PubMed

Methods Mol Biol. 2023;2642:163-177. doi: 10.1007/978-1-0716-3044-0_9.ABSTRACTBiostimulants show potentials as sustainable strategies for improved crop development and stress resilience. However, the cellular and molecular mechanisms, in particular the signaling and regulatory events, governing the agronomically observed positive effects of biostimulants on plants remain enigmatic, thus hampering novel formulation and exploration of biostimulants. Metabolomics offers opportunities to elucidate metabolic and regulatory processes that define biostimulant-induced changes in the plant's biochemistry and physiology, thus contributing to decode the modes of action of biostimulants. Here, we describe an application of metabolomics to elucidate biostimulant effects on crop plants. Using the case study of a humic substance (HS)-based biostimulant applied on maize plants, under normal and nutrient-starved stress conditions, this chapter proposes key methodological guidance and considerations of computational metabolomics approach to investigate metabolic and regulatory reconfiguration and networks underlying biostimulant-induced physiological changes in plants. Computational metabolome mining tools, in the Global Natural Products Social Molecular Networking (GNPS) ecosystem, are highlighted as well as metabolic pathway and network analysis for biological interpretation of the data.PMID:36944878 | DOI:10.1007/978-1-0716-3044-0_9

Methods Mol Biol. 2023;2642:151-161. doi: 10.1007/978-1-0716-3044-0_8.ABSTRACTLabeling plant material such as detached leaves with 15NH4+ is a very instrumental method for the characterization of metabolic pathways of mineral nitrogen assimilation and incorporation into amino acids. A procedure of labeling, followed by amino acid extraction, purification, and derivatization for gas chromatography coupled to mass spectrometry (GC/MS) analysis, is presented. The rationale of heavy isotope abundance calculations and amino acid quantification is detailed. This method is adaptable to various plant species and various kinds of investigations, such as elucidating physiological changes occurring as a result of gene mutations (overexpression or inhibition) in natural variants or genetically modified crops, or characterization of metabolic fluxes in genotypes exhibiting contrasted physiological or developmental adaptive responses to biotic and/or abiotic environmental stresses. Furthermore, the benefit of working on detached organs or pieces of organs is to investigate finely the metabolism of species that are not amenable to laboratory work, such as plants growing in natural environments or under agricultural conditions in the field.PMID:36944877 | DOI:10.1007/978-1-0716-3044-0_8

Nat Commun. 2023 Mar 21;14(1):1292. doi: 10.1038/s41467-023-36904-3.ABSTRACTThe pristine sample from the near-Earth carbonaceous asteroid (162173) Ryugu collected by the Hayabusa2 spacecraft enabled us to analyze the pristine extraterrestrial material without uncontrolled exposure to the Earth's atmosphere and biosphere. The initial analysis team for the soluble organic matter reported the detection of wide variety of organic molecules including racemic amino acids in the Ryugu samples. Here we report the detection of uracil, one of the four nucleobases in ribonucleic acid, in aqueous extracts from Ryugu samples. In addition, nicotinic acid (niacin, a B3 vitamer), its derivatives, and imidazoles were detected in search for nitrogen heterocyclic molecules. The observed difference in the concentration of uracil between A0106 and C0107 may be related to the possible differences in the degree of alteration induced by energetic particles such as ultraviolet photons and cosmic rays. The present study strongly suggests that such molecules of prebiotic interest commonly formed in carbonaceous asteroids including Ryugu and were delivered to the early Earth.PMID:36944653 | DOI:10.1038/s41467-023-36904-3

Food Chem Toxicol. 2023 Mar 19:113737. doi: 10.1016/j.fct.2023.113737. Online ahead of print.ABSTRACTObesity caused by endocrine disruptors (EDCs) has become a hot topic threatening human health. Recently, Nanoselenium Siraitia grosvenorii (NSG) has been shown to have potential health-modulating uses. Based on the results of 16S rRNA sequencing and metabolomics analysis, NSG has the unique function of improving gut microbiota and inhibiting obesity. Specifically, NSG can enhance gut microbiota diversity and change their composition. A significant positive correlation exists between the liver change in lysine and the high-importance dominant species ([Ruminococcus]_gnavus, Alistipes_finegoldii, etc.). NSG metabolites analysis showed that the lysine level increased by 44.45% and showed a significantly negatively correlated with (TG, TC, Leptin, etc.). Significantly, NSG reduces the degradation of lysine metabolism in the liver and inhibits fatty acid β-oxidation. In addition, NSG decreased Acetyl-CoA levels by 24% and regulated the downregulation of TCA genes (CS, Ogdh, Fh1, and Mdh2) and the upregulation of ketone body production genes (BDH1). NSG may have a positive effect on obesity by reducing the participation of Acetyl-CoA in the TCA cycle pathway and enhancing the ketogenic conversion of Acetyl-CoA. In conclusion, the results of this study may provide a new dietary intervention strategy for preventing endocrine disruptor-induced obesity.PMID:36944396 | DOI:10.1016/j.fct.2023.113737

Bioinformatics. 2023 Mar 21:btad143. doi: 10.1093/bioinformatics/btad143. Online ahead of print.ABSTRACTSUMMARY: Data integration workflows for multiomics data take many forms across academia and industry. Efforts with limited resources often encountered in academia can easily fall short of data integration best practices for processing and combining high content imaging, proteomics, metabolomics and other omics data. We present Phenonaut, a Python software package designed to address the data workflow needs of migration, control, integration, and auditability in the application of literature and proprietary techniques for data source and structure agnostic workflow creation.AVAILABILITY AND IMPLEMENTATION: Source code: https://github.com/CarragherLab/phenonaut, Documentation: https://carragherlab.github.io/phenonaut, PyPI package: https://pypi.org/project/phenonaut/.SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.PMID:36944259 | DOI:10.1093/bioinformatics/btad143

Anal Chem. 2023 Mar 21. doi: 10.1021/acs.analchem.2c04402. Online ahead of print.ABSTRACTMulticlass metabolomics has been widely applied in clinical practice to understand pathophysiological processes involved in disease progression and diagnostic biomarkers of various disorders. In contrast to the binary problem, the multiclass classification problem is more difficult in terms of obtaining reliable and stable results due to the increase in the complexity of determining exact class decision boundaries. In particular, methods of biomarker discovery and classification have a significant effect on the multiclass model because different methods with significantly varied theories produce conflicting results even for the same dataset. However, a systematic assessment for selecting the most appropriate methods of biomarker discovery and classification for multiclass metabolomics is still lacking. Therefore, a comprehensive assessment is essential to measure the suitability of methods in multiclass classification models from multiple perspectives. In this study, five biomarker discovery methods and nine classification methods were assessed based on four benchmark datasets of multiclass metabolomics. The performance assessment of the biomarker discovery and classification methods was performed using three evaluation criteria: assessment a (cluster analysis of sample grouping), assessment b (biomarker consistency in multiple subgroups), and assessment c (accuracy in the classification model). As a result, 13 combining strategies with superior performance were selected under multiple criteria based on these benchmark datasets. In conclusion, superior strategies that performed consistently well are suggested for the discovery of biomarkers and the construction of a classification model for multiclass metabolomics.PMID:36944135 | DOI:10.1021/acs.analchem.2c04402

PLoS One. 2023 Mar 21;18(3):e0283147. doi: 10.1371/journal.pone.0283147. eCollection 2023.ABSTRACTThe fresh leaves of Mitragyna speciosa (Korth.) Havil. have been traditionally consumed for centuries in Southeast Asia for its healing properties. Although the alkaloids of M. speciosa have been studied since the 1920s, comparative and systematic studies of metabolite composition based on different leaf maturity levels are still lacking. This study assessed the secondary metabolite composition in two different leaf stages (young and mature) of M. speciosa, using an untargeted liquid chromatography-electrospray ionisation-time-of-flight-mass spectrometry (LC-ESI-TOF-MS) metabolite profiling. The results revealed 86 putatively annotated metabolite features (RT:m/z value) comprising 63 alkaloids, 10 flavonoids, 6 terpenoids, 3 phenylpropanoids, and 1 of each carboxylic acid, glucoside, phenol, and phenolic aldehyde. The alkaloid features were further categorised into 14 subclasses, i.e., the most abundant class of secondary metabolites identified. As per previous reports, indole alkaloids are the most abundant alkaloid subclass in M. speciosa. The result of multivariate analysis (MVA) using principal component analysis (PCA) showed a clear separation of 92.8% between the young and mature leaf samples, indicating a high variance in metabolite levels between them. Akuammidine, alstonine, tryptamine, and yohimbine were tentatively identified among the many new alkaloids reported in this study, depicting the diverse biological activities of M. speciosa. Besides delving into the knowledge of metabolite distribution in different leaf stages, these findings have extended the current alkaloid repository of M. speciosa for a better understanding of its pharmaceutical potential.PMID:36943850 | DOI:10.1371/journal.pone.0283147

Food Funct. 2023 Mar 21. doi: 10.1039/d2fo04085a. Online ahead of print.ABSTRACTTo investigate the prebiotic potential of two Laminaria japonica polysaccharide (LJP) fractions with different molecular weights and structures, we conducted in vitro simulated digestion and fermentation with hyperlipidemia-associated human gut microbiota. The results indicated that the LJP fraction with higher molecular weight (HLJP) appeared to have a more complex monosaccharide composition and microstructure than did the LJP fraction with lower molecular weight (LLJP), and both fractions could not be digested by in vitro simulated digestion. After in vitro fermentation, HLJP generated more short-chain fatty acids (SCFAs) and showed stronger ability to regulate core metabolites. Intriguingly, LLJP is better at promoting the proliferation of Akkermansiaceae, while HLJP is more effective in reducing the Firmicutes/Bacteroidetes ratio and increasing the content of Bacteroidaceae and Tannerellaceae. The present study indicates that LLJP and HLJP may have probiotic effects through different approaches and these differences may be related to the molecular weight and structure of the polysaccharides.PMID:36943742 | DOI:10.1039/d2fo04085a

Microbiol Spectr. 2023 Mar 21:e0469122. doi: 10.1128/spectrum.04691-22. Online ahead of print.ABSTRACTOuter membrane vesicles (OMVs) are a primary means of communication for Gram-negative bacteria. The specific role of vesicle components in cellular communication and how components are packaged are still under investigation, but a correlation exists between OMV biogenesis and content. The two primary mechanisms of OMV biogenesis are membrane blebbing and explosive cell lysis, and vesicle content is based on the biogenesis mechanism. Hypervesiculation, which can be induced by stress conditions, also influences OMV content. Norovirus interaction with Enterobacter cloacae induces stress responses leading to increased OMV production and changes in DNA content, protein content, and vesicle size. The presence of genomic DNA and cytoplasmic proteins in these OMVs suggests some of the vesicles are formed by explosive cell lysis, so reduction or loss of these components indicates a shift away from this mechanism of biogenesis. Based on this, further investigation into bacterial stability and OMV content was conducted. Results showed that norovirus induced a dramatic shift in OMV lipid content. Specifically, the increased accumulation of phospholipids is associated with increased blebbing, thereby supporting previous observations that noroviruses shift the mechanism of OMV biogenesis. Slight differences in OMV metabolite content were also observed. While norovirus induced changes in OMV content, it did not change the lipid content of the bacterial outer membrane or the metabolite content of the bacterial cell. Overall, these results indicate that norovirus induces significant changes to OMV lipid architecture and cargo, which may be linked to a change in the mechanism of vesicle biogenesis. IMPORTANCE Extracellular vesicles from commensal bacteria are recognized for their importance in modulating host immune responses, and vesicle content is related to their impact on the host. Therefore, understanding how vesicles are formed and how their content shifts in response to stress conditions is necessary for elucidating their downstream functions. Our recent work has demonstrated that interactions between noroviruses and Enterobacter cloacae induce bacterial stress responses leading to hypervesiculation. In this article, we characterize and compare the lipid and metabolomic cargo of E. cloacae vesicles generated in the presence and absence of norovirus and show that viral interactions induce significant changes in vesicle content. Furthermore, we probe how these changes and changes to the bacterial cell may be indicative of a shift in the mechanism of vesicle biogenesis. Importantly, we find that noroviruses induce significant changes in vesicle lipid architecture and cargo that may be responsible for the immunogenic activity of these vesicles.PMID:36943087 | DOI:10.1128/spectrum.04691-22

Microbiol Spectr. 2023 Mar 21:e0333022. doi: 10.1128/spectrum.03330-22. Online ahead of print.ABSTRACTThe Integrative Human Microbiome Project and other cohort studies have indicated that inflammatory bowel disease is accompanied by dysbiosis of gut microbiota, decreased production of secondary bile acids, and increased levels of primary bile acids. Secondary bile acids, such as ursodeoxycholic acid (UDCA) and lithocholic acid (LCA), have been reported to be anti-inflammatory, yet it remains to be studied whether introducing selected bacteria strains to restore bile acid metabolism of the gut microbiome can alleviate intestinal inflammation. In this study, we screened human gut bacterial strains for bile acid metabolism and designed a consortium of three species, including Clostridium AP sp000509125, Bacteroides ovatus, and Eubacterium limosum, and named it BAC (bile acid consortium). We showed that the three-strain gut bacterial consortium BAC is capable of converting conjugated primary bile acids taurochenodeoxycholic acid and glycochenodeoxycholic acid to secondary bile acids UDCA and LCA in vitro. Oral gavage treatment with BAC in mice resulted in protective effects against dextran sulfate sodium (DSS)-induced colitis, including reduced weight loss and increased colon length. Furthermore, BAC treatment increased the fecal level of bile acids, including UDCA and LCA. BAC treatment enhanced intestinal barrier function, which may be attributed to the increased activation of the bile acid receptor TGR5 by secondary bile acids. Finally, we examined the remodeling of gut microbiota by BAC treatment. Taken together, the three-strain gut bacterial consortium BAC restored the dysregulated bile acid metabolism and alleviated DSS-induced colitis. Our study provides a proof-of-concept demonstration that a rationally designed bacterial consortium can reshape the metabolism of the gut microbiome to treat diseases. IMPORTANCE Secondary bile acids have been reported to be anti-inflammatory, yet it remains to be studied whether introducing selected bacteria strains to restore bile acid metabolism of the gut microbiome can alleviate intestinal inflammation. To address this gap, we designed a consortium of human gut bacterial strains based on their metabolic capacity to produce secondary bile acids UDCA and LCA, and we evaluated the efficacy of single bacterial strains and the bacterial consortium in treating the murine colitis model. We found that oral gavage of the bacterial consortium to mice restored secondary bile acid metabolism to increase levels of UDCA and LCA, which induced the activation of TGR5 to improve gut-barrier integrity and reduced the inflammation in murine colitis. Overall, our study demonstrates that rationally designed bacterial consortia can reshape the metabolism of the gut microbiome and provides novel insights into the application of live biotherapeutics for treating IBD.PMID:36943054 | DOI:10.1128/spectrum.03330-22

Biomed Chromatogr. 2023 Mar 21:e5620. doi: 10.1002/bmc.5620. Online ahead of print.ABSTRACTCitronella is used as a spice and traditional herbal medicine. Dried citronella is easy to store and transport, and it is unclear whether dried citronella has increased or decreased medicinal components compared to fresh citronella. In the present study, various metabolites in fresh and dry citronella were detected using a widely targeted metabolomics strategy. we identified 712 metabolites, and classified as 31 categories, and discovered 132 flavonoids. After the drying of citronella, the contents of most kinds of flavonoids increased, but the contents of amino acids, organic acids and vitamins decreased, and the content of quercetin increased significantly. Therefore, the medicinal value of citronella after drying treatment may be increased, but the nutritional value of amino acids and vitamins may be decreased. The results of this study may serve as a new theoretical reference for deal with citronella and promote the nutrition and medicinal chemical composition of citronella.PMID:36942894 | DOI:10.1002/bmc.5620

Gut Microbes. 2023 Jan-Dec;15(1):2192151. doi: 10.1080/19490976.2023.2192151.ABSTRACTThe development of infant gut microbiome is a pivotal process affecting the ecology and function of the microbiome, as well as host health. While the establishment of the infant microbiome has been of interest for decades, the focus on gut microbial metabolism and the resulting small molecules (metabolites) has been rather limited. However, technological and computational advances are now enabling researchers to profile the plethora of metabolites in the infant gut, allowing for improved understanding of how gut microbial-derived metabolites drive microbiome community structuring and host-microbial interactions. Here, we review the current knowledge on development of the infant gut microbiota and metabolism within the first year of life, and discuss how these microbial metabolites are key for enhancing our basic understanding of interactions during the early life developmental window.PMID:36942883 | DOI:10.1080/19490976.2023.2192151

Curr Opin Clin Nutr Metab Care. 2023 Jan 2. doi: 10.1097/MCO.0000000000000906. Online ahead of print.ABSTRACTPURPOSE OF REVIEW: This review provides an overview of most recent research studies employing nuclear magnetic resonance (NMR)-based metabolomics in the assessment of effects of diet and food ingestion.RECENT FINDINGS: NMR metabolomics is a useful tool in the elucidation of specific diets, for example, the Mediterranean diet, the New Nordic diet types, and also for comparing vegan, vegetarian and omnivore diets where specific diet-linked metabolite perturbations have been identified. Another core area where NMR metabolomics is employed involves research focused on examining specific food components or ingredients, including dietary fibers and other functional components. In several cases, NMR metabolomics has aided to document how specific food components exert effects on the metabolic activity of the gut microbiota. Research has also demonstrated the potential use of NMR metabolomics in assessing diet quality and interactions between specific food components such as meat and diet quality. The implications of these findings are important as they address that background diet can be decisive for if food items turn out to exert either harmful or health-promoting effects.SUMMARY: NMR metabolomics can provide important mechanistic insight and aid to biomarker discovery with implications for compliance and food registration purposes.PMID:36942870 | DOI:10.1097/MCO.0000000000000906

Biotechnol Genet Eng Rev. 2023 Mar 21:1-18. doi: 10.1080/02648725.2023.2191069. Online ahead of print.ABSTRACTOBJECTIVE: To explore and analyze the diagnostic value of metabolic markers in cerebrospinal fluid (CSF) in leptomeningeal metastases (LM) of non-small cell lung cancer (NSCLC).METHODS: Forty-six CSF samples from patients with NSCLC-LM were collected. Another 48 CSF samples from patients with nonmalignant neurological diseases were selected as control group. Metabolomic analysis of CSF was performed by high-performance liquid chromatography-mass spectrometry. Principal component analysis (PCA) and orthogonal partial least squares discriminant analysis (OPLS-DA) were applied for modeling. A multi-criteria evaluation system (variable importance value >1, multiple of change >2 and P < 0.05 for univariate analysis) was used to find differential metabolites between two groups. The subject working characteristic curves and pathway enrichment analysis were used to screen metabolites and pathways associated with NSCLC-LM.RESULTS: The PCA model and OPLS-DA model showed good overall data quality. Thirty endogenous differential metabolites were screened, and six potential biomarkers were further identified, including tyrosine (t = 3.37, P = 0.024, AUC = 0.967), phenylalanine (t = 3.98, P < 0.001, AUC = 0.992), pyruvate (t = 4.48, P < 0.001, AUC = 0.976), tryptophan (t = -2.5, P = 0.014, AUC = 0.935), adenosine monophosphate (t = -6.13, P < 0.001, AUC = 0.932) and glucose (t = -4.00, P < 0.001, AUC = 0.993). Thirty differential metabolites screened were subjected to metabolic pathway enrichment analysis and matched to 20 relevant metabolic pathways, of which the four most likely to cause metabolite changes were as follows: glycolysis and sugar metabolism synthesis, pyruvate metabolism, phenylalanine metabolism, and phenylalanine, tyrosine and tryptophan biosynthesis.CONCLUSIONS: Untargeted metabolomics can effectively screen for CSF metabolites specific to NSCLC-LM patients, and six potential metabolites and their metabolic pathways might be involved in the pathogenesis of NSCLC-LM.PMID:36942709 | DOI:10.1080/02648725.2023.2191069

J Sci Food Agric. 2023 Mar 21. doi: 10.1002/jsfa.12563. Online ahead of print.ABSTRACTBACKGROUND: Panax quinquefolius L. is one of the most important foods and herbs because of its high nutritional value and medicinal potential. In our previous study we found that the content of ginsenoside in P. quinquefolius was improved by arbuscular mycorrhizal fungi (AMF). However, little research has been conducted on the molecular mechanisms in P. quinquefolius roots induced by AMF colonization. To identify the metabolomic and transcriptomic mechanisms of P. quinquefolius induced by AMF, the non-mycorrhized (Control) and mycorrhized (AMF) of P. quinquefolius were used as experimental materials for comparative analysis of transcriptome and metabolome.RESULTS: Compared with the control, 182 metabolites and 545 genes were significantly changed at the metabolic and transcriptional levels in AMF treatment. The metabolic pattern of AMF was changed, and the contents of ginsenosides (Rb1, Rg2), threonine and glutaric acid were significantly increased. There were significant differences in the expression of genes involved in plant hormone signal transduction, glutathione metabolism, and the plant-pathogen interaction pathway. In addition, several transcription factors from NAC, WRKY and bHLH families were identified in AMF vs the control. Furthermore, the combined analysis of "transcriptomic-metabolomics" analysis showed that "Plant hormone signal transduction", "Amino sugar and nucleotide sugar metabolism" and "Glutathione metabolism" pathway were the important enriched pathway in response to AMF colonization.CONCLUSION: Overall, these results provide new insights into P. quinquefolius response to AMF, which improve our understanding of the molecular mechanisms of P. quinquefolius induced by AMF. This article is protected by copyright. All rights reserved.PMID:36942522 | DOI:10.1002/jsfa.12563

Mater Today Bio. 2023 Mar 4;19:100602. doi: 10.1016/j.mtbio.2023.100602. eCollection 2023 Apr.ABSTRACTBlack phosphorus quantum dots (BPQDs) have shown potential in tumor therapy, however, their anti-angiogenic functions have not been studied. Although BPQDs are easily degraded to non-toxic phosphrous, the reported toxicity, poor stability, and non-selectivity largely limit their further application in medicine. In this study, a vascular targeting, biocompatible, and cell metabolism-disrupting nanoplatform is engineered by incorporating BPQDs into exosomes modified with the Arg-Gly-Asp (RGD) peptide (BPQDs@RGD-EXO nanospheres, BREs). BREs inhibit endothelial cells (ECs) proliferation, migration, tube formation, and sprouting in vitro. The anti-angiogenic role of BREs in vivo is evaluated using mouse retinal vascular development model and oxygen-induced retinopathy model. Combined RNA-seq and metabolomic analysis reveal that BREs disrupt glucose metabolism, which is further confirmed by evaluating metabolites, ATP production and the c-MYC/Hexokinase 2 pathway. These BREs are promising anti-angiogenic platforms for the treatment of pathological retinal angiogenesis with minimal side effects.PMID:36942311 | PMC:PMC10024194 | DOI:10.1016/j.mtbio.2023.100602

PeerJ. 2023 Mar 15;11:e15051. doi: 10.7717/peerj.15051. eCollection 2023.ABSTRACTBACKGROUND: Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) is an autoimmune systemic disease, and the majority of AAV patients have renal involvement presenting as rapid progressive glomerulonephritis (GN). Currently, the clinically available AAV markers are limited, and some of the newly reported markers are still in the nascent stage. The particular mechanism of the level changes of various markers and their association with the pathogenesis of AAV are not well defined. With the help of metabolomics analysis, this study aims to explore metabolic changes in AAV patients with renal involvement and lay the foundation for the discovery of novel biomarkers for AAV-related kidney damage.METHODS: We performed liquid chromatography-tandem mass spectrometry (LC-MS/MS)-based on serum samples from patients with AAV (N = 33) and healthy controls (N = 33) in order to characterize the serum metabolic profiling. The principal component analysis (PCA) and orthogonal partial least-squares-discriminant analysis (OPLS-DA) were used to identify the differential metabolites. Least Absolute Shrinkage and Selection Operator (LASSO) and eXtreme Gradient Boosting (XGBoost) analysis were further conducted to identify the potential diagnostic biomarker. A receiver operating characteristic (ROC) curve analysis was conducted to evaluate the diagnostic performance of the identified potential biomarker.RESULTS: A total of 455 metabolites were detected by LC-MS analysis. PCA and OPLS-DA demonstrated a significant difference between AAV patients with renal involvement and healthy controls, and 135 differentially expressed metabolites were selected, with 121 upregulated and 14 downregulated. Ninety-two metabolic pathways were annotated and enriched based on the KEGG database. N-acetyl-L-leucine, Acetyl-DL-Valine, 5-hydroxyindole-3-acetic acid, and the combination of 1-methylhistidine and Asp-phe could accurately distinguish AAV patients with renal involvement from healthy controls. And 1-methylhistidine was found to be significantly associated with the progression and prognosis of AAV with renal impairment. Amino acid metabolism exhibits significant alternations in AAV with renal involvement.CONCLUSION: This study identified metabolomic differences between AAV patients with renal involvement and non-AAV individuals. Metabolites that could accurately distinguish patients with AAV renal impairment from healthy controls in this study, and metabolites that were significantly associated with disease progression and prognosis were screened out. Overall, this study provides information on changes in metabolites and metabolic pathways for future studies of AAV-related kidney damage and lays a foundation for the exploration of new biomarkers of AAV-related kidney damage.PMID:36942002 | PMC:PMC10024486 | DOI:10.7717/peerj.15051

Mol Ecol Resour. 2023 Mar 20. doi: 10.1111/1755-0998.13786. Online ahead of print.ABSTRACTAlthough being famous for sequestering milkweed cardenolides, the mechanism of sequestration and where cardenolides are localized in caterpillars of the monarch butterfly (Danaus plexippus, Lepidoptera: Danaini) is still unknown. While monarchs tolerate cardenolides by a resistant Na+ /K+ -ATPase, it is unclear how closely related species such as the non-sequestering common crow butterfly (Euploea core, Lepidoptera: Danaini) cope with these toxins. Using novel atmospheric-pressure scanning microprobe matrix-assisted laser/desorption ionization mass spectrometry imaging, we compared the distribution of cardenolides in caterpillars of D. plexippus and E. core. Specifically, we tested at which physiological scale quantitative differences between both species are mediated and how cardenolides distribute across body tissues. Whereas D. plexippus sequestered most cardenolides from milkweed (Asclepias curassavica), no cardenolides were found in the tissues of E. core. Remarkably, quantitative differences already manifest in the gut lumen: while monarchs retain and accumulate cardenolides above plant concentrations, the toxins are degraded in the gut lumen of crows. We visualized cardenolide transport over the monarch midgut epithelium and identified integument cells as the final site of storage where defenses might be perceived by predators. Our study provides molecular insight into cardenolide sequestration and highlights the great potential of mass spectrometry imaging for understanding the kinetics of multiple compounds including endogenous metabolites, plant toxins, or insecticides in insects.PMID:36941779 | DOI:10.1111/1755-0998.13786

Nat Med. 2023 Mar 20. doi: 10.1038/s41591-023-02248-0. Online ahead of print.ABSTRACTMultiomic profiling can reveal population heterogeneity for both health and disease states. Obesity drives a myriad of metabolic perturbations and is a risk factor for multiple chronic diseases. Here we report an atlas of cross-sectional and longitudinal changes in 1,111 blood analytes associated with variation in body mass index (BMI), as well as multiomic associations with host polygenic risk scores and gut microbiome composition, from a cohort of 1,277 individuals enrolled in a wellness program (Arivale). Machine learning model predictions of BMI from blood multiomics captured heterogeneous phenotypic states of host metabolism and gut microbiome composition better than BMI, which was also validated in an external cohort (TwinsUK). Moreover, longitudinal analyses identified variable BMI trajectories for different omics measures in response to a healthy lifestyle intervention; metabolomics-inferred BMI decreased to a greater extent than actual BMI, whereas proteomics-inferred BMI exhibited greater resistance to change. Our analyses further identified blood analyte-analyte associations that were modified by metabolomics-inferred BMI and partially reversed in individuals with metabolic obesity during the intervention. Taken together, our findings provide a blood atlas of the molecular perturbations associated with changes in obesity status, serving as a resource to quantify metabolic health for predictive and preventive medicine.PMID:36941332 | DOI:10.1038/s41591-023-02248-0

Signal Transduct Target Ther. 2023 Mar 20;8(1):132. doi: 10.1038/s41392-023-01399-3.ABSTRACTMetabolic abnormalities lead to the dysfunction of metabolic pathways and metabolite accumulation or deficiency which is well-recognized hallmarks of diseases. Metabolite signatures that have close proximity to subject's phenotypic informative dimension, are useful for predicting diagnosis and prognosis of diseases as well as monitoring treatments. The lack of early biomarkers could lead to poor diagnosis and serious outcomes. Therefore, noninvasive diagnosis and monitoring methods with high specificity and selectivity are desperately needed. Small molecule metabolites-based metabolomics has become a specialized tool for metabolic biomarker and pathway analysis, for revealing possible mechanisms of human various diseases and deciphering therapeutic potentials. It could help identify functional biomarkers related to phenotypic variation and delineate biochemical pathways changes as early indicators of pathological dysfunction and damage prior to disease development. Recently, scientists have established a large number of metabolic profiles to reveal the underlying mechanisms and metabolic networks for therapeutic target exploration in biomedicine. This review summarized the metabolic analysis on the potential value of small-molecule candidate metabolites as biomarkers with clinical events, which may lead to better diagnosis, prognosis, drug screening and treatment. We also discuss challenges that need to be addressed to fuel the next wave of breakthroughs.PMID:36941259 | DOI:10.1038/s41392-023-01399-3