PubMed

Front Microbiol. 2024 Jul 3;15:1435503. doi: 10.3389/fmicb.2024.1435503. eCollection 2024.ABSTRACTINTRODUCTION: Streptococcus mutans was the primary pathogenic organism responsible for dental caries. Lonicera japonica flos (LJF) is a traditional herb in Asia and Europe and consumed as a tea beverage for thousands of years.METHODS: The inhibitory effect and mechanism of LJF on biofilm formation by S. mutans was investigated. The active extracts of LJF were validated for their inhibitory activity by examining changes in surface properties such as adherence, hydrophobicity, auto-aggregation abilities, and exopolysaccharides (EPS) production, including water-soluble glucan and water-insoluble glucan.RESULTS AND DISCUSSION: LJF primarily inhibited biofilm formation through the reduction of EPS production, resulting in alterations in cell surface characteristics and growth retardation in biofilm formation cycles. Integrated transcriptomic and untargeted metabolomics analyses revealed that EPS production was modulated through two-component systems (TCS), quorum sensing (QS), and phosphotransferase system (PTS) pathways under LJF stress conditions. The sensing histidine kinase VicK was identified as an important target protein, as LJF caused its dysregulated expression and blocked the sensing of autoinducer II (AI-2). This led to the inhibition of response regulator transcriptional factors, down-regulated glycosyltransferase (Gtf) activity, and decreased production of water-insoluble glucans (WIG) and water-soluble glucans (WSG). This is the first exploration of the inhibitory effect and mechanism of LJF on S. mutans, providing a theoretical basis for the application of LJF in functional food, oral health care, and related areas.PMID:39027105 | PMC:PMC11256199 | DOI:10.3389/fmicb.2024.1435503

bioRxiv [Preprint]. 2024 Jul 13:2024.07.10.601875. doi: 10.1101/2024.07.10.601875.ABSTRACTAnnotating compounds with high confidence is a critical element in metabolomics. 13 C-detection NMR experiment INADEQUATE (incredible natural abundance double-quantum transfer experiment) stands out as a powerful tool for structural elucidation, whereas this valuable experiment is not often included in metabolomics studies. This is partly due to the lack of community platform that provides structural information based INADEQUATE. Also, it is often the case that a single study uses various NMR experiments synergistically to improve the quality of information or balance total NMR experiment time, but there is no public platform that can integrate the outputs of INADEQUATE and other NMR experiments either. Here, we introduce PyINETA, Python-based INADEQUATE network analysis. PyINETA is an open-source platform that provides structural information of molecules using INADEQUATE, conducts database search, and integrates information of INADEQUATE and a complementary NMR experiment 13 C J -resolved experiment ( 13 C-JRES). Those steps are carried out automatically, and PyINETA keeps track of all the pipeline parameters and outputs, ensuring the transparency of annotation in metabolomics. Our evaluation of PyINETA using a model mouse study showed that our pipeline successfully integrated INADEQUATE and 13 C-JRES. The results showed that 13 C-labeled amino acids that were fed to mice were transferred to different tissues, and, also, they were transformed to other metabolites. The distribution of those compounds was tissue-specific, showing enrichment of particular metabolites in liver, spleen, pancreas, muscle, or lung. The value of PyINETA was not limited to those known compounds; PyINETA also provided fragment information for unknown compounds. PyINETA is available on NMRbox.PMID:39026850 | PMC:PMC11257532 | DOI:10.1101/2024.07.10.601875

bioRxiv [Preprint]. 2024 Jul 13:2024.07.13.603378. doi: 10.1101/2024.07.13.603378.ABSTRACTPseudomonas aeruginosa (PA), an opportunistic gram-negative pathogen, is the most common pathogen identified in all culture positive cases of infectious keratitis. Extracellular vesicles (EVs) are released by most cells in the body and function in intercellular communication. We have previously reported a change in the proteome of host-derived EVs from corneal epithelial cells during PA infection. In the present study, we investigated changes in the metabolome of host-derived EVs from PA infected (PA-C EVs) and non-infected cells (C EVs). We found that one metabolite, palmitoyl carnitine (PAMC), was significantly upregulated in PA-C EVs. To determine the significance of PAMC release, we investigated the effect of PAMC treatment on corneal epithelial cells and neutrophils. EVs were isolated from culture media using size exclusion chromatography. EVs were then characterized using nanoparticle tracking analysis, transmission electron microscopy, and western blot. Metabolomics was performed using an untargeted approach. We found that palmitoyl carnitine (PAMC) was the most abundant metabolite present in PA-C EVs and was increased more than 3 fold compared to C EVs. Treatment of corneal epithelial cells with increasing levels of PAMC increased nuclear translocation of the NF-κB subunit p65. This was associated with an increase in IL-8 production and neutrophil migration. PAMC also increased levels of mitochondrial calcium. Upon inoculation of corneal epithelial cells with PA, 50 μM PAMC completely eradicated intracellular PA, but stimulated growth of extracellular PA. Taken together, these findings suggest that PA exploits EV release by host cells to deplete PAMC from the intracellular environment.PMID:39026691 | PMC:PMC11257627 | DOI:10.1101/2024.07.13.603378

Front Immunol. 2024 Jul 4;15:1424332. doi: 10.3389/fimmu.2024.1424332. eCollection 2024.ABSTRACTBACKGROUND: The protective role of gut microbiota and its metabolites against intestinal damage in sepsis patients remain unclear.METHODS: Fecal samples were acquired from patients categorized into sepsis and non-sepsis groups for analysis of microbial composition via 16S rRNA sequencing and untargeted metabolomics analysis. We assessed the impact of gut microbiota from sepsis patients on intestinal barriers in antibiotic-treated mice. Furthermore, We conducted spearman's correlation analysis to examine the relationship between metabolites and the severity of sepsis. Additionally, we performed animal experiments to validate the functionality of identified metabolites.RESULTS: The diversity of intestinal flora is decreased in patients with sepsis compared to the control group. Through fecal microbiota transplantation experiments, it was discovered that the gut microbiota derived from sepsis patients could induce intestinal damage in antibiotic-treated mice. Metabolomics analysis of the microbiota revealed a significant enrichment of the Valine, leucine, and isoleucine biosynthesis pathway. Further analysis showed a significant decrease in the abundance of L-valine in sepsis patients, which was negatively correlated with APACHE-II and SOFA scores. In sepsis mouse experiments, it was found that L-valine could alleviate sepsis-induced intestinal damage.CONCLUSION: Alterations in microbial and metabolic features in the gut can affect the severity of sepsis. Furthermore, L-valine can protect against sepsis-induced intestinal injury.PMID:39026673 | PMC:PMC11254637 | DOI:10.3389/fimmu.2024.1424332

RSC Med Chem. 2024 Apr 11;15(7):2286-2299. doi: 10.1039/d4md00057a. eCollection 2024 Jul 17.ABSTRACTSeveral scientific evidences report that a central role in the pathogenesis of Alzheimer's disease is played by the deposition of insoluble aggregates of β-amyloid proteins in the brain. Because Aβ is self-assembling, one possible design strategy is to inhibit the aggregation of Aβ peptides using short peptide fragments homologous to the full-length wild-type Aβ protein. In the past years, several studies have reported on the synthesis of some short synthetic peptides called β-sheet breaker peptides (BSBPs). Herein, we present the synthesis of novel (cell-permeable) N-methyl BSBPs, designed based on literature information on the structural key features of BSBPs. Three-dimensional GRID-based pharmacophore peptide screening combined with PT-WTE metadynamics was performed to support the results of the design and microwave-assisted synthesis of peptides 2 and 3 prepared and analyzed for their fibrillogenesis inhibition activity and cytotoxicity. An HR-MS-based cell metabolomic approach highlighted their cell permeability properties.PMID:39026638 | PMC:PMC11253850 | DOI:10.1039/d4md00057a

Clin Exp Emerg Med. 2024 Jul 19. doi: 10.15441/ceem.24.211. Online ahead of print.ABSTRACTSepsis accounts for high cases of morbidity and mortality in hospitalized patients. It has a very complex pathophysiology and swiftly progresses to a severe form of the disease, such as septic shock leading to organ dysfunction, organ failure, and death. Metabolomics has transformed sepsis's clinical and research topography with its application in prognosis, diagnosis, and risk assessment in patients with sepsis and septic shock. Metabolites in blood and urine are detected and analyzed, which helps in understanding the pathogenesis of the disease and aid in better disease management by identifying biomarkers early on. Metabolomics, sepsis and septic shock were the keywords were searched in PubMed and Scopus, from its inception to Dec 2023. This article provides information regarding metabolic profiling performed in sepsis and septic shock We demonstrated that metabolomics will change the world of sepsis by analyzing and detecting the diagnosis, prognosis, mortality, and treatment response biomarkers.PMID:39026452 | DOI:10.15441/ceem.24.211

J Nutr Biochem. 2024 Jul 16:109703. doi: 10.1016/j.jnutbio.2024.109703. Online ahead of print.ABSTRACTSestrin2 is a highly conserved protein that can be induced under various stress conditions. Researches have revealed that the signaling pathway of the mammalian target of rapamycin (mTOR) is essential in modulating both glucose and lipid metabolism. However, the precise involvement of Sestrin2 in the hypothalamus, particularly in pro-opiomelanocortin (POMC) neurons, in control of energy homeostasis remains uncertain. In this study, we aimed to investigate the functional role of Sestrin2 in hypothalamic POMC neurons in regulation of energy balance, as well as revealing the underlying mechanisms. Therefore, Cre-dependent AAV virus encoding or silencing Sestrin2 was injected into the hypothalamic ARC of Pomc-cre transgenic mice. The results demonstrated that Sestrin2 overexpression in POMC neurons ameliorated high-fat diet (HFD)-induced obesity and increased energy expenditure. Conversely, Sestrin2 deficiency in POMC neurons predisposed mice to HFD induced obesity. Additionally, the thermogenesis of brown adipose tissue and lipolysis of inguinal white adipose tissue were both enhanced by the increased sympathetic nerve innervation in Sestrin2 overexpressed mice. Further exploration revealed that Sestrin2 overexpression inhibited the mTOR signaling pathway in hypothalamic POMC neurons, which may account for the alleviation of systematic metabolic disturbance induced by HFD in these mice. Collectively, our findings demonstrate that Sestrin2 in POMC neurons plays a pivotal role in maintaining energy balance in a context of HFD-induced obesity by inhibiting the mTOR pathway, providing new insights into how hypothalamic neurons respond to nutritional signals to protect against obesity-associated metabolic dysfunction.PMID:39025457 | DOI:10.1016/j.jnutbio.2024.109703

J Biol Chem. 2024 Jul 16:107582. doi: 10.1016/j.jbc.2024.107582. Online ahead of print.ABSTRACTThe Ccr4-Not complex contains the poorly understood Not4 ubiquitin ligase that functions in transcription, mRNA decay, translation, proteostasis, and endolysosomal nutrient signaling. To gain further insight into the in vivo functions of the ligase, we performed quantitative proteomics in Saccharomyces cerevisiae using yeast cells lacking Not4, or cells overexpressing wild-type Not4 or an inactive Not4 mutant. Herein, we provide evidence that balanced Not4 activity maintains ribosomal protein (RP) homeostasis independent of changes to RP mRNA or known Not4 ribosomal substrates. Intriguingly, we also find that Not4 loss activates 40S ribosomal autophagy independently of canonical Atg7-dependent macroautophagy, indicating that microautophagy is responsible. We previously demonstrated that Ccr4-Not stimulates target of rapamycin complex 1 (TORC1) signaling, which activates RP expression and inhibits autophagy, by maintaining vacuole V-ATPase H+ pump activity. Importantly, combining Not4 deficient cells with a mutant that blocks vacuole H+ export fully restores RP expression and increases 40S RP autophagy efficiency. In contrast, restoring TORC1 activity alone fails to rescue either process, indicating that Not4 loss disrupts additional endolysosomal functions that regulate RP expression and 40S autophagy. Analysis of the Not4 regulated proteome reveals increases in endolysosomal and autophagy-related factors that functionally interact with Not4 to control RP expression and affect 40S autophagy. Collectively, our data indicate that balanced Ccr4-Not ubiquitin ligase signaling maintains RP homeostasis and inhibits 40S autophagy via the ligase's emerging role as an endolysosomal regulator.PMID:39025453 | DOI:10.1016/j.jbc.2024.107582

Biochem Pharmacol. 2024 Jul 16:116435. doi: 10.1016/j.bcp.2024.116435. Online ahead of print.ABSTRACTAcute kidney injury (AKI) is one of the most serious complications of cisplatin anticancer therapies. Cilastatin is a highly promising nephroprotective agent to eventually enter clinical use, but its biochemical mechanism is still not fully understood. We have employed an untargeted metabolomics approach based on capillary electrophoresis mass spectrometry (CE-MS) analysis of serum and urine from an in vivo rat model, to explore the metabolic pathways involved in cisplatin-induced AKI and cilastatin nephroprotection. A total of 155 and 76 identified metabolites were found to be significantly altered during cisplatin treatment in urine and serum, respectively. Most of these altered metabolites were either partially or totally recovered by cilastatin and cisplatin co-treatment. The main metabolic pathways disturbed by cisplatin during AKI involved diverse amino acids metabolism and biosynthesis, tricarboxylic acids (TCA) cycle, nicotinate and nicotinamide metabolism, among others. Cilastatin was proved to protect diverse cisplatin-altered pathways involving metabolites related to immunomodulation, inflammation, oxidative stress and amino acid metabolism in proximal tubules. However, cisplatin-altered mitochondrial metabolism (especially, the energy-producing TCA cycle) remained largely unprotected by cilastatin, suggesting an unresolved mitochondrial direct damage. Multivariate analysis allowed effective discrimination of cisplatin-induced AKI and cilastatin renoprotection based on metabolic features. A number of potential serum and urine biomarkers could also be foreseen for cisplatin-induced AKI detection and cilastatin nephroprotection.PMID:39025411 | DOI:10.1016/j.bcp.2024.116435

Gene. 2024 Jul 16:148772. doi: 10.1016/j.gene.2024.148772. Online ahead of print.ABSTRACTCumulus cells play a crucial role in the oocyte growth and maturation processes through providing necessary nutrients and growth signals by gap junction communication. However, a global overview of metabolic events in goat cumulus cells is still lacking. In the present study, we collected cumulus cells from goat cumulus-oocyte complexes (COCs) at different developmental stages. Metabolomics analysis was performed to investigate the global metabolic patterns in cumulus cells during oocyte in vitro maturation. In particular, we revealed the several significantly altered metabolic pathways and metaboliccharacteristics in goat cumulus cells, including the accumulation of fatty acids, steroid hormones metabolism, active catabolism of arginine during meiotic resumption, and a progressive decline in nucleotide metabolism. In conclusion, the dataset generated by our metabolomic profiling will provide valuable information to understand the key metabolic pathways and metabolites involved in COCs development.PMID:39025339 | DOI:10.1016/j.gene.2024.148772

Ann Vasc Surg. 2024 Jul 16:S0890-5096(24)00426-6. doi: 10.1016/j.avsg.2024.05.037. Online ahead of print.ABSTRACTOBJECTIVES: This pilot study aimed to investigate the association between the single nucleotide polymorphism (SNP) rs3918226 in the promoter of the nitric oxide synthase (NOS3) gene and the risk of peripheral artery disease (PAD).METHODS: DNA samples from 1263 unrelated subjects of Slavic origin, including 620 patients with PAD and 643 controls, were genotyped for the SNP rs3918226 using the MassArray-4 system.RESULTS: The rs3918226 polymorphism was found to be strongly associated with an increased risk of PAD regardless of coronary artery disease, hypertension, or cigarette smoking (OR=2.86, 95%CI 1.89-4.32, Pperm<0.0001). The SNP-PAD association was in almost three times stronger in females (OR=8.31 95%CI 3.07-22.48) than in males (OR=1.79 95%CI 1.10-2.93). SNP rs3918226 was correlated with ankle brachial index (ABI) and total plasma cholesterol in patients with PAD (Рperm<0.05). The NOS3 polymorphism was closely associated with SNPs rs7692387 and rs13139571 in GUCY1A3 to determine the risk of PAD, suggesting that the rs3918226 polymorphism may disrupt signaling in the nitric oxide-soluble guanylyl cyclase pathway. Diplotypes with wild-type alleles, such as NOS3 rs3918226-C/C×GUCY1A1 rs7692387G/G and NOS3 rs3918226-C/C×GUCY1A1 rs13139571C/C, showed strong protection against disease risk (FDR≤0.001). Functional SNP annotation revealed that the allele rs3918226-T was associated with decreased expression of NOS3, most strongly in the tibial arteries than in the coronary artery or aorta.CONCLUSIONS: The present study is the first to show that the rs3918226 polymorphism of NOS3 is a novel susceptibility marker for peripheral artery disease. Further research in independent populations is necessary to reproduce the association between polymorphism rs3918226 and disease risk.PMID:39025213 | DOI:10.1016/j.avsg.2024.05.037

Animal. 2024 Jun 20;18(8):101224. doi: 10.1016/j.animal.2024.101224. Online ahead of print.ABSTRACTThe low-birth-weight of piglets is an important factor affecting pig enterprises. The placenta, as a key organ for material exchange between mother and foetus, directly influences the growth and development of the foetus. Allicin exhibits various biological activities, including anti-inflammatory and antioxidant properties. It may also play a crucial role in enhancing sow reproductive performance and placental angiogenesis. In this study, we used 70 lactating Landrace × Yorkshire binary heterozygous sows to explore the effect of allicin on the reproductive performance of sows and placental development. The sows were randomly assigned into the Allicin group (Allicin), which was fed with a diet containing 0.25% allicin, and the negative control group, which was fed with basal feed. The experimental period lasted for 114 d from the date of mating to the end of farrowing. The results showed that the addition of allicin to the gestation diets increased the number of total born piglets, born alive piglets, and high-birth-weight piglets, reduced peripartum oxidative stress, alleviated dysregulation of glucose-lipid metabolism in sows, and increased the levels of antioxidant markers in the placenta. Differential analysis of metabolites in maternal plasma and placenta samples by non-targeted metabolomics revealed that allicin improved cholesterol metabolism, steroid biosynthesis, and increased plasma progesterone levels in sows. Allicin promoted sulphur metabolism, cysteine and methionine metabolism in placental samples and increased the hydrogen sulphide (H2S) content in the placenta. In addition, Quantitative Real-time PCR, Western blot and immunofluorescence results showed that allicin upregulated the expression of angiogenesis-related genes, VEGF-A, FLK 1 and Ang 1, in the placenta, implying that it promoted placental angiogenesis. These results indicate that supplementing the diet of pregnant sows with allicin reduces oxidative stress, alleviates dysregulation of glucose-lipid metabolism during the periparturient period, and promotes placental angiogenesis and foetal development by increasing plasma progesterone level and placental H2S content.PMID:39024999 | DOI:10.1016/j.animal.2024.101224

Ecotoxicol Environ Saf. 2024 Jul 17;282:116734. doi: 10.1016/j.ecoenv.2024.116734. Online ahead of print.ABSTRACTHepatic diseases pose a significant threat to community health, impacting the quality of life and longevity of millions worldwide. Despite revolutionary advancements in treatment, liver diseases remain a pressing issue, necessitating the development of more effective therapeutic approaches. Here, we conducted a comprehensive multi-omics analysis to investigate the underlying mechanism of Swertiamarin in alleviating hepatic injuries induced by CCl4 in mice. We divided 100 Kunming mice into five groups: RC (control), RM (CCl4), RD (15 mg/Kg Swertiamarin), RZ (30 mg/Kg Swertiamarin), and RG (60 mg/Kg Swertiamarin). Animals in groups RD, RZ, and RG received daily Swertiamarin via gavage, while those in groups RM, RD, RZ, and RG were treated with CCl4 solution intraperitoneally every four days, nine times in total. Our findings revealed that mice in the RM group exhibited slightly lower average weights compared to other groups, along with significantly higher liver weight (p<0.0001) and liver index (p<0.0001). Pathological analysis indicated liver damage characterized by cell degeneration, inflammatory cell infiltration, and hepatic fibrosis in the CCl4-induced group. In contrast, Swertiamarin supplementation mitigated these effects, reducing denatured cells, inflammatory cells, and collagenous fibers in the liver. Serum analysis showed elevated levels of TNF-α (p<0.001), IL-6 (p<0.05), ALT (p<0.001), AST (p<0.0001), MDA (p<0.001), and Hyp (p<0.001) in CCl4-induced animals, along with lower levels of T-AOC (p<0.001), GSH-px (p<0.0001), SOD (p<0.001), and CAT (p<0.01). Microbiome analysis revealed significant differences among groups, with pathogenic taxa such as Arthrinium and Aureobasidium, and probiotic Saccharomyces showing notable variations. Metabolomics analysis identified numerous differentially abundant metabolites, with Swertiamarin-treated animals exhibiting distinct profiles. Our findings highlight the potential of Swertiamarin ameliorating CCl4-induced liver toxicity through modulation of antioxidant capacity, inflammatory response, gut microbiota, and metabolites. These insights may inform the development of novel therapies for liver injury.PMID:39024951 | DOI:10.1016/j.ecoenv.2024.116734

Food Chem. 2024 Jul 11;459:140433. doi: 10.1016/j.foodchem.2024.140433. Online ahead of print.ABSTRACTOolong tea, a semi-fermented tea, has a prominent fruity and floral aroma, resembling green tea's astringency and pungency but lacking black tea's mellowness. Oolong tea incorporating black tea fermentation techniques (OT-IBTFT) not only retained its excellent floral and fruity aroma but also reduced astringency and enriched taste. However, metabolite changes remain unknown. In this study, widely targeted metabolomic analysis showed OT-IBTFT reduced prunin, gallocatechin, methyl gallate, and increased loliolide by changing the flavonoid biosynthesis and biosynthesis of secondary metabolites pathways, thereby reducing the astringency and increasing the mellow taste and richness to improve oolong tea quality. In addition, Wrap-rolling 5 times increased fermentation, improving the color and aroma of oolong tea by increasing theaflavic acid and 2-furoic acid, is more significant than wrap-rolling once. In conclusion, these findings provide a theoretical basis for the improvement of oolong tea processing techniques and flavor and quality control.PMID:39024882 | DOI:10.1016/j.foodchem.2024.140433

Food Chem. 2024 Jul 1;460(Pt 1):140308. doi: 10.1016/j.foodchem.2024.140308. Online ahead of print.ABSTRACTEffect of part differences on metabolite molecule alterations in refrigerated pork was investigated. A metabolomics methodology combined with chemometric analysis was successfully established to identify key compounds and their conversion pathways, including precursors and volatile metabolites, in the Longissimus lumborum as well as the breast and flank stored for 11 days. In total, 12 discriminative precursors were identified using the Short Time-series Expression Miner. In tandem with Random Forest and ANOVA analyses, nine volatile metabolites were identified as key compounds that could be attributed to differences in pork sections. Bidirectional orthogonal partial least squares analysis revealed a potential correlation between these key metabolites and discriminative precursors. Metabolic pathway enrichment analysis demonstrated that the primary metabolic process affected by variations in pork sections is linoleic acid metabolism, which participates in the metabolism of cysteine and glutamic acid to produce methoxy-phenyl-oxime. This study provides valuable insights into the identification of differential metabolites.PMID:39024809 | DOI:10.1016/j.foodchem.2024.140308

J Pharm Biomed Anal. 2024 Jul 16;249:116368. doi: 10.1016/j.jpba.2024.116368. Online ahead of print.ABSTRACTIn this study, we first screened and evaluated the inhibitory effects of seven medicinal fungi on diseases such as hyperuricemia (HUA). Then, using metabolomics and gut microbiome methods, the focus was on analyzing and evaluating the effects of the aqueous extract of Cordyceps. militaris (CME) and cordycepin on potassium oxyzinate induced HUA mice. It was found that CME exhibits good uric acid lowering activity in both in vivo and in vitro experiments. It can relieve hyperuricemia by inhibiting xanthine oxidase enzyme activity, reducing the production of xanthine precursors, and inhibiting insulin resistance. The uric acid-lowering efficacy of cordycepin in vivo is comparable to that of CME. The species abundance of Oscillibacter, Alistipes, Prevotellaaceae_NK3B31, Lachnospiraceae_NK4A136 were decreased after treatment with CME and cordycepin. The metabolomics analysis of cecal contents and fecal samples elucidated the mechanism of intervention of CME on hyperuricemia from different perspectives. This suggests that we should consider carefully when selecting samples. This current research provides the scientific foundation for the medicinal research of C. militaris and the maintenance of human health.PMID:39024793 | DOI:10.1016/j.jpba.2024.116368

Poult Sci. 2024 Jun 23;103(9):103976. doi: 10.1016/j.psj.2024.103976. Online ahead of print.ABSTRACTPekin ducks and Shaoxing ducks are 2 Chinese local duck breeds, both domesticated from mallard, but after domestication and long-term artificial selection, the body weight of Pekin ducks is significantly higher than that of Shaoxing ducks. It is no debate that genetic factors are the main factors responsible for this difference, but whether intestinal microbiota contribute to this difference is yet unknown. Thus, we performed comparative intestinal metagenomics and metabolomics analysis between Pekin ducks and Shaoxing ducks. We found obvious differentiation of intestinal metagenome and metabolome between the 2 breeds. Four cecal microbial genera, including Fusobacterium, Methanobrevibacter, Butyricicoccus, and Anaerotignum showed higher abundance in Pekin ducks. Among them, Methanobrevibacter and Butyricicoccus may positively correlate with fat deposition and body weight. A total of 310 metabolites showed difference between the 2 breeds. Functions of these differential metabolites were mainly enriched in amino acid metabolism, including energy metabolism-related histidine metabolism. Integrated omics analysis showed that microbial changes were closely related to altered metabolites. Especially, Butyricicoccus showing higher abundance in Pekin ducks was significantly negatively correlated with D-glucosamine-6-phosphate, which has been reported to prevent body weight gains. These findings may contribute to further understand the difference in body weight between Pekin ducks and Shaoxing ducks.PMID:39024692 | DOI:10.1016/j.psj.2024.103976

BMC Med. 2024 Jul 19;22(1):302. doi: 10.1186/s12916-024-03516-7.ABSTRACTBACKGROUND: The prevalence of autism in Denmark has been increasing, reaching 1.65% among 10-year-old children, and similar trends are seen elsewhere. Although there are several factors associated with autism, including genetic, environmental, and prenatal factors, the molecular etiology of autism is largely unknown. Here, we use untargeted metabolomics to characterize the neonatal metabolome from dried blood spots collected shortly after birth.METHODS: We analyze the metabolomic profiles of a subset of a large Danish population-based cohort (iPSYCH2015) consisting of over 1400 newborns, who later are diagnosed with autism and matching controls and in two Swedish population-based cohorts comprising over 7000 adult participants. Mass spectrometry analysis was performed by a timsTOF Pro operated in QTOF mode, using data-dependent acquisition. By applying an untargeted metabolomics approach, we could reproducibly measure over 800 metabolite features.RESULTS: We detected underlying molecular perturbations across several metabolite classes that precede autism. In particular, the cyclic dipeptide cyclo-leucine-proline (FDR-adjusted p = 0.003) and the carnitine-related 5-aminovaleric acid betaine (5-AVAB) (FDR-adjusted p = 0.03), were associated with an increased probability for autism, independently of known prenatal and genetic risk factors. Analysis of genetic and dietary data in adults revealed that 5-AVAB was associated with increased habitual dietary intake of dairy (FDR-adjusted p < 0.05) and with variants near SLC22A4 and SLC22A5 (p < 5.0e - 8), coding for a transmembrane carnitine transporter protein involved in controlling intracellular carnitine levels.CONCLUSIONS: Cyclo-leucine-proline and 5-AVAB are associated with future diagnosis of autism in Danish neonates, both representing novel early biomarkers for autism. 5-AVAB is potentially modifiable and may influence carnitine homeostasis.PMID:39026322 | DOI:10.1186/s12916-024-03516-7

Microb Cell Fact. 2024 Jul 18;23(1):201. doi: 10.1186/s12934-024-02479-x.ABSTRACTBACKGROUND: Ethanol shock significantly affects expression of over 1200 genes in Streptomyces venezuelae NRRL B-65,442, including those involved in secondary metabolite biosynthesis and a cryptic gene pepX, which encodes a 19-amino acid peptide with an unknown function.RESULTS: To establish a possible correlation between the PepX peptide and secondary metabolism in S. venezuelae, its gene was deleted, followed by analyses of the transcriptome and secondary metabolome of the mutant. Although the secondary metabolome of the pepX mutant was not strongly affected, pepX deletion, similar to ethanol shock, mostly resulted in downregulated expression of secondary metabolite biosynthesis gene clusters (BGCs). At the same time, there was a reverse correlation between the expression of certain extracytoplasmic function sigma factors (ECFs) and several BGCs. Individual deletions of three selected ECF-coding genes conserved in Streptomyces that were upregulated upon both pepX deletion and ethanol shock, had a profound positive effect on the expression of BGCs, which also correlated with the overproduction of specific secondary metabolites. Deletion of one such ECF-coding gene in a marine sponge-derived Streptomyces sp. also significantly altered the secondary metabolite profile, suggesting an important role of this ECF in the regulation of secondary metabolism.CONCLUSIONS: These findings pave the way for the activation or upregulation of BGCs in Streptomyces bacteria harboring genes for ECFs homologous to those identified in this study, hereby assisting in the discovery of novel bioactive secondary metabolites.PMID:39026318 | DOI:10.1186/s12934-024-02479-x

BMC Cancer. 2024 Jul 18;24(1):854. doi: 10.1186/s12885-024-12416-1.ABSTRACTBACKGROUND: Metabolic dysregulation is recognized as a significant hallmark of cancer progression. Although numerous studies have linked specific metabolic pathways to cancer incidence, the causal relationship between blood metabolites and lung cancer risk remains unclear.METHODS: Genomic data from 29,266 lung cancer patients and 56,450 control individuals from the Transdisciplinary Research in Cancer of the Lung and the International Lung Cancer Consortium (TRICL-ILCCO) were utilized, and findings were replicated using additional data from the FinnGen consortium. The analysis focused on the associations between 486 blood metabolites and the susceptibility to overall lung cancer and its three major clinical subtypes. Various Mendelian randomization methods, including inverse-variance weighting, weighted median estimation, and MR-Egger regression, were employed to ensure the robustness of our findings.RESULTS: A total of 19 blood metabolites were identified with significant associations with lung cancer risk. Specifically, oleate (OR per SD = 2.56, 95% CI: 1.51 to 4.36), 1-arachidonoylglyceropholine (OR = 1.79, 95% CI: 1.22 to 2.65), and arachidonate (OR = 1.67, 95% CI: 1.16 to 2.40) were associated with a higher risk of lung cancer. Conversely, 1-linoleoylglycerophosphoethanolamine (OR = 0.57, 95% CI: 0.40 to 0.82), ADpSGEGDFXAEGGGVR, a fibrinogen cleavage peptide (OR = 0.60, 95% CI: 0.47 to 0.77), and isovalerylcarnitine (OR = 0.62, 95% CI: 0.49 to 0.78) were associated with a lower risk of lung cancer. Notably, isoleucine (OR = 9.64, 95% CI: 2.55 to 36.38) was associated with a significantly higher risk of lung squamous cell cancer, while acetyl phosphate (OR = 0.11, 95% CI: 0.01 to 0.89) was associated with a significantly lower risk of small cell lung cancer.CONCLUSION: This study reveals the complex relationships between specific blood metabolites and lung cancer risk, highlighting their potential as biomarkers for lung cancer prevention, screening, and treatment. The findings not only deepen our understanding of the metabolic mechanisms of lung cancer but also provide new insights for future treatment strategies.PMID:39026146 | DOI:10.1186/s12885-024-12416-1