Significant Differential Metabolites Research Articles

Comparison of the quality of suansun product between starter inoculation and natural fermentation

Suansun (fermented bamboo shoots) was prepared by natural fermentation (NF) and inoculation fermentation (IF) with a starter culture containing Lactococcus lactis, Leuconostoc citreum, and Lactiplantibacillus plantarum in this study, to evaluate the effects of inoculation mixed starter culture on physicochemical, flavor and sensory characteristics of suansun. The results showed that IF suansun acidified faster and to a greater extent than NF. Besides, the accelerated acidification process significantly decreased the nitrite content, shortened the fermentation time and improved the food safety of the final suansun product in IF. At the end of fermentation, the lactic acid concentration was significantly higher in IF (6.17 ± 0.25 g/L) than in NF (3.83 ± 0.28 g/L). Twenty-seven volatile compounds were identified as the characteristic flavor compounds in suansun and the relative content of nonanal, hexanal, 1-octen-3-ol and 3-octanone (ROAV >1) was higher in IF than in NF at the late stage of fermentation. In addition, 132 non-volatile compounds were identified as significant differential metabolites, which were mainly small peptides and fatty acids in both NF and IF. Sensory evaluation found that the aroma, taste, texture and overall quality scores of IF suansun were all superior to those of NF suansun. The above results demonstrated that the use of mixed starter cultures of Lac. lactis, Leu. citreum, and L. plantarum contributed to improving the quality of suansun product, and might provide a feasible approach for standardized production of suansun in the future.

Liquid chromatography coupled to mass spectrometry metabolomic analysis of cerebrospinal fluid revealed the metabolic characteristics of moyamoya disease.

Metabolomics has found extensive applications in the field of neurological diseases, significantly contributing to their diagnosis and treatment. However, there has been limited research applying metabolomics to moyamoya disease (MMD). This study aims to investigate and identify differential metabolites associated with MMD. We employed a liquid chromatography coupled with mass spectrometry (LC-MS) approach, complemented by univariate and multivariate analyses, to discern metabolic biomarkers in cerebrospinal fluid samples. We then compared these biomarkers between MMD patients and healthy controls (Ctl). Sixteen patients diagnosed with MMD via cerebral angiography and eight healthy controls were enrolled in this study. Comparative analyses, including univariate and multivariate analyses, correlation studies, heatmaps, Volcano Plots, and KEGG pathway enrichment, were performed between MMD patients and controls. As a result, we identified 129 significant differential metabolites in the cerebrospinal fluid between MMD patients and controls. These metabolic biomarkers are associated with various pathways, with notable involvement in purine and pyrimidine metabolism. Utilizing an LC-MS-based metabolomics approach holds promise for enhancing the clinical diagnosis of MMD. The identified biomarkers offer potential avenues for the development of novel diagnostic methods for MMD and offer fresh insights into the pathogenesis of the disease.

Metabolomic profiling of ocular tissues in rabbit myopia: Uncovering differential metabolites and pathways

To investigate the metabolic difference among tissue layers of the rabbits’ eye during the development of myopia using metabolomic techniques and explore any metabolic links or cascades within the ocular wall. Ultra Performance Liquid Chromatography - Mass Spectrometry (UPLC-MS) was utilized for untargeted metabolite screening (UMS) to identify the significant differential metabolites produced between myopia (MY) and control (CT) (horizontal). Subsequently, we compared those key metabolites among tissues (Sclera, Choroid, Retina) of MY for distribution and variation (longitudinal). A total of 6285 metabolites were detected in the three tissues. The differential metabolites were screened and the metabolic pathways of these metabolites in each myopic tissue were labeled, including tryptophan and its metabolites, pyruvate, taurine, caffeine metabolites, as well as neurotransmitters like glutamate and dopamine. Our study suggests that multiple metabolic pathways or different metabolites under the same pathway, might act on different parts of the eyeball and contribute to the occurrence and development of myopia by affecting the energy supply to the ocular tissues, preventing antioxidant stress, affecting scleral collagen synthesis, and regulating various neurotransmitters mutually.

Utilizing serum metabolomics for assessing postoperative efficacy and monitoring recurrence in gastric cancer patients

Objective(1) This study aims to identify distinct serum metabolites in gastric cancer patients compared to healthy individuals, providing valuable insights into postoperative efficacy evaluation and monitoring of gastric cancer recurrence; (2) Methods: Serum samples were collected from 15 healthy individuals, 16 gastric cancer patients before surgery, 3 months after surgery, 6 months after surgery, and 15 gastric cancer recurrence patients. T-test and analysis of variance (ANOVA) were performed to screen 489 differential metabolites between the preoperative group and the healthy control group. Based on the level of the above metabolites in the recurrence, preoperative, three-month postoperative, and six-month postoperative groups, we further selected 18 significant differential metabolites by ANOVA and partial least squares discriminant analysis (PLS-DA). The result of hierarchical clustering analysis about the above metabolites showed that the samples were regrouped into the tumor-bearing group (comprising the original recurrence and preoperative groups) and the tumor-free group (comprising the original three-month postoperative and six-month postoperative groups). Based on the results of PLS-DA, 7 differential metabolites (VIP > 1.0) were further selected to distinguish the tumor-bearing group and the tumor-free group. Finally, the results of hierarchical clustering analysis showed that these 7 metabolites could well identify gastric cancer recurrence; (3) Results: Lysophosphatidic acids, triglycerides, lysine, and sphingosine-1-phosphate were significantly elevated in the three-month postoperative, six-month postoperative, and healthy control groups, compared to the preoperative and recurrence groups. Conversely, phosphatidylcholine, oxidized ceramide, and phosphatidylglycerol were significantly reduced in the three-month postoperative, six-month postoperative, and healthy control groups compared to the preoperative and recurrence groups. However, these substances did not show significant differences between the preoperative and recurrence groups, nor between the three-month postoperative, six-month postoperative, and healthy control groups; (4) Conclusions: Our findings demonstrate the presence of distinct metabolites in the serum of gastric cancer patients compared to healthy individuals. Lysophosphatidic acid, triglycerides, lysine, sphingosine-1-phosphate, phosphatidylcholine, oxidized ceramide, and phosphatidylglycerol hold potential as biomarkers for evaluating postoperative efficacy and monitoring recurrence in gastric cancer patients. These metabolites exhibit varying concentrations across different sample categories.

Reprogramming of arachidonic acid metabolism using α-terpineol to alleviate asthma: insights from metabolomics.

Asthma is a chronic inflammatory disorder in airways with typical pathologic features of airway inflammation and mucus hypersecretion. α-Terpineol is a monocyclic terpene found in many natural plants and foods. It has been reported to possess a wide range of pharmacological activities including anti-inflammatory and expectorant effects. However, the role of α-terpineol in asthma and its potential protective mechanism have not been well elucidated. This study is designed to investigate the pharmacological effect and mechanism of α-terpineol on asthmatic mice using the metabolomics platform. A murine model of asthma was established using ovalbumin (OVA) sensitization and then challenged for one week. The leukocyte count and inflammatory cytokines in the bronchoalveolar lavage fluid (BALF), lung histopathology, inflammatory infiltrate and mucus secretion were evaluated. An ultra-high performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS)-based metabolomics study was performed on lung tissues and serum to explore endogenous small molecule metabolites affected by α-terpineol in asthmatic mice. After α-terpineol treatment, leukocyte count, inflammatory cytokines in the BALF, and peribronchial inflammation infiltration were significantly downregulated. Goblet cell hyperplasia and mucus secretion were attenuated, with the level of Muc5ac in BALF decreased. These results proved the protective effect of α-terpineol against airway inflammation, mucus hypersecretion and Th1/Th2 immune imbalance. To further investigate the underlying mechanisms of α-terpineol in asthma treatment, UPLC-MS/MS-based metabolomics analysis was performed. 26 and 15 identified significant differential metabolites were found in the lung tissues and serum of the control, model and α-terpineol groups, respectively. Based on the above differential metabolites, enrichment analysis showed that arachidonic acid (AA) metabolism was reprogrammed in both mouse lung tissues and serum. 5-Lipoxygenase (5-LOX) and cysteinyl leukotrienes (CysLTs) are the key enzyme and the end product of AA metabolism, respectively. In-depth studies have shown that pretreatment with α-terpineol can alleviate asthma by decreasing the AA level, downregulating the expression of 5-LOX and reducing the accumulation of CysLTs in mouse lung tissues. In summary, this study demonstrates that α-terpineol is a potential agent that can prevent asthma via regulating disordered AA metabolism.

Integrated serum, urine metabolomics and 16S rRNA sequencing to investigate the modulatory effect of Ziziphi Spinosae Folium flavonoid on D-galactose-induced aging of rats

Ziziphi Spinosae Folium, the leaf of Ziziphus jujuba Mill. var. spinosa (Bunge) Hu ex H. F. Chou (LZJS), was widely distributed in northern China. Our previous study showed that LZJS flavonoid (LZJSF) exerted antioxidant activity at chemical and PC12 cell levels, respectively. Here, we further studied the function of LZJSF on aging-related oxidative stress in D-galactose (D-gal)-induced rats and the potential mechanisms were explored. The aging model was established by intraperitoneal injection of D-gal (300 mg·kg−1·day−1) for 36 days, the low-dose of LZJSF (LLZJSF 100 mg·kg−1·day−1) and the high-dose of LZJSF (HLZJSF, 200 mg·kg−1·day−1) were administered daily by oral gavage at the same time, respectively. Their spatial and learning memory abilities were evaluated by the Morris water maze test. HLZJSF was observed to significantly ameliorate cognitive ability and oxidative indexes, such as reduction of MDA and augmentation of SOD, GSH-Px, T-AOC and CAT, and the effect of HLZJSF on these indexes was stronger than that of LLZJSF. A precise and well-defined research strategy was successfully applied to screen serum differential metabolites. Furthermore, integrated serum and urine metabolomics showed that the derivations of nine significant differential metabolites could be regulated by administration of HLZJSF, which suggested that the intervention effect of HLZJSF against aging may involve in the amino acid metabolism including D-Glutamine and D-glutamate, alanine, aspartate and glutamate, arginine and proline metabolism and arginine biosynthesis. 16S rRNA sequencing analysis showed that HLZJSF could descend the relative abundance of Firmicutes and Actinobacteria, as well as the ratio of Firmicutes/Bacteroidetes, and increase the relative abundance of Bacteroidetes and Proteobacteria. Finally, correlation analysis further showed that the beneficial effects of HLZJSF resulted from the regulation of the disturbance of gut microbiota through the “microbiota-gut-brain” axis to affect amino acid metabolism and regulate oxidative stress. This study will provide a foundation for the development and utilization of LZJSF as functional foods and healthy beneficial food products.

Urine metabolomics phenotyping and urinary biomarker exploratory in mild cognitive impairment and Alzheimer's disease.

Alzheimer's disease is a prevalent disease with a heavy global burden and is suggested to be a metabolic disease in the brain in recent years. The metabolome is considered to be the most promising phenotype which reflects changes in genetic, transcript, and protein profiles as well as environmental effects. Aiming to obtain a comprehensive understanding and convenient diagnosis of MCI and AD from another perspective, researchers are working on AD metabolomics. Urine is more convenient which could reflect the change of disease at an earlier stage. Thus, we conducted a cross-sectional study to investigate novel diagnostic panels. We first enrolled participants from China-Japan Friendship Hospital from April 2022 to November 2022, collected urine samples and conducted an LC-MS/MS analysis. In parallel, clinical data were collected and clinical examinations were performed. After statistical and bioinformatics analyzes, significant risk factors and differential urinary metabolites were determined. We attempt to investigate diagnostic panels based on machine learning including LASSO and SVM. Fifty-seven AD patients, 43 MCI patients and 62 CN subjects were enrolled. A total of 2,140 metabolites were identified among which 125 significantly differed between the AD and CN groups, including 46 upregulated ones and 79 downregulated ones. In parallel, there were 93 significant differential metabolites between the MCI and CN groups, including 23 upregulated ones and 70 downregulated ones. AD diagnostic panel (30 metabolites+ age + APOE) achieved an AUC of 0.9575 in the test set while MCI diagnostic panel (45 metabolites+ age + APOE) achieved an AUC of 0.7333 in the test set. Atropine, S-Methyl-L-cysteine-S-oxide, D-Mannose 6-phosphate (M6P), Spiculisporic Acid, N-Acetyl-L-methionine, 13,14-dihydro-15-keto-tetranor Prostaglandin D2, Pyridoxal 5'-Phosphate (PLP) and 17(S)-HpDHA were considered valuable for both AD and MCI diagnosis and defined as hub metabolites. Besides, diagnostic metabolites were weakly correlated with cognitive functions. In conclusion, the procedure is convenient, non-invasive, and useful for diagnosis, which could assist physicians in differentiating AD and MCI from CN. Atropine, M6P and PLP were evidence-based hub metabolites in AD.

Widely targeted metabolomics analysis reveals the formation of nonvolatile flavor qualities during oolong tea manufacturing: a case study of Jinguanyin.

The manufacturing processes of oolong tea significantly impact its nonvolatile components, leading to the emergence of distinct flavor attributes. Understanding the dynamic changes in nonvolatile components during the manufacturing stages of the Jinguanyin (JGY) cultivar is crucial for unraveling the potential mechanism behind flavor formation. Comprehensive metabolomics and sensomics analyses were conducted to investigate the dynamic changes in nonvolatile components throughout various phases of oolong tea processing, focusing on the JGY cultivar. A total of 1,005 nonvolatile metabolites were detected, with 562 recognized as significant differential metabolites during various phases of oolong tea processing. Notably, the third turning-over, third setting, and high-temperature treatments exhibited the most significant effects on the nonvolatile metabolites of oolong tea. JGY finished tea demonstrated a characteristic flavor profile, marked by mellowness, sweetness in aftertaste, and a significant Yin rhyme. This flavor profile was collectively promoted by the accumulation of amino acids and organic acids, the decrease in flavonols (3-O-glycosides) and sugar substances, the alteration of phenolic acids, and the stabilization of caffeine. This study contribute to the understanding of the formation of oolong tea flavor qualities. The dynamic changes observed in various types of nonvolatile compounds during oolong tea processing shed light on the intricate interplay of metabolites and their influence on the final flavor characteristics.

Effects of four diets on the metabolism of megalopa metamorphosis of the mud crab, Scylla paramamosain

Dietary intake is an essential source of energy and nutrients, and plays an irreplaceable role in the breeding of S. paramamosain seedlings. In this study, live Artemia nauplii (LA), compound feeds (CF), frozen copepods (FC) and frozen adult Artemia (FA) were utilized as feed during the megalopa stage. To determine the impact that diet has on the metabolism of crablets that underwent metamorphosis from the megalopa stage, analyses of both metabolomics and fatty acid content were conducted. In the LC-MS-based metabolomics analysis, a total of 104, 205 and 83 significantly different metabolites (SDMs) were identified after being fed with FC, FA, and CF, respectively, as compared to the LA group. Furthermore, significant differences in KEGG compounds among the three comparisons exhibited similarity and were mainly associated with categories such as “Lipids”, “Hormones and transmitters”, and “Peptides”. The fatty acid content analysis indicated that the ΣMUFA was significantly higher in the LA and CF groups compared to the other two groups. In contrast, the highest level of ΣPUFA was found in the LA group. In addition, the CF group showed significantly higher expression levels of the fatty acid synthesis genes, FAS and ACC. Conversely, the expression level of the fatty acid decomposition-related gene CPT1 was the highest in the LA group. In comparison with the FA group, the expression level of FABP3 was significantly decreased in the LA and CF groups. In summary, there were significant differences observed in the metabolic profiles of crablets that metamorphosed from the megalopa under different diets. Our experimental results suggested that LA is more advantageous in the cultivation of the S. paramamosain megalopa compared to the other three diets. While it remains a diet that cannot be entirely substituted at present, LA has the potential to improve the culture performance of the S. paramamosain megalopa. The current study could provide valuable data into the development of artificial diets necessary for the future of the mud crab seedling breeding industry.

Transcriptomics and metabolomics study in mouse kidney of the molecular mechanism underlying energy metabolism response to hypoxic stress in highland areas.

Exposure to hypoxia disrupts energy metabolism and induces inflammation. However, the pathways and mechanisms underlying energy metabolism disorders caused by hypoxic conditions remain unclear. In the present study, a hypoxic animal model was created and transcriptomic and non-targeted metabolomics techniques were applied to further investigate the pathways and mechanisms of hypoxia exposure that disrupt energy metabolism. Transcriptome results showed that 3,007 genes were significantly differentially expressed under hypoxic exposure, and Gene Ontology annotation analysis and Kyoto Encyclopaedia of Genes and Genomes (KEGG) enrichment analysis showed that the differentially expressed genes (DEGs) were mainly involved in energy metabolism and were significantly enriched in the tricarboxylic acid (TCA) cycle and oxidative phosphorylation (OXPHOS) pathway. The DEGs IDH3A, SUCLA2, and MDH2 in the TCA cycle and the DEGs NDUFA3, NDUFS7, UQCRC1, CYC1 and UQCRFS1 in the OXPHOS pathway were validated using mRNA and protein expression, and the results showed downregulation. The results of non-targeted metabolomics showed that 365 significant differential metabolites were identified under plateau hypoxia stress. KEGG enrichment analysis showed that the differential metabolites were mainly enriched in metabolic processes, such as energy, nucleotide and amino acid metabolism. Hypoxia exposure disrupted the TCA cycle and reduced the synthesis of amino acids and nucleotides by decreasing the concentration of cis-aconitate, α-ketoglutarate, NADH, NADPH and that of most amino acids, purines, and pyrimidines. Bioinformatics analysis was used to identify inflammatory genes related to hypoxia exposure and some of them were selected for verification. It was shown that the mRNA and protein expression levels of IL1B, IL12B, S100A8 and S100A9 in kidney tissues were upregulated under hypoxic exposure. The results suggest that hypoxia exposure inhibits the TCA cycle and the OXPHOS signalling pathway by inhibiting IDH3A, SUCLA2, MDH2, NDUFFA3, NDUFS7, UQCRC1, CYC1 and UQCRFS1, thereby suppressing energy metabolism, inducing amino acid and nucleotide deficiency and promoting inflammation, ultimately leading to kidney damage.

Integrative transcriptomics and metabolomics analysis of body color formation in the common carp

The coloration of aquatic animals influences their adaptability to environment and economic values. The skin color of common carp (Cyprinus carpio) is various between different strains. Hebao red carp is famous for its bright red color, which is different from the brown skin color of wild-type common carp. To reveal the different components and molecular mechanism between skins with red and brown colors, LC-MS and transcript analysis were conducted. 614 significantly different metabolites (SDM) and 392 differentially expressed genes (DEG) were detected between skins of Hebao red carp (HB) and Yellow River carp (YR). There are 35 KEGG pathways shared by DEGs and SDMs, among which microbial metabolism in diverse environments (ko01120), carbon metabolism (ko01200) and metabolic pathways (ko01100) were significantly enriched by DEGs and SDMs. Pathways related to melanin synthesis and retinal metabolism were down-regulated in HB, such as adh8a, adh8b, cyp3a, dhrs3b, mart1, hgd, hpd and maiA, which may induce the disappear of melanocytes and accumulation of carotenoid. The content of lutein in HB skin was significantly higher than in YR. This study shows retinol and carotenoid metabolism is vital in the common carp body color formation, and will help understand the mechanism of color determination in common carp.

Untargeted metabolomics analysis of plasma metabolic characteristics in patients with acne and insulin resistance.

Acne vulgaris is a chronic inflammatory disease with high incidence, diverse clinical manifestations, poor clinical efficacy, and easy recurrence. Recent studies have found that the occurrence of acne is related to metabolic factors such as insulin resistance; however, the specific mechanism of action remains unclear. This study aimed to identify significantly different metabolites and related metabolic pathways in the serum of acne vulgaris patients with or without insulin resistance. LC-MS/MS was used to analyze serum samples from patients about acne with insulin resistance (n = 51) and acne without insulin resistance (n = 69) to identify significant metabolites and metabolic pathways. In this study, 18 significant differential metabolites were screened for the first time. In the positive-ion mode, the upregulated substances were creatine, sarcosine, D-proline, uracil, Phe-Phe, L-pipecolic acid, and DL-phenylalanine; the downregulated substances were tridecanoic acid (tridecylic acid), L-lysine, cyclohexylamine, sphingomyelin (d18:1/18:0), gamma-L-Glu-epsilon-L-Lys, and 1,2-dioleoyl-sn-glycero-3-phosphatidylcholine. In the negative-ion mode, the upregulated substance was cholesterol sulfate, and the downregulated substances were D(-)-beta-hydroxybutyric acid, myristic acid, D-galacturonic acid, and dihydrothymine. Cholesterol sulfate showed the most significant expression among all differential metabolites (VIP = 7.3411). Based on the KEGG database, necroptosis and ABC transporters were the most significantly enriched metabolic pathways in this experiment. The differential metabolites and pathways identified in this study may provide new possibilities for the clinical diagnosis and development of targeted drugs for acne patients with insulin resistance.

Untargeted metabolomics reveals sour jujube kernel benefiting the nutritional value and flavor of Morchella esculenta.

Nucleosides, organic acids, and amino acids separated from Morchella esculenta are well known for their nutritional value and flavor. However, how to increase their content in a better way has been a challenge. In this study, the effect of adding jujube kernel on the active components of M. esculenta was investigated by untargeted metabolomics using UPLC-MS/MS. A total of 1,243 metabolites were identified, of which 262 metabolites (21.078%) were organic acids and derivatives, 245 metabolites (19.71%) were lipids and lipid-like molecules, and 26 metabolites (2.092%) were nucleosides, nucleotides, and analogues. Subsequently, differential metabolites between groups were screened by the orthogonal partial least squares-discriminant analysis model, which showed that 256 metabolites were identified as significantly different for the positive ion model and 149 for the negative ion model. Moreover, significant differential metabolites (VIP > 1, P < 0.05) in annotation of kyoto encyclopedia of genes and genomes pathway were investigated, which showed that ABC transporters were the most commonly observed transporters, followed by pyrimidine metabolism and purine metabolism. The results indicated that the main components of jujube kernel might be conducive to the accumulation of nucleoside organic acids and amino acid metabolites in M. esculenta. These results provide important information for the understanding of more suitable way for cultivation of M. esculenta.

Integrated metabolome, full-length sequencing, and transcriptome analyses unveil the molecular mechanisms of color formation of the canary yellow and red bracts of Bougainvillea × buttiana 'Chitra'.

Bougainvillea is a typical tropical flower of great ornamental value due to its colorful bracts. The molecular mechanism behind color formation is not well-understood. Therefore, this research conducted metabolome analysis, transcriptome analysis, and multi-flux full-length sequencing in two color bracts of Bougainvillea × buttiana 'Chitra' to investigate the significantly different metabolites (SDMs) and differentially expressed genes (DEGs). Overall, 261 SDMs, including 62 flavonoids and 26 alkaloids, were detected, and flavonols and betalains were significantly differentially accumulated among the two bracts. Furthermore, the complete-length transcriptome of Bougainvillea × buttiana was also developed, which contained 512 493 non-redundant isoforms. Among them, 341 210 (66.58%) displayed multiple annotations in the KOG, GO, NR, KEGG, Pfam, Swissprot, and NT databases. RNA-seq findings revealed that 3610 DEGs were identified between two bracts. Co-expression analysis demonstrated that the DEGs and SDMs involved in flavonol metabolism (such as CHS, CHI, F3H, FLS, CYP75B1, kaempferol, and quercetin) and betacyanin metabolism (DODA, betanidin, and betacyanins) were the main contributors for the canary yellow and red bract formation, respectively. Further investigation revealed that several putative transcription factors (TFs) might interact with the promoters of the genes mentioned above. The expression profiles of the putative TFs displayed that they may positively and negatively regulate the structural genes' expression profiles. The data revealed a potential regulatory network between important genes, putative TFs, and metabolites in the flavonol and betacyanin biosynthesis of Bougainvillea × buttiana 'Chitra' bracts. These findings will serve as a rich genetic resource for future studies that could create new color bracts.

Multi-dimensional metabolomic profiling reveals dysregulated ornithine metabolism hallmarks associated with a severe acute pancreatitis phenotype

To reveal dysregulated metabolism hallmark that was associated with a severe acute pancreatitis (SAP) phenotype. In this study, LC-MS/MS-based targeted metabolomics was used to analyze plasma samples from 106 acute pancreatitis (AP) patients (34 mild, 38 moderate, and 34 severe) admitted within 48 hours from abdominal pain onset and 41 healthy controls. Temporal metabolic profiling was performed on days 1, 3, and 7 after admission. A random forest (RF) was performed to significantly determine metabolite differences between SAP and non-SAP (NSAP) groups. Mass spectrometry imaging (MSI) and immunohistochemistry were conducted for the examination of pancreatic metabolite and metabolic enzyme alterations, respectively, on necrosis and paracancerous tissues. Simultaneously determination of serum and pancreatic tissue metabolic alterations using an L-ornithine-induced AP model to discover metabolic commonalities. Twenty-two significant differential metabolites screened by RF were selected to build an accurate model for the prediction of SAP from NSAP (AUC = 0.955). Six of 22 markers were found by MSI with significant alterations in pancreatic lesions, reduced ornithine-related metabolites were also identified. The abnormally expressed arginase2 and ornithine transcarboxylase were further discovered in combination with time-course metabolic profiling in the SAP animal models, the decreased ornithine catabolites were found at a late stage of inflammation, but ornithine-associated metabolic enzymes were activated during the inflammatory process. The plasma metabolome of AP patients is distinctive, which shows promise for early SAP diagnosis. AP aggravation is linked to the activated ornithine metabolic pathway and its inadequate levels of catabolites in in-situ lesion.

Comparison of the flavor qualities between two varieties of Mercenaria mercenaria

The saltwater hard clam Mercenaria mercenaria (M. mercenaria) as a representative of low-value shellfish, enhancing its flavor quality, is the key to enter the high-end market. Nevertheless, there has not been reported research on the flavor quality of M. mercenaria. This study compared the flavor quality of selective and non-selective saltwater hard clams of M. mercenaria by using various indicators: proximate component, free amino acids, nucleotides, and metabolomic analysis. The results indicated that selective breeding contributed to the significant improvement contents of crude protein, flavor-associated free amino acids (glutamic acid, aspartic acid, proline, etc.), and nucleotides (AMP) (P < 0.05). Then, the metabolome was utilized to assess the metabolite changes in the pre/post-selective breeding of M. mercenaria and further understand the flavor characteristics and metabolic status. In the metabolomics assay, among the 3143 quantified metabolites, a total of 102 peaks were identified as significantly different metabolites (SDMs) between the selective and non-selective varieties of M. mercenaria (VIP > 1 and P < 0.05). These results can provide new insights for future research on improving the quality of saltwater bivalves through selective breeding.

Therapeutic efficacy and underlying mechanisms of Gastrodia elata polysaccharides on dextran sulfate sodium-induced inflammatory bowel disease in mice: Modulation of the gut microbiota and improvement of metabolic disorders

Inflammatory bowel disease (IBD) is a chronic inflammatory gastrointestinal disease, and an imbalance in the gut microbiota is a critical factor in its development. Gastrodia elata (G. elata), an Orchidaceae plant, is recognized for its nutritional and medicinal value. Studies have shown that G. elata polysaccharides (GBP) have anti-inflammatory properties that may ameliorate IBD. However, the therapeutic effects of GBP on gut microbiota metabolism remain unknown. Therefore, we aimed to examine the therapeutic potential of G. elata extract and GBP in dextran sulfate sodium (DSS)-induced IBD mice. GBP demonstrated the best therapeutic effect by reducing IBD symptoms in mice to the greatest extent. Administering GBP resulted in significant increases in the relative abundances of bacteria with potential anti-inflammatory effects, such as Ligilactobacillus and Alloprevotella, and decreases in the levels of bacteria associated with proinflammatory responses, such as Bacteroides and Escherichia-Shigella. Furthermore, 36 significant differential metabolites between the model and GBP groups were identified in feces, which were mainly enriched in amino acid metabolism, including tryptophan and cysteine, vitamin B6 metabolism and steroid hormone biosynthesis. Consequently, investigating the metabolic regulation of the gut microbiota is a promising approach to evaluate the therapeutic effect of GBP on IBD.

Identifying potential toxic organic substances in leachates from tire wear particles and their mechanisms of toxicity to Scenedesmus obliquus

Tire wear particles (TWPs) are increasingly being found in the aquatic environment. However, there is limited information available on the environmental consequences of TWP constituents that may be release into water. In this study, TWP leachate samples were obtained by immersing TWPs in ultrapure water. Using high-resolution mass spectrometry and toxicity identification, we identified potentially toxic organic substances in the TWP leachates. Additionally, we investigated their toxicity and underlying mechanisms. Through our established workflow, we structurally identified 13 substances using reference standards. The median effective concentration (EC50) of TWP leachates on Scenedesmus obliquus growth was comparable to that of simulated TWP leachates prepared with consistent concentrations of the 13 identified substances, indicating their dominance in the toxicity of TWP leachates. Among these substances, cyclic amines (EC50: 1.04–3.65 mg/L) were found to be toxic to S. obliquus. We observed significant differential metabolites in TWP leachate-exposed S. obliquus, primarily associated with linoleic acid metabolism and purine metabolism. Oxidative stress was identified as a crucial factor in algal growth inhibition. Our findings shed light on the risk posed by TWP leachable substances to aquatic organisms.

Protective Effects of White Kidney Bean (Phaseolus vulgaris L.) against Diet-Induced Hepatic Steatosis in Mice Are Linked to Modification of Gut Microbiota and Its Metabolites.

Disturbances in the gut microbiota and its derived metabolites are closely related to the occurrence and development of hepatic steatosis. The white kidney bean (WKB), as an excellent source of protein, dietary fiber, and phytochemicals, has recently received widespread attention and might exhibit beneficial effects on a high-fat diet (HFD)-induced hepatic steatosis via targeting gut microbiota and its metabolites. The results indicated that HFD, when supplemented with WKB for 12 weeks, could potently reduce obesity symptoms, serum lipid profiles, and glucose, as well as improve the insulin resistance and liver function markers in mice, thereby alleviating hepatic steatosis. An integrated fecal microbiome and metabolomics analysis further demonstrated that WKB was able to normalize HFD-induced gut dysbiosis in mice, thereby mediating the alterations of a wide range of metabolites. Particularly, WKB remarkably increased the relative abundance of probiotics (Akkermansiaceae, Bifidobacteriaceae, and norank_f_Muribaculaceae) and inhibited the growth of hazardous bacteria (Mucispirillum, Enterorhabdus, and Dubosiella) in diet-induced hepatic steatosis mice. Moreover, the significant differential metabolites altered by WKB were annotated in lipid metabolism, which could ameliorate hepatic steatosis via regulating glycerophospholipid metabolism. This study elucidated the role of WKB from the perspective of microbiome and metabolomics in preventing nonalcoholic fatty liver disease, which provides new insights for its application in functional foods.

Metabolomics in rare minnow (Gobiocypris rarus) after infection by attenuated and virulent grass carp reovirus genotype Ⅱ

Grass carp reovirus genotype Ⅱ (GCRV Ⅱ) causes hemorrhagic disease in a variety fish, seriously affecting the aquaculture industry in China. However, the pathogenesis of GCRV Ⅱ is unclear. Rare minnow is an ideal model organism to study the pathogenesis of GCRV Ⅱ. Herein, we applied liquid chromatography-tandem mass spectrometry metabolomics to investigate metabolic responses in the spleen and hepatopancreas of rare minnow injected with virulent GCRV Ⅱ isolate DY197 and attenuated isolate QJ205. Results indicated that marked metabolic changes were identified in both the spleen and hepatopancreas after GCRV Ⅱ infection, and the virulent DY197 strain induced more significantly different metabolites (SDMs) than the attenuated QJ205 strain. Moreover, most SDMs were downregulated in the spleen and tend to be upregulated in hepatopancreas. The Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis showed that tissue-specific metabolic responses were identified after viruses infection, and the virulent DY197 strain induced more SDMs involved in amino acid metabolism in the spleen, especially the tryptophan metabolism, cysteine and methionine metabolism, which were essential for immune regulation in host; Meanwhile, nucleotide metabolism, protein synthesis and metabolism related pathways were enriched in the hepatopancreas by both virulent and attenuated strains. Our findings revealed the large scale metabolic alterations in rare minnow in response to attenuated and virulent GCRV Ⅱ infection, which will lead to a better understanding of the pathogenesis of viruses and host-pathogens interactions.