PubMed
Updated perspectives on the contribution of the microbiome to the pathogenesis of mucositis using the MASCC/ISOO framework
Support Care Cancer. 2024 Jul 31;32(8):558. doi: 10.1007/s00520-024-08752-4.ABSTRACTAdvances in the treatment of cancer have significantly improved mortality rates; however, this has come at a cost, with many treatments still limited by their toxic side effects. Mucositis in both the mouth and gastrointestinal tract is common following many anti-cancer agents, manifesting as ulcerative lesions and associated symptoms throughout the alimentary tract. The pathogenesis of mucositis was first defined in 2004 by Sonis, and almost 20 years on, the model continues to be updated reflecting ongoing research initiatives and more sophisticated analytical techniques. The most recent update, published by the Multinational Association for Supportive Care in Cancer and the International Society for Oral Oncology (MASCC/ISOO), highlights the numerous co-occurring events that underpin mucositis development. Most notably, a role for the ecosystem of microorganisms that reside throughout the alimentary tract (the oral and gut microbiota) was explored, building on initial concepts proposed by Sonis. However, many questions remain regarding the true causal contribution of the microbiota and associated metabolome. This review aims to provide an overview of this rapidly evolving area, synthesizing current evidence on the microbiota's contribution to mucositis development and progression, highlighting (i) components of the 5-phase model where the microbiome may be involved, (ii) methodological challenges that have hindered advances in this area, and (iii) opportunities for intervention.PMID:39080025 | DOI:10.1007/s00520-024-08752-4
Pharmacogenomic associations of cyclophosphamide pharmacokinetic candidate genes with 4hydroxycyclophosphamide formation in children with Cancer
Cancer Chemother Pharmacol. 2024 Jul 30. doi: 10.1007/s00280-024-04703-2. Online ahead of print.ABSTRACTPURPOSE: 4-hydroxycyclophosphamide (4HCY) is the principal precursor to the cytotoxic metabolite of cyclophosphamide (CY), which is often used as first-line treatment of children with cancer. There is conflicting data regarding the relationship between CY efficacy, toxicity, and pharmacokinetics with the genes encoding proteins involved in 4HCY pharmacokinetics, specifically its formation and elimination.METHODS: We evaluated germline pharmacogenetics in children with various malignancies receiving their first CY dose. Using linear regression, we analyzed the associations between two pharmacokinetic outcomes - how fast a child cleared CY (i.e., CY clearance) and the ratio of the 4HCY/CY exposure, specifically area under the plasma concentration-time curve (AUC), and 372 single nucleotide polymorphisms (SNP) in 14 drug-metabolizing transporters or enzymes involved in 4HCY formation or elimination.RESULTS: Age was associated with the ratio of 4HCY/CY AUC (P = 0.004); Chemotherapy regimen was associated with CY clearance (P = 0.003). No SNPs were associated with CY clearance or the ratio of 4HCY/CY AUC after controlling for a false discovery rate.CONCLUSION: Age and chemotherapy regimen, but not germline pharmacogenomics, were associated with CY clearance or the ratio of 4HCY/CY AUC. Other methods, such as metabolomics or lipidomics, should be explored.PMID:39080017 | DOI:10.1007/s00280-024-04703-2
Extraction recovery and speciation of selenium in Se-enriched yeast
Anal Bioanal Chem. 2024 Jul 30. doi: 10.1007/s00216-024-05448-w. Online ahead of print.ABSTRACTThe complete characterization of selenium-enriched yeast in terms of selenium species has been the goal of extensive research for the last three decades. This contribution addresses the two outstanding questions: the mass balance of the identified and reported selenium species and the possible presence of inorganic selenium. For this purpose, four procedures have been designed combining, in diverse order, the principal steps of selenium speciation analysis in Se-rich yeast: extraction of the Se-metabolome, derivatization of cysteine and Se-cysteine (SeCys) residues, proteolysis, and definitive Se recovery using SDS extraction, followed by mineralization. The recovery of selenium in each step and its speciation were controlled by ICP MS and by reversed-phase HPLC-ICP MS, respectively. The study, carried out for the SELM-1 reference material, demonstrated the presence of about 10% of inorganic selenium and a serious risk of losses of SeCys during derivatization and proteolysis. As result of our work, we postulate the following values for SELM-1: Se-metabolome fraction (SeMF) 14.8 ± 0.7%; total selenomethionine (SeMet) 66.2 ± 2.7% (including ca. 1.5% SeMet present in the SeMF); total SeCys 12.5 ± 1.5% (including 2% of SeCys present in the Se-MF); total inorganic selenium 9.7 ± 1.7%, accounting for > 99.8% of the selenium.PMID:39079983 | DOI:10.1007/s00216-024-05448-w
Differential in vitro cytotoxic effects and metabolomic insights into raw and powdered Manuka honey through UPLC-Q-TOF-MS
Sci Rep. 2024 Jul 30;14(1):17551. doi: 10.1038/s41598-024-68387-7.ABSTRACTManuka honey (MH) has garnered much attention due to its remarkable antimicrobial, anticancer, immunomodulatory and wound-healing properties. This study compared the antiproliferative effects of raw and powdered MH (pMH) on various human and murine cancer cell lines. A detailed metabolomics analysis was also carried out using untargeted ultrahigh-performance liquid chromatography-quadrupole-time-of-flight-mass spectrometry (UPLC-Q-TOF-MS) to compare the constituents in raw MH and pMH. The results of the viability studies showed that both raw MH and pMH caused a dose-dependent inhibition of tumor cell growth at concentrations of > 1% w/v (equivalent to ~ 10 mg/ml). A differential susceptibility to MH was observed among the cell lines with the human MDA-MB-231 and A549 cells and murine B16.F10 cells being relatively resistant to MH while the murine MC38 colorectal adeno-carcinoma cells showing the most sensitivity. The effect of raw MH and pMH on cell viability was validated using 2 indepndent assays. Metabolomics analysis detected 2440 compounds, out of which 833 were successfully identified. Among these, 90 phytochemical compounds, predominantly comprising terpenoids, flavonoids, coumarins and derivatives, and phenylpropanoic acids, and 79 lipids were identifiable. Significant differences in 5 metabolite classes, including flavonoids, phenols, terpenoids, carbohydrates, and organic acids were observed between the raw and pMH. Moreover, several altered metabolic pathways were identified in pMH compared to raw MH, such as energy metabolism, amino acid metabolism, and various other pathways that collectively influence biological functions associated with cellular growth, signaling, and stress response.PMID:39079967 | DOI:10.1038/s41598-024-68387-7
The metabolites mainly composed of lipids in tongue coating are non-invasive potential biomarkers for chronic gastritis
Sci Rep. 2024 Jul 30;14(1):17574. doi: 10.1038/s41598-024-68261-6.ABSTRACTThe changes in tongue coating metabolites in patients with chronic gastritis (CG) under different gastroscopy indicators were analyzed, and these metabolites were screened for potential non-invasive biomarkers to assist in the diagnosis of chronic gastritis. The technology of gas chromatography and liquid chromatography combined with mass spectrometry has been used to more comprehensively detect tongue coating metabolites of 350 CG patients. Spearman correlation analysis and random forest algorithm were used to screen metabolites that can serve as potential biomarkers. Compared with healthy individuals, CG group showed significant changes in the content of 101 metabolites, with an increase in the content of 54 metabolites and a decrease in the content of 47 metabolites. These differential metabolites are mainly composed of 47 lipids and lipid like substances. 1 metabolite was associated with bile reflux, 1 metabolite was associated with gastric mucosal erosion, 10 metabolites were associated with atrophy, 10 metabolites were associated with intestinal metaplasia, and 3 metabolites were associated with Helicobacter pylori infection. The ROC model composed of 5 metabolites can distinguish between CG group and healthy individuals, with an accuracy of 95.4%. The ROC model composed of 5,6-Dihydroxyindole can distinguish between chronic superficial gastritis group and chronic atrophic gastritis group, with an accuracy of 75.3%. The lipids and lipid like metabolites were the main abnormal metabolites in patients with chronic gastritis. It was worth noting that the content of Sphinganine 1-phase, 4-Ipomenol, and Nervonic acid in tongue coating increased, and the content of 1-Methyladenosine and 3-Hydroxycapric acid decreased, which helped to identify CG patients. The decrease in the content of 5,6-dihydroxyindole reminded patients that the development trend of CG was shifting from superficial to atrophic or even intestinal metaplasia. The detection of these metabolic markers of tongue coating was expected to be developed as a non-invasive and convenient technology in the future to assist us in monitoring and diagnosing the occurrence and development of CG.PMID:39079952 | DOI:10.1038/s41598-024-68261-6
Using neural networks to obtain NMR spectra of both small and macromolecules from blood samples in a single experiment
Commun Chem. 2024 Jul 31;7(1):167. doi: 10.1038/s42004-024-01251-x.ABSTRACTMetabolomics plays a crucial role in understanding metabolic processes within biological systems. Using specific pulse sequences, NMR-based metabolomics detects small and macromolecular metabolites that are altered in blood samples. Here we proposed a method called spectral editing neural network, which can effectively edit and separate the spectral signals of small and macromolecules in 1H NMR spectra of serum and plasma based on the linewidth of the peaks. We applied the model to process the 1H NMR spectra of plasma and serum. The extracted small and macromolecular spectra were then compared with experimentally obtained relaxation-edited and diffusion-edited spectra. Correlation analysis demonstrated the quantitative capability of the model in the extracted small molecule signals from 1H NMR spectra. The principal component analysis showed that the spectra extracted by the model and those obtained by NMR spectral editing methods reveal similar group information, demonstrating the effectiveness of the model in signal extraction.PMID:39079950 | DOI:10.1038/s42004-024-01251-x
Single-electron transfer between sulfonium and tryptophan enables site-selective photo crosslinking of methyllysine reader proteins
Nat Chem. 2024 Jul 30. doi: 10.1038/s41557-024-01577-y. Online ahead of print.ABSTRACTThe identification of readers, an important class of proteins that recognize modified residues at specific sites, is essential to uncover the biological roles of post-translational modifications. Photoreactive crosslinkers are powerful tools for investigating readers. However, existing methods usually employ synthetically challenging photoreactive warheads, and their high-energy intermediates generated upon irradiation, such as nitrene and carbene, may cause substantial non-specific crosslinking. Here we report dimethylsulfonium as a methyllysine mimic that binds to specific readers and subsequently crosslinks to a conserved tryptophan inside the binding pocket through single-electron transfer under ultraviolet irradiation. The crosslinking relies on a protein-templated σ-π electron donor-acceptor interaction between sulfonium and indole, ensuring excellent site selectivity for tryptophan in the active site and orthogonality to other methyllysine readers. This method could escalate the discovery of methyllysine readers from complex cell samples. Furthermore, this photo crosslinking strategy could be extended to develop other types of microenvironment-dependent conjugations to site-specific tryptophan.PMID:39079947 | DOI:10.1038/s41557-024-01577-y
Magnoflorine alleviates dextran sulfate sodium-induced ulcerative colitis via inhibiting JAK2/STAT3 signaling pathway
Phytother Res. 2024 Jul 30. doi: 10.1002/ptr.8271. Online ahead of print.ABSTRACTMagnoflorine (Mag), a natural alkaloid component originating from the Ranunculaceae Juss. Family, has a various of pharmacological activities. This study aimed to investigate the therapeutic effects and potential mechanism of Mag on dextran sulfate sodium (DSS)-induced ulcerative colitis (UC) based on comprehensive approaches. Therapeutic effects of Mag on 3% DSS-induced UC mice were analyzed. UHPLC-Q-TOF/MS was performed to investigate the potential metabolites and signaling pathway of Mag on DSS-induced UC. Furthermore, the predicted mRNA and protein levels of JAK2/STAT3 signaling pathway in colon tissue were verified and assessed by qRT-PCR and Western Blotting, respectively. Therapeutic effects of Mag on UC mice were presented in down-regulation serum biochemical indices, alleviating histological damage of colon tissue. Serum untargeted metabolomics analysis showed that the potential mechanism of Mag on UC is mainly associated with the regulation of six biomarkers and 11 pathways, which may be responsible for the therapeutic efficacy of UC. The "component-metabolites-targets" interactive network indicated that Mag exerts its anti-UC effect by regulating PTGS1 and PTGS2, thereby regulating arachidonic acid. Moreover, the results of qRT-PCR showed that Mag could substantially decrease the relative mRNA expression level of Hub genes. In addition, it was found that Mag could inhibit the relative mRNA and protein expression of JAK2/STAT3 signaling pathway. The present results highlighted the role of Mag ameliorated colon injury in DSS-induced UC mice by inhibiting the JAK2/STAT3 signaling pathway. These results suggest that Mag may be an effective agent for the treatment of UC.PMID:39079890 | DOI:10.1002/ptr.8271
Regulation of cancer cell Ferroptosis by PTRF/Cavin-1
Free Radic Res. 2024 Jul 30:1-16. doi: 10.1080/10715762.2024.2386457. Online ahead of print.ABSTRACTOvarian cancer, marked by high rate of recurrence, novel therapeutic strategies are needed to improve patient outcome. One of the potential strategies is inducing ferroptosis in ovarian cancer cells. Ferroptosis is an iron-dependent, lipid peroxidation-driven mode of cell death primarily occurring on the cell membrane. PTRF, an integral component of the caveolae structures located on the cell membrane, is involved in a multitude of physiological processes, including but not limited to, endocytosis, signal transduction, and lipid metabolism. This study elucidates the relationship between PTRF and ferroptosis in ovarian cancer, offering a fresh perspective for the development of new therapeutic strategies. We knocked down PTRF employing siRNA in the ovarian cancer cell lines HEY and SKOV3, following which we stimulated ferroptosis with Erastin (Era). Our research indicates that the lack of PTRF sensitizes cancer cell to ferroptosis, likely by altering membrane stability and tension, thereby affecting signal pathways related to ferroptosis, such as lipid and atherosclerosis, fluid shear stress and atherosclerosis. Our findings provide new insights for developing new treatments for ovarian cancer.PMID:39079051 | DOI:10.1080/10715762.2024.2386457
Unveiling Pathophysiological Insights: Serum Metabolic Dysregulation in Acute Respiratory Distress Syndrome Patients with Acute Kidney Injury
J Proteome Res. 2024 Jul 30. doi: 10.1021/acs.jproteome.4c00138. Online ahead of print.ABSTRACTAcute respiratory distress syndrome (ARDS) is associated with high mortality rates, which are further exacerbated when accompanied by acute kidney injury (AKI). Presently, there is a lack of comprehensive studies thoroughly elucidating the metabolic dysregulation in ARDS patients with AKI leading to poor outcomes. We hypothesized that metabolomics can be a potent tool to highlight the differences in the metabolic profile unraveling unidentified pathophysiological mechanisms of ARDS patients with and without AKI. 1H nuclear magnetic resonance spectroscopy was used to identify key metabolites in the serum samples of 75 patients. Distinct clusters of both groups were obtained as the study's primary outcome using multivariate analysis. Notable alternations in the levels of nine metabolites were identified. Pathway analysis revealed the dysregulation of five significant cycles, which resulted in various complications, such as hyperammonemia, higher energy requirements, and mitochondrial dysfunction causing oxidative stress. Identified metabolites also showed a significant correlation with clinical scores, indicating severity. This study shows the alterations in the metabolite concentration highlighting the difference in the pathophysiology of both patient groups and its association with outcome, pointing in the direction of a personalized medicine approach and holding significant promise for application in critical care settings to improve clinical outcomes.PMID:39078945 | DOI:10.1021/acs.jproteome.4c00138
Simulated LC-MS Data Set for Assessing the Metabolomics Data Processing Pipeline Implemented into MVAPACK
Anal Chem. 2024 Jul 30. doi: 10.1021/acs.analchem.3c04979. Online ahead of print.ABSTRACTMetabolomics commonly relies on using one-dimensional (1D) 1H NMR spectroscopy or liquid chromatography-mass spectrometry (LC-MS) to derive scientific insights from large collections of biological samples. NMR and MS approaches to metabolomics require, among other issues, a data processing pipeline. Quantitative assessment of the performance of these software platforms is challenged by a lack of standardized data sets with "known" outcomes. To resolve this issue, we created a novel simulated LC-MS data set with known peak locations and intensities, defined metabolite differences between groups (i.e., fold change > 2, coefficient of variation ≤ 25%), and different amounts of added Gaussian noise (0, 5, or 10%) and missing features (0, 10, or 20%). This data set was developed to improve benchmarking of existing LC-MS metabolomics software and to validate the updated version of our MVAPACK software, which added gas chromatography-MS and LC-MS functionality to its existing 1D and two-dimensional NMR data processing capabilities. We also included two experimental LC-MS data sets acquired from a standard mixture andMycobacterium smegmatiscell lysates since a simulated data set alone may not capture all the unique characteristics and variability of real spectra needed to assess software performance properly. Our simulated and experimental LC-MS data sets were processed with the MS-DIAL and XCMSOnline software packages and our MVAPACK toolkit to showcase the utility of our data sets to benchmark MVAPACK against community standards. Our results demonstrate the enhanced objectivity and clarity of software assessment that can be achieved when both simulated and experimental data are employed since distinctly different software performances were observed with the simulated and experimental LC-MS data sets. We also demonstrate that the performance of MVAPACK is equivalent to or exceeds existing LC-MS software programs while providing a single platform for processing and analyzing both NMR and MS data sets.PMID:39078713 | DOI:10.1021/acs.analchem.3c04979
Percutaneous ablation versus robotic‑assisted partial nephrectomy for cT1 renal cell carcinoma: an evidence-based analysis of comparative outcomes
J Robot Surg. 2024 Jul 30;18(1):301. doi: 10.1007/s11701-024-02037-y.ABSTRACTThis investigation sought to conduct a comprehensive meta-analysis to assess the comparative effectiveness and safety of percutaneous ablation (PCA) versus robotic-assisted partial nephrectomy (RAPN) among individuals diagnosed with cT1 renal tumors. This study rigorously followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines to conduct a systematic review and meta-analysis. A systematic search was carried out in the PubMed, Embase, Web of Science, and Cochrane Library databases, focusing on studies published in English through February 2024. We focused on evaluating primary outcomes, specifically perioperative outcomes, functional outcomes, and oncological outcomes. In this analysis, data from 1534 patients across 13 studies were evaluated. PCA was found to have advantageous outcomes in comparison to RAPN regarding hospital stay durations, with a Weighted Mean Difference (WMD) of - 2.03 days (95% Confidence Interval [CI]: -3.78 to - 0.27; p = 0.02), operative times (WMD: -106.75 min; 95% CI: - 170.78 to - 42.72; p = 0.001), and overall complication rates (Odds Ratio [OR]: 0.61; 95% CI: 0.42 to 0.89; p = 0.01). Conversely, PCA showed a higher incidence of local recurrence compared to RAPN, with an OR of 3.20 (95% CI: 1.91 to 5.35; p < 0.00001). Moreover, there were no statistically significant differences between the two treatments in terms of major complications, declines in estimated glomerular filtration rates (eGFR), variations in creatinine levels, overall survival rates, and recurrence-free survival. While PCA exhibits higher local recurrence rates than RAPN, it also presents significant advantages, such as shorter hospital stays, decreased operative durations, and lower complication rates. This juxtaposition underscores the urgent need for further, more rigorous research to substantiate these findings.PMID:39078530 | DOI:10.1007/s11701-024-02037-y
Pharmacological induction of the hypoxia response pathway in Huh7 hepatoma cells limits proliferation but increases resilience under metabolic stress
Cell Mol Life Sci. 2024 Jul 30;81(1):320. doi: 10.1007/s00018-024-05361-6.ABSTRACTThe hypoxia response pathway enables adaptation to oxygen deprivation. It is mediated by hypoxia-inducible factors (HIF), which promote metabolic reprogramming, erythropoiesis, angiogenesis and tissue remodeling. This led to the successful development of HIF-inducing drugs for treating anemia and some of these molecules are now in clinic. However, elevated levels of HIFs are frequently associated with tumor growth, poor prognosis, and drug resistance in various cancers, including hepatocellular carcinoma (HCC). Consequently, there are concerns regarding the recommendation of HIF-inducing drugs in certain clinical situations. Here, we analyzed the effects of two HIF-inducing drugs, Molidustat and Roxadustat, in the well-characterized HCC cell line Huh7. These drugs increased HIF-1α and HIF-2α protein levels which both participate in inducing hypoxia response genes such as BNIP3, SERPINE1, LDHA or EPO. Combined transcriptomics, proteomics and metabolomics showed that Molidustat increased the expression of glycolytic enzymes, while the mitochondrial network was fragmented and cellular respiration decreased. This metabolic remodeling was associated with a reduced proliferation and a lower demand for pyrimidine supply, but an increased ability of cells to convert pyruvate to lactate. This was accompanied by a higher resistance to the inhibition of mitochondrial respiration by antimycin A, a phenotype confirmed in Roxadustat-treated Huh7 cells and Molidustat-treated hepatoblastoma cells (Huh6 and HepG2). Overall, this study shows that HIF-inducing drugs increase the metabolic resilience of liver cancer cells to metabolic stressors, arguing for careful monitoring of patients treated with HIF-inducing drugs, especially when they are at risk of liver cancer.PMID:39078527 | DOI:10.1007/s00018-024-05361-6
A novel Bacillus aerolatus CX253 attenuates inflammation induced by Streptococcus pneumoniae in childhood and pregnant rats by regulating gut microbiome
Cell Mol Life Sci. 2024 Jul 29;81(1):319. doi: 10.1007/s00018-024-05232-0.ABSTRACTStreptococcus pneumoniae (Spn) is the predominant pathogen responsible for community-acquired pneumonia (CAP) in children under five years old, and it can induce over 17% of pregnant women. However, no more effective measures exist to prevent infection induced by Spn in these two special populations. The beneficial microbes can antagonize Spn and provide new targets for preventing pneumococcal infections. This study used 16S rRNA gene sequencing and targeted metabolomics to evaluate the role of the Bacillus aerolatus CX253 (CX253) in alleviating Spn infection. Additionally, the colonization of CX253 was observed in nose, trachea, and lung by using confocal laser scanning microscopy and fluorescent labeling techniques. Compared with the model group, the expression level of interleukin-1β was dropped 1.81-fold and 2.22-fold, and interleukin-6 was decreased 2.39-fold and 1.84-fold. The express of tumor necrosis factor-α was down 2.30-fold and 3.84-fold in prevention group of childhood and pregnant rats, respectively. The 16S rRNA sequencing results showed that CX253 administration alone significantly increased the abundance of Lactobacillus, Limosilactobacillus, and Prevotella in the gut of childhood and pregnant rats. Furthermore, the CX253 increased propionate in the gut of childhood rats and increased propionate and butyrate in the gut of pregnant rats to inhibit pulmonary inflammation. In summary, CX253 attenuated Spn-induced inflammation by regulating the gut microbiota and SCFAs. The research provides valuable information for the prevention of pneumonia.PMID:39078497 | DOI:10.1007/s00018-024-05232-0
Bacterial metabolomics: current applications for human welfare and future aspects
J Asian Nat Prod Res. 2024 Jul 30:1-24. doi: 10.1080/10286020.2024.2385365. Online ahead of print.ABSTRACTAn imbalanced microbiome is linked to several diseases, such as cancer, inflammatory bowel disease, obesity, and even neurological disorders. Bacteria and their by-products are used for various industrial and clinical purposes. The metabolites under discussion were chosen based on their biological impacts on host and gut microbiota interactions as established by metabolome research. The separation of bacterial metabolites by using statistics and machine learning analysis creates new opportunities for applications of bacteria and their metabolites in the environmental and medical sciences. Thus, the metabolite production strategies, methodologies, and importance of bacterial metabolites for human well-being are discussed in this review.PMID:39078342 | DOI:10.1080/10286020.2024.2385365
Correction to: "Pubertal Girls With Overweight/Obesity Have Higher Androgen Levels-Can Metabolomics Tell us Why?"
J Clin Endocrinol Metab. 2024 Jul 30:dgae515. doi: 10.1210/clinem/dgae515. Online ahead of print.NO ABSTRACTPMID:39078099 | DOI:10.1210/clinem/dgae515
Gut microbiota, plasma metabolites, and osteoporosis: unraveling links via Mendelian randomization
Front Microbiol. 2024 Jul 15;15:1433892. doi: 10.3389/fmicb.2024.1433892. eCollection 2024.ABSTRACTOBJECTIVE: Osteoporosis, characterized by reduced bone density and heightened fracture risk, is influenced by genetic and environmental factors. This study investigates the interplay between gut microbiota, plasma metabolomics, and osteoporosis, identifying potential causal relationships mediated by plasma metabolites.METHODS: Utilizing aggregated genome-wide association studies (GWAS) data, a comprehensive two-sample Mendelian Randomization (MR) analysis was performed involving 196 gut microbiota taxa, 1,400 plasma metabolites, and osteoporosis indicators. Causal relationships between gut microbiota, plasma metabolites, and osteoporosis were explored.RESULTS: The MR analyses revealed ten gut microbiota taxa associated with osteoporosis, with five taxa positively linked to increased risk and five negatively associated. Additionally, 96 plasma metabolites exhibited potential causal relationships with osteoporosis, with 49 showing positive associations and 47 displaying negative associations. Mediation analyses identified six causal pathways connecting gut microbiota to osteoporosis through ten mediating relationships involving seven distinct plasma metabolites, two of which demonstrated suppression effects.CONCLUSION: This study provides suggestive evidence of genetic correlations and causal links between gut microbiota, plasma metabolites, and osteoporosis. The findings underscore the complex, multifactorial nature of osteoporosis and suggest the potential of gut microbiota and plasma metabolite profiles as biomarkers or therapeutic targets in the management of osteoporosis.PMID:39077745 | PMC:PMC11284117 | DOI:10.3389/fmicb.2024.1433892
Combined analysis of the microbiome and metabolome to reveal the characteristics of saliva from different diets: a comparison among vegans, seafood-based omnivores, and red meat (beef and lamb) omnivores
Front Microbiol. 2024 Jul 15;15:1419686. doi: 10.3389/fmicb.2024.1419686. eCollection 2024.ABSTRACTINTRODUCTION: Revealing individual characteristics is supportive for identifying individuals in forensic crime. As saliva is one of the most common biological samples used in crime scenes, it is important to make full use of the rich individual information contained in saliva. The aim of this study was to explore the application of the microbiome in forensic science by analysing differences in the salivary microbiome and metabolome of healthy individuals with different dietary habits.METHODS: We performed 16S rDNA sequencing analysis based on oral saliva samples collected from 12 vegetarians, 12 seafood omnivores and 12 beef and lamb omnivores. Non-targeted metabolomics analyses were also performed based on saliva samples from healthy individuals.RESULTS: The results showed that the dominant flora of vegetarians was dominated by Neisseria (belonging to the phylum Proteobacteria), while seafood omnivores and beef and lamb omnivores were dominated by Streptococcus (belonging to the phylum Firmicutes). NDMS-based and cluster analyses showed that vegetarian dieters were significantly differentiated from meat dieters (seafood omnivores and beef and lamb omnivores), which may be related to the fact that high-fiber diets can create a different salivary flora structure. Variants were also detected in salivary metabolic pathways, including positive correlations with Lipid metabolism, Amino acid metabolism, Carbohydrate metabolism, and Nucleotide metabolism in vegetarians, and correlations in seafood omnivores. In order to select salivary microorganisms and metabolic markers that can distinguish different dietary profiles, a random forest classifier model was constructed in this study, and the results showed that individuals with different dietary profiles could be successfully distinguished based on the core genera and metabolites such as Streptococcus, Histidinyl-Valine.CONCLUSION: Our study provides a supportive basis for the application of salivary polyomics in order to reveal the dietary characteristics of individuals for forensic investigation and crime solving.PMID:39077734 | PMC:PMC11284149 | DOI:10.3389/fmicb.2024.1419686
The influence of benzene on the composition, diversity and performance of the anodic bacterial community in glucose-fed microbial fuel cells
Front Microbiol. 2024 Jul 15;15:1384463. doi: 10.3389/fmicb.2024.1384463. eCollection 2024.ABSTRACTBioelectrochemical systems offer unique opportunities to remove recalcitrant environmental pollutants in a net positive energy process, although it remains challenging because of the toxic character of such compounds. In this study, microbial fuel cell (MFC) technology was applied to investigate the benzene degradation process for more than 160 days, where glucose was used as a co-metabolite and a control. We have applied an inoculation strategy that led to the development of 10 individual microbial communities. The electrochemical dynamics of MFC efficiency was observed, along with their 1H NMR metabolic fingerprints and analysis of the microbial community. The highest power density of 120 mW/m2 was recorded in the final period of the experiment when benzene/glucose was used as fuel. This is the highest value reported in a benzene/co-substrate system. Metabolite analysis confirmed the full removal of benzene, while the dominance of fermentation products indicated the strong occurrence of non-electrogenic reactions. Based on 16S rRNA gene amplicon sequencing, bacterial community analysis revealed several petroleum-degrading microorganisms, electroactive species and biosurfactant producers. The dominant species were recognised as Citrobacter freundii and Arcobacter faecis. Strong, positive impact of the presence of benzene on the alpha diversity was recorded, underlining the high complexity of the bioelectrochemically supported degradation of petroleum compounds. This study reveals the importance of supporting the bioelectrochemical degradation process with auxiliary substrates and inoculation strategies that allow the communities to reach sufficient diversity to improve the power output and degradation efficiency in MFCs beyond the previously known limits. This study, for the first time, provides an outlook on the syntrophic activity of biosurfactant producers and petroleum degraders towards the efficient removal and conversion of recalcitrant hydrophobic compounds into electricity in MFCs.PMID:39077733 | PMC:PMC11284109 | DOI:10.3389/fmicb.2024.1384463
High-Throughput Metabolomics Applications in Pathogenesis and Diagnosis of Valvular Heart Disease
Rev Cardiovasc Med. 2023 Jun 8;24(6):169. doi: 10.31083/j.rcm2406169. eCollection 2023 Jun.ABSTRACTHigh-throughput metabolomics techniques are a useful tool to understand many disease conditions including cardiovascular disease such as valvular heart disease(s) (VHD). VHD involves damage to heart valves, mostly presenting as stenosis, regurgitation or prolapse and can be classified into degenerative, rheumatic, congenital, or prosthetic valve disease. Gaps remain in our understanding of the pathogenesis of the common VHD. It is now fitting to place into perspective the contribution of metabolomics in the mechanism of development, diagnosis, and prognosis of VHD. A structured search for metabolomics studies centred on human VHD was undertaken. Biomarkers associated with the pathogenesis of bicuspid aortic valve disease, mitral valve disease, rheumatic heart disease, and degenerative aortic valve stenosis are reviewed and discussed. In addition, metabolic biomarkers reported to prognosticate patient outcomes of post-valve repair or replacement are highlighted. Finally, we also review the pitfalls and limitations to consider when designing metabolomics studies, especially from a clinician's viewpoint. In the future, reliable and simple metabolic biomarker(s) may supplement the existing diagnostic tools in the early diagnosis of VHD.PMID:39077521 | PMC:PMC11264134 | DOI:10.31083/j.rcm2406169