PubMed

Anal Bioanal Chem. 2023 Jan 30. doi: 10.1007/s00216-023-04556-3. Online ahead of print.ABSTRACTEmerging insights from metabolomic-based studies of major depression disorder (MDD) are mainly related to biochemical processes such as energy or oxidative stress, in addition to neurotransmission linked to specific metabolite intermediates. Hub metabolites represent nodes in the biochemical network playing a critical role in integrating the information flow in cells between metabolism and signaling pathways. Limited technical-scientific studies have been conducted to understand the effects of ayahuasca (Aya) administration in the metabolism considering MDD molecular context. Therefore, this work aims to investigate an in vitro primary astrocyte model by untargeted metabolomics of two cellular subfractions: secretome and intracellular content after pre-defined Aya treatments, based on DMT concentration. Mass spectrometry (MS)-based metabolomics data revealed significant hub metabolites, which were used to predict biochemical pathway alterations. Branched-chain amino acid (BCAA) metabolism, and vitamin B6 and B3 metabolism were associated to Aya treatment, as "housekeeping" pathways. Dopamine synthesis was overrepresented in the network results when considering the lowest tested DMT concentration (1 µmol L-1). Building reaction networks containing significant and differential metabolites, such as nicotinamide, L-DOPA, and L-leucine, is a useful approach to guide on dose decision and pathway selection in further analytical and molecular studies.PMID:36717401 | DOI:10.1007/s00216-023-04556-3

Wien Klin Wochenschr. 2023 Jan 30. doi: 10.1007/s00508-022-02146-4. Online ahead of print.ABSTRACTINTRODUCTION: Obesity is a multifactorial chronic disease that cannot be addressed by simply promoting better diets and more physical activity. To date, not a single country has successfully been able to curb the accumulating burden of obesity. One explanation for the lack of progress is that lifestyle intervention programs are traditionally implemented without a comprehensive evaluation of an individual's diagnostic biomarkers. Evidence from genome-wide association studies highlight the importance of genetic and epigenetic factors in the development of obesity and how they in turn affect the transcriptome, metabolites, microbiomes, and proteomes.OBJECTIVE: The purpose of this review is to provide an overview of the different types of omics data: genomics, epigenomics, transcriptomics, proteomics, metabolomics and illustrate how a multi-omics approach can be fundamental for the implementation of precision obesity management.RESULTS: The different types of omics designs are grouped into two categories, the genotype approach and the phenotype approach. When applied to obesity prevention and management, each omics type could potentially help to detect specific biomarkers in people with risk profiles and guide healthcare professionals and decision makers in developing individualized treatment plans according to the needs of the individual before the onset of obesity.CONCLUSION: Integrating multi-omics approaches will enable a paradigm shift from the one size fits all approach towards precision obesity management, i.e. (1) precision prevention of the onset of obesity, (2) precision medicine and tailored treatment of obesity, and (3) precision risk reduction and prevention of secondary diseases related to obesity.PMID:36717394 | DOI:10.1007/s00508-022-02146-4

J Cyst Fibros. 2023 Jan 28:S1569-1993(23)00019-X. doi: 10.1016/j.jcf.2023.01.013. Online ahead of print.ABSTRACTBACKGROUND: Adults with cystic fibrosis (CF) are at increased risk for colon cancer. CF patients have reductions in intestinal bacteria that produce short chain fatty acids (SCFAs), although it is unclear whether this corresponds with intestinal SCFA levels and the presence of colonic neoplasia. The aim of this study was to compare gut microbiome and SCFA composition in patients with and without CF, and to assess associations with colonic adenomas.METHODS: Colonic aspirates were obtained from adults with and without CF undergoing colon cancer screening or surveillance colonoscopy. Microbiome characterization was performed by 16S rRNA V3-V4 sequencing. Targeted profiling of SCFAs and related metabolites was performed by LC-MS.RESULTS: 42 patients (21 CF, 21 control) were enrolled. CF patients had significantly reduced alpha diversity and decreased relative abundance of many SCFA-producing taxa. There were no significant differences in SCFA levels in CF patients, although there were reduced levels of branched chain fatty acids (BCFAs) and related metabolites. CF patients with adenomas, but not controls with adenomas, had significantly increased relative abundance of Bacteroides fragilis. CF microbiome composition was significantly associated with isovalerate concentration and the presence of adenomas.CONCLUSIONS: CF patients have marked disturbances in the gut microbiome, and CF patients with adenomas had notably increased relative abundance of B. fragilis, a pathogen known to promote colon cancer. Reductions in BCFAs but not SCFAs were found in CF. Further studies are warranted to evaluate the role of B. fragilis as well the biological significance of reductions in BCFAs in CF.PMID:36717332 | DOI:10.1016/j.jcf.2023.01.013

Arch Bronconeumol. 2023 Jan 18:S0300-2896(23)00013-3. doi: 10.1016/j.arbres.2022.12.018. Online ahead of print.ABSTRACTThe clinical presentation of chronic obstructive pulmonary disease (COPD) is highly heterogeneous. Attempts have been made to define subpopulations of patients who share clinical characteristics (phenotypes and treatable traits) and/or biological characteristics (endotypes), in order to offer more personalized care. Assigning a patient to any of these groups requires the identification of both clinical and biological markers. Ideally, biological markers should be easily obtained from blood or urine, but these may lack specificity. Biomarkers can be identified initially using conventional or more sophisticated techniques. However, the more sophisticated techniques should be simplified in the future if they are to have clinical utility. The -omics approach offers a methodology that can assist in the investigation and identification of useful markers in both targeted and blind searches. Specifically, metabolomics is the science that studies biological processes involving metabolites, which can be intermediate or final products. The metabolites associated with COPD and their specific phenotypic and endotypic features have been studied using various techniques. Several compounds of particular interest have emerged, namely, several types of lipids and derivatives (mainly phospholipids, but also ceramides, fatty acids and eicosanoids), amino acids, coagulation factors, and nucleic acid components, likely to be involved in their function, protein catabolism, energy production, oxidative stress, immune-inflammatory response and coagulation disorders. However, clear metabolomic profiles of the disease and its various manifestations that may already be applicable in clinical practice still need to be defined.PMID:36717301 | DOI:10.1016/j.arbres.2022.12.018

RMD Open. 2023 Jan;9(1):e002819. doi: 10.1136/rmdopen-2022-002819.ABSTRACTJapanese rheumatology and immunology have contributed to progress in the field and advancement of rheumatology, including postmarketing surveillance, development of IL-6-targeting therapy and concept of drug tapering, have accelerated in the 21st century. The 67th Annual Scientific Meeting of the Japan College of Rheumatology, held on Fukuoka on 24 April 2023-26 April 2023, will go ahead and beyond such an advancement. Profound discussion on future perspectives such as precision medicine, the elucidation of pathology and genome-based drug discovery by multilayered integration with various types of omics information, information on metabolome and proteome of blood metabolites, and database of target proteins and compounds for drug discovery will be discussed.PMID:36717187 | DOI:10.1136/rmdopen-2022-002819

Sci Total Environ. 2023 Jan 27:161861. doi: 10.1016/j.scitotenv.2023.161861. Online ahead of print.ABSTRACTBACKGROUND: Long-term exposure to inorganic arsenic may lead to arsenicosis. There are, however, currently no validated metabolic biomarkers used for the identification of arsenicosis risk. This study aims to identify metabolites associated with arsenicosis and establish prediction models for risk assessment based on untargeted metabolomics and machine learning algorithms.METHODS: In total, 105 coal-borne arsenicosis patients, with 35 subjects in each of the mild, moderate, and severe subgroups according to their symptom severity, and 60 healthy residents were enrolled from Guizhou, China. Ultra-high performance liquid chromatography-tandem mass spectrometer (UHPLC-MS/MS) was utilized to acquire the plasma metabolic profiles of the studied subjects. Statistical analysis was used to identify disease-associated metabolites. Machine learning algorithms and the identified metabolic biomarkers were resorted to assess the arsenicosis risk.RESULTS: A total of 143 metabolic biomarkers, with organic acids being the majority, were identified to be closely associated with arsenicosis, and the most involved pathway was glycine, serine, and threonine metabolism. Comparative analysis of metabolites in arsenicosis patients with different symptom severity revealed 422 altered molecules, where disrupted metabolism of beta-alanine and arginine demonstrated the most significance. For risk assessment, the model established by a single biomarker (L-carnosine) could undoubtedly discriminate arsenicosis patients from the healthy. For classifying arsenicosis patients with different severity, the model established using 52 metabolites and linear discriminate analysis (LDA) algorithm yielded an accuracy of 0.970-0.979 on calibration set (n = 132) and 0.818-0.848 on validation set (n = 33).CONCLUSION: Altered metabolites and disrupted pathways are prevalent in arsenicosis patients; The disrupted metabolism of one carbon and dysfunction of antioxidant defense system may partially be causes of the systematic multi-organ damage and carcinogenesis in arsenicosis patients; Metabolic biomarkers, combined with machine learning algorithms, could be efficient for risk assessment and early identification of arsenicosis.PMID:36716877 | DOI:10.1016/j.scitotenv.2023.161861

Food Chem. 2023 Jan 25;412:135577. doi: 10.1016/j.foodchem.2023.135577. Online ahead of print.ABSTRACTRoasting influences the color, flavor, and antioxidant activities of peanuts. However, the biochemical mechanisms that occur during roasting are not well known. In this study, the dynamic changes in non-volatile and volatile metabolites in raw, light, and dark roasted peanuts were investigated using ultra-performance liquid chromatography with a widely targeted metabolomic approach based on tandem mass spectrometry and gas chromatography-mass spectrometry. A total of 738 non-volatile metabolites (comprising 12 subclasses) and 71 volatile metabolites (comprising 14 subclasses) were identified in raw and roasted peanuts. Significantly different non-volatile and volatile metabolites were detected. Among them, amino acids, sugars, and lipids (lysophosphatidylethanolamines and oxidized fatty acids) were found to be highly linked to flavor formation. In addition, the enhanced color and antioxidant activities of peanuts were attributed to the Maillard reaction and sugar degradation. These results provide comprehensive insights into the quality improvements of peanuts during roasting.PMID:36716629 | DOI:10.1016/j.foodchem.2023.135577

Proc Natl Acad Sci U S A. 2023 Feb 7;120(6):e2219630120. doi: 10.1073/pnas.2219630120. Epub 2023 Jan 30.ABSTRACTEndothelial progenitor cells (EPCs) play an important role in vascular repair and re-endothelialization after vessel injury. EPCs in blood vessels are subjected to cyclic stretch (CS) due to the pulsatile pressure, but the role of CS in metabolic reprogramming of EPC, particularly its vascular homing and repair, is largely unknown. In the current study, physiological CS applied to EPCs at a magnitude of 10% and a frequency of 1 Hz significantly promoted their vascular adhesion and endothelial differentiation. CS enhanced mitochondrial elongation and oxidative phosphorylation (OXPHOS), as well as adenosine triphosphate production. Metabolomic study and Ultra-high performance liquid chromatography-mass spectrometry assay revealed that CS significantly decreased the content of long-chain fatty acids (LCFAs) and markedly induced long-chain fatty acyl-CoA synthetase 1 (Acsl1), which in turn facilitated the catabolism of LCFAs in mitochondria via fatty acid β-oxidation and OXPHOS. In a rat carotid artery injury model, transplantation of EPCs overexpressing Acsl1 enhanced the adhesion and re-endothelialization of EPCs in vivo. MRI and vascular morphology staining showed that Acsl1 overexpression in EPCs improved vascular repair and inhibited vascular stenosis. This study reveals a mechanotransduction mechanism by which physiological CS enhances endothelial repair via EPC patency.PMID:36716379 | DOI:10.1073/pnas.2219630120

PLoS Pathog. 2023 Jan 30;19(1):e1011100. doi: 10.1371/journal.ppat.1011100. Online ahead of print.ABSTRACTVerticillium transcription activator of adhesion 3 (Vta3) is required for plant root colonization and pathogenicity of the soil-borne vascular fungus Verticillium dahliae. RNA sequencing identified Vta3-dependent genetic networks required for growth in tomato xylem sap. Vta3 affects the expression of more than 1,000 transcripts, including candidates with predicted functions in virulence and morphogenesis such as Egh16-like virulence factor 1 (Elv1) and Master transcription factor 1 (Mtf1). The genes encoding Elv1 and Mtf1 were deleted and their functions in V. dahliae growth and virulence on tomato (Solanum lycopersicum) plants were investigated using genetics, plant infection experiments, gene expression studies and phytohormone analyses. Vta3 contributes to virulence by promoting ELV1 expression, which is dispensable for vegetative growth and conidiation. Vta3 decreases disease symptoms mediated by Mtf1 in advanced stages of tomato plant colonization, while Mtf1 induces the expression of fungal effector genes and tomato pathogenesis-related protein genes. The levels of pipecolic and salicylic acids functioning in tomato defense signaling against (hemi-) biotrophic pathogens depend on the presence of MTF1, which promotes the formation of resting structures at the end of the infection cycle. In summary, the presence of VTA3 alters gene expression of virulence factors and tames the Mtf1 genetic subnetwork for late stages of plant disease progression and subsequent survival of the fungus in the soil.PMID:36716333 | DOI:10.1371/journal.ppat.1011100

Anal Chem. 2023 Jan 30. doi: 10.1021/acs.analchem.2c02598. Online ahead of print.ABSTRACTLipid analysis at the molecular species level represents a valuable opportunity for clinical applications due to the essential roles that lipids play in metabolic health. However, a comprehensive and high-throughput lipid profiling remains challenging given the lipid structural complexity and exceptional diversity. Herein, we present an 'omic-scale targeted LC-MS/MS approach for the straightforward and high-throughput quantification of a broad panel of complex lipid species across 26 lipid (sub)classes. The workflow involves an automated single-step extraction with 2-propanol, followed by lipid analysis using hydrophilic interaction liquid chromatography in a dual-column setup coupled to tandem mass spectrometry with data acquisition in the timed-selective reaction monitoring mode (12 min total run time). The analysis pipeline consists of an initial screen of 1903 lipid species, followed by high-throughput quantification of robustly detected species. Lipid quantification is achieved by a single-point calibration with 75 isotopically labeled standards representative of different lipid classes, covering lipid species with diverse acyl/alkyl chain lengths and unsaturation degrees. When applied to human plasma, 795 lipid species were measured with median intra- and inter-day precisions of 8.5 and 10.9%, respectively, evaluated within a single and across multiple batches. The concentration ranges measured in NIST plasma were in accordance with the consensus intervals determined in previous ring-trials. Finally, to benchmark our workflow, we characterized NIST plasma materials with different clinical and ethnic backgrounds and analyzed a sub-set of sera (n = 81) from a clinically healthy elderly population. Our quantitative lipidomic platform allowed for a clear distinction between different NIST materials and revealed the sex-specificity of the serum lipidome, highlighting numerous statistically significant sex differences.PMID:36716250 | DOI:10.1021/acs.analchem.2c02598

J Assoc Res Otolaryngol. 2023 Jan 30. doi: 10.1007/s10162-023-00887-1. Online ahead of print.ABSTRACTDysfunction of the endolymphatic sac (ES) is one of the etiologies of Meniere's disease (MD), the mechanism of which remains unclear. The aim of the present study was to explore the molecular pathological characteristics of ES during the development of MD. Metabolomic profiling of ES luminal fluid from patients with MD and patients with acoustic neuroma (AN) was performed. Diluted ES luminal fluid (ELF) samples were obtained from 10 patients who underwent endolymphatic duct blockage for the treatment of intractable MD and from 6 patients who underwent translabyrinthine surgery for AN. ELF analysis was performed using liquid chromatography-mass spectrometry before the raw data were normalized and subjected to subsequent statistical analysis by MetaboAnalyst. Using thresholds of P ≤ 0.05 and variable important in projection > 1, a total of 111 differential metabolites were screened in the ELF, including 52 metabolites in negative mode and 59 in positive mode. Furthermore, 15 differentially altered metabolites corresponding to 15 compound names were identified using a Student's t-test, including 7 significant increased metabolites and 8 significant decreased metabolites. Moreover, two differentially altered metabolites, hyaluronic acid (HA) and 4-hydroxynonenal (4-HNE), were validated to be upregulated in the epithelial lining of the ES, as well as in the subepithelial connective-tissue in patients with MD comparing with that in patients with AN. Among these differentially altered metabolites, an upregulated expression of HA detected in the ES lumen of the patients with MD was supposed to be associated with the increased endolymph in ES, while an increased level of 4-HNE found in the ELF of the patients with MD provided direct evidence to support that oxidative damage and inflammatory lesions underlie the mechanism of MD. Furthermore, citrate and ethylenediaminetetraacetic acid were detected to be decreased substantially in the ELF of the patients with MD, suggesting the elevated endolymphatic Ca2+ in the ears with chronic endolymphatic hydrops is likely to be associated with the reduction of these two chelators of Ca2+ in ES. The results in the present study indicate metabolomic analysis in the ELF of the patients with MD can potentially improve our understanding on the molecular pathophysiological mechanism in the ES during the development of MD.PMID:36715893 | DOI:10.1007/s10162-023-00887-1

Environ Monit Assess. 2023 Jan 30;195(2):344. doi: 10.1007/s10661-023-10935-1.ABSTRACTIt is crucial to understand the effects caused by experimental parameters such as temperature, light, and food type on lab and field-based ecotoxicology experiments, as these variables, and combinations thereof, can affect results. The type of substrate used in exposure experiments, however, is generally assumed to have no effect. This may not always be correct. The metabolic changes in the freshwater crustacean, Austrochiltonia subtenuis exposed to copper, using three common substrates, gauze; toilet paper; and cellulose were investigated. Substrate alone did not affect survival, but each substrate elicited a different metabolic response and adult and juvenile amphipods had different substrate preferences. Several classes of metabolites were shown to change in response to different substrates and toxicant. These included disaccharides, monosaccharides, fatty acids, and tricarboxylic acid cycle intermediates. The results illustrate that metabolomic responses can differ in response to experimental factors that were previously thought not to be significant. In fact, our data indicate that substrate should be viewed as an experimental factor as important to control for as more well-known confounders such as temperature or food, thus challenging the current paradigm. Assuming substrate type has no effect on the experiment could potentially lead to errors in contaminant toxicity assessments. We propose that ideal good practise would be that all experimental factors should be evaluated for their potential influence on metabolomic profiles prior to contaminant response experiments being undertaken.PMID:36715783 | DOI:10.1007/s10661-023-10935-1

Hum Mol Genet. 2023 Jan 30:ddad020. doi: 10.1093/hmg/ddad020. Online ahead of print.ABSTRACTTandem CAG repeat sizes of 36 or more in the huntingtin gene (HTT) cause Huntington disease. Apart from neuropsychiatric complications, the disease is also accompanied by metabolic dysregulation and weight loss, which contribute to a progressive functional decline. Recent studies also reported an association between repeats below the pathogenic threshold (<36) for Huntington's disease and body mass index (BMI), suggesting that HTT repeat sizes in the non-pathogenic range are associated with metabolic dysregulation. In this study we hypothesized that HTT repeat sizes < 36 are associated with metabolite levels, possibly mediated through reduced BMI. We pooled data from three European cohorts (n = 10 228) with genotyped HTT CAG repeat size and metabolomic measurements. All 145 metabolites were measured on the same targeted platform in all studies. Multilevel mixed-effects analysis using the CAG repeat size in HTT identified 67 repeat size-metabolite associations. Overall, the metabolomic profile associated with larger CAG repeat sizes in HTT were unfavorable-similar to those of higher risk of coronary artery disease and type 2 diabetes-and included elevated levels of amino acids, fatty acids, LDL, VLDL and IDL related metabolites whilst with decreased levels of very large HDL related metabolites. Furthermore, the associations of 50 metabolites, in particular specific very large HDL related metabolites, were mediated by lower BMI. However, no mediation effect was found for 17 metabolites related to LDL and IDL. In conclusion, our findings indicate that large non-pathogenic CAG repeat sizes in HTT are associated with an unfavorable metabolomic profile despite their association with a lower BMI.PMID:36715614 | DOI:10.1093/hmg/ddad020

mBio. 2023 Jan 30:e0266322. doi: 10.1128/mbio.02663-22. Online ahead of print.ABSTRACTNumerous studies have described specific metabolites as biomarkers of severe liver diseases, but very few have measured gut microbiota (GM)-produced metabolites in fatty liver disease. We aimed at finding GM signatures and metabolite markers in plasma and feces related to high liver fat content. Based on imaging, we divided study participants into low (<5%, LF, n = 25) and high (>5%, HF, n = 39) liver fat groups. Fecal (LF n = 14, HF n = 25) and plasma (LF n = 11, HF n = 7) metabolomes of subsets of participants were studied using liquid chromatography/high resolution mass spectrometry. The GM were analyzed using 16S rRNA gene sequencing. Additionally, blood clinical variables and diet were studied. Dyslipidemia, higher liver enzymes and insulin resistance characterized the HF group. No major differences in diet were found between the groups. In the GM, the HF group had lower abundance of Bacteroides and Prevotellaceae NK3B31 group than the LF group after adjusting for metformin use or obesity. In feces, the HF group had higher levels of lysine and histidine degradation products, while 6-hydroxybetatestosterone (metabolized by CYP3A4) was low. Higher plasma levels of caffeine and its metabolites in the HF group indicate that the activity of hepatic CYP1A2 was lower than in the LF group. Our results suggest, that low fecal Prevotellaceae NK3B31 and Bacteroides abundance, and increased lysine and histidine degradation may serve as GM biomarkers of high liver fat. Altered plasma caffeine metabolites and lowered testosterone metabolism may specify decreased CYP activities, and their potential utility, as biomarkers of fatty liver disease. IMPORTANCE Because the high prevalence of nonalcoholic fatty liver disease sets diagnostic challenges to health care, identification of new biomarkers of the disease that in the future could have potential utility as diagnostic biomarkers of high liver fat content is important. Our results show that increased amino acid degradation products in the feces may be such biomarkers. In the blood, molecules that indicate defective hepatic metabolic enzyme activities were identified in individuals with high liver fat content.PMID:36715540 | DOI:10.1128/mbio.02663-22

Anal Chem. 2023 Jan 30. doi: 10.1021/acs.analchem.2c04196. Online ahead of print.ABSTRACTLiquid chromatography-mass spectrometry (LC-MS)-based metabolomics usually combines hydrophilic interaction liquid chromatography (HILIC) and reversed-phase (RP) chromatography to cover a wide range of metabolomes, requiring both significant sample consumption and analysis time for separate workflows. We developed an integrated workflow enabling the coverage of both polar and nonpolar metabolites with only one injection of the sample for each ionization mode using heart-cutting trapping to combine HILIC and RP separations. This approach enables the trapping of some compounds eluted from the first chromatographic dimension for separation later in the second dimension. In our case, we applied heart-cutting to non-retained metabolites in the first dimension. For that purpose, two independent miniaturized one-dimensional HILIC and RP methods were developed by optimizing the chromatographic and ionization conditions using columns with an inner diameter of 1 mm. They were then merged into one two-dimensional micro LC-MS method by optimization of the trapping conditions. Equilibration of the HILIC column during elution on the RP column and vice versa reduced the overall analysis time, and the multidimensionality allows us to avoid signal measurements during the solvent front. To demonstrate the benefits of this approach to metabolomics, it was applied to the analysis of the human plasma standard reference material SRM 1950, enabling the detection of hundreds of metabolites without the significant loss of some of them while requiring an injection volume of only 0.5 μL.PMID:36715352 | DOI:10.1021/acs.analchem.2c04196

Compr Physiol. 2023 Jan 30;13(1):4295-4319. doi: 10.1002/cphy.c220010.ABSTRACTIn the over 100 years since the recognition of pulmonary hypertension (PH), immense progress and significant achievements have been made with regard to understanding the pathophysiology of the disease and its treatment. These advances have been mostly in idiopathic pulmonary arterial hypertension (IPAH), which was classified as Group 1 Pulmonary Hypertension (PH) at the Second World Symposia on PH in 1998. However, the pathobiology of PH due to chronic lung disease, classified as Group 3 PH, remains poorly understood and its treatments thus remain limited. We review the history of the classification of the five groups of PH and aim to provide a state-of-the-art review of the understanding of the pathogenesis of Group 1 PH and Group 3 PH including insights gained from novel high-throughput omics technologies that have revealed heterogeneities within these categories as well as similarities between them. Leveraging the substantial gains made in understanding the genomics, epigenomics, proteomics, and metabolomics of PAH to understand the full spectrum of the complex, heterogeneous disease of PH is needed. Multimodal omics data as well as supervised and unbiased machine learning approaches after careful consideration of the powerful advantages as well as of the limitations and pitfalls of these technologies could lead to earlier diagnosis, more precise risk stratification, better predictions of disease response, new sub-phenotype groupings within types of PH, and identification of shared pathways between PAH and other types of PH that could lead to new treatment targets. © 2023 American Physiological Society. Compr Physiol 13:4295-4319, 2023.PMID:36715285 | DOI:10.1002/cphy.c220010

J Anim Sci. 2023 Jan 28:skad034. doi: 10.1093/jas/skad034. Online ahead of print.ABSTRACTThe microbes that reside within the equine hindgut create a complex and dynamic ecosystem. The equine hindgut microbiota is intimately associated with health and, as such, represents an area which can be beneficially modified. Synbiotics, supplements that combine probiotic microorganisms with prebiotic ingredients, are a potential means of influencing the hindgut microbiota to promote health and prevent disease. The objective of the current study was to evaluate the influence of an equine probiotic/prebiotic supplement on characteristics of the microbiota and metabolite production in vitro. Equine cecal fluid and fecal material were collected from an abattoir in QC, CAN. Five hundred ml of cecal fluid was used to inoculate chemostat vessels maintained as batch fermenters (chemostat cecal, n=11) with either 0g (control) or 0.44g of supplement added at 12h intervals. One hundred ml of cecal fluid (anaerobic cecal, n=15) or 5% fecal slurry (anaerobic fecal, n=6) were maintained in an anaerobic chamber with either 0g (control) or 0.356g of supplement added at the time of vessel establishment. Samples were taken from vessels at vessel establishment (0h), 24h, or 48h of incubation. Illumina sequencing of the V4 region of the 16S rRNA gene and bioinformatics were performed for microbiome analysis. Metabolite data was obtained via NMR spectroscopy. All statistical analyses were run in SAS 9.4. There was no effect of treatment at 24h or 48h on alpha or beta diversity indices and limited taxonomic differences were noted. Acetate, propionate, and butyrate were higher in treated compared to untreated vessels in all methods. A consistent effect of supplementation on the metabolic profile with no discernable impact on the microbiota of these in vitro systems indicates inoculum microbe viability and a utilization of the provided fermentable substrate within the systems. Although no changes within the microbiome were apparent, the consistent changes in metabolites indicates a potential prebiotic effect of the added supplement and merits further exploration.PMID:36715114 | DOI:10.1093/jas/skad034

Biotechnol Genet Eng Rev. 2023 Jan 30:1-46. doi: 10.1080/02648725.2022.2152627. Online ahead of print.ABSTRACTPrebiotics as a part of dietary nutrition can play a crucial role in structuring the composition and metabolic function of intestinal microbiota and can thus help in managing a clinical scenario by preventing diseases and/or improving health. Among the different prebiotics, non-digestible carbohydrates are molecules that selectively enrich a typical class of bacteria with probiotic potential. This review summarizes the current knowledge about the different aspects of prebiotics, such as its production, characterization and purification by various techniques, and its link to novel product development at an industrial scale for wide-scale use in diverse range of health management applications. Furthermore, the path to effective valorization of agricultural residues in prebiotic production has been elucidated. This review also discusses the recent developments in application of genomic tools in the area of prebiotics for providing new insights into the taxonomic characterization of gut microorganisms, and exploring their functional metabolic pathways for enzyme synthesis. However, the information regarding the cumulative effect of prebiotics with beneficial bacteria, their colonization and its direct influence through altered metabolic profile is still getting established. The future of this area lies in the designing of clinical condition specific functional foods taking into consideration the host genotypes, thus facilitating the creation of balanced and required metabolome and enabling to maintain the healthy status of the host.PMID:36714949 | DOI:10.1080/02648725.2022.2152627

PNAS Nexus. 2022 Sep 27;1(4):pgac215. doi: 10.1093/pnasnexus/pgac215. eCollection 2022 Sep.ABSTRACTIn Leydig cells, intrinsic factors that determine cellular steroidogenic efficiency is of functional interest to decipher and monitor pathophysiology in many contexts. Nevertheless, beyond basic regulation of cholesterol storage and mobilization, systems biology interpretation of the metabolite networks in steroidogenic function is deficient. To reconstruct and describe the different molecular systems regulating steroidogenesis, we profiled the metabolites in resting MA-10 Leydig cells. Our results identified 283-annotated components (82 neutral lipids, 154 membrane lipids, and 47 other metabolites). Neutral lipids were represented by an abundance of triacyglycerols (97.1%), and low levels of cholesterol esters (2.0%). Membrane lipids were represented by an abundance of glycerophospholipids (77.8%), followed by sphingolipids (22.2%). Acylcarnitines, nucleosides, amino acids and their derivatives were the other metabolite classes identified. Among nonlipid metabolites, we recognized substantial reserves of aspartic acid, choline, creatine, betaine, glutamine, homoserine, isoleucine, and pantothenic acid none of which have been previously considered as a requirement in steroidogenic function. Individually limiting use of betaine, choline, or pantothenic acid, during luteinizing hormone-induced steroidogenesis in MA-10 cells resulted in substantial decreases to acute steroidogenic capacity, explained by intermediary metabolite imbalances affecting homeostasis. As such, our dataset represents the current level of baseline characterization and unravels the functional resting state of steroidogenic MA-10 Leydig cells. In identifying metabolite stockpiles and causal mechanisms, these results serve to further comprehend the cellular setup and regulation of steroid biosynthesis.PMID:36714831 | PMC:PMC9802464 | DOI:10.1093/pnasnexus/pgac215

Front Plant Sci. 2023 Jan 13;13:1110724. doi: 10.3389/fpls.2022.1110724. eCollection 2022.ABSTRACTAs low environmental temperature adversely affects the growth, development and geographical distribution, plants have evolved multiple mechanisms involving changing physiological and metabolic processes to adapt to cold stress. In this study, we revealed that nucleoporin-coding gene OsSEH1 was a positive regulator of cold stress in rice. Physiological assays showed that the activity of antioxidant enzymes showed a significant difference between osseh1 knock-out lines and wild type under cold stress. Metabolome analysis revealed that the contents of large-scale flavonoids serving as ROS scavengers were lower in osseh1 mutants compared with wild type under cold stress. Transcriptome analysis indicated that the DEGs between osseh1 knock-out lines and wild type plants were enriched in defense response, regulation of hormone levels and oxidation-reduction process. Integration of transcriptomic and metabolic profiling revealed that OsSEH1 plays a role in the oxidation-reduction process by coordinately regulating genes expression and metabolite accumulation involved in phenylpropanoid and flavonoid biosynthetic pathway. In addition, Exogenous ABA application assays indicated that osseh1 lines had hypersensitive phenotypes compared with wild type plants, suggesting that OsSEH1 may mediate cold tolerance by regulating ABA levels.PMID:36714747 | PMC:PMC9880419 | DOI:10.3389/fpls.2022.1110724