PubMed

Front Microbiol. 2023 Sep 15;14:1250891. doi: 10.3389/fmicb.2023.1250891. eCollection 2023.ABSTRACTINTRODUCTION: The accelerated aging of the global population has emerged as a critical public health concern, with increasing recognition of the influential role played by the microbiome in shaping host well-being. Nonetheless, there remains a dearth of understanding regarding the functional alterations occurring within the microbiota and their intricate interactions with metabolic pathways across various stages of aging.METHODS: This study employed a comprehensive metagenomic analysis encompassing saliva and stool samples obtained from 45 pigs representing three distinct age groups, alongside serum metabolomics and lipidomics profiling.RESULTS: Our findings unveiled discernible modifications in the gut and oral microbiomes, serum metabolome, and lipidome at each age stage. Specifically, we identified 87 microbial species in stool samples and 68 in saliva samples that demonstrated significant age-related changes. Notably, 13 species in stool, including Clostridiales bacterium, Lactobacillus johnsonii, and Oscillibacter spp., exhibited age-dependent alterations, while 15 salivary species, such as Corynebacterium xerosis, Staphylococcus sciuri, and Prevotella intermedia, displayed an increase with senescence, accompanied by a notable enrichment of pathogenic organisms. Concomitant with these gut-oral microbiota changes were functional modifications observed in pathways such as cell growth and death (necroptosis), bacterial infection disease, and aging (longevity regulating pathway) throughout the aging process. Moreover, our metabolomics and lipidomics analyses unveiled the accumulation of inflammatory metabolites or the depletion of beneficial metabolites and lipids as aging progressed. Furthermore, we unraveled a complex interplay linking the oral-gut microbiota with serum metabolites and lipids.DISCUSSION: Collectively, our findings illuminate novel insights into the potential contributions of the oral-gut microbiome and systemic circulating metabolites and lipids to host lifespan and healthy aging.PMID:37789859 | PMC:PMC10542583 | DOI:10.3389/fmicb.2023.1250891

Front Microbiol. 2023 Sep 18;14:1171563. doi: 10.3389/fmicb.2023.1171563. eCollection 2023.ABSTRACTDried distillers' grains with solubles (DDGS) are rich in nutrients, and partially alternative feeding of DDGS effectively reduces cost of feed and improves animals' growth. We used 16S rDNA gene sequencing and LC/MS-based metabolomics to explore the effect of feeding cattle with a basal diet (BD) and a Jiang-flavor DDGS diet (replaces 25% concentrate of the diet) on microbiome and metabolome of ruminal and cecal contents in Guanling yellow cattle. The results showed that the ruminal and cecal contents shared the same dominance of Bacteroidetes, Firmicutes and Proteobacteria in two groups. The ruminal dominant genera were Prevotella_1, Rikenellaceae_RC9_gut_group, and Ruminococcaceae_UCG-010; and the cecal dominant genera were Ruminococcaceae_UCG-005, Ruminococcaceae_UCG-010, and Rikenellaceae_RC9_gut_group. Linear discriminant analysis effect size analysis (LDA > 2, P < 0.05) revealed the significantly differential bacteria enriched in the DDGS group, including Ruminococcaceae_UCG_012, Prevotellaceae_UCG_004 and Anaerococcus in the ruminal contents, which was associated with degradation of plant polysaccharides. Besides, Anaerosporobacter, Anaerovibrio, and Caproiciproducens in the cecal contents were involved in fatty acid metabolism. Compared with the BD group, 20 significantly different metabolites obtained in the ruminal contents of DDGS group were down-regulated (P < 0.05), and based on them, 4 significantly different metabolic pathways (P < 0.05) were enriched including "Linoleic acid metabolism," "Biosynthesis of unsaturated fatty acids," "Taste transduction," and "Carbohydrate digestion and absorption." There were 65 significantly different metabolites (47 were upregulated, 18 were downregulated) in the cecal contents of DDGS group when compared with the BD group, and 4 significantly different metabolic pathways (P < 0.05) were enriched including "Longevity regulating pathway," "Bile secretion," "Choline metabolism in cancer," and "HIF-1 signaling pathway." Spearman analysis revealed close negative relationships between the top 20 significantly differential metabolites and Anaerococcus in the ruminal contents. Bacteria with high relevance to cecal differential metabolites were Erysipelotrichaceae_UCG-003, Dielma, and Solobacterium that affect specific metabolic pathways in cattle. Collectively, our results suggest that feeding cattle with a DDGS diet improves the microbial structure and the metabolic patterns of lipids and carbohydrates, thus contributing to the utilization efficiency of nutrients and physical health to some extent. Our findings will provide scientific reference for the utilization of DDGS as feed in cattle industry.PMID:37789852 | PMC:PMC10543695 | DOI:10.3389/fmicb.2023.1171563

Front Microbiol. 2023 Sep 18;14:1191392. doi: 10.3389/fmicb.2023.1191392. eCollection 2023.ABSTRACTINTRODUCTION: Recently, the research on pig intestinal microbiota has become a hot topic in the field of animal husbandry. There are few articles describing the dynamic changes of porcine fecal microbiota and metabolites at different time points from birth to market.METHODS: In the present study, 381 fecal samples were collected from 633 commercial pigs at 7 time points, including the 1st day, the 10th day, the 25th day, the 45th day, the 70th day, the 120th day, and the 180th day after the birth of swine, were used for microbiome analysis by Illumina MiSeq sequencing methods while 131 fecal samples from 3 time points, the 10th day, the 25th day, and 70th day after birth, were used for metabolome analysis by LC-MS methods.RESULTS: For the microbiome analysis, the fecal microbial richness increased over time from day 1 to 180 and the β-diversity of fecal microbiota was separated significantly at different time points. Firmicutes were the main phyla from day 10 to 180, followed by Bacteroides. The abundance of Lactobacillus increased significantly on day 120 compared with the previous 4 time points. From day 120 to day 180, the main porcine fecal microbes were Lactobacillus, Clostridium_sensu_stricto_1, Terrisporobacter and Streptococcus. Clostridium_sensu_stricto_1 and Terrisporobacter increased over time, while Lactobacillus, Escherichia-Shigella, Lachnoclostridium decreased with the time according to the heatmap, which showed the increase or decrease in microbial abundance over time. For the metabolome analysis, the PLS-DA plot could clearly distinguish porcine fecal metabolites on day 10, 25, and 70. The most different metabolic pathways of the 3 time points were Tryptophan metabolism, Sphingolipid signaling pathway, Protein digestion and absorption. Some metabolites increased significantly over time, such as Sucrose, L-Arginine, Indole, 2,3-Pyridinedicarboxylic acid and so on, while D-Maltose, L-2-Aminoadipic acid, 2,6-diaminohexanoic acid, L-Proline were opposite. The correlation between fecal metabolites and microbiota revealed that the microbes with an increasing trend were positively correlated with the metabolites affecting the tryptophan metabolic pathway from the overall trend, while the microbes with a decreasing trend were opposite. In addition, the microbes with an increasing trend were negatively correlated with the metabolites affecting the lysine pathway.DISCUSSION: In conclusion, this study elucidated the dynamic changes of porcine fecal microbiota and metabolites at different stages from birth to market, which may provide a reference for a comprehensive understanding of the intestinal health status of pigs at different growth stages.PMID:37789849 | PMC:PMC10543884 | DOI:10.3389/fmicb.2023.1191392

Life Sci. 2023 Oct 1:122137. doi: 10.1016/j.lfs.2023.122137. Online ahead of print.ABSTRACTCirculating metabolites are indicators of systemic metabolic dysfunction and can be detected through contemporary techniques in metabolomics. These metabolites are involved in numerous mitochondrial metabolic processes including glycolysis, fatty acid β-oxidation, and amino acid catabolism, and changes in abundance of these metabolites is implicated in the pathogenesis of cardiometabolic diseases (CMDs). Epigenetic regulation and direct metabolite-protein interactions modulate the metabolism, both within cells and in the circulation. Dysfunction of multiple mitochondrial components stemming from mitochondrial DNA mutations are implicated in disease pathogenesis. This review will summarize the current state of knowledge regarding: i) the interactions between metabolites found within the mitochondrial environment during CMDs, ii) various metabolites' effects on cellular and systemic function, iii) how harnessing the power of metabolomic analyses represents the next frontier of precision medicine, and iv) how these concepts integrate to expand the clinical potential for translational cardiometabolic medicine.PMID:37788764 | DOI:10.1016/j.lfs.2023.122137

J Nutr Biochem. 2023 Oct 1:109454. doi: 10.1016/j.jnutbio.2023.109454. Online ahead of print.ABSTRACTA metabolomic study was performed on the kidneys and skeletal muscles of rats fed diets containing varying contents of Mg for 4 weeks. The kidneys are divided into two parts, the aerobic cortex and the anaerobic medulla, that differ in metabolism. The relative contents of 3-phosphoglyceric acid, 2-phosphoglyceric acid, and phosphoenolpyruvic acid increased with Mg restriction in both renal regions. In contrast, pyruvic acid content decreased with Mg restriction in the diets, suggesting an inhibitory conversion of phosphoenolpyruvic acid to pyruvic acid. The lactic acid content increased in both regions of the kidneys of Mg-restricted rats, implying changes towards a more glycolytic metabolism, possibly resulting from the impairment of mitochondrial function. There are two types of muscle fibers: glycolytic fast and oxidative slow muscle fibers. The soleus muscle consists of slow muscle fibers, whereas the gastrocnemius muscle consists of a combination of fast and slow muscle fibers. Similar to the changes in the kidneys, the contents of 3-phosphoglyceric acid, 2-phosphoglyceric acid, phosphoenolpyruvic acid, and lactic acid increased in the soleus and gastrocnemius muscles with dietary Mg restriction. Unlike in the kidney, pyruvic acid content increased in the soleus muscle in response to Mg restriction. Severe Mg restriction decreased contents of carnosine and its constituent β-alanine and increased the levels of purine derivatives such as xanthine and uric acid in the gastrocnemius muscle. The present study suggests a region-dependent sensitivity to dietary restriction of Mg, which may lead to the onset of various metabolic disorders.PMID:37788722 | DOI:10.1016/j.jnutbio.2023.109454

Plant Physiol Biochem. 2023 Sep 27;203:108059. doi: 10.1016/j.plaphy.2023.108059. Online ahead of print.ABSTRACTThe perennial herb Houttuynia cordata has long been cultivated and used as medicinal and edible plant in Asia. Nowadays, increasing attention is attracted due to its numerous health benefits. Flavonoids are the main chemical constituents exerting pharmacological activities. In the present study, we investigated both metabolome and transcriptome of two H. cordata accessions (6# and 7#) with distinct flavonoids contents. In total 397 metabolites, i.e., 220 flavonoids, 92 amino acids and derivatives, 20 vitamins, and 65 saccharides were abundant in aboveground part. Cyanidin-3-O-rutinoside and quercetin-3-O-galactoside were the most abundant flavonoids, which can be categorized into seven classes, namely anthocyanidins, chalcones, flavanols, flavanones, flavanonols, flavones, and flavonols. Flavonols was the most abundant group. Contents of 112 flavonoids differed significantly between the two accessions, with catechin-(7,8-bc)-4α-(3,4-dihydroxyphenyl)-dihydro-2-(3H)-one, cinchonain Id, and cinchonain Ic being the dominant flavonoid metabolites among them. Pinocembrin-7-O-neohesperidoside, pinocembrin-7-O-rutinoside, and kaempferol-3-O-galactoside-4'-O-glucoside were uniquely abundant in accession 7. Transcriptome data revealed a total of 110 different expressed genes related to flavonoid metabolism, with more highly expressed genes observed in 7#. We annotated a total of 19 differential flavonoid metabolites and 34 differentially expressed genes that are associated with the flavonoid metabolic network. Based on the transcriptome and qPCR data a total of 8 key candidate genes involved in flavonoid metabolism were identified. The ANS gene were found to play an important role in the synthesis of cyanidin-3-O-glucoside, while the CHI, F3'H and FLS genes were mainly responsible for controlling the levels of flavanones, flavones, and flavonols, respectively. Collectively, the present study provides important insights into the molecular mechanism underlying flavonoid metabolism in H. cordata.PMID:37788539 | DOI:10.1016/j.plaphy.2023.108059

Biochem Biophys Res Commun. 2023 Sep 29;682:1-20. doi: 10.1016/j.bbrc.2023.09.064. Online ahead of print.ABSTRACTMetabolic disorders are increasingly prevalent worldwide, leading to high rates of morbidity and mortality. The variety of metabolic illnesses can be addressed through personalized medicine. The goal of personalized medicine is to give doctors the ability to anticipate the best course of treatment for patients with metabolic problems. By analyzing a patient's metabolomic, proteomic, genetic profile, and clinical data, physicians can identify relevant diagnostic, and predictive biomarkers and develop treatment plans and therapy for acute and chronic metabolic diseases. To achieve this goal, real-time modeling of clinical data and multiple omics is essential to pinpoint underlying biological mechanisms, risk factors, and possibly useful data to promote early diagnosis and prevention of complex diseases. Incorporating cutting-edge technologies like artificial intelligence and machine learning is crucial for consolidating diverse forms of data, examining multiple variables, establishing databases of clinical indicators to aid decision-making, and formulating ethical protocols to address concerns. This review article aims to explore the potential of personalized medicine utilizing omics approaches for the treatment of metabolic disorders. It focuses on the recent advancements in genomics, epigenomics, proteomics, metabolomics, and nutrigenomics, emphasizing their role in revolutionizing personalized medicine.PMID:37788525 | DOI:10.1016/j.bbrc.2023.09.064

Mol Hortic. 2021 Oct 11;1(1):13. doi: 10.1186/s43897-021-00016-7.ABSTRACTPetals and leaves share common evolutionary origins but have different phenotypic characteristics, such as the absence of stomata in the petals of most angiosperm species. Plant NAC transcription factor, NAP, is involved in ABA responses and regulates senescence-associated genes, and especially those that affect stomatal movement. However, the regulatory mechanisms and significance of NAP action in senescing astomatous petals is unclear. A major limiting factor is failure of flower opening and accelerated senescence. Our goal is to understand the finely regulatory mechanism of dehydration tolerance and aging in rose flowers. We functionally characterized RhNAP, an AtNAP-like transcription factor gene that is induced by dehydration and aging in astomatous rose petals. Cytokinins (CKs) are known to delay petal senescence and we found that a cytokinin oxidase/dehydrogenase gene 6 (RhCKX6) shares similar expression patterns with RhNAP. Silencing of RhNAP or RhCKX6 expression in rose petals by virus induced gene silencing markedly reduced petal dehydration tolerance and delayed petal senescence. Endogenous CK levels in RhNAP- or RhCKX6-silenced petals were significantly higher than those of the control. Moreover, RhCKX6 expression was reduced in RhNAP-silenced petals. This suggests that the expression of RhCKX6 is regulated by RhNAP. Yeast one-hybrid experiments and electrophoresis mobility shift assays showed that RhNAP binds to the RhCKX6 promoter in heterologous in vivo system and in vitro, respectively. Furthermore, the expression of putative signal transduction and downstream genes of ABA-signaling pathways were also reduced due to the repression of PP2C homolog genes by RhNAP in rose petals. Taken together, our study indicates that the RhNAP/RhCKX6 interaction represents a regulatory step enhancing dehydration tolerance in young rose petals and accelerating senescence in mature petals in a stomata-independent manner.PMID:37789474 | DOI:10.1186/s43897-021-00016-7

Mol Hortic. 2022 Jul 23;2(1):17. doi: 10.1186/s43897-022-00038-9.ABSTRACTOver the past decade, systems biology and plant-omics have increasingly become the main stream in plant biology research. New developments in mass spectrometry and bioinformatics tools, and methodological schema to integrate multi-omics data have leveraged recent advances in proteomics and metabolomics. These progresses are driving a rapid evolution in the field of plant research, greatly facilitating our understanding of the mechanistic aspects of plant metabolisms and the interactions of plants with their external environment. Here, we review the recent progresses in MS-based proteomics and metabolomics tools and workflows with a special focus on their applications to plant biology research using several case studies related to mechanistic understanding of stress response, gene/protein function characterization, metabolic and signaling pathways exploration, and natural product discovery. We also present a projection concerning future perspectives in MS-based proteomics and metabolomics development including their applications to and challenges for system biology. This review is intended to provide readers with an overview of how advanced MS technology, and integrated application of proteomics and metabolomics can be used to advance plant system biology research.PMID:37789425 | DOI:10.1186/s43897-022-00038-9

Mol Hortic. 2023 Sep 26;3(1):18. doi: 10.1186/s43897-023-00067-y.ABSTRACTCell heterogeneity shapes the morphology and function of various tissues and organs in multicellular organisms. Elucidation of the differences among cells and the mechanism of intercellular regulation is essential for an in-depth understanding of the developmental process. In recent years, the rapid development of high-throughput single-cell transcriptome sequencing technologies has influenced the study of plant developmental biology. Additionally, the accuracy and sensitivity of tools used to study the epigenome and metabolome have significantly increased, thus enabling multi-omics analysis at single-cell resolution. Here, we summarize the currently available single-cell multi-omics approaches and their recent applications in plant research, review the single-cell based studies in fruit, vegetable, and ornamental crops, and discuss the potential of such approaches in future horticulture research.PMID:37789394 | DOI:10.1186/s43897-023-00067-y

BMC Plant Biol. 2023 Oct 3;23(1):458. doi: 10.1186/s12870-023-04480-9.ABSTRACTBACKGROUND: Duckweeds are small, rapidly growing aquatic flowering plants. Due to their ability for biomass production at high rates they represent promising candidates for biofuel feedstocks. Duckweeds are also excellent model organisms because they can be maintained in well-defined liquid media, usually reproduce asexually, and because genomic resources are becoming increasingly available. To demonstrate the utility of duckweed for integrated metabolic studies, we examined the metabolic adaptation of growing Lemna gibba cultures to different nutritional conditions.RESULTS: To establish a framework for quantitative metabolic research in duckweeds we derived a central carbon metabolism network model of Lemna gibba based on its draft genome. Lemna gibba fronds were grown with nitrate or glutamine as nitrogen source. The two conditions were compared by quantification of growth kinetics, metabolite levels, transcript abundance, as well as by 13C-metabolic flux analysis. While growing with glutamine, the fronds grew 1.4 times faster and accumulated more protein and less cell wall components compared to plants grown on nitrate. Characterization of photomixotrophic growth by 13C-metabolic flux analysis showed that, under both metabolic growth conditions, the Calvin-Benson-Bassham cycle and the oxidative pentose-phosphate pathway are highly active, creating a futile cycle with net ATP consumption. Depending on the nitrogen source, substantial reorganization of fluxes around the tricarboxylic acid cycle took place, leading to differential formation of the biosynthetic precursors of the Asp and Gln families of proteinogenic amino acids. Despite the substantial reorganization of fluxes around the tricarboxylic acid cycle, flux changes could largely not be associated with changes in transcripts.CONCLUSIONS: Through integrated analysis of growth rate, biomass composition, metabolite levels, and metabolic flux, we show that Lemna gibba is an excellent system for quantitative metabolic studies in plants. Our study showed that Lemna gibba adjusts to different nitrogen sources by reorganizing central metabolism. The observed disconnect between gene expression regulation and metabolism underscores the importance of metabolic flux analysis as a tool in such studies.PMID:37789269 | DOI:10.1186/s12870-023-04480-9

Sci Rep. 2023 Oct 3;13(1):16578. doi: 10.1038/s41598-023-43824-1.ABSTRACTBurkholderia pseudomallei, an etiological agent of melioidosis is an environmental bacterium that can survive as an intracellular pathogen. The biofilm produced by B. pseudomallei is crucial for cellular pathogenesis of melioidosis. The purpose of this investigation is to explore the role of biofilm in survival of B. pseudomallei during encounters with Acanthamoeba sp. using B. pseudomallei H777 (a biofilm wild type), M10 (a biofilm defect mutant) and C17 (a biofilm-complemented strain). The results demonstrated similar adhesion to amoebae by both the biofilm wild type and biofilm mutant strains. There was higher initial internalisation, but the difference diminished after longer encounter with the amoeba. Interestingly, confocal laser scanning microscopy demonstrated that pre-formed biofilm of B. pseudomallei H777 and C17 were markedly more persistent in the face of Acanthamoeba sp. grazing than that of M10. Metabolomic analysis revealed a significant increased level of 8-O-4'-diferulic acid, a superoxide scavenger metabolite, in B. pseudomallei H777 serially passaged in Acanthamoeba sp. The interaction between B. pseudomallei with a free-living amoeba may indicate the evolutionary pathway that enables the bacterium to withstand superoxide radicals in intracellular environments. This study supports the hypothesis that B. pseudomallei biofilm persists under grazing by amoebae and suggests a strategy of metabolite production that turns this bacterium from saprophyte to intracellular pathogen.PMID:37789212 | DOI:10.1038/s41598-023-43824-1

Chem Biodivers. 2023 Oct 3:e202301135. doi: 10.1002/cbdv.202301135. Online ahead of print.ABSTRACTOne of the endangered plant species in Saint Catherine protectorate is Hypericum sinaicum Boiss which is endemic to Egypt, Jordan, and Saudi Arabia. The fungus-host relationship can assist in the investigation of bioactive compounds produced by H. sinaicum paving the way for economic and medicinal implications. Therefore, a comprehensive metabolic approach via MS and chemical analysis was used to track and compare metabolites from H. sinaicum and Aspergillus foetidus var. pallidus, the endophytic fungus, with Hypericum perforatum. Metabolomics analysis revealed the presence of 25 metabolites distributed among samples and the discovery of new chemotaxonomic compounds, i.e., phloroglucinols and xanthones, allowing the discrimination between species. A. foetidus extract is considered a reliable source of furohyperforin and naphthodianthrone derivatives. In conclusion, using A. foetidus as an in vitro technique for producing potential phytoconstituents was cost effective, having easier optimization conditions and faster growth with fewer contamination rates than other in vitro methods.PMID:37788977 | DOI:10.1002/cbdv.202301135

Microbiol Spectr. 2023 Oct 3:e0142223. doi: 10.1128/spectrum.01422-23. Online ahead of print.ABSTRACTInsect sepsis is a severe consequence that arises from the invasion of the hemocoel by symbionts of entomopathogenic nematodes and bacteria. In the present study, we unveiled the heightened virulence of the entomopathogenic nematode Steinernema feltiae and the entomopathogenic bacteria Xenorhabdus bovienii, which operate symbiotically, against the wax moth Galleria mellonella. Maximum mortality was observed at 25°C while the optimal infestation efficiency was 20 nematodes per host. After infestation, G. mellonella displayed rapid darkening and softening, accompanied by an escalated esterase activity at 9 h. The X. bovienii, released by S. feltiae, underwent substantial proliferation and discharged toxins that attacked hemocytes, thus triggering extensive hemolysis and sepsis. The host G. mellonella was usually killed within 24 h due to disseminated septicemia. Additionally, X. bovienii infestation led to the upregulation of metabolites like 3-hydroxyanthranilic acid. Strikingly, we identified the perilous actinomycin D, generated through kynurenine metabolites, representing a novel biomarker of insect sepsis. Furthermore, a comprehensive transcriptomic analysis unveiled a noteworthy upregulation of gene expression associated with actinomycin D. Overall, X. bovienii induced apoptosis and sepsis through actinomycin D production, indicating its pivotal role in infestation activity. These findings open up new avenues for studying the mechanism of sepsis and developing innovative biotic pesticides. IMPORTANCE As a current biocontrol resource, entomopathogenic nematodes and their symbiotic bacterium can produce many toxin factors to trigger insect sepsis, having the potential to promote sustainable pest management. In this study, we found Steinernema feltiae and Xenorhabdus bovienii were highly virulent against the insects. After infective juvenile injection, Galleria mellonella quickly turned black and softened with increasing esterase activity. Simultaneously, X. bovienii attacked hemocytes and released toxic components, resulting in extensive hemolysis and sepsis. Then, we applied high-resolution mass spectrometry-based metabolomics and found multiple substances were upregulated in the host hemolymph. We found extremely hazardous actinomycin D produced via 3-hydroxyanthranilic acid metabolites. Moreover, a combined transcriptomic analysis revealed that gene expression of proteins associated with actinomycin D was upregulated. Our research revealed actinomycin D might be responsible for the infestation activity of X. bovienii, indicating a new direction for exploring the sepsis mechanism and developing novel biotic pesticides.PMID:37787562 | DOI:10.1128/spectrum.01422-23

J Periodontal Res. 2023 Oct 3. doi: 10.1111/jre.13183. Online ahead of print.ABSTRACTOBJECTIVE: The aim of this study was to investigate metabolomics markers in the saliva of patients with periodontal health, gingivitis and periodontitis.BACKGROUND: The use of metabolomics for diagnosing and monitoring periodontitis is promising. Although several metabolites have been reported to be altered by inflammation, few studies have examined metabolomics in saliva collected from patients with different periodontal phenotypes.METHODS: Saliva samples collected from a total of 63 patients were analysed by nuclear magnetic resonance (NMR) followed by ELISA for interleukin (IL)-1β. The patient sample, well-characterised clinically, included periodontal health (n = 8), gingivitis (n = 19) and periodontitis (n = 36) cases, all non-smokers and not diabetic.RESULTS: Periodontal diagnosis (healthy/gingivitis/periodontitis) was not associated with any salivary metabolites in this exploratory study. Periodontal staging showed nominal associations with acetoin (p = .030) and citrulline (p = .047). Among other investigated variables, the use of systemic antibiotics in the previous 3 months was associated with higher values of the amino acids taurine, glycine and ornithine (p = .002, p = .05 and p = .005, respectively, at linear regression adjusted for age, gender, ethnicity, body mass index and staging).CONCLUSION: While periodontal staging was marginally associated with some salivary metabolites, other factors such as systemic antibiotic use may have a much more profound effect on the microbial metabolites in saliva. Metabolomics in periodontal disease is still an underresearched area that requires further observational studies on large cohorts of patients, aiming to obtain data to be used for clinical translation.PMID:37787434 | DOI:10.1111/jre.13183

Int J Syst Evol Microbiol. 2023 Oct;73(10). doi: 10.1099/ijsem.0.006017.ABSTRACTFour obligately anaerobic Gram-positive bacteria representing one novel genus and two novel species were isolated from the female genital tract. Both novel species, designated UPII 610-JT and KA00274T, and an additional isolate of each species were characterized utilizing biochemical, genotypic and phylogenetic analyses. All strains were non-motile and non-spore forming, asaccharolytic, non-cellulolytic and indole-negative coccobacilli. Fatty acid methyl ester analysis for UPII 610-JT and KA00274T and additional isolates revealed C16 : 0, C18 : 0, C18:1ω9c and C18:2ω6,9c to be the major fatty acids for both species. UPII 610-JT had a 16S rRNA gene sequence similarity of 99.4 % to an uncultured clone sequence (AY724740) designated as Bacterial Vaginosis Associated Bacterium 2 (BVAB2). KA00274T had a 16S rRNA gene sequence similarity of 96.5 % to UPII 610-JT. Whole genomic DNA mol% G+C content was 42.2 and 39.3 % for UPII 610-JT and KA00274T, respectively. Phylogenetic analyses indicate these isolates represent a novel genus and two novel species within the Oscillospiraceae family. We propose the names Amygdalobacter indicium gen. nov., sp. nov., for UPII 610-JT representing the type strain of this species (=DSM 112989T, =ATCC TSD-274T) and Amygdalobacter nucleatus gen. nov., sp. nov., for KA00274T representing the type strain of this species (=DSM 112988T, =ATCC TSD-275T).PMID:37787404 | DOI:10.1099/ijsem.0.006017

Am J Physiol Lung Cell Mol Physiol. 2023 Oct 3. doi: 10.1152/ajplung.00177.2023. Online ahead of print.ABSTRACTBACKGROUND: Understanding metabolic evolution underlying pulmonary arterial hypertension (PAH) development may clarify pathobiology and reveal disease-specific biomarkers. Systemic sclerosis (SSc) patients are regularly surveilled for PAH, presenting an opportunity to examine metabolic change as disease develops in an at-risk cohort.METHODS: We performed mass spectrometry-based metabolomics on longitudinal serum samples collected prior to and near SSc-PAH diagnosis, compared to time-matched SSc subjects without PAH, in a SSc surveillance cohort. We validated metabolic differences in a second cohort and determined metabolite-phenotype relationships. In parallel, we performed serial metabolomic and hemodynamic assessments as disease developed in a preclinical model. For differentially expressed metabolites, we investigated corresponding gene expression in human and rodent PAH lungs.RESULTS: Kynurenine and its ratio to tryptophan (kyn/trp) increased over the surveillance period in SSc patients who developed PAH. Higher kyn/trp measured two years prior to diagnostic right heart catheterization increased the odds of SSc-PAH diagnosis (OR 1.57, 95% CI 1.05-2.36, p = 0.028). The slope of kyn/trp rise during SSc surveillance predicted PAH development and mortality. In both clinical and experimental PAH, higher kynurenine pathway metabolites correlated with adverse pulmonary vascular and RV measurements. In human and rodent PAH lungs, expression of TDO2, which catalyzes tryptophan conversion to kynurenine, was significantly upregulated and tightly correlated with pulmonary hypertensive features.CONCLUSIONS: Upregulated kynurenine pathway metabolism occurs early in PAH, localizes to the lung, and may be modulated by TDO2. Kynurenine pathway metabolites may be candidate PAH biomarkers.PMID:37786941 | DOI:10.1152/ajplung.00177.2023

bioRxiv. 2023 Sep 18:2023.09.18.558236. doi: 10.1101/2023.09.18.558236. Preprint.ABSTRACTKnockout (KO) of the fatty acid-activation enzyme very long-chain acyl-CoA synthetase 3 (ACSVL3; SLC27A3) in U87MG glioblastoma cells reduced their malignant growth properties both in vitro and in xenografts. These U87-KO glioma cells grew at a slower rate, became adherence-dependent, and were less invasive than parental U87 cells. U87-KO cells produced fewer, slower-growing subcutaneous and intracranial tumors when implanted in NOD-SCID mice. Thus, depleting U87MG cells of ACSVL3 restored these cells to a phenotype more like that of normal astrocytes. To understand the mechanisms underlying these beneficial changes, we investigated several possibilities, including the effects of ACSVL3 depletion on carbohydrate metabolism. Proteomic and metabolomic profiling indicated that ACSVL3 KO produced changes in glucose and energy metabolism. Even though protein levels of glucose transporters GLUT1 and GLUT3 were reduced by KO, cellular uptake of labeled 2-deoxyglucose was unaffected. Glucose oxidation to CO 2 was reduced nearly 7-fold by ACSVL3 depletion, and the cellular glucose level was 25% higher in KO cells. Glycolytic enzymes were upregulated by KO, but metabolic intermediates were essentially unchanged. Surprisingly, lactate production and the levels of lactate dehydrogenase isozymes LDHA and LDHB were elevated by ACSVL3 KO. The activity of the pentose phosphate pathway was found to be lower in KO cells. Citric acid cycle enzymes, electron transport chain complexes, and ATP synthase protein levels were all reduced by ACSVL3 depletion. Mitochondria were elongated in KO cells, but had a more punctate morphology in U87 cells. The mitochondrial potential was unaffected by lack of ACSVL3. We conclude that the beneficial effects of ACSVL3 depletion in human glioblastoma cells may result in part from alterations in diverse metabolic processes that are not directly related to role(s) of this enzyme in fatty acid and/or lipid metabolism. (Supported by NIH 5R01NS062043 and KKI institutional funds.).PMID:37786718 | PMC:PMC10541593 | DOI:10.1101/2023.09.18.558236

bioRxiv. 2023 Sep 18:2023.09.18.558167. doi: 10.1101/2023.09.18.558167. Preprint.ABSTRACTStickland-fermenting Clostridia preferentially ferment amino acids to generate energy and anabolic substrates for growth. In gut ecosystems, these species prefer dual redox substrates, particularly mucin-abundant leucine. Here, we establish how theronine, a more prevalent, mucin-abundant substrate, supports dual redox metabolism in the pathogen Clostridioides difficile . Real-time, High-Resolution Magic Angle Spinning NMR spectroscopy, with dynamic flux balance analyses, inferred dynamic recruitment of four distinct threonine fermentation pathways, including ones with intermediate accrual that supported changing cellular needs for energy, redox metabolism, nitrogen cycling, and growth. Model predictions with 13 C isotopomer analyses of [U- 13 C]threonine metabolites inferred threonine's reduction to butyrate through the reductive leucine pathway, a finding confirmed by deletion of the hadA 2-hydroxyisocaproate CoA transferase. In vivo metabolomic and metatranscriptomic analyses illustrate how threonine metabolism in C. difficile and the protective commensal Paraclostridium bifermentans impacts pathogen colonization and growth, expanding the range of dual-redox substrates that modulate host risks for disease.PMID:37786668 | PMC:PMC10541586 | DOI:10.1101/2023.09.18.558167

Compr Rev Food Sci Food Saf. 2023 Oct 2. doi: 10.1111/1541-4337.13246. Online ahead of print.ABSTRACTWith the development of metabolomics analytical techniques, relevant studies have increased in recent decades. The procedures of metabolomics analysis mainly include sample preparation, data acquisition and pre-processing, multivariate statistical analysis, as well as maker compounds' identification. In the present review, we summarized the published articles of tea metabolomics regarding different analytical tools, such as mass spectrometry, nuclear magnetic resonance, ultraviolet-visible spectrometry, and Fourier transform infrared spectrometry. The metabolite variation of fresh tea leaves with different treatments, such as biotic/abiotic stress, horticultural measures, and nutritional supplies was reviewed. Furthermore, the changes of chemical composition of processed tea samples under different processing technologies were also profiled. Since the identification of critical or marker metabolites is a complicated task, we also discussed the procedure of metabolite identification to clarify the importance of omics data analysis. The present review provides a workflow diagram for tea metabolomics research and also the perspectives of related studies in the future.PMID:37786329 | DOI:10.1111/1541-4337.13246