Metabolomic Characteristics Research Articles

Altered metabolic profiles of dermatomyositis with different myositis-specific autoantibodies associated with clinical phenotype.

Dermatomyositis (DM) is an idiopathic inflammatory myopathy. Because of clinical heterogeneity, the metabolite profile of DM patients with different myositis-specific autoantibodies (MSAs) remains elusive. This study aimed to explore the metabolomics characteristics of the serum in DM with different MSAs, low or high disease activity, and interstitial lung disease. Untargeted metabolomics profiling was performed in the serum of a discovery cohort (n=96) and a validation cohort (n=40), consisting of DM patients with MSAs, low or high disease activity, and/or interstitial lung disease (DM-ILD) compared to age- and gender-matched healthy controls (HCs). The lipid profile in DM was found to be abnormal, especially dysregulated glycerophospholipid metabolism and fatty acid oxidation, which might affect the pathogenesis of DM by disrupting the balance of Th17 and Treg. We identified potential biomarkers of DM that can distinguish between low or high disease activity and reflect lung involvement. Two metabolite combinations including pro-leu, FA 14:0;O can distinguish high disease activity DM from low disease activity DM and HCs, and five including indole-3-lactic acid, dihydrosphingosine, SM 32:1;O2, NAE 17:1, and cholic acid can distinguish DM-ILD from DM without ILD (DM-nonILD). DM with different MSAs had unique metabolic characteristics, which can distinguish between MDA5+DM, Jo-1+DM, and TIF1-γ+DM, and from the antibody-negative groups. The sphingosine metabolism has been found to play an important role in MDA5+DM, which was associated with the occurrence of ILD. Altered metabolic profiles of dermatomyositis were associated with different myositisspecific autoantibodies, disease activity, and interstitial lung disease, which can help in the early diagnosis, prognosis, or selection of new therapeutic targets for DM.

Plasma metabolomic characteristics of atrial fibrillation patients with spontaneous echo contrast

BackgroundThe spontaneous echo contrast (SEC) in patients with atrial fibrillation (AF) indicates a prethrombic state that ultimately progresses into thrombus formation. A comprehensive understanding of specific plasma metabolomics characteristics may protect AF patients from thrombus, particularly in the early stage.ObjectivesThrough the investigation of metabolic pathways, we endeavor to uncover the metabolomic characteristics associated with SEC states, and to examine the differential metabolites by which may exert their influence on thrombotic states.MethodsPatients with AF were enrolled, and the participants were divided into three groups based on the results of the echocardiogram: non-SEC, low-SEC and high-SEC group. Samples were collected and subjected to non-targeted metabolomics analysis. The analytical process included data quality control, metabolite difference analysis, component analysis, Kegg cluster analysis, etc.ResultsOur metabolic phenotype revealed a clear differential metabolic pattern between the SEC and non-SEC. Specifically, we identified 35 and 142 significantly differential metabolites in venous and atrial plasma, respectively, suggesting that SEC may be involved in pervasive metabolic dysregulation and that the degree of metabolic dysregulation in atrial plasma is more severe than that in venous blood.ConclusionPatients with SEC have a significantly different metabolic pattern compared to those without SEC. Our work promoted the understanding of mechanism of the occurrence and development of SEC, facilitated the screening of the target metabolites for its therapeutic intervention, and provided evidence for the prevention and treatment of SEC or thrombosis in AF. Our work also provided new directions for subsequent research in related fields. In conclusion, our study not only provides a theoretical basis for understanding the occurrence and development of SEC in AF, but also provides recommendations for the daily diet of AF patients with SEC, such as a balanced intake of essential amino acids, avoiding excessive intake of benzoic acid, and intake of appropriate inositol.Clinical trial numberNot applicable.

Metabolomic characteristics and anthraquinones accumulation patterns of Rhubarb in different tissues and roots from different developmental stages

Rhubarb's multifaceted value in culinary and medicine is renowned, especially Rheum tanguticum (Rhubarb), whose bountiful content of anthraquinones (AQs) makes it increasingly attractive in the realms of dietary supplements and natural edible pigments. Current understanding of the spatiotemporal dynamics of AQs accumulation in Rhubarb remains limited, and the knowledge of other valuable metabolites is even more scarce. This gap limits the ability to fully explore Rhubarb's potential as a food ingredient and hinders its efficient use in food development, potentially leading to unnecessary resource waste. This study integrated widely targeted metabolomics and AQs quantification to determine the metabolic profiles in four tissues and the roots at three developmental stages in Rhubarb. The high levels of malic and citric acids in the stems paved the way for their use in flavored beverages and substantiated the practice of traditional consumption. The abundance of flavonoids in the leaves and seeds, and the AQs, phenolic acids of the seeds, which potentially bestowed upon them exceptional antioxidant capabilities, underscore the significant potential of edible product development. The widespread traditional use of roots was mirrored by the preferential accumulation of AQs, and the roots' value escalated in tandem with the time-accumulated increase of AQs. The root bark and root tip with high AQs should be given attention in production and not simply discarded. This research clarifies the chemical composition and spatiotemporal variation patterns of Rhubarb's characteristic components, offering valuable scientific insights for their efficient use and value enhancement in the food industry.

Study on serum metabolomics characteristics of obese patients with erectile dysfunction.

Erectile dysfunction (ED) is a common male sexual health problem that can be associated with obesity. This study aimed to identify serum metabolic differences and pathways related to ED in obese men using non-targeted metabolomics techniques. We included 54 obese male patients with (n = 27) and without (n = 27) ED. We collected 5 mL of fasting elbow vein blood and analyzed serum metabolites using ultra-high-performance liquid chromatography-mass spectrometry. Multivariate statistical methods (principal component analysis and orthogonal partial least squares discriminant analysis) were used to identify differential metabolites between the groups. Finally, pathway analysis using the Kyoto encyclopedia of genes and genomes database identified 4 differential metabolic pathways in obese men with ED compared to obese men without ED. A total of 77 differential metabolites were identified in obese men with ED compared to the control group (obese men without ED) using a threshold of variable importance in the projection > 1 and P < .05. Pathway analysis revealed 4 main differences: glycine, serine and threonine metabolism, glycerophospholipid metabolism, aminoacyl-tRNA biosynthesis, and D-glutamine and D-glutamate metabolism. Specific metabolites associated with these pathways included betaine aldehyde, choline, L-threonine, phosphatidylcholine, L-serine, and D-glutamine. Our findings suggest abnormalities in fatty acid metabolism, phospholipid metabolism, and amino acid metabolism between obese men with and without ED. Metabolites such as betaine aldehyde, choline, L-threonine, phosphatidylcholine, L-serine, and D-glutamine may be potential biomarkers for distinguishing obese men with ED.

Metabolomics identifies metabolite markers in plasma and extracellular vesicles within plasma in patients with asthma

BackgroundPlasma and extracellular vesicles (EVs) derived from plasma are important sources of information regarding individual health. Metabolomic analysis of plasma and EVs may provide new methods for predicting disease occurrence. This study aims to analyze the metabolomic characteristics of plasma and plasma EVs in asthma patients. MethodsPlasma samples were collected from healthy individuals and asthma patients. EVs were isolated from the plasma using ultracentrifugation. The isolated EVs were characterized by nanoparticle tracking analysis and flow cytometry. Metabolomic analysis was performed using a liquid chromatography-mass spectrometry platform. ResultsThis study successfully extracted EVs from plasma samples. Metabolomic analysis revealed that the composition of differential metabolites in the plasma and EVs of asthma patients was similar. KEGG pathway analysis indicated that the number of upregulated metabolic pathways enriched with differential metabolites in the plasma EVs of asthma patients was significantly greater than that in the plasma samples. Pathways associated with the onset of asthma included asthma, systemic lupus erythematosus, glycerophospholipid metabolism, and autophagy – other, primarily involving the following five metabolites: PS(18:1(9Z)/18:2(9Z,12Z)), PC(18:1(9Z)e/2:0), PS(24:1(15Z)/22:2(13Z,16Z)), PE(22:4(7Z,10Z,13Z,16Z)/22:5(4Z,7Z,10Z,13Z,16Z)), and PE(16:0/20:3(8Z,11Z,14Z)). Receiver operating characteristic analysis results suggested that these five differential metabolites may serve as potential biomarkers for asthma. ConclusionWe identified the metabolic characteristics of plasma and EVs in asthma patients, confirming that the metabolites in plasma EVs may serve as potential biomarkers for asthma. This finding not only enhances our understanding of the pathogenesis of asthma but also opens new avenues for targeted therapy.

Exploring the therapeutic potential of Bifidobacterium longum subsp. longum CCFM1029 in Parkinson's disease: Insights from behavioral, neurophysiological, gut microbiota, and microbial metabolites analysis

AbstractThe pathogenesis of Parkinson's disease (PD) is closely related to the gut microbiota, and microecological therapies based on gut probiotics have received widespread attention, among which Bifidobacterium has been demonstrated to have a potential neuroprotective effect, but specific mechanisms have been lacking in the investigation. Here, we show that Bifidobacterium longum subsp. longum CCFM1029 significantly inhibited LPS‐induced inflammatory responses in microglia and alleviated 1‐methyl‐4‐phenyl‐1,2,3,6‐tetrahydropyridine (MPTP)‐induced motor dysfunction, dopaminergic neuronal damage, and neuroinflammation in PD mice. Subsequently, the mechanism of action of CCFM1029 in PD was systematically elucidated by the neurochemical and biochemical analysis in PD mice, together with microbiomic and metabolomic analysis. It was found that CCFM1029 intervention restores dysbiosis in the gut microbiota linked to PD and reverses alterations in microbial metabolites. We established the interactions among the gut microbiota, metabolites, and brain by integrating behavioral and neurophysiological data with changes in the composition of the gut microbiota and metabolomic characteristics. We found that CCFM1029 intervention increases levels of the beneficial gut microbial metabolites indole‐3‐acrylic acid and short‐chain fatty acid (acetic and butyric acid) and decreases levels of the neuroinflammation‐associated metabolite N‐acetylhistamine. To summarize, our findings suggest CCFM1029 as a novel dietary supplement can prevent and mitigate the progression of PD through the microbiota‐gut‐brain axis.

Comparison of Growth and Metabolomic Profiles of Two Afforestation Cypress Species Cupressus chengiana and Platycladus orientalis Grown at Minjiang Valley in Southwest China.

In recent years, afforestation has been conducted in China's hot and dry valleys. However, there is still a paucity of knowledge regarding the performance of tree species in these semi-arid regions, particularly with regard to interspecies differences. The present study compares the growth and metabolome characteristics of two widely used cypress species, namely Cupressus chengiana and Platycladus orientalis, grown at two sites with distinct climate conditions in the hot and dry Minjiang Valley in southwestern China. The findings indicate that C. chengiana trees exhibit superior growth rates compared to P. orientalis trees at both study sites. In comparison to P. orientalis trees, C. chengiana trees demonstrated a greater tendency to close their stomata in order to prevent water loss at the hotter and drier site, Llianghekou (LHK). Additionally, C. chengiana trees exhibited significantly lower hydrogen peroxide levels than P. orientalis trees, either due to lower production and/or higher scavenging of reactive oxygen species. C. chengiana trees accumulated soluble sugars as well as sugar derivatives, particularly those involved in sucrose and galactose metabolisms under stressful conditions. The species-specific differences were also reflected in metabolites involved in the tricarboxylic acid cycle, nitrogen, and secondary metabolisms. The metabolome profiles of the two species appeared to be influenced by the prevailing climatic conditions. It appeared that the trees at the drier and hotter site, LHK, were capable of efficient nitrogen uptake from the soil despite the low soil nitrogen concentration. This study is the first to compare the growth performance and metabolic profiles of two widely used tree species with high resistance to adverse conditions. In addition to the species-specific differences and adaptations to different sites, the present study also provides insights into potential management strategies to alleviate abiotic stress, particularly with regard to nitrogen nutrients, in the context of climate change.

ADRA2A promotes the classical/progenitor subtype and reduces disease aggressiveness of pancreatic cancer.

Pancreatic ductal adenocarcinoma (PDAC) manifests diverse molecular subtypes, including the classical/progenitor and basal-like/squamous subtypes, with the latter known for its aggressiveness. We employed integrative transcriptome and metabolome analyses to identify potential genes contributing to the molecular subtype differentiation and its metabolic features. Our comprehensive analysis revealed that adrenoceptor alpha 2A (ADRA2A) was downregulated in the basal-like/squamous subtype, suggesting its potential role as a candidate suppressor of this subtype. Reduced ADRA2A expression was significantly associated with a high frequency of lymph node metastasis, higher pathological grade, advanced disease stage, and decreased survival among PDAC patients. In vitro experiments demonstrated that ADRA2A transgene expression and ADRA2A agonist inhibited PDAC cell invasion. Additionally, ADRA2A-high condition downregulated the basal-like/squamous gene expression signature, while upregulating the classical/progenitor gene expression signature in our PDAC patient cohort and PDAC cell lines. Metabolome analysis conducted on the PDAC cohort and cell lines revealed that elevated ADRA2A levels were associated with suppressed amino acid and carnitine/acylcarnitine metabolism, which are characteristic metabolic profiles of the classical/progenitor subtype. Collectively, our findings suggest that heightened ADRA2A expression induces transcriptome and metabolome characteristics indicative of classical/progenitor subtype with decreased disease aggressiveness in PDAC patients. These observations introduce ADRA2A as a candidate for diagnostic and therapeutic targeting in PDAC.

Metabolomic analysis in Amycolatopsis keratiniphila disrupted the competing ECO0501 pathway for enhancing the accumulation of vancomycin.

Vancomycin is a clinically important glycopeptide antibiotic against Gram-positive pathogenic bacteria, especially methicillin-resistant Staphylococcus aureus. In the mutant strain of Amycolatopsis keratiniphila HCCB10007 Δeco-cds4-27, the production of ECO-0501 was disrupted, but enhanced vancomycin yield by 55% was observed compared with the original strain of A. keratiniphila HCCB10007. To gain insights into the mechanism of the enhanced production of vancomycin in the mutant strain, comparative metabolomics analyses were performed between the mutant strain and the original strain, A. keratiniphila HCCB10007 via GC-TOF-MS and UPLC-HRMS. The results of PCA and OPLS-DA revealed a significant distinction of the intracellular metabolites between the two strains during the fermentation process. 64 intracellular metabolites, which involved in amino acids, fatty acids and central carbon metabolism, were identified as differential metabolites. The high-yield mutant strain maintained high levels of glucose-1-phosphate and glucose-6-phosphate and they declined with the increases of vancomycin production. Particularly, a strong association of fatty acids accumulation as well as 3,5-dihydroxyphenylacetic acid and non-proteinogenic amino acid 3,5-dihydroxyphenylglycine (Dpg) with enhancement of vancomycin production was observed in the high-yield mutant strain, indicating that the consumption of fatty acid pools might be beneficial for giving rise to 3,5-dihydroxyphenylacetic acid and Dpg which further lead to improve vancomycin production. In addition, the lower levels of glyoxylic acid and lactic acid and the higher levels of sulfur amino acids might be beneficial for improving vancomycin production. These findings proposed more advanced elucidation of metabolomic characteristics in the high-yield strain for vancomycin production and could provide potential strategies to enhance the vancomycin production.

Microbiomic and metabolomic dynamics in chrysanthemum waste at different fermentation stages

The microbial community and metabolite profile during the fermentation of chrysanthemum waste (CW) were studied, as well as the effect of feeding fermented chrysanthemum waste (FCW) to sows. The nutritional value of CW fermented for 30–90 days was similar to that of CW fermented for 7 days. With increasing time, the number of bacterial species, richness index, and diversity index increased. The main genera were Pediococcus. A total of 270 different metabolites were identified in FCW, among which benzenoids, amino acids, flavonoids, fatty acids, and peptides were the most significantly different metabolites. Flavone and flavonol biosynthesis, and flavonoid biosynthesis were the most important metabolic pathways in fermentation. Feeding FCW to sows was beneficial for their production performance. These provide new insights into the characteristics of microbiome and metabolome associated with CW during long-term fermentation and the feed availability of FCW.

Harnessing Bacillus amyloliquefaciens for Amazake Production: Comparison with Aspergillus oryzae Amazake for Metabolomic Characteristics, Microbial Diversity, and Sensory Profile.

Amazake is a traditional, sweet, non-alcoholic Japanese beverage typically produced through koji fermentation by the fungus Aspergillus oryzae. However, alternative microorganisms such as Bacillus amyloliquefaciens offer potential advantages and novel possibilities for producing similar fermented beverages. This study aimed to replicate the ancestral beverage of amazake by replacing A. oryzae (W-20) with B. amyloliquefaciens (NCIMB 12077) and comparing their fermentation processes and resulting products. Our results show that the production of amazake with B. amyloliquefaciens (ABA) is not only possible but also results in a beverage that is otherwise distinct from traditional amazake (AAO). Saccharification was achievable in ABA at higher temperatures than in AAO, albeit with lower reducing sugar and enzymatic activity values. Amino acids and organic acids were more abundant in AAO, with cysteine being uniquely present in AAO and shikimic acid only being present in ABA. The volatile aroma compound profiles differed between the two beverages, with AAO exhibiting a greater abundance of aldehydes, and ABA a greater abundance of ketones and alcohols. Interestingly, despite these compositional differences, the two beverages showed similar consumer panel acceptance rates. An analysis of their microbial communities revealed pronounced differences between the amazakes, as well as temporal changes in ABA but not in AAO. This study provides promising insights into harnessing the potential of B. amyloliquefaciens as the primary microorganism in the fermentation process of amazake-like beverages, marking an important advancement in the field of fermented low-alcohol beverage production, with possible applications in other fermented foods.

Preliminary study of metabonomic changes during the progression of atherosclerosis in miniature pigs.

To explore potential biomarkers for early diagnosis of atherosclerosis (AS) and provide basic data for further research on AS, the characteristics of serum metabolomics during the progression of AS in mini-pigs were observed dynamically. An AS model in Bama miniature pigs was established by a high-cholesterol and high-fat diet. Fasting serum samples were collected monthly for metabolomics and serum lipid detection. At the end of the treatment period, pathological analysis of the abdominal aorta and coronary artery was performed to evaluate the lesions of AS, thereby distinguishing the susceptibility of mini-pigs to AS. The metabolomics was detected using a high-resolution untargeted metabolomic approach. Statistical analysis was used to identify metabolites associated with AS susceptibility. Based on pathological analysis, mini-pigs were divided into two groups: a susceptible group (n = 3) and a non-susceptible group (n = 6). A total of 1318 metabolites were identified, with significant shifting of metabolic profiles over time in both groups. Dynamic monitoring analysis highlighted 57 metabolites that exhibited an obvious trend of differential changes between two groups with the advance of time. The KEGG (Kyoto Encyclopedia of Genes and Genomes) pathway enrichment analysis indicated significant disorders in cholesterol metabolism, primary bile acid metabolism, histidine metabolism, as well as taurine and hypotaurine metabolism. During the progression of AS in mini-pigs induced by high-cholesterol/high-fat diet, the alterations in serum metabolic profile exhibited a time-dependent pattern, accompanied by notable disturbances in lipid metabolism, cholesterol metabolism, and amino acid metabolism. These metabolites may become potential biomarkers for early diagnosis of AS.

The Difference in Serum Metabolomic Profiles between the Good and Poor Outcome Groups at 3 Months in the Early and Late Phases of Aneurysmal Subarachnoid Hemorrhage.

We aimed to investigate the characteristics of serum metabolomics in aneurysmal subarachnoid hemorrhage patients (aSAH) with different 3-month outcomes (good = modified Rankin score: 0-3 vs. poor = mRS 4-6). We collected serum samples from 46 aSAH patients at 24 (D1) and 168 (D7) hours after injury for analysis by liquid chromatography-mass spectrometry. Ninety-six different metabolites were identified. Groups were compared using multivariate (orthogonal partial least squares discriminant analysis), univariate, and receiving operator characteristic (ROC) methods. We observed a marked decrease in serum homocysteine levels at the late phase (D7) compared to the early phase (D1). At both D1 and D7, mannose and sorbose levels were notably higher, alongside elevated levels of kynurenine (D1) and increased 2-hydroxybutyrate, methyl-galactoside, creatine, xanthosine, p-hydroxyphenylacetate, N-acetylalanine, and N-acetylmethionine (all D7) in the poor outcome group. Conversely, levels of guanidinoacetate (D7) and several amino acids (both D1 and D7) were significantly lower in patients with poor outcomes. Our results indicate significant changes in energy metabolism, shifting towards ketosis and alternative energy sources, both in the early and late phases, even with adequate enteral nutrition, particularly in patients with poor outcomes. The early activation of the kynurenine pathway may also play a role in this process.

Endocrine system, cell growth and death, and energy metabolism induced by Sb(III) exposure in earthworm (Pheretima guillemi) revealed by transcriptome and metabolome analysis

Antimony (Sb) is known for its severe and extensive toxicity, and earthworms are considered important indicator organisms in soil ecosystems. Therefore, the present study investigated the mechanism of toxicity of the Sb at different concentrations (50, 200 mg/kg) on earthworms using biochemical indicators, pathological sections, as well as metabolomics and transcriptomics analyses. The results showed that as the exposure concentration increased, both the antioxidant system of earthworms, extent of intestinal damage, and their metabolomic characteristics were significantly enhanced. In the 50 and 200 mg/kg Sb treatment group, 30 and 177 significant differentially changed metabolites (DCMs) were identified, respectively, with the most DCMs being down- and up-regulated, respectively. Metabolomics analysis showed that the contents of dl-tryptophan, glutamic acid, glycine, isoleucine, l-methionine, involved in the protein digestion and absorption as well as aminoacyl-tRNA biosynthesis were significantly up-regulated under the 200 mg/kg treatment. At the transcriptional level, Sb mainly affected the immune system, nervous system, amino acid metabolism, endocrine system, and carbohydrate metabolism in earthworms. The integration of transcriptomic and metabolomic data indicated that high doses of Sb regulated the metabolites and genes related to the oxidative phosphorylation pathway in earthworms. Overall, these results revealed global responses beyond the scope of conventional toxicity endpoints and facilitated a more in-depth and comprehensive assessment of the toxic effects of Sb.

Irisin alleviated the reproductive endocrinal disorders of PCOS mice accompanied by changes in gut microbiota and metabolomic characteristics

IntroductionFolliculogenesis and oligo/anovulation are common pathophysiological characteristics in polycystic ovary syndrome (PCOS) patients, and it is also accompanied by gut microbiota dysbiosis. It is known that physical activity has beneficial effects on improving metabolism and promoting ovulation and menstrual cycle disorder in PCOS patients, and it can also modulate the gastrointestinal microbiota in human beings. However, the mechanism remains vague. Irisin, a novel myokine, plays a positive role in the mediating effects of physical activity.MethodsMice were randomly divided into the control group, PCOS group and PCOS+irisin group. PCOS model was induced by dehydroepiandrosterone (DHEA) and high-fat diet (HFD). The PCOS+irisin group was given irisin 400μg/kg intraperitoneal injection every other day for 21 days. The serum sex hormones were measured by radioimmunoassay. Hematoxylin and Eosin (H&amp;amp;E) Staining and immunohistochemistry (IHC) were conducted on ovarian tissue. The feces microbiota and metabolomic characteristics were collected by 16S rRNA gene sequencing and liquid chromatography-mass spectrometry (LC–MS).ResultsIn this study, we demonstrated that irisin supplementation alleviated reproductive endocrine disorders of PCOS mice, including estrous cycle disturbance, ovarian polycystic degeneration, and hyperandrogenemia. Irisin also improved the PCOS follicles dysplasia and ovulation disorders, while it had no significant effect on the quality of oocytes. Moreover, irisin could mitigate the decreased bacteria of Odoribacter and the increased bacteria of Eisenbergiella and Dubosiella in PCOS mice model. Moreover, irisin could alleviate the increased fecal metabolites: Methallenestril and PS (22:5(4Z,7Z,10Z,13Z,16Z)/ LTE4).ConclusionThese results suggest that irisin may alleviate the status of PCOS mice model by modulating androgen-induced gut microbiota dysbiosis and fecal metabolites. Hence, our study provided evidence that irisin may be considered as a promising strategy for the treatment of PCOS.

#2227 Exploring the interplay between gut microbiome, fecal metabolomics and ambulatory blood pressure in white-coat hypertensive patients

Abstract Background and Aims Recent evidence showed the relationship between gut microbiota with hypertension. Few studies also demonstrated that ambulatory blood pressure monitoring variables such as dipping status and linear variability are associated with fecal microbiota and metabolomics. However, the relationship between gut microbiota and metabolomic composition of white-coat hypertensive patients has not been studied yet. In addition, although the link between gut microbiota, blood pressure variability and high salt intake has been shown, none of the studies addressed these changes simultaneously in the same study population. Here, we aimed to investigate the interplay between the gut microbiome, fecal metabolites and 24-hour urine sodium levels between hypertensive, white-coat hypertensive (WCH) and healthy participants diagnosed with ambulatory blood pressure monitoring. Method The study included 18 newly diagnosed hypertensive, 8 WCH, and 21 healthy participants from our tertiary center. Ambulatory blood pressure (BP) monitoring was performed in all participants and nighttime dipping, morning BP surge (MBPS), pre-wake MBPS and linear BP variability were calculated. 16S rRNA sequencing was performed using Illumina MiSeq sequencer. DeSeq2 and linear discriminant analysis effect size (LEfSe) were performed with R. Fecal metabolite levels were analyzed by GC-MS. A partial least squares-discriminant analysis (PLS-DA) model was constructed for the feature selector and classifier. The variable importance in the projection (VIP) coefficient was calculated based on the PLS-DA model. Results ANOVA and post-hoc Tukey test showed WHC and hypertensive groups had higher blood pressure variability and morning-thorough MBPS than normotensive patients (p = 0.02 and 0.04, respectively), whereas 24-h urine Na levels were statistically similar between WCH and hypertensive groups (p = 0.11). There were no significant differences in α- and β-diversity metrics of gut microbiome between study groups. Select taxa were specific to WHC patients, notably Rikenellaceae family and Mitsuokella were higher in WHC against normotensive patients, whereas Ruminococcus callidus, Roseburia, Clostridium, Lactobacillus ruminis, Sutterall, Lachospiraceae and Muribaculaceae were decreased in WHC against normotensive patients in DeSeq2 analysis. Dialister was increased, whereas Bacteroides genus and Bacteroides fragilis were decreased in WHC against hypertensive patients. LEfSe analysis showed positive enrichment in Proteobacteria phylum and negative enrichment in Mitsuokella genus in WHC against hypertensive group. Enterococcus, Lachnobacterium, Odoribacter and Pseudomonas genera had positive; whereas Lactobacillus and Clostridium had negative correlations with 24-h urine Na levels. Positive correlations were shown between linear BP variability and Bacteroides and Paraprevotella genera. Several genera and species were enriched in Q3-4 against Q1-2 quartiles of pre-wake and sleep-thorough MBPS in LEfSe analyzes (Fig. 1). Normotensive and essential hypertensive groups could also be differentiated based on fecal metabolomic composition. Specifically, metabolites with the highest VIP values discriminating WCH from normotensive and hypertensive groups were methyl-palmitoleate, oxalic acid and phenyl β-D-glucopyranoside, respectively (Fig. 2). Conclusion In conclusion, we performed the first study focusing on the fecal microbiome and metabolomic characteristics of white-coat hypertensive patients. Urine Na levels and ambulatory blood pressure variables of the WCH group are different than those of the normotensive and similar to the hypertensive group. Comparative and correlation analyses revealed novel relationships between ambulatory blood pressure variables and gut microbiome of both WCH and hypertensive patients. Fecal metabolomic differences between study groups imply possible mechanisms underlying the effects of gut microbiome on blood pressure. Gut microbiota and metabolites may become valuable targets for interventions of both white-coat and essential hypertension in the near future.

Identification of blood exosomal metabolomic profiling for high-altitude cerebral edema

High-altitude cerebral edema (HACE) is a severe neurological condition that can occur at high altitudes. It is characterized by the accumulation of fluid in the brain, leading to a range of symptoms, including severe headache, confusion, loss of coordination, and even coma and death. Exosomes play a crucial role in intercellular communication, and their contents have been found to change in various diseases. This study analyzed the metabolomic characteristics of blood exosomes from HACE patients compared to those from healthy controls (HCs) with the aim of identifying specific metabolites or metabolic pathways associated with the development of HACE conditions. A total of 21 HACE patients and 21 healthy controls were recruited for this study. Comprehensive metabolomic profiling of the serum exosome samples was conducted using ultraperformance liquid chromatography–tandem mass spectrometry (UPLC‒MS/MS). Additionally, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis was performed to identify the metabolic pathways affected in HACE patients. Twenty-six metabolites, including ( +)-camphoric acid, choline, adenosine, adenosine 5′-monophosphate, deoxyguanosine 5′-monophosphate, guanosine, and hypoxanthine-9-β-D-arabinofuranoside, among others, exhibited significant changes in expression in HACE patients compared to HCs. Additionally, these differentially abundant metabolites were confirmed to be potential biomarkers for HACE. KEGG pathway enrichment analysis revealed several pathways that significantly affect energy metabolism regulation (such as purine metabolism, thermogenesis, and nucleotide metabolism), estrogen-related pathways (the estrogen signaling pathway, GnRH signaling pathway, and GnRH pathway), cyclic nucleotide signaling pathways (the cGMP-PKG signaling pathway and cAMP signaling pathway), and hormone synthesis and secretion pathways (renin secretion, parathyroid hormone synthesis, secretion and action, and aldosterone synthesis and secretion). In patients with HACE, adenosine, guanosine, and hypoxanthine-9-β-D-arabinofuranoside were negatively correlated with height. Deoxyguanosine 5′-monophosphate is negatively correlated with weight and BMI. Additionally, LPE (18:2/0:0) and pregnanetriol were positively correlated with age. This study identified potential biomarkers for HACE and provided valuable insights into the underlying metabolic mechanisms of this disease. These findings may lead to potential targets for early diagnosis and therapeutic intervention in HACE patients.

Metabolomic profiles predict clinical severity in patients with obstructive sleep apnea-hypopnea syndrome.

Obstructive sleep apnea-hypopnea syndrome (OSAHS) poses a significant health hazard, intermittent hypoxia inflicts damage throughout the body and is considered a critical risk factor for metabolic disorders. The aim of this study was to establish a metabolic profile for patients with OSAHS using nontargeted metabolomics detection techniques, providing a basis for OSAHS diagnosis and novel biological marker identification. 45 patients with OSAHS composed the OSAHS group, and 44 healthy volunteers composed the control group. Nontargeted metabolomics technology was used to analyze participants' urinary metabolites. Differentially abundant metabolites were screened and correlated through hierarchical clustering analysis. We constructed a composite metabolite diagnostic model using a random forest model. Simultaneously, we analyzed the relationships between 20 metabolites involved in model construction and OSAHS severity. The urinary metabolomics pattern of the OSAHS group exhibited significant changes, demonstrating noticeable differences in metabolic products. Urinary metabolite analysis revealed differences between the mild-to-moderate OSAHS and severe OSAHS groups. The composite metabolite model constructed in this study demonstrated excellent diagnostic performance not only in distinguishing healthy control participants from patients with mild-to-moderate OSAHS (area under the curve = 0.78) and patients with severe OSAHS (area under the curve = 0.78), but also in discriminating between patients with mild-to-moderate and severe OSAHS (area under the curve = 0.71). This study comprehensively analyzed the urinary metabolomic characteristics of patients with OSAHS. The established composite metabolite model provides robust support for OSAHS diagnosis and severity assessment. Twenty metabolites associated with OSAHS disease severity offer a new perspective for diagnosis. Wang X, Zhao J, Wang X, Zhang L. Metabolomic profiles predict clinical severity in patients with obstructive sleep apnea-hypopnea syndrome. J Clin Sleep Med. 2024;20(9):1445-1453.

Combined Analysis of Metabolomics and Biochemical Changes Reveals the Nutritional and Functional Characteristics of Red Palm Weevil Rhynchophus ferrugineus (Coleoptera: Curculionidae) Larvae at Different Developmental Stages.

In this study, the changes in the conventional nutrient and mineral compositions as well as the metabolomics characteristics of the red palm weevil (RPW) Rhynchophus ferrugineus Olivier (Curculionidae: Coleoptera) larvae at early (EL), middle (ML) and old (OL) developmental stages were investigated. Results showed that the EL and ML had the highest content of protein (53.87 g/100 g dw) and fat (67.95 g/100 g), respectively, and three kinds of RPW larvae were all found to be rich in unsaturated fatty acids (52.17-53.12%), potassium (5707.12-15,865.04 mg/kg) and phosphorus (2123.87-7728.31 mg/kg). In addition, their protein contained 17 amino acids with the largest proportion of glutamate. A total of 424 metabolites mainly including lipids and lipid-like molecules, organic acids and their derivatives, organic heterocycle compounds, alkaloids and their derivatives, etc. were identified in the RPW larvae. There was a significant enrichment in the ABC transport, citrate cycle (TCA cycle), aminoacyl-tRNA biosynthesis, and mTOR signaling pathways as the larvae grow according to the analysis results of the metabolic pathways of differential metabolites. The water extract of EL exhibited relatively higher hydroxyl, 2,2-diphenyl-1-pyrroline hydrochloride (DPPH) and 2,2'-azobis (3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) radical-scavenging ability with the EC50 values of 1.12 mg/mL, 11.23 mg/mL, and 2.52 mg/mL, respectively. These results contribute to a better understanding of the compositional changes of the RPW larvae during its life cycle and provide a theoretical grounding for its deep processing and high-value utilization.

ELAPOR1 induces the classical/progenitor subtype and contributes to reduced disease aggressiveness through metabolic reprogramming in pancreatic cancer.

Pancreatic ductal adenocarcinoma (PDAC) is a heterogeneous disease with distinct molecular subtypes described as classical/progenitor and basal-like/squamous PDAC. We hypothesized that integrative transcriptome and metabolome approaches can identify candidate genes whose inactivation contributes to the development of the aggressive basal-like/squamous subtype. Using our integrated approach, we identified endosome-lysosome associated apoptosis and autophagy regulator 1 (ELAPOR1/KIAA1324) as a candidate tumor suppressor in both our NCI-UMD-German cohort and additional validation cohorts. Diminished ELAPOR1 expression was linked to high histological grade, advanced disease stage, the basal-like/squamous subtype, and reduced patient survival in PDAC. In vitro experiments demonstrated that ELAPOR1 transgene expression not only inhibited the migration and invasion of PDAC cells but also induced gene expression characteristics associated with the classical/progenitor subtype. Metabolome analysis of patient tumors and PDAC cells revealed a metabolic program associated with both upregulated ELAPOR1 and the classical/progenitor subtype, encompassing upregulated lipogenesis and downregulated amino acid metabolism. 1-Methylnicotinamide, a known oncometabolite derived from S-adenosylmethionine, was inversely associated with ELAPOR1 expression and promoted migration and invasion of PDAC cells in vitro. Taken together, our data suggest that enhanced ELAPOR1 expression promotes transcriptome and metabolome characteristics that are indicative of the classical/progenitor subtype, whereas its reduction associates with basal-like/squamous tumors with increased disease aggressiveness in PDAC patients. These findings position ELAPOR1 as a promising candidate for diagnostic and therapeutic targeting in PDAC.