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

Potential of algae-derived alginate oligosaccharides and β-glucan to counter inflammation in adult zebrafish intestine

Mon, 05/06/2023 - 12:00
Front Immunol. 2023 May 19;14:1183701. doi: 10.3389/fimmu.2023.1183701. eCollection 2023.ABSTRACTAlginate oligosaccharides (AOS) are natural bioactive compounds with anti-inflammatory properties. We performed a feeding trial employing a zebrafish (Danio rerio) model of soybean-induced intestinal inflammation. Five groups of fish were fed different diets: a control (CT) diet, a soybean meal (SBM) diet, a soybean meal+β-glucan (BG) diet and 2 soybean meal+AOS diets (alginate products differing in the content of low molecular weight fractions - AL, with 31% < 3kDa and AH, with 3% < 3kDa). We analyzed the intestinal transcriptomic and plasma metabolomic profiles of the study groups. In addition, we assessed the expression of inflammatory marker genes and histological alterations in the intestine. Dietary algal β-(1, 3)-glucan and AOS were able to bring the expression of certain inflammatory genes altered by dietary SBM to a level similar to that in the control group. Intestinal transcriptomic analysis indicated that dietary SBM changed the expression of genes linked to inflammation, endoplasmic reticulum, reproduction and cell motility. The AL diet suppressed the expression of genes related to complement activation, inflammatory and humoral response, which can likely have an inflammation alleviation effect. On the other hand, the AH diet reduced the expression of genes, causing an enrichment of negative regulation of immune system process. The BG diet suppressed several immune genes linked to the endopeptidase activity and proteolysis. The plasma metabolomic profile further revealed that dietary SBM can alter inflammation-linked metabolites such as itaconic acid, taurochenodeoxycholic acid and enriched the arginine biosynthesis pathway. The diet AL helped in elevating one of the short chain fatty acids, namely 2-hydroxybutyric acid while the BG diet increased the abundance of a vitamin, pantothenic acid. Histological evaluation revealed the advantage of the AL diet: it increased the goblet cell number and length of villi of the intestinal mucosa. Overall, our results indicate that dietary AOS with an appropriate amount of < 3kDa can stall the inflammatory responses in zebrafish.PMID:37275890 | PMC:PMC10235609 | DOI:10.3389/fimmu.2023.1183701

Widely targeted metabolomics reveals the antioxidant and anticancer activities of different colors of <em>Dianthus caryophyllus</em>

Mon, 05/06/2023 - 12:00
Front Nutr. 2023 May 19;10:1166375. doi: 10.3389/fnut.2023.1166375. eCollection 2023.ABSTRACTCarnation is edible flower that has potent antioxidant properties and is used in traditional Chinese medicinal system and food industry. The phytochemicals responsible for these various proprieties, however, are not fully understood. Thus, in order to recognize metabolite diversity and variability in carnation flowers of different colors and to discover key metabolites that contribute to the differences in antioxidant and anticancer activities, widely targeted LC-MS/MS-based metabolomics analysis was conducted on purple, green, yellow, and white carnation flowers. We identified and chemically categorized 932 metabolites. Metabolic compounds varied significantly with flower color. Several flavonoids, organic acids, phenolic acids, and nucleotides and their derivatives were found to be specific differential metabolites in purple flowers. A total of 128 key differential metabolites were screened. The purple flowers were found to have the highest antioxidant and anticancer activities compared to the other colored flowers. Correlation analysis revealed that the 6-hydroxykaempferol-3,6-O-diglucoside, 6-hydroxykaempferol-7-O-glucoside, quercetin-3-O-sophoroside, and 2'-deoxyguanosine were found to be the major constituents of the antioxidant and anticancer activities. 2'-Deoxyguanosine has effective antiproliferative activity against A549 and U2OS cells for the first report. At the same time, the combination of 2'-deoxyguanosine with 6-hydroxykaempferol-3, 6-O-diglucoside, or quercetin-3-O-sophoroside have also been found to increase the antitumor activity of 2'-deoxyguanosine. These discoveries enrich information on the phytochemical composition of carnation of different colors and provide resources for the overall use and improvement of carnation flowers quality.PMID:37275648 | PMC:PMC10235515 | DOI:10.3389/fnut.2023.1166375

Comprehensive metabolic analyses provide new insights into primary and secondary metabolites in different tissues of Jianghua Kucha tea (<em>Camellia sinensis</em> var. <em>assamica</em> cv. Jianghua)

Mon, 05/06/2023 - 12:00
Front Nutr. 2023 May 19;10:1181135. doi: 10.3389/fnut.2023.1181135. eCollection 2023.ABSTRACTBACKGROUND: Jianghua Kucha (JHKC) is a special tea germplasm with enriched specialized secondary metabolites, including theacrine, non-epimeric flavanols and methylated flavanols. Moreover, primary metabolites provide precursors and energy for the production of secondary metabolites. However, the accumulation patterns of primary and secondary metabolites in different tissues of JHKC are unclear.METHODS: The changes of primary and secondary metabolites and related metabolic pathways (primary and secondary metabolism) in different JHKC tissues (the bud, 1st-4th leaves, and new stem) were investigated via metabolomics analysis with ultra-high-performance liquid chromatography quadrupole time-of-flight mass spectrometry (UHPLC-QTOF/MS).RESULTS: Significant differences were observed in 68 primary and 51 secondary metabolites mainly related with the pathways of starch and sucrose, amino acids, caffeine, and flavanols metabolism and TCA cycle. The bud exhibited higher levels of glucose-6-phosphate, citric acid, most amino acids, theobromine, catechin-gallate, epicatechin-gallate, procyanidins, and theasinensins; the 1st leaf showed higher levels of caffeine and epigallocatechin-3-gallate; and the 4th leaf contained higher levels of most monosaccharides, theacrine, and epigallocatechin-3-O-(3"-O-methyl)-gallate. In addition, primary metabolites and important secondary metabolites had certain correlations.CONCLUSION: This study provides comprehensive insight into primary and secondary metabolites in JHKC and offers guidelines for efficiently utilizing specialized metabolites of JHKC in the future.PMID:37275632 | PMC:PMC10235520 | DOI:10.3389/fnut.2023.1181135

Response of <em>Salmonella enterica</em> serovar Typhimurium to alginate oligosaccharides fermented with fecal inoculum: integrated transcriptomic and metabolomic analyses

Mon, 05/06/2023 - 12:00
Mar Life Sci Technol. 2023 May 29;5(2):242-256. doi: 10.1007/s42995-023-00176-z. eCollection 2023 May.ABSTRACTAlginate oligosaccharides (AOS), extracted from marine brown algae, are a common functional feed additive; however, it remains unclear whether they modulate the gut microbiota and microbial metabolites. The response of Salmonella enterica serovar Typhimurium, a common poultry pathogen, to AOS fermented with chicken fecal inocula was investigated using metabolomic and transcriptomic analyses. Single-strain cultivation tests showed that AOS did not directly inhibit the growth of S. Typhimurium. However, when AOS were fermented by chicken fecal microbiota, the supernatant of fermented AOS (F-AOS) exhibited remarkable antibacterial activity against S. Typhimurium, decreasing the abundance ratio of S. Typhimurium in the fecal microbiota from 18.94 to 2.94%. Transcriptomic analyses showed that the 855 differentially expressed genes induced by F-AOS were mainly enriched in porphyrin and chlorophyll metabolism, oxidative phosphorylation, and Salmonella infection-related pathways. RT-qPCR confirmed that F-AOS downregulated key genes involved in flagellar assembly and the type III secretory system of S. Typhimurium, indicating metabolites in F-AOS can influence the growth and metabolism of S. Typhimurium. Metabolomic analyses showed that 205 microbial metabolites were significantly altered in F-AOS. Among them, the increase in indolelactic acid and 3-indolepropionic acid levels were further confirmed using HPLC. This study provides a new perspective for the application of AOS as a feed additive against pathogenic intestinal bacteria.SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s42995-023-00176-z.PMID:37275545 | PMC:PMC10232696 | DOI:10.1007/s42995-023-00176-z

UPLC-Q-TOF/MS-based metabolomic analysis reveals the effects of asomate on the citrus fruit

Mon, 05/06/2023 - 12:00
Curr Res Food Sci. 2023 May 20;6:100523. doi: 10.1016/j.crfs.2023.100523. eCollection 2023.ABSTRACTThe regulation of the sugar-acid ratio is of great significance to the improvement of citrus fruit quality. The citric acid level in fruit is influenced by many factors. Among them, cultivar selection and production practices are the most important strategies under the grower's control. In recent years, an arsenic-containing preparation called "Tianmisu", with the main ingredient of asomate, has occasionally been reported to be used in citrus cultivation to improve the sweetness of fruits. In order to reveal the effects of the pesticide on citrus fruits, 'Harumi' tangor was treated with "Tianmisu", and the impact of this pesticide on fruit quality and metabolites was investigated through UPLC-Q-TOF/MS-based metabolomic analysis. Compared with the control, the concentration of titratable acidity, in particular citric acid, in the pulp of 'Harumi' tangor treated with the pesticide, was significantly reduced by 60.5%. The differences in metabolites between the pesticide-treated samples and the control were illustrated by Principal Component Analysis (PCA) and Partial Least Squares Discriminant Analysis (PLS-DA). The PLS-DA analysis demonstrated a clear discrimination, with R2Y and Q2 values of 0.982 and 0.933 in the positive mode and 0.984 and 0.900 in the negative mode, respectively. A total of 155 compounds were identified, and 63 characteristic components were screened out from the pesticide-treated samples compared to the control. Aside from the upregulation observed for a few metabolites, the majority of the compounds, including citric acid and various lipids, were down-regulated in the treated citrus fruits compared to the control. This study can serve as a basis for understanding the regulatory mechanism of organic acids in citrus and will be helpful in developing different strategies to improve citrus quality.PMID:37275389 | PMC:PMC10232657 | DOI:10.1016/j.crfs.2023.100523

Multi-omics study and ncRNA regulation of anti-BmNPV in silkworms, <em>Bombyx mori</em>: an update

Mon, 05/06/2023 - 12:00
Front Microbiol. 2023 May 18;14:1123448. doi: 10.3389/fmicb.2023.1123448. eCollection 2023.ABSTRACTBombyx mori silkworm is an important economic insect which has a significant contribution to the improvement of the economy. Bombyx mori nucleopolyhedrovirus (BmNPV) is a vitally significant purulent virus that impedes the sustainable and stable development of the silkworm industry, resulting in substantial economic losses. In recent years, with the development of biotechnology, transcriptomics, proteomics, metabolomics, and the related techniques have been used to select BmNPV-resistant genes, proteins, and metabolites. The regulatory networks between viruses and hosts have been gradually clarified with the discovery of ncRNAs, such as miRNA, lncRNA, and circRNA in cells. Thus, this paper aims to highlight the results of current multi-omics and ncRNA studies on BmNPV resistance in the silkworm, providing some references for resistant strategies in the silkworm to BmNPV.PMID:37275131 | PMC:PMC10232802 | DOI:10.3389/fmicb.2023.1123448

Genome-wide search identified DNA methylation sites that regulate the metabolome

Mon, 05/06/2023 - 12:00
Front Genet. 2023 May 18;14:1093882. doi: 10.3389/fgene.2023.1093882. eCollection 2023.ABSTRACTBackground: Identifying DNA methylation sites that regulate the metabolome is important for several purposes. In this study, publicly available GWAS data were integrated to find methylation sites that impact metabolome through a discovery and replication scheme and by using Mendelian randomization. Results: The outcome of analyses revealed 107 methylation sites associated with 84 metabolites at the genome-wide significance level (p<5e-8) at both the discovery and replication stages. A large percentage of the observed associations (85%) were with lipids, significantly higher than expected (p = 0.0003). A number of CpG (methylation) sites showed specificity e.g., cg20133200 within PFKP was associated with glucose only and cg10760299 within GATM impacted the level of creatinine; in contrast, there were sites associated with numerous metabolites e.g., cg20102877 on the 2p23.3 region was associated with 39 metabolites. Integrating transcriptome data enabled identifying genes (N = 82) mediating the impact of methylation sites on the metabolome and cardiometabolic traits. For example, PABPC4 mediated the impact of cg15123755-HDL on type-2 diabetes. KCNK7 mediated the impact of cg21033440-lipids on hypertension. POC5, ILRUN, FDFT1, and NEIL2 mediated the impact of CpG sites on obesity through metabolic pathways. Conclusion: This study provides a catalog of DNA methylation sites that regulate the metabolome for downstream applications.PMID:37274792 | PMC:PMC10233745 | DOI:10.3389/fgene.2023.1093882

Insight into the mechanisms of therapeutic hypothermia for asphyxia cardiac arrest using a comprehensive approach of GC-MS/MS and UPLC-Q-TOF-MS/MS based on serum metabolomics

Mon, 05/06/2023 - 12:00
Heliyon. 2023 May 19;9(6):e16247. doi: 10.1016/j.heliyon.2023.e16247. eCollection 2023 Jun.ABSTRACTCardiac arrest (CA) is a severe worldwide health problem. Therapeutic hypothermia is widely used to reduce the cardiac injury and improve the neurological outcomes after CA. However, a few studies have reported the changes of serum metabolic characteristics after CA. The healthy male New Zealand Rabbits successfully resuscitated from 10-min asphyxia-induced CA were divided randomly into the normothermia (NT) group and mild therapeutic hypothermia (HT) group. The sham group underwent sham-operation. Survival was recorded and neurological deficit score (NDS) was assessed. The serum non-targeted metabolomics were detected using ultra-high-performance liquid chromatography-quadrupole time-of-flight tandem mass spectrometry (UPLC-Q-TOF-MS/MS) and gas chromatography tandem mass spectrometry (GC-MS/MS) at 15 min, 3 h, 6 h and 24 h after return of spontaneous circulation (ROSC). Our study showed that the heart rate (HR) significantly slowed down during 0.5-6 h post ROSC, consistent with the decreasing trend of body temperature in the HT group. Compared with the NT group, the levels of Lac and PCO2 at 24 h post ROSC were lower, while a significant increase in PO2 level at 24 h post ROSC was observed in the HT group. The survival rate of the HT group was significantly higher than that of the NT group, and NDS scores were remarkably increased at 24 h post ROSC in the NT group. Significant differences in metabolic profiles at 15 min, 3 h, 6 h and 24 h post ROSC were observed among the Sham, NT and HT groups. The differential metabolites detected by UPLC-Q-TOF-MS/MS and GC-MS/MS were screened for further study between every two groups (NT vs sham, HT vs sham and HT vs NT) at 15 min, 3 h, 6 h and 24 h post ROSC. Phenylalanine metabolism, alanine, aspartate and glutamate metabolism and tricarboxylic acid (TCA) cycle were enriched in NT vs sham, HT vs sham and HT vs NT respectively. Our study demonstrated that therapeutic hypothermia improves the survival and neurological outcomes in rabbit model of cardiac arrest, and firstly represents the dynamic metabolic changes in the hypothermia therapy for CA by comprehensive UPLC-Q-TOF-MS/MS- and GC-MS/MS-based metabolomics.PMID:37274716 | PMC:PMC10238693 | DOI:10.1016/j.heliyon.2023.e16247

Walking 200 min per day keeps the bariatric surgeon away

Mon, 05/06/2023 - 12:00
Heliyon. 2023 May 22;9(6):e16556. doi: 10.1016/j.heliyon.2023.e16556. eCollection 2023 Jun.ABSTRACTExercise and increased physical activity are vital components of the standard treatment guidelines for many chronic diseases such as diabetes, obesity and cardiovascular disease. Although strenuous exercise cannot be recommended to people with numerous chronic conditions, walking is something most people can perform. In comparison to high-intensity training, the metabolic consequences of low-intensity walking have been less well studied. We present here a feasibility study of a subject who performed an exercise intervention of low-intensity, non-fatiguing walking on a deskmill/treadmill for 200 min daily, approximately the average time a German spends watching television per day. This low-impact physical activity has the advantages that it can be done while performing other tasks such as reading or watching TV, and it can be recommended to obese patients or patients with heart disease. We find that this intervention led to substantial weight loss, comparable to that of bariatric surgery. To study the metabolic changes caused by this intervention, we performed an in-depth metabolomic profiling of the blood both directly after walking to assess the acute changes, as well as 1.5 days after physical activity to identify the long-term effects that persist. We find changes in acylcarnitine levels suggesting that walking activates fatty acid beta oxidation, and that this mitochondrial reprogramming is still visible 1.5 days post-walking. We also find that walking mildly increases gut permeability, leading to increased exposure of the blood to metabolites from the gut microbiome. Overall, these data provide a starting point for designing future intervention studies with larger cohorts.PMID:37274680 | PMC:PMC10238728 | DOI:10.1016/j.heliyon.2023.e16556

Integration of UHPLC/Q-OrbitrapMS-based metabolomics and activities evaluation to rapidly explore the anti-inflammatory components from lasianthus

Mon, 05/06/2023 - 12:00
Heliyon. 2023 May 23;9(6):e16117. doi: 10.1016/j.heliyon.2023.e16117. eCollection 2023 Jun.ABSTRACTLasianthus, belonging to Rubiaceae, has been verified to improve clinical syndrome in immune diseases (e.g., hepatitis, nephritis, and rheumatoid arthritis). Both the anti-inflammatory function and chemical composition of Lasianthus vary considerably between different species but few studies focus. So essential it is to explore lasianthus and further search for anti-inflammatory substances. The target of this artical is to analyze the anti-inflammatory activity and chemical composition of lasianthus of different species. And the subsequent active compounds were explored. Primary, the anti-inflammatory activity among seven species of lasianthus (e.g., L. fordii., L. wallichii., L. hookeri C., L. verticillatus., L. sikkimensis., L. appressihirtus., and L. hookeri var) were evaluated by vitro experiments (RAW 264.7 cells). Next, UHPLC/Q-Orbitrap-MS-based metabolomics and the mass defect filter (MDF) algorithm were performed to explore metabolites. In addition, principal component analysis (PCA) was to screen out differential compounds in seven species. Finally, the correlation analysis between activities and composition to rapidly discover the active compounds (compounds were verified pharmacologically). Among the 7 species of lasianthus, the L. fordii. and L. hookeri C indicated the best anti-inflammatory activity. Untargeted metabolomics and MDF show 112 compounds, classified into six dominant types (e.g., flavonoids, phenolic acids, alkaloids, iridoids, coumarins, and anthraquinones). Furthermore, 33 differential metabolites were confirmed by PCA. Then according to correlation analysis and pharmacological validation, 7 compounds IC50<100 (e.g., scopoletin, asperulosidic acid, chlorogenic acid, ferulic acid, betaine, syringic acid, and emodin) were verified as anti-inflammatory compounds and conduct quantitative analysis. Metabolomics integrated with activities evaluation might be a rapid and effective strategy to explore the active compounds from natural products.PMID:37274662 | PMC:PMC10238613 | DOI:10.1016/j.heliyon.2023.e16117

Therapeutic effects of Zhuling Jianpi capsule on experimental ulcerative colitis and characterization of its chemical constituents and metabolomics using UHPLC-Q-TOF-MS

Mon, 05/06/2023 - 12:00
Heliyon. 2023 May 24;9(6):e16553. doi: 10.1016/j.heliyon.2023.e16553. eCollection 2023 Jun.ABSTRACTZhuling Jianpi Capsule (Zhuling) is a traditional Chinese medicinal formula used to treat symptoms such as abdominal pain, bloating and diarrhea associated with inflammatory bowel disease (IBD). However, the protective effects of Zhuling on experimental ulcerative colitis (UC) and the effective substance responsible for its efficacy have rarely been reported. In this study, we evaluated the therapeutic effects of orally administrated Zhuling on DSS-induced UC in mice. The chemical constituents and metabolomics of Zhuling were qualitatively analyzed by ultra-high performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (UHPLC-Q-TOF-MS). The results showed that Zhuling treatment markedly alleviated DSS-induced clinical symptoms, restrained the secretion of pro-inflammatory cytokines, and improved intestinal epithelial barrier function. Furthermore, a total of 167 compounds have been identified or characterized, and 120 prototype components were detected in the urine, plasma, bile and feces of mice. Among them, altogether 26 representative prototypes were associated with 139 metabolites via the corresponding biotransformation pathways, and both of them mainly contained flavonoids, alkaloids, organic acids, monoterpenes, phenylpropanoids, triterpenoids, sesquiterpenoids and anthraquinones. Finally, 12 potent compounds mainly containing flavonoids, terpenoids and phenylpropanoids were screened out as potential quality control index components and might be the main substances that exert a pharmacological effect. Our data indicated that Zhuling administration prominently alleviates DSS-induced colitis in mice. Additionally, the chemical and metabolic profiling provided helpful information on the potential pharmacodynamic substances of Zhuling, which can be further investigated in the future.PMID:37274655 | PMC:PMC10238897 | DOI:10.1016/j.heliyon.2023.e16553

Wide identification of chemical constituents in fermented licorice and explore its efficacy of anti-neurodegeneration by combining quasi-targeted metabolomics and in-depth bioinformatics

Mon, 05/06/2023 - 12:00
Front Neurosci. 2023 May 18;17:1156037. doi: 10.3389/fnins.2023.1156037. eCollection 2023.ABSTRACTLicorice (Gan-Cao in Chinese) is one of the most famous herbal medicines around the world. The fermentation of probiotics and herbs can change the chemical constituents and significantly improve the efficacy. However, it is still unknown whether licorice fermented with probiotics would produce beneficial therapeutic effects. This study aimed to comprehensively analyze the chemical constituents in fermented licorice via quasi-targeted metabolomics, predict the potential efficacy of fermentation products via diverse bioinformatic methods, and further verify the efficacy of fermentation products through in vitro and in vivo experiments. As a result, 1,435 compounds were identified totally. Among them, 424 natural medicinal products were classified with potentially important bioactivities, including 11 anthocyanins, 10 chalcones and dihydrochalcones, 25 flavanones, 45 flavones and flavonols, 117 flavonoids, 34 isoflavonoids, 21 phenols and its derivatives, 20 phenylpropanoids and polyketides, 96 terpenoids and 25 coumarins and derivatives. Interestingly, bioinformatic prediction showed that the targets of some important compounds were related to neurodegeneration, oxidoreductase activity and response to stress. In vitro and in vivo tests further verified that fermented licorice had excellent effects of DPPH clearance, anti-oxidation, anti-neurodegeneration, and anti-stress. Thus, this study would provide a reference method for related research and the development of fermented licorice-related products.PMID:37274217 | PMC:PMC10234426 | DOI:10.3389/fnins.2023.1156037

The mechanism of trans-δ-viniferin inhibiting the proliferation of lung cancer cells A549 by targeting the mitochondria

Mon, 05/06/2023 - 12:00
Front Pharmacol. 2023 May 18;14:1190127. doi: 10.3389/fphar.2023.1190127. eCollection 2023.ABSTRACTTrans-δ-viniferin (TVN), as a natural extract, is a resveratrol dimer with attractive biological activities, particularly its anti-tumor character. However, the mechanism of TVN interfering with cancerous proliferation has not been fully understood. Herein in this study, we found that TVN could trigger cancerous mitochondrial membrane potential (ΔΨm) reduction, with intracellular reactive oxidative species (ROS) level increasing, leading to apoptosis, which makes TVN a promising candidate for lung cancer cells A549 treatment. Therefore, this study provides TVN as an option to meet the demand for higher antitumor availability with lower biotoxicity and other clinical applications.PMID:37274109 | PMC:PMC10232840 | DOI:10.3389/fphar.2023.1190127

Multi-omics in Crohn's disease: New insights from inside

Mon, 05/06/2023 - 12:00
Comput Struct Biotechnol J. 2023 May 13;21:3054-3072. doi: 10.1016/j.csbj.2023.05.010. eCollection 2023.ABSTRACTCrohn's disease (CD) is an inflammatory bowel disease (IBD) with complex clinical manifestations such as chronic diarrhea, weight loss and hematochezia. Despite the increasing incidence worldwide, cure of CD remains extremely difficult. The rapid development of high-throughput sequencing technology with integrated-omics analyses in recent years has provided a new means for exploring the pathogenesis, mining the biomarkers and designing targeted personalized therapeutics of CD. Host genomics and epigenomics unveil heredity-related mechanisms of susceptible individuals, while microbiome and metabolomics map host-microbe interactions in CD patients. Proteomics shows great potential in searching for promising biomarkers. Nonetheless, single omics technology cannot holistically connect the mechanisms with heterogeneity of pathological behavior in CD. The rise of multi-omics analysis integrates genetic/epigenetic profiles with protein/microbial metabolite functionality, providing new hope for comprehensive and in-depth exploration of CD. Herein, we emphasized the different omics features and applications of CD and discussed the current research and limitations of multi-omics in CD. This review will update and deepen our understanding of CD from integration of broad omics spectra and will provide new evidence for targeted individualized therapeutics.PMID:37273853 | PMC:PMC10238466 | DOI:10.1016/j.csbj.2023.05.010

Chemical Profiling of Wines Produced in Bulgaria and Distinction from International Grape Varieties

Mon, 05/06/2023 - 12:00
ACS Omega. 2023 May 16;8(21):18702-18713. doi: 10.1021/acsomega.3c00636. eCollection 2023 May 30.ABSTRACTDistinguishing the botanical and geographical origin of wine is important to prevent wine adulteration and to determine its quality. The combined use of 1H NMR profiling and chemometrics allows the quantification of 31 common organic components in the NMR spectra of 70 wines from different sources. Using the NMR metabolomics approach, a successful differentiation of wines produced from Bulgarian and international grape varieties is achieved using linear discriminant analysis. Wines produced from typical local grape varieties contain higher average amounts of galacturonic, malic, tartaric, and succinic acid, alanine, choline, several alcohols, and saccharides arabinose, galactose, and sucrose than imported wine assortments. A practical decision tree is proposed for distinguishing 15 different grape varieties based on the amounts of the common wine components. An example of distinction of real from diluted wine via creation of a PLS-DA model is presented. Wines from the two subregions officially recognized by the EU at the Protected Geographical Indication (PGI) level are unequivocally recognized.PMID:37273597 | PMC:PMC10233681 | DOI:10.1021/acsomega.3c00636

Age-related alterations in metabolome and microbiome provide insights in dietary transition in giant pandas

Mon, 05/06/2023 - 12:00
mSystems. 2023 Jun 5:e0025223. doi: 10.1128/msystems.00252-23. Online ahead of print.ABSTRACTWe conducted UPLC-MS-based metabolomics, 16S rRNA, and metagenome sequencing on the fecal samples of 44 captive giant pandas (Ailuropoda melanoleuca) from four age groups (i.e., Cub, Young, Adult, and Old) to comprehensively understand age-related changes in the metabolism and gut microbiota of giant pandas. We characterized the metabolite profiles of giant pandas based on 1,376 identified metabolites, with 152 significantly differential metabolites (SDMs) found across the age groups. We found that the metabolites and the composition/function of the gut microbiota changed in response to the transition from a milk-dominant diet in panda cubs to a bamboo-specific diet in young and adult pandas. Lipid metabolites such as choline and hippuric acid were enriched in the Cub group, and many plant secondary metabolites were significantly higher in the Young and Adult groups, while oxidative stress and inflammatory related metabolites were only found in the Old group. However, there was a decrease in the α-diversity of gut microbiota in adult and old pandas, who exclusively consume bamboo. The abundance of bacteria related to the digestion of cellulose-rich food, such as Firmicutes, Streptococcus, and Clostridium, significantly increased from the Cub to the Adult group, while the abundance of beneficial bacteria such as Faecalibacterium, Sarcina, and Blautia significantly decreased. Notably, several potential pathogenic bacteria had relatively high abundances, especially in the Young group. Metagenomic analysis identified 277 CAZyme genes including cellulose degrading genes, and seven of the CAZymes had abundances that significantly differed between age groups. We also identified 237 antibiotic resistance genes (ARGs) whose number and diversity increased with age. We also found a significant positive correlation between the abundance of bile acids and gut bacteria, especially Lactobacillus and Bifidobacterium. Our results from metabolome, 16S rRNA, and metagenome data highlight the important role of the gut microbiota-bile acid axis in the regulation of age-related metabolism and provide new insights into the lipid metabolism of giant pandas.IMPORTANCEThe giant panda is a member of the order Carnivora but is entirely herbivorous. The giant panda's specialized diet and related metabolic mechanisms have not been fully understood. It is therefore crucial to investigate the dynamic changes in metabolites as giant pandas grow and physiologically adapt to their herbivorous diet. This study conducted UPLC-MS-based metabolomics 16S rRNA, and metagenome sequencing on the fecal samples of captive giant pandas from four age groups. We found that metabolites and the composition/function of gut microbiota changed in response to the transition from a milk-dominant diet in cubs to a bamboo-specific diet in young and adult pandas. The metabolome, 16S rRNA, and metagenome results highlight that the gut microbiota-bile acid axis has an important role in the regulation of age-related metabolism, and our study provides new insights into the lipid metabolism of giant pandas.PMID:37273228 | DOI:10.1128/msystems.00252-23

Effects of Probiotic Enterococcus faecium from Yak on the Intestinal Microflora and Metabolomics of Mice with Salmonella Infection

Mon, 05/06/2023 - 12:00
Probiotics Antimicrob Proteins. 2023 Jun 5. doi: 10.1007/s12602-023-10102-5. Online ahead of print.ABSTRACTSalmonella spp. are pathogenic bacteria that cause diarrhea, abortion, and death in yak and severely harm livestock breeding. Therefore, it is vital to identify a probiotic that effectively antagonizes Salmonella. To the best of our knowledge, few prior studies have investigated the efficacy of Enterococcus faecium against Salmonella. Here, we evaluated the enteroprotective mechanism of E. faecium in a mouse Salmonella infection model using hematoxylin-eosin (H&E) staining, quantitative real-time polymerase chain reaction (Q-PCR) technology, microbial diversity sequencing, and metabonomics. Enterococcus faecium inhibited the proinflammatory cytokines IL-1β, IL-6, TNF-α, and IFN-γ and promoted the anti-inflammatory cytokine IL-10. The Firmicutes/Bacteroidota (F/B) ratio and the abundances of Firmicutes and Akkermansia were significantly higher in the E. faecium than in the Salmonella group. Metabonomics and microbial diversity sequencing disclosed five different metabolites with variable importance in the projection (VIP) > 3 that were characteristic of both the Salmonella and E. faecium groups. Combined omics revealed that Lactobacillus and Bacteroides were negatively and positively correlated, respectively, with cholic acid, while Desulfovibrio was positively correlated with lipids in both the control and Salmonella groups. Desulfovibrio was also positively correlated with lipids in both the Salmonella and E. faecium groups. Enterococcus faecium antagonizes Salmonella by normalizing the abundance of the intestinal microorganisms and modulating their metabolic pathways. Hence, it may efficaciously protect the host intestine against Salmonella infection.PMID:37273089 | DOI:10.1007/s12602-023-10102-5

Fecal metabonomics combined with 16S rDNA sequencing to analyze the changes of gut microbiota in rats fed with different protein source diets

Mon, 05/06/2023 - 12:00
Eur J Nutr. 2023 Jun 5. doi: 10.1007/s00394-023-03168-y. Online ahead of print.ABSTRACTPURPOSE: When blended, animal and plant proteins can complement each other in terms of amino acid composition and release time. In this study, we investigated whether the blended protein diet has a better feeding effect than the single protein diet, and to reveal the differences in growth and intestinal microbiota composition caused by the blended protein diet.METHODS: Forty Sprague Dawley (SD) rats received diets with different protein sources, including casein (C), whey protein (WP), black soybean protein (BSP), and black soybean-whey blended protein (BS-WP), for eight weeks. To investigate the effects of blended protein supplement on gut microbiota and metabolites, we performed a high throughput 16S rDNA sequencing and fecal metabolomics profiling. In addition, we determined growth and serum biochemical indices, and conducted intestinal morphology analyses.RESULTS: Compared to those in the BSP and WP groups, the daily body weight gain and feed conversion efficiency increased in the BS-WP group. Serum biochemical indices indicated that the protein utilization efficiency of the WP and BS-WP groups was relatively high, and the BS-WP blended protein diet improved the protein adoption rate. The BS-WP blended protein diet also improved intestinal tissue morphology and promoted intestinal villi development compared to the single protein diets. Furthermore, dietary protein altered the composition of gut microbiota, the gut microbial diversity of rats fed with the BS-WP diet was significantly (P < 0.05) higher than that of the other groups. The difference in dietary protein corresponded with an alteration of fecal amino acids and their metabolites, and tryptophan and tyrosine metabolism were the key mechanisms leading to the changes in fecal microbial composition.CONCLUSION: Dietary protein sources played an important role in the growth and development of rats by influencing intestinal metabolism and microbial composition. The BS-WP blended protein diet was more conducive to nutrient absorption than the single protein diet. Furthermore, blended protein increased the diversity of intestinal microbes and aided the establishment of intestinal barrier function.PMID:37273002 | DOI:10.1007/s00394-023-03168-y

Characterisation of acetogen formatotrophic potential using Eubacterium limosum

Mon, 05/06/2023 - 12:00
Appl Microbiol Biotechnol. 2023 Jun 5. doi: 10.1007/s00253-023-12600-6. Online ahead of print.ABSTRACTFormate is a promising energy carrier that could be used to transport renewable electricity. Some acetogenic bacteria, such as Eubacterium limosum, have the native ability to utilise formate as a sole substrate for growth, which has sparked interest in the biotechnology industry. However, formatotrophic metabolism in E. limosum is poorly understood, and a system-level characterisation in continuous cultures is yet to be reported. Here, we present the first steady-state dataset for E. limosum formatotrophic growth. At a defined dilution rate of 0.4 d-1, there was a high specific uptake rate of formate (280 ± 56 mmol/gDCW/d; gDCW = gramme dry cell weight); however, most carbon went to CO2 (150 ± 11 mmol/gDCW/d). Compared to methylotrophic growth, protein differential expression data and intracellular metabolomics revealed several key features of formate metabolism. Upregulation of phosphotransacetylase (Pta) appears to be a futile attempt of cells to produce acetate as the major product. Instead, a cellular energy limitation resulted in the accumulation of intracellular pyruvate and upregulation of pyruvate formate ligase (Pfl) to convert formate to pyruvate. Therefore, metabolism is controlled, at least partially, at the protein expression level, an unusual feature for an acetogen. We anticipate that formate could be an important one-carbon substrate for acetogens to produce chemicals rich in pyruvate, a metabolite generally in low abundance during syngas growth. KEY POINTS: First Eubacterium limosum steady-state formatotrophic growth omics dataset High formate specific uptake rate, however carbon dioxide was the major product Formate may be the cause of intracellular stress and biofilm formation.PMID:37272938 | DOI:10.1007/s00253-023-12600-6

Genomic analysis of <em>Kazachstania aerobia</em> and <em>Kazachstania servazzii</em> reveals duplication of genes related to acetate ester production

Mon, 05/06/2023 - 12:00
Microb Genom. 2023 Jun;9(6). doi: 10.1099/mgen.0.001029.ABSTRACTKazachstania aerobia and Kazachstania servazzii can affect wine aroma by increasing acetate ester concentrations, most remarkably phenylethyl acetate and isoamyl acetate. The genetic basis of this is unknown, there being little to no sequence data available on the genome architecture. We report for the first time the near-complete genome sequence of the two species using long-read (PacBio) sequencing (K. aerobia 20 contigs, one scaffold; and K. servazzii 22 contigs, one scaffold). The annotated genomes of K. aerobia (12.5 Mb) and K. servazzii (12.3 Mb) were compared to Saccharomyces cerevisiae genomes (laboratory strain S288C and wine strain EC1118). Whilst a comparison of the two Kazachstania spp. genomes revealed few differences between them, divergence was evident in relation to the genes involved in ester biosynthesis, for which gene duplications or absences were apparent. The annotations of these genomes are valuable resources for future research into the evolutionary biology of Kazachstania and other yeast species (comparative genomics) as well as understanding the metabolic processes associated with alcoholic fermentation and the production of secondary 'aromatic' metabolites (transcriptomics, proteomics and metabolomics).PMID:37272916 | DOI:10.1099/mgen.0.001029

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