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

Lanhuashen stimulates the positive cross-regulation mediated by the S1P axis to ameliorate the disorder of glucolipid metabolism induced by the high sucrose diet in Drosophila melanogaster

Sat, 07/10/2023 - 12:00
J Ethnopharmacol. 2023 Oct 5:117248. doi: 10.1016/j.jep.2023.117248. Online ahead of print.ABSTRACTETHNOPHARMACOLOGICAL RELEVANCE: Herba Wanlenbergiae, named 'Lanhuashen' (LHS) in Chinese, is derived from the dried herba of Wahlenbergia marginata (Thunb.) A.DC. It is an abundant resource that has been used in traditional Chinese medicine (TCM) for over 600 years. LHS has the effects of enriching consumptive disease and relieving deficient heat, consistent with the therapy for type 2 diabetes mellitus (T2DM) in TCM. As the basic remedy of Yulan Jiangtang capsules, a listed Chinese medicine specifically for treating T2DM, LHS is a potential candidate for an anti-T2DM drug. However, due to the lack of pharmacodynamic studies and chemical component analysis, the application and development of LHS as a treatment for T2DM have been hindered.AIM OF THE STUDY: To evaluate the regulation of the disorder of glucolipid metabolism using LHS extracts and its therapeutic potential in T2DM.MATERIALS AND METHODS: Chemical components in LHS extracts were analysed using UPLC-Q Exactive-Orbitrap-MS. Subsequently, high sucrose diet (HSD)-induced Drosophila melanogaster were used as suitable models for T2DM in vivo. Behavioural and biochemical tests were performed to evaluate the regulation of the disorder of glucolipid metabolism using LHS in T2DM flies. Furthermore, integrative metabolomic and transcriptomic analysis was applied to reveal the specific effects of LHS extracts on metabolites and genes. Meanwhile, bioinformatic analysis was carried out to predict the targeted transcription factors (TFs) and potentially effective components of LHS extracts.RESULTS: We redefined the chemical profile of LHS with 76 identified chemical components, including 65 chemical components for the first time. As indicated by decreased trehalose, glucose and triglyceride levels and increased total protein levels, LHS extracts were perceived to alleviate the disorder of glucolipid metabolism in HSD-induced T2DM fruit flies. Integrative metabolomic and transcriptomic analysis revealed that LHS extracts eliminated the accumulation of sphingolipids and subsequently stimulated the positive cross-regulation mediated by the sphingosine 1-phosphate (S1P) axis, resulting in the activation of the phosphatidylinositol-3-kinase (PI3K)-protein kinase B (Akt) signalling pathway and inhibition of lysosome-mediated apoptosis. Bioinformatic analysis revealed that the upstream TFs, transcriptional enhancer factor TEF-5 (TEAD3) and peroxisome proliferator-activated receptor alpha (PPARA), were the potential targets of atractylenolide III, dihydrokaempferol and syringaldehyde, the potentially effective components of LHS extracts. Therefore, this TF network was plausibly the basis for the efficacy.CONCLUSIONS: LHS extracts broadly modulated TF-dependent gene expression and subsequently stimulated the positive cross-regulation mediated by the S1P axis to ameliorate the disorder of glucolipid metabolism. Our study provides critical evidence considering LHS as a potential drug candidate for T2DM, inspiring the discovery and development of innovative therapeutic agents based on the cross-regulation mediated by the S1P axis for treating T2DM and related complications.PMID:37804923 | DOI:10.1016/j.jep.2023.117248

The primary neurotoxic factor, Lansamide I, from Clausena lansium fruits and metabolic dysfunction invoked

Sat, 07/10/2023 - 12:00
Food Chem Toxicol. 2023 Oct 5:114087. doi: 10.1016/j.fct.2023.114087. Online ahead of print.ABSTRACTWampee (Clausena lansium) is a common fruit in South Asia. The pulp is a tasty food, and the seed is a typical traditional herb in China. However, we identified a primary toxic compound, Lansamide I, by NMR and X-ray diffraction of single-crystal. The compound occurred at 4.17 ± 0.16 mg/kg of dried seed and 0.08 ± 0.01 g/kg of fresh fruit. In our phenotype-based toxicity investigation, the compound caused decreased hatchability of zebrafish eggs, increased malformations such as enlarged yolk sacs and pericardial edema, and delayed body length development. Moreover, the compound also caused nerve cell damage and decreased locomotor activity. The compound caused an increase in peroxidation levels in vivo, with increases in both malondialdehyde and superoxide dismutase levels, but did not interfere with acetylcholinesterase levels. Metabolomic studies found that the compound caused significant up-regulation of 16 metabolites, mainly amino acids and peptides, which were involved in the nucleotide metabolism pathway and the betaine biosynthesis module. The qRT-PCR revealed that the substance interfered with the mRNA expression of tat and dctpp. These discoveries offer fresh perspectives on the toxicity mechanisms and metabolic response to the primary harmful moleculesin wampee, which could inform the rational usage of wampee resources.PMID:37804914 | DOI:10.1016/j.fct.2023.114087

Metabolic support by macrophages sustains colonic epithelial homeostasis

Sat, 07/10/2023 - 12:00
Cell Metab. 2023 Sep 29:S1550-4131(23)00341-8. doi: 10.1016/j.cmet.2023.09.010. Online ahead of print.ABSTRACTThe intestinal epithelium has a high turnover rate and constantly renews itself through proliferation of intestinal crypt cells, which depends on insufficiently characterized signals from the microenvironment. Here, we showed that colonic macrophages were located directly adjacent to epithelial crypt cells in mice, where they metabolically supported epithelial cell proliferation in an mTORC1-dependent manner. Specifically, deletion of tuberous sclerosis complex 2 (Tsc2) in macrophages activated mTORC1 signaling that protected against colitis-induced intestinal damage and induced the synthesis of the polyamines spermidine and spermine. Epithelial cells ingested these polyamines and rewired their cellular metabolism to optimize proliferation and defense. Notably, spermine directly stimulated proliferation of colon epithelial cells and colon organoids. Genetic interference with polyamine production in macrophages altered global polyamine levels in the colon and modified epithelial cell proliferation. Our results suggest that macrophages act as "commensals" that provide metabolic support to promote efficient self-renewal of the colon epithelium.PMID:37804836 | DOI:10.1016/j.cmet.2023.09.010

Xie Zhuo Tiao Zhi formula modulates intestinal microbiota and liver purine metabolism to suppress hepatic steatosis and pyroptosis in NAFLD therapy

Sat, 07/10/2023 - 12:00
Phytomedicine. 2023 Sep 23;121:155111. doi: 10.1016/j.phymed.2023.155111. Online ahead of print.ABSTRACTBACKGROUND: Current evidence indicates a rising global prevalence of Non-Alcoholic Fatty Liver Disease (NAFLD), which is closely associated to conditions such as obesity, dyslipidemia, insulin resistance, and metabolic syndrome. The relationship between the gut microbiome and metabolites in NAFLD is gaining attention understanding the pathogenesis and progression of dysregulated lipid metabolism and inflammation. The Xie Zhuo Tiao Zhi (XZTZ) decoction has been employed in clinical practice for alleviating hyperlipidemia and symptoms related to metabolic disorders. However, the pharmacological mechanisms underlying the effects of XZTZ remain to be elucidated.PURPOSE: The objective of this study was to examine the pharmacological mechanisms underlying the hypolipidemic and anti-inflammatory effects of XZTZ decoction in a mouse model of NAFLD, as well as the effects of supplementing exogenous metabolites on PO induced cell damage and lipid accumulation in cultured hepatocytes.METHODS: A high-fat diet (HFD) mouse model was established to examine the effects of XZTZ through oral gavage. The general condition of mice and the protective effect of XZTZ on liver injury were evaluated using histological and biochemical methods. Hematoxylin and eosin staining (H&E) staining and oil red O staining were performed to assess inflammatory and lipid accumulation detection, and cytokine levels were quantitatively analyzed. Additionally, the study included full-length 16S rRNA sequencing, liver transcriptome analysis, and non-targeted metabolomics analysis to investigate the relationship among intestinal microbiome, liver metabolic function, and XZTZ decoction.RESULTS: XZTZ had a significant impact on the microbial community structure in NAFLD mice. Notably, the abundance of Ileibacterium valens, which was significantly enriched by XZTZ, exhibited a negative correlation with liver injury biomarkers such as, alanine transaminase (ALT) and aspartate transaminase (AST) activity. Moreover, treatment with XZTZ led to a significant enrichment of the purine metabolism pathway in liver tissue metabolites, with inosine, a purine metabolite, showing a significant positive correlation with the abundance of I. valens. XZTZ and inosine also significantly enhanced fatty acid β-oxidation, which led to a reduction in the expression of pro-inflammatory cytokines and the inhibition of liver pyroptosis. These effects contributed to the mitigation of liver injury and hepatocyte damage, both in vivo and vitro. Furthermore, the utilization of HPLC fingerprints and UPLC-Q-TOF-MS elucidated the principal constituents within the XZTZ decoction, including naringin, neohesperidin, atractylenolide III, 23-o-Acetylalisol B, pachymic acid, and ursolic acid which are likely responsible for its therapeutic efficacy. Further investigations are imperative to fully uncover and validate the pharmacodynamic mechanisms underlying these observations.CONCLUSION: The administration of XZTZ decoction demonstrates a protective effect on the livers of NAFLD mice by inhibiting lipid accumulation and reducing hepatocyte inflammatory damage. This protective effect is mediated by the upregulation of I.valens abundance in the intestine, highlighting the importance of the gut-liver axis. Furthermore, the presesnce of inosine, adenosine, and their derivatives are important in promoting the protective effects of XZTZ. Furthermore, the in vitro approaching, we provide hitherto undocumented evidence indicating that the inosine significantly improves lipid accumulation, inflammatory damage, and pyroptosis in AML12 cells incubated with free fatty acids.PMID:37804819 | DOI:10.1016/j.phymed.2023.155111

Molecular insights: Proteomic and metabolomic dissection of plasma-induced growth and functional compound accumulation in Raphanus sativus

Sat, 07/10/2023 - 12:00
Food Chem. 2023 Sep 22;435:137548. doi: 10.1016/j.foodchem.2023.137548. Online ahead of print.ABSTRACTThis study investigated the impact of plasma-activated water (PAW) on Raphanus sativus (radish) roots at the level of proteins and metabolites. PAW treatment induced the accumulation of reactive oxygen species (ROS) and nitrogen oxide species (NOx) in radish and enhanced the activities of antioxidant enzymes. Proteomic analysis resulted in the identification of 6054 proteins, including 1845 PAW-modulated proteins that were majorly associated with energy metabolism, ROS-detoxification, phytohormones signaling, and biosynthesis of glucosinolates. Subsequent metabolomics analysis identified 314 metabolites, of which 194 showed significant differences in response to PAW treatment. In particular, PAW treatment triggered the accumulation of functional compounds such as vitamin C, vitamin B5, glutathione, and glucosinolates, the well-known characteristic compounds of the Brassicaceae family. Further, integrating proteomics and metabolomics data provided novel insights into the molecular mechanism governing plasma-induced growth and the accumulation of these functional compounds in radish plants.PMID:37804729 | DOI:10.1016/j.foodchem.2023.137548

Re-discovering Prunus fruit varieties as antiangiogenic agents by metabolomic and bioinformatic approach

Sat, 07/10/2023 - 12:00
Food Chem. 2023 Sep 28;435:137574. doi: 10.1016/j.foodchem.2023.137574. Online ahead of print.ABSTRACTIn this work, a comparative chemical-biological study of nine plum varieties (Prunus domestica L. and Prunus salicina Lindl.) with two commercial ones was carried out to improve their cultivation and use in the agri-food chain. The chemical quali-quantitative fingerprint by HR-Orbitrap/ESI-MS showed similar profiles, being 'Rossa Casa Velasco' the richest in phenols and anthocyanins. All the extracts were investigated for their in vitro antioxidant as well as antiangiogenic activity by two in vivo models, chick chorioallantoic membrane and zebrafish embryos. Among investigated varieties 'Scarrafona', 'Rusticano', 'Marisa', 'Rossa Casa Velasco', 'Verdone', and 'Sangue di Drago' showed the best antiangiogenic activities (30-50 % inhibition). Finally, the chemical/biological datasets processed with a bioinformatic approach revealed that a large group of flavonoids, procyanidins, and anthocyanins significantly correlated with all the three antioxidant tests (DPPH, FRAP, and ABTS), while quinic acid and icariside F2 resulted positively correlated with CAM at both 100 and 200 μg/egg.PMID:37804727 | DOI:10.1016/j.foodchem.2023.137574

The metabolite butyrate produced by gut microbiota inhibits cachexia-associated skeletal muscle atrophy by regulating intestinal barrier function and macrophage polarization

Sat, 07/10/2023 - 12:00
Int Immunopharmacol. 2023 Oct 4;124(Pt B):111001. doi: 10.1016/j.intimp.2023.111001. Online ahead of print.ABSTRACTOBJECTIVE: Cachexia, marked by muscle atrophy, poses substantial challenges for prevention and treatment. This study delves into the unclear role of butyrate, a gut microbiota metabolite, in cachexia by examining gut microbiota and short-chain fatty acid (SCFA) profiles in human and mouse fecal samples.METHODS: We analyzed cachexia-associated gut microbiota and SCFA profiles using 16S rRNA sequencing and metabolomic techniques. Mouse cachexia models were developed with C26 cells, and LPS was used to induce muscle cell atrophy in C2C12 cells. We evaluated butyrate's in vivo effects on intestinal health, muscle preservation, inflammation, and macrophage activity. In vitro studies focused on butyrate's influence on macrophage polarization and the subsequent effects on muscle cells.RESULTS: Both cachexia patients and mice exhibited gut microbiota imbalances, irregular butyrate concentrations, and a decline in butyrate-producing bacteria. In vivo tests showed that butyrate counteract cachexia-induced muscle atrophy by adjusting the Akt/mTOR/Foxo3a and Fbox32/Trim63 pathways. These butyrate also bolstered intestinal barrier integrity, minimized endotoxin migration, and mitigated oxidative stress. Furthermore, butyrate curtailed inflammation and macrophage penetration in muscles. In vitro experimental results demonstrate that butyrate inhibit macrophage polarization towards the M1 phenotype and promote polarization towards the M2 phenotype. Both M1 and M2 macrophages influence the aforementioned pathways and oxidative stress, participating in the regulation of muscle cell atrophy.CONCLUSION: Our study delineates the intricate interplay between gut microbiota dysbiosis, butyrate fluctuations, and cachexia progression. Butyrate not only reinforces the intestinal barrier but also orchestrates macrophage polarization, mitigating muscle atrophy and averting cachexia-induced muscle deterioration. Concurrently, the M1 and M2 macrophages play pivotal roles in modulating skeletal muscle cell atrophy. This highlights the potential of utilizing the gut-derived metabolite butyrate as a promising therapeutic approach for addressing cachexia-related issues.PMID:37804658 | DOI:10.1016/j.intimp.2023.111001

Selective inhibition of indoleamine and tryptophan 2,3-dioxygenases: Comparative study on kynurenine pathway in cell lines via LC-MS/MS-based targeted metabolomics

Sat, 07/10/2023 - 12:00
J Pharm Biomed Anal. 2023 Sep 26;237:115750. doi: 10.1016/j.jpba.2023.115750. Online ahead of print.ABSTRACTIn the last decade, the kynurenine pathway, which is the primary metabolic route for tryptophan (TRP) catabolism, has sparked great interest in the pharmaceutical sciences due to its role in immune regulation and cancer immunoediting. In this context, the development of cell-based assays might represent a tool to: i) characterize the cell secretome according to cell types; ii) gain more insight into the role of kynurenines in different disease scenarios; iii) screen hIDO1 (human indoleamine 2,3-dioxygenase) inhibitors and evaluate their effect on downstream TRP-catabolizing enzymes. This paper reports a validated Liquid Chromatography with tandem mass spectrometry (LC-MS/MS) method to simultaneously quantify TRP, L-kynurenine (KYN), xanthurenic acid (XA), 3-hydroxykynurenine (3OHKYN), kynurenic acid (KA), 3-hydroxyanthranilic acid (3OHAA), anthranilic acid (AA), 5-hydroxytryptamine (serotonin, 5HT) and tryptamine (TRYP) in Dulbecco's Modified Eagle and Eagle's Minimum Essential Media (DMEM and EMEM, respectively). The quantitative method was validated according to FDA, ICH and EMA guidelines, later applied: i) to assess the impact of selective inhibition of hIDO1 or hTDO (human tryptophan 2,3-dioxygenase) on the kynurenine pathway in A375 (melanoma), MDA-MB-231 (breast cancer), and U87 (glioblastoma) cell lines using multivariate analysis (MVA); ii) to determine the IC50 values of both well-known (i.e., epacadostat, linrodostat) and the novel hIDO1 inhibitor (i.e., BL5) in the aforementioned cell lines. The proposed LC-MS/MS method is reliable and robust. Furthermore, it is highly versatile and suitable for applications in the preclinical drug research and in vitro assays.PMID:37804639 | DOI:10.1016/j.jpba.2023.115750

Nutritional metabolomics: Recent developments and future needs

Sat, 07/10/2023 - 12:00
Curr Opin Chem Biol. 2023 Oct 5;77:102400. doi: 10.1016/j.cbpa.2023.102400. Online ahead of print.ABSTRACTMetabolomics has rapidly been adopted as one of the key methods in nutrition research. This review focuses on the recent developments and updates in the field, including the analytical methodologies that encompass improved instrument sensitivity, sampling techniques and data integration (multiomics). Metabolomics has advanced the discovery and validation of dietary biomarkers and their implementation in health research. Metabolomics has come to play an important role in the understanding of the role of small molecules resulting from the diet-microbiota interactions when gut microbiota research has shifted towards improving the understanding of the activity and functionality of gut microbiota rather than composition alone. Currently, metabolomics plays an emerging role in precision nutrition and the recent developments therein are discussed.PMID:37804582 | DOI:10.1016/j.cbpa.2023.102400

NTRC and thioredoxins m1/m2 underpin the light acclimation of plants on proteome and metabolome levels

Sat, 07/10/2023 - 12:00
Plant Physiol. 2023 Oct 7:kiad535. doi: 10.1093/plphys/kiad535. Online ahead of print.ABSTRACTDuring photosynthesis, plants must manage strong fluctuations in light availability on different time scales, leading to long-term acclimation and short-term responses. However, little is known about the regulation and coordination of these processes and the modulators involved. In this study, we used proteomics, metabolomics, and reverse genetics to investigate how different light environmental factors, such as intensity or variability, affect long-term and short-term acclimation responses of Arabidopsis (Arabidopsis thaliana) and the importance of the chloroplast redox network in their regulation. In the wild type, high light, but not fluctuating light, led to large quantitative changes in the proteome and metabolome, accompanied by increased photosynthetic dynamics and plant growth. This finding supports light intensity as a stronger driver for acclimation than variability. Deficiencies in NADPH-thioredoxin reductase C (NTRC) or thioredoxins m1/m2, but not thioredoxin f1, almost completely suppressed the reengineering of the proteome and metabolome, with both the induction of proteins involved in stress and redox responses and the repression of those involved in cytosolic and plastid protein synthesis and translation being strongly attenuated. Moreover, the correlations of protein or metabolite levels with light intensity were severely disturbed, suggesting a general defect in the light-dependent acclimation response, resulting in impaired photosynthetic dynamics. These results indicate a previously unknown role of NTRC and thioredoxins m1/m2 in modulating light acclimation at proteome and metabolome levels to control dynamic light responses. NTRC, but not thioredoxins m1/m2 or f1, also improves short-term photosynthetic responses by balancing the Calvin-Benson cycle in fluctuating light.PMID:37804523 | DOI:10.1093/plphys/kiad535

Single-cell omics techniques to elucidate cell-to-cell variability in signaling cascades involved in human diseases

Sat, 07/10/2023 - 12:00
Expert Rev Proteomics. 2023 Oct 7. doi: 10.1080/14789450.2023.2268836. Online ahead of print.NO ABSTRACTPMID:37804136 | DOI:10.1080/14789450.2023.2268836

Hyperoxia caused intestinal metabolism disorder in mice

Sat, 07/10/2023 - 12:00
Zhonghua Wei Zhong Bing Ji Jiu Yi Xue. 2023 Sep;35(9):980-983. doi: 10.3760/cma.j.cn121430-20230607-00427.ABSTRACTOBJECTIVE: To investigate the effect of hyperoxia on intestinal metabolomics in mice.METHODS: Sixteen 8-week-old male C57BL/6 mice were randomly divided into hyperoxia group and control group, with 8 mice in each group. The hyperoxia group was exposed to 80% oxygen for 14 days. Mice were anesthetized and euthanized, and cecal contents were collected for untargeted metabolomics analysis by liquid chromatography-mass spectrometry (LC-MS) combined detection. Orthogonal partial least square discriminant analysis (OPLS-DA), volcano plot analysis, heat map analysis, and Kyoto Encyclopedia of Genes and Genomes (KEGG) were used to analyze the effects of hyperoxia on metabolism.RESULTS: (1) OPLS-DA analysis showed that R2Y was 0.967 and Q2 was 0.796, indicating that the model was reliable. (2) Volcano plot and heat map analysis showed significant statistical differences in the expression levels of metabolites between the two groups, with 541 up-regulated metabolites, 64 down-regulated metabolites, and 907 no differences, while the elevated 5-hydroxy-L-lysine was the most significant differential metabolite induced by high oxygen. (3) KEGG pathway enrichment analysis showed that porphyrin and chlorophyll metabolism (P = 0.005), lysine degradation (P = 0.047), and aromatic compound degradation (P = 0.024) were the targets affected by hyperoxia. (4) Differential analysis of metabolic products through KEGG enrichment pathway showed that hyperoxia had a significant impact on the metabolism of porphyrin and chlorophyll, lysine, and aromatic compounds such as benzene and o-cresol.CONCLUSIONS: Hyperoxia significantly induces intestinal metabolic disorders. Hyperoxia enhances the metabolism of porphyrins and chlorophyll, inhibits the degradation of lysine, and delays the degradation of aromatic compounds such as benzene and o-cresol.PMID:37803959 | DOI:10.3760/cma.j.cn121430-20230607-00427

Revealing the role of gut microbiota in immune regulation and organ damage in sepsis using 16s rRNA and untargeted metabolomics

Sat, 07/10/2023 - 12:00
Zhonghua Wei Zhong Bing Ji Jiu Yi Xue. 2023 Sep;35(9):927-932. doi: 10.3760/cma.j.cn121430-20230517-00378.ABSTRACTOBJECTIVE: To analyze the composition and metabolites of gut microbiota in septic rats by fecal 16s rRNA sequencing and untargeted metabolomics, and to preliminarily explore the effect and potential mechanism of gut microbiota and its metabolites on inflammatory response and multiple organ damage in sepsis.METHODS: Ten males healthy male Wistar rats were randomly divided into a sham operated group (Sham group) and sepsis model group (CLP group) using a random number table method, with 5 rats in each group. A rat sepsis model was established by cecal ligation and perforation (CLP) method. The animals were sacrificed 24 hours after modeling, the levels of tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) in peripheral blood were detected by enzyme-linked immunosorbent assay (ELISA). Hematoxylin-eosin (HE) staining was used to observe the pathological changes of lung and kidney tissues, and the pathological scores were evaluated. Fecal samples were collected, and 16s rRNA high-throughput sequencing and non-targeted metabolomics were used to screen microbiota, metabolites and potential signal pathways that may play an important role in disease outcomes. Spearman correlation analysis was conducted to jointly analyze the gut microbiota and non-targeted metabolism.RESULTS: Compared with the Sham group, the degree of pathological damage to lung and kidney tissues in the CLP group was significantly increased (lung tissue score: 3.60±0.80 vs. 0.00±0.00, kidney tissue score: 2.40±0.80 vs. 0.00±0.00, both P < 0.01), the level of IL-6 and TNF-α in peripheral blood significantly increased [TNF-α (ng/L): 248.12±55.98 vs. 143.28±36.57, IL-6 (ng/L): 260.26±39.47 vs. 116.01±26.43, both P < 0.05], the species diversity of intestinal flora of rats in the CLP group was significantly reduced, the relative abundance of Morganella, Bacteroides and Escherichia-Shigella were significantly increased, and the relative abundance of Lachnospiraceae NK4A136, Ruminococcus, Romboutsia and Roseburia were significantly reduced. In addition, the biosynthesis and bile secretion of phenylalanine, tyrosine, and tryptophan in the gut microbiota of the CLP group were significantly increased, while the biosynthesis of secondary bile acids was significantly reduced. There was a significant correlation between differential metabolites and differential microbiota.CONCLUSIONS: Sepsis can cause significant changes in the characteristics of gut microbiota and fecal metabolites in rats, which provides a basis for translational research to seek new targets for the treatment of sepsis.PMID:37803951 | DOI:10.3760/cma.j.cn121430-20230517-00378

Peanut skin procyanidins reduce intestinal glucose transport protein expression, regulate serum metabolites and ameliorate hyperglycemia in diabetic mice

Sat, 07/10/2023 - 12:00
Food Res Int. 2023 Nov;173(Pt 2):113471. doi: 10.1016/j.foodres.2023.113471. Epub 2023 Sep 11.ABSTRACTOne of diabetic characteristics is the postprandial hyperglycemia. Inhibiting glucose uptake may be beneficial for controlling postprandial blood glucose levels and regulating the glucose metabolism Peanut skin procyanidins (PSP) have shown a potential for lowering blood glucose; however, the underlying mechanism through which PSP regulate glucose metabolism remains unknown. In the current study, we investigated the effect of PSP on intestinal glucose transporters and serum metabolites using a mouse model of diabetic mice. Results showed that PSP improved glucose tolerance and systemic insulin sensitivity, which coincided with decreased expression of sodium-glucose cotransporter 1 and glucose transporter 2 in the intestinal epithelium induced by an activation of the phospholipase C β2/protein kinase C signaling pathway. Moreover, untargeted metabolomic analysis of serum samples revealed that PSP altered arachidonic acid, sphingolipid, glycerophospholipid, bile acids, and arginine metabolic pathways. The study provides new insight into the anti-diabetic mechanism of PSP and a basis for further research.PMID:37803795 | DOI:10.1016/j.foodres.2023.113471

Use of reconstituted kefir consortia to determine the impact of microbial composition on kefir metabolite profiles

Sat, 07/10/2023 - 12:00
Food Res Int. 2023 Nov;173(Pt 2):113467. doi: 10.1016/j.foodres.2023.113467. Epub 2023 Sep 12.ABSTRACTKefir is fermented traditionally with kefir grains, but commercial kefir production often relies on fermentation with planktonic cultures. Kefir has been associated with many health benefits, however, the utilization of kefir grains to facilitate large industrial production of kefir is challenging and makes to difficult to ensure consistent product quality and consistency. Notably, the microbial composition of kefir fermentations has been shown to impact kefir associated health benefits. This study aimed to compare volatile compounds, organic acids, and sugar composition of kefir produced through a traditional grain fermentation and through a reconstituted kefir consortium fermentation. Additionally, the impact of two key microbial communities on metabolite production in kefir was assessed using two modified versions of the consortium, with either yeasts or lactobacilli removed. We hypothesized that the complete kefir consortium would closely resemble traditional kefir, while the consortia without yeasts or lactobacilli would differ significantly from both traditional kefir and the complete consortium fermentation. Kefir fermentations were examined after 12 and 18 h using two-dimensional gas chromatography-time-of-flight mass spectrometry (GC × GC-TOFMS) to identify volatile compounds and high performance liquid chromatography (HPLC) to identify organic acid and sugar composition. The traditional kefir differed significantly from the kefir consortium fermentation with the traditional kefir having 15-20 log2(fold change) higher levels of esters and the consortium fermented kefir having between 1 and 3 log2(fold change) higher organic acids including lactate and acetate. The use of a version of kefir consortium that lacked lactobacilli resulted in between 2 and 20 log2(fold change) lower levels of organic acids, ethanol, and butanoic acid ethyl ester, while the absence of yeast from the consortium resulted in minimal change. In summary, the kefir consortium fermentation is significantly different from traditional grain fermented kefir with respect to the profile of metabolites present, and seems to be driven by lactobacilli, as evidenced by the significant decrease in multiple metabolites when the lactobacilli were removed from the fermentation and minimal differences observed upon the removal of yeast.PMID:37803789 | DOI:10.1016/j.foodres.2023.113467

Refined mackerel oil increases hepatic lipid accumulation and reduces choline and choline-containing metabolites in the liver tissue in mice fed a Western diet

Sat, 07/10/2023 - 12:00
Food Res Int. 2023 Nov;173(Pt 2):113450. doi: 10.1016/j.foodres.2023.113450. Epub 2023 Sep 11.ABSTRACTIn this study, we aimed to evaluate the impact of consuming refined mackerel oil (MO) from rest raw material on hepatic fat accumulation, glucose tolerance, and metabolomic changes in the liver from male C57BL/6N mice. The mice were fed either a Western diet (WD) or a chow diet, with 30 g or 60 g MO per kg of diet (3% or 6%) for 13 weeks. Body weight, energy intake, and feed efficiency were monitored throughout the experiment. A glucose tolerance test was conducted after 11 weeks, and metabolomic analyses of the liver were performed at termination. Inclusion of MO in the WD, but not in the chow diet, led to increased liver weight, hepatic lipid accumulation, elevated fasting blood glucose, reduced glucose tolerance, and insulin sensitivity. Hepatic levels of eicosapentaenoic and docosahexaenoic acid increased, but no changes in levels of saturated and monounsaturated fatty acids were observed. The liver metabolomic profile was different between mice fed a WD with or without MO, with a reduction in choline ether lipids, phosphatidylcholines, and sphingomyelins in mice fed MO. This study demonstrates that supplementing the WD, but not the chow diet, with refined MO accelerates accumulation of hepatic fat droplets and negatively affects blood glucose regulation. The detrimental effects of supplementing a WD with MO were accompanied by increased fat digestibility and overall energy intake, and lower levels of choline and choline-containing metabolites in liver tissue.PMID:37803779 | DOI:10.1016/j.foodres.2023.113450

Metabolomic analysis reveals linkage between chemical composition and sensory quality of different floral honey samples

Sat, 07/10/2023 - 12:00
Food Res Int. 2023 Nov;173(Pt 2):113454. doi: 10.1016/j.foodres.2023.113454. Epub 2023 Sep 11.ABSTRACTHoney has a distinct flavor characterized by various volatiles and non-volatiles from diverse origins. In this study, metabolomics combined with sensory analysis was performed to identify relationships between chemical profile and sensory quality of honey. Targeted metabolomic analysis was conducted to determine volatile and non-volatile profiles of seven different honey. Volatile profile was analyzed using headspace solid-phase microextraction (HS-SPME) coupled to GC - MS. LC - MS/MS, HPLC - UV, and HPLC-RI were employed to analyze flavonoids, organic acids, and sugars, respectively. Authentic standards were utilized for confirmation of metabolites. Sensory evaluation included quantitative descriptive analysis and consumer acceptance test. The results showed that sucrose (sweetness) was responsible for a positive hedonic perception, while organic acids and flavonoids (sourness, astringency, bitterness) negatively affected consumer acceptance. Volatiles with floral notes (e.g. decyl formate) were preferred, but others with off-flavors (e.g. 2-methylbenzofuran) were not preferred by consumers. Flavor familiarity was strongly correlated with the consumer acceptance of honey, indicating that the balance between volatiles and non-volatiles is significant for honey flavor quality. This work demonstrates the role of key flavor compounds in honey quality, and may be applicable to the quality control of honey.PMID:37803778 | DOI:10.1016/j.foodres.2023.113454

Main urinary biomarkers of golden berries (Physalis peruviana) following acute and short-term nutritional intervention in healthy human volunteers

Sat, 07/10/2023 - 12:00
Food Res Int. 2023 Nov;173(Pt 2):113443. doi: 10.1016/j.foodres.2023.113443. Epub 2023 Sep 11.ABSTRACTThe metabolites entering the bloodstream and being excreted in urine as a result of consuming golden berries are currently unidentified. However, these metabolites potentially underlie the health benefits observed in various in vitro, animal, and human models. A nutritional intervention with 18 healthy human volunteers was performed, and urine was collected at baseline and after acute and short-term fruit consumption for 19 days. After UPLC-ESI/QToF-MS analysis, untargeted metabolomics was performed on the urine samples, and from the 50 most discriminant ions (VIP > 2) generated by a validated PLS-DA model (CV-ANOVA = 3.7e-35; R^2Y = 0.86, Q^2Y = 0.62 and no overfitting), 22 compounds were identified with relatively high confidence. The most discriminant metabolites confirmed by DHS/GC-MS2 analysis of volatiles in urine were sesquiterpenes (C15H22): 3 stereoisomers, β-vatirenene, β-vetivenene, and β-vetispirene, and 2 isomers, eremophila-1(10),8,11-triene and α-curcumene. Another major urinary biomarker was 4β-hydroxywithanolide E and its phase II derivatives, which were observed in urine for all individual up to 24 h after the fruit was consumed; thus, the bioavailability of this biomarker in humans was demonstrated for the first time. Additionally, the excretion of certain acylcarnitines and hypoxanthine in urine increased after golden berry consumption, which may be associated with a detoxifying effect and may occur because fats were utilized rather than carbohydrates to meet the body's energy needs. The main biomarkers of golden berry consumption are specific to this fruit, confirming its potential for the functional food market.PMID:37803771 | DOI:10.1016/j.foodres.2023.113443

Adequate pre-freezing handling slows the quality deterioration of frozen obscure pufferfish: Revealed by untargeted metabolomics

Sat, 07/10/2023 - 12:00
Food Res Int. 2023 Nov;173(Pt 2):113423. doi: 10.1016/j.foodres.2023.113423. Epub 2023 Aug 30.ABSTRACTTo investigate the effect of different pre-freezing handling methods on the frozen quality of farmed obscure pufferfish, live pufferfish were treated with commercial slaughter (CS), spinal cord cutting (SCC), or spinal cord cutting and precooling (SCCP) before freezing. The metabolic status was evaluated by metabolomics before freezing, and quality attributes were analyzed through the water-holding capacity and texture properties of dorsal muscle during frozen storage. The results showed that quality loss followed the order of CS > SCC > SCCP, as revealed by thawing loss, cooking loss, and springiness. A total of 654 metabolites were identified from pufferfish samples; 33 and 25 differential metabolites were screened from the SCC/CS and SCCP/CS groups, respectively. Different pre-freezing handling methods significantly affected arginine and histidine metabolism, fatty acid biosynthesis, and purine metabolism, which may inhibit protein denaturation and ice crystal growth, thereby slowing the quality degradation of frozen pufferfish.PMID:37803762 | DOI:10.1016/j.foodres.2023.113423

Effect of inoculating Pichia spp. starters on flavor formation of fermented chili pepper: Metabolomics and genomics approaches

Sat, 07/10/2023 - 12:00
Food Res Int. 2023 Nov;173(Pt 2):113397. doi: 10.1016/j.foodres.2023.113397. Epub 2023 Aug 23.ABSTRACTThe influence of Pichia spp. on flavor formation and metabolic pathways during chili pepper fermentation was investigated in this study. Multiple omics approaches were employed, including metabolomics analysis to identify volatile and non-volatile flavor compounds, and genomic analysis to gain insights into the underlying molecular mechanism driving flavor formation of chili peppers inoculated with Pichia spp. The results showed that inoculation with Pichia spp. accelerated fermentation process of chili peppers compared to spontaneous fermentation. Metabolomics analysis showed P. fermentans promoted characteristic terpenes [e.g., (Z)-β-ocimene and linalool], L-glutamate, gamma-aminobutyric acid, and succinate production, while P. manshurica produced more alcohols (e.g., isoamyl alcohol and phenylethyl alcohol) and phenols (e.g., 4-ethylguaiacol and 2-methoxy-4-methylphenol). Genomics analysis revealed that a substantial portion of the genes in Pichia spp. were associated with amino acid and carbohydrate metabolism. Specifically, the pathways involved in amino acid metabolism and the release of glycoside-bound aromatic compounds were identified as the primary drivers behind the unique flavor of fermented chili peppers, facilitated by Pichia spp.PMID:37803735 | DOI:10.1016/j.foodres.2023.113397

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