PubMed

Microbiol Spectr. 2023 Mar 13:e0360922. doi: 10.1128/spectrum.03609-22. Online ahead of print.ABSTRACTWith the exploding growth of the global market for probiotics and the rapid awakening of public awareness to manage health by probiotic intervention, there is still an active debate about whether the consumption of probiotics is beneficial for nonpatients, which is due to the lack of systematic analysis based on time series multiomics data sets. In this study, we recruited 100 adults from a college in China and performed a random case-control study by using a probiotic (Lacticaseibacillus rhamnosus Probio-M9) as an intervention for 6 weeks, aiming to achieve a comprehensive evaluation and understanding of the beneficial effect of Probio-M9 consumption. By testing advanced blood immunity indicators, sequencing the gut microbiome, and profiling the gut metabolome at baseline and the end of the study, we found that although the probiotic intervention has a limited impact on the human immunity and the gut microbiome and metabolome, the associations between the immunity indicators and multiomics data were strengthened, and further analysis of the gut microbiome's genetic variations revealed inhibited generation of single nucleotide variants (SNVs) by probiotic consumption. Taken together, our findings indicated an underestimated influence of the probiotic, not on altering the microbial composition but on strengthening the association between human immunity and commensal microbes and stabilizing the genetic variations of the gut microbiome. IMPORTANCE Although the global market for probiotics is growing explosively, there is still an active debate about whether the consumption of probiotics is beneficial for nonpatients. In this study, we recruited 100 adults from a college in China and performed 6 weeks of intervention for half of the volunteers. By analyzing the time series multiomics data in this study, we found that the probiotic intervention (i) has a limited effect on human immunity or the global structure of the gut microbiome and metabolome, (ii) can largely influence the correlation of the development between multiomics data and immunity, which was not able to be discovered by conventional differential abundance analysis, and (iii) can inhibit the generation of SNVs in the gut microbiome instead of promoting it.PMID:36912650 | DOI:10.1128/spectrum.03609-22

Chem Res Toxicol. 2023 Mar 13. doi: 10.1021/acs.chemrestox.2c00346. Online ahead of print.ABSTRACTThe health and safety of using e-cigarette products (vaping) have been challenging to assess and further regulate due to their complexity. Inhaled e-cigarette aerosols contain chemicals with under-recognized toxicological profiles, which could influence endogenous processes once inhaled. We urgently need more understanding on the metabolic effects of e-cigarette exposure and how they compare to combustible cigarettes. To date, the metabolic landscape of inhaled e-cigarette aerosols, including chemicals originated from vaping and perturbed endogenous metabolites in vapers, is poorly characterized. To better understand the metabolic landscape and potential health consequences of vaping, we applied liquid chromatography-mass spectrometry (LC-MS) based nontargeted metabolomics to analyze compounds in the urine of vapers, cigarette smokers, and nonusers. Urine from vapers (n = 34), smokers (n = 38), and nonusers (n = 45) was collected for verified LC-HRMS nontargeted chemical analysis. The altered features (839, 396, and 426 when compared smoker and control, vaper and control, and smoker and vaper, respectively) among exposure groups were deciphered for their structural identities, chemical similarities, and biochemical relationships. Chemicals originating from e-cigarettes and altered endogenous metabolites were characterized. There were similar levels of nicotine biomarkers of exposure among vapers and smokers. Vapers had higher urinary levels of diethyl phthalate and flavoring agents (e.g., delta-decalactone). The metabolic profiles featured clusters of acylcarnitines and fatty acid derivatives. More consistent trends of elevated acylcarnitines and acylglycines in vapers were observed, which may suggest higher lipid peroxidation. Our approach in monitoring shifts of the urinary chemical landscape captured distinctive alterations resulting from vaping. Our results suggest similar nicotine metabolites in vapers and cigarette smokers. Acylcarnitines are biomarkers of inflammatory status and fatty acid oxidation, which were dysregulated in vapers. With higher lipid peroxidation, radical-forming flavoring, and higher level of specific nitrosamine, we observed a trend of elevated cancer-related biomarkers in vapers as well. Together, these data present a comprehensive profiling of urinary biochemicals that were dysregulated due to vaping.PMID:36912507 | DOI:10.1021/acs.chemrestox.2c00346

Heliyon. 2023 Mar;9(3):e14029. doi: 10.1016/j.heliyon.2023.e14029. Epub 2023 Mar 1.ABSTRACTAcute lung injury (ALI) is a clinically severe lung illness with high incidence rate and mortality. Especially, coronavirus disease 2019 (COVID-19) poses a serious threat to world wide governmental fitness. It has distributed to almost from corner to corner of the universe, and the situation in the prevention and control of COVID-19 remains grave. Traditional Chinese medicine plays a vital role in the precaution and therapy of sicknesses. At present, there is a lack of drugs for treating these diseases, so it is necessary to develop drugs for treating COVID-19 related ALI. Fagopyrum dibotrys (D. Don) Hara is an annual plant of the Polygonaceae family and one of the long-history used traditional medicine in China. In recent years, its rhizomes (medicinal parts) have attracted the attention of scholars at home and abroad due to their significant anti-inflammatory, antibacterial and anticancer activities. It can work on SARS-COV-2 with numerous components, targets, and pathways, and has a certain effect on coronavirus disease 2019 (COVID-19) related acute lung injury (ALI). However, there are few systematic studies on its aerial parts (including stems and leaves) and its potential therapeutic mechanism has not been studied. The phytochemical constituents of rhizome of F. dibotrys were collected using TCMSP database. And metabolites of F. dibotrys' s aerial parts were detected by metabonomics. The phytochemical targets of F. dibotrys were predicted by the PharmMapper website tool. COVID-19 and ALI-related genes were retrieved from GeneCards. Cross targets and active phytochemicals of COVID-19 and ALI related genes in F. dibotrys were enriched by gene ontology (GO) and KEGG by metscape bioinformatics tools. The interplay network entre active phytochemicals and anti COVID-19 and ALI targets was established and broke down using Cytoscape software. Discovery Studio (version 2019) was used to perform molecular docking of crux active plant chemicals with anti COVID-19 and ALI targets. We identified 1136 chemicals from the aerial parts of F. dibotrys, among which 47 were active flavonoids and phenolic chemicals. A total of 61 chemicals were searched from the rhizome of F. dibotrys, and 15 of them were active chemicals. So there are 6 commonly key active chemicals at the aerial parts and the rhizome of F. dibotrys, 89 these phytochemicals's potential targets, and 211 COVID-19 and ALI related genes. GO enrichment bespoken that F. dibotrys might be involved in influencing gene targets contained numerous biological processes, for instance, negative regulation of megakaryocyte differentiation, regulation of DNA metabolic process, which could be put down to its anti COVID-19 associated ALI effects. KEGG pathway indicated that viral carcinogenesis, spliceosome, salmonella infection, coronavirus disease - COVID-19, legionellosis and human immunodeficiency virus 1 infection pathway are the primary pathways obsessed in the anti COVID-19 associated ALI effects of F. dibotrys. Molecular docking confirmed that the 6 critical active phytochemicals of F. dibotrys, such as luteolin, (+) -epicatechin, quercetin, isorhamnetin, (+) -catechin, and (-) -catechin gallate, can combine with kernel therapeutic targets NEDD8, SRPK1, DCUN1D1, and PARP1. In vitro activity experiments showed that the total antioxidant capacity of the aerial parts and rhizomes of F. dibotrys increased with the increase of concentration in a certain range. In addition, as a whole, the antioxidant capacity of the aerial part of F. dibotrys was stronger than that of the rhizome. Our research afford cues for farther exploration of the anti COVID-19 associated ALI chemical compositions and mechanisms of F. dibotrys and afford scientific foundation for progressing modern anti COVID-19 associated ALI drugs based on phytochemicals in F. dibotrys. We also fully developed the medicinal value of F. dibotrys' s aerial parts, which can effectively avoid the waste of resources. Meanwhile, our work provides a new strategy for integrating metabonomics, network pharmacology, and molecular docking techniques which was an efficient way for recognizing effective constituents and mechanisms valid to the pharmacologic actions of traditional Chinese medicine.PMID:36911881 | PMC:PMC9977108 | DOI:10.1016/j.heliyon.2023.e14029

Front Mol Biosci. 2023 Feb 24;10:1030661. doi: 10.3389/fmolb.2023.1030661. eCollection 2023.ABSTRACTObjective: Non-alcoholic fatty liver disease (NAFLD) and Type 2 diabetes mellitus (T2DM) often coexist and drive detrimental effects in a synergistic manner. This study was designed to understand the changes in circulating lipid and lipoprotein metabolism in patients with T2DM with or without NAFLD. Methods: Four hundred thirty-four T2DM patients aged 18-60 years were included in this study. Fatty liver was assessed by FibroScan. The comprehensive metabolic lipid profiling of serum samples was assessed by using high-throughput proton NMR metabolomics. Results: Our data revealed a significant association between steatosis and serum total lipids in VLDL and LDL lipoprotein subclasses, while total lipids in HDL subclasses were negatively associated. A significant positive association was found between steatosis and concentration of lipids, phospholipids, cholesterol, and triglycerides in VLDL and LDL subclasses, while HDL subclasses were negatively associated. Furthermore, a significant, association was observed between fibrosis and concentrations of lipids, phospholipids, cholesterol, and triglycerides in very small VLDL, large, and very large HDL subclasses. Subgroup analysis revealed a decrease in the concentrations of lipids, phospholipids, cholesterol, and other lipid biomolecules in patients using antilipemic medications. Conclusion: The metabolomics results provide evidence that patients with T2DM with higher steatosis grades have altered lipid metabolomics compared to patients without steatosis. Increased lipid, phospholipids, cholesterol, and triglycerides concentration of VLDL and LDL subclasses are associated with steatosis in patients with T2DM.PMID:36911526 | PMC:PMC9999296 | DOI:10.3389/fmolb.2023.1030661

Int J Clin Exp Pathol. 2023 Feb 15;16(2):20-31. eCollection 2023.ABSTRACTOBJECTIVES: How chronic pelvic inflammatory disease (CPID), the most common cause of infertility, affects metabolic profiles of follicular fluid (FF) remains unknown. This study aimed to identify candidate biomarkers in FF of infertile women with CPID.METHOD: FF samples were collected from infertile women with CPID (n = 8) and healthy controls (n = 8) at the time of oocyte retrieval. Untargeted metabolomic profiling of FF samples was conducted using the liquid chromatography-tandem mass spectrometry (LC-MS/MS).RESULTS: A total of 240 differential metabolites (104 named biochemicals and 136 unnamed biochemicals) were screened out and identified. Among them, pregnane-3,3-diol, pc(p-18:1(11z)/18:3(6z,9z,12z)), and 1-octadecanoyl-2-(4z,7z,10z,13z,16z,19z-docosahexaenoyl)-sn-glycero-3-phosphoethanolamine were markedly down-regulated, while 17,21-dihydroxypregnenolone was significantly up-regulated in infertile women with CPID. Furthermore, KEGG biological pathway analysis revealed that these metabolites were especially enriched in steroid hormone biosynthesis, glyoxylate and dicarboxylate metabolism, glucagon signaling pathway, and the tricarboxylic acid (TCA) cycle.CONCLUSION: FF of infertile women with CPID showed unique metabolic changes that may be involved in the pathogenesis of infertility and serve as new therapeutic targets or diagnostic biomarkers.PMID:36910890 | PMC:PMC9993017

Nano Today. 2022 Aug;45:101559. doi: 10.1016/j.nantod.2022.101559. Epub 2022 Jul 23.ABSTRACTCeO2 nanoparticles (NPs) have been shown to cause lung fibrosis, however, the exact underlying molecular mechanisms are poorly understood. In this study, we have conducted a mass spectrometry-based global metabolomic analysis of human bronchial epithelial BEAS-2B cells treated by CeO2 NPs with different aspect ratios and assessed their toxicity on the bronchial epithelial cells by various cell-based functional assays. Although CeO2 NPs at doses ranging from 12.5 μg/mL to 25 μg/mL displayed low cytotoxicity on the bronchial epithelial cells, the metabolomic analysis revealed a number of metabolites in the cellular metabolic pathways of sphingosine-1-phosphate, fatty acid oxidation, inflammation, etc. were significantly altered by CeO2 NPs, especially those with high aspect ratios. More importantly, the robustness of metabolomics findings was further successfully validated in mouse models upon acute and chronic exposures to CeO2 NPs. Mechanistically, CeO2 NPs upregulated transforming growth factor beta-1 (TGF-β1) levels in BEAS-2B cells in an aspect ratio-dependent manner through enhancing the expression of early growth response protein 1 (EGR-1). In addition, both in vitro and in vivo studies demonstrated that CeO2 NPs significantly induced the expression of sphingosine kinase 1 (SHPK1), phosphorylated Smad2/3 and lung fibrosis markers. Moreover, targeting SPHK1, TGFβ receptor or Smad3 phosphorylation significantly attenuated the fibrosis-promoting effects of CeO2 NPs, and SPHK1-S1P pathway exerted a greater effect on the TGF-β1-mediated lung fibrosis compared to the conventional Smad2/3 pathway. Collectively, our studies have identified the metabolomic changes in BEAS-2B cells exposed to CeO2 NPs with different aspect ratios and revealed the subtle changes in metabolic activities that traditional approaches might have missed. More importantly, we have discovered a previously unknown molecular mechanism underlying CeO2 NP-induced lung fibrosis with different aspect ratios, shedding new insights on the environmental hazard potential of CeO2 NPs.PMID:36910843 | PMC:PMC9997866 | DOI:10.1016/j.nantod.2022.101559

Front Microbiol. 2023 Feb 22;14:1127958. doi: 10.3389/fmicb.2023.1127958. eCollection 2023.ABSTRACTINTRODUCTION: Root-associated microorganisms promote plant growth and provide protection from stresses. Halophytes are the fundamental components maintaining ecosystem functions of coastal salt marshes; however, it is not clear how their microbiome are structured across large spatial scales. Here, we investigated the rhizosphere bacterial communities of typical coastal halophyte species (Phragmites australis and Suaeda salsa) in temperate and subtropical salt marshes across 1,100 km in eastern China.METHODS: The sampling sites were located from 30.33 to 40.90°N and 119.24 to 121.79°E across east China. A total of 36 plots were investigated in the Liaohe River Estuary, the Yellow River Estuary, Yancheng, and Hangzhou Bay in August 2020. We collected shoot, root, and rhizosphere soil samples. the number of pakchoi leaves, total fresh and dry weight of the seedlings was counted. The soil properties, plant functional traits, the genome sequencing, and metabolomics assay were detected.RESULTS: The results showed that soil nutrients (total organic carbon, dissolved organic carbon, total nitrogen, soluble sugars, and organic acids) are high in the temperate marsh, while root exudates (measured by metabolite expressions) are significantly higher in the subtropical marsh. We observed higher bacterial alpha diversity, more complex network structure, and more negative connections in the temperate salt marsh, which suggested intense competition among bacterial groups. Variation partitioning analysis showed that climatic, edaphic, and root exudates had the greatest effects on the bacteria in the salt marsh, especially for abundant and moderate subcommunities. Random forest modeling further confirmed this but showed that plant species had a limited effect.CONCLUTIONS: Taken together, the results of this study revealed soil properties (chemical properties) and root exudates (metabolites) had the greatest influence on the bacterial community of salt marsh, especially for abundant and moderate taxa. Our results provided novel insights into the biogeography of halophyte microbiome in coastal wetlands and can be beneficial for policymakers in decision-making on the management of coastal wetlands.PMID:36910212 | PMC:PMC9992437 | DOI:10.3389/fmicb.2023.1127958

Front Microbiol. 2023 Feb 23;14:1092435. doi: 10.3389/fmicb.2023.1092435. eCollection 2023.ABSTRACTThe strong survival ability of Salmonella in low-moisture foods (LMFs) has been of public concern, and is considered a threat to people's health. Recently, the development of omics technology has promoted research on the molecular mechanisms of the desiccation stress response of pathogenic bacteria. However, multiple analytical aspects related to their physiological characteristics remain unclear. We explored the physiological metabolism changes of S. enterica Enteritidis exposed to a 24 h-desiccation treatment and a subsequent 3-month desiccation storage in skimmed milk powder (SMP) with an approach of gas chromatography-mass spectrometry (GC-MS) and ultra-performance liquid chromatography-Q Exactive-mass spectrometry (UPLC-QE-MS). A total of 8,292 peaks were extracted, of which 381 were detected by GC-MS and 7,911 peaks were identified by LC-MS/MS, respectively. Through analyses of differentially expressed metabolites (DEMs) and key pathways, a total of 58 DEMs emerged from the 24 h-desiccation treatment, which exhibited the highest relevance for five metabolic pathways, involving glycine, serine, and threonine metabolism, pyrimidine metabolism, purine metabolism, vitamin B6 metabolism, and pentose phosphate pathway. After 3-month SMP storage, 120 DEMs were identified, which were related to several regulatory pathways including arginine and proline metabolism, serine and threonine metabolism, β-alanine metabolism, glycerolipid metabolism, and glycolysis. The analyses of key enzyme activities of XOD, PK, and G6PDH and ATP content provided further evidence that supported the metabolic responses such as nucleic acid degradation, glycolysis, and ATP production played an important role in Salmonella's adaptation to desiccation stress. This study enables a better understanding of metabolomics-based responses of Salmonella at the initial stage of desiccation stress and the following long-term adaptive stage. Meanwhile, the identified discriminative metabolic pathways may serve as potentially useful targets in developing strategies for the control and prevention of desiccation-adapted Salmonella in LMFs.PMID:36910198 | PMC:PMC9996163 | DOI:10.3389/fmicb.2023.1092435

Front Microbiol. 2023 Feb 23;14:1060458. doi: 10.3389/fmicb.2023.1060458. eCollection 2023.ABSTRACTINTRODUCTION: Chinese indigenous chicken breeds are widely used as food in China but their slow growth rate and long farming cycle has limited their industrial production.METHODS: In the current study we examined whether the market weights of native chicken breeds were related to specific cecal bacteria, serum metabolites and inflammatory cytokines. We examined cecal bacterial taxa using 16S rDNA analysis along with untargeted serum metabolites and serum inflammatory cytokines.RESULTS: We found that the cecal microbiota could explain 10.1% of the individual differences in chicken weights and identified key cecal bacterial genera that influenced this phenotype. The presence of Sphaerochaeta spp. improved growth performance via bovinic acid metabolism. In contrast, Synergistes and norank_f_Desulfovibrionaceae had a negative effect on growth by inducing expression of the inflammatory cytokine IL-6.DISCUSSION: We were able to link specific bacterial genera with growth promotion in chickens and this study will allow further development of their use as probiotics in these animals.PMID:36910194 | PMC:PMC9995838 | DOI:10.3389/fmicb.2023.1060458

Front Microbiol. 2023 Feb 24;14:1076011. doi: 10.3389/fmicb.2023.1076011. eCollection 2023.ABSTRACTINTRODUCTION: Extreme environments at high altitudes pose a significant physiological challenge to animals. We evaluated the gut microbiome and fecal metabolism in Sanhe heifers from different altitudes.METHODS: Twenty Sanhe heifers (body weight: 334.82 ± 13.22 kg, 15-month-old) selected from two regions of China: the Xiertala Cattle Breeding Farm in Hulunbeier, Inner Mongolia [119°57' E, 47°17' N; approximately 700 m altitude, low altitude (LA)] and Zhizhao Dairy Cow Farm in Lhasa, Tibet [91°06' E, 29°36' N; approximately 3,650 m altitude, high altitude (HA)], were used in this study. Fecal samples were collected and differences in the gut microbiota and metabolomics of Sanhe heifers were determined using 16S rRNA gene sequencing and metabolome analysis.RESULTS AND DISCUSSION: The results showed that altitude did not significantly affect the concentrations of fecal volatile fatty acids, including acetate, propionate, butyrate, and total volatile fatty acids (p > 0.05). However, 16S rRNA gene sequencing showed that altitude significantly affected gut microbial composition. Principal coordinate analysis based on Bray-Curtis dissimilarity analysis revealed a significant difference between the two groups (p = 0.001). At the family level, the relative abundances of Peptostreptococcaceae, Christensenellaceae, Erysipelotrichaceae, and Family_XIII were significantly lower (p < 0.05) in LA heifers than in HA heifers. In addition, the relative abundances of Lachnospiraceae, Domibacillus, Bacteroidales_S24-7_group, Bacteroidales_RF16_group, Porphyromonadaceae, and Spirochaetaceae were significantly higher in HA heifers than in LA heifers (p < 0.05). Metabolomic analysis revealed the enrichment of 10 metabolic pathways, including organismal systems, metabolism, environmental information processing, genetic information processing, and disease induction. The genera Romboutsia, Paeniclostridium, and g_unclassified_f_Lachnospiraceae were strongly associated with the 28 differential metabolites. This study is the first to analyze the differences in the gut microbiome and metabolome of Sanhe heifers reared at different altitudes and provides insights into the adaptation mechanism of Sanhe heifers to high-altitude areas.PMID:36910192 | PMC:PMC10002979 | DOI:10.3389/fmicb.2023.1076011

Front Microbiol. 2023 Feb 22;14:1092360. doi: 10.3389/fmicb.2023.1092360. eCollection 2023.ABSTRACTOBJECTIVE: To investigate the characteristic changes in the gut microbiota of patients with type A aortic dissection (AAD) and provide a theoretical basis for future microbiome-oriented interventional studies.METHODS: High-throughput 16S rDNA sequencing was performed on the stool samples of patients with and without (healthy control subjects) AAD. Using alpha and beta diversity analysis, we compared the gut microbiota composition of 20 patients with AAD and 20 healthy controls matched for gender, age, BMI, and geographical region. The accuracy of AAD prediction by differential microbiome was calculated using the random forest machine learning model. Targeted measurement of the plasma concentration of short-chain fatty acids (SCFAs), which are the main metabolites of the gut microbiome, was performed using gas chromatography-mass spectrometry (GC-MS). Spearman's correlation analysis was conducted to determine the relationships of gut microbiome and SCFAs with the clinical characteristics of subjects.RESULTS: The differences in gut microbiota alpha diversity between patients with AAD and the healthy controls were not statistically significant (Shannon index: p = 0.19; Chao1: p = 0.4); however, the microbiota composition (beta diversity) was significantly different between the two groups (Anosim, p = 0.001). Bacteroidota was enriched at the phylum level, and the SCFA-producing genera Prevotella, Porphyromonas, Lachnospiraceae, and Ruminococcus and inflammation-related genera Fenollaria and Sutterella were enriched at the genus level in the AAD group compared with those in the control group. The random forest model could predict AAD from gut microbiota composition with an accuracy of 87.5% and the area-under-curve (AUC) of the receiver operating characteristic curve was 0.833. The SCFA content of patients with AAD was higher than that of the control group, with the difference being statistically significant (p < 0.05). The different microflora and SCFAs were positively correlated with inflammatory cytokines.CONCLUSION: To the best of our knowledge, this is the first demonstration of the presence of significant differences in the gut microbiome of patients with AAD and healthy controls. The differential microbiome exhibited high predictive potential toward AAD and was positively correlated with inflammatory cytokines. Our results will assist in the development of preventive and therapeutic treatment methods for patients with AAD.PMID:36910178 | PMC:PMC9992204 | DOI:10.3389/fmicb.2023.1092360

Front Microbiol. 2023 Feb 23;14:1016872. doi: 10.3389/fmicb.2023.1016872. eCollection 2023.ABSTRACTThe intestinal microbiota and fecal metabolome have been shown to play a vital role in human health, and can be affected by genetic and environmental factors. We found that individuals with Down syndrome (DS) had abnormal serum cytokine levels indicative of a pro-inflammatory environment. We investigated whether these individuals also had alterations in the intestinal microbiome. High-throughput sequencing of bacterial 16S rRNA gene in fecal samples from 17 individuals with DS and 23 non-DS volunteers revealed a significantly higher abundance of Prevotella, Escherichia/Shigella, Catenibacterium, and Allisonella in individuals with DS, which was positively associated with the levels of pro-inflammatory cytokines. GC-TOF-MS-based fecal metabolomics identified 35 biomarkers (21 up-regulated metabolites and 14 down-regulated metabolites) that were altered in the microbiome of individuals with DS. Metabolic pathway enrichment analyses of these biomarkers showed a characteristic pattern in DS that included changes in valine, leucine, and isoleucine biosynthesis and degradation; synthesis and degradation of ketone bodies; glyoxylate and dicarboxylate metabolism; tyrosine metabolism; lysine degradation; and the citrate cycle. Treatment of mice with fecal bacteria from individuals with DS or Prevotella copri significantly altered behaviors often seen in individuals with DS, such as depression-associated behavior and impairment of motor function. These studies suggest that changes in intestinal microbiota and the fecal metabolome are correlated with chronic inflammation and behavior disorders associated with DS.PMID:36910172 | PMC:PMC9998045 | DOI:10.3389/fmicb.2023.1016872

Front Cell Infect Microbiol. 2023 Feb 23;13:1068809. doi: 10.3389/fcimb.2023.1068809. eCollection 2023.ABSTRACTBACKGROUND: Multiple regimens have been widely used in the eradication treatment of Helicobacter pylori infection in children. However, there is a lack of comparison and evaluation of their effectiveness in different regions of the world.METHODS: Randomized controlled trials were retrieved. Review Manager 5.4, Stata SE 15 and R 4.0.4 statistical software were used to analyze date. The ranking probability is assessed according to the surfaces under cumulative ranking (SUCRA).RESULTS: 163 studies were eligible for this study, involving 336 arms and 18,257 children, and 10 different interventions. The results showed that the eradication rates of sequential therapy with probiotics (SP), bismuth-containing quadruple (Quadruple) therapy, concomitant therapy and PCN therapy were at least 90%. Cumulative ranking showed that SP therapy had the best eradication effect (SUCRA 92.7%) whereas Bismuth-containing triple therapy (B) had the worst (SUCRA 3.5%). Subgroup analysis suggested that SP therapy ranked first in China and other regions, and the ranking of Triple therapy with probiotics therapy (TP) was equally stable (SUCRA 72.0% vs 76.4% respectively). The security of the SP and TP therapy had great advantages.CONCLUSIONS: As for the eradication treatment of Helicobacter pylori infection in children, SP therapy ranks highest. SP and TP therapies are most safe.PMID:36909732 | PMC:PMC9995679 | DOI:10.3389/fcimb.2023.1068809

Front Cell Infect Microbiol. 2023 Feb 24;13:1127041. doi: 10.3389/fcimb.2023.1127041. eCollection 2023.ABSTRACTBACKGROUND: Increasing evidence supports that gut microbiota plays an important role in the development of cardiovascular diseases. The prevalence of sarcopenia is increasing in patients with heart failure. Muscle wasting is an independent predictor of death in heart failure patients.AIMS: In this study, we aimed to explore the characteristics of gut microbiota and metabolites in heart failure patients with or without sarcopenia.METHODS: Fecal samples of 33 heart failure patients without sarcopenia, 29 heart failure patients with sarcopenia, and 15 controls were collected. The intestinal microbiota was analyzed using 16S rRNA sequencing and the metabolites were detected using the gas chromatography-mass spectrometry method.RESULTS: There were significant differences in the overall microbial community structure and diversity between control and heart failure patients with or without sarcopenia. However, no clear clustering of samples was observed in heart failure with and without sarcopenia patients. Several bacterial, particularly Nocardiaceae, Pseudonocardiaceae, Alphaproteobacteria, and Slackia were significantly enriched in the heart failure patients without sarcopenia, while Synergistetes was more abundant in the heart failure patients with sarcopenia. Isobutyric acid, isovaleric acid, and valeric acid were lower in heart failure patients with sarcopenia than that without sarcopenia but lacked significance.CONCLUSIONS: This study demonstrates that there are differences in the gut microbiota between control individuals and heart failure patients with or without sarcopenia. Modulating the gut microbiota may be a new target for the prevention and treatment of sarcopenia in heart failure patients.PMID:36909727 | PMC:PMC9998919 | DOI:10.3389/fcimb.2023.1127041

bioRxiv. 2023 Feb 27:2023.02.27.530280. doi: 10.1101/2023.02.27.530280. Preprint.ABSTRACTThis exploratory study tested and validated the use of data fusion and machine learning techniques to probe high-throughput omics and clinical data with a goal of exploring the etiology of developmental dyslexia. Developmental dyslexia is the leading learning disability in school aged children affecting roughly 5-10% of the US population. The complex biological and neurological phenotype of this life altering disability complicates its diagnosis. Phenome, exome, and metabolome data was collected allowing us to fully explore this system from a behavioral, cellular, and molecular point of view. This study provides a proof of concept showing that data fusion and ensemble learning techniques can outperform traditional machine learning techniques when provided small and complex multi-omics and clinical datasets. Heterogenous stacking classifiers consisting of single-omic experts/models achieved an accuracy of 86%, F1 score of 0.89, and AUC value of 0.83. Ensemble methods also provided a ranked list of important features that suggests exome single nucleotide polymorphisms found in the thalamus and cerebellum could be potential biomarkers for developmental dyslexia and heavily influenced the classification of DD within our machine learning models.PMID:36909570 | PMC:PMC10002702 | DOI:10.1101/2023.02.27.530280

Res Sq. 2023 Feb 28:rs.3.rs-2511186. doi: 10.21203/rs.3.rs-2511186/v1. Preprint.ABSTRACTWithin the field of amyloid and prion disease there is a need for a more comprehensive understanding of the fundamentals of disease biology. In order to facilitate the progression treatment and underpin comprehension of toxicity, fundamental understanding of the disruption to normal cellular biochemistry and trafficking is needed. Here, by removing the complex biochemistry of the brain, we have utilised known prion forming strains of Saccharomyces cerevisiae carrying different conformational variants of the Rnq1p to obtain Liquid Chromatography-Mass Spectrometry (LC-MS) metabolic profiles and identify key perturbations of prion presence. These studies reveal that prion containing [ RNQ + ] cells display a significant reduction in amino acid biosynthesis and distinct perturbations in sphingolipid metabolism, with significant downregulation in metabolites within these pathways. Moreover, that native Rnq1p appears to downregulate ubiquinone biosynthesis pathways within cells, suggesting that Rnq1p may play a lipid/mevalonate-based cytoprotective role as a regulator of ubiquinone production. These findings contribute to the understanding of how prion proteins interact in vivo in both their prion and non-prion confirmations and indicate potential targets for the mitigation of these effects. We demonstrate specific sphingolipid centred metabolic disruptions due to prion presence and give insight into a potential cytoprotective role of the native Rnq1 protein. This provides evidence of metabolic similarities between yeast and mammalian cells as a consequence of prion presence and establishes the application of metabolomics as a tool to investigate prion/amyloid-based phenomena.PMID:36909567 | PMC:PMC10002837 | DOI:10.21203/rs.3.rs-2511186/v1

bioRxiv. 2023 Mar 1:2023.02.28.530478. doi: 10.1101/2023.02.28.530478. Preprint.ABSTRACTAberrant tumor metabolism is a hallmark of cancer in which metabolic rewiring can support tumor growth under nutrient deficient conditions. KRAS mutations occur in 35-45% of all colorectal cancer (CRC) cases and are difficult to treat. The relationship between mutant KRAS and aberrant metabolism in CRCs has not been fully explored and could be a target for intervention. We previously acquired non-targeted metabolomics data from 161 tumor tissues and 39 normal colon tissues from stage I-III chemotherapy naïve CRC patients. In this study, we revealed that tumors from male patients with KRAS mutations only, had several altered pathways that suppress ferroptosis, including glutathione biosynthesis, transsulfuration activity, and methionine metabolism. To validate this phenotype, MC38 CRC cells (KRAS G13R ) were treated with a ferroptosis inducer; RAS-selected lethal (RSL3). RSL3 altered metabolic pathways in the opposite direction to that seen in KRAS mutant tumors from male patients confirming a suppressed ferroptosis metabolic phenotype in these patients. We further validated gene expression data from an additional CRC patient cohort (Gene Expression Omnibus (GEO), and similarly observed differences in ferroptosis-related genes by sex and KRAS status. Further examination of the relationship between these genes and overall survival (OS) in the GEO cohort showed that KRAS mutant tumors are associated with poorer 5-year OS compared to KRAS wild type tumors, and only in male patients. Additionally, high compared to low expression of GPX4, FTH1, FTL , which suppressed ferroptosis, were associated with poorer 5-year OS only in KRAS mutant tumors from male CRC patients. Low compared to high expression of ACSL4 was associated with poorer OS for this group. Our results show that KRAS mutant tumors from male CRC patients have suppressed ferroptosis, and gene expression changes that suppress ferroptosis associate with adverse outcomes for these patients, revealing a novel potential avenue for therapeutic approaches.PMID:36909561 | PMC:PMC10002683 | DOI:10.1101/2023.02.28.530478

bioRxiv. 2023 Mar 2:2023.03.01.530642. doi: 10.1101/2023.03.01.530642. Preprint.ABSTRACTNuclear Magnetic Resonance is a powerful platform that reveals the metabolomics profiles within biofluids or tissues and contributes to personalized treatments in medical practice. However, data volume and complexity hinder the exploration of NMR spectra. Besides, the lack of fast and accurate computational tools that can handle the automatic identification and quantification of essential metabolites from NMR spectra also slows the wide application of these techniques in clinical. We present NMRQNet, a deep-learning-based pipeline for automatic identification and quantification of dominant metabolite candidates within human plasma samples. The estimated relative concentrations could be further applied in statistical analysis to extract the potential biomarkers. We evaluate our method on multiple plasma samples, including species from mice to humans, curated using three anticoagulants, covering healthy and patient conditions in neurological disorder disease, greatly expanding the metabolomics analytical space in plasma. NMRQNet accurately reconstructed the original spectra and obtained significantly better quantification results than the earlier computational methods. Besides, NMRQNet also proposed relevant metabolites biomarkers that could potentially explain the risk factors associated with the condition. NMRQNet, with improved prediction performance, highlights the limitations in the existing approaches and has shown strong application potential for future metabolomics disease studies using plasma samples.PMID:36909516 | PMC:PMC10002723 | DOI:10.1101/2023.03.01.530642

Front Plant Sci. 2023 Feb 24;14:1144449. doi: 10.3389/fpls.2023.1144449. eCollection 2023.ABSTRACTFlavonoids are one of the most important bioactive components in litchi (Litchi chinensis Sonn.) seeds and have broad-spectrum antiviral and antitumor activities. Litchi seeds have been shown to inhibit the proliferation of cancer cells and induce apoptosis, particularly effective against breast and liver cancers. Elucidating the distribution of flavonoids is important for understanding their physiological and biochemical functions and facilitating their efficient extraction and utilization. However, the spatial distribution patterns and expression states of flavonoids in litchi seeds remain unclear. Herein, matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI-MSI) was used for in situ detection and imaging of the distribution of flavonoids in litchi seed tissue sections for the first time. Fifteen flavonoid ion signals, including liquiritigenin, apigenin, naringenin, luteolin, dihydrokaempferol, daidzein, quercetin, taxifolin, kaempferol, isorhamnetin, myricetin, catechin, quercetin 3-β-d-glucoside, baicalin, and rutin, were successfully detected and imaged in situ through MALDI-MSI in the positive ion mode using 2-mercaptobenzothiazole as a matrix. The results clearly showed the heterogeneous distribution of flavonoids, indicating the potential of litchi seeds for flavonoid compound extraction. MALDI-MS-based multi-imaging enhanced the visualization of spatial distribution and expression states of flavonoids. Thus, apart from improving our understanding of the spatial distribution of flavonoids in litchi seeds, our findings also facilitate the development of MALDI-MSI-based metabolomics as a novel effective molecular imaging tool for evaluating the spatial distribution of endogenous compounds.PMID:36909412 | PMC:PMC9998689 | DOI:10.3389/fpls.2023.1144449

Front Plant Sci. 2023 Feb 24;14:1137630. doi: 10.3389/fpls.2023.1137630. eCollection 2023.ABSTRACTApple scar skin viroid (ASSVd) can infect apple trees and cause scar skin symptoms. However, the associated physiological mechanisms are unclear in young saplings. In this study, ASSVd-infected and control 'Odysso' and 'Tonami' apple saplings were examined to clarify the effects of ASSVd on apple tree growth and physiological characteristics as well as the leaf metabolome. The results indicated that leaf ASSVd contents increased significantly after grafting and remained high in the second year. Leaf size, tree height, stem diameter, branch length, and leaf photosynthetic efficiency decreased significantly in viroid-infected saplings. In response to the ASSVd infection, the chlorophyll a and b contents decreased significantly in 'Odysso', but were unchanged in 'Tonami'. Moreover, the N, P, K, Fe, Mn, and Ca contents decreased significantly in the leaves of viroid-infected 'Odysso' or 'Tonami'. Similarly, the CAT and POD contents decreased significantly in the viroid-infected saplings, but the SOD content increased in the viroid-infected 'Tonami' saplings. A total of 15 and 40 differentially abundant metabolites were respectively identified in the metabolome analyses of 'Odysso' and 'Tonami' leaves. Specifically, in the viroid-infected 'Odysso' and 'Tonami' samples, the L-2-aminobutyric acid, 6″-O-malonyldaidzin, and D-xylose contents increased, while the coumarin content decreased. These metabolites are related to the biosynthesis of isoflavonoids and phenylpropanoids as well as the metabolism of carbohydrates and amino acids. These results imply that ASSVd affects apple sapling growth by affecting physiological characteristics and metabolism of apple leaves. The study data may be useful for future investigations on the physiological mechanisms underlying apple tree responses to ASSVd.PMID:36909405 | PMC:PMC9998556 | DOI:10.3389/fpls.2023.1137630