PubMed

Microbiol Spectr. 2023 Apr 10:e0206722. doi: 10.1128/spectrum.02067-22. Online ahead of print.ABSTRACTHepatectomy is a common clinical procedure for the treatment of many liver diseases, and the successful recovery of a patient's liver metabolism and function after surgery is crucial for a good prognosis. The objective of this study was to elucidate the metabolic response to hepatectomy using high-throughput sequencing analysis of 16S rRNA gene, metabolomics, and proteomics data. Fecal and serum samples from beagle dogs were collected on day 0 (LH0), day 7 (LH7), and day 28 (LH28) after laparoscopic partial hepatectomy. Liver tissue samples were taken on LH0 and LH7. Dysbiosis in the fecal microbiota was explored, and host-microbiome interactions based on global metabolic and protein profiles and inflammatory processes were determined. Results showed that the relative abundance of Allobaculum and Turicibacter was decreased and that of Escherichia-Shigella was increased after hepatectomy (P < 0.05); the phenylalanine, tyrosine, and tryptophan biosynthetic pathway, along with the phenylalanine and aminoacyl-tRNA biosynthetic pathway, was significantly associated with liver injury. The serum metabolites l-phenylalanine and l-arginine were useful as biomarkers, and the fecal metabolite l-threonine was a signature target monitor for liver recovery. The proteomics profile revealed 412 significantly different proteins and further highlighted two key signaling pathways (mitogen-activated protein kinase [MAPK] and peroxisome proliferator-activated receptor [PPAR]) involved in the response to liver injury. We systematically explored the metabolic mechanism of liver injury and recovery, providing new insights into effective ways to promote recovery after hepatectomy and improve liver function and long-term survival. These fundamental studies on hepatectomy will provide the basis for future advances in treatment and recovery from common liver diseases. IMPORTANCE As the largest parenchymal organ, the liver is a target for bacterial and viral infections, nonalcoholic fatty liver disease (NAFLD), cirrhosis, cancer, and many other diseases, constituting a serious worldwide problem. The treatment for many of these diseases involves hepatectomy. Here, we show that aberrant inflammatory processes after hepatectomy of the liver as reflected in the association between liver metabolism and gut microbiota create a grave risk. This study investigated the mechanisms of gut microbiota and host metabolism involved in liver injury and recovery after hepatectomy, using proteomics to reveal the mechanisms of postoperative liver injury and a comprehensive multi-omics approach to identify changes in metabolism after hepatectomy.PMID:37036349 | DOI:10.1128/spectrum.02067-22

Curr Protoc. 2023 Apr;3(4):e720. doi: 10.1002/cpz1.720.ABSTRACTWith the rapid increase in clinical exome and genome sequencing, the number of variants of uncertain significance (VUS) that are reported continues to rise, which poses a significant barrier to interpretation of genetic findings. For metabolic disorders, biochemical testing can help alleviate this burden of variant interpretation by providing functional validation of uncertain genetic findings in many cases. However, a major limitation of traditional biochemical testing is the targeted, narrow range of analytes clinically available, resulting in delays in diagnosis if testing is negative. Untargeted metabolomic screening offers higher diagnostic yield and assays for thousands of metabolites across multiple metabolic pathways in a single test, saving time and resources for patients, families, and physicians. When integrated with exome or genome sequencing, untargeted metabolomic screening improves diagnostic outcomes by providing functional validation of genetic findings, particularly for VUS. Here, we present representative cases across the breadth of metabolic pathways as examples of the utility of metabolomics in genomic variant classification. © 2023 Wiley Periodicals LLC.PMID:37036266 | DOI:10.1002/cpz1.720

J Vis Exp. 2023 Mar 24;(193). doi: 10.3791/65029.ABSTRACTHuman industries generate hundreds of thousands of chemicals, many of which have not been adequately studied for environmental safety or effects on human health. This deficit of chemical safety information is exacerbated by current testing methods in mammals that are expensive, labor-intensive, and time-consuming. Recently, scientists and regulators have been working to develop new approach methodologies (NAMs) for chemical safety testing that are cheaper, more rapid, and reduce animal suffering. One of the key NAMs to emerge is the use of invertebrate organisms as replacements for mammalian models to elucidate conserved chemical modes of action across distantly related species, including humans. To advance these efforts, here, we describe a method that uses the fruit fly, Drosophila melanogaster, to assess chemical safety. The protocol describes a simple, rapid, and inexpensive procedure to measure the viability and feeding behavior of exposed adult flies. In addition, the protocol can be easily adapted to generate samples for genomic and metabolomic approaches. Overall, the protocol represents an important step forward in establishing Drosophila as a standard model for use in precision toxicology.PMID:37036230 | DOI:10.3791/65029

Bioact Mater. 2023 Mar 28;26:452-464. doi: 10.1016/j.bioactmat.2023.03.012. eCollection 2023 Aug.ABSTRACTDeveloping functional ductal organoids (FDOs) is essential for liver regenerative medicine. We aimed to construct FDOs with biliary tree networks in rat decellularized liver scaffolds (DLSs) with primary cholangiocytes isolated from mouse bile ducts. The developed FDOs were dynamically characterized by functional assays and metabolomics for bioprocess clarification. FDOs were reconstructed in DLSs retaining native structure and bioactive factors with mouse primary cholangiocytes expressing enriched biomarkers. Morphological assessment showed that biliary tree-like structures gradually formed from day 3 to day 14. The cholangiocytes in FDOs maintained high viability and expressed 11 specific biomarkers. Basal-apical polarity was observed at day 14 with immunostaining for E-cadherin and acetylated α-tubulin. The rhodamine 123 transport assay and active collection of cholyl-lysyl-fluorescein exhibited the specific functions of bile secretion and transportation at day 14 compared to those in monolayer and hydrogel culture systems. The metabolomics analysis with 1075 peak pairs showed that serotonin, as a key molecule of the tryptophan metabolism pathway linked to biliary tree reconstruction, was specifically expressed in FDOs during the whole period of culture. Such FDOs with biliary tree networks and serotonin expression may be applied for disease modeling and drug screening, which paves the way for future clinical therapeutic applications.PMID:37035760 | PMC:PMC10073412 | DOI:10.1016/j.bioactmat.2023.03.012

World J Diabetes. 2023 Mar 15;14(3):255-270. doi: 10.4239/wjd.v14.i3.255.ABSTRACTBACKGROUND: In recent years, the incidence of type 2 diabetes (T2DM) has shown a rapid growth trend. Goto Kakizaki (GK) rats are a valuable model for the study of T2DM and share common glucose metabolism features with human T2DM patients. A series of studies have indicated that T2DM is associated with the gut microbiota composition and gut metabolites. We aimed to systematically characterize the faecal gut microbes and metabolites of GK rats and analyse the relationship between glucose and insulin resistance.AIM: To evaluate the gut microbial and metabolite alterations in GK rat faeces based on metagenomics and untargeted metabolomics.METHODS: Ten GK rats (model group) and Wistar rats (control group) were observed for 10 wk, and various glucose-related indexes, mainly including weight, fasting blood glucose (FBG) and insulin levels, homeostasis model assessment of insulin resistance (HOMA-IR) and homeostasis model assessment of β cell (HOMA-β) were assessed. The faecal gut microbiota was sequenced by metagenomics, and faecal metabolites were analysed by untargeted metabolomics. Multiple metabolic pathways were evaluated based on the differential metabolites identified, and the correlations between blood glucose and the gut microbiota and metabolites were analysed.RESULTS: The model group displayed significant differences in weight, FBG and insulin levels, HOMA-IR and HOMA-β indexes (P < 0.05, P < 0.01) and a shift in the gut microbiota structure compared with the control group. The results demonstrated significantly decreased abundances of Prevotella sp. CAG:604 and Lactobacillus murinus (P < 0.05) and a significantly increased abundance of Allobaculum stercoricanis (P < 0.01) in the model group. A correlation analysis indicated that FBG and HOMA-IR were positively correlated with Allobaculum stercoricanis and negatively correlated with Lactobacillus murinus. An orthogonal partial least squares discriminant analysis suggested that the faecal metabolic profiles differed between the model and control groups. Fourteen potential metabolic biomarkers, including glycochenodeoxycholic acid, uric acid, 13(S)-hydroxyoctadecadienoic acid (HODE), N-acetylaspartate, β-sitostenone, sphinganine, 4-pyridoxic acid, and linoleic acid, were identified. Moreover, FBG and HOMA-IR were found to be positively correlated with glutathione, 13(S)-HODE, uric acid, 4-pyridoxic acid and allantoic acid and ne-gatively correlated with 3-α, 7-α, chenodeoxycholic acid glycine conjugate and 26-trihydroxy-5-β-cholestane (P < 0.05, P < 0.01). Allobaculum stercoricanis was positively correlated with linoleic acid and sphinganine (P < 0.01), and 2-methyl-3-hydroxy-5-formylpyridine-4-carboxylate was negatively associated with Prevotella sp. CAG:604 (P < 0.01). The metabolic pathways showing the largest differences were arginine biosynthesis; primary bile acid biosynthesis; purine metabolism; linoleic acid metabolism; alanine, aspartate and glutamate metabolism; and nitrogen metabolism.CONCLUSION: Metagenomics and untargeted metabolomics indicated that disordered compositions of gut microbes and metabolites may be common defects in GK rats.PMID:37035219 | PMC:PMC10075032 | DOI:10.4239/wjd.v14.i3.255

Front Plant Sci. 2023 Mar 24;14:1155258. doi: 10.3389/fpls.2023.1155258. eCollection 2023.ABSTRACTPlants have evolved circadian clock systems that enable biological processes to occur in tandem with periodic changes in the environment. However, it is largely unknown whether crosstalk occurs between the circadian clock and the response to herbicide in rice. We identified 19 conserved rhythmic metabolites which were response to pesticide application and their metabolic abundance peaked mainly at ZT2 or ZT14-ZT18. We found a series of glyphosate, s-Metolachlor, fenclorim, metcamifen and GA3 response genes were expressed following stable circadian rhythms. In order to determine the patterns of their temporal expression, co-expression network analysis was done on 10,467 genes that were periodically expressed throughout a 24-hour period. Next, we identified 4,031 potential direct target genes of OsCCA1 in using DAP-seq data for OsCCA1. Of these, 339, 22, 53, 53 and 63 genes showed a response to glyphosate, s-Metolachlor, fenclorim, metcamifen and GA3 application, respectively. And they were mainly phased from dusk to midnight. Interestingly, we identified significant OsCCA1 binding peaks in the promoter regions of four herbicide resistance genes, including OsCYP81A12, OsCYP81E22, OsCYP76C2, and OsCYP76C4. Finally, we found that herbicide application could affects the expression of some of the central oscillator genes of the rice circadian clock. Here, we used multi-omics data to reveal the crosstalk between the circadian clock and herbicide response processes at the epigenomics, transcriptome, and metabolome levels in rice. This work will serve as a theoretical guide for identifying rhythmic herbicide targets, leading to the creation of new herbicides or the breeding of crops resistant to herbicides.PMID:37035069 | PMC:PMC10080033 | DOI:10.3389/fpls.2023.1155258

Front Plant Sci. 2023 Mar 22;14:1025932. doi: 10.3389/fpls.2023.1025932. eCollection 2023.ABSTRACTWhile Cannabis sativa L. varieties have been traditionally characterized by their major cannabinoid profile, it is now well established that other plant metabolites can also have physiological effects, including minor cannabinoids, terpenes, and flavonoids. Given the multiple applications of cannabis in the medical field, it is therefore critical to characterize it according to its chemical composition (i.e., its metabolome) and not only its botanical traits. With this in mind, the cannabinoid and metabolomic profiles from inflorescences of two C. sativa varieties with either high Δ9-tetrahydrocannabinolic acid (THCA) or high cannabidiolic acid (CBDA) contents harvested at different times were studied. According to results from HPLC and NMR-based untargeted metabolomic analyses of organic and aqueous plant material extracts, we show that in addition to expected variations according to cannabinoid profiles, it is possible to distinguish between harvests of the same variety. In particular, it was possible to correlate variations in the metabolome with presence of powdery mildew, leading to the identification of molecular markers associated with this fungal infection in C. sativa.PMID:37035042 | PMC:PMC10075229 | DOI:10.3389/fpls.2023.1025932

Front Plant Sci. 2023 Mar 24;14:1159511. doi: 10.3389/fpls.2023.1159511. eCollection 2023.ABSTRACTBupleurum scorzonerifolium Willd. is a medicinal herb. Its root has a high content of volatile oil (BSVO), which shows a variety of biological activities. Currently, BSVO in the injectable form is used for treating fever in humans and livestock. The yield and quality of volatile oils depends on the developmental stages of plants. However, the changes in BSVO yield and quality during root development in Bupleurum scorzonerifolium and the underlying molecular regulatory mechanisms remain unclear. This knowledge gap is limiting the improvement in the quality of BSVO. In the present study, B. scorzonerifolium root was collected at germinative, vegetative, florescence, fruiting and defoliating stages. The yield of BSVO, metabolic profile of volatile components and transcriptome of root samples at various developmental stages were comprehensively determined and compared. BSVO continuously accumulated from the germinative to fruiting stages, and its level slightly decreased from the fruiting to defoliating stages. A total of 82 volatile components were detected from B. scorzonerifolium root, of which 22 volatiles were identified as differentially accumulated metabolites (DAMs) during the root development. Of these volatiles, fatty acids and their derivatives accounted for the largest proportion. The contents of most major volatiles were highest at the fruiting stage. A large number of differentially expressed genes (DEGs) were detected during B. scorzonerifolium root development, of which 65 DEGs encoded various enzymes and transcription factors regulating the biosynthesis of fatty acids and their derivatives. In further analysis, 42 DEGs were identified to be significantly correlated with DAMs, and these DEGs may be the key genes for the biosynthesis of volatiles. To the best of our knowledge, this is the first study to comprehensively report the changes in the composition and content of volatiles and underlying mechanism during B. scorzonerifolium root development. This study provided important reference for future studies to determine the harvest time of B. scorzonerifolium roots and improve the quality of BSVO.PMID:37035038 | PMC:PMC10079991 | DOI:10.3389/fpls.2023.1159511

Res Sq. 2023 Mar 29:rs.3.rs-2674668. doi: 10.21203/rs.3.rs-2674668/v1. Preprint.ABSTRACTIdentifying genes whose expression is associated with schizophrenia (SCZ) risk by transcriptome-wide association studies (TWAS) facilitates downstream experimental studies. Here, we integrated multiple published datasets of TWAS (including FUSION, PrediXcan, summary-data-based Mendelian randomization (SMR), joint-tissue imputation approach with Mendelian randomization (MR-JTI)), gene coexpression, and differential gene expression analysis to prioritize SCZ candidate genes for functional study. Convergent evidence prioritized Propionyl-CoA Carboxylase Subunit Beta ( PCCB ), a nuclear-encoded mitochondrial gene, as an SCZ risk gene. However, the PCCB ’s contribution to SCZ risk has not been investigated before. Using dual luciferase reporter assay, we identified that SCZ-associated SNP rs35874192, an eQTL SNP for PCCB , showed differential allelic effects on transcriptional activities. PCCB knockdown in human forebrain organoids (hFOs) followed by RNA-seq revealed dysregulation of genes enriched with multiple neuronal functions including gamma-aminobutyric acid (GABA)-ergic synapse, as well as genes dysregulated in postmortem brains of SCZ patients or in cerebral organoids derived from SCZ patients. The metabolomic and mitochondrial function analyses confirmed the deceased GABA levels resulted from reduced tricarboxylic acid cycle in PCCB knockdown hFOs. Multielectrode array recording analysis showed that PCCB knockdown in hFOs resulted into SCZ-related phenotypes including hyper-neuroactivities and decreased synchronization of neural network. In summary, this study utilized hFOs-based multi-omics data and revealed that PCCB downregulation may contribute to SCZ risk through regulating GABAergic system, highlighting the mitochondrial function in SCZ.PMID:37034773 | PMC:PMC10081387 | DOI:10.21203/rs.3.rs-2674668/v1

bioRxiv. 2023 Mar 30:2023.03.25.534225. doi: 10.1101/2023.03.25.534225. Preprint.ABSTRACTBiological interpretation of metabolomics datasets often ends at a pathway analysis step to find the over-represented metabolic pathways in the list of statistically significant metabolites. However, definitions of biochemical pathways and metabolite coverage vary among different curated databases, leading to inaccurate and contradicting interpretations. For the lists of gene, transcripts and proteins, Gene Ontology (GO) terms over-presentation analysis has become a standardized approach for the biological interpretation. GO terms are not limited to predefined pathways but can also include relevant metabolic processes that are not included in pathway databases. Despite the several advantages of GO terms over traditional pathway maps, GO analysis has not been achieved for metabolomics datasets. To overcome this, we present a new knowledgebase and the online tool, Gene Ontology Analysis by the Integrated Data Science Laboratory for Metabolomics and Exposomics (IDSL.GOA) to conduct GO over-representation analysis for a metabolite list. The IDSL.GOA knowledgebase covers 2,324 metabolic GO terms and associated 2,818 genes, 22,264 transcripts, 20,158 proteins, 1,482 EC annotations, 2,430 reactions and 2,212 metabolites. IDSL.GOA analysis of a case study of older vs young female brain cortex metabolome highlighted over 250 GO terms being significantly overrepresented (FDR <0.05). The analysis suggested that in the older female brain cortex region, nucleotide salvage processes are severely affected. On contrast, for the same metabolite list, MetaboAnalyst and Reactome Pathway Analysis suggested less than 5 pathways at FDR <0.05, and none of them were related to nucleotide salvage pathways. We showed how IDSL.GOA identified key and relevant GO metabolic processes that were not mentioned by alternative pathway analysis approaches. Overall, we suggest that metabolomics researchers should not limit the interpretation of metabolite lists to only pathway maps and can also leverage GO terms as well. IDSL.GOA provides a powerful tool for this purpose, allowing for a more comprehensive and accurate analysis of metabolite pathway data. IDSL.GOA tool can be accessed at https://goa.idsl.me/.PMID:37034715 | PMC:PMC10081191 | DOI:10.1101/2023.03.25.534225

medRxiv. 2023 Mar 30:2023.03.29.23287640. doi: 10.1101/2023.03.29.23287640. Preprint.ABSTRACTINTRODUCTION: Epilepsy is a common central nervous system disorder characterized by abnormal brain electrical activity. We aimed to compare the metabolic profiles of plasma from patients with epilepsy across different etiologies, seizure frequency, seizure type, and patient age to try to identify common disrupted pathways.MATERIAL AND METHODS: We used data from three separate cohorts. The first cohort (PED-C) consisted of 31 pediatric patients with suspicion of a genetic disorder with unclear etiology; the second cohort (AD-C) consisted of 250 adults from the Estonian Biobank (EstBB), and the third cohort consisted of 583 adults ≥ 69 years of age from the EstBB (ELD-C). We compared untargeted metabolomics and lipidomics data between individuals with and without epilepsy in each cohort.RESULTS: In the PED-C, significant alterations (p-value <0.05) were detected in sixteen different glycerophosphatidylcholines (GPC), dimethylglycine and eicosanedioate (C20-DC). In the AD-C, nine significantly altered metabolites were found, mainly triacylglycerides (TAG), which are also precursors in the GPC synthesis pathway. In the ELD-C, significant changes in twenty metabolites including multiple TAGs were observed in the metabolic profile of participants with previously diagnosed epilepsy. Pathway analysis revealed that among the metabolites that differ significantly between epilepsy-positive and epilepsy-negative patients in the PED-C, the lipid superpathway (p = 3.2*10-4) and phosphatidylcholine (p = 9.3*10-8) and lysophospholipid (p = 5.9*10-3) subpathways are statistically overrepresented. Analogously, in the AD-C, the triacylglyceride subclass turned out to be statistically overrepresented (p = 8.5*10-5) with the lipid superpathway (p = 1.4*10-2). The presented p-values are FDR-corrected.CONCLUSION: Our results suggest that cell membrane fluidity may have a significant role in the mechanism of epilepsy, and changes in lipid balance may indicate epilepsy. However, further studies are needed to evaluate whether untargeted metabolomics analysis could prove helpful in diagnosing epilepsy earlier.PMID:37034709 | PMC:PMC10081398 | DOI:10.1101/2023.03.29.23287640

Res Sq. 2023 Mar 28:rs.3.rs-2652887. doi: 10.21203/rs.3.rs-2652887/v1. Preprint.ABSTRACTAmbient air pollution has been associated with bone damage. However, no studies have evaluated the metabolomic response to air pollutants and its potential influence on bone health in postmenopausal women. We analyzed data from WHI participants with plasma samples. Whole-body, total hip, femoral neck, and spine BMD at enrollment and follow-up (Y1, Y3, Y6). Daily particulate matter NO, NO 2 , PM 10 and SO 2 were averaged over 1-, 3-, and 5-year periods before metabolomic assessments. Statistical analyses included multivariable-adjusted linear mixed models, pathways analyses, and mediation modeling. NO, NO 2 , and SO 2 , but not PM 10 , were associated with taurine, inosine, and C38:4 phosphatidylethanolamine (PE), at all averaging periods. We found a partial mediation of C38:4 PE in the association between 1-year average NO and lumbar spine BMD ( p -value: 0.032). This is the first study suggesting that a PE may partially mediate air pollution-related bone damage in postmenopausal women.PMID:37034583 | PMC:PMC10081369 | DOI:10.21203/rs.3.rs-2652887/v1

bioRxiv. 2023 Mar 28:2023.03.27.534395. doi: 10.1101/2023.03.27.534395. Preprint.ABSTRACTT-cell Acute Lymphoblastic Leukemia (T-ALL) is a hematological malignancy in need of novel therapeutic approaches. Here, we identify the ATP-citrate lyase ACLY as a novel therapeutic target in T-ALL. Our results show that ACLY is overexpressed in T-ALL, and its expression correlates with NOTCH1 activity. To test the effects of ACLY in leukemia progression and the response to NOTCH1 inhibition, we developed an isogenic model of NOTCH1-induced Acly conditional knockout leukemia. Importantly, we observed intrinsic antileukemic effects upon loss of ACLY, which further synergized with NOTCH1 inhibition in vivo . Gene expression profiling analyses showed that the transcriptional signature of ACLY loss very significantly correlates with the signature of NOTCH1 inhibition in vivo , with significantly downregulated pathways related to oxidative phosphorylation, electron transport chain, ribosomal biogenesis and nucleosome biology. Consistently, metabolomic profiling upon ACLY loss revealed a metabolic crisis with accumulation of nucleotide intermediates and reduced levels of several amino acids. Overall, our results identify a link between NOTCH1 and ACLY and unveil ACLY as a novel promising target for T-ALL treatment.PMID:37034581 | PMC:PMC10081278 | DOI:10.1101/2023.03.27.534395

Adv Redox Res. 2023 Apr;7:100065. doi: 10.1016/j.arres.2023.100065. Epub 2023 Feb 18.ABSTRACTCadmium (Cd) is a toxic environmental metal that interacts with selenium (Se) and contributes to many lung diseases. Humans have widespread exposures to Cd through diet and cigarette smoking, and studies in rodent models show that Se can protect against Cd toxicities. We sought to identify whether an antagonistic relationship existed between Se and Cd burdens and determine whether this relationship may associate with metabolic variation within human lungs. We performed metabolomics of 31 human lungs, including 25 with end-stage lung disease due to idiopathic pulmonary fibrosis, cystic fibrosis, chronic obstructive lung disease (COPD)/emphysema and other causes, and 6 non-diseased lungs. Results showed pathway associations with Cd including amino acid, lipid and energy-related pathways. Metabolic pathways varying with Se had considerable overlap with these pathways. Hierarchical cluster analysis (HCA) of individuals according to metabolites associated with Cd showed partial separation of disease types, with COPD/emphysema in the cluster with highest Cd, and non-diseased lungs in the cluster with the lowest Cd. When compared to HCA of metabolites associated with Se, the results showed that the cluster containing COPD/emphysema had the lowest Se, and the non-diseased lungs had the highest Se. A greater number of pathway associations occurred for Cd to Se ratio than either Cd or Se alone, indicating that metabolic patterns were more dependent on Cd to Se ratio than on either alone. Network analysis of interactions of Cd and Se showed network centrality was associated with pathways linked to polyunsaturated fatty acids involved in inflammatory signaling. Overall, the data show that metabolic pathway responses in human lung vary with Cd and Se in a pattern suggesting that Se is antagonistic to Cd toxicity in humans.PMID:37034445 | PMC:PMC10078579 | DOI:10.1016/j.arres.2023.100065

Front Allergy. 2023 Mar 24;4:1149008. doi: 10.3389/falgy.2023.1149008. eCollection 2023.ABSTRACTThe prevalence of food allergy continues to rise globally, carrying with it substantial safety, economic, and emotional burdens. Although preventative strategies do exist, the heterogeneity of allergy trajectories and clinical phenotypes has made it difficult to identify patients who would benefit from these strategies. Therefore, further studies investigating the molecular mechanisms that differentiate these trajectories are needed. Large-scale omics studies have identified key insights into the molecular mechanisms for many different diseases, however the application of these technologies to uncover the drivers of food allergy development is in its infancy. Here we review the use of omics approaches in food allergy and highlight key gaps in knowledge for applying these technologies for the characterization of food allergy development.PMID:37034151 | PMC:PMC10080041 | DOI:10.3389/falgy.2023.1149008

Front Immunol. 2023 Mar 22;14:1140564. doi: 10.3389/fimmu.2023.1140564. eCollection 2023.ABSTRACTBacillus licheniformis (B. licheniformis) is a well-accepted probiotic that has many benefits on both humans and animals. This study explored the effects of B. licheniformis on growth performance, intestinal mucosal barrier functions, immunity as well as serum metabolome in the weaned piglets exposed to lipopolysaccharide (LPS). One hundred and twenty piglets weaned at four weeks of age were separated into two groups that received a basal diet (the control group, CON), and a basal diet complemented with B. licheniformis (500 mg/kg, the BL group, BL). Twenty-four piglets were chosen from the above two groups and 12 piglets were injected with LPS intraperitoneally at a concentration of 100 μg/kg and the others were injected with sterile saline solution of the same volume. All the piglets were sacrificed 4 h after LPS challenge. Results showed that B. licheniformis enhanced the ADG and final body weight and lowered the F/G and diarrhea rate. Pre-treatment with B. licheniformis markedly attenuated intestinal mucosal damage induced by LPS challenge. Supplementation with B. licheniformis strengthened immune function and suppressed inflammatory response by elevating the concentrations of serum immunoglobulin (Ig) A and jejunum mucosal IgA and IgG and decreasing serum IL-6 and jejunum mucosal IL-1β. In addition, B. licheniformis pretreatment prevented LPS-induced intestinal injury by regulating the NLRP3 inflammasome. Furthermore, pretreatment with B. licheniformis tended to reverse the reduction of acetate and propionic acids in the colonic contents that occurred due to LPS stress. B. licheniformis markedly modulated the metabolites of saccharopine and allantoin from lysine and purine metabolic pathways, respectively. Overall, these data emphasize the potentiality of B. licheniformis as a dietary supplement to overcome the challenge of bacterial LPS in the animal and to enhance the food safety.PMID:37033995 | PMC:PMC10073459 | DOI:10.3389/fimmu.2023.1140564

Front Immunol. 2023 Mar 23;14:1158137. doi: 10.3389/fimmu.2023.1158137. eCollection 2023.ABSTRACTINTRODUCTION: Test anxiety is a common issue among college students, which can affect their physical and psychological health. However, effective interventions or therapeutic strategies are still lacking. This study aims to evaluate the potential effects of Lactobacillus plantarum JYLP-326 on test anxious college students.METHODS: Sixty anxious students were enrolled and randomly allocated to the placebo group and the probiotic group. Both groups were instructed to take placebo and JYLP-326 products twice per day for three weeks, respectively. Thirty unanxious students with no treatments were assigned to a regular control group. The anxiety, depression, and insomnia questionnaires were used to measure students' mental states at the baseline and the end of this study. 16S rRNA sequencing and untargeted metabolomics were performed to analyze the changes in the gut microbiota and fecal metabolism.RESULTS: The questionnaire results suggested that JYLP-326 administration could relieve the symptoms of anxiety, depression, and insomnia in test anxious students. The gut microbiomes of the placebo group showed a significantly greater diversity index than the control group (p < 0.05). An increased abundance of Bacteroides and Roseburia at the genus level was observed in the placebo group, and the relative abundance of Prevotella and Bifidobacterium decreased. Whereas, JYLP-326 administration could partly restore the disturbed gut microbiota. Additionally, test anxiety was correlated with disordered fecal metabolomics such as a higher Ethyl sulfate and a lower Cyclohexylamine, which could be reversed after taking JYLP-326. Furthermore, the changed microbiota and fecal metabolites were significantly associated with anxiety-related symptoms.CONCLUSION: The results indicate that the intervention of L. plantarum JYLP-326 could be an effective strategy to alleviate anxiety, depression, and insomnia in test anxious college students. The potential mechanism underlying this effect could be related to the regulation of gut microbiota and fecal metabolites.PMID:37033942 | PMC:PMC10077425 | DOI:10.3389/fimmu.2023.1158137

Front Immunol. 2023 Mar 23;14:1116760. doi: 10.3389/fimmu.2023.1116760. eCollection 2023.ABSTRACTINTRODUCTION: Immunometabolism examines the links between immune cell function and metabolism. Dysregulation of immune cell metabolism is now an established feature of innate immune cell activation. Advances in liquid chromatography mass spectrometry (LC-MS) technologies have allowed discovery of unique insights into cellular metabolomics. Here we have studied and compared different sample preparation techniques and data normalisation methods described in the literature when applied to metabolomic profiling of human monocytes.METHODS: Primary monocytes stimulated with lipopolysaccharide (LPS) for four hours was used as a study model. Monocytes (n=24) were freshly isolated from whole blood and stimulated for four hours with lipopolysaccharide (LPS). A methanol-based extraction protocol was developed and metabolomic profiling carried out using a Hydrophilic Interaction Liquid Chromatography (HILIC) LC-MS method. Data analysis pipelines used both targeted and untargeted approaches, and over 40 different data normalisation techniques to account for technical and biological variation were examined. Cytokine levels in supernatants were measured by ELISA.RESULTS: This method provided broad coverage of the monocyte metabolome. The most efficient and consistent normalisation method was measurement of residual protein in the metabolite fraction, which was further validated and optimised using a commercial kit. Alterations to the monocyte metabolome in response to LPS can be detected as early as four hours post stimulation. Broad and profound changes in monocyte metabolism were seen, in line with increased cytokine production. Elevated levels of amino acids and Krebs cycle metabolites were noted and decreases in aspartate and β-alanine are also reported for the first time. In the untargeted analysis, 154 metabolite entities were significantly altered compared to unstimulated cells. Pathway analysis revealed the most prominent changes occurred to (phospho-) inositol metabolism, glycolysis, and the pentose phosphate pathway.DISCUSSION: These data report the emergent changes to monocyte metabolism in response to LPS, in line with reports from later time points. A number of these metabolites are reported to alter inflammatory gene expression, which may facilitate the increases in cytokine production. Further validation is needed to confirm the link between metabolic activation and upregulation of inflammatory responses.PMID:37033938 | PMC:PMC10077522 | DOI:10.3389/fimmu.2023.1116760

ACS Omega. 2023 Mar 21;8(13):12310-12326. doi: 10.1021/acsomega.3c00019. eCollection 2023 Apr 4.ABSTRACTThe pathophysiological mechanisms of acute pancreatitis (AP) are complex and have remained a mystery to date, but metabolism is gradually recognized as an important driver of AP onset and development. We used a cerulein-induced AP mouse model to conduct liquid chromatography-mass spectrometry (LC-MS/MS)-based time-course proteomics and lipidomics in order to better understand the underlying metabolic alterations linked with AP. Results showed that a series of significant changes in proteins over time with a boost in expression were enriched in lipase activity, lipoprotein, and lipids absorption and transport regulation. Furthermore, 16 proteins associated with lipid metabolism and signaling pathways together with the whole lipid species changing profile led to the vital identification of changing law in glycerides, phosphoglycerides, and free fatty acids. In addition to lipid metabolism and regulation-associated proteins, several digestive enzymes and adaptive anti-trypsin, stress response, and energy metabolism-related proteins showed an increment in abundance. Notably, central carbon and branched chain amino acid metabolism were enhanced during 0-24 h from the first cerulein stimulation. Taken together, this integrated proteomics and lipidomics revealed a novel metabolic insight into metabolites transforming rules that might be relevant to their function and drug targets investigation. (Created with Biorender.com.).PMID:37033809 | PMC:PMC10077560 | DOI:10.1021/acsomega.3c00019

Front Pharmacol. 2023 Mar 22;14:1092693. doi: 10.3389/fphar.2023.1092693. eCollection 2023.ABSTRACTRhizoma Gastrodia (Orchidaceae; Gastrodia elata Blume), the rhizome of Gastrodia elata Blume (GE), is traditionally used as both a medicinal and functional food, with proven efficacy in treating mental disorders. In traditional processing, GE is washed, steamed with water, dried, and sliced. In this study, a novel processing technology-alcohol steamed GE (AGE) was proposed as an alternative. Totally, 17 compounds were identified in fresh GE and AGE. Compared with fresh GE, the relative content of parishin A and parishin E decreased after alcohol steaming, whereas gastrodin (GAS), p-hydroxylbenzyl alcohol (HBA), Parishin B, and Parishin C were increased. Additionally, the pentobarbital-induced sleep mice model and Chronic Restraint Stress (CRS) model were applied to evaluate the pharmacological effects of fresh GE and steamed GE, and both fresh and steamed GE showed an intensive hypnotic and anti-anxiety effect. Furthermore, the anti-anxiety mechanism based on serum metabolic was investigated and the tryptophan metabolic pathway was considered the response to the anti-anxiety effect of GE. Although the optimization of the processing technology of AGE still needs to be further explored, the current results have provided new thoughts for the processing technology and clinical application of GE.PMID:37033659 | PMC:PMC10073492 | DOI:10.3389/fphar.2023.1092693