Integrative Molecular Phenotyping
INTEGRATIVE MOLECULAR
PHENOTYPING
WHEELOCK LABORATORY
DEPARTMENT OF MEDICAL
BIOCHEMISTRY AND BIOPHYSICS
WHEELOCK LABORATORY
DEPARTMENT OF MEDICAL
BIOCHEMISTRY AND BIOPHYSICS
WHEELOCK LABORATORY
DEPARTMENT OF MEDICAL
BIOCHEMISTRY AND BIOPHYSICS
WHEELOCK LABORATORY
DEPARTMENT OF MEDICAL
BIOCHEMISTRY AND BIOPHYSICS
WHEELOCK LABORATORY
DEPARTMENT OF MEDICAL
BIOCHEMISTRY AND BIOPHYSICS
WHEELOCK LABORATORY

PubMed

Untargeted and targeted metabolomics identify metabolite biomarkers for Salmonella enteritidis in chicken meat

Mon, 02/01/2023 - 12:00
Food Chem. 2022 Dec 24;409:135294. doi: 10.1016/j.foodchem.2022.135294. Online ahead of print.ABSTRACTSalmonella Enteritidis easily contaminate chicken during slaughtering, processing, transportation, and sales, which seriously endangers human health. This study aimed to identify metabolite biomarkers for Salmonella Enteritidis contamination in chicken meat. UPLC-Q-Orbitrap MS untargeted metabolomics analysis identified 441 and 240 confidently metabolites in positive and negative ion mode, respectively. Thirty metabolites were defined as potential biomarkers for Salmonella enteritidis contamination in chicken meat. UPLC-QQQ-MS based targeted metabolomics was used to quantitatively analyze candidate metabolite biomarkers in Salmonella enteritidis contaminated and fresh chicken samples. A total of 10 candidate metabolite biomarkers were confirmed in the validation set, among which acetylcholine, l-Methionine, l-Proline, l-Valine, and l-Norleucine were identified as biomarkers for Salmonella Enteritidis contamination in chicken. The combined receiver operating characteristic curve analysis of the five biomarkers achieved an AUC of 0.956, indicating their high sensitivity and specificity in predicting Salmonella Enteritidis in raw chicken. In conclusion, the present study identified five metabolite biomarkers for Salmonella enteritidis in raw chicken. These results provide a potential theoretical basis for developing Salmonella Enteritidis detection methods in raw chicken.PMID:36592604 | DOI:10.1016/j.foodchem.2022.135294

NMR-based metabolomic analysis of the physiological role of the electron-bifurcating FeFe-hydrogenase Hnd in Solidesulfovibrio fructosivorans under pyruvate fermentation

Mon, 02/01/2023 - 12:00
Microbiol Res. 2022 Dec 22;268:127279. doi: 10.1016/j.micres.2022.127279. Online ahead of print.ABSTRACTSolidesulfovibrio fructosivorans (formely Desulfovibrio fructosovorans), an anaerobic sulfate-reducing bacterium, possesses six gene clusters encoding six hydrogenases catalyzing the reversible oxidation of hydrogen gas (H2) into protons and electrons. One of these, named Hnd, was demonstrated to be an electron-bifurcating hydrogenase Hnd (Kpebe et al., 2018). It couples the exergonic reduction of NAD+ to the endergonic reduction of a ferredoxin with electrons derived from H2 and whose function has been recently shown to be involved in ethanol production under pyruvate fermentation (Payne 2022). To understand further the physiological role of Hnd in S. fructosivorans, we compared the mutant deleted of part of the hnd gene with the wild-type strain grown on pyruvate without sulfate using NMR-based metabolomics. Our results confirm that Hnd is profoundly involved in ethanol metabolism, but also indirectly intervenes in global carbon metabolism and additional metabolic processes such as the biosynthesis of branched-chain amino acids. We also highlight the metabolic reprogramming induced by the deletion of hndD that leads to the upregulation of several NADP-dependent pathways.PMID:36592576 | DOI:10.1016/j.micres.2022.127279

Visualization and metabolome for the migration and distribution behavior of pesticides residue in after-ripening of banana

Mon, 02/01/2023 - 12:00
J Hazard Mater. 2022 Dec 29;446:130665. doi: 10.1016/j.jhazmat.2022.130665. Online ahead of print.ABSTRACTExploring the behavior of pesticide residues in fruits is important for effectively applying pesticides and minimizing the risk of pesticide exposure to humans. However, most studies do not consider in situ visual analysis of residues and migration patterns in fresh fruit samples. We investigated the migration patterns of thiram, propamocarb, imidacloprid and pyraclostrobin in fresh bananas based on ambient mass spectrometry imaging, metabolome and transcriptome analysis. The systemic pesticides entered via lateral penetration and vertical migration over time, which began to internally migrate to the inner core after 6 h. The non-systemic pesticide thiram did not enter the interior of the bananas, and remained only in the peel. The transportation rate of the pesticides increased with the decrease of water-octanol partition coefficient and the relative molecular mass. Moreover, the pesticide migrated fast with the increase of banana ripeness. The pesticides significantly enhanced pyruvate kinase, NADP-dependent malic enzyme, and malate synthase activities in the banana peels through carbohydrate metabolism. The banana pulp was also protected against the external toxicity of pesticides by the ascorbate-glutathione cycle. These results can provide guidelines for the appropriate application of pesticides and their safety evaluation.PMID:36592559 | DOI:10.1016/j.jhazmat.2022.130665

Impact of sulfur-fumigation on carbohydrate components of Atractylodis Macrocephalae Rhizoma

Mon, 02/01/2023 - 12:00
J Pharm Biomed Anal. 2022 Dec 29;225:115217. doi: 10.1016/j.jpba.2022.115217. Online ahead of print.ABSTRACTAtractylodis Macrocephalae Rhizoma (AMR) is one of commonly used medicinal and edible herbs in China. It is often sulfur-fumigated during post-harvest processing. Carbohydrates are important active components of AMR. However, it is unknown whether sulfur-fumigation would induce changes on carbohydrates. Here, carbohydrates including polysaccharides, oligosaccharides and free monosaccharides were comprehensively analyzed to characterize the quality changes of sulfur-fumigated AMR. Determination of both homemade sulfur-fumigated AMR samples and commercial samples from market revealed that sulfur-fumigation did not affect molecular weight distribution of polysaccharides, but altered polysaccharides content and its ratios of constituent monosaccharides, especially glucose (Glc) and fructose (Fru), as well as the contents of oligosaccharides DP2-10 and free monosaccharide Fru. Moreover, the variations enhanced with the increasing of residual SO2 content. The potential transformation mechanisms could be due to the hydrolysis of polysaccharides. The research outcomes could provide a chemical basis for the safety and efficacy evaluations of sulfur-fumigated AMR.PMID:36592540 | DOI:10.1016/j.jpba.2022.115217

From research cohorts to the patient - a role for "omics" in diagnostics and laboratory medicine?

Mon, 02/01/2023 - 12:00
Clin Chem Lab Med. 2023 Jan 4. doi: 10.1515/cclm-2022-1147. Online ahead of print.ABSTRACTHuman pathologies are complex and might benefit from a more holistic diagnostic approach than currently practiced. Omics is a concept in biological research that aims to comprehensively characterize and quantify large numbers of biological molecules in complex samples, e.g., proteins (proteomics), low molecular weight molecules (metabolomics), glycans (glycomics) or amphiphilic molecules (lipidomics). Over the past decades, respective unbiased discovery approaches have been intensively applied to investigate functional physiological and pathophysiological relationships in various research study cohorts. In the context of clinical diagnostics, omics approaches seem to have potential in two main areas: (i) biomarker discovery i.e. identification of individual marker analytes for subsequent translation into diagnostics (as classical target analyses with conventional laboratory techniques), and (ii) the readout of complex, higher-dimensional signatures of diagnostic samples, in particular by means of spectrometric techniques in combination with biomathematical approaches of pattern recognition and artificial intelligence for diagnostic classification. Resulting diagnostic methods could potentially represent a disruptive paradigm shift away from current one-dimensional (i.e., single analyte marker based) laboratory diagnostics. The underlying hypothesis of omics approaches for diagnostics is that complex, multigenic pathologies can be more accurately diagnosed via the readout of "omics-type signatures" than with the current one-dimensional single marker diagnostic procedures. While this is indeed promising, one must realize that the clinical translation of high-dimensional analytical procedures into routine diagnostics brings completely new challenges with respect to long-term reproducibility and analytical standardization, data management, and quality assurance. In this article, the conceivable opportunities and challenges of omics-based laboratory diagnostics are discussed.PMID:36592431 | DOI:10.1515/cclm-2022-1147

Clinical lipidomics in the era of the big data

Mon, 02/01/2023 - 12:00
Clin Chem Lab Med. 2023 Jan 4. doi: 10.1515/cclm-2022-1105. Online ahead of print.ABSTRACTLipidomics as a branch of metabolomics provides unique information on the complex lipid profile in biological materials. In clinically focused studies, hundreds of lipids together with available clinical information proved to be an effective tool in the discovery of biomarkers and understanding of pathobiochemistry. However, despite the introduction of lipidomics nearly twenty years ago, only dozens of big data studies using clinical lipidomics have been published to date. In this review, we discuss the lipidomics workflow, statistical tools, and the challenges of standartisation. The consequent summary divided into major clinical areas of cardiovascular disease, cancer, diabetes mellitus, neurodegenerative and liver diseases is demonstrating the importance of clinical lipidomics. In these publications, the potential of lipidomics for prediction, diagnosis or finding new targets for the treatment of selected diseases can be seen. The first of these results have already been implemented in clinical practice in the field of cardiovascular diseases, while in other areas we can expect the application of the results summarized in this review in the near future.PMID:36592414 | DOI:10.1515/cclm-2022-1105

Metabolomics as a Critical Tool for Studying Clinical Surgery

Mon, 02/01/2023 - 12:00
Crit Rev Anal Chem. 2023 Jan 2:1-14. doi: 10.1080/10408347.2022.2162810. Online ahead of print.ABSTRACTMetabolomics enables the analysis of metabolites within an organism, which offers the closest direct measurement of the physiological activity of the organism, and has advanced efforts to characterize metabolic states, identify biomarkers, and investigate metabolic pathways. A high degree of innovation in analytical techniques has promoted the application of metabolomics, especially in the study of clinical surgery. Metabolomics can be employed as a clinical testing method to maximize therapeutic outcomes, and has been applied in rapid diagnosis of diseases, timely postoperative monitoring, prognostic assessment, and personalized medicine. This review focuses on the use of mass spectrometry and nuclear magnetic resonance-based metabolomics in clinical surgery, including identifying metabolic changes before and after surgery, finding disease-associated biomarkers, and exploring the potential of personalized therapy. Challenges and opportunities of metabolomics in organ transplantation are also discussed, with a particular emphasis on metabolomics in donor organ evaluation and protection, prognostic outcome prediction, as well as postoperative adverse reaction monitoring. In the end, current limitations of metabolomics in clinical surgery and future research directions are presented.PMID:36592066 | DOI:10.1080/10408347.2022.2162810

Visualization of Metabolites Identified in the Spatial Metabolome of Traditional Chinese Medicine Using DESI-MSI

Mon, 02/01/2023 - 12:00
J Vis Exp. 2022 Dec 16;(190). doi: 10.3791/64912.ABSTRACTThe medicinal use of traditional Chinese medicine is mainly due to its secondary metabolites. Visualization of the distribution of these metabolites has become a crucial topic in plant science. Mass spectrometry imaging can extract huge volumes of data and provide spatial distribution information about these by analyzing tissue slices. With the advantage of high throughput and higher accuracy, desorption electrospray ionization mass spectrometry imaging (DESI-MSI) is often used in biological research and in the study of traditional Chinese medicine. However, the procedures used in this research are complicated and not affordable. In this study, we optimized sectioning and DESI imaging procedures and developed a more cost-effective method to identify the distribution of metabolites and categorize these compounds in plant tissues, with a special focus on traditional Chinese medicines. The study will promote the utilization of DESI in metabolite analysis and standardization of traditional Chinese medicine/ethnic medicine for research-related technologies.PMID:36591997 | DOI:10.3791/64912

Co-Fermentation of Marsdenia tenacissima with Ganoderma lucidum and Anti-Lung Cancer Effect of the Fermentation Products

Mon, 02/01/2023 - 12:00
J Vis Exp. 2022 Dec 16;(190). doi: 10.3791/64687.ABSTRACTMarsdenia tenacissima (Roxb.) Wight et Arn. (MT), as a traditional Chinese and Dai herbal medicine, has anti-inflammatory, antibacterial, and antitumor properties. However, most of its main active substances are aglycones, such as tenacigenin A and tenacigenin B. As the bioavailability of MT is low and its medicinal active components are challenging to synthesize, it is primarily studied by biotransformation. This study aims to produce biotransformation products rich in pungent saponins by using MT as a fermentation medium for Ganoderma lucidum (G. lucidum). Through the preliminary screening of three medicinal fungi, it was found that G. lucidum and Ophiocordyceps sinensis (O. sinensis) can generally grow in the medium for MT; hence, the efficacy of the fermentation of the two types of fungi was screened using a mouse model of lung cancer. Finally, the co-fermentation of G. lucidum and MT was selected for further investigation. Non-target metabolomics analysis was performed on the products of MT with G. lucidum co-fermentation. We identified 12 specific saponins of MT from the fermentation products, and obtained a monomeric compound, tenacigenin A, from fermentation products. Most of the tenacigenin showed a significant upward trend, through tenacigenin A and tenacigenin B levels. The results showed that the efficacy of MT improved after fermentation by G. lucidum. Furthermore, the biotransformation of C21 steroidal glycosides in MT was the central reaction in this fermentation process. In summary, this study established a systematic and comprehensive co-fermentation system and pharmacodynamic evaluation method for MT, which not only enhanced the full utilization of effective active substances in MT but also provided a methodological reference for the development of other ethnic drugs.PMID:36591966 | DOI:10.3791/64687

Identification of circulating plasma ceramides as a potential sexually dimorphic biomarker of pancreatic cancer-induced cachexia

Mon, 02/01/2023 - 12:00
JCSM Rapid Commun. 2022 Jul-Dec;5(2):254-265. doi: 10.1002/rco2.68. Epub 2022 Jun 20.ABSTRACTBACKGROUND: Cancer patients who exhibit cachexia lose weight and have low treatment tolerance and poor outcomes compared to cancer patients without weight loss. Despite the clear increased risk for patients, diagnosing cachexia still often relies on self-reported weight loss. A reliable biomarker to identify patients with cancer cachexia would be a valuable tool to improve clinical decision making and identification of patients at risk of adverse outcomes.METHODS: Targeted metabolomics, that included panels of amino acids, tricarboxylic acids, fatty acids, acylcarnitines, and sphingolipids, were conducted on plasma samples from patients with confirmed pancreatic ductal adenocarcinoma (PDAC) with and without cachexia and control patients without cancer (n=10/group, equally divided by sex). Additional patient samples were analyzed (total n=95) and Receiver Operating Characteristic (ROC) analyses were performed to establish if any metabolite could effectively serve as a biomarker of cachexia.RESULTS: Targeted profiling revealed that cachectic patients had decreased circulating levels of three sphingolipids compared to either non-cachectic PDAC patients or patients without cancer. The ratio of C18-ceramide to C24-ceramide (C18:C24) outperformed a number of other previously proposed biomarkers of cachexia (area under ROC = 0.810). It was notable that some biomarkers, including C18:C24, were only altered in cachectic males.CONCLUSIONS: Our findings identify C18:C24 as a potentially new biomarker of PDAC-induced cachexia that also highlight a previously unappreciated sexual dimorphism in cancer cachexia.PMID:36591536 | PMC:PMC9797184 | DOI:10.1002/rco2.68

Towards the Development of a Diagnostic Test for Autism Spectrum Disorder: Big Data Meets Metabolomics

Mon, 02/01/2023 - 12:00
Can J Chem Eng. 2023 Jan;101(1):9-17. doi: 10.1002/cjce.24594. Epub 2022 Aug 10.ABSTRACTAutism spectrum disorder (ASD) is defined as a neurodevelopmental disorder which results in impairments in social communications and interactions as well as repetitive behaviors. Despite current estimates showing that approximately 2.2% of children are affected in the United States, relatively little about ASD pathophysiology is known in part due to the highly heterogenous presentation of the disorder. Given the limited knowledge into the biological mechanisms governing its etiology, the diagnosis of ASD is performed exclusively based on an individual's behavior assessed by a clinician through psychometric tools. Although there is no readily available biochemical test for ASD diagnosis, multivariate statistical methods show considerable potential for effectively leveraging multiple biochemical measurements for classification and characterization purposes. In this work, markers associated with the folate dependent one-carbon metabolism and transulfuration (FOCM/TS) pathways analyzed via both Fisher Discriminant Analysis and Support Vector Machine showed strong capability to distinguish between ASD and TD cohorts. Furthermore, using Kernel Partial Least Squares regression it was possible to assess some degree of behavioral severity from metabolomic data. While the results presented need to be replicated in independent future studies, they represent a promising avenue for uncovering clinically relevant ASD biomarkers.PMID:36591338 | PMC:PMC9799131 | DOI:10.1002/cjce.24594

Tuberculosis alters immune-metabolic pathways resulting in perturbed IL-1 responses

Mon, 02/01/2023 - 12:00
Front Immunol. 2022 Dec 14;13:897193. doi: 10.3389/fimmu.2022.897193. eCollection 2022.ABSTRACTTuberculosis (TB) remains a major public health problem and we lack a comprehensive understanding of how Mycobacterium tuberculosis (M. tb) infection impacts host immune responses. We compared the induced immune response to TB antigen, BCG and IL-1β stimulation between latently M. tb infected individuals (LTBI) and active TB patients. This revealed distinct responses between TB/LTBI at transcriptomic, proteomic and metabolomic levels. At baseline, we identified a novel immune-metabolic association between pregnane steroids, the PPARγ pathway and elevated plasma IL-1ra in TB. We observed dysregulated IL-1 responses after BCG stimulation in TB patients, with elevated IL-1ra responses being explained by upstream TNF differences. Additionally, distinct secretion of IL-1α/IL-1β in LTBI/TB after BCG stimulation was associated with downstream differences in granzyme mediated cleavage. Finally, IL-1β driven signalling was dramatically perturbed in TB disease but was completely restored after successful treatment. This study improves our knowledge of how immune responses are altered during TB disease, and may support the design of improved preventive and therapeutic tools, including host-directed strategies.PMID:36591308 | PMC:PMC9795069 | DOI:10.3389/fimmu.2022.897193

Host biomarker-based quantitative rapid tests for detection and treatment monitoring of tuberculosis and COVID-19

Mon, 02/01/2023 - 12:00
iScience. 2022 Dec 26:105873. doi: 10.1016/j.isci.2022.105873. Online ahead of print.ABSTRACTDiagnostic services for tuberculosis (TB) are not sufficiently accessible in low-resource settings, where most cases occur, which was aggravated by the COVID-19 pandemic. Early diagnosis of pulmonary TB can reduce transmission. Current TB-diagnostics rely on detection of Mycobacterium tuberculosis (Mtb) in sputum requiring costly, time-consuming methods, and trained staff. In this study, quantitative lateral flow (LF) assays were used to measure levels of seven host proteins in sera from pre-COVID-19 TB-patients diagnosed in Europe and latently Mtb-infected individuals (LTBI), and from COVID-19 patients and healthy controls. Analysis of host proteins showed significantly lower levels in LTBI versus TB (AUC:0·94) and discriminated healthy individuals from COVID-19 patients (0·99) and severe COVID-19 from TB. Importantly, these host proteins allowed treatment monitoring of both respiratory diseases. This study demonstrates the potential of non-sputum LF assays as adjunct diagnostics and treatment monitoring for COVID-19 and TB based on quantitative detection of multiple host biomarkers.PMID:36590898 | PMC:PMC9791715 | DOI:10.1016/j.isci.2022.105873

Revealing the role of microalgae-bacteria niche for boosting wastewater treatment and energy reclamation in response to temperature

Mon, 02/01/2023 - 12:00
Environ Sci Ecotechnol. 2022 Dec 6;14:100230. doi: 10.1016/j.ese.2022.100230. eCollection 2023 Apr.ABSTRACTConventional biological treatment usually cannot achieve the same high water quality as advanced treatment when conducted under varied temperatures. Here, satisfactory wastewater treatment efficiency was observed in a microalgae-bacteria consortia (MBC) over a wide temperature range because of the predominance of microalgae. Microalgae contributed more toward wastewater treatment at low temperature because of the unsatisfactory performance of the accompanying bacteria, which experienced cold stress (e.g., bacterial abundance below 3000 sequences) and executed defensive strategies (e.g., enrichment of cold-shock proteins). A low abundance of amoA-C and hao indicated that conventional nitrogen removal was replaced through the involvement of microalgae. Diverse heterotrophic bacteria for nitrogen removal were identified at medium and high temperatures, implying this microbial niche treatment contained diverse flexible consortia with temperature variation. Additionally, pathogenic bacteria were eliminated through microalgal photosynthesis. After fitting the neutral community model and calculating the ecological niche, microalgae achieved a maximum niche breadth of 5.21 and the lowest niche overlap of 0.38, while the accompanying bacterial community in the consortia were shaped through deterministic processes. Finally, the maximum energy yield of 87.4 kJ L-1 and lipid production of 1.9 g L-1 were achieved at medium temperature. Altogether, this study demonstrates that advanced treatment and energy reclamation can be achieved through microalgae-bacteria niche strategies.PMID:36590875 | PMC:PMC9800309 | DOI:10.1016/j.ese.2022.100230

Monoclonal Gammopathy of Renal Significance: A Molecular Middle Earth between Oncology, Nephrology, and Pathology

Mon, 02/01/2023 - 12:00
Kidney Dis (Basel). 2022 Nov 2;8(6):446-457. doi: 10.1159/000527056. eCollection 2022 Dec.ABSTRACTBACKGROUND: The renal biopsy represents a cornerstone in the definition of monoclonal gammopathy of renal significance (MGRS), helping in identifying patients with sub-detectable neoplastic clones (MGUS) that would deserve aggressive chemotherapies. However, the rising complexity of this onco-nephrology field is significantly challenging the daily work of nephrologists and nephropathologists, leading to the formation of ultra-specialized international centers with dedicated personnel/instrumentation and stressing the need for a better understanding of the underlying molecular landscape of these entities.SUMMARY: In this setting, the application of proteomic techniques, some with in situ capabilities (e.g., MALDI-MS imaging), for the investigation of the most challenging MGRS is progressively shedding light on the pathobiology of these diseases, providing new insights in the diagnosis and prognosis of these cases. This transformation is further enhanced by the application of next-generation digital pathology platforms, leading to a significant improvement of the cultural background for physicians thanks to second opinions, database and atlas creation, enhancement of diagnostic reports, with obvious repercussions for patients both in terms of turnaround time and appropriateness.KEY MESSAGES: The present review is aimed at bridging the gap between clinical questions (i.e., a better characterization of MGRS) and the molecular landscape of onco-nephrology entities.PMID:36590677 | PMC:PMC9798844 | DOI:10.1159/000527056

Breathomics profiling of metabolic pathways affected by major depression: Possibilities and limitations

Mon, 02/01/2023 - 12:00
Front Psychiatry. 2022 Dec 14;13:1061326. doi: 10.3389/fpsyt.2022.1061326. eCollection 2022.ABSTRACTBACKGROUND: Major depressive disorder (MDD) is one of the most common psychiatric disorders with multifactorial etiologies. Metabolomics has recently emerged as a particularly potential quantitative tool that provides a multi-parametric signature specific to several mechanisms underlying the heterogeneous pathophysiology of MDD. The main purpose of the present study was to investigate possibilities and limitations of breath-based metabolomics, breathomics patterns to discriminate MDD patients from healthy controls (HCs) and identify the altered metabolic pathways in MDD.METHODS: Breath samples were collected in Tedlar bags at awakening, 30 and 60 min after awakening from 26 patients with MDD and 25 HCs. The non-targeted breathomics analysis was carried out by proton transfer reaction mass spectrometry. The univariate analysis was first performed by T-test to rank potential biomarkers. The metabolomic pathway analysis and hierarchical clustering analysis (HCA) were performed to group the significant metabolites involved in the same metabolic pathways or networks. Moreover, a support vector machine (SVM) predictive model was built to identify the potential metabolites in the altered pathways and clusters. The accuracy of the SVM model was evaluated by receiver operating characteristics (ROC) analysis.RESULTS: A total of 23 differential exhaled breath metabolites were significantly altered in patients with MDD compared with HCs and mapped in five significant metabolic pathways including aminoacyl-tRNA biosynthesis (p = 0.0055), branched chain amino acids valine, leucine and isoleucine biosynthesis (p = 0.0060), glycolysis and gluconeogenesis (p = 0.0067), nicotinate and nicotinamide metabolism (p = 0.0213) and pyruvate metabolism (p = 0.0440). Moreover, the SVM predictive model showed that butylamine (p = 0.0005, pFDR=0.0006), 3-methylpyridine (p = 0.0002, pFDR = 0.0012), endogenous aliphatic ethanol isotope (p = 0.0073, pFDR = 0.0174), valeric acid (p = 0.005, pFDR = 0.0162) and isoprene (p = 0.038, pFDR = 0.045) were potential metabolites within identified clusters with HCA and altered pathways, and discriminated between patients with MDD and non-depressed ones with high sensitivity (0.88), specificity (0.96) and area under curve of ROC (0.96).CONCLUSION: According to the results of this study, the non-targeted breathomics analysis with high-throughput sensitive analytical technologies coupled to advanced computational tools approaches offer completely new insights into peripheral biochemical changes in MDD.PMID:36590606 | PMC:PMC9795849 | DOI:10.3389/fpsyt.2022.1061326

Gut microbiota and fecal metabolic signatures in rat models of disuse-induced osteoporosis

Mon, 02/01/2023 - 12:00
Front Cell Infect Microbiol. 2022 Dec 14;12:1018897. doi: 10.3389/fcimb.2022.1018897. eCollection 2022.ABSTRACTBACKGROUND: Assessing the correlation between gut microbiota (GM) and bone homeostasis has increasingly attracted research interest. Meanwhile, GM dysbiosis has been found to be associated with abnormal bone metabolism. However, the function of GM in disuse-induced osteoporosis (DIO) remains poorly understood. In our research, we evaluated the characteristics of GM and fecal metabolomics to explore their potential correlations with DIO pathogenesis.METHODS: DIO rat models and controls (CON) underwent micro-CT, histological analyses, and three-point bending tests; subsequently, bone microstructures and strength were observed. ELISAs were applied for the measurement of the biochemical markers of bone turnover while GM abundance was observed using 16S rDNA sequencing. Metabolomic analyses were used to analyze alterations fecal metabolites. The potential correlations between GM, metabolites, and bone loss were then assessed.RESULTS: In the DIO group, the abundance of GM was significantly altered compared to that in the CON group. Moreover, DIO significantly altered fecal metabolites. More specifically, an abnormally active pathway associated with bile acid metabolism, as well as differential bacterial genera related to bone/tissue volume (BV/TV), were identified. Lithocholic acid, which is the main secondary bile acid produced by intestinal bacteria, was then found to have a relationship with multiple differential bacterial genera. Alterations in the intestinal flora and metabolites in feces, therefore, may be responsible for DIO-induced bone loss.CONCLUSIONS: The results indicated that changes in the abundance of GM abundance and fecal metabolites were correlated with DIO-induced bone loss, which might provide new insights into the DIO pathogenesis. The detailed regulatory role of GM and metabolites in DIO-induced bone loss needs to be explored further.PMID:36590590 | PMC:PMC9798431 | DOI:10.3389/fcimb.2022.1018897

New metabolic signature for Chagas disease reveals sex steroid perturbation in humans and mice

Mon, 02/01/2023 - 12:00
Heliyon. 2022 Dec 15;8(12):e12380. doi: 10.1016/j.heliyon.2022.e12380. eCollection 2022 Dec.ABSTRACTThe causative agent of Chagas disease (CD), Trypanosoma cruzi, claims thousands of lives each year. Current diagnostic tools are insufficient to ensure parasitological detection in chronically infected patients has been achieved. A host-derived metabolic signature able to distinguish CD patients from uninfected individuals and assess antiparasitic treatment efficiency is introduced. Serum samples were collected from chronic CD patients, prior to and three years after treatment, and subjected to untargeted metabolomics analysis against demographically matched CD-negative controls. Five metabolites were confirmed by high-resolution tandem mass spectrometry. Several database matches for sex steroids were significantly altered in CD patients. A murine experiment corroborated sex steroid perturbation in T. cruzi-infected mice, particularly in male animals. Proteomics analysis also found increased steroidogenesis in the testes of infected mice. Metabolic alterations identified in this study shed light on the pathogenesis and provide the basis for developing novel assays for the diagnosis and screening of CD patients.PMID:36590505 | PMC:PMC9800200 | DOI:10.1016/j.heliyon.2022.e12380

Modulating gut microbiota and metabolites with dietary fiber oat β-glucan interventions to improve growth performance and intestinal function in weaned rabbits

Mon, 02/01/2023 - 12:00
Front Microbiol. 2022 Dec 15;13:1074036. doi: 10.3389/fmicb.2022.1074036. eCollection 2022.ABSTRACTThe effect of oat β-glucan on intestinal function and growth performance of weaned rabbits were explored by multi-omics integrative analyses in the present study. New Zealand White rabbits fed oat β-glucan [200 mg/kg body weight (BW)] for 4 weeks, and serum markers, colon histological alterations, colonic microbiome, colonic metabolome, and serum metabolome were measured. The results revealed that oat β-glucan increased BW, average daily gain (ADG), average daily food intake (ADFI), and decreased serum tumor necrosis factor-α (TNF-α) interleukin-1β (IL-1β), and lipopolysaccharide (LPS) contents, but did not affect colonic microstructure. Microbiota community analysis showed oat β-glucan modulated gut microbial composition and structure, increased the abundances of beneficial bacteria Lactobacillus, Prevotellaceae_UCG-001, Pediococcus, Bacillus, etc. Oat β-glucan also increased intestinal propionic acid, valeric acid, and butyric acid concentrations, decreased lysine and aromatic amino acid (AAA) derivative contents. Serum metabolite analysis revealed that oat β-glucan altered host carbohydrate, lipid, and amino acid metabolism. These results suggested that oat β-glucan could inhibit systemic inflammation and protect intestinal function by regulating gut microbiota and related metabolites, which further helps to improve growth performance in weaned rabbits.PMID:36590438 | PMC:PMC9798315 | DOI:10.3389/fmicb.2022.1074036

Effects of oat (<em>Avena sativa</em> L.) hay diet supplementation on the intestinal microbiome and metabolome of Small-tail Han sheep

Mon, 02/01/2023 - 12:00
Front Microbiol. 2022 Dec 16;13:1032622. doi: 10.3389/fmicb.2022.1032622. eCollection 2022.ABSTRACTSupplementation of the sheep diet with oats (Avena sativa L.) improves animal growth and meat quality, however effects on intestinal microbes and their metabolites was not clear. This study aimed to establish the effect of dietary oat supplementation on rumen and colonic microbial abundance and explore the relationship with subsequent changes in digesta metabolites. Twenty Small-tail Han sheep were randomly assigned to a diet containing 30 g/100 g of maize straw (Control) or oat hay (Oat). After 90-days on experimental diets, rumen and colon digesta were collected and microbial diversity was determined by 16S rRNA gene Illumina NovaSeq sequencing and metabolomics was conducted using Ultra-high performance liquid chromatography Q-Exactive mass spectrometry (UHPLC-QE-MS). Compared to Control group, oat hay increased the abundance of Bacteroidetes and Fibrobacteres as well as known short-chain fatty acid (SCFA) producers Prevotellaceae, Ruminococcaceae and Fibrobacteraceae in rumen (p < 0.05). In rumen digesta, the Oat group showed had higher levels of (3Z,6Z)-3,6-nonadienal, Limonene-1,2-epoxide, P-tolualdehyde, and Salicylaldehyde compared to Control (p < 0.05) and these metabolites were positively correlated with the abundance of cecal Prevotellaceae NK3B31. In conclusion, supplementation of the sheep diet with oat hay improved desirable microbes and metabolites in the rumen, providing insight into mechanisms whereby meat quality can be improved by oat hay supplementation.PMID:36590432 | PMC:PMC9801518 | DOI:10.3389/fmicb.2022.1032622

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