PubMed

Pharmacol Res. 2023 Jul 15:106856. doi: 10.1016/j.phrs.2023.106856. Online ahead of print.ABSTRACTDiverse microbial communities colonize different habitats of the human body, including gut, oral cavity, nasal cavity and tissues. These microbial communities are known as human microbiome, plays a vital role in maintaining the health. However, changes in the composition and functions of human microbiome can result in chronic low-grade inflammation, which can damage the epithelial cells and allows pathogens and their toxic metabolites to translocate into other organs such as the liver, heart, and kidneys, causing metabolic inflammation. This dysbiosis of human microbiome has been directly linked to the onset of several non-communicable diseases. Recent metabolomics studies have revealed that pathogens produce several uraemic toxins. These metabolites can serve as inter-kingdom signals, entering the circulatory system and altering host metabolism, thereby aggravating a variety of diseases. Interestingly, Enterobacteriaceae, a critical member of Proteobacteria, has been commonly associated with several non-communicable diseases, and the abundance of this family has been positively correlated with uraemic toxin production. Hence, this review provides a comprehensive overview of Enterobacterial translocation and their metabolites role in non-communicable diseases. This understanding may lead to the identification of novel biomarkers for each metabolic disease as well as the development of novel therapeutic drugs.PMID:37460001 | DOI:10.1016/j.phrs.2023.106856

Sci Total Environ. 2023 Jul 15:165517. doi: 10.1016/j.scitotenv.2023.165517. Online ahead of print.ABSTRACTThe role played by metabolites in exhaled breath condensate (EBC) in the effect of PM on schoolchildren's pulmonary function has received little attention. Accordingly, we examined whether metabolites in EBC mediated the effect of PM10, PM2.5, and PM1 on the pulmonary function of schoolchildren at a residential primary school who had received an air-cleaner cross-over intervention. Samples of EBC were collected from a total of 60 schoolchildren and subjected to metabolomics analysis. We found that the effect of PM on six pulmonary function indicators was mediated by the following nine lipid peroxidation-related and energy metabolism-related metabolites present in EBC: 4-hydroxynonenal, arachidoyl ethanolamide, dl-pyroglutamic acid, 5-deoxy-d-glucose, myristic acid, lauric acid, linoleic acid, l-proline, and palmitic acid. However, while all nine of these metabolites mediated the effects of PM on boys' pulmonary function, only 4-hydroxynonenal, arachidoyl ethanolamide, and dl-pyroglutamic acid mediated the effects of PM on girls' pulmonary function. Overall, our results show that (1) short-term exposure to PM affected the schoolchildren's pulmonary function by causing an imbalance between lipid peroxidation and glutathione-based antioxidant activity and by perturbing energy metabolism in respiratory system and (2) there was a sex-dependent antioxidant response to PM exposure, with boys being less resistant than girls.PMID:37459994 | DOI:10.1016/j.scitotenv.2023.165517

J Hepatol. 2023 Jul 15:S0168-8278(23)04981-4. doi: 10.1016/j.jhep.2023.07.005. Online ahead of print.ABSTRACTBACKGROUND & AIMS: Recent studies have highlighted the role of gut microbiome and metabolites in non-alcoholic fatty liver disease-associated hepatocellular carcinoma (NAFLD-HCC). We aimed to investigate the specific beneficial bacteria species as novel prophylaxis for NAFLD-HCC.METHODS: The role of Bifidobacterium pseudolongum was assessed in two NAFLD-HCC mice models induced by diethylnitrosamine with high-fat/high-cholesterol diet or with choline-deficient/high-fat diet. Germ-free mice were used for B. pseudolongum metabolic study. Stool, portal vein and liver tissues were collected from mice for non-targeted and targeted metabolomic profiles. B. pseudolongum conditioned medium (B.p CM) or candidate metabolite were co-cultured with two human NAFLD-HCC cell lines (HKCI2 and HKCI10).RESULTS: B. pseudolongum was the top depleted bacterium in NAFLD-HCC in mice. Oral gavage of B. pseudolongum significantly suppressed NAFLD-HCC formation in two mouse models (P<0.01). NAFLD-HCC cells co-incubation with B.p CM significantly suppressed cell proliferation, inhibited the G1/S phase transition and induced apoptosis. Acetate was identified as the critical metabolite generated from B. pseudolongum in B.p CM and confirmed in germ-free mice. Acetate inhibited cell proliferation and induced cell apoptosis in NAFLD-HCC cell lines and suppressed NAFLD-HCC tumor formation in vivo. B. pseudolongum restored heathy gut microbiome composition and improved gut barrier function. Mechanistically, B. pseudolongum-produced acetate entered portal vein to reach to the liver and bind to G coupled-protein receptor 43 (GPR43) on hepatocytes. GPR43 activation suppressed IL-6/JAK1/STAT3 signaling pathway, thereby preventing NAFLD-HCC progression.CONCLUSIONS: B. pseudolongum protected against NAFLD-HCC by secreting anti-tumor metabolite acetate through gut-liver axis. B. pseudolongum is a potential probiotic for NAFLD-HCC prevention.IMPACT AND IMPLICATIONS: Non-alcoholic fatty liver disease-associated hepatocellular carcinoma (NAFLD-HCC) is an increasing healthcare burden worldwide. There is an urgent need to develop effective agents to prevent NAFLD-HCC progression. Herein, we show probiotic Bifidobacterium pseudolongum significantly suppressed NAFLD-HCC progression by secreting acetate, which bind to hepatic G coupled-protein receptor 43 (GPR43) through gut-liver axis and suppressed hepatic oncogenic IL-6/JAK1/STAT3 signaling pathway. Bifidobacterium pseudolongum is a potential novel probiotic for NAFLD-HCC prevention.PMID:37459922 | DOI:10.1016/j.jhep.2023.07.005

Prostaglandins Other Lipid Mediat. 2023 Jul 15:106764. doi: 10.1016/j.prostaglandins.2023.106764. Online ahead of print.ABSTRACTCaloric restriction (CR) is a dietetic intervention based on the reduction of daily calorie intake by 10-30%. When subjected to CR, the organism adjusts its metabolism to the changing availability of key nutrients. However, fatty acids' content in organisms subjected to long-term CR has not been evaluated. The aim of the research was to analyze the influence of long-term CR on the contents of medium- and long-chain fatty acids, as well as on the contents of fatty acid derivatives in liver. The study was performed on C57BL female (n = 12) and male (n = 12) mice subjected to lifelong 30% calorie restriction. Fatty acids were analyzed using gas chromatography, while fatty acid derivatives were analyzed with liquid chromatography. The dynamics of change of the lipid profile of the labeled fatty acids observed in the liver tissue confirms that lipolysis actively takes place in this organ when hungry. Moreover, it is highly possible that de novo synthesis of acids takes place, with the aim to ensure energy substrates to the body. Moreover, an increase of concentration was observed for fatty acid derivatives, those with anti-inflammatory properties (resolvin, LTX A4). However, there was no increase in the concentration of pro-inflammatory eicosanoids. The results suggest that it is important to take into consideration the introduction of appropriate supplements when using CR.PMID:37459907 | DOI:10.1016/j.prostaglandins.2023.106764

Genome Med. 2023 Jul 17;15(1):52. doi: 10.1186/s13073-023-01209-z.ABSTRACTBACKGROUND: Metabolic pathways are related to physiological functions and disease states and are influenced by genetic variation and environmental factors. Hispanics/Latino individuals have ancestry-derived genomic regions (local ancestry) from their recent admixture that have been less characterized for associations with metabolite abundance and disease risk.METHODS: We performed admixture mapping of 640 circulating metabolites in 3887 Hispanic/Latino individuals from the Hispanic Community Health Study/Study of Latinos (HCHS/SOL). Metabolites were quantified in fasting serum through non-targeted mass spectrometry (MS) analysis using ultra-performance liquid chromatography-MS/MS. Replication was performed in 1856 nonoverlapping HCHS/SOL participants with metabolomic data.RESULTS: By leveraging local ancestry, this study identified significant ancestry-enriched associations for 78 circulating metabolites at 484 independent regions, including 116 novel metabolite-genomic region associations that replicated in an independent sample. Among the main findings, we identified Native American enriched genomic regions at chromosomes 11 and 15, mapping to FADS1/FADS2 and LIPC, respectively, associated with reduced long-chain polyunsaturated fatty acid metabolites implicated in metabolic and inflammatory pathways. An African-derived genomic region at chromosome 2 was associated with N-acetylated amino acid metabolites. This region, mapped to ALMS1, is associated with chronic kidney disease, a disease that disproportionately burdens individuals of African descent.CONCLUSIONS: Our findings provide important insights into differences in metabolite quantities related to ancestry in admixed populations including metabolites related to regulation of lipid polyunsaturated fatty acids and N-acetylated amino acids, which may have implications for common diseases in populations.PMID:37461045 | DOI:10.1186/s13073-023-01209-z

Anal Bioanal Chem. 2023 Jul 18. doi: 10.1007/s00216-023-04826-0. Online ahead of print.ABSTRACTIn the present study, we developed and validated a fast, simple, and sensitive quantitative method for the simultaneous determination of eleven nucleosides and deoxynucleosides from urine samples. The analyses were performed with the use of liquid chromatography coupled with triple quadrupole mass spectrometry. The sample pretreatment procedure was limited to centrifugation, vortex mixing of urine samples with a methanol/water solution (1:1, v/v), evaporation and dissolution steps. The analysis lasted 20 min and was performed in dynamic multiple reaction monitoring mode (dMRM) in positive polarity. Process validation was conducted to determine the linearity, precision, accuracy, limit of quantification, stability, recovery and matrix effect. All validation procedures were carried out in accordance with current FDA and EMA regulations. The validated method was applied for the analysis of 133 urine samples derived from bladder cancer patients before tumor resection and 24 h, 2 weeks, and 3, 6, 9, and 12 months after the surgery. The obtained data sets were analyzed using a linear mixed-effect model. The analysis revealed that concentration level of 2-methylthioadenosine was decreased, while for inosine, it was increased 24 h after tumor resection in comparison to the preoperative state. The presented quantitative longitudinal study of urine nucleosides and deoxynucleosides before and up to 12 months after bladder tumor resection brings additional prospective insight into the metabolite excretion pattern in bladder cancer disease. Moreover, incurred sample reanalysis was performed proving the robustness and repeatability of the developed targeted method.PMID:37460824 | DOI:10.1007/s00216-023-04826-0

Sci Rep. 2023 Jul 17;13(1):11522. doi: 10.1038/s41598-023-38750-1.ABSTRACTTo understand differences between asymptomatic colonized and infected states of indwelling medical devices, we sought to determine penile prosthesis biofilm composition, microbe-metabolite interaction networks, and association with clinical factors. Patients scheduled for penile prosthesis removal/revision were included. Samples from swabbed devices and controls underwent next-generation sequencing, metabolomics, and culture-based assessments. Biofilm formation from device isolates was reconstituted in a continuous-flow stir tank bioreactor. 93% of 27 analyzed devices harbored demonstrable biofilm. Seven genera including Faecalibaculum and Jeotgalicoccus were more abundant in infected than uninfected device biofilms (p < 0.001). Smokers and those with diabetes mellitus or cardiac disease had lower total normalized microbial counts than those without the conditions (p < 0.001). We identified microbe-metabolite interaction networks enriched in devices explanted for infection and pain. Biofilm formation was recapitulated on medical device materials including silicone, PTFE, polyurethane, and titanium in vitro to facilitate further mechanistic studies. Nearly all penile prosthesis devices harbor biofilms. Staphylococcus and Escherichia, the most common causative organisms of prosthesis infection, had similar abundance irrespective of infection status. A series of other uncommon genera and metabolites were differentially abundant, suggesting a complex microbe-metabolite pattern-rather than a single organism-is responsible for the transition from asymptomatic to infected or painful states.PMID:37460611 | DOI:10.1038/s41598-023-38750-1

Nat Commun. 2023 Jul 17;14(1):4271. doi: 10.1038/s41467-023-39769-8.ABSTRACTMultiple myeloma bone disease is characterized by the development of osteolytic bone lesions. Recent work identified matrix metalloproteinase 13 as a myeloma-derived fusogen that induces osteoclast activation independent of its proteolytic activity. We now identify programmed death-1 homolog, PD-1H, as the bona fide MMP-13 receptor on osteoclasts. Silencing PD-1H or using Pd-1h-/- bone marrow cells abrogates the MMP-13-enhanced osteoclast fusion and bone-resorptive activity. Further, PD-1H interacts with the actin cytoskeleton and plays a necessary role in supporting c-Src activation and sealing zone formation. The critical role of PD-1H in myeloma lytic bone lesions was confirmed using a Pd-1h-/- myeloma bone disease mouse model wherein myeloma cells injected into Pd-1h-/-Rag2-/- results in attenuated bone destruction. Our findings identify a role of PD-1H in bone biology independent of its known immunoregulatory functions and suggest that targeting the MMP-13/PD-1H axis may represent a potential approach for the treatment of myeloma associated osteolysis.PMID:37460553 | DOI:10.1038/s41467-023-39769-8

Cell Death Discov. 2023 Jul 17;9(1):251. doi: 10.1038/s41420-023-01549-0.ABSTRACTThe ketogenic diet (KD) is a low carbohydrate and high-fat protein diet. It plays a protective role in neurodegenerative diseases by elevating the levels of ketone bodies in blood, regulating central and peripheral metabolism and mitochondrial functions, inhibiting neuroinflammation and oxidative stress, and altering the gut microbiota. However, studies on ketogenic therapy for Parkinson's disease (PD) are still in their infancy. Therefore, we examined the possible protective effect of KD in a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced PD mouse model, examined the mouse gut microbiota and its metabolites, and performed transcriptomics and metabolomics on the substantia nigra of mice. Our results showed that a long-term medium-chain triglyceride KD (MCT-KD) significantly reduced MPTP-induced damage to dopaminergic (DA) neurons, exerted antioxidant stress through the PI3K/Akt/Nrf2 pathway, and reversed oxidative stress in DA neurons. The MCT-KD also reduced mitochondrial loss, promoted ATP production, and inhibited the activation of microglia to protect DA neurons in MPTP-induced PD mice. MCT-KD altered the gut microbiota and consequently changed the metabolism of substantia nigra neurons through gut microbiota metabolites. Compared to the MPTP group, MCT-KD increased the abundance of gut microbiota, including Blautia and Romboutsia. MCT-KD also affects purine metabolism in the substantia nigra pars compacta (SNpc) by altering fecal metabolites. This study shows that MCT-KD has multiple protective effects against PD.PMID:37460539 | DOI:10.1038/s41420-023-01549-0

Zhonghua Xin Xue Guan Bing Za Zhi. 2023 Jul 24;51(7):722-730. doi: 10.3760/cma.j.cn112148-20230329-00182.ABSTRACTObjective: To reveal the similarities and differences in myocardial metabolic characteristics between heart failure with preserved ejection fraction (HFpEF) and heart failure with reduced ejection fraction (HFrEF) mice using metabolomics. Methods: The experimental mice were divided into 4 groups, including control, HFpEF, sham and HFrEF groups (10 mice in each group). High fat diet and Nω-nitroarginine methyl ester hydrochloride (L-NAME) were applied to construct a"two-hit"HFpEF mouse model. Transverse aortic constriction (TAC) surgery was used to construct the HFrEF mouse model. The differential expression of metabolites in the myocardium of HFpEF and HFrEF mice was detected by untargeted metabolomics (UHPLC-QE-MS). Variable importance in projection>1 and P<0.05 were used as criteria to screen and classify the differentially expressed metabolites between the mice models. KEGG functional enrichment and pathway impact analysis demonstrated significantly altered metabolic pathways in both HFpEF and HFrEF mice. Results: One hundred and nine differentially expressed metabolites were detected in HFpEF mice, and 270 differentially expressed metabolites were detected in HFrEF mice. Compared with the control group, the most significantly changed metabolite in HFpEF mice was glycerophospholipids, while HFrEF mice presented with the largest proportion of carboxylic acids and their derivatives. KEGG enrichment and pathway impact analysis showed that the differentially expressed metabolites in HFpEF mice were mainly enriched in pathways such as biosynthesis of unsaturated fatty acids, ether lipid metabolism, amino sugar and nucleotide sugar metabolism, glycerophospholipid metabolism, arachidonic acid metabolism and arginine and proline metabolism. The differentially expressed metabolites in HFrEF mice were mainly enriched in arginine and proline metabolism, glycine, serine and threonine metabolism, pantothenate and CoA biosynthesis, glycerophospholipid metabolism, nicotinate and nicotinamide metabolism and arachidonic acid metabolism, etc. Conclusions: HFpEF mice have a significantly different myocardial metabolite expression profile compared with HFrEF mice. In addition, biosynthesis of unsaturated fatty acids, arachidonic acid metabolism, glycerophospholipid metabolism and arginine and proline metabolism are significantly altered in both HFpEF and HFrEF mice, suggesting that these metabolic pathways may play an important role in disease progression in both types of heart failure.PMID:37460426 | DOI:10.3760/cma.j.cn112148-20230329-00182

J Pharm Biomed Anal. 2023 Jul 13;234:115573. doi: 10.1016/j.jpba.2023.115573. Online ahead of print.ABSTRACTTripterygium wilfordii (TW), a well-known traditional Chinese medicine, was widely used in the treatment of autoimmune disorders and inflammatory diseases. However, the clinical use of TW was limited by severe toxicities, such as hepatotoxicity and nephrotoxicity. Our previous studies indicated that roasting was an effective approach for reducing TW-induced toxicity. After roasting, celastrol was completely decomposed, partially converted into 1-hydroxy-2,5,8-trimethyl-9-fluorenone and the total alkaloids content were significantly reduced. However, the detoxication mechanisms of roasting on TW were poorly unknown. This study aimed to explore the toxicity and detoxification mechanisms of TW after roasting based on urine metabolomics. Promising biomarkers were evaluated by multiple comparison analyses. Sixteen toxicity biomarkers were identified between control group and total extract group. Twelve toxicity biomarkers were identified between control group and total alkaloids group. Eight toxicity biomarkers were identified between control group and celastrol group. These metabolites were mainly involved in seven metabolic pathways, summarized as pentose and glucuronate interconversions, lipid metabolism (sphingolipid metabolism, glycerophospholipid metabolisms, fatty acid biosynthesis and steroid hormone biosynthesis) and amino acid metabolism (taurine and hypotaurine metabolism, tryptophan metabolism). After roasting, the toxicities of total extract, total alkaloids and celastrol were relieved by ameliorative serum parameters and pathological changes in hepatic and renal tissues which revealed that the reduction of celastrol and total alkaloids played important roles in the detoxification of roasting on TW. Furthermore, roasting regulated the levels of fourteen potential biomarkers in the total extract group, ten potential biomarkers in the total alkaloids group and seven candidate biomarkers in the celastrol group to normal levels. Biological pathway analysis revealed that roasting may ameliorate TW-induced metabolic disorders in pentose and glucuronate interconversions, lipid metabolism and amino acid metabolism. This study provided evidence for the application of roasting in TW.PMID:37459834 | DOI:10.1016/j.jpba.2023.115573

Biomed Pharmacother. 2023 Jul 15;165:115160. doi: 10.1016/j.biopha.2023.115160. Online ahead of print.ABSTRACTEssential hypertension (EH) is a leading cause of cardiovascular morbidity and mortality. Fructus Tribuli (FT), as a traditional medicine, has been frequently used for thousands of years. The crude Fructus Tribuli (CFT), decoction pieces being processed to remove impurities, have been listed as an important medicine for the treatment of hypertension in the elderly. According to the theory of traditional Chinese medicine, the CFT can enhance the EH treatment after being stir-fried into stir-fried Fructus Tribuli (SFT). At present, whether the SFT can enhance the EH treatment and its potential pharmacodynamic substances and mechanism are unknown. In this study, an integrated "spectrum-effect relationship-network pharmacology-metabolomics" strategy was used. Using male spontaneously hypertensive rats as an experimental model, we compared the therapeutic effects of CFT and SFT on EH. Subsequently, to define the pharmacodynamic material basis of SFT in enhancing the EH treatment, the steroidal saponins (main active components of FT) were selected for spectrum-effect relationship analysis. Furthermore, we applied the joint pathway analysis of network pharmacology and metabolomics to explore the underlying mechanism of SFT in enhancing the EH treatment. Results showed that SFT was better than CFT in the EH treatment. The steroidal saponins transformed by stir-frying were the potential pharmacodynamic substances that SFT could enhance the EH treatment. And the mechanism of action might be associated with regulating glycerophospholipid metabolism and arachidonic acid metabolism, especially arachidonic acid metabolism. This study provided a scientific basis for the clinical use of SFT as an important medicine for the EH treatment.PMID:37459662 | DOI:10.1016/j.biopha.2023.115160

Proc Natl Acad Sci U S A. 2023 Jul 25;120(30):e2301538120. doi: 10.1073/pnas.2301538120. Epub 2023 Jul 17.ABSTRACTPseudomonas aeruginosa (PA) CbpD belongs to the lytic polysaccharide monooxygenases (LPMOs), a family of enzymes that cleave chitin or related polysaccharides. Here, we demonstrate a virulence role of CbpD in PA pneumonia linked to impairment of host complement function and opsonophagocytic clearance. Following intratracheal challenge, a PA ΔCbpD mutant was more easily cleared and produced less mortality than the wild-type parent strain. The x-ray crystal structure of the CbpD LPMO domain was solved to subatomic resolution (0.75Å) and its two additional domains modeled by small-angle X-ray scattering and Alphafold2 machine-learning algorithms, allowing structure-based immune epitope mapping. Immunization of naive mice with recombinant CbpD generated high IgG antibody titers that promoted human neutrophil opsonophagocytic killing, neutralized enzymatic activity, and protected against lethal PA pneumonia and sepsis. IgG antibodies generated against full-length CbpD or its noncatalytic M2+CBM73 domains were opsonic and protective, even in previously PA-exposed mice, while antibodies targeting the AA10 domain were not. Preexisting antibodies in PA-colonized cystic fibrosis patients primarily target the CbpD AA10 catalytic domain. Further exploration of LPMO family proteins, present across many clinically important and antibiotic-resistant human pathogens, may yield novel and effective vaccine antigens.PMID:37459522 | DOI:10.1073/pnas.2301538120

J Econ Entomol. 2023 Jul 17:toad132. doi: 10.1093/jee/toad132. Online ahead of print.ABSTRACTDetection of sex pheromones of insects relies on the antennae. The female pheromone signal transmission in the male antennae ultimately initiates the courtship and mating behaviors of males. To investigate the proteins and metabolites involved in this neural transduction, integrative proteomics and metabolomics analysis including tandem mass tag (TMT) proteomic quantification and liquid chromatography tandem mass spectrometry (LC/MS)-based metabolomics was adopted for comparing proteomic and metabolic changes between the antennae of male moths following stimulation by females and the non-stimulated males of Antheraea pernyi (Guérin-Méneville, Lepidoptera: Saturniidae) in this study. A total of 92 differentially expressed proteins (DEPs) containing 52 upregulated and 40 downregulated proteins and 545 differentially expressed metabolites (DEMs) including 218 upregulated and 327 downregulated metabolites were identified from the antennae of female-stimulated male moths based on the proteome and metabolome data, respectively. Bioinformatics analysis was performed for the 45 DEPs and 160 DEMs, including Gene Ontology (GO), Clusters of Orthologous Groups (COG), and Kyoto Encylopaedia of Genes and Genomes (KEGG) enrichment analysis and Human Metabolome Database (HMDB) annotation. A number of DEPs and DEMs related to neural transmission of female pheromone signals in the male antennae of A. pernyi were screened, including tyrosine hydroxylase, cryptochrome-1, tachykinin, arylalkylamine N-acetyltransferase, cadherin-23, glutathione S-transferase delta 3, tyramine, tryptamine, n-oleoyl dopamine, n-stearoyl dopamine, and n-stearoyl tyrosine. The altered expression levels of those proteins or metabolites were speculated involved in regulating the neuron activity for enhanced transmission of neural impulses and continuous perception, reception, and transduction of female pheromone signals. Our findings yielded novel insights into the potential mechanisms in the antennae of male A. pernyi responding to female attraction.PMID:37459048 | DOI:10.1093/jee/toad132

Eur J Nutr. 2023 Jul 17. doi: 10.1007/s00394-023-03181-1. Online ahead of print.ABSTRACTPURPOSE: The influence of vitamin D status on exercise-induced immune dysfunction remains unclear. The aim of this study was to investigate the effects of vitamin D status (circulating 25(OH)D) on innate immune responses and metabolomic profiles to prolonged exercise.METHODS: Twenty three healthy, recreationally active males (age 25 ± 7 years; maximal oxygen uptake [[Formula: see text]max] 56 ± 9 mL·kg-1·min-1), classified as being deficient (n = 7) or non-deficient n = 16) according to plasma concentrations of 25(OH)D, completed 2.5 h of cycling at 15% Δ (~ 55-60% [Formula: see text]max). Venous blood and unstimulated saliva samples were obtained before and after exercise.RESULTS: Participants with deficient plasma 25(OH)D on average had lower total lymphocyte count (mean difference [95% confidence interval], 0.5 cells × 109 L [0.1, 0.9]), p = 0.013) and greater neutrophil:lymphocyte ratio (1.3 cells × 109 L, [0.1, 2.5], p = 0.033). The deficient group experienced reductions from pre-exercise to 1 h post-exercise (- 43% [- 70, - 15], p = 0.003) in bacterial stimulated elastase in blood neutrophils compared to non-deficient participants (1% [- 20, 21], p = 1.000) Multivariate analyses of plasma metabolomic profiles showed a clear separation of participants according to vitamin D status. Prominent sources of variation between groups were purine/pyrimidine catabolites, inflammatory markers (linoleic acid pathway), lactate and tyrosine/adrenaline.CONCLUSION: These findings provide evidence of the influence of vitamin D status on exercise-induced changes in parameters of innate immune defence and metabolomic signatures such as markers of inflammation and metabolic stress.PMID:37458775 | DOI:10.1007/s00394-023-03181-1

Anal Chem. 2023 Jul 17. doi: 10.1021/acs.analchem.3c01358. Online ahead of print.ABSTRACTGastric cancer is one of the most common malignant digestive cancers, and its diagnostic has still faced challenges based on metabolic analysis due to complex sample pretreatment and low metabolite abundance. In this study, inspired by the structure of bovine omasum, we in situ synthesized a novel interfacial carbon-based nanocomposite of graphene supported nickel nanoparticles-encapsulated in the nitrogen-doped carbon nanotube (Ni/N-CNT/rGO), which was served as a novel matrix with enhanced ionization efficiency for the matrix-assisted laser desorption/ionization time of flight mass spectrometry (MALDI-TOF MS) saliva metabolic analysis of gastric cancer. Benefiting from its high sp2 graphitic degree, large surface area, strong UV absorption, and rich active sites, Ni/N-CNT/rGO matrix exhibited excellent performances of reproducibility, coverage, salt-tolerance, sensitivity, and adsorption ability in MALDI-TOF MS. The differential scanning calorimetry (DSC) and thermal conversion behaviors explained the highly efficient LDI mechanism. Based on saliva metabolic fingerprints, Ni/N-CNT/rGO assisted LDI MS with cross-validation analysis could successfully distinguish gastric cancer patients from healthy controls through the screening of four potential biomarkers with an accuracy of 92.50%, specificity of 88.03%, and sensitivity of 97.12%. This work provided a fast and sensitive MS sensing platform for the metabolomics characterization of gastric cancer and might have potential value for precision medicine in the future.PMID:37458487 | DOI:10.1021/acs.analchem.3c01358

mSystems. 2023 Jul 17:e0015123. doi: 10.1128/msystems.00151-23. Online ahead of print.ABSTRACTColon cancer onset is strongly associated with the differences in microbial taxa in the gastrointestinal tract. Although recent studies highlight the role of individual taxa, the effect of a complex gut microbiome (GM) on the metabolome and host transcriptome is still unknown. We used a multi-omics approach to determine how differences in the GM affect the susceptibility to adenoma development in a rat model of human colon cancer. Ultra-high performance liquid chromatography mass spectrometry of feces collected prior to observable disease onset identified putative metabolite profiles that likely predict future disease severity. Transcriptome analyses performed after disease onset from normal colonic epithelium and tumor tissues show a correlation between GM and host gene expression. Integrated pathway analyses of the metabolome and transcriptome based on putatively identified metabolic features indicate that bile acid biosynthesis is enriched in rats with high tumors along with increased fatty acid metabolism and mucin biosynthesis. Targeted pyrosequencing of the Pirc allele indicates that the GM alters the mechanism of adenoma development and may drive an epigenetic pathway of tumor suppressor silencing. This study reveals how untargeted metabolomics identifies signatures of susceptibility and integrated analyses uncover pathways of differential mechanisms of loss of tumor suppressor gene function and for potential prevention and therapeutic intervention. IMPORTANCE The association between the gut microbiome and colon cancer is significant but difficult to test in model systems. This study highlights the association of differences in the pathogen-free gut microbiome to changes in the host transcriptome and metabolome that correlate with colon adenoma initiation and development in a rat genetic model of early colon cancer. The utilization of a multi-omics approach integrating metabolomics and transcriptomics reveals differences in pathways including bile acid biosynthesis and fatty acid metabolism. The study also shows that differences in gut microbiomes significantly alter the mechanism of adenoma formation, shifting from genetic changes to epigenetic changes that initiate the early loss of tumor suppressor function. These findings enhance our understanding of the gut microbiome's role in colon cancer susceptibility, offer insights into potential biomarkers and therapeutic targets, and may pave the way for future prevention and intervention strategies.PMID:37458451 | DOI:10.1128/msystems.00151-23

J Food Sci. 2023 Jul 17. doi: 10.1111/1750-3841.16701. Online ahead of print.ABSTRACTThe nutritional and volatile profiles of pulp and flavedo samples from four distinct local pummelo landraces ("Siji," "Pingshan," "Wendan," and "Guanxi") cultivated in Fujian province of China were investigated. "Guanxi" pummelo exhibited relatively high contents of vitamin C (42.01 mg/100 mL) and phenols (360.61 mg/L) and displayed a robust antioxidant capacity (41.15 mg/100 mL). Conversely, the red pulp from "Pingshan" demonstrated relatively high values of carotenoids (55.96 µg/g) and flavonoids (79.79 mg/L). Considerable differences were observed in volatile compositions between the two fruit tissues and among the four genotypes. A total of 166 and 255 volatile compounds were detected in the pulp and flavedo samples, respectively. Notably, limonene and β-myrcene were identified as the principal volatile compounds in flavedo, whereas hexanal was highly abundant in the pulp of "Siji," "Pingshan," and "Guanxi." "Wendan" displayed distinct separation from the other three pummelo cultivars in principal component analysis based on the pulp volatile compositions. This distinction was attributed to the higher number and content of volatile compounds in "Wendan" pulp, particularly the remarkable enrichment of β-myrcene. The newly characterized pummelo landraces and genotype/tissue-dependent variations in volatiles provide essential information for the genetic improvement of pummelo aroma, as well as for fruit processing and utilization.PMID:37458289 | DOI:10.1111/1750-3841.16701

J Food Sci. 2023 Jul 17. doi: 10.1111/1750-3841.16698. Online ahead of print.ABSTRACTBambara groundnut (BG) (Vigna subterranean) is an underutilized, indigenous crop in South Africa that has nutritional and associated health benefits. Decreasing the antinutrients in food sources can potentially increase the digestibility of proteins and mineral absorption. To determine the effect of traditional processing (cooking) on the antinutrient content and metabolome of this crop, BG was sampled from 12 rural farms in three districts of the Mpumalanga province, South Africa. The four main colors that were identified (cream, orange, brown, and purple) were pooled together according to the district they were obtained from. One-half of each color sample obtained from each of the three districts was dehulled, color sorted, milled, and subjected to subsequent antinutrient and metabolome analyses, while the other half was cooked, air-dried, and milled prior to analyses. Samples were analyzed for phytate and tannins (antinutrients) by hydrochloric acid extraction methods as well as metabolome constituents by ultraperformance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (UPLC-QTOF-MS). Phytate, tannins, as well as other metabolomic constituents, namely, catechin, epicatechin, procyanidin, as well as citric acid, were identified in all raw and cooked BG samples. The cooking process resulted in a significant decrease (p < 0.05) in the phytate and tannin content as well as an increase in the health-associated phenolic compounds.PMID:37458285 | DOI:10.1111/1750-3841.16698

Eur J Clin Invest. 2023 Jul 17:e14063. doi: 10.1111/eci.14063. Online ahead of print.ABSTRACTBACKGROUND: H-type hypertension (HHT) is a disease combined with hyperhomocysteinaemia and hypertension (HT). This study aims to find specific metabolic changes and reveal the pathophysiological mechanism of HHT, which provide the theoretical basis for the early prevention and treatment of HHT.METHODS: Serum samples from three groups including 53 HHT patients, 36 HT patients and 46 healthy controls (HC) were collected. The targeted and untargeted metabolomics analyses were performed to determine the metabolic changes. Based on multivariate statistical analysis, the serum potential metabolites were screened and different metabolic pathways were explored.RESULTS: Our results demonstrated that there were 28 important potential metabolites for distinguishing HT from HHT patients. Metabolic pathway analysis showed that the different metabolic pathways between HHT and HC group were arginine biosynthesis, arginine and proline metabolism, and tyrosine metabolism. The changed metabolic pathway of HT and HC group included linoleic acid metabolism. The specific metabolic pathways of HT-HHT comparison group had phenylalanine metabolism; phenylalanine, tyrosine and tryptophan biosynthesis; glycine, serine and threonine metabolism.CONCLUSIONS: Metabolomics analysis by mass spectrometry multi-platform revealed the differences of metabolic profiles between HHT and HT subjects. This work laid the groundwork for understanding the aetiology of HHT, and these findings may provide the useful information for explaining the HHT metabolic alterations and try to prevent HHT.PMID:37458276 | DOI:10.1111/eci.14063