PubMed

Rhinology. 2023 Aug 21. doi: 10.4193/Rhin23.236. Online ahead of print.ABSTRACTBACKGROUND: Metabolomics has proven to be a valuable tool in gaining new insights into disease progression and prognosis, the specific metabolic alterations in the serum of recurrent chronic rhinosinusitis with nasal polyps (CRSwNP) patients remain unknown. This study aims to explore the serum metabolomic profiles of recurrent CRSwNP and identify potential predictive biomarkers.METHODS: A prospective, single-center study was conducted on CRSwNP patients prior to endoscopic sinus surgery. Serum samples were subjected to untargeted metabolomic profiling. Patients were followed up for over 2 years and categorized into recurrence and non-recurrence groups. Metabolite differences between the two groups were compared, and the identified differentially regulated metabolites were subsequently validated in a large clinical cohort.RESULTS: 67 CRSwNP patients completed the follow-up schedule, with 47 classified into the non-recurrent group and 20 into the recurrent group. Significant differences were found in the metabolomic profiles between both groups, and serum uric acid (SUA) showed promising predictive potential for postoperative recurrence in both positive and negative ion models. A validation cohort comprising 398 non-recurrent and 142 recurrent CRSwNP patients was recruited, and a significant elevation in SUA levels was observed in recurrent cases. Patients were stratified into tertiles based on the distribution of baseline SUA levels. Multivariate Cox regression analysis showed that higher tertiles of SUA were associated with an increased risk of CRSwNP recurrence compared to lower tertiles, even after adjusting for potential confounding factors. The receiver operating characteristic curve and Kaplan-Meier survival analysis highlighted that elevated SUA levels exhibited potential predictive values for postoperative recurrence.CONCLUSION: Serum metabolic signatures might predict postoperative recurrence in CRSwNP patients. Increased SUA concentrations were found to be associated with a higher risk of future postoperative recurrence in CRSwNP, independent of traditional risk factors.PMID:37602858 | DOI:10.4193/Rhin23.236

Food Funct. 2023 Aug 21. doi: 10.1039/d3fo01751f. Online ahead of print.ABSTRACTIt has been found previously that Bifidobacterium longum, Bacteroides ovatus, Enterococcus faecalis, and Lactobacillus gasseri can form a biofilm better when co-cultured in vitro and B. longum is the core biofilm-formation-promoting strain in this community. B. longum is part of the core microbiota in the gut and is widely recognized as a probiotic. Therefore, it is necessary to explore its role in mixed-species biofilms through transcriptomics and metabolomics. Metabolomics showed that the increase in amino acid and purine content could promote biofilm formation. In transcriptomic analysis, many genes related to carbohydrate metabolism, amino acid metabolism, and environmental tolerance of B. longum were up-regulated. Combined with the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis and Gene Ontology (GO) analysis, the differentially expressed genes (DEGs) of B. longum in mixed-species biofilms were mainly correlated to "quorum sensing (QS)", "ABC transporters", "biosynthesis of amino acids", "microbial metabolism in different environments", "carbohydrate metabolism" and "two-component system". In addition, the rpl and rps gene families, which function in the metabolism of organic substances and the biosynthesis of amino acids, were the core DEGs according to the analysis of the protein-protein interaction (PPI) network. Finally, by combining metabolomics and quorum sensing mechanisms, it was found that the metabolism of autoinducer peptides (proliylglycine and glycylleucine), N-acyl homoserine lactone (N-(3-oxo hydroxy) homoserine lactone), and AI-2 can promote the formation of biofilms, both mono- and mixed-species biofilms composed of B. longum. Our research enabled us to understand the critical role of B. longum in mixed-species biofilms and the interactions between biofilm metabolism and gut health. In addition, the generated knowledge will be of great significance for us to develop biofilm products with beneficial functions in future.PMID:37602484 | DOI:10.1039/d3fo01751f

Pharm Biol. 2023 Dec;61(1):1260-1273. doi: 10.1080/13880209.2023.2244533.ABSTRACTCONTEXT: Yiqi Liangxue Shengji prescription (YQLXSJ) is a traditional Chinese medicine (TCM) formula that has long been used for treatment after percutaneous coronary intervention (PCI).OBJECTIVE: To investigate the putative pharmacological mechanism of YQLXSJ on restenosis through an integrated approach utilizing metabolomics and network pharmacology.MATERIALS AND METHODS: Forty male Sprague-Dawley rats were divided into sham, model, YQLXSJ, and positive groups. YQLXSJ group received the treatment of YQLXSJ (6 g/kg/d, i.g.) and the positive group was treated with atorvastatin (2 mg/kg/d, i.g.). After 4 weeks, the improvement in intimal hyperplasia was evaluated by ultrasound, H&E staining, and immunofluorescence. UPLC-MS/MS technology was utilized to screen the differential metabolites. Network pharmacology was conducted using TCMSP, GeneCards, and Metascape, etc., in combination with metabolomics. Eventually, the core targets were acquired and validated.RESULTS: Compared to models, YQLXSJ exhibited decreased intima-media thickness on ultrasound (0.23 ± 0.02 mm vs. 0.20 ± 0.01 mm, p < 0.01) and reduced intima thickness by H&E (30.12 ± 6.05 μm vs. 14.32 ± 1.37 μm, p < 0.01). We identified 18 differential metabolites and 5 core targets such as inducible nitric oxide synthase (NOS2), endothelial nitric oxide synthase (NOS3), vascular endothelial growth factor-A (VEGFA), ornithine decarboxylase-1 (ODC1) and group IIA secretory phospholipase A2 (PLA2G2A). These targets were further confirmed by molecular docking and ELISA.DISCUSSION AND CONCLUSIONS: This study confirms the effects of YQLXSJ on restenosis and reveals some biomarkers. TCM has great potential in the prevention and treatment of restenosis by improving metabolic disorders.PMID:37602438 | DOI:10.1080/13880209.2023.2244533

Front Mol Biosci. 2023 Aug 3;10:1222133. doi: 10.3389/fmolb.2023.1222133. eCollection 2023.ABSTRACTIntroduction: Acute aortic dissection (AAD) often leads to the development of acute lung injury (ALI). However, the early detection and diagnosis of AAD in patients with ALI pose significant challenges. The objective of this study is to investigate distinct metabolic alterations in the plasma samples of AAD patients with ALI, AAD patients without ALI, and healthy individuals. Method: Between September 2019 and September 2022, we retrospectively collected data from 228 AAD patients who were diagnosed with ALI through post-surgery chest X-ray and PaO2/FiO2 assessments. Univariate analysis was employed to identify pre-surgery risk factors for ALI. Additionally, we conducted high-throughput target metabolic analysis on 90 plasma samples, comprising 30 samples from AAD patients with ALI, 30 from patients with AAD only, and 30 from healthy controls. After LC-MS spectral processing and metabolite quantification, the recursive feature elimination with cross-validation (RFECV) analysis based on the random forest was used to select the optimal metabolites as a diagnostic panel for the detection of AAD patients with ALI. The support vector machines (SVM) machine learning model was further applied to validate the diagnostic accuracy of the established biomarker panel. Results: In the univariate analysis, preoperative β-HB and TNF-α exhibited a significant association with lung injury (OR = 0.906, 95% CI 0.852-0.965, p = 0.002; OR = 1.007, 95% CI 1.003-1.011, p < 0.0001). The multiple-reaction monitoring analysis of 417 common metabolites identified significant changes in 145 metabolites (fold change >1.2 or <0.833, p < 0.05) across the three groups. Multivariate statistical analysis revealed notable differences between AAD patients and healthy controls. When compared with the non-ALI group, AAD patients with ALI displayed remarkable upregulation in 19 metabolites and downregulation in 4 metabolites. Particularly, combining citric acid and glucuronic acid as a biomarker panel improved the classification performance for distinguishing between the ALI and non-ALI groups. Discussion: Differentially expressed metabolites in the ALI group were primarily involved in amino acids biosynthesis, carbohydrate metabolism (TCA cycle), arginine and proline metabolism, and glucagon signaling pathway. These findings demonstrate a great potential of the targeted metabolomic approach for screening, routine surveillance, and diagnosis of pulmonary injury in patients with AAD.PMID:37602331 | PMC:PMC10434778 | DOI:10.3389/fmolb.2023.1222133

Front Mol Biosci. 2023 Aug 4;10:1230282. doi: 10.3389/fmolb.2023.1230282. eCollection 2023.ABSTRACTThis mini review focuses on the opportunities provided by current and emerging separation techniques for mass spectrometry metabolomics. The purpose of separation technologies in metabolomics is primarily to reduce complexity of the heterogeneous systems studied, and to provide concentration enrichment by increasing sensitivity towards the quantification of low abundance metabolites. For this reason, a wide variety of separation systems, from column chemistries to solvent compositions and multidimensional separations, have been applied in the field. Multidimensional separations are a common method in both proteomics applications and gas chromatography mass spectrometry, allowing orthogonal separations to further reduce analytical complexity and expand peak capacity. These applications contribute to exponential increases in run times concomitant with first dimension fractionation followed by second dimension separations. Multidimensional liquid chromatography to increase peak capacity in metabolomics, when compared to the potential of running additional samples or replicates and increasing statistical confidence, mean that uptake of these methods has been minimal. In contrast, in the last 15 years there have been significant advances in the resolution and sensitivity of ion mobility spectrometry, to the point where high-resolution separation of analytes based on their collision cross section approaches chromatographic separation, with minimal loss in sensitivity. Additionally, ion mobility separations can be performed on a chromatographic timescale with little reduction in instrument duty cycle. In this review, we compare ion mobility separation to liquid chromatographic separation, highlight the history of the use of ion mobility separations in metabolomics, outline the current state-of-the-art in the field, and discuss the future outlook of the technology. "Where there is one, you're bound to divide it. Right in two", James Maynard Keenan.PMID:37602325 | PMC:PMC10436490 | DOI:10.3389/fmolb.2023.1230282

Front Vet Sci. 2023 Aug 4;10:1239651. doi: 10.3389/fvets.2023.1239651. eCollection 2023.ABSTRACTThe study aimed to investigate the impact of Bovine Respiratory Disease (BRD) on the metabolism of beef steers during a 35-d receiving period using plasma metabolomics. In this study, 77 newly weaned crossbred (Angus × Hereford) beef steers (BW = 206 ± 12 kg and age = 180 ± 17 days) were categorized into two groups: Healthy and Sick groups. The Sick group comprised beef steers diagnosed with BRD at any time during the 35-day period (n = 31), while the Healthy group did not show any signs of BRD (n = 46). Blood samples were collected from the coccygeal vessels on day 35, and plasma samples were subjected to targeted metabolomics analysis using Nuclear Magnetic Resonance spectroscopy. Data and statistical analyses, including biomarker and pathway enrichment analyses, were performed using Metaboanalyst 5.0. Results of the growth performance showed that sick steers had lower (p ≤ 0.05) ADG (1.44 vs. 1.64 kg/d) and higher (p = 0.01) feed:gain ratio (3.57 vs. 3.13) compared to healthy steers. A total of 50 metabolites were quantified. The partial least squares discriminant scores plot showed a slight separation between the two groups of steers, indicating some metabolic differences. Furthermore, the plasma concentrations of four metabolites (sarcosine, methionine, dimethyl sulfone, and L-histidine) were greater (p ≤ 0.05) in healthy steers compared to sick steers. Among these metabolites, sarcosine and methionine qualified as candidate biomarkers associated with BRD infection based on an area under the curve >0.70. Additionally, quantitative enrichment analysis revealed that cysteine and methionine metabolism was enriched in healthy steers compared to sick steers. This suggests that these metabolic pathways may play a role in the response to BRD infection. The findings of this study highlight the altered plasma metabolome in steers with BRD during the receiving period. Understanding these metabolic changes can contribute to the development of effective management strategies and nutritional interventions to mitigate the negative impact of BRD on beef cattle health and immune function.PMID:37601765 | PMC:PMC10436613 | DOI:10.3389/fvets.2023.1239651

Front Vet Sci. 2023 Aug 2;10:1178093. doi: 10.3389/fvets.2023.1178093. eCollection 2023.ABSTRACTHolstein cattle are well known for their high average milk yield but are more susceptible to disease and have lower fecundity than other breeds of cattle. The purpose of this study was to explore the relationship between ruminal metabolites and both milk performance and ruminal microbiota composition as a means of assessing the benefits of crossbreeding Montbéliarde and Holstein cattle. This experiment crossbred Holstein with Montbéliarde cattle, aimed to act as a reference for producing high-quality dairy products and improving the overall efficiency of dairy cattle breeding. Based on similar age, parity and lactation time, 46 cows were selected and divided into two groups (n = 23 per group) for comparison experiment and fed the same formula: Montbéliarde×Holstein (MH, DIM = 33.23 ± 5.61 d), Holstein (H, DIM = 29.27 ± 4.23 d). Dairy herd improvement (DHI) data is an important basis for evaluating the genetic quality of bulls, understanding the quality level of milk, and improving feeding management. We collected the DHI data of these cows in the early lactation, middle lactation and late lactation period of 10 months. The results showed that the average milk production and protein content in Montbéliarde×Holstein were 1.76 kg (34.41 kg to 32.65 kg, p > 0.05) and 0.1% (3.54 to 3.44%, p < 0.05) higher than in Holstein cattle. Moreover, milk from Montbéliarde×Holstein cattle had lesser somatic cell score (1.66 to 2.02) than Holstein cattle (p < 0.01). A total of 10 experimental cattle in early lactation were randomly selected in the two groups (Lactation time = 92.70 ± 6.81), and ruminal fluid were collected by oral gastric tube. Using 16S rRNA microbial sequencing, we compared the ruminal microbiota composition and found that Montbéliarde×Holstein cattle had a lower abundance of Alphaproteobacteria (p < 0.05) and higher abundance of Selenomonas than Holstein cattle (p < 0.05). These bacteria play roles in protein degradation, nitrogen fixation and lactic acid degradation. The abundance of Succiniclasticum was also greater in Montbéliarde×Holstein cattle (p = 0.053). Through ruminal metabolome analysis, we found that the levels of trans-ferulic acid, pyrrole-2-carboxylic acid, and quinaldic acid were significantly increased in Montbéliarde×Holstein cattle, while that of lathosterol was significantly decreased. The changes in the levels of these metabolites could confer improved antioxidant, anti-inflammatory, and antibacterial activities.PMID:37601757 | PMC:PMC10433227 | DOI:10.3389/fvets.2023.1178093

Front Microbiol. 2023 Aug 2;14:1210890. doi: 10.3389/fmicb.2023.1210890. eCollection 2023.ABSTRACTPlant-associated microbes include taxonomically diverse communities of bacteria, archaebacteria, fungi, and viruses, which establish integral ecological relationships with the host plant and constitute the phyto-microbiome. The phyto-microbiome not only contributes in normal growth and development of plants but also plays a vital role in the maintenance of plant homeostasis during abiotic stress conditions. Owing to its immense metabolic potential, the phyto-microbiome provides the host plant with the capability to mitigate the abiotic stress through various mechanisms like production of antioxidants, plant growth hormones, bioactive compounds, detoxification of harmful chemicals and toxins, sequestration of reactive oxygen species and other free radicals. A deeper understanding of the structure and functions of the phyto-microbiome and the complex mechanisms of phyto-microbiome mediated abiotic stress mitigation would enable its utilization for abiotic stress alleviation of crop plants and development of stress-resistant crops. This review aims at exploring the potential of phyto-microbiome to alleviate drought, heat, salinity and heavy metal stress in crop plants and finding sustainable solutions to enhance the agricultural productivity. The mechanistic insights into the role of phytomicrobiome in imparting abiotic stress tolerance to plants have been summarized, that would be helpful in the development of novel bioinoculants. The high-throughput modern approaches involving candidate gene identification and target gene modification such as genomics, metagenomics, transcriptomics, metabolomics, and phyto-microbiome based genetic engineering have been discussed in wake of the ever-increasing demand of climate resilient crop plants.PMID:37601386 | PMC:PMC10433232 | DOI:10.3389/fmicb.2023.1210890

Front Microbiol. 2023 Aug 3;14:1159637. doi: 10.3389/fmicb.2023.1159637. eCollection 2023.ABSTRACTThe changes in the composition of intestinal microbiota and metabolites have been linked to digestive disorders in calves, especially neonatal calf diarrhea. Bovine rotavirus (BRV) and bovine coronavirus (BCoV) are known to be the primary culprits behind neonatal calf diarrhea. In this study, we analyzed changes in the fecal microbiota and metabolites of calves with neonatal diarrhea associated with BRV and BCoV infection using high-throughput 16S rRNA sequencing and metabolomics technology. The microbial diversity in the feces of calves infected with BRV and BCoV with diarrhea decreased significantly, and the composition changed significantly. The significant increase of Fusobacterium and the reductions of some bacteria genera, including Faecalibacterium, Bifidobacterium, Ruminococcus, Subdoligranulum, Parabacteroides, Collinsella, and Olsenella, etc., were closely related to diarrhea associated with BRV and BCoV infection. Metabolites in the feces of BRV and BCoV-infected calves with diarrhea were significantly changed. Phosphatidylcholine [PC; 16:1(9 Z)/16:1(9 Z)], lysophosphatidylethanolamine (LysoPE; 0:0/22:0), lysophosphatidylcholine (LysoPC; P-16:0) and LysoPE (0:0/18:0) were significantly higher in the feces of BRV-infected calves with diarrhea. In contrast, some others, such as desthiobiotin, were significantly lower. BRV infection affects glycerophospholipid metabolism and biotin metabolism in calves. Two differential metabolites were significantly increased, and 67 differential metabolites were significantly reduced in the feces of BCoV-infected calves with diarrhea. Seven significantly reduced metabolites, including deoxythymidylic acid (DTMP), dihydrobiopterin, dihydroneopterin triphosphate, cortexolone, cortisol, pantetheine, and pregnenolone sulfate, were enriched in the folate biosynthesis, pantothenate and CoA biosynthesis, pyrimidine metabolism, and steroid hormone biosynthesis pathway. The decrease in these metabolites was closely associated with increased harmful bacteria and reduced commensal bacteria. The content of short-chain fatty acids (SCFAs) such as acetic acid and propionic acid in the feces of BRV and BCoV-infected calves with diarrhea was lower than that of healthy calves, which was associated with the depletion of SCFAs-producing bacteria such as Parabacteroides, Fournierella, and Collinsella. The present study showed that BRV and BCoV infections changed the composition of the calf fecal microbiota and were associated with changes in fecal metabolites. This study lays the foundation for further revealing the roles of intestinal microbiota in neonatal calf diarrhea associated with BRV and BCoV infection.PMID:37601373 | PMC:PMC10434556 | DOI:10.3389/fmicb.2023.1159637

Front Microbiol. 2023 Aug 2;14:1219491. doi: 10.3389/fmicb.2023.1219491. eCollection 2023.ABSTRACTINTRODUCTION: Microorganisms play an important role in the multifunctionality of soil ecosystems. Soil microbial diversity and functions have a great impact on plant growth and development. The interactions between tea trees and soil microbiota can be linked with planting patterns and management strategies, whose effects on soil microbial community structure and metabolites are still unclear.METHODS: Here we used amplicon sequencing and metabolomic analysis to investigate the differences in soil microbial composition and metabolites among three tea production systems: organic, non-organic, and intercropping.RESULTS: We detected significant differences among the three systems and found that Firmicutes, Proteobacteria, Acidobacteriota, Actinobacteriota and Chloroflexi were the main bacteria in the three soil groups, although they varied in relative abundance. Acidobacteria bacterium increased significantly in the organic and intercropping groups. For fungi, Ascomycota and Basidiomycota were the main differential fungal phyla. Fungi alpha-diversity in the non-organic group was significantly higher than that in the other two groups, and was correlated with multiple soil physical and chemical factors. Moreover, network analysis showed that bacteria and fungi were strongly correlated. The changes in soil microorganisms caused by management and planting patterns may affect soil quality through corresponding changes in metabolites. Metabolomic analysis showed differences in metabolite composition among different groups. It was also found that the arachidonic acid metabolic pathway was affected by changes in soil microorganisms, and may further affect soil quality in an essential manner.DISCUSSION: Planting patterns and management strategies may significantly affect soil microorganisms and therefore metabolites. Changes in soil microorganisms, especially in fungi, may alter soil quality by affecting soil physicochemical properties and metabolites. This study will provide new insights into soil quality monitoring from a microbiological perspective.PMID:37601365 | PMC:PMC10433390 | DOI:10.3389/fmicb.2023.1219491

Front Microbiol. 2023 Aug 4;14:1229407. doi: 10.3389/fmicb.2023.1229407. eCollection 2023.ABSTRACTBACKGROUND: Noise exposure could lead to hearing loss and disorders of various organs. Recent studies have reported the close relations of environmental noise exposure to the metabolomics dysregulations and gut microbiota disturbance in the exposers. However, the associations between gut microbial homeostasis and the body metabolism during noise-induced hearing loss (NIHL) were unclear. To get a full understanding of their synergy in noise-associated diseases, it is essential to uncover their impacts and associations under exposure conditions.METHODS: With ten male rats with background noise exposure (≤ 40 dB) as controls (Ctr group), 20 age- and weight-matched male rats were exposed to 95 dB Sound pressure level (SPL) (LN group, n = 10) or 105 dB SPL noise (HN group, n = 10) for 30 days with 4 h/d. The auditory brainstem response (ABR) of the rats and their serum biochemical parameters were detected to investigate their hearing status and the potential effects of noise exposure on other organs. Metabolomics (UPLC/Q-TOF-MS) and microbiome (16S rDNA gene sequencing) analyses were performed on samples from the rats. Multivariate analyses and functional enrichments were applied to identify the dysregulated metabolites and gut microbes as well as their associated pathways. Pearson correlation analysis was performed to investigate the associations of the dysregulations of microbiota and the metabolites.RESULTS: NIHL rat models were constructed. Many biochemical parameters were altered by noise exposure. The gut microbiota constitution and serum metabolic profiles of the noise-exposed rats were also dysregulated. Through metabolomics analysis, 34 and 36 differential metabolites as well as their associated pathways were identified in LN and HN groups, respectively. Comparing with the control rats, six and 14 florae were shown to be significantly dysregulated in the LN group and HN group, respectively. Further association analysis showed significant correlations between differential metabolites and differential microbiota.CONCLUSION: There were cochlea injuries and abnormalities of biochemical parameters in the rats with NIHL. Noise exposure could also disrupt the metabolic profiles and the homeostatic balance of gut microbes of the host as well as their correlations. The dysregulated metabolites and microbiota might provide new clues for prevention of noise-related disorders.PMID:37601356 | PMC:PMC10436299 | DOI:10.3389/fmicb.2023.1229407

PeerJ. 2023 Aug 14;11:e15731. doi: 10.7717/peerj.15731. eCollection 2023.ABSTRACTMarine biofouling is a natural process by which many organisms colonize and grow in submerged structures, causing serious economic consequences for the maritime industry. Geniculate calcareous algae (GCA; Corallinales, Rhodophyta) produce bioactive secondary metabolites and are a promise for new antifouling compounds. Here, we investigated the antifouling activity of four GCA species-Amphiroa beauvoisii, Jania sagittata (formerly Cheilosporum sagittatum), Jania crassa, and Jania prolifera (formerly Amphiroa flabellata)-from the Brazilian coast against macro- and microorganisms. Simultaneously, metabolomic tools were applied to assess the chemical profiles of these seaweeds using gas chromatography coupled to mass spectrometry (GC-MS). Data analysis by principal component and molecular networking analyses used the global natural products social molecular networking platform (GNPS). Our results showed that all extracts were active against different strains of marine bacteria and that the J. sagittata (JsSI) extract showed the highest percentage of bacterial inhibition. The J. sagittata (JsSI) extract was the most active against the mussel Perna perna, showing 100% byssus inhibition. Regarding toxicity, only the J. crassa (JcP) extract showed a 20% mortality rate. The chemical profiles of the evaluated GCA extracts differed qualitatively and quantitatively. Yet, the steroid (3β)-cholest-5-en-3-ol was the major compound commonly identified in all extracts, with the exception of J. sagittata (JsSI). Moreover, we observed intra- and interspecific chemical variabilities among GCA extracts for the different populations, which could explain their antifouling activity variability. This study contributed new information about the chemical compounds produced by this group of seaweeds and showed its antifouling potential. These GCA species may be the subject of future studies to obtain new bioactive compounds with biotechnological potential in maritime areas.PMID:37601267 | PMC:PMC10434099 | DOI:10.7717/peerj.15731

Front Pharmacol. 2023 Aug 3;14:1178724. doi: 10.3389/fphar.2023.1178724. eCollection 2023.ABSTRACTLeukopenia caused by radiation hinders the continuous treatment of cancers. Danggui Buxue Decoction (DBD) has been widely used in clinical owing to low toxicity and definite therapeutic effects to increase leukocytes. Meanwhile, icaritin (ICT) has also been proved to have the effect of boosting peripheral blood cells proliferation. However, there is no study to prove the efficacy of MDBD (Modified Danggui Buxue Decoction), a derivative herbal formula composed of DBD and ICT, in the treatment of radiation-induced leukopenia. In this study, we performed a model of 3.5 Gy whole-body radiation to induce leukopenia in mice. The results of pharmacodynamic studies demonstrated that MDBD could significantly increase the white blood cells in peripheral blood by improving the activity of bone marrow nuclear cells, reducing bone marrow damage, modulating spleen index, and regulating hematopoietic factors to alleviate leukopenia. We also analyzed the integrated results of metabolomics and transcriptomics and found that MDBD could relieve leukopenia and alleviate bone marrow damage by targeting steroid biosynthesis and IL-17 signaling pathway, in which the key genes are Jun, Cxcl2 and Egr1. Therefore, our study provides a basis for the effectiveness and compatibility in the combination of traditional Chinese medicine formula and small molecule drugs.PMID:37601071 | PMC:PMC10434993 | DOI:10.3389/fphar.2023.1178724

Front Cell Infect Microbiol. 2023 Aug 2;13:1218326. doi: 10.3389/fcimb.2023.1218326. eCollection 2023.ABSTRACTBACKGROUND: Type 2 diabetes mellitus (T2DM) is a prevalent metabolic disease that causes multi-organ complications, seriously affecting patients' quality of life and survival. Understanding its pathogenesis remains challenging, with current clinical treatment regimens often proving ineffective.METHODS: In this study, we established a mouse model of T2DM and employed 16s rDNA sequencing to detect changes in the species and structure of gut flora. Additionally, we used UPLC-Q-TOF-MS to identify changes in urinary metabolites of T2DM mice, analyzed differential metabolites and constructed differential metabolic pathways. Finally, we used Pearman correlation analysis to investigate the relationship between intestinal flora and differential metabolites in T2DM mice, aiming to elucidate the pathogenesis of T2DM and provide an experimental basis for its clinical treatment.RESULTS: Our findings revealed a reduction in both the species diversity and abundance of intestinal flora in T2DM mice, with significantly decreased levels of beneficial bacteria such as Lactobacillus and significantly increased levels of harmful bacteria such as Helicobacter pylori. Urinary metabolomics results identified 31 differential metabolites between T2DM and control mice, including Phosphatidylcholine, CDP-ethanolamine and Leukotriene A4, which may be closely associated with the glycerophospholipid and arachidonic acid pathways. Pearman correlation analysis showed a strong correlation between dopamine and gonadal, estradiol and gut microbiota, may be a novel direction underlying T2DM.CONCLUSION: In conclusion, our study suggests that alterations in gut microbiota and urinary metabolites are characteristic features of T2DM in mice. Furthermore, a strong correlation between dopamine, estradiol and gut microbiota, may be a novel direction underlying T2DM, the aim is to provide new ideas for clinical treatment and basic research.PMID:37600949 | PMC:PMC10433779 | DOI:10.3389/fcimb.2023.1218326

Anim Nutr. 2023 Jun 19;14:281-302. doi: 10.1016/j.aninu.2023.06.002. eCollection 2023 Sep.ABSTRACTOxidative stress is a common phenomenon in poultry production. Several molecules, including antioxidant genes, miRNAs, and gut microbiota metabolites, have been reported to participate in redox regulation. Lactiplantibacillus plantarum P8 (P8) was shown to improve the antioxidant capacity of chickens, but the specific molecular mechanisms remain unclear. In this study, 400 broilers were allocated to 4 treatment groups: control diet (Con group), control diet + dexamethasone injection (DEX group), control diet containing 1 × 108 CFU/g P8 (P8 group), and control diet containing 1 × 108 CFU/g P8 + DEX injection (DEX_P8 group). Integrated analysis of the microbiome, metabolomics, and miRNAomics was conducted to investigate the roles of P8 in oxidative stress in broilers. Results demonstrated that P8 supplementation significantly improved growth performance, jejunal morphology, and antioxidant function in DEX-treated broilers. Analysis of the gut microbiota revealed a higher abundance of Barnesiella (P = 0.01) and Erysipelatoclostridium (P = 0.05) in the DEX_P8 group than in the DEX group. Functional prediction indicated that certain pathways, including the phenylacetate degradation pathway, were enriched in the DEX_P8 group compared to the DEX group. Metabolites in the cecal contents were distinct between the groups. P8 supplementation increased the content of metabolites with antioxidant capacity, e.g., urobilinogen (P < 0.01), and decreased that of metabolites related to oxidative stress, e.g., genistein (P < 0.01). Functional prediction indicated that metabolites that differed between the DEX_P8 and DEX groups were enriched in pathways including "tryptophan metabolism" and "primary bile acid biosynthesis". The miRNAomics analysis further showed that, compared to the DEX group, several miRNAs in the jejunum, such as gga-miR-21-3p (P = 0.03), were increased, whereas gga-miR-455-3p (P = 0.02) was decreased in the DEX_P8 group. The PI3K-Akt, Ras, and Rap1 signaling pathways were enriched in the DEX_P8 group compared to the DEX group through KEGG analysis. Correlation analysis revealed potential interactions between growth performance, oxidation/antioxidation, jejunal morphology, gut microbiota, cecal content metabolites, and jejunal miRNAs. Overall, our results indicate that P8 supplementation may improve the growth performance, jejunal morphology and antioxidant capacity of DEX-treated broilers by regulating gut microbiota, its metabolites, and intestinal miRNAs.PMID:37600839 | PMC:PMC10432922 | DOI:10.1016/j.aninu.2023.06.002

Ann Surg Open. 2022 Dec 7;3(4):e224. doi: 10.1097/AS9.0000000000000224. eCollection 2022 Dec.ABSTRACTMetabolic reprogramming is closely linked to the tumorigenesis and drug resistance of gastrointestinal stromal tumors (GISTs). Mapping the metabolic orbit of GISTs is a prerequisite if intervention against the metabolic vulnerability of refractory GISTs is desirable.METHODS: A total of 43 patients with treatment-naïve GISTs who had undergone surgical resections were enrolled, on whom a metabolomics profile detected from surgical specimens was constructed based on the 1H-nuclear magnetic resonance (NMR) platform. The mRNA and protein levels of GLUT1, HK2, ACSS2, and FASN were assayed. Dual-tracer 18F-FDG/11C-acetate PET imaging was introduced before surgery in 15 patients.RESULTS: 1H-NMR-based metabolomics revealed that GISTs were characterized by upregulation of glutamate, ascorbate, aspartate and glycine and downregulation of choline, creatine, glucose and glycerol. Bioinformatics analysis showed that the TCA cycle and alanine, aspartate, and glutamate metabolism were the two leading pathways. High- and nonhigh-risk (including intermediate-, low-, and very low-risk) GISTs preferentially displayed upregulation of HK2 and ACSS2, respectively, echoed by in vivo imaging that high- and nonhigh-risk GISTs preferentially exhibited higher uptake of 18F-FDG and 11C-acetate, respectively, while 18F-FDG and 11C-acetate were complementary to each other. Nuclear ACSS2 was exclusively identified in high-risk GISTs.CONCLUSION: We describe a metabolic landscape of GISTs that read aspartate as a de facto "oncometabolite," which was replenished via the TCA cycle and alanine, aspartate, and glutamate metabolism. Glycolysis and ACSS2-mediated acetate metabolism competed and complemented fatty acid synthesis, although glycolysis remained an aggressive phenotype.PMID:37600289 | PMC:PMC10406007 | DOI:10.1097/AS9.0000000000000224

Front Drug Discov (Lausanne). 2023 May 10;3:fddsv.2023.1185679. doi: 10.3389/fddsv.2023.1185679.ABSTRACTUnderstanding the target and mode of action of compounds identified by phenotypic screening can greatly facilitate the process of drug discovery and development. Here, we outline the tools currently available for target identification against the neglected tropical diseases, human African trypanosomiasis, visceral leishmaniasis and Chagas' disease. We provide examples how these tools can be used to identify and triage undesirable mechanisms, to identify potential toxic liabilities in patients and to manage a balanced portfolio of target-based campaigns. We review the primary targets of drugs that are currently in clinical development that were initially identified via phenotypic screening, and whose modes of action affect protein turnover, RNA trans-splicing or signalling in these protozoan parasites.PMID:37600222 | PMC:PMC7614965 | DOI:10.3389/fddsv.2023.1185679

Front Plant Sci. 2023 Aug 4;14:1223720. doi: 10.3389/fpls.2023.1223720. eCollection 2023.ABSTRACTFritillaria unibracteata (FU) is a renowned herb in China that requires strict growth conditions in its cultivation process. During this process, the soil microorganisms and their metabolites may directly affect the growth and development of FU, for example, the pathogen infection and sipeimine production. However, few systematic studies have reported the changes in the microbiome and metabolites during FU cultivation thus far. In this work, we simultaneously used metagenomics and metabolomics technology to monitor the changes in microbial communities and metabolites in the rhizosphere of FU during its cultivation for one, two, and three years. Moreover, the interaction between microorganisms and metabolites was investigated by co-occurrence network analysis. The results showed that the microbial composition between the three cultivation-year groups was significantly different (2020-2022). The dominant genera changed from Pseudomonas and Botrytis in CC1 to Mycolicibacterium and Pseudogymnoascus in CC3. The relative abundances of beneficial microorganisms decreased, while the relative abundances of harmful microorganisms showed an increasing trend. The metabolomics results showed that significant changes of the of metabolite composition were observed in the rhizosphere soil, and the relative abundances of some beneficial metabolites showed a decreasing trend. In this study, we discussed the changes in the microbiome and metabolites during the three-year cultivation of FU and revealed the relationship between microorganisms and metabolites. This work provides a reference for the efficient and sustainable cultivation of FU.PMID:37600181 | PMC:PMC10436506 | DOI:10.3389/fpls.2023.1223720

iScience. 2023 Jul 3;26(8):107263. doi: 10.1016/j.isci.2023.107263. eCollection 2023 Aug 18.ABSTRACTSalmonella, a foodborne pathogen, has become a major public health concern because of its widespread drug resistance, including resistance to multiple drugs such as third-generation cephalosporin, ceftriaxone (CRO). However, the metabolic profile changes and associated mechanisms engendered by cephalosporin-resistant mutations remain uncharted. In this study, we have employed the LC-MS/MS metabolomics platform to determine the metabolic profiles of 138 strains of Salmonella. Our results show that metabolic profiles correspond to specific serotypes, sources, processing stages, and antibiotic resistance patterns. Notably, we observed that Salmonella Derby (S. Derby) with drug resistance to CRO has a different metabolic status with changes in glutathione biosynthesis. Specifically, glutathione oxidized (GSSG) and citrulline abundances are greatly suppressed in CRO-resistant S. Derby. Furthermore, exogenous GSSG or citrulline, but not glutathione reduced (GSH), restored the susceptibility of multidrug-resistant S. Derby to CRO. This study establishes a strategy based on functional metabolomics to manage the survival of antibiotic-resistant bacteria.PMID:37599819 | PMC:PMC10432962 | DOI:10.1016/j.isci.2023.107263

Front Nutr. 2023 Aug 3;10:1203430. doi: 10.3389/fnut.2023.1203430. eCollection 2023.ABSTRACTINTRODUCTION: The polysaccharides found in Cordyceps cicadae (C. cicadae) have received increasing academic attention owing to their wide variety of therapeutic activities.METHODS: This study evaluated the hypoglycemic, antioxidant, and anti-inflammatory effects of polysaccharides from C. cicadae (CH-P). In addition, 16s rDNA sequencing and untargeted metabolomics analysis by liquid chromatography-mass spectrometry (LC-MS) were used to estimate the changes and regulatory relationships between gut microbiota and its metabolites. The fecal microbiota transplantation (FMT) was used to verify the therapeutic effects of microbial remodeling.RESULTS: The results showed that CH-P treatment displayed hypoglycemic, antioxidant, and anti-inflammatory effects and alleviated tissue damage induced by diabetes. The CH-P treatment significantly reduced the Firmicutes/Bacteroidetes ratio and increased the abundance of Bacteroides, Odoribacter, Alloprevotella, Parabacteroides, Mucispirillum, and significantly decreased the abundance of Helicobacter and Lactobacillus compared to the diabetic group. The alterations in the metabolic pathways were mostly related to amino acid biosynthesis and metabolic pathways (particularly those involving tryptophan) according to the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis. Correlation analysis showed that Bacteroides, Odoribacter, Alloprevotella, Parabacteroides, and Mucispirillum were positively correlated with indole and its derivatives, such as 5-hydroxyindole-3-acetic acid. Indole intervention significantly improved hyperglycemic symptoms and insulin sensitivity, and increased the secretion of glucagon-like peptide-1 (GLP-1) in diabetic mice. FMT reduced blood glucose levels, improved glucose tolerance, and increased insulin sensitivity in diabetic mice. However, FMT did not significantly improve GLP-1 levels.DISCUSSION: This indicates that C. cicadae polysaccharides alleviate hyperglycemia by regulating the production of metabolites other than indole and its derivatives by gut microbiota. This study provides an important reference for the development of novel natural products.PMID:37599693 | PMC:PMC10434777 | DOI:10.3389/fnut.2023.1203430