PubMed

Talanta. 2023 Oct 9;268(Pt 1):125295. doi: 10.1016/j.talanta.2023.125295. Online ahead of print.ABSTRACTBACKGROUND: The COVID-19 pandemic challenged the management of technical and human resources in intensive care units (ICU) across the world. Several long-term predictors for COVID-19 disease progression have been discovered. However, predictors to support short-term planning of resources and medication that can be translated to future pandemics are still missing. A workflow was established to identify a predictor for short-term COVID-19 disease progression in the acute phase of intensive care patients to support clinical decision-making.METHODS: Thirty-two patients with SARS-CoV-2 infection were recruited on admission to the ICU and clinical data collected. During their hospitalization, plasma samples were acquired from each patient on multiple occasions, excepting one patient for which only one time point was possible, and the proteome (Inflammation, Immune Response and Organ Damage panels from Olink® Target 96), metabolome and lipidome (flow injection analysis and liquid chromatography-mass spectrometry) analyzed for each sample. Patient visits were grouped according to changes in disease severity based on their respiratory and organ function, and evaluated using a combination of statistical analysis and machine learning. The resulting short-term predictor from this multi-omics approach was compared to the human assessment of disease progression. Furthermore, the potential markers were compared to the baseline levels of 50 healthy subjects with no known SARS-CoV-2 or other viral infections.RESULTS: A total of 124 clinical parameters, 271 proteins and 782 unique metabolites and lipids were assessed. The dimensionality of the dataset was reduced, selecting 47 from the 1177 parameters available following down-selection, to build the machine learning model. Subsequently, two proteins (C-C motif chemokine 7 (CCL7) and carbonic anhydrase 14 (CA14)) and one lipid (hexosylceramide 18:2; O2/20:0) were linked to disease progression in the studied SARS-CoV-2 infections. Thus, a predictor delivering the prognosis of an upcoming worsening of the patient's condition up to five days in advance with a reasonable accuracy (79 % three days prior to event, 84 % four to five days prior to event) was found. Interestingly, the predictor's performance was complementary to the clinicians' capabilities to foresee a worsening of a patient.CONCLUSION: This study presents a workflow to identify omics-based biomarkers to support clinical decision-making and resource management in the ICU. This was successfully applied to develop a short-term predictor for aggravation of COVID-19 symptoms. The applied methods can be adapted for future small cohort studies.PMID:37866305 | DOI:10.1016/j.talanta.2023.125295

Water Res. 2023 Oct 12;246:120738. doi: 10.1016/j.watres.2023.120738. Online ahead of print.ABSTRACTTraditional research on biodegradation of emerging organic pollutants involves slow and labor-intensive experimentation. Currently, fast-developing metagenome, metatranscriptome, and metabolome technologies promise to expedite mechanistic research on biodegradation of emerging organic pollutants. Integrating the metagenome, metatranscriptome, and metabolome (i.e., tri-omics) makes it possible to link gene abundance and expression with the biotransformation of the contaminant and the formation of metabolites from this biotransformation. In this study, we used this tri-omics approach to study the biotransformation pathways for cetyltrimethylammonium bromide (CTAB) under aerobic conditions. The tri-omics analysis showed that CTAB undergoes three parallel first-step mono-/di-oxygenations (to the α, β, and ω-carbons); intermediate metabolites and expressed enzymes were identified for all three pathways, and the β-carbon mono-/di-oxygenation is a novel pathway; and the genes related to CTAB biodegradation were associated with Pseudomonas spp. Four metabolites - palmitic acid, trimethylamine N-oxide (TMAO), myristic acid, and betaine - were the key identified biodegradation intermediates of CTAB, and they were associated with first-step mono-/di-oxygenations at the α/β-C. This tri-omics approach with CTAB demonstrates its power for identifying promising paths for future research on the biodegradation of complex organics by microbial communities.PMID:37866246 | DOI:10.1016/j.watres.2023.120738

Cell Immunol. 2023 Oct 15;393-394:104777. doi: 10.1016/j.cellimm.2023.104777. Online ahead of print.ABSTRACTVaccinations in early life elicit variable antibody and cellular immune responses, sometimes leaving fully vaccinated children unprotected against life-threatening infectious diseases. Specific immune cell populations and immune networks may have a critical period of development and calibration in a window of opportunity occurring during the first 100 days of early life. Among the early life determinants of vaccine responses, this review will focus on modifiable factors involving development of the infant microbiota and metabolome: antibiotic exposure, breast versus formula feeding, and Caesarian section versus vaginal delivery of newborns. How microbiota may serve as natural adjuvants for vaccine responses and how microbiota-derived metabolites influence vaccine responses are also reviewed. Early life poor vaccine responsiveness can be linked to increased infection susceptibility because both phenotypes share similar immunity dysregulation profiles. An early life pre-vaccination endotype, when interventions have the highest potential for success, should be sought that predicts vaccine response trajectories.PMID:37866234 | DOI:10.1016/j.cellimm.2023.104777

Poult Sci. 2023 Sep 27;102(12):103154. doi: 10.1016/j.psj.2023.103154. Online ahead of print.ABSTRACTThe process of egg yolk formation involves the transport and uptake of a large number of small molecule metabolites. A qualitative and relative quantitative analysis of metabolites in the 3 formation periods of egg yolk was performed by a liquid chromatography-tandem mass spectrometry (LC-MS/MS) analytical workflow. A total of 398 metabolites were identified, of which "amino acids and their metabolites", "lipid", and "organic acids and their derivatives" were the dominant egg yolk metabolite categories with the most metabolite species. The findings suggested that a number of amino acids, organic acids, nucleotides and their metabolites were deposited during follicular development to provide material support for later embryonic development. At the same time, some vitamins and carbohydrates were consumed during follicular development to support the normal development process. In addition, the small hierarchical follicle (SF) period may be a critical period for the regulation of the transport and deposition of some active ingredients. These results contribute to a comprehensive understanding of the nutrient deposition pattern and nutritional properties of egg yolk.PMID:37866223 | DOI:10.1016/j.psj.2023.103154

J Pharm Biomed Anal. 2023 Oct 18;238:115806. doi: 10.1016/j.jpba.2023.115806. Online ahead of print.ABSTRACTBACKGROUND: Cholelithiasis is a gastrointestinal disease that is associated with the highest socioeconomic cost. A diagnosis of cholelithiasis based on clinical features is significantly limited, and direct molecular insights into cholelithiasis and the relationship between cholelithiasis and clinical biochemical parameters are unclear.OBJECTIVES: Uncovering direct molecular insights into cholelithiasis and the relationship between cholelithiasis and clinical biochemical parameters. Identifying sensitive and specific biomarkers for this disease.METHODS: Parallel metabolomic and proteomic analyses of plasma from cholelithiasis patients (CPs) and healthy control individuals (HCs) without cholelithiasis were performed using ultrahigh-performance liquid chromatography-tandem mass spectrometry. A multimodule coexpression network analysis and integrated machine learning methods, including least absolute shrinkage and selection operator, random forest, and support vector machine, were used for bioinformatic analyses. An independent cohort and the cross-validation of the combination of two cohorts were used to evaluate the diagnostic performance of the panel.RESULTS: Arachidonic acid metabolism was significantly different between the CP and HC groups. Glyceraldehyde-3-phosphate dehydrogenase, actin beta, phosphoglycerate mutase 1, Enolase 1, Myeloperoxidase, and actin alpha 1 were identified as potential proteins related to cholelithiasis. The correlation between the merged modules and clinical biochemical tests was calculated. A diagnostic panel composed of four candidate biomarkers, including 3-oxotetradecanoic acid, 12-hydroxydodecanoic acid, hemoglobin subunit delta (HBD), and fibrinogen beta chain (FGB), was proposed based on three modules that were significantly associated with cholelithiasis. The classification according to the diagnostic panel detected CPs with an area under the curve (AUC) of 0.955. External validation in an independent cohort resulted in similar accuracy (AUC=0.995).CONCLUSIONS: This study provided some direct molecular insights into cholelithiasis by showing the differences in plasma metabolic and protein profiles between CPs and HCs and presented a potential biomarker panel with two metabolites (3-oxotetradecanoic acid, 12-hydroxydodecanoic acid) and two proteins (HBD, FGB) for predicting cholelithiasis. We also explored the potential correlation of clinical biochemical parameters with combined modules. These findings may provide some reference for the diagnosis of cholelithiasis in clinical practice.PMID:37866078 | DOI:10.1016/j.jpba.2023.115806

Biomed Pharmacother. 2023 Oct 20;168:115722. doi: 10.1016/j.biopha.2023.115722. Online ahead of print.ABSTRACTAlbeit remarkable achievements in anti-cancer endeavors, the prevention and treatment of cancer remain unresolved challenges. Hence, there is an urgent need to explore new and efficacious natural compounds with potential anti-cancer therapeutic agents. One such group of compounds is alisols, tetracyclic triterpene alcohols extracted from alisma orientale. Alisols play a significant role in cancer therapy as they can suppress cancer cell proliferation and migration by regulating signaling pathways such as mTOR, Bax/Bcl-2, CHOP, caspase, NF-kB and IRE1. Pharmacokinetic studies showed that alisols can be absorbed entirely, rapidly, and evenly distributed in vivo. Moreover, alisols are low in toxicity and relatively safe to take. Remarkably, each alisol can be converted into many compounds with different pathways to their anti-cancer effects in the body. Thus, alisols are regarded as promising anti-cancer agents with minimal side effects and low drug resistance. This review will examine and discuss alisols' anti-cancer molecular mechanism, pharmacokinetics and metabolism. Based on a comprehensive analysis of nearly 20 years of research, we evaluate the therapeutic potential of alisols for various types of cancer and offer insights and strategies for developing new cancer treatments.PMID:37865991 | DOI:10.1016/j.biopha.2023.115722

World J Biol Psychiatry. 2023 Oct 22:1-27. doi: 10.1080/15622975.2023.2271965. Online ahead of print.ABSTRACTThis study aimed to explore the relationship between alterations in plasma metabolites and treatment responses amongst antipsychotic-naïve female patients with schizophrenia. A total of 38 antipsychotic-naïve female schizophrenia patients (ANS) and 19 healthy female controls (HC) were recruited. Plasma samples were obtained from all participants, and targeted metabolomics were measured with FIA-MS/MS and LC-MS/MS. The positive and negative syndrome scale (PANSS) was used to assess the severity of psychotic symptoms before and after eight weeks of treatment. Receiver operator characteristics (ROC) curves were used to predict diagnostic and therapeutic responses. A total of 186 metabolites passed quality control procedures and were used in statistical analysis to identify potential biomarkers. Before treatment, the ANS patients had lower levels of γ -Aminobutyric Acid (GABA) and higher levels of Cholesteryl esters (CE) (20:3), Cholic Acid (CA) and Glycocholic Acid (GCA) compared to the HCs. These four differential metabonomic markers were synthesized into a combinatorial biomarker panel. This panel significantly distinguished ANS from HC. Moreover, this biomarker panel was able to effectively predict therapeutic responses. Our results suggest that plasma CE (20:3), CA, GCA, and GABA levels may be useful for diagnosing and predicting antipsychotic efficacy amongst female schizophrenia patients.PMID:37867221 | DOI:10.1080/15622975.2023.2271965

Mol Nutr Food Res. 2023 Oct 22:e2300398. doi: 10.1002/mnfr.202300398. Online ahead of print.ABSTRACTSCOPE: Olive oil, rapeseed oil, and lard are dietary fats rich in monounsaturated fatty acids, but the effects of dietary oils enriched in monounsaturated fatty acids on hepatic lipid deposition have seldom been compared.METHODS AND RESULTS: Ninety 8-week-old C57BL/6J male mice are randomly divided into six groups and fed diets containing lard, rapeseed oil, or olive oil with a 10% or 45% fat energy supply for 16 weeks. Under high-fat conditions, serum total cholesterol levels in the lard and olive oil groups are significantly higher than those in the rapeseed oil group. Hepatic lipid content in the olive oil group is higher than that in the other two groups. Compared with rapeseed oil, lard increases the liver levels of arachidonic, palmitic, and myristic acids and decreases the levels of eicosapentaenoic linolenic acid and linoleic acid. Olive oil increases the liver levels of docosatrienoic, arachidonic, oleic, and myristic acids; maltose; and fructose and decreases the levels of eicosapentaenoic, linolenic, and linoleic acids.CONCLUSION: Olive oil probably causes hepatic lipid deposition in mice, which may enhance hepatic lipid synthesis by activating the starch and sucrose metabolic pathways. By contrast, rapeseed oil shows a significant anti-lipid deposition effect on the liver.PMID:37867207 | DOI:10.1002/mnfr.202300398

Int J Biol Macromol. 2023 Oct 19:127559. doi: 10.1016/j.ijbiomac.2023.127559. Online ahead of print.ABSTRACTThe interaction between wheat germ polysaccharide (WGP) and gut microbiota remains relatively less investigated. Thus, this study explored their interaction via in vitro batch fecal fermentation. WGP elevated dramatically the relative abundances of Bacteroides (especially Ba. xylanisolvens, Ba. uniformis, and Ba. intestinalis), Bifidobacterium (especially Bi. pseudocatenulatum) and Eubacterium, and decreased Alistipes, Klebsiella, Bilophila and Sutterella. Moreover, the metabolomics and Spearman correlation results showed that these alterations in gut microbiota gave rise to over 13-fold augmentation in the quantities of short-chain fatty acids (SCFAs) and indole-3-lactic acid, as well as 7.17- and 4.23-fold increase in acetylcholine and GABA, respectively, at 24 h of fermentation. Interestingly, PICRUSt analysis showed that WGP markedly reduced aging pathway, and enriched nervous system pathway. Therefore, the D-gal-induced aging mice model was used to further verify these effects. The results demonstrated that WGP had a protective effect on D-gal-induced behavioral deficits, particularly in locomotor activity, and spatial and recognition memory. WGP elevated dramatically the relative abundances of Bacteroides (especially Ba. sartorii and Ba. uniformis), Bifidobacterium (especially Bi. pseudocatenulatum) and Parabacteroides, and decreased Alistipes and Candidatus Arthromitus. These findings highlight the potential utility of WGP as a dietary supplement for retarding the aging process and mitigating age-associated learning and memory decline via the targeted enrichment of Bacteroides and Bifidobacterium and the related metabolites.PMID:37865367 | DOI:10.1016/j.ijbiomac.2023.127559

Plant Sci. 2023 Oct 19:111901. doi: 10.1016/j.plantsci.2023.111901. Online ahead of print.ABSTRACTSunflowers are well-known ornamental plants, while sunflowers with red corolla are rare and the mechanisms underlying red coloration remain unclear. Here, a comprehensive analysis of metabolomics and transcriptomics on flavonoid pathway was performed to investigate the molecular mechanisms underlying the differential color formation between red sunflower Pc103 and two yellow sunflowers (Yr17 and Y35). Targeted metabolomic analysis revealed higher anthocyanin levels but lower flavonol content in Pc103 compared to the yellow cultivars. RNA-sequencing and phylogenetic analysis identified multiple genes involved in the flavonoid pathway, including series of structural genes and three MYB and bHLH genes. Specifically, HaMYBA and HabHLH1 were up-regulated in Pc103, whereas HaMYBF exhibited reduced expression. HaMYBA was found to interact with HabHLH1 in vivo and in vitro, while HaMYBF does not. Transient expression analysis further revealed that HabHLH1 and HaMYBA cooperatively regulate increased expression of dihydroflavonol 4-reductase (DFR), leading to anthocyanin accumulation. On the other hand, ectopic expression of HaMYBF independently modulates flavonol synthase (FLS) expression, but hindered anthocyanin production. Collectively, our findings suggest that the up-regulation of HaMYBA and HabHLH1, as well as the down-regulation of HaMYBF, contribute to the red coloration in Pc103. It offers a theoretical basis for improving sunflower color through genetic engineering.PMID:37865209 | DOI:10.1016/j.plantsci.2023.111901

Plant Physiol Biochem. 2023 Oct 14;204:108097. doi: 10.1016/j.plaphy.2023.108097. Online ahead of print.ABSTRACTSalt stress adversely affects the growth, development, and yield of tomato (Solanum lycopersicum). SAM Synthetase (SAMS), which is responsible for the biosynthesis of S-adenosylmethionine (SAM, a precursor of polyamine biosynthesis), participates in plant response to abiotic stress. However, the regulatory mechanism of SAMS-mediated salt stress tolerance remains elusive. In this study, we characterized a SAMS homologue SlSAMS1 in tomato. We found that SlSAMS1 is highly expressed in tomato roots, and its expression can be induced by salt stress. Crucially, overexpression of SlSAMS1 in tomato enhances salt stress tolerance. Through metabolomic profiling, we identified some differentially accumulated metabolites, especially, a secondary messenger guanosine 3',5'-cyclic monophosphate (cGMP) which may play a key role in SlSAMS1-regulated salt tolerance. A series of physiological and biochemical data suggest that cGMP alleviates salt stress-induced growth inhibition, and potentially acts downstream of the polyamine-nitric oxide (PA-NO) signaling pathway to trigger H2O2 signaling in response to salt stress. Taken together, the study reveals that SlSAMS1 regulates tomato salt tolerance via the PA-NO-cGMP-H2O2 signal module. Our findings elucidate the regulatory pathway of SlSAMS1-induced plant response to salt stress and indicate a pivotal role of cGMP in salt tolerance.PMID:37864930 | DOI:10.1016/j.plaphy.2023.108097

Meat Sci. 2023 Oct 14;207:109370. doi: 10.1016/j.meatsci.2023.109370. Online ahead of print.ABSTRACTThe underlying mechanism of myostatin (MSTN) gene mutation impact on porcine carcass and meat quality has not yet been fully understood. The meat quality trait testing of the second filial generation wild-type (WT) and homozygous MSTN mutant (MSTN-/-) castrated male finishing pigs, and RNA-seq and metabolomics on the longissimus thoracis (LT) and subcutaneous adipose tissues (SAT) were performed. Compared with WT pigs, MSTN-/- pigs had higher carcass lean percentage and lower backfat thickness (all P < 0.01), and also had lower shear force (P < 0.01) and meat redness (P < 0.05). The gene and metabolite expression profiles were different between two groups. Metabolites and genes related to purine metabolism (such as xanthine metabolite (P < 0.05), AMPD3 and XDH genes (all padj < 0.01)), PI3K/Akt/mTOR signaling pathway (such as Phe-Phe and Glu-Glu metabolites (all P < 0.05), WNT4 and AKT2 genes (all padj < 0.01)), antioxidant related pathway (such as GPX2, GPX3, and GPX7 genes (all padj < 0.01)), and extracellular matrix related pathway (such as COL1A1 and COL3A1 genes (all padj < 0.01)) were significantly altered in LT. While metabolites and genes associated to lipid metabolism (such as trans-elaidic acid and PE(18:1(9Z)/0:0) metabolites (all P < 0.05), ACOX1, ACAT1 and HADH genes (all padj < 0.01)) were significantly changed in SAT. This study revealed the biological mechanisms of homozygous MSTN mutation regulated porcine carcass and meat quality, such as lean meat percentage, fat deposition and tenderness, which provides reference for the utilization of MSTN-/- pigs.PMID:37864922 | DOI:10.1016/j.meatsci.2023.109370

Biomed Pharmacother. 2023 Oct 19;168:115659. doi: 10.1016/j.biopha.2023.115659. Online ahead of print.ABSTRACTThe anti-tumoral effects of metformin have been widely studied in several types of cancer, including thyroid cancer; however, the underlying molecular mechanisms remain poorly understood. As an oral hypoglycemic drug, metformin facilitates glucose catabolism and disrupts metabolic homeostasis. Metabolic reprogramming, particularly cellular glucose metabolism, is an important characteristic of malignant tumors. This study aimed to explore the therapeutic effects of metformin in thyroid cancer and the underlying metabolic mechanism. In the present study, it was shown that metformin reduced cell viability, invasion, migration, and EMT, and induced apoptosis and cell cycle G1 phase arrest in thyroid cancer. Transcriptome analysis demonstrated that the differentially expressed genes induced by metformin were involved in several signaling pathways including apoptosis singling pathways, TGF-β signaling, and cell cycle regulation in human thyroid cancer cell lines. In addition, the helicase activity of the CDC45-MCM2-7-GINS complex and DNA replication related genes such as RPA2, RAD51, and PCNA were downregulated in metformin-treated thyroid cancer cells. Moreover, metabolomics analysis showed that metformin-induced significant alterations in metabolic pathways such as glutathione metabolism and polyamine synthesis. Integrative analysis of transcriptomes and metabolomics revealed that metformin suppressed glycolysis by downregulating the key glycolytic enzymes LDHA and PKM2 and upregulating IDH1 expression in thyroid cancer. Furthermore, the anti-tumor role of metformin in thyroid cancer in vivo was shown. Together these results show that metformin plays an anti-tumor role by inhibiting glycolysis and restraining DNA replication in thyroid cancer.PMID:37864896 | DOI:10.1016/j.biopha.2023.115659

Placenta. 2023 Oct 12;143:80-86. doi: 10.1016/j.placenta.2023.10.006. Online ahead of print.ABSTRACTINTRODUCTION: Our understanding of the etiology of preterm birth (PTB) is incomplete; however, recent evidence has found a strong association between placental dysfunction and PTB. Altered placental metabolism may precede placental dysfunction and therefore the study of placental metabolic profiles could identify early biomarkers of PTB. In this study, we evaluated the placental metabolome in PTB in intact tissue samples using nuclear magnetic resonance (NMR) and spectral editing.METHODS: Placental tissue samples were collected from nine term pregnancies and nine preterm pregnancies (<37 weeks' gestation). 1H NMR experiments on unprocessed tissue samples were performed using a high field magnet (500 MHz spectrometer) and a comprehensive multiphase NMR probe. The relative concentrations of 23 metabolites were corrected for gestational age and compared between groups.RESULTS: The relative concentration of valine, glutamate and creatine were significantly decreased while alanine, choline and glucose were elevated in placentas from PTB pregnancies compared to controls (p < 0.05). Multivariate analysis using principal component analysis showed the PTB and control groups were significantly separated (p < 0.0001) and pathway analysis identified perturbations in the glycine, serine and threonine metabolism, aminoacyl-tRNA biosynthesis and valine, leucine and isoleucine biosynthesis pathways.CONCLUSION: PTB is associated with significant alterations in placental metabolism. This study helps improve our understanding of the etiology of PTB. It also highlights the potential for small molecule metabolites to serve as placental metabolic biomarkers to aid in the prediction and diagnosis of PTB. The results can be translated to clinical use via in utero magnetic resonance spectroscopy.PMID:37864887 | DOI:10.1016/j.placenta.2023.10.006

Metabolomics. 2023 Oct 21;19(11):89. doi: 10.1007/s11306-023-02054-2.ABSTRACTINTRODUCTION: Twisted-leaf garlic (Allium obliquum L.) is a wild Allium species, which is traditionally used as aroma plant for culinary purposes due to its unique, garlic-like flavor. It represents an interesting candidate for domestication, breeding and cultivation.OBJECTIVES: The objective of this work was to explore and comprehensively characterize polar and semi-polar phytochemicals accumulating in leaves and bulbs of A. obliquum.METHOD: Plant material obtained from a multiyear field trial was analyzed using a metabolite profiling workflow based on ultra-high performance liquid chromatography-coupled electrospray ionization quadrupole time-of-flight mass spectrometry (UHPLC/ESI-QTOFMS) and two chromatographic methods. For annotation of metabolites, tandem mass spectrometry experiments were carried out and the resulting accurate-mass collision-induced dissociation (CID) mass spectra interpreted. Onion and garlic bulb extracts were used as reference samples.RESULTS: Important metabolite classes influencing nutritional, sensory and technological properties were detected and structurally characterized including fructooligosaccharides with a degree of polymerization of 3-5, S-alk(en)ylcysteine sulfoxides and other S-substituted cysteine conjugates, flavonoids including O- and C-glycosylated flavones as well as O-glycosylated flavonols, steroidal saponins, hydroxycinnamic acid conjugates, phenylethanoids and free sphingoid bases. In addition, quantitative data for non-structural carbohydrates, S-alk(en)ylcysteine sulfoxides and flavonoids are provided.CONCLUSION: The compiled analytical data including CID mass spectra of more than 160 annotated metabolites provide for the first time a phytochemical inventory of A. obliquum and lay the foundation for its further use as aroma plant in food industry.PMID:37864615 | DOI:10.1007/s11306-023-02054-2

J Dent Res. 2023 Oct 21:220345231196536. doi: 10.1177/00220345231196536. Online ahead of print.ABSTRACTIt is of great importance to uncover causal biomarkers to gain insight into the pathogenesis of oral diseases and identify novel treatment targets for prevention and treatment thereof. This study aimed to systematically evaluate the causal effects of hundreds of metabolites on 10 dental traits using a 2-sample Mendelian randomization (MR) approach. Genetic variants from genome-wide association studies of 309 known metabolites were used as instrumental variables. We selected 10 dental traits, including clinical measures of dental diseases, from the Gene-Lifestyle Interactions in Dental Endpoints Consortium and self-reported oral health data from the UK Biobank. The causal relationships between metabolites and dental traits were inferred using the inverse variance-weighted approach and further controlled for horizontal pleiotropy using 5 additional MR methods. After correcting for multiple tests, 5 metabolites were identified as causal biomarkers. Genetically predicted increased levels of mannose were associated with lower risk of bleeding gums (odds ratio [OR] = 0.72; 95% confidence interval [CI], 0.61-0.85; P = 9.9 × 10-5). MR also indicated 4 metabolites on the causal pathway to dentures, with fructose (OR = 0.50; 95% CI, 0.36-0.70; P = 5.2 × 10-5) and 1-palmitoleoyl-glycerophosphocholine (OR = 0.67; 95% CI, 0.56-0.81; P = 4.8 × 10-5) as potential protective factors and glycine (OR = 1.22; 95% CI, 1.11-1.35; P = 5.6×10-5) and 1,5-anhydroglucitol (OR = 1.32; 95% CI, 1.14-1.52; P = 1.5 × 10-4) as risk factors. The causal associations were robust in various sensitivity analyses. We further observed some shared metabolites among different dental traits, implying similar biological mechanisms underlying the pathogenic processes. Finally, the pathway analysis revealed several significant metabolic pathways that may be involved in the development of dental disorders. Our study provides novel insights into the combination of metabolomics and genomics to reveal the pathogenesis of and therapeutic strategies for dental disorders. It highlighted 5 metabolites and several pathways as causal candidates, warranting further investigation.PMID:37864545 | DOI:10.1177/00220345231196536

J Exp Bot. 2023 Oct 21:erad384. doi: 10.1093/jxb/erad384. Online ahead of print.ABSTRACTClassically fruit ripening and development was studied using genetic approaches with understanding of metabolic changes that occurred in concert largely focused on a handful of metabolites including sugars, organic acids, cell wall components and phytohormones. The advent and widespread application of metabolomics has however led to far greater understanding of metabolic components that play a crucial role not only in this process but also in influencing the organoleptic and nutritive properties of the fruits. Here we review how the study of natural variation, mutants, transgenics and gene-edited fruits has led to a considerable increase in our understanding of these aspects. We focus on flesh fruits such as tomato but also review berries and receptacle as well as stone-bearing fruits. Finally, we offer a perspective as to how comparative analyses and machine learning will likely further improve our comprehension of the functional importance of various metabolites in the future.PMID:37864494 | DOI:10.1093/jxb/erad384

BMC Genomics. 2023 Oct 20;24(1):626. doi: 10.1186/s12864-023-09713-7.ABSTRACTBACKGROUND: Phytophthora root rot caused by the oomycete Phytophthora capsici is the most devastating disease in pepper production worldwide, and current management strategies have not been effective in preventing this disease. Therefore, the use of resistant varieties was regarded as an important part of disease management of P. capsici. However, our knowledge of the molecular mechanisms underlying the defense response of pepper roots to P. capsici infection is limited.METHODS: A comprehensive transcriptome and metabolome approaches were used to dissect the molecular response of pepper to P. capsici infection in the resistant genotype A204 and the susceptible genotype A198 at 0, 24 and 48 hours post-inoculation (hpi).RESULTS: More genes and metabolites were induced at 24 hpi in A204 than A198, suggesting the prompt activation of defense responses in the resistant genotype, which can attribute two proteases, subtilisin-like protease and xylem cysteine proteinase 1, involved in pathogen recognition and signal transduction in A204. Further analysis indicated that the resistant genotype responded to P. capsici with fine regulation by the Ca2+- and salicylic acid-mediated signaling pathways, and then activation of downstream defense responses, including cell wall reinforcement and defense-related genes expression and metabolites accumulation. Among them, differentially expressed genes and differentially accumulated metabolites involved in the flavonoid biosynthesis pathways were uniquely activated in the resistant genotype A204 at 24 hpi, indicating a significant role of the flavonoid biosynthesis pathways in pepper resistance to P. capsici.CONCLUSION: The candidate transcripts may provide genetic resources that may be useful in the improvement of Phytophthora root rot-resistant characters of pepper. In addition, the model proposed in this study provides new insight into the defense response against P. capsici in pepper, and enhance our current understanding of the interaction of pepper-P. capsici.PMID:37864214 | DOI:10.1186/s12864-023-09713-7

Mar Biotechnol (NY). 2023 Oct 21. doi: 10.1007/s10126-023-10261-0. Online ahead of print.ABSTRACTCompensatory growth (CG) in fish is heavily influenced by nutrient metabolism. However, there are limited studies examining how nutrient metabolism is regulated during this process. For silver pomfret, an important commercial marine fish, it's crucial to establish effective starvation and re-feeding strategies to ensure good water quality and fast growth. To identify the complete compensatory growth model of silver pomfret, we conducted an experiment with a control group (normal feeding) and three starvation/re-feeding groups. We observed that the recovery of weight and condition factor in the 14-day starvation and 14-day re-feeding groups was significantly faster than other groups, indicating full compensatory growth. Thus, we selected this group for the next experiment. We performed untargeted metabolomics and transcriptome analysis of muscle tissue on Day 14, 21 and 28 (CG process), and examined the key regulatory genes of nutrient metabolism on Day 0, 7, 14, 21 and 28 (starvation and re-feeding process). Our data revealed that during starvation, silver pomfret first utilized carbohydrates and short-chain lipids, followed by proteins and long-chain lipids. After re-feeding, lipids accumulated first, resulting in rapid growth, followed by the recovery of protein content in muscle. During starvation, the expression of anabolic-related genes such as TER and CALR decreased, and catabolic-related genes such as TSC2 and MLYCD increased, promoting the AMPK pathway. During re-feeding, anabolic-related gene expression increased without AMPK inhibition. Our findings provide insights into the energy utilization strategies of fish and molecular regulation during compensatory growth in fish.PMID:37864114 | DOI:10.1007/s10126-023-10261-0

Sci Rep. 2023 Oct 20;13(1):17943. doi: 10.1038/s41598-023-45066-7.ABSTRACTType 2 Diabetes Mellitus has reached epidemic levels globally, and several studies have confirmed a link between gut microbial dysbiosis and aberrant glucose homeostasis among people with diabetes. While the assumption is that abnormal metabolomic signatures would often accompany microbial dysbiosis, the connection remains largely unknown. In this study, we investigated how diet changed the gut bacteriome, mycobiome and metabolome in people with and without type 2 Diabetes.1 Differential abundance testing determined that the metabolites Propionate, U8, and 2-Hydroxybutyrate were significantly lower, and 3-Hydroxyphenyl acetate was higher in the high fiber diet compared to low fiber diet in the healthy control group. Next, using multi-omics factor analysis (MOFA2), we attempted to uncover sources of variability that drive each of the different groups (bacterial, fungal, and metabolite) on all samples combined (control and DM II). Performing variance decomposition, ten latent factors were identified, and then each latent factor was tested for significant correlations with age, BMI, diet, and gender. Latent Factor1 was the most significantly correlated. Remarkably, the model revealed that the mycobiome explained most of the variance in the DM II group (12.5%) whereas bacteria explained most of the variance in the control group (64.2% vs. 10.4% in the DM II group). The latent Factor1 was significantly correlated with dietary intake (q < 0.01). Further analyses of the impact of bacterial and fungal genera on Factor1 determined that the nine bacterial genera (Phocaeicola, Ligilactobacillus, Mesosutterella, Acidaminococcus, Dorea A, CAG-317, Caecibacter, Prevotella and Gemmiger) and one fungal genus (Malassezia furfur) were found to have high factor weights (absolute weight > 0.6). Alternatively, a linear regression model was fitted per disease group for each genus to visualize the relationship between the factor values and feature abundances, showing Xylose with positive weights and Propionate, U8, and 2-Hydroxybutyrate with negative weights. This data provides new information on the microbially derived changes that influence metabolic phenotypes in response to different diets and disease conditions in humans.PMID:37863978 | DOI:10.1038/s41598-023-45066-7