynthesis, as well as fatty acid biosynthesis, and unsaturated fatty acid biosynthesis. In conclusion, dietary Ile supplementation can improve immunity, colonic barrier function, colonic microbiota, and colonic metabolism of RV-infected weaned piglets. These findings provide valuable insights into the role of isoleucine in the prevention and control of RV.PMID:39770598 | DOI:10.3390/microorganisms12122396