PubMed

J Lipid Res. 2023 Jun 21:100405. doi: 10.1016/j.jlr.2023.100405. Online ahead of print.ABSTRACTAlpha/beta hydrolase domain-containing protein 4 (ABHD4) catalyzes the deacylation of N-acyl phosphatidyl-ethanolamine (NAPE) and lyso-NAPE to produce glycerophospho-N-acyl ethanolamine (GP-NAE). Through a variety of metabolic enzymes, NAPE, lyso-NAPE, and GP-NAE are ultimately converted into NAE, a group of bioactive lipids that control many physiological processes including inflammation, cognition, food intake, and lipolysis (i.e., oleoylethanolamide or OEA). In a diet-induced obese mouse model, adipose tissue ABHD4 gene expression positively correlated with adiposity. However, it is unknown whether ABHD4 is a causal or a reactive gene to obesity. To fill this knowledge gap, we generated an ABHD4 knockout (KO) 3T3-L1 pre-adipocyte. During adipogenic stimulation, ABHD4 KO pre-adipocytes had increased adipogenesis and lipid accumulation, suggesting ABHD4 is responding to (a reactive gene), not contributing to (not a causal gene), adiposity and may serve as a mechanism for protecting against obesity. However, we did not observe any differences in adiposity and metabolic outcomes between whole body ABHD4 KO or adipocyte specific ABHD4 KO mice and their littermate control mice (both male and female) on chow or a high fat diet. This might be because we found that deletion of ABHD4 did not affect NAE such as OEA production, even though ABHD4 was highly expressed in adipose tissue and correlated with fasting adipose OEA levels and lipolysis. These data suggest that ABHD4 plays a role in adipocyte differentiation in vitro but not in adipose tissue lipid metabolism in mice despite nutrient overload, possibly due to compensation from other NAPE and NAE metabolic enzymes.PMID:37352974 | DOI:10.1016/j.jlr.2023.100405

Food Chem. 2023 Jun 11;426:136588. doi: 10.1016/j.foodchem.2023.136588. Online ahead of print.ABSTRACTWhile the "farm to fork" strategy ticks many boxes in the sustainability agenda, it does not go far enough in addressing how we can improve crop nutraceutical quality. Here, we explored whether supplementary ultraviolet (UV) radiation exposure during growth of broccoli and Chinese cabbage can induce bioactive tryptophan- and glucosinolate-specific metabolite accumulation thereby enhancing Aryl hydrocarbon receptor (AhR) activation in human intestinal cells. By combining metabolomics analysis of both plant extracts and in vitro human colonic fermentation extracts with AhR reporter cell assay, we reveal that human colonic fermentation of UVB-exposed Chinese cabbage led to enhanced AhR activation in human intestinal cells by 23% compared to plants grown without supplementary UV. Thus, by exploring aspects beyond "from farm to fork", our study highlights a new strategy to enhance nutraceutical quality of Brassicaceae, while also providing new insights into the effects of cruciferous vegetables on human intestinal health.PMID:37352713 | DOI:10.1016/j.foodchem.2023.136588

Food Chem. 2023 Jun 8;426:136507. doi: 10.1016/j.foodchem.2023.136507. Online ahead of print.ABSTRACTThis work investigated microplastic (MP) pollution in a commercially-important tuna species Katsuwonus pelamis (K. pelamis) from the Eastern Pacific and health implications. 125 MPs were extracted from gills, esophagus, stomachs, intestinal tracts, and muscle of K. pelamis. MPs in the esophagus was the highest, ∼7.6 times higher than that in the gill. Polyester and polyethylene terephthalate (PET) were dominant. Molecular docking implied that PET stabilized the complex via forming 4 new hydrogen bonds that interacted with Arg83, Gln246, Thr267, and Gly268, given that PET can enter glycerol kinase protein active pocket. Metabonomic results suggested that Glycerol 3-phosphate up expressed 1.66 more times that of control groups with no MPs in the muscle. This confirmed that MPs would lie in the glycerol kinase protein active pocket, which triggered menace to K. pelamis. The results provided insights into suggested the potential influence of MPs on the sustainability of fisheries and seafood safety.PMID:37352712 | DOI:10.1016/j.foodchem.2023.136507

Plant Physiol Biochem. 2023 Jun 18;201:107839. doi: 10.1016/j.plaphy.2023.107839. Online ahead of print.ABSTRACTThe compositions and yield of flavonoid compounds of Polygonatum cyrtonema Hua (PC) are important indices of the quality of medicinal materials. However, the flavonoids compositions and accumulation mechanism are still unclear in PC. Here, we identified 22 flavonoids using widely-targeted metabolome analysis in 15 genotypes of PC. Then weighted gene co-expression network analysis based on 45 transcriptome samples was performed to construct 12 co-expressed modules, in which blue module highly correlated with flavonoids was identified. Furthermore, 4 feature genes including PcCHS1, PcCHI, PcCHS2 and PcCHR5 were identified from 94 hub genes in blue module via machine learning methods support vector machine-recursive feature elimination (SVM-RFE) and random forest (RF), and their functions on metabolic flux of flavonoids pathway were confirmed by tobacco transient expression system. Our findings identified representative flavonoids and key enzymes in PC that provided new insight for elite breeding rich in flavonoids, and thus will be beneficial for rapid development of great potential economic and medicinal value of PC.PMID:37352696 | DOI:10.1016/j.plaphy.2023.107839

PLoS Pathog. 2023 Jun 23;19(6):e1011449. doi: 10.1371/journal.ppat.1011449. Online ahead of print.ABSTRACTMalaria parasite release (egress) from host red blood cells involves parasite-mediated membrane poration and rupture, thought to involve membrane-lytic effector molecules such as perforin-like proteins and/or phospholipases. With the aim of identifying these effectors, we disrupted the expression of two Plasmodium falciparum perforin-like proteins simultaneously and showed that they have no essential roles during blood stage egress. Proteomic profiling of parasite proteins discharged into the parasitophorous vacuole (PV) just prior to egress detected the presence in the PV of a lecithin:cholesterol acyltransferase (LCAT; PF3D7_0629300). Conditional ablation of LCAT resulted in abnormal egress and a reduced replication rate. Lipidomic profiles of LCAT-null parasites showed drastic changes in several phosphatidylserine and acylphosphatidylglycerol species during egress. We thus show that, in addition to its previously demonstrated role in liver stage merozoite egress, LCAT is required to facilitate efficient egress in asexual blood stage malaria parasites.PMID:37352369 | DOI:10.1371/journal.ppat.1011449

PLoS Comput Biol. 2023 Jun 23;19(6):e1011221. doi: 10.1371/journal.pcbi.1011221. Online ahead of print.ABSTRACTThe intricate dependency structure of biological "omics" data, particularly those originating from longitudinal intervention studies with frequently sampled repeated measurements renders the analysis of such data challenging. The high-dimensionality, inter-relatedness of multiple outcomes, and heterogeneity in the studied systems all add to the difficulty in deriving meaningful information. In addition, the subtle differences in dynamics often deemed meaningful in nutritional intervention studies can be particularly challenging to quantify. In this work we demonstrate the use of quantitative longitudinal models within the repeated-measures ANOVA simultaneous component analysis+ (RM-ASCA+) framework to capture the dynamics in frequently sampled longitudinal data with multivariate outcomes. We illustrate the use of linear mixed models with polynomial and spline basis expansion of the time variable within RM-ASCA+ in order to quantify non-linear dynamics in a simulation study as well as in a metabolomics data set. We show that the proposed approach presents a convenient and interpretable way to systematically quantify and summarize multivariate outcomes in longitudinal studies while accounting for proper within subject dependency structures.PMID:37352364 | DOI:10.1371/journal.pcbi.1011221

Metabolomics. 2023 Jun 23;19(7):61. doi: 10.1007/s11306-023-02025-7.ABSTRACTINTRODUCTION: Polar metabolites in Caenorhabditis elegans (C. elegans) have predominantly been analyzed using hydrophilic interaction liquid chromatography coupled to mass spectrometry (HILIC-MS). Capillary electrophoresis coupled to mass spectrometry (CE-MS) represents another complementary analytical platform suitable for polar and charged analytes.OBJECTIVE: We compared CE-MS and HILIC-MS for the analysis of a set of 60 reference standards relevant for C. elegans and specifically investigated the strengths of CE separation. Furthermore, we employed CE-MS as a complementary analytical approach to study polar metabolites in C. elegans samples, particularly in the context of longevity, in order to address a different part of its metabolome.METHOD: We analyzed 60 reference standards as well as metabolite extracts from C. elegans daf-2 loss-of-function mutants and wild-type (WT) samples using HILIC-MS and CE-MS employing a Q-ToF-MS instrument.RESULTS: CE separations showed narrower peak widths and a better linearity of the estimated response function across different concentrations which is linked to less saturation of the MS signals. Additionally, CE exhibited a distinct selectivity in the separation of compounds compared to HILIC-MS, providing complementary information for the analysis of the target compounds. Analysis of C. elegans metabolites of daf-2 mutants and WT samples revealed significant alterations in shared metabolites identified through HILIC-MS, as well as the presence of distinct metabolites.CONCLUSION: CE-MS was successfully applied in C. elegans metabolomics, being able to recover known as well as identify novel putative biomarkers of longevity.PMID:37351740 | DOI:10.1007/s11306-023-02025-7

Metabolomics. 2023 Jun 23;19(7):62. doi: 10.1007/s11306-023-02026-6.ABSTRACTINTRODUCTION: Assessing intraspecific variation in plant volatile organic compounds (VOCs) involves pitfalls that may bias biological interpretation, particularly when several laboratories collaborate on joint projects. Comparative, inter-laboratory ring trials can inform on the reproducibility of such analyses.OBJECTIVES: In a ring trial involving five laboratories, we investigated the reproducibility of VOC collections with polydimethylsiloxane (PDMS) and analyses by thermal desorption-gas chromatography-mass spectrometry (TD-GC-MS). As model plant we used Tanacetum vulgare, which shows a remarkable diversity in terpenoids, forming so-called chemotypes. We performed our ring-trial with two chemotypes to examine the sources of technical variation in plant VOC measurements during pre-analytical, analytical, and post-analytical steps.METHODS: Monoclonal root cuttings were generated in one laboratory and distributed to five laboratories, in which plants were grown under laboratory-specific conditions. VOCs were collected on PDMS tubes from all plants before and after a jasmonic acid (JA) treatment. Thereafter, each laboratory (donors) sent a subset of tubes to four of the other laboratories (recipients), which performed TD-GC-MS with their own established procedures.RESULTS: Chemotype-specific differences in VOC profiles were detected but with an overall high variation both across donor and recipient laboratories. JA-induced changes in VOC profiles were not reproducible. Laboratory-specific growth conditions led to phenotypic variation that affected the resulting VOC profiles.CONCLUSION: Our ring trial shows that despite large efforts to standardise each VOC measurement step, the outcomes differed both qualitatively and quantitatively. Our results reveal sources of variation in plant VOC research and may help to avoid systematic errors in similar experiments.PMID:37351733 | DOI:10.1007/s11306-023-02026-6

Gut Microbes. 2023 Jan-Dec;15(1):2226915. doi: 10.1080/19490976.2023.2226915.ABSTRACTAge-related gut microbes and urine metabolites were investigated in 568 healthy individuals using metataxonomics and metabolomics. The richness and evenness of the fecal microbiota significantly increased with age, and the abundance of 16 genera differed between the young and old groups. Additionally, 17 urine metabolites contributed to the differences between the young and old groups. Among the microbes that differed by age, Bacteroides and Prevotella 9 were confirmed to be correlated with some urine metabolites. The machine learning algorithm eXtreme gradient boosting (XGBoost) was shown to produce the best performing age predictors, with a mean absolute error of 5.48 years. The accuracy of the model improved to 4.93 years with the inclusion of urine metabolite data. This study shows that the gut microbiota and urine metabolic profiles can be used to predict the age of healthy individuals with relatively good accuracy.PMID:37351626 | DOI:10.1080/19490976.2023.2226915

Front Pharmacol. 2023 Jun 7;14:1172963. doi: 10.3389/fphar.2023.1172963. eCollection 2023.ABSTRACTIntroduction: Polysaccharides from Grifola frondosa (Dicks.) Gray (HSH) and Inonotus obliquus (Fr.) Pilat (BHR) showed noticeable effects on dextran sulfate sodium (DSS)-induced colitis, but their systemic modulation effects have not been fully revealed. This study aimed to investigate the regulation of the gut microbiota and systemic metabolism by HSH and BHR in DSS-induced colitis. Methods: C57BL/6J mice were given DSS (2.5%) in water and were treated with HSH and BHR (200 mg/kg/day) by gavage. Body weight and colon length were recorded, and H&E and AB-PAS staining of the colon were conducted to evaluate the model and the protective effect of the polysaccharides. Additionally, an LC-QTOF/MS-based untargeted metabolomic platform was used to identify the metabolites in the serum, colon tissue, gut contents, and faeces and investigate differential metabolites and metabolic pathways. 16S rDNA gene sequencing was used to measure the composition of bacterial communities. Results: The results showed that the mouse colitis model was established successfully, as evidenced by an increased disease activity index score [2.83 ± 0.62 vs. 0.06 ± 0.14 (p < 0.001)] and shortened colon length [5.43 ± 0.64 cm vs. 7.04 ± 0.29 cm (p < 0.001)], and HSH and BHR ameliorated DSS-induced colitis by improving the disease activity index (2.17 ± 0.28 and 1.83 ± 0.29, respectively) and restoring the colon length (6.12 ± 0.30 cm and 6.62 ± 0.35 cm, respectively). HSH and BHR significantly modulated metabolites involved in aromatic amino acid metabolism, the citrate cycle, purine metabolism, pyrimidine metabolism, etc. HSH and BHR increased the Chao1 index by 64.25% and 60.25%, respectively, and they increased the Shannon index by 13.02% and 10.23%, respectively. They both reversed the increase in the abundances of g_Odoribacter, g_Clostridium, g_AF12, g_Parabacteroides and g_Turicibacter and reversed the decrease in the abundance of g_unclassified_Bacteria induced by DSS. Specifically, HSH reversed the reductions in g_unclassified_Lactobacillales and g_Ruminococcus, and BHR reversed the decreases in g_unidentified_Coriobacteriaceae and g_unclassified_Firmicutes. Discussion: These results suggested that HSH and BHR may ameliorate DSS-induced colitis by global modulation of systemic metabolism and the gut microbiota. Targeting the gut microbiota may be a potentially effective strategy to modulate systemic metabolism and treat colitis.PMID:37351508 | PMC:PMC10282762 | DOI:10.3389/fphar.2023.1172963

Front Plant Sci. 2023 Jun 7;14:1109460. doi: 10.3389/fpls.2023.1109460. eCollection 2023.ABSTRACTSoil salinization is a major environmental stressor hindering global crop production. Hydropriming has emerged as a promising approach to reduce salt stress and enhance crop yields on salinized land. However, a better mechanisitic understanding is required to improve salt stress tolerance. We used a biochemical and metabolomics approach to study the effect of salt stress of hydroprimed maize to identify the types and variation of differentially accumulated metabolites. Here we show that hydropriming significantly increased catalase (CAT) activity, soluble sugar and proline content, decreased superoxide dismutase (SOD) activity and peroxide (H2O2) content. Conversely, hydropriming had no significant effect on POD activity, soluble protein and MDA content under salt stress. The Metabolite analysis indicated that salt stress significantly increased the content of 1278 metabolites and decreased the content of 1044 metabolites. Ethisterone (progesterone) was the most important metabolite produced in the roots of unprimed samples in response to salt s tress. Pathway enrichment analysis indicated that flavone and flavonol biosynthesis, which relate to scavenging reactive oxygen species (ROS), was the most significant metabolic pathway related to salt stress. Hydropriming significantly increased the content of 873 metabolites and significantly decreased the content of 1313 metabolites. 5-Methyltetrahydrofolate, a methyl donor for methionine, was the most important metabolite produced in the roots of hydroprimed samples in response to salt stress. Plant growth regulator, such as melatonin, gibberellin A8, estrone, abscisic acid and brassinolide involved in both treatment. Our results not only verify the roles of key metabolites in resisting salt stress, but also further evidence that flavone and flavonol biosynthesis and plant growth regulator relate to salt tolerance.PMID:37351217 | PMC:PMC10282767 | DOI:10.3389/fpls.2023.1109460

Theranostics. 2023 May 21;13(10):3188-3203. doi: 10.7150/thno.80435. eCollection 2023.ABSTRACTDiabetic kidney disease (DKD) is the most common microvascular complication of diabetes, and there is an urgent need to discover reliable biomarkers for early diagnosis. Here, we established an effective urine multi-omics platform and integrated metabolomics and peptidomics to investigate the biological changes during DKD pathogenesis. Methods: Totally 766 volunteers (221 HC, 198 T2DM, 175 early DKD, 125 overt DKD, and 47 grey-zone T2DM patients with abnormal urinary mALB concentration) were included in this study. Non-targeted metabolic fingerprints of urine samples were acquired on matrix-free LDI-MS platform by the tip-contact extraction method using fluorinated ethylene propylene coated silicon nanowires chips (FEP@SiNWs), while peptide profiles hidden in urine samples were uncovered by MALDI-TOF MS after capturing urine peptides by porous silicon microparticles. Results: After multivariate analysis, ten metabolites and six peptides were verified to be stepwise regulated in different DKD stages. The altered metabolic pathways and biological processes associated with the DKD pathogenesis were concentrated in amino acid metabolism and cellular protein metabolic process, which were supported by renal transcriptomics. Interestingly, multi-omics significantly increased the diagnostic accuracy for both early DKD diagnosis and DKD status discrimination. Combined with machine learning, a stepwise prediction model was constructed and 89.9% of HC, 75.5% of T2DM, 69.6% of early DKD and 75.7% of overt DKD subjects in the external validation cohort were correctly classified. In addition, 87.5% of grey-zone patients were successfully distinguished from T2DM patients. Conclusion: This multi-omics platform displayed a satisfactory ability to explore molecular information and provided a new insight for establishing effective DKD management.PMID:37351171 | PMC:PMC10283058 | DOI:10.7150/thno.80435

Front Med (Lausanne). 2023 Jun 7;10:1183484. doi: 10.3389/fmed.2023.1183484. eCollection 2023.ABSTRACTOBJECTIVE: To compare and analyze the mucosal metabolites and mucosal microbiota of different parts of colon in patients with IBS.METHODS: A total of 10 patients with IBS-D and six healthy controls (HC) were enrolled. All enrolled participants underwent two biopsies of the ileocecal and sigmoid colon during colonoscopy. Metabolomic profiling of one piece of tissue was conducted using desorption electrospray ionization-mass spectrometry (DESI-MS), and the gut flora of the other piece was examined using 16S rRNA sequencing. The metabolic profiles and flora of the ileocecal and sigmoid colonic mucosa in each group were further analyzed in this study.RESULTS: (1) Principal components analysis (PCA) indicated that mucosal metabolites did not differ in different parts of the colon in either the IBS-D or HC groups. (2) In the mucosal microbiome analyses, no differences between the microbiota of the two parts of the colon were found by using Principal Co-ordinates Analysis (PCoA). In IBS group, comparing with sigmoid mucosa, the chao1 richness indice was higher and the Shannon index was lower in the ileocecal mucosa (p = 0.40, p = 0.22). However, in the HC group, microbiome analysis of the ileocecal mucosa showed lower values for Chao 1 and Shannon indices than those of the sigmoid colon mucosa (p = 0.06, p = 0.86). (3) Compared with the HC group, 1,113 metabolic signal peaks were upregulated, whereas 594 metabolites were downregulated in the IBS-D samples. Moreover, the PCA of the metabolites showed significant separation between the IBS-D and HC groups. (4) Chao1 expression was significantly higher in the mucosal microbiota with IBS-D than in the HC (p = 0.03). The Shannon index was lower in IBS-D, but the difference was not statistically significant (p = 0.53). PCoA revealed a significant difference in the microflora structure between the IBS-D and HC groups.CONCLUSION: The mucosal metabolic profile and mucosal flora structure of the colon were similar, despite different locations in IBS and healthy subjects. IBS had abnormal colonic mucosal metabolism and flora disturbances.PMID:37351069 | PMC:PMC10282601 | DOI:10.3389/fmed.2023.1183484

Front Med (Lausanne). 2023 Jun 7;10:1187941. doi: 10.3389/fmed.2023.1187941. eCollection 2023.NO ABSTRACTPMID:37351067 | PMC:PMC10282990 | DOI:10.3389/fmed.2023.1187941

Anal Chem. 2023 Jun 23. doi: 10.1021/acs.analchem.3c01343. Online ahead of print.ABSTRACTSubcellular compartmentalization ensures orderly and efficient intracellular metabolic activities in eukaryotic life. Investigation of the subcellular metabolome could provide in-depth insight into cellular biological activities. However, the sensitive measurement of multi-subcellular metabolic profiles is still a significant challenge. Herein, we present a comprehensive subcellular fractionation, characterization, and metabolome analysis strategy. First, six subcellular fractions including nuclei, mitochondria, lysosomes, peroxisomes, microsomes, and cytoplasm were generated from a single aliquot of liver homogenate. Then, a dansyl-labeling-assisted liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for measuring 151 amino/phenol- or carboxyl-containing metabolites in the subcellular fractions was established and validated. Last, the strategy was applied to a rat model of carbon tetrachloride (CCl4)-induced acute liver injury (ALI). The metabolic profile of individual organelles was compared with that of the liver. Interestingly, many unique changes were observed specifically in organelles, while the liver failed to capture these changes. This result indicates that metabolic investigation at the tissue level might lead to erroneous results due to the leveling effect. Our study demonstrates a feasible approach for the broad-spectrum-targeted metabolic profiling of multi-subcellular fractions, which can be of great use in driving our further understanding of intracellular metabolic activities in various physical and pathological conditions.PMID:37350701 | DOI:10.1021/acs.analchem.3c01343

mBio. 2023 Jun 23:e0034023. doi: 10.1128/mbio.00340-23. Online ahead of print.ABSTRACTNicotinamide adenine dinucleotide (NAD) and its phosphorylated derivative (NADP) are essential cofactors that participate in hundreds of biochemical reactions and have emerged as therapeutic targets in cancer, metabolic disorders, neurodegenerative diseases, and infections, including tuberculosis. The biological basis for the essentiality of NAD(P) in most settings, however, remains experimentally unexplained. Here, we report that inactivation of the terminal enzyme of NAD synthesis, NAD synthetase (NadE), elicits markedly different metabolic and microbiologic effects than those of the terminal enzyme of NADP biosynthesis, NAD kinase (PpnK), in Mycobacterium tuberculosis (Mtb). Inactivation of NadE led to parallel reductions of both NAD and NADP pools and Mtb viability, while inactivation of PpnK selectively depleted NADP pools but only arrested growth. Inactivation of each enzyme was accompanied by metabolic changes that were specific for the affected enzyme and associated microbiological phenotype. Bacteriostatic levels of NAD depletion caused a compensatory remodeling of NAD-dependent metabolic pathways in the absence of an impact on NADH/NAD ratios, while bactericidal levels of NAD depletion resulted in a disruption of NADH/NAD ratios and inhibition of oxygen respiration. These findings reveal a previously unrecognized physiologic specificity associated with the essentiality of two evolutionarily ubiquitous cofactors. IMPORTANCE The current course for cure of Mycobacterium tuberculosis (Mtb)-the etiologic agent of tuberculosis (TB)-infections is lengthy and requires multiple antibiotics. The development of shorter, simpler treatment regimens is, therefore, critical to the goal of eradicating TB. NadE, an enzyme required for the synthesis of the ubiquitous cofactor NAD, is essential for survival of Mtb and regarded as a promising drug target. However, the basis of this essentiality was not clear due to its role in the synthesis of both NAD and NADP. Here, we resolve this ambiguity through a combination of gene silencing and metabolomics. We specifically show that NADP deficiency is bacteriostatic, while NAD deficiency is bactericidal due to its role in Mtb's respiratory capacity. These results argue for a prioritization of NAD biosynthesis inhibitors in anti-TB drug development.PMID:37350592 | DOI:10.1128/mbio.00340-23

Cancer Med. 2023 Jun 23. doi: 10.1002/cam4.6233. Online ahead of print.ABSTRACTBACKGROUND: Carbohydrate antigen (CA) 19-9 is a known pancreatic cancer (PC) biomarker, but is not commonly used for general screening due to its low sensitivity and specificity. This study aimed to develop a serum metabolites-based diagnostic calculator for detecting PC with high accuracy.METHODS: A targeted quantitative approach of direct flow injection-tandem mass spectrometry combined with liquid chromatography-tandem mass spectrometry was employed for metabolomic analysis of serum samples using an Absolute IDQ™ p180 kit. Integrated metabolomic analysis was performed on 241 pooled or individual serum samples collected from healthy donors and patients from nine disease groups, including chronic pancreatitis, PC, other cancers, and benign diseases. Orthogonal partial least squares discriminant analysis (OPLS-DA) based on characteristics of 116 serum metabolites distinguished patients with PC from those with other diseases. Sparse partial least squares discriminant analysis (SPLS-DA) was also performed, incorporating simultaneous dimension reduction and variable selection. Predictive performance between discrimination models was compared using a 2-by-2 contingency table of predicted probabilities obtained from the models and actual diagnoses.RESULTS: Predictive values obtained through OPLS-DA for accuracy, sensitivity, specificity, balanced accuracy, and area under the receiver operating characteristic curve (AUC) were 0.9825, 0.9916, 0.9870, 0.9866, and 0.9870, respectively. The number of metabolite candidates was narrowed to 76 for SPLS-DA. The SPLS-DA-obtained predictive values for accuracy, sensitivity, specificity, balanced accuracy, and AUC were 0.9773, 0.9649, 0.9832, 0.9741, and 0.9741, respectively.CONCLUSIONS: We successfully developed a 76 metabolome-based diagnostic panel for detecting PC that demonstrated high diagnostic performance in differentiating PC from other diseases.PMID:37350558 | DOI:10.1002/cam4.6233

Aging Cell. 2023 Jun 23:e13902. doi: 10.1111/acel.13902. Online ahead of print.ABSTRACTThe study of age-related biomarkers from different biofluids and tissues within the same individual might provide a more comprehensive understanding of age-related changes within and between compartments as these changes are likely highly interconnected. Understanding age-related differences by compartments may shed light on the mechanism of their reciprocal interactions, which may contribute to the phenotypic manifestations of aging. To study such possible interactions, we carried out a targeted metabolomic analysis of plasma, skeletal muscle, and urine collected from healthy participants, age 22-92 years, and identified 92, 34, and 35 age-associated metabolites, respectively. The metabolic pathways that were identified across compartments included inflammation and cellular senescence, microbial metabolism, mitochondrial health, sphingolipid metabolism, lysosomal membrane permeabilization, vascular aging, and kidney function.PMID:37350292 | DOI:10.1111/acel.13902

Mol Plant. 2023 Jun 21:S1674-2052(23)00170-3. doi: 10.1016/j.molp.2023.06.004. Online ahead of print.ABSTRACTAlthough the plant kingdom provides an enormous diversity of metabolites with potentially beneficial applications for humankind, a large fraction of these metabolites and their biosynthetic pathways remains unknown. Resolving metabolite structures and their biosynthetic pathways is key to gaining biological understanding and to allow metabolic engineering. In order to retrieve novel biosynthetic genes involved in specialized metabolism, we developed a novel untargeted system-wide method in Arabidopsis thaliana, subjecting qualitative metabolic traits to a genome-wide association study (designated as Qualitative Trait GWAS or QT-GWAS), along with the more conventional metabolite GWAS (mGWAS) that considers the quantitative variation of metabolites. As proof of the validity of the QT-GWAS and mGWAS, 23 and 15 of the retrieved associations were supported by previous research. Furthermore, seven gene-metabolite associations retrieved by QT-GWAS were confirmed in this study through reverse genetics combined with metabolomics and/or in vitro enzyme assays. As such, we established that CYTOCHROME P450 706A5 (CYP706A5) is involved in the biosynthesis of chroman derivatives, UGT76C3 is able to hexosylate guanine in vitro and in planta, and SULFOTRANSFERASE 202B1 (SULT202B1) catalyzes the sulfation of neolignans in vitro.PMID:37349988 | DOI:10.1016/j.molp.2023.06.004

FEMS Microbiol Ecol. 2023 Jun 22:fiad068. doi: 10.1093/femsec/fiad068. Online ahead of print.ABSTRACTFecal microbiota transplantation (FMT) is an emerging technique for modulating the pig microbiota, however, donor variability is one of the major reasons for inconsistent outcomes across studies. Cultured microbial communities may address some limitations of FMT; however, no study has tested cultured microbial communities as inocula in pigs. This pilot study compared the effects of microbiota transplants derived from sow feces to cultured mixed microbial community (MMC) following weaning. Control, FMT4X, and MMC4X were applied 4 times, while treatment FMT1X was administered once (n = 12/group). On postnatal day 48, microbial composition was modestly altered in pigs receiving FMT in comparison with Control (Adonis, P = 0.003), mainly attributed to reduced inter-animal variations in pigs receiving FMT4X (Betadispersion, P = 0.018). Pigs receiving FMT or MMC had consistently enriched ASVs assigned to genera Dialister and Alloprevotella. Microbial transplantation increased propionate production in the cecum. MMC4X piglets showed a trend of higher acetate and isoleucine compared to Control. A consistent enrichment of metabolites from amino acid metabolism in pigs that received microbial transplantation coincided with enhanced aminoacyl-tRNA biosynthesis pathway. No differences were observed among treatment groups for body weight or cytokine/chemokine profiles. Overall, FMT and MMC exerted similar effects on gut microbiota composition and metabolite production.PMID:37349964 | DOI:10.1093/femsec/fiad068