PubMed

PLoS One. 2023 Jun 15;18(6):e0287121. doi: 10.1371/journal.pone.0287121. eCollection 2023.ABSTRACTMedulloblastoma is one of the most frequent malignant brain tumors in infancy and childhood. Early diagnosis and treatment are quite crucial for the prognosis. However, the pathogenesis of medulloblastoma is still not completely clarified. High-resolution mass spectrometry has enabled a comprehensive investigation on the mechanism of disease from the perspective of metabolism. Herein, we compared the difference of metabolic profiles of serum between medulloblastoma (n = 33) and healthy control (HC, n = 16) by using UPLC-Q/E-MS/MS. Principal component analysis and orthogonal projections to latent structures discriminant analysis (OPLS-DA) intuitively revealed the significantly distinct metabolic profiles between medulloblastoma and HC (p < 0.01 for permutation test on OPLS-DA model). Total of 25 significantly changed metabolites were identified. ROC analysis reported that six of them (Phosphatidic acid (8:0/15:0), 3'-Sialyllactose, Isocoproporphyrin, Acetylspermidine, Fructoseglycine and 3-Hydroxydodecanedioate) showed high specificity and precision to be potential diagnosis biomarkers (AUC > 0.98). Functional analysis discovered that there are four pathways notably perturbed for medulloblastoma. These pathways are related with the dysfunction of arachidonic acid metabolism, steroid hormone biosynthesis, and folate-related metabolism. The target intervention on these pathways may reduce the mortality of medulloblastoma.PMID:37319142 | DOI:10.1371/journal.pone.0287121

Proc Natl Acad Sci U S A. 2023 Jun 20;120(25):e2219373120. doi: 10.1073/pnas.2219373120. Epub 2023 Jun 15.ABSTRACTFungus-growing ants depend on a fungal mutualist that can fall prey to fungal pathogens. This mutualist is cultivated by these ants in structures called fungus gardens. Ants exhibit weeding behaviors that keep their fungus gardens healthy by physically removing compromised pieces. However, how ants detect diseases of their fungus gardens is unknown. Here, we applied the logic of Koch's postulates using environmental fungal community gene sequencing, fungal isolation, and laboratory infection experiments to establish that Trichoderma spp. can act as previously unrecognized pathogens of Trachymyrmex septentrionalis fungus gardens. Our environmental data showed that Trichoderma are the most abundant noncultivar fungi in wild T. septentrionalis fungus gardens. We further determined that metabolites produced by Trichoderma induce an ant weeding response that mirrors their response to live Trichoderma. Combining ant behavioral experiments with bioactivity-guided fractionation and statistical prioritization of metabolites in Trichoderma extracts demonstrated that T. septentrionalis ants weed in response to peptaibols, a specific class of secondary metabolites known to be produced by Trichoderma fungi. Similar assays conducted using purified peptaibols, including the two previously undescribed peptaibols trichokindins VIII and IX, suggested that weeding is likely induced by peptaibols as a class rather than by a single peptaibol metabolite. In addition to their presence in laboratory experiments, we detected peptaibols in wild fungus gardens. Our combination of environmental data and laboratory infection experiments strongly support that peptaibols act as chemical cues of Trichoderma pathogenesis in T. septentrionalis fungus gardens.PMID:37319116 | DOI:10.1073/pnas.2219373120

Anal Chem. 2023 Jun 15. doi: 10.1021/acs.analchem.3c00909. Online ahead of print.ABSTRACTAmino metabolites are essential for life activities and can be used clinically as biomarkers for disease diagnosis and treatment. Solid-phase-supported chemoselective probes can simplify sample handling and enhance detection sensitivity. However, the low efficiency and complicated preparation of traditional probes limit their further application. In this work, a novel solid-phase-supported probe Fe3O4-SiO2-polymers-phenyl isothiocyanate (FSP-PITC) was developed by immobilizing phenyl isothiocyanate on magnetic beads with disulfide as an orthogonal cleavage site, which can couple amino metabolites directly regardless of whether proteins and other matrixes were removed. After purification, the targeted metabolites were released by dithiothreitol and detected by high-resolution mass spectrometry. The simplified processing steps shorten the analysis time, and the introduction of polymers results in a 100-1000-fold increase in probe capacity. With high stability and specificity, FSP-PITC pretreatment allows accurate qualitative and quantitative (R2 > 0.99) analysis, facilitating the detection of metabolites in subfemtomole quantities. Using this strategy, 4158 metabolite signals were detected in negative ion mode. Among them, 352 amino metabolites including human cells (226), serum (227), and mouse samples (274) were searched from the Human Metabolome Database. These metabolites participate in metabolic pathways of amino acids, biogenic amine, and the urea cycle. All these results indicate that FSP-PITC is a promising probe for novel metabolite discovery and high-throughput screening.PMID:37318774 | DOI:10.1021/acs.analchem.3c00909

Biotechnol Lett. 2023 Jun 15. doi: 10.1007/s10529-023-03404-9. Online ahead of print.ABSTRACTPURPOSE: The accumulation of carbon dioxide during large-scale culture of animal cells brings adverse effects, appropriate aeration strategies alleviate CO2 accumulation while improper reactor operation may lead to the presence of low CO2 partial pressure (pCO2) condition as occurs in many industrial cases. Thus, this study aims to reveal the in-depth influence of low pCO2 on Chinese Hamster Ovary (CHO) cells for providing a reference for design space determination of CO2 control with regard to the Quality by Design (QbD) guidelines.METHODS AND RESULTS: The headspace air over purging caused the ultra-low pCO2 (ULC) where the monoclonal antibody production as well as the aerobic metabolic activity were reduced. Intracellular metabolomics analysis indicated a less efficient aerobic glucose metabolic state under ULC conditions. Based on the increase of intracellular pH and lactate dehydrogenase activity, the shortage of intracellular pyruvate could be the cause of the deficient aerobic metabolism, which could be partially mitigated by pyruvate addition under ULC conditions. Finally, a semi-empirical mathematical model was used to better understand, predict and control the occurrence of extreme pCO2 conditions during the cultures of CHO cells.CONCLUSION: Low pCO2 steers CHO cells into a defective metabolic state. A predictive relation among pCO2, lactate, and pH control was applied to get new insights into CHO cell culture for better and more robust metabolic behavior and process performance and the determination of QbD design space for CO2 control.PMID:37318718 | DOI:10.1007/s10529-023-03404-9

Appl Environ Microbiol. 2023 Jun 15:e0023823. doi: 10.1128/aem.00238-23. Online ahead of print.ABSTRACTMetabolic degeneracy describes the phenomenon that cells can use one substrate through different metabolic routes, while metabolic plasticity, refers to the ability of an organism to dynamically rewire its metabolism in response to changing physiological needs. A prime example for both phenomena is the dynamic switch between two alternative and seemingly degenerate acetyl-CoA assimilation routes in the alphaproteobacterium Paracoccus denitrificans Pd1222: the ethylmalonyl-CoA pathway (EMCP) and the glyoxylate cycle (GC). The EMCP and the GC each tightly control the balance between catabolism and anabolism by shifting flux away from the oxidation of acetyl-CoA in the tricarboxylic acid (TCA) cycle toward biomass formation. However, the simultaneous presence of both the EMCP and GC in P. denitrificans Pd1222 raises the question of how this apparent functional degeneracy is globally coordinated during growth. Here, we show that RamB, a transcription factor of the ScfR family, controls expression of the GC in P. denitrificans Pd1222. Combining genetic, molecular biological and biochemical approaches, we identify the binding motif of RamB and demonstrate that CoA-thioester intermediates of the EMCP directly bind to the protein. Overall, our study shows that the EMCP and the GC are metabolically and genetically linked with each other, demonstrating a thus far undescribed bacterial strategy to achieve metabolic plasticity, in which one seemingly degenerate metabolic pathway directly drives expression of the other. IMPORTANCE Carbon metabolism provides organisms with energy and building blocks for cellular functions and growth. The tight regulation between degradation and assimilation of carbon substrates is central for optimal growth. Understanding the underlying mechanisms of metabolic control in bacteria is of importance for applications in health (e.g., targeting of metabolic pathways with new antibiotics, development of resistances) and biotechnology (e.g., metabolic engineering, introduction of new-to-nature pathways). In this study, we use the alphaproteobacterium P. denitrificans as model organism to study functional degeneracy, a well-known phenomenon of bacteria to use the same carbon source through two different (competing) metabolic routes. We demonstrate that two seemingly degenerate central carbon metabolic pathways are metabolically and genetically linked with each other, which allows the organism to control the switch between them in a coordinated manner during growth. Our study elucidates the molecular basis of metabolic plasticity in central carbon metabolism, which improves our understanding of how bacterial metabolism is able to partition fluxes between anabolism and catabolism.PMID:37318336 | DOI:10.1128/aem.00238-23

Microbiol Spectr. 2023 Jun 15:e0002223. doi: 10.1128/spectrum.00022-23. Online ahead of print.ABSTRACTAlicyclobacillus acidoterrestris, which has strong acidophilic and heat-resistant properties, can cause spoilage of pasteurized acidic juice. The current study determined the physiological performance of A. acidoterrestris under acidic stress (pH 3.0) for 1 h. Metabolomic analysis was carried out to investigate the metabolic responses of A. acidoterrestris to acid stress, and integrative analysis with transcriptome data was also performed. Acid stress inhibited the growth of A. acidoterrestris and altered its metabolic profiles. In total, 63 differential metabolites, mainly enriched in amino acid metabolism, nucleotide metabolism, and energy metabolism, were identified between acid-stressed cells and the control. Integrated transcriptomic and metabolomic analysis revealed that A. acidoterrestris maintains intracellular pH (pHi) homeostasis by enhancing amino acids decarboxylation, urea hydrolysis, and energy supply, which was verified using real-time quantitative PCR and pHi measurement. Additionally, two-component systems, ABC transporters, and unsaturated fatty acid synthesis also play crucial roles in resisting acid stress. Finally, a model of the responses of A. acidoterrestris to acid stress was proposed. IMPORTANCE Fruit juice spoilage caused by A. acidoterrestris contamination has become a major concern and challenge in the food industry, and this bacterium has been suggested as a target microbe in the design of the pasteurization process. However, the response mechanisms of A. acidoterrestris to acid stress still remain unknown. In this study, integrative transcriptomic, metabolomic, and physiological approaches were used to uncover the global responses of A. acidoterrestris to acid stress for the first time. The obtained results can provide new insights into the acid stress responses of A. acidoterrestris, which will point out future possible directions for the effective control and application of A. acidoterrestris.PMID:37318333 | DOI:10.1128/spectrum.00022-23

J Agric Food Chem. 2023 Jun 15. doi: 10.1021/acs.jafc.3c01377. Online ahead of print.ABSTRACTHerbicide-resistant soybeans are among the most widely planted transgenic crops. The in situ evaluation of spatial lipidomics in transgenic and non-transgenic soybeans is important for directly assessing the unintended effects of exogenous gene introduction. In this study, matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI-MSI)-based non-targeted analytical strategies were used for the first time for in situ detection and imaging of endogenous lipid distributions in transgenic (EPSPS and PAT genes) herbicide-resistant soybean (Glycine max Merrill) (S4003.14) and non-transgenic soybean (JACK) seeds. Statistical analysis revealed significant differences in lipids between S4003.14 and JACK seeds. The variable importance of projection analysis further revealed that 18 identified lipids, including six phosphatidylcholines (PCs), four phosphatidylethanolamines (PEs), five triacylglycerols (TAGs), and three cytidine diphosphate-diacylglycerols (CDP-DAGs), had the strongest differential expression between S4003.14 and JACK seeds. Among those, the upregulated expressions of PC(P-36:1), PC(36:2), PC(P-36:0), PC(37:5), PE(40:2), TAG(52:1), TAG(55:5), and CDP-DAG(37:2) and the downregulated expressions of PC (36:1), TAG(43:0), and three PEs (i.e., PE(P-38:1), PE(P-38:0), and PE(P-40:3)) were successfully found in the S4003.14 seeds, compared to these lipids detected in the JACK seeds. Meanwhile, the lipids of PC (44:8), CDP-DAG(38:0), and CDP-DAG(42:0) were uniquely detected in the S4003.14 soybean seeds, and TAG(45:2) and TAG(57:10) were detected as the unique lipids in the JACK seeds. The heterogeneous distribution of these lipids in the soybean seeds was also clearly visualized using MALDI-MSI. MSI results showed that lipid expression was significantly up/downregulated in S4003.14 seeds, compared to that in JACK seeds. This study improves our understanding of the unintended effects of herbicide-resistant EPSPS and PAT gene transfers on spatial lipidomes in soybean seeds and enables the continued progression of MALDI-MSI as an emerging, reliable, and rapid molecular imaging tool for evaluating unintended effects in transgenic plants.PMID:37318082 | DOI:10.1021/acs.jafc.3c01377

J Exp Bot. 2023 Jun 15:erad230. doi: 10.1093/jxb/erad230. Online ahead of print.ABSTRACTFruit quality traits are determined to a large extent by their metabolome. The metabolite content of climacteric fruit changes drastically during ripening and postharvest storage and has been investigated extensively. However, the spatial distribution of metabolites and how it changes in time has received much less attention as fruit are usually considered as homogenous plant organs. Yet, spatio-temporal changes of starch, which is hydrolysed during ripening, has been used for ages as a ripening index. As vascular transport of water, and, hence, convective transport of metabolites slows down in mature fruit and even stalls after detachment, spatio-temporal changes in their concentration are likely affected by diffusive transport of gaseous molecules that act as substrate (O2), inhibitor (CO2) or regulator (ethylene, NO) of the metabolic pathways that are active during climacteric ripening. In this review we discuss such spatio-temporal changes of the metabolome and how they are affected by transport of metabolic gases and gaseous hormones. As there are currently no measurement techniques available to measure the metabolite distribution repeatedly by nondestructive means, we introduce reaction-diffusion models as an in silico tool to compute it. We show how the different components of such a model can be integrated and used to better understand the role of spatio-temporal changes of the metabolome in ripening and postharvest storage of climacteric fruit that is detached from the plant and discuss future research needs.PMID:37317945 | DOI:10.1093/jxb/erad230

Hosp Pediatr. 2023 Jun 15:e2022007012. doi: 10.1542/hpeds.2022-007012. Online ahead of print.ABSTRACTBiomarkers are commonly used in pediatric medicine to identify disease and guide clinical management for children. Biomarkers can be used to predict risk of disease, provide diagnostic clarification, and offer prognostic expectations. Specimens for biomarker testing might require noninvasive collection (eg, urine, exhaled breath) or invasive procedures (eg, blood, bronchoalveolar lavage) and testing might use various methodologies (eg, genomics, transcriptomics, proteomics, metabolomics). Specimen type and testing methodology depends on the disease of interest, ability to obtain sample, and availability of biomarker testing. To develop a new biomarker, researchers must first identify and validate the target, and then determine the test characteristics of the biomarker. Once it has undergone initial development and testing, a new biomarker is then tested in the clinical setting before being implemented into practice. An ideal biomarker is one that is feasible to obtain, readily quantifiable, and offers meaningful information that impacts care. Learning how to reliably interpret the performance and clinical application of a new biomarker is an important skillset for all pediatricians in the hospital setting. Here we provide a high-level overview of the process from biomarker discovery to application. In addition, we provide an example for the real-world application of biomarkers as an opportunity for clinicians to build on their ability to critically evaluate, interpret, and implement biomarkers in clinical practice.PMID:37317806 | DOI:10.1542/hpeds.2022-007012

Clin Transl Med. 2023 Jun;13(6):e1298. doi: 10.1002/ctm2.1298.ABSTRACTBACKGROUND: Differentiated thyroid cancer (DTC) affects thousands of lives worldwide each year. Typically, DTC is a treatable disease with a good prognosis. Yet, some patients are subjected to partial or total thyroidectomy and radioiodine therapy to prevent local disease recurrence and metastasis. Unfortunately, thyroidectomy and/or radioiodine therapy often worsen(s) quality of life and might be unnecessary in indolent DTC cases. On the other hand, the lack of biomarkers indicating a potential metastatic thyroid cancer imposes an additional challenge to managing and treating patients with this disease.AIM: The presented clinical setting highlights the unmet need for a precise molecular diagnosis of DTC and potential metastatic disease, which should dictate appropriate therapy.MATERIALS AND METHODS: In this article, we present a differential multi-omics model approach, including metabolomics, genomics, and bioinformatic models, to distinguish normal glands from thyroid tumours. Additionally, we are proposing biomarkers that could indicate potential metastatic diseases in papillary thyroid cancer (PTC), a sub-class of DTC.RESULTS: Normal and tumour thyroid tissue from DTC patients had a distinct yet well-defined metabolic profile with high levels of anabolic metabolites and/or other metabolites associated with the energy maintenance of tumour cells. The consistency of the DTC metabolic profile allowed us to build a bioinformatic classification model capable of clearly distinguishing normal from tumor thyroid tissues, which might help diagnose thyroid cancer. Moreover, based on PTC patient samples, our data suggest that elevated nuclear and mitochondrial DNA mutational burden, intra-tumour heterogeneity, shortened telomere length, and altered metabolic profile reflect the potential for metastatic disease.DISCUSSION: Altogether, this work indicates that a differential and integrated multi-omics approach might improve DTC management, perhaps preventing unnecessary thyroid gland removal and/or radioiodine therapy.CONCLUSIONS: Well-designed, prospective translational clinical trials will ultimately show the value of this integrated multi-omics approach and early diagnosis of DTC and potential metastatic PTC.PMID:37317665 | DOI:10.1002/ctm2.1298

J Pineal Res. 2023 Jun 15. doi: 10.1111/jpi.12892. Online ahead of print.ABSTRACTThe accelerated pace of life at the present time has resulted in tremendous alterations in living patterns. Changes in diet and eating patterns, in particular, coupled with irregular light-dark cycles (LD) will further induce circadian misalignment and lead to disease. Emerging data has highlighted the regulatory effects of diet and eating patterns on the host microbe interactions with the circadian clock (CC), immunity, and metabolism. Herein, we studied how LD cycles regulate the homeostatic crosstalk among the gut microbiome (GM), hypothalamic and hepatic CC oscillations, and immunity and metabolism using multi-omics approaches. Our data demonstrated that central CC oscillations lost rhythmicity under irregular LD cycles, but LD cycles had minimal effects on diurnal expression of peripheral CC genes in the liver including Bmal1. We further demonstrated that the GM could regulate hepatic circadian rhythms under irregular LD cycles, the candidate bacteria including Limosilactobacillus, Actinomyces, Veillonella, Prevotella, Campylobacter, Faecalibacterium, Kingella, Clostridia vadinBB60, Veillonella. A comparative transcriptomic study of innate immune genes indicated that different LD cycles had varying effects on immune functions, while irregular LD cycles had greater impacts on hepatic innate immune functions than those in the hypothalamus. Extreme LD cycle alterations (LD0/24 and LD24/0) had worse impacts than slight alterations (LD8/16 and LD16/8), and led to gut dysbiosis in mice receiving antibiotics. Metabolome data also demonstrated that hepatic tryptophan metabolism mediated the homeostatic crosstalk among GM-liver-brain axis in response to different LD cycles. These research findings highlighted that GM could regulate immune and metabolic disorders induced by circadian dysregulation. Further, the data provided potential targets for developing probiotics for individuals with circadian disruption such as shift workers. This article is protected by copyright. All rights reserved.PMID:37317652 | DOI:10.1111/jpi.12892

Microorganisms. 2023 May 17;11(5):1319. doi: 10.3390/microorganisms11051319.ABSTRACTSolid-state fermentation is known to improve plant-based feed nutritional quality; however, the association between microbes and metabolite production in fermented feed remains unclear. We inoculated corn-soybean-wheat bran (CSW) meal feed with Bacillus licheniformis Y5-39, Bacillus subtilis B-1, and lactic acid bacteria RSG-1. Then, 16S rDNA sequencing and untargeted metabolomic profiling were applied to investigate changes in the microflora and metabolites, respectively, and their integrated correlations during fermentation were assessed. The results indicated that trichloroacetic acid soluble protein levels showed a sharp increase, while glycinin and β-conglycinin levels showed a sharp decrease in the fermented feed, as confirmed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Pediococcus, Enterococcus, and Lactobacillus were predominant in the fermented feed. Overall, 699 significantly different metabolites were identified before and after fermentation. Arginine and proline, cysteine and methionine, and phenylalanine and tryptophan metabolism were the key pathways, with arginine and proline metabolism being the most important pathway in the fermentation process. By analyzing the correlation between the microbiota and metabolite production, lysyl-valine and lysyl-proline levels were found to be positively correlated with Enterococcus and Lactobacillus abundance. However, Pediococcus was positively correlated with some metabolites contributing to nutritional status and immune function. According to our data, Pediococcus, Enterococcus, and Lactobacillus mainly participate in protein degradation, amino acid metabolism, and lactic acid production in fermented feed. Our results provide new insights into the dynamic changes in metabolism that occurred during the solid-state fermentation of corn-soybean meal feed using compound strains and should facilitate the optimization of fermentation production efficiency and feed quality.PMID:37317292 | DOI:10.3390/microorganisms11051319

Gut Microbes. 2023 Dec 31;15(1):2223330. doi: 10.1080/19490976.2023.2223330.ABSTRACTIndividuals with nonalcoholic fatty liver disease (NAFLD) have an altered gut microbiota composition. Moreover, hepatic DNA methylation may be altered in the state of NAFLD. Using a fecal microbiota transplantation (FMT) intervention, we aimed to investigate whether a change in gut microbiota composition relates to altered liver DNA methylation in NAFLD. Moreover, we assessed whether plasma metabolite profiles altered by FMT relate to changes in liver DNA methylation. Twenty-one individuals with NAFLD underwent three 8-weekly vegan allogenic donor (n = 10) or autologous (n = 11) FMTs. We obtained hepatic DNA methylation profiles from paired liver biopsies of study participants before and after FMTs. We applied a multi-omics machine learning approach to identify changes in the gut microbiome, peripheral blood metabolome and liver DNA methylome, and analyzed cross-omics correlations. Vegan allogenic donor FMT compared to autologous FMT induced distinct differential changes in I) gut microbiota profiles, including increased abundance of Eubacterium siraeum and potential probiotic Blautia wexlerae; II) plasma metabolites, including altered levels of phenylacetylcarnitine (PAC) and phenylacetylglutamine (PAG) both from gut-derived phenylacetic acid, and of several choline-derived long-chain acylcholines; and III) hepatic DNA methylation profiles, most importantly in Threonyl-TRNA Synthetase 1 (TARS) and Zinc finger protein 57 (ZFP57). Multi-omics analysis showed that Gemmiger formicillis and Firmicutes bacterium_CAG_170 positively correlated with both PAC and PAG. E siraeum negatively correlated with DNA methylation of cg16885113 in ZFP57. Alterations in gut microbiota composition by FMT caused widespread changes in plasma metabolites (e.g. PAC, PAG, and choline-derived metabolites) and liver DNA methylation profiles in individuals with NAFLD. These results indicate that FMTs might induce metaorganismal pathway changes, from the gut bacteria to the liver.PMID:37317027 | DOI:10.1080/19490976.2023.2223330

Food Res Int. 2023 Aug;170:112977. doi: 10.1016/j.foodres.2023.112977. Epub 2023 May 22.ABSTRACTPolar lipids play essential biological functions in energy storage, both as structural components of cell membranes and as signaling molecules. In this study, a comprehensive UHPLC-QTRAP-MS-based lipidomic analysis of mature breast milk (BM) and ewe milk (EM) was conducted. Through the analysis, a total of 362 polar lipid species from 14 subclasses were characterized, including 60 phosphatidylethanolamines (PEs), 59 phosphatidylcholines (PCs), 38 phosphatidylinositols (PIs), 35 sphingomyelins (SMs), and 34 ceramides (Cers). Of these, 139 lipid molecules were screened as significantly differentially expressed polar lipids (SDPLs) between the two kinds of milk based on the following criteria: a variable importance in projection (VIP) value > 1.0, a false discovery rate-adjusted P-value < 0.0001, and a fold change (FC) of either > 2.0 or < 0.5; these included 111 upregulated and 28 downregulated SDPLs in EM compared to BM. Among these SDPLs, the content of PE (16:1_18:0) was found to be significantly higher in EM compared to BM (FC = 69.5853, P < 0.0001). Moreover, sphingolipid metabolism and glycerophospholipid metabolism were determined to be vital metabolic pathways. This was derived from the finding that PE, PC, SM, and PI were key lipid metabolites in the two kinds of milk that were related to these two metabolic pathways. This study provides new insights into the characterization of SDPLs in mammalian milk, and also provides a theoretical basis for optimizing infant formula.PMID:37316057 | DOI:10.1016/j.foodres.2023.112977

Food Res Int. 2023 Aug;170:113020. doi: 10.1016/j.foodres.2023.113020. Epub 2023 May 21.ABSTRACTThe production and use of ozone micro-nano bubble water (O3-MNBW) is an innovative technology that prolongs the reactivity of aqueous-phase ozone and maintains the freshness and quality of fruits and vegetables by removing pesticides, mycotoxins, and other contaminants. The quality of parsley treated with different concentrations of O3-MNBW was investigated during storage at 20 ℃ for 5 d, and found that a ten-minute exposure of parsley to 2.5 mg·L-1 O3-MNBW effectively preserved the sensory quality of parsley, and resulted in lower weight loss, respiration rate, ethylene production, MDA levels, and a higher level of firmness, vitamin C, and chlorophyll content, relative to untreated parsley. The O3-MNBW treatment also increased the level of total phenolics and flavonoids, enhanced peroxidase and ascorbate peroxidase activity, and inhibited polyphenol oxidase activity in stored parsley. Five volatile signatures identified using an electronic nose (W1W, sulfur-compounds; W2S, ethanol; W2W, aromatic- and organic- sulfur compounds; W5S, oxynitride; W1S, methane) exhibited a significant decrease in response to the O3-MNBW treatment. A total of 24 major volatiles were identified. A metabolomic analysis identified 365 differentially abundant metabolites (DMs). Among them, 30 and 19 DMs were associated with characteristic volatile flavor substance metabolism in O3-MNBW and control groups, respectively. The O3-MNBW treatment increased the abundance of most DMs related to flavor metabolism and reduced the level of naringin and apigenin. Our results provide insight into the mechanisms that are regulated in response to the exposure of parsley to O3-MNBW, and confirmed the potential use of O3-MNBW as a preservation technology.PMID:37316085 | DOI:10.1016/j.foodres.2023.113020

Food Res Int. 2023 Aug;170:112992. doi: 10.1016/j.foodres.2023.112992. Epub 2023 May 19.ABSTRACTDark tea fermentation involves various fungi, but studies focusing on the mixed fermentation in tea remain limited. This study investigated the influences of single and mixed fermentation on the dynamical alterations of tea metabolites. The differential metabolites between unfermented and fermented teas were determined using untargeted metabolomics. Dynamical changes in metabolites were explored by temporal clustering analysis. Results indicated that Aspergillus cristatus (AC) at 15 days, Aspergillus neoniger (AN) at 15 days, and mixed fungi (MF) at 15 days had respectively 68, 128 and 135 differential metabolites, compared with unfermentation (UF) at 15 days. Most of metabolites in the AN or MF group showed a down-regulated trend in cluster 1 and 2, whereas most of metabolites in the AC group showed an up-regulated trend in cluster 3 to 6. The three key metabolic pathways mainly composed of flavonoids and lipids included flavone and flavonol biosynthesis, glycerophospholipid metabolism and flavonoid biosynthesis. Based on the dynamical changes and metabolic pathways of the differential metabolites, AN showed a predominant status in MF compared with AC. Together, this study will advance the understanding of dynamic changes in tea fermentation and provide valuable insights into the processing and quality control of dark tea.PMID:37316065 | DOI:10.1016/j.foodres.2023.112992

Food Res Int. 2023 Aug;170:112965. doi: 10.1016/j.foodres.2023.112965. Epub 2023 May 14.ABSTRACTThe scandal of detecting 1, 2-propanediol (PL) in milk brought a crisis to the trust of consumers in the dairy industry, and the potential toxicity of PL has aroused the public concern about dietary exposure. A total of 200 pasteurized milk samples were collected from 15 regions, and the quantity of PL ranged between 0 and 0.31 g kg-1. Pseudo-targeted quantitative metabolomics integrated with proteomics demonstrated that PL enhanced the reduction of κ-casein, β-casein, and 107 substances (41 amines and 66 amides) containing amide bonds. Pathway enrichment and topological analysis indicated that PL induced the metabolism of lipids, amino acids, oligosaccharide nucleotides, and alkaloids by accelerating the rate of nucleophilic reaction, and acetylcholinesterase, sarcosine oxidase, and prolyl 4-hydroxylase were determined as the vital enzymes related to the degradation of above nutrients. The results of molecular simulation calculation illustrated that the number of hydrogen bonds between acetylcholinesterase, sarcosine oxidase, and substrate increased to 2 and 3, respectively, while the position of hydrogen bonds between prolyl 4-hydroxylase and proline was shifted, indicating the change of conformation and the enhancement of hydrogen bond force were essential factors for the up-regulation of enzyme activity. This study first revealed the mechanism of deposition and transformation of PL in milk, which contributed to the knowledge of the quality control of milk and provided vital indicators to evaluate the adverse risks of PL in dairy products.PMID:37316053 | DOI:10.1016/j.foodres.2023.112965

Food Res Int. 2023 Aug;170:112963. doi: 10.1016/j.foodres.2023.112963. Epub 2023 May 15.ABSTRACTThe present study attempted for the first time to explore the effects of the daily oral intake of a phenolics-rich extract from chestnut shells (CS) on the metabolomic profiling of rat tissues by liquid chromatography coupled to Orbitrap-mass spectrometry (LC-ESI-LTQ-Orbitrap-MS) targeted to polyphenolics and their metabolites and screen potential oxidative stress biomarkers, validating its use as a promising nutraceutical ingredient with outstanding antioxidant properties for the prevention and co-therapy of lifestyle-related diseases triggered by oxidative stress. The results demonstrated new insights into the metabolomic fingerprinting of polyphenols from CS, confirming their absorption and biotransformation by phase I (hydrogenation) and II (glucuronidation, methylation, and sulfation) enzymes. Phenolic acids were the main polyphenolic class, followed by hydrolyzable tannins, flavanols, and lignans. In contrast to the liver, sulfated conjugates were the principal metabolites reaching the kidneys. The multivariate data analysis predicted an exceptional contribution of polyphenols and their microbial and phase II metabolites to the in-vivo antioxidant response of the CS extract in rats, recommending its use as an appealing source of anti-aging molecules for nutraceuticals. This is the first study that explored the relation between metabolomic profiling of rat tissues and in-vivo antioxidant effects after oral treatment with a phenolics-rich CS extract.PMID:37316050 | DOI:10.1016/j.foodres.2023.112963

Food Res Int. 2023 Aug;170:112953. doi: 10.1016/j.foodres.2023.112953. Epub 2023 May 14.ABSTRACTMany healthy people suffer from milk-related gastrointestinal discomfort (GID) despite not being lactose intolerant; the mechanisms underpinning such condition are unknown. This study aimed to explore milk protein digestion and related physiological responses (primary outcome), gut microbiome and gut permeability in 19 lactose-tolerant healthy nonhabitual milk consumers [NHMCs] reporting GID after consuming cow milk compared to 20 habitual milk consumers [HMCs] without GID. NHMCs and HMCs participated in a milk-load (250 mL) test, underwent blood sample collection at 6 time points over 6 h after milk consumption and collected urine samples and GID self-reports over 24 h. We measured the concentrations of 31 milk-derived bioactive peptides (BAPs), 20 amino acids, 4 hormones, 5 endocannabinoid system mediators, glucose and the dipeptidyl peptidase-IV (DPPIV) activity in blood and indoxyl sulfate in urine samples. Subjects also participated in a gut permeability test and delivered feces sample for gut microbiome analysis. Results showed that, compared to HMCs, milk consumption in NHMCs, along with GID, elicited a slower and lower increase in circulating BAPs, lower responses of ghrelin, insulin, and anandamide, a higher glucose response and serum DPPIV activity. The gut permeability of the two groups was similar, while the habitual diet, which was lower in dairy products and higher in the dietary-fibre-to-protein ratio in NHMCs, possibly shaped the gut microbiome; NHMCs exhibited lower abundance of Bifidobacteria, higher abundance of Prevotella and lower abundance of protease-coding genes, which may have reduced protein digestion, as evidenced by lower urinary excretion of indoxyl sulfate. In conclusion, the findings showed that a less efficient digestion of milk proteins, supported by a lower proteolytic capability of the gut microbiome, may explain GID in healthy people after milk consumption.PMID:37316045 | DOI:10.1016/j.foodres.2023.112953

Food Res Int. 2023 Aug;170:112753. doi: 10.1016/j.foodres.2023.112753. Epub 2023 Apr 7.ABSTRACTIn this study, antioxidant and anti-aging studies were carried out by mannoprotein-rich yeast cell wall enzymatic hydrolysate (MYH) obtained by enzymatic hydrolysis of yeast cell wall through the Caenorhabditis elegans (C. elegans) model. It was found that MYH could improve the lifespan and anti-stress ability of C. elegans by increasing the activity of antioxidant enzymes such as T-SOD, GSH-PX and CAT, and reducing the levels of MDA, ROS and apoptosis. At the same time, through the verification expression of corresponding mRNA, it was found that MYH exerted antioxidant and anti-aging activities by up-regulating the translation of MTL-1, DAF-16, SKN-1 and SOD-3 mRNA, and down-regulating the translation of AGE-1 and DAF-2 mRNA. In addition, it was found that MYH could improve the composition and distribution of the gut microbiota of C. elegans, and significantly improve the level of metabolites through the sequencing of gut microbiota and untargeted metabolomic studies. It has contributed to studying the antioxidant and anti-aging activities of microorganisms such as yeast through the level of gut microbiota and metabolites and the development of related functional foods.PMID:37316035 | DOI:10.1016/j.foodres.2023.112753