PubMed

Eur Heart J. 2022 Nov 25:ehac446. doi: 10.1093/eurheartj/ehac446. Online ahead of print.ABSTRACTAIMS: Observational studies of diet in cardiometabolic-cardiovascular disease (CM-CVD) focus on self-reported consumption of food or dietary pattern, with limited information on individual metabolic responses to dietary intake linked to CM-CVD. Here, machine learning approaches were used to identify individual metabolic patterns related to diet and relation to long-term CM-CVD in early adulthood.METHODS AND RESULTS: In 2259 White and Black adults (age 32.1 ± 3.6 years, 45% women, 44% Black) in the Coronary Artery Risk Development in Young Adults (CARDIA) study, multivariate models were employed to identify metabolite signatures of food group and composite dietary intake across 17 food groups, 2 nutrient groups, and healthy eating index-2015 (HEI2015) diet quality score. A broad array of metabolites associated with diet were uncovered, reflecting food-related components/catabolites (e.g. fish and long-chain unsaturated triacylglycerols), interactions with host features (microbiome), or pathways broadly implicated in CM-CVD (e.g. ceramide/sphingomyelin lipid metabolism). To integrate diet with metabolism, penalized machine learning models were used to define a metabolite signature linked to a putative CM-CVD-adverse diet (e.g. high in red/processed meat, refined grains), which was subsequently associated with long-term diabetes and CVD risk numerically more strongly than HEI2015 in CARDIA [e.g. diabetes: standardized hazard ratio (HR): 1.62, 95% confidence interval (CI): 1.32-1.97, P < 0.0001; CVD: HR: 1.55, 95% CI: 1.12-2.14, P = 0.008], with associations replicated for diabetes (P < 0.0001) in the Framingham Heart Study.CONCLUSION: Metabolic signatures of diet are associated with long-term CM-CVD independent of lifestyle and traditional risk factors. Metabolomics improves precision to identify adverse consequences and pathways of diet-related CM-CVD.PMID:36424694 | DOI:10.1093/eurheartj/ehac446

Sci Rep. 2022 Nov 23;12(1):20168. doi: 10.1038/s41598-022-24382-4.ABSTRACTEnterococci are a common cause of urinary tract infections. The severity of enterococcal infections is associated with their ability to form biofilms. Morus leaves are known as a natural antibacterial, however, their antibiofilm activity against Enterococcus remains unveiled. This study aimed to evaluate the ability of four polyphenol-rich Morus leaves extracts (Morus nigra, M. rubra, M. macroura, and M. alba) to inhibit biofilm formed by enterococcal clinical isolates in relation to their metabolic profiling. Results revealed that 48% of the isolates formed strong biofilm, 28% formed moderate biofilm, 20% formed weak biofilm, and only 4% did not form a biofilm. The strong biofilm-forming isolates were E. faecalis, and hence were chosen for this study. The antibiofilm activity of the four polyphenol-rich Morus leaves extracts revealed that the M. nigra extract exhibited the highest percentage of biofilm inhibition followed by M. rubra then M. macroura and the least inhibition was detected in M. alba, and these results were in accordance with the phenolic and flavonoid contents of each extract. UPLC-ESI-MS/MS identified 61 polyphenolic compounds in the four extracts. Further, multivariate analysis confirmed clear segregation of M. nigra from the other species suggesting disparity in its metabolome, with accumulation of flavonoids, anthocyanidins, phenolic acids and coumarin derivatives. Quercetin and kaempferol glycosides were found to be positively and significantly correlated to the antibiofilm activity. In conclusion, M. nigra ethanolic extracts showed the highest phenolic content and antibiofilm activity and they could be developed as a complementary treatment for the development of antimicrobial agents.PMID:36424446 | DOI:10.1038/s41598-022-24382-4

Sci Rep. 2022 Nov 23;12(1):20161. doi: 10.1038/s41598-022-24687-4.ABSTRACTBioreactors are one of the most important, basic pieces of equipment in the biopharmaceutical industry. Understanding the effects of mechanical damage and other factors on the physiological state of cells during cell matrix culture is the basis for continuously achieving greater efficiency and higher product quality. In this study, Vero cells were used as a model and apoptosis, senescence, transcriptomics, proteomics, and metabolomics were carried out for analysis at the cellular and molecular levels. The results showed that compared with cells cultured in the simulated natural state, the cells cultured in the basket bioreactor displayed no obvious senescence. Additionally, the proportion of early apoptotic cells increased, but the proportions of damaged, late apoptotic and dead cells did not change significantly. The transcription levels of aminoacyl-tRNA synthetase and cyclin D1 and the expression levels of DNA replication licensing factor, methenyltetrahydrofolate cyclohydrolase, arachidonic acid and other metabolites of cells cultured in the basket bioreactor were significantly increased. These results suggest that DNA replication, protein translation and the metabolic activities in cells cultured in basket bioreactors are more active, which is more conducive to cell amplification and target product production. In this study, the growth and physiological state of cells in a basket bioreactor were characterized at the molecular level for the first time. Additionally, a tool to evaluate the physiological state of cells in a bioreactor was established, which can be used to guide the development and optimization of cell matrix culture conditions in industrial production and improve the production efficiency of the target products.PMID:36424406 | DOI:10.1038/s41598-022-24687-4

Hum Immunol. 2022 Nov 21:S0198-8859(22)00232-4. doi: 10.1016/j.humimm.2022.11.004. Online ahead of print.ABSTRACTAlthough decades of the reductionist approach achieved great milestones in optimizing the immunosuppression therapy, traditional clinical parameters still fail in predicting both acute and chronic (mainly) rejection events leading to higher rates across all solid organ transplants. To clarify the underlying immune-related cellular and molecular mechanisms, current biomedical research is increasingly focusing on "transplantomics" which relies on a huge quantity of big data deriving from genomics, transcriptomics, epigenomics, proteomics, and metabolomics platforms. The AlloMap (gene expression) and the AlloSure (donor-derived cell-free DNA) tests represent two successful examples of how omics and liquid biopsy can really improve the precision medicine of heart and kidney transplantation. One of the major challenges in translating big data in clinically useful biomarkers is the integration and interpretation of the different layers of omics datasets. Network Medicine offers advanced bioinformatic-molecular strategies which were widely used to integrate large omics datasets and clinical information in end-stage patients to prioritize potential biomarkers and drug targets. The application of network-oriented approaches to clarify the complex nature of graft rejection is still in its infancy. Here, we briefly discuss the real-life clinical applications derived from omics datasets as well as novel opportunities for establishing predictive tests in solid organ transplantation. Also, we provide an original "graft rejection interactome" and propose network-oriented strategies which can be useful to improve precision medicine of solid organ transplantation.PMID:36424231 | DOI:10.1016/j.humimm.2022.11.004

Environ Pollut. 2022 Nov 21:120701. doi: 10.1016/j.envpol.2022.120701. Online ahead of print.ABSTRACTStudies exploring the association of tetrabromobisphenol A (TBBPA) with breast cancer and related mechanisms are limited. To investigate the relationship between TBBPA levels in breast adipose and breast cancer, we carried out case-control research. As well as further examine the mediating role of adipose metabolites between TBBPA and breast cancer using the metabolomics approach. In this study, the concentration of TBBPA was determined utilizing ultra-performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS) after a solid phase extraction (SPE) pretreatment. High-performance liquid chromatography tandem mass spectrometry (HPLC-MS/MS) was employed to analyze adipose metabolomics. Evaluation of metabolites linked to TBBPA exposure and breast cancer was performed utilizing mediation analysis. With an estimated OR (95%CI) of 1.153 (1.023, 1.299), TBBPA was firmly linked with breast cancer. We also used propensity score matching analysis and sensitivity analysis to reduce the effect of confounding factors on the results. Metabolomics of adipose suggested significant perturbation in the linoleic acid metabolism pathway. In addition, for PC (16:0/16:0) as phospholipids, a mediation effect on the associations of TBBPA exposure with breast cancer risks was observed (estimated mediation percentage: 56.58%). Understanding the relationship between TBBPA exposure and the risk of breast cancer may be facilitated by the findings, which point to potential mediation metabolites.PMID:36423888 | DOI:10.1016/j.envpol.2022.120701

Pharmacol Res. 2022 Nov 21:106570. doi: 10.1016/j.phrs.2022.106570. Online ahead of print.ABSTRACTHypercholesterolemia is a major driver of atherosclerosis, thus contributing to high morbidity and mortality worldwide. Gut microbiota have been identified as modulator of blood lipids including cholesterol levels. Few studies have already linked certain bacteria and microbial mechanisms to host cholesterol. However, in particular mouse models revealed conflicting results depending on genetics and experimental protocol. To gain further insights into the relationship between intestinal bacteria and host cholesterol metabolism, we first performed fecal 16S rRNA targeted metagenomic sequencing in a human cohort (n = 24) naïve for cholesterol lowering drugs. Here, we show alterations in the gut microbiota composition of hypercholesterolemic patients with depletion of Bifidobacteria, expansion of Clostridia and increased Firmicutes/Bacteroidetes ratio. To test whether pharmacological intervention in gut microbiota impacts host serum levels of cholesterol, we treated hypercholesterolemic Apolipoprotein E knockout with oral largely non-absorbable antibiotics. Antibiotics increased serum cholesterol, but only when mice were fed normal chow diet and cholesterol was measured in the random fed state. These elevations in cholesterol already occurred few days after treatment initiation and were reversible after stopping antibiotics with re-acquisition of intestinal bacteria. Gene expression analyses pointed to increased intestinal cholesterol uptake mediated by antibiotics in the fed state. Non-targeted serum metabolomics suggested that diminished plant sterol levels and reduced bile acid cycling were involved microbial mechanisms. In conclusion, our work further enlightens the link between gut microbiota and host cholesterol metabolism. Pharmacological disruption of the gut flora by antibiotics was able to exacerbate serum cholesterol and may impact cardiovascular disease.PMID:36423788 | DOI:10.1016/j.phrs.2022.106570

Bioresour Technol. 2022 Nov 21:128370. doi: 10.1016/j.biortech.2022.128370. Online ahead of print.ABSTRACTAstaxanthin is used extensively in the nutraceutical, aquaculture, and cosmetic industries. The current market necessitates higher astaxanthin production from Phaffia rhodozyma (P. rhodozyma) due to its higher cost compared to chemical synthesis. In this study, a bubble discharge reactor was developed to generate plasma-activated water (PAW) to produce PAW-made yeast malt (YM) medium. Due to oxidative stress induced by PAW, strains cultured in 15 and 30 min-treated PAW-made medium produced 7.9±1.2% and 12.6±1.4% more carotenoids with 15.5±3.3% and 22.1±1.3% more astaxanthin, respectively. Reactive oxygen species (ROS) assay results showed that ROS generated by plasma-water interactions elevated intracellular ROS levels. Proteomic analysis revealed increased expression of proteins involved in the cellular response to oxidative stress as well as carotenoid biosynthesis, both of which contribute to higher yields of astaxanthin. Overall, this study supports the potential of PAW to increase astaxanthin yields for industrial-scale production.PMID:36423765 | DOI:10.1016/j.biortech.2022.128370

J Pharm Biomed Anal. 2022 Nov 14;224:115162. doi: 10.1016/j.jpba.2022.115162. Online ahead of print.ABSTRACTThis work reports on targeted UHPLC-tandem mass spectrometry methods for the chiral separation of anteiso-methyl branched fatty acids (aiFAs). The methods involve precolumn derivatization with 1-naphthylamine and chiral separation on Chiralpak IG-U. anteiso-Methyl branched fatty acids with up to eight carbons can be separated. A method was used for the assignment of the absolute configuration of an aiFA present as fatty acyl residue of the teicoplanin mixture, namely teicoplanin RS3. Furthermore, the excellent methylene selectivity and improved selectivity for constitutional isomers of the polysaccharide columns was exploited for the elucidation and structural confirmation of previously unknown fatty acyl residues in teicoplanin. This shows the versatility and practical applicability of polysaccharide columns as orthogonal stationary phases to reversed-phase for structural elucidation of natural compounds. The developed methods are useful tools for related subdisciplines such as targeted metabolomics and lipidomics.PMID:36423498 | DOI:10.1016/j.jpba.2022.115162

J Hazard Mater. 2022 Nov 10;444(Pt A):130368. doi: 10.1016/j.jhazmat.2022.130368. Online ahead of print.ABSTRACTPesticide thiram is widely used in agriculture and has been demonstrated to cause tibial dyschondroplasia (TD) in birds. However, the underlying mechanism remains unclear. This work used multi-omics analysis to evaluate the molecular pathways of TD in broilers that were exposed to low level of thiram. Integrative analysis of transcriptomic, proteomic, and metabolomic revealed thiram activity in enhancing pathological ECM remodeling via attenuating the glycolysis pathway and activating the hexosamine and glucuronic acid pathways. Intriguingly, we found hyperglycemia as a crucial factor for ECM overproduction, which resulted in the development of TD. We further demonstrated that high glucose levels are caused by islet secretion dysfunction in thiram-treated broilers. A combination of factors, including lipid disorder, low-grade inflammation, and gut flora disturbance, might contribute to the dysregulation of insulin secretion. The current work revealed the underlying toxicological mechanisms of thiram-induced tibial dyschondroplasia through blood glucose disorder via the gut-pancreas axis in chickens for the first time, which makes it easier to figure out the health risks of pesticides for worldwide policy decisions.PMID:36423455 | DOI:10.1016/j.jhazmat.2022.130368

J Hazard Mater. 2022 Nov 11;444(Pt A):130376. doi: 10.1016/j.jhazmat.2022.130376. Online ahead of print.ABSTRACTThe bacterial interactions that regulate Cd sorption and As bioreduction in co-contaminated systems are poorly understood. We isolated two bacterial strains, i.e., Pseudomonas aeruginosa and Bacillus licheniformis from a Cd and As co-contaminated soil and compared the effects of monoculture and coculture on microbial Cd sorption and As bioreduction efficiency in the media with different Cd (0, 0.5, 5, 10, 50, 100 mg/L) and As(Ⅴ) (0, 90 mg/L) concentrations. Compared with monoculture, the bacterial coculture increased the Cd sorption efficiency by up to 32% and the As bioreduction (As(Ⅴ) to As(Ⅲ)) efficiency by up to 28%, associated with the increased abundance of As reduction gene arsB. Based on SEM-TEM and metabolomics, the enhanced efficiency was attributed to bacterial interactions, supported by the differential secretion of extracellular polymeric substances. Notably, the differential lipids and lipid-like molecules, and organoheterocyclic compounds resulted from bacterial interactions compared to monoculture exhibited the highest Cd sorption and As bioreduction. The increased efficiencies by bacterial coculture were verified by soil incubation experiments. These results provide insight on applying specific bacterial coculture and their metabolites to enhance Cd sorption and As bioreduction in effective and sustainable remediation of co-contaminated environments.PMID:36423454 | DOI:10.1016/j.jhazmat.2022.130376

Environ Int. 2022 Nov 19;170:107636. doi: 10.1016/j.envint.2022.107636. Online ahead of print.ABSTRACTAmbient air pollution was classified as carcinogenic to humans (Group 1) for lung cancer. DNA damage was an important first step in the process of carcinogenesis, and could also be induced by air pollution. In this study, intratracheal instillation and real-time air exposure system were combined to establish SHP (short-term high-level PM2.5) and LLPO (long-term low-level PM2.5 and O3) exposure patterns, respectively. Hierarchical levels of genetic biomarkers were analyzed to explore DNA damage effects in rats. Representative DNA repair genes from different repair pathways were selected to explore the relative expression levels. The methylation level of differentially expressed repair genes were also determined. Besides, miRNA sequencing and non-targeted metabolomic analysis were performed in rat lungs. KEGG and multi-omics analysis were used to explore the potential mechanism of genetic damage under different air pollution patterns. We found that LLPO exposure induced DSBs and chromosome damage. SHP exposure could induce DSBs and DNA oxidative damage, and the effects of genetic damage under this pollution pattern could be repaired by natural repair. Repair genes involved in two pattern were different. SHP exposure could induce higher methylation levels of RAD51, which might be a potential epigenetic mechanism for high-level PM2.5 induced down-regulated expression of RAD51 and DSBs. Besides, 29 overlapped alterations in metabolic pathways were identified by metabolomic and miRNA sequencing, including purine metabolism and pyrimidine metabolism after LLPO exposure. Differential miRNAs expression in lung tissue were associated with apoptosis, DNA damage and damage repair. We concluded that under different air pollution patterns, DNA damage biomarkers and activated targets of DNA damage repair network were both different. The genetic damage effects caused by high-level short-term PM2.5 can be alleviated by natural repair. We provided possible mechanisms by multi-omics which could explain the increased carcinogenic risk caused by air pollution.PMID:36423397 | DOI:10.1016/j.envint.2022.107636

Vet Sci. 2022 Nov 16;9(11):637. doi: 10.3390/vetsci9110637.ABSTRACTVaginal myiasis is one of the most serious parasitic diseases in Bactrian camels. At present, there are no reports on biological control measures of the disease. In this paper, the metabolomic analysis of vaginal secretions from susceptible and non-susceptible camels was performed by ACQUITY UPLC H-Class Ultra Performance Liquid Chromatograph. The results matched in 140 vaginal compounds. Methylheptenone, 1-octen-3-ol, and propyl butyrate and their mixtures were selected for gas chromatography-electroantennography (GC-EAD), electroantennography (EAG), behavioral experiments and trapping experiments of Wohlfahrtia magnifica (W. magnifica). Results showed that the W. magnifica had EAG responses to the three compounds, respectively. The EAG responses of female flies to different concentrations of methylheptenone were significantly different, but to the others had no significant difference, and there was no significant difference in the same compounds between the different sexes. Behavioral and trapping experiments showed that methylheptenone and 1-octen-3-ol have significant attraction to W. magnifica, but there was no significant difference to propyl butyrate. When methylheptenone and 1-octen-3-ol were mixed in different proportions, it was found that a mixture at the ratio of 1:1 and 0.5:1 had extremely significant and significant attraction, respectively, to both male and female W. magnifica. The study showed that, except for propyl butyrate, the higher the concentrations of the other two compounds, the stronger the attractivity to the W. magnifica, and a mixture at the ratio of 1:1 could enhance the attractivity to the W. magnifica.PMID:36423086 | DOI:10.3390/vetsci9110637

Toxics. 2022 Nov 14;10(11):688. doi: 10.3390/toxics10110688.ABSTRACTGiant pandas in zoo captivity are situated in residential areas, where environmental pollutants and anthropogenic factors have an impact on their health. Hair metabolomics has been applied in numerous environmental toxicological studies. Therefore, the panda fur metabolome could be a reliable approach to reflect endogenous and exogenous metabolic changes related to environmental exposure. However, there is no established extraction protocol to study the fur metabolome of pandas. The aim of this research was to optimize the extraction of panda fur metabolome for high-throughput metabolomics analysis using gas chromatography-mass spectrometry. Fur samples were collected from five pandas. Eight different extraction methods were investigated and evaluated for their reproducibility, metabolite coverage, and extraction efficiency, particularly in relation to the biochemical compound classes such as amino acids, tricarboxylic acid cycle derivatives, fatty acids, and secondary metabolites. Our results demonstrated that HCl + ACN were the superior extraction solvents for amino acid and secondary metabolite extraction, and NaOH + MeOH was ideal for fatty acid extraction. Interestingly, the metabolomic analysis of panda fur was capable of discriminating the longitudinal metabolite profile between black and white furs. These extraction protocols can be used in future study protocols for the analysis of the fur metabolome in pandas.PMID:36422896 | DOI:10.3390/toxics10110688

Metabolites. 2022 Nov 21;12(11):1154. doi: 10.3390/metabo12111154.ABSTRACTClinical endocrinology entails an understanding of the mechanisms involved in the regulation of tumors that occur in the endocrine system. The exact cause of endocrine cancers remains an enigma, especially when discriminating malignant lesions from benign ones and early diagnosis. In the past few years, the concepts of personalized medicine and metabolomics have gained great popularity in cancer research. In this systematic review, we discussed the clinical metabolomics studies in the diagnosis of endocrine cancers within the last 12 years. Cancer metabolomic studies were largely conducted using nuclear magnetic resonance (NMR) and mass spectrometry (MS) combined with separation techniques such as gas chromatography (GC) and liquid chromatography (LC). Our findings revealed that the majority of the metabolomics studies were conducted on tissue, serum/plasma, and urine samples. Studies most frequently emphasized thyroid cancer, adrenal cancer, and pituitary cancer. Altogether, analytical hyphenated techniques and chemometrics are promising tools in unveiling biomarkers in endocrine cancer and its metabolism disorders.PMID:36422294 | DOI:10.3390/metabo12111154

Metabolites. 2022 Nov 21;12(11):1152. doi: 10.3390/metabo12111152.ABSTRACTEndosymbiotic relationship has played a significant role in the evolution of marine species, allowing for the development of biochemical machinery for the synthesis of diverse metabolites. In this work, we explore the chemical space of exogenous compounds from shipworm endosymbionts using LC-MS-based metabolomics. Priority T. turnerae strains (1022X.S.1B.7A, 991H.S.0A.06B, 1675L.S.0A.01) that displayed antimicrobial activity, isolated from shipworms collected from several sites in the Philippines were cultured, and fractionated extracts were subjected for profiling using ultrahigh-performance liquid chromatography with high-resolution mass spectrometry quadrupole time-of-flight mass analyzer (UHPLC-HRMS QTOF). T. turnerae T7901 was used as a reference microorganism for dereplication analysis. Tandem MS data were analyzed through the Global Natural Products Social (GNPS) molecular networking, which resulted to 93 clusters with more than two nodes, leading to four putatively annotated clusters: lipids, lysophosphatidylethanolamines, cyclic dipeptides, and rhamnolipids. Additional clusters were also annotated through molecular networking with cross-reference to previous publications. Tartrolon D cluster with analogues, turnercyclamycins A and B; teredinibactin A, dechloroteredinibactin, and two other possible teredinibactin analogues; and oxylipin (E)-11-oxooctadec-12-enoic acid were putatively identified as described. Molecular networking also revealed two additional metabolite clusters, annotated as lyso-ornithine lipids and polyethers. Manual fragmentation analysis corroborated the putative identification generated from GNPS. However, some of the clusters remained unclassified due to the limited structural information on marine natural products in the public database. The result of this study, nonetheless, showed the diversity in the chemical space occupied by shipworm endosymbionts. This study also affirms the use of bioinformatics, molecular networking, and fragmentation mechanisms analysis as tools for the dereplication of high-throughput data to aid the prioritization of strains for further analysis.PMID:36422292 | DOI:10.3390/metabo12111152

Metabolites. 2022 Nov 21;12(11):1151. doi: 10.3390/metabo12111151.ABSTRACTThe global threat of COVID-19 has led to an increased use of metabolomics to study SARS-CoV-2 infections in animals and humans. In spite of these efforts, however, understanding the metabolome of SARS-CoV-2 during an infection remains difficult and incomplete. In this study, metabolic responses to a SAS-CoV-2 challenge experiment were studied in nasal washes collected from an asymptomatic ferret model (n = 20) at different time points before and after infection using an LC-MS-based metabolomics approach. A multivariate analysis of the nasal wash metabolome data revealed several statistically significant features. Despite no effects of sex or interaction between sex and time on the time course of SARS-CoV-2 infection, 16 metabolites were significantly different at all time points post-infection. Among these altered metabolites, the relative abundance of taurine was elevated post-infection, which could be an indication of hepatotoxicity, while the accumulation of sialic acids could indicate SARS-CoV-2 invasion. Enrichment analysis identified several pathways influenced by SARS-CoV-2 infection. Of these, sugar, glycan, and amino acid metabolisms were the key altered pathways in the upper respiratory channel during infection. These findings provide some new insights into the progression of SARS-CoV-2 infection in ferrets at the metabolic level, which could be useful for the development of early clinical diagnosis tools and new or repurposed drug therapies.PMID:36422291 | DOI:10.3390/metabo12111151

Metabolites. 2022 Nov 20;12(11):1144. doi: 10.3390/metabo12111144.ABSTRACTThis study examined the effect of sleep disturbance on gut microbiota (GM), atrial substrate, and atrial fibrillation (AF) inducibility. C57BL/6 mice were subjected to six weeks of sleep deprivation (SD) using the method of modified multiple-platform. Transesophageal burst pacing was performed to evaluate AF inducibility. Feces, plasma, and an atrium were collected and analyzed by 16s rRNA sequencing, liquid chromatography-mass spectrometry (LC-MS)-based metabolome, histological studies, and transcriptome. Higher AF inducibility (2/30 of control vs. 15/30 of SD, p = 0.001) and longer AF duration (p &lt; 0.001), concomitant with aggravated fibrosis, collagen, and lipid accumulation, were seen in the SD mice compared to control mice. Meanwhile, elevated alpha diversity, higher abundance of Flavonifractor, Ruminococcus, and Alloprevotella, as well as imbalanced functional pathways, were observed in the gut of SD mice. Moreover, the global patterns for the plasma metabolome were altered, e.g., the decreased butanoate metabolism intermediates in SD mice. In addition, disrupted metabolic homeostasis in the SD atrium, such as fatty acid metabolism, was analyzed by the transcriptome. These results demonstrated that the crosstalk between GM and atrial metabolism might be a promising target for SD-mediated AF susceptibility.PMID:36422284 | DOI:10.3390/metabo12111144

Metabolites. 2022 Nov 19;12(11):1140. doi: 10.3390/metabo12111140.ABSTRACTHereditary angioedema (HAE) is a rare and potentially life-threatening disease with heterogeneous clinical symptoms. The metabolomic profile of HAE remains unknown. Uncovering the metabolic signatures of HAE may provide inspiration for a comprehensive understanding of HAE pathogenesis and may help explore potential new metabolic biomarkers. We performed a comprehensive metabolic analysis using high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS). Urine samples from 34 HAE patients and 82 healthy controls (HCs) were collected to characterize the metabolic signatures associated with HAE. The metabolomes of HAE patients carrying different mutation types were also compared. A total of 795 metabolites were accurately detected and quantified. We considered 73 metabolites as differential metabolites in HAE patients (with an importance in projection (VIP) value &gt; 1.0, q-value &lt; 0.05, and fold change (FC) ≥ 1.2 or FC ≤ 0.8). Several metabolites associated with riboflavin metabolism, the citrate cycle, oxidative stress, and inflammation, including xanthine, oxypurinol, vitamin B2, and isocitrate, were significantly altered in HAE patients. No significantly different metabolites were found in HAE patients carrying different mutation types. The present study highlights that metabolic disturbances in the purine metabolism, riboflavin metabolism, and TCA cycle may be involved in the pathogenesis of HAE. Although biochemical significance requires further experimental verification, these findings may help to identify novel candidate metabolite biomarkers associated with HAE.PMID:36422280 | DOI:10.3390/metabo12111140

Metabolites. 2022 Nov 19;12(11):1139. doi: 10.3390/metabo12111139.ABSTRACTIdentifying the predisposing factors to chronic or end-stage kidney disease is essential to preventing or slowing kidney function decline. Therefore, here, we investigated the genetic variants related to a rapid decline in the estimated glomerular filtration rate (eGFR) (i.e., a loss of &gt;5 mL/min/1.73 m2 per year) and verified the relationships between variant-related diseases and metabolic pathway signaling in patients with chronic kidney disease. We conducted a genome-wide association study that included participants with diabetes, hypertension, and rapid eGFR decline from two Korean data sources (N = 115 and 69 for the discovery and the validation cohorts, respectively). We identified a novel susceptibility locus: 4q32.3 (rs10009742 in the MARCHF1 gene, beta = -3.540, P = 4.11 × 10-8). Fine-mapping revealed 19 credible, causal single-nucleotide polymorphisms, including rs10009742. The pimelylcarnitine and octadecenoyl carnitine serum concentrations were associated with rs10009742 (beta = 0.030, P = 7.10 × 10-5, false discovery rate (FDR) = 0.01; beta = 0.167, P = 8.11 × 10-4, FDR = 0.08). Our results suggest that MARCHF1 is associated with a rapid eGFR decline in patients with hypertension and diabetes. Furthermore, MARCHF1 affects the pimelylcarnitine metabolite concentration, which may mediate chronic kidney disease progression by inducing oxidative stress in the endoplasmic reticulum.PMID:36422279 | DOI:10.3390/metabo12111139

Metabolites. 2022 Nov 18;12(11):1136. doi: 10.3390/metabo12111136.ABSTRACTThe complex microbiota and sialylated oligosaccharides in breastmilk are important bioactive components that affect the gut microbiota. However, the effect of breastmilk microbiota and sialylated oligosaccharides on the gut microbiota during the neonatal period has been largely overlooked. Here, 16S rRNA gene sequencing and metabolomics analysis were applied to the breastmilk and feces of 69 newborns to clarify the link between breastmilk components and the newborn gut. Results showed that Staphylococcus, Enterococcus, and Bacteroides were commonly shared and positively correlated between breastmilk and the neonatal intestine and they were the main bacteria of breastmilk that interacted with the newborn fecal metabolome. Breastmilk Staphylococcus mainly interacted with amino acids, whereas Bacteroides was involved in the tryptophan, nucleotide, and vitamin metabolism. Breastmilk sialylated oligosaccharides were related to Bacteroides and amino acids of the newborn fecal metabolites. Moreover, Bacteroides was related to the interaction between breastmilk 3'-sialyllactose and newborn fecal metabolites in the mediation effect models. Finally, we pointed out that breastmilk Bacteroides was important in the milk-gut interaction, and it was negatively associated with waist circumference in infants aged 1 year. Our study provides a scientific basis for understanding the role of breastmilk in the development of newborn gut microbiota and metabolome.PMID:36422276 | DOI:10.3390/metabo12111136