Selected Recent Publications Using Metwarebio's Panels And Services
As a leading CRO in the field of metabolomics, MetWareBio possesses extensive experience in metabolomics analysis and multi-omics integrative analysis. In 2023, MetWareBio collaborated with over 300 research teams worldwide, supporting their research practices and contributing to published research findings. Here, we present a selection of our recent publications in popular areas of human medicine research, including colorectal cancer, inflammatory bowel disease, liver disease, bone disorders, cachexia and sepsis, and also researchs in arguiculture and breeding. If you are interested in our services, please feel free to contact us. We look forward to the opportunity to collaborate with you.
Colorectal Cancer: Unveiling Gender-Based Differences and Resistance Mechanisms
Wang, Ling et al. “Male-Biased Gut Microbiome and Metabolites Aggravate Colorectal Cancer Development.” Advanced science (Weinheim, Baden-Wurttemberg, Germany) vol. 10,25 (2023): e2206238. doi:10.1002/advs.202206238
The authors used our service of TM Widely-Targeted Metabolomics to investigate the potential causes of such sexual dimorphism in CRC from the perspective of sex-biased gut microbiota and metabolites. The results show that sexual dimorphism in colorectal tumorigenesis is observed in both ApcMin/ + mice and azoxymethane (AOM)/dextran sulfate sodium (DSS)-treated mice with male mice have significantly larger and more tumors, accompanied by more impaired gut barrier function. In conclusion, the sex-biased gut microbiome and metabolites contribute to sexual dimorphism in CRC. Modulating sex-biased gut microbiota and metabolites could be a potential sex-targeting therapeutic strategy of CRC.
Wang, Chenran et al. “ENO2-derived phosphoenolpyruvate functions as an endogenous inhibitor of HDAC1 and confers resistance to antiangiogenic therapy.” Nature metabolism vol. 5,10 (2023): 1765-1786. doi:10.1038/s42255-023-00883-y
The authors used our service of Energy Targeted Metabolomics to explore the molecular mechanisms of metabolic reprogramming regulating resistance to antiangiogenic therapy in cancer. They identify the glycolytic enzyme enolase 2 (ENO2) as a driver of resistance to antiangiogenic therapy in colorectal cancer (CRC) mouse models and human participants. The findings reveal that ENO2 constitutes a useful predictive biomarker and therapeutic target for resistance to antiangiogenic therapy in CRC, and uncover a previously undefined and metabolism-independent role of PEP in regulating resistance to antiangiogenic therapy by functioning as an endogenous HDAC1 inhibitor.
Sepsis: Identifying Novel Therapeutic Peptides
Xie, Shihao et al. “Novel tripeptide RKH derived from Akkermansia muciniphila protects against lethal sepsis.” Gut vol. 73,1 78-91. 7 Dec. 2023, doi:10.1136/gutjnl-2023-329996
The authors performed untargeted and targeted metabolomics analysis to evaluate the potential contribution of AKK to lethal sepsis development. Metabolomics analysis and germ-free mouse validation experiments revealed that live AKK was able to generate a novel tripeptide Arg-Lys-His (RKH). RKH exerted protective effects against sepsis-induced death and organ damage. The study reveals that RKH may serve as a novel potential therapeutic approach to combat lethal sepsis after successfully translating its efficacy into clinical practice.
Liver Disease: Insights into Inflammation and Protection
Zhang, Liangjun et al. “Runt-related transcription factor-1 ameliorates bile acid-induced hepatic inflammation in cholestasis through JAK/STAT3 signaling.” Hepatology (Baltimore, Md.) vol. 77,6 (2023): 1866-1881. doi:10.1097/HEP.0000000000000041
The authors used our service of Bile Acids Targeted Metabolomics to investigate the role of hepatic RUNX1 and its underlying mechanisms in cholestasis. Mechanistic studies indicated that elevated bile acids stimulated RUNX1 expression by activating the RUNX1 -P2 promoter through JAK/STAT3 signaling. Increased RUNX1 is directly bound to the promotor region of inflammatory chemokines, including CCL2 and CXCL2 , and transcriptionally repressed their expression in hepatocytes, leading to attenuation of liver inflammatory response. This study has gained initial evidence establishing the functional role of hepatocyte RUNX1 in alleviating liver inflammation during cholestasis through JAK/STAT3 signaling. Modulating hepatic RUNX1 activity could be a new therapeutic target for cholestasis.
Lin, Zihan et al. “Protective effects of yeast extract against alcohol-induced liver injury in rats.” Frontiers in microbiology vol. 14 1217449. 20 Jul. 2023, doi:10.3389/fmicb.2023.1217449
The authors performed 16S rRNA gene sequencing analysis and TM widely targeted metabolomics analysis to explore the effects of yeast extract (YE) efficacy on alcoholic liver injury. The results showed that the groups treated with both low-dose yeast extract (YEL) and high-dose yeast extract (YEH) had lower degrees of alcohol-induced liver injury. The abundance of Peptococcus and Ruminococcus reduced in the low-dose yeast extract (YEL) group, while that of Peptococcus, Romboutsia, Parasutterella, and Faecalibaculum reduced in the high-dose (YEH) group. For the analysis of differential metabolites and enriched pathways in the YEL group, the abundance of lysophosphatidylcholine (16:0/0:0) significantly increased, and then the levels of histamine, adenosine and 5' -adenine nucleotide were remarkedly elevated in the YEH group. These findings suggest that both high and low doses of YE can have different protective effects on liver injury in alcoholic liver disease (ALD) rats, in addition to improving gut microbiota disorder.
Bone Disorders: Microbiome-Linked Pathways for Bone Health
Lin, Xu et al. “Gut microbiota impacts bone via Bacteroides vulgatus-valeric acid-related pathways.” Nature communications vol. 14,1 6853. 27 Oct. 2023, doi:10.1038/s41467-023-42005-y
The authors performed integrative analyses in a Chinese cohort of peri-/post-menopausal women with metagenomics / short chain fatty acids targeted metabolomics / whole-genome sequencing to identify novel microbiome-related biomarkers for bone health. The findings suggest that Bacteroides vulgatus and Serum valeric acid (VA) may represent promising targets for osteoporosis prevention/treatment.
Inflammatory Bowel Disease: Lipidomics Analysis in Crohn's Disease
Wu, Fengfei et al. “A CCL2+DPP4+ subset of mesenchymal stem cells expedites aberrant formation of creeping fat in humans.” Nature communications vol. 14,1 5830. 20 Sep. 2023, doi:10.1038/s41467-023-41418-z
The authors performed Quantitative Lipidomics analysis on Crohn's disease patients (sixteen males, six females) and healthy controls (five males, ten females) to investigate the creeping fat formation. The result reveals abnormal lipid metabolism in creeping fat between the two groups. Further experiments (tissues from five males, one female) confirm that both CCL20+CD14+ monocytes and IL-6 activate DPP4+ mesenchymal stem cells towards a pro-adipogenic phenotype. This study provides a comprehensive investigation of creeping fat formation and offers a conceptual framework for discovering therapeutic targets for treatment of Crohn's disease.
Cachexia: Understanding Cancer-Induced Wasting through Metabolomics
Hu, Yong et al. “Cancer-cell-secreted miR-204-5p induces leptin signalling pathway in white adipose tissue to promote cancer-associated cachexia.” Nature communications vol. 14,1 5179. 24 Aug. 2023, doi:10.1038/s41467-023-40571-9
The authors used our service of Widely Targeted Lipidomics to investigate the mechanism of tumour-derived sEVs possiblely regulating white adipose tissue (WAT) browning and fat loss. The study reveals circulating miR-204-5p induces hypoxia-mediated leptin signalling pathway to promote lipolysis and WAT browning, shedding light on both preventive screenings and early intervention for cancer-associated cachexia.
Plant Nutrition: Metabolomics in Agriculture and Breeding
He, Yuqing et al. “The OsBZR1-OsSPX1/2 Module Fine-tunes the Growth-Immunity Trade-off in Adaptation to Phosphate Availability in Rice.” Molecular plant, S1674-2052(23)00397-0. 7 Dec. 2023, doi:10.1016/j.molp.2023.12.003
The authors used our services of combined analysis of widely-targeted metabolomics and transcriptomics, discovered that OsSPX1/2 interacted with OsBZR1 irrespective of Pi-sufficient or Pi-deficient conditions, inhibiting BR-responsive genes. This result shows the OsBZR1-SPX1/2 module balances plant growth-immunity trade-off in response to Pi availability.
Liu, Chunling et al. “Metabolomics combined with physiology and transcriptomics reveal key metabolic pathway responses in apple plants exposure to different selenium concentrations.” Journal of hazardous materials vol. 464 (2024): 132953. doi:10.1016/j.jhazmat.2023.132953
The authors used our services of combined analysis of widely-targeted metabolomics and transcriptomics to explore the molecular mechanism underlying the plant response to Se. The transcriptome and metabolome revealed that Se mainly affected three pathways, namely the 'biosynthesis of amino acids', 'starch and sucrose metabolism', and 'phenylpropanoid biosynthesis' pathways. 9 μM Se improved the synthesis, catabolism and utilization of amino acids and sugars, ultimately promoted plant growth. However, 24 μM Se up-regulated the related genes expression of PK, GPT, P5CS, SUS, SPS and CYP98A, and accumulated a large number of osmoregulation substances, such as citric acid, L-proline, D-sucrose and chlorogenic acid in the roots, ultimately affected the balance between plant growth and defense. In conclusion, this study reveals new insights into the key metabolic pathway in apple plants responses to Se.
Stress Resistance: Enhancing Crop Tolerance through Metabolomics
Liu, Jiong et al. “Trade-offs between the accumulation of cuticular wax and jasmonic acid-mediated herbivory resistance in maize.” Journal of integrative plant biology, 10.1111/jipb.13586. 17 Nov. 2023, doi:10.1111/jipb.13586
The authors used our services of plant quantitative lipidomics and discovered the function of Glossy 8 (ZmGL8), which encodes a 3-ketoacyl reductase belonging to the fatty acid elongase complex, in orchestrating wax production and jasmonic acid (JA)-mediated defenses against herbivores in maize (Zea mays). Comprehensive transcriptomic and lipidomic analyses indicated that the gl8 mutant confers chemical resistance to herbivores by remodeling VLCFA-related lipid metabolism and subsequent JA biosynthesis and signaling. These results suggest that VLCFA-related lipid metabolism has a critical role in regulating the trade-offs between cuticular wax and JA-mediated chemical defenses.
Wang, Tianzuo et al. “Integrated metabolomics and transcriptomics analysis reveals γ-aminobutyric acid enhances the ozone tolerance of wheat by accumulation of flavonoids.” Journal of hazardous materials, vol. 465 133202. 8 Dec. 2023, doi:10.1016/j.jhazmat.2023.133202
The authors used our services of flavonoids targeted metabolomics and provided a comprehensive insight on the role of GABA in enhancing the O3-tolerance of wheat. Elevated O3 triggered the accumulation of dihydroflavone, flavonols, and flavanols. Exogenous GABA enhanced dihydroflavone and dihydroflavonol, and also altered the expression of genes encoding some key enzymes in the flavonoid synthesis pathway. The result showed that GABA alleviated the grain yield loss from 19.6% to 9.6% induced by elevated O3. The research provided a new avenue to mitigate O3 damage to the productivity of crops.
Mu, Meiqi et al. “Physiological characteristics, rhizosphere soil properties, and root-related microbial communities of Trifolium repens L. in response to Pb toxicity.” The Science of the total environment vol. 907 (2024): 167871. doi:10.1016/j.scitotenv.2023.167871
The authors used our services of 16S sequencing to investigate the response mechanism of microorganisms in three root niches of metal tolerant plants to Pb. The results showed that microbial interaction existed between bulk and rhizosphere soil. Rhizosphere bacterium Haliangium was positively correlated with urease activity and soil nutrients. Endophytic bacterium Pseudomonas was positively correlated with plant biomass and played an important role in Pb tolerance of T. repens. This study provided a theoretical basis for the further development of microbial cooperation with plant remediation of heavy metal contaminated soil.
Disease Resistance
Ling, Yueming et al. “Comparative Analysis of Transcriptomics and Metabolomics Reveals Defense Mechanisms in Melon Cultivars against Pseudoperonospora cubensis Infection.” International journal of molecular sciences vol. 24,24 17552. 16 Dec. 2023, doi:10.3390/ijms242417552
The authors utilized integrative transcriptomics and metabolomics approaches in this study to identify potential resistance-associated genes and delineate the strategies involved in the defense against DM in two melon cultivars: the resistant 'PI442177' ('K10-1') and the susceptible 'Huangdanzi' ('K10-9'), post-P. cubensis infection. The complex interplay of transcriptomic and metabolic responses elucidated by this study provides foundational insights into melon's defense mechanisms against DM. The robust resilience of 'K10-1' to DM is attributed to the synergistic interaction of its inherent transcriptomic and metabolic reactions.
Plant Flavor
Li, Chenxue et al. “An integrated metabolomic and transcriptomic analysis reveals the dynamic changes of key metabolites and flavor formation over Tieguanyin oolong tea production.” Food chemistry: X vol. 20 100952. 21 Oct. 2023, doi:10.1016/j.fochx.2023.100952
The authors used widely-targeted metabolomics and transcriptomics approaches to investigate the dynamic changes of key flavor components in samples from various processing steps of Tieguanyin oolong tea production and interpret the formation characteristic flavor during oolong tea manufacturing process. As a result, a total of 1078 metabolites were determined, of which 62 compounds were identified as biomarkers significantly changed over the manufacturing process. Quantitative determination of the total 50,343 transcripts showed 7480 of them were co-expressed different genes. Glutamic acid served as a critical metabolism hub and a signaling molecule for diverse stress responses.
Crop Improvement
Li, Mingjuan et al. “Knockout of the sugar transporter OsSTP15 enhances grain yield by improving tiller number due to increased sugar content in the shoot base of rice (Oryza sativa L.).” The New phytologist vol. 241,3 (2024): 1250-1265. doi:10.1111/nph.19411
The authors used our services of phytohormone targeted metabolomics and elucidated the mechanism by which knockout of the sugar transporter OsSTP15 enhances grain yield via increasing the tiller number in rice. Higher glucose, sucrose, and Tre6P contents were observed at the shoot base of stp15 plants. Transcriptome and metabolome analyses of the shoot base demonstrated that OsSTP15 knockout upregulated the expression of cytokinin (CK) synthesis- and signaling pathway-related genes and increased CK levels. Subsequent accumulation of glucose, sucrose, and Tre6P in the shoot base promotes tillering by stimulating the CK signaling pathway.
Sun, Jiaqi et al. “UV-B irradiation-activated E3 ligase GmILPA1 modulates gibberellin catabolism to increase plant height in soybean.” Nature communications vol. 14,1 6262. 7 Oct. 2023, doi:10.1038/s41467-023-41824-3
The authors used our services of gibberellin targeted metabolomics and found that UV-B irradiation-activated E3 ligase GmILPA1 modulates gibberellin catabolism. The study discovers UV-B promotes the accumulation of GmILPA1, which ubiquitinate the GA catabolic enzyme GA2 OXIDASE-like (GmGA2ox-like), resulting in its degradation in a UV-B-dependent manner. Another E3 ligase, GmUBL1, also ubiquitinate GmGA2ox-like and enhance the GmILPA1-mediated degradation of GmGA2ox-like, which suggest that GmILPA1-GmGA2ox-like module counteract the UV-B-mediated reduction of bioactive GAs.
Plant Coloration
Ye, Lixia et al. “Transcriptome and metabolome analyses of anthocyanin biosynthesis in post-harvest fruits of a full red-type kiwifruit (Actinidia arguta) 'Jinhongguan'.” Frontiers in plant science vol. 14 1280970. 9 Oct. 2023, doi:10.3389/fpls.2023.1280970
The authors used our services of anthocyanin targeted metabolomics and identified the genes related to anthocyanin biosynthesis and the types of anthocyanins in the 'Jinhongguan' fruit. The results show that cyanidin-3-O-galactoside as the main anthocyanin type and revealed key candidate genes of red coloration of post-harvest fruit in Actinidia arguta. These findings provided new insights into the color formation mechanism of post-harvest fruit and offered a theoretical basis for color regulation in kiwifruit.
Tang, Yaping et al. “Identification of carotenoids and candidate genes shaping high pigment chili pepper variety.” Scientia Horticulturae, Volume 327, 2024, 112799, doi: 10.1016/j.scienta.2023.112799.
The authors used our services of carotenoids targeted metabolomics to decipher the regulatory mechanism of high pigment accumulation in mature red pepper (C. annuum) fruit. The results found that total carotenoids of high-pigment genotype (GB23) increased by 168 times during fruit ripening, especially carotenoid compounds such as zeaxanthin, β-cryptoxanthin and capsanthin. Moreover, the difference in the transcript level of genes encoding phytoene synthase 1 (PSY1), β-carotene hydroxylase 1 (BCH1), and capsanthin-capsorubin synthase (CCS) was consistent with the difference in carotenoid accumulation between GB23 and GB42 (low-pigment genotype). The authors further identified eight transcription factors, namely bHLH13, Zinc finger protein ZFP3, MADS-RIN, NAC68, PIF3, and WRKY6, as potential regulators of PSY1, BCH1, or CCS genes. This comprehensive study sheds light on the regulatory mechanism underlying capsanthin accumulation in chili pepper, offering new insights into this important trait.
