PubMed

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

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

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

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

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

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

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

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

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

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

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

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

J Cell Sci. 2023 Jun 5:jcs.260717. doi: 10.1242/jcs.260717. Online ahead of print.ABSTRACTMyofibrils are long intracellular cables specific to muscles, composed mainly of actin and myosin filaments. The actin and myosin filaments are organized into repeated units called sarcomeres, which form the myofibrils. Muscle contraction is achieved by the simultaneous shortening of sarcomeres, which requires all sarcomeres to be the same size. Muscles have a variety of ways to ensure sarcomere homogeneity. We previously showed that the controlled oligomerization of Zasp proteins sets the diameter of the myofibril. Here we looked for Zasp-binding proteins at the Z-disc to identify additional proteins coordinating myofibril growth and assembly. We found that the E1 subunit of the oxoglutarate dehydrogenase complex localizes to both the Z-disc and the mitochondria, and is recruited to the Z-disc by Zasp52. The three subunits of the oxoglutarate dehydrogenase complex are required for myofibril formation. Using super-resolution microscopy, we revealed the overall organization of the complex at the Z-disc. Metabolomics identified an amino acid imbalance affecting protein synthesis as a possible cause of myofibril defects, which is supported by OGDH-dependent localization of ribosomes at the Z-disc.PMID:37272588 | DOI:10.1242/jcs.260717

Plant Signal Behav. 2023 Dec 31;18(1):2215618. doi: 10.1080/15592324.2023.2215618.ABSTRACTArabidopsis NADK2 (NAD kinase 2) is a chloroplast-localized enzyme involved in NADP+ synthesis, which acts as the final electron acceptor in the photosynthetic electron transfer chain. The NADK2-deficient mutant (nadk2) was used to analyze the effect of NAD(P)(H) unbalance in the dark-induced leaf senescence. During senescence, WT plants and nadk2 mutants showed a similar reduction in chlorophyll content. NAD(P)(H) quantification showed that the amount of total NAD(P)(H) decreased on the day 7 in WT but on the day 3 in nadk2. The phosphorylation ratio (i.e. NADP(H)/NAD(H)) decreased on day 1 in WT. In contrast, the nadk2 showed lower phosphorylation ratio at 0 day and no change throughout the aging process. Metabolome analysis showed that the metabolic profiles of both WT plants and nadk2 mutants subjected to dark-induced senescence adopted similar patterns as the senescence progressed. However, the changes in individual metabolites in the nadk2 mutants were different from those of the WT during dark-induced senescence.PMID:37272565 | DOI:10.1080/15592324.2023.2215618

Plant J. 2023 Jun 5. doi: 10.1111/tpj.16277. Online ahead of print.ABSTRACTThe process of crop domestication leads to a dramatic reduction in the gene expression associated with metabolic diversity. Genes involved in specialized metabolism appear to be particularly affected. Although there is ample evidence of these effects at the genetic level, a reduction in diversity at the metabolite level has been taken for granted despite having never been adequately accessed and quantified. Here we leveraged the high coverage of ultra high performance liquid chromatography-high-resolution mass spectrometry based metabolomics to investigate the metabolic diversity in the common bean (Phaseolus vulgaris). Information theory highlights a shift towards lower metabolic diversity and specialization when comparing wild and domesticated bean accessions. Moreover, molecular networking approaches facilitated a broader metabolite annotation than achieved to date, and its integration with gene expression data uncovers a metabolic shift from specialized metabolism towards central metabolism upon domestication of this crop.PMID:37272491 | DOI:10.1111/tpj.16277

Biotechnol Bioeng. 2023 Jun 5. doi: 10.1002/bit.28450. Online ahead of print.ABSTRACTOptimization and monitoring of bioprocesses requires the measurement of several process parameters and quality attributes. Mass spectrometry (MS)-based techniques such as those coupled to gas chromatography (GCMS) and liquid Chromatography (LCMS) enable the simultaneous measurement of hundreds of metabolites with high sensitivity. When applied to spent media, such metabolome analysis can help determine the sequence of substrate uptake and metabolite secretion, consequently facilitating better design of initial media and feeding strategy. Furthermore, the analysis of metabolite diversity and abundance from spent media will aid the determination of metabolic phases of the culture and the identification of metabolites as surrogate markers for product titer and quality. This review covers the recent advances in metabolomics analysis applied to the development and monitoring of bioprocesses. In this regard, we recommend a stepwise workflow and guidelines that a bioprocesses engineer can adopt to develop and optimize a fermentation process using spent media analysis. Finally, we show examples of how the use of MS can revolutionize the design and monitoring of bioprocesses.PMID:37272489 | DOI:10.1002/bit.28450

Environ Microbiol. 2023 Jun 5. doi: 10.1111/1462-2920.16433. Online ahead of print.NO ABSTRACTPMID:37272427 | DOI:10.1111/1462-2920.16433

Basic Clin Pharmacol Toxicol. 2023 Jun 5. doi: 10.1111/bcpt.13909. Online ahead of print.ABSTRACTIn this study, we aimed to determine whether asiatic acid (AA) exerts any therapeutic effects on rifampicin (RFP)-and isoniazid (INH)-induced liver injury and elucidate the underlying mechanisms. Briefly, liver injury in mice was induced via RFP and INH administration. We investigated the effects and potential action mechanisms of AA on liver injury using transcriptomics, metabolomics, and various examinations. We found that AA significantly ameliorated the pathological changes in liver tissues and decreased the transaminase activity, inflammation, and oxidative stress damage. Transcriptomics revealed 147 differentially expressed genes (DEGs) between the AA and model groups that were enriched in metabolic and mitogen-activated protein kinase (MAPK) signaling pathways. Metabolomics revealed 778 differentially expressed metabolites between the AA and model groups. Furthermore, integrated transcriptomics and metabolomics analyses revealed strong correlations between DEGs and differentially expressed metabolites and indicated that AA regulates the sphingolipid metabolism by inhibiting the expression of delta 4-desaturase, sphingolipid 1. Experimental results confirmed that AA inhibited the MAPK signaling pathway. In summary, AA inhibits inflammation and oxidative stress damage by regulating sphingolipid metabolism pathway and blocking the MAPK signaling pathway, thereby relieving the RFP/INH-induced liver injury.PMID:37272388 | DOI:10.1111/bcpt.13909

Mol Omics. 2023 Jun 5. doi: 10.1039/d3mo00040k. Online ahead of print.ABSTRACTThe interactive network of hosts with pathogenic microbes is still questionable. It has been hypothesized and reported that the host shows altered regulatory mechanisms for different pathogens. Several studies using transcriptomics and proteomics revealed the altered pathways and sequential regulations displayed by the host during bacterial interactions. Still, there is a gap in understanding the triggering molecule at transcriptomic and proteomic levels due to the lack of the knowledge of the interactive metabolites produced during their interactions. In this study, the global metabolomic approach was performed in the nematode model organism Caenorhabditis elegans upon exposure to a Gram-negative bacteria, Salmonella enterica Serovar Typhi, and a Gram-positive bacteria, Staphylococcus aureus, and the whole metabolome was categorized as endo-metabolome (internally produced) and exo-metabolome (externally releasing). The extracted metabolites were subjected to liquid chromatography mass spectrometry (ESI-LC/qToF-MS/MS). In total 5578, 4554 and 4046 endo-metabolites and 4451, 3625 and 1281 exo-metabolites were identified in C. elegans when exposed to E. coli OP50, S. Typhi and S. aureus, respectively. Both the multivariate and univariate analyses were performed. The variation in endo- and exo-metabolome during candidate bacterial interactions was observed. The results indicated that, during S. aureus interaction, the exclusively enriched metabolites were significantly involved in alpha-linoleic acid metabolism. Similarly, the exclusively enriched metabolites during the interaction of S. Typhi were significantly involved in the phosphatidylinositol signalling system. The whole metabolomic profile presented here will build the scope to understand the role of metabolites and the respective pathways in host response during the early period of bacterial infections.PMID:37272185 | DOI:10.1039/d3mo00040k

Animal Model Exp Med. 2023 Jun 4. doi: 10.1002/ame2.12328. Online ahead of print.ABSTRACTBACKGROUND: The purpose of our study was to study the composition and content of the feline plasma metabolome revealing the critical metabolites and metabolic pathways associated with age during growth and development.METHODS: Blood samples were collected from juvenile and adult groups for blood routine tests and serum biochemistry tests. Non-targeted metabolomics analyses of plasma were also performed to investigate changes in metabolites and metabolic pathways.RESULTS: In this study, we found that the red blood cell counts, liver function indexes (albumin and gamma-glutamyl transpeptidase), and the concentration of triglyceride and glucose changed significant with growth and development. The metabolomics results revealed that 1427 metabolites were identified in the plasma of young and adult cats. Most of these metabolites belong to major classes of lipids and lipid-like molecules. The most obvious age-related metabolites include reduced levels of chenodeoxycholate, taurocholate, cholate, and taurochenodeoxycholate but increased levels of L-cysteine and taurocyamine in the adult cat's serum. These metabolites are mainly involved in the primary bile acid biosynthesis pathway, the bile secretion pathway, and the taurine and hypotaurine metabolism pathway.CONCLUSION: This study revealed many age-related metabolite alterations in the feline plasma. These age-varying metabolites, especially in the bile acid biosynthesis and secretion metabolism pathways, indicate that the regulation of these pathways is involved in the growth and development of cats. This study promotes our understanding of the mechanism of feline growth and provides new insights into nutrition and medicine for cats of different ages.PMID:37271879 | DOI:10.1002/ame2.12328