Integrative Molecular Phenotyping
INTEGRATIVE MOLECULAR
PHENOTYPING
WHEELOCK LABORATORY
DEPARTMENT OF MEDICAL
BIOCHEMISTRY AND BIOPHYSICS
WHEELOCK LABORATORY
DEPARTMENT OF MEDICAL
BIOCHEMISTRY AND BIOPHYSICS
WHEELOCK LABORATORY
DEPARTMENT OF MEDICAL
BIOCHEMISTRY AND BIOPHYSICS
WHEELOCK LABORATORY
DEPARTMENT OF MEDICAL
BIOCHEMISTRY AND BIOPHYSICS
WHEELOCK LABORATORY
DEPARTMENT OF MEDICAL
BIOCHEMISTRY AND BIOPHYSICS
WHEELOCK LABORATORY

PubMed

Comparison of volatile and nonvolatile metabolites in green tea under hot-air drying and four heat-conduction drying patterns using widely targeted metabolomics

Mon, 02/10/2023 - 12:00
Food Chem X. 2023 Jun 24;19:100767. doi: 10.1016/j.fochx.2023.100767. eCollection 2023 Oct 30.ABSTRACTHot-air and heat-conduction drying are the most common drying patterns in green tea production. However, the differences between them in terms of the resulting green tea chemical compounds have not been illustrated systematically. In this study, 515 volatile and 204 nonvolatile metabolites were selected to compare the differences between hot-air drying green tea (HAGT) and four heat-conduction drying green teas (HCDGTs) using widely targeted metabolomics. The results showed notable changes in volatile compounds; for example, two kinds of HCDGTs preferred to form chestnut-like and caramel-like key odorants. In addition, 14 flavonol glycosides, 10 catechins, 9 phenolic acids, 8 amino acids, 7 flavonols, and 3 sugars were significantly changed between HAGT and HCDGTs (p < 0.05), presenting a tremendous discrepancy in the transformation of nonvolatile compounds. Our results provide clear guidance for the precise manufacturing of green tea by four common heat-drying patterns and hot air-drying patterns.PMID:37780330 | PMC:PMC10534119 | DOI:10.1016/j.fochx.2023.100767

Variations in microbial diversity and chemical components of raw dark tea under different relative humidity storage conditions

Mon, 02/10/2023 - 12:00
Food Chem X. 2023 Sep 2;19:100863. doi: 10.1016/j.fochx.2023.100863. eCollection 2023 Oct 30.ABSTRACTRaw dark tea (RDT) usually needs to be stored for a long time to improve its quality under suitable relative humidity (RH). However, the impact of RH on tea quality is unclear. In this study, we investigated the metabolites and microbial diversity, and evaluated the sensory quality of RDT stored under three RH conditions (1%, 57%, and 88%). UHPLC-Q-TOF-MS analysis identified 144 metabolites, including catechins, flavonols, phenolic acids, amino acids, and organic acids. 57% RH led to higher levels of O-methylated catechin derivatives, polymerized catechins, and flavonols/flavones when compared to 1% and 88% RH. The best score in sensory evaluation was also obtained by 57% RH. Aspergillus, Gluconobacter, Kluyvera, and Pantoea were identified as the core functional microorganisms in RDT under different RH storage conditions. Overall, the findings provided new insights into the variation of microbial communities and chemical components under different RH storage conditions.PMID:37780317 | PMC:PMC10534245 | DOI:10.1016/j.fochx.2023.100863

Alfalfa leaf meal as a new protein feedstuff improves meat quality by modulating lipid metabolism and antioxidant capacity of finishing pigs

Mon, 02/10/2023 - 12:00
Food Chem X. 2023 Jul 27;19:100815. doi: 10.1016/j.fochx.2023.100815. eCollection 2023 Oct 30.ABSTRACTThe effects of alfalfa leaf meal (ALM) on the meat quality of finishing pigs are largely unknown. Here, we investigated the effects of ALM diet on meat quality by replacing 0%, 25%, 50%, and 75% of soybean meal in the diet of finishing pigs, respectively. The findings showed that 25% ALM diet increased the IMF, cooked meat rate, a* and antioxidant capacity of longissimus dorsi (LD), improved amino acid composition, increased MUFA content, and increased LD lipid synthesis and mRNA expression of antioxidation-related genes. At the same time, ALM diet altered serum lipid metabolism (TG, FFA). Correlation analysis showed that antioxidant capacity was positively correlated with meat quality. In addition, metabolomic analysis of LD showed that the main metabolites of 25% ALM diet altered stachydrine and l-carnitine were associated with meat quality and antioxidant capacity. In conclusion, ALM replacing 25% soybean meal diet can improve the meat quality of pigs.PMID:37780297 | PMC:PMC10534147 | DOI:10.1016/j.fochx.2023.100815

Regulatory effect of lactulose on intestinal flora and serum metabolites in colitis mice: <em>In vitro</em> and <em>in vivo</em> evaluation

Mon, 02/10/2023 - 12:00
Food Chem X. 2023 Aug 11;19:100821. doi: 10.1016/j.fochx.2023.100821. eCollection 2023 Oct 30.ABSTRACTLactulose is a common component in foods. However, the effect of lactulose on intestinal flora and overall metabolic levels remains unclear. Therefore, this study aims to explore the regulative role of lactulose on intestinal flora and serum metabolites via in vitro simulated colonic fermentation model and in vivo colitis mouse model. The results showed that lactulose significantly enriched beneficial bacteria including Dubosiella and Bifidobacterium, and reduced pathogenic bacteria such as Fusobacterium. Moreover, lactulose significantly inhibited dextran sodium sulfate-induced body weight loss, colon shortening, colonic inflammatory infiltration, and pro-inflammatory cytokines IL-6, TNF-α, IL-17, and IL-1β. Lactulose significantly affected serum metabolome in colitis mice and total 24 metabolites representing a high inter-group difference were obtained. Correlation analysis revealed that the changes in serum metabolites were closely associated with the role of intestinal flora, and thus affected phenotypic indicators. Our study provides a reference for nutritional characteristics and application scenarios of dietary lactulose.PMID:37780294 | PMC:PMC10534180 | DOI:10.1016/j.fochx.2023.100821

Untargeted metabolomics and conventional quality characterization of rowanberry pomace ingredients in meatballs

Mon, 02/10/2023 - 12:00
Food Chem X. 2023 Jun 28;19:100761. doi: 10.1016/j.fochx.2023.100761. eCollection 2023 Oct 30.ABSTRACTIn this study, a rowanberry pomace defatted with supercritical CO2 (2%-AC), its ethanolic extract (1%-E) and extraction residue (2%-R), were tested in meatball preparation. The meatballs with 1%-E demonstrated the highest in vitro radical scavenging capacity. In the case of 1%-E the pH of meatballs was significantly lower compared to the control sample (P = 0.0132) on the 5-day. The lowest cooking loss was achieved when the meatballs contained mainly fibre-rich 2%-R. The UHPLC method detected 184 metabolites, including strong antioxidants, such as chlorogenic acids, 3',4'-methylenedioxy-5,7-dimethylepicatechin, hyperin, isoquercitrin. The 1%-E was particularly effective against the development of unpleasant off-flavours caused by carbonyl compounds. Consistently, the decrease in lipid oxidation, indicated by reduced 7-dodecenal and 2,4-heptadienal contents, has been observed following the addition of rowanberry extract to meatballs. Metabolomics coupled with conventional quality evaluations provided a deeper understanding of the potential utilization and valorisation of different rowanberry pomace extracts as meat ingredients.PMID:37780283 | PMC:PMC10534112 | DOI:10.1016/j.fochx.2023.100761

A comprehensive review of the current trends and recent advancements on the authenticity of honey

Mon, 02/10/2023 - 12:00
Food Chem X. 2023 Aug 28;19:100850. doi: 10.1016/j.fochx.2023.100850. eCollection 2023 Oct 30.ABSTRACTThe authenticity of honey currently poses challenges to food quality control, thus requiring continuous modernization and improvement of related analytical methodologies. This review provides a comprehensively overview of honey authenticity challenges and related analytical methods. Firstly, direct and indirect methods of honey adulteration were described in detail, commenting the existing challenges in current detection methods and market supervision approaches. As an important part, the integrated metabolomic workflow involving sample processing procedures, instrumental analysis techniques, and chemometric tools in honey authenticity studies were discussed, with a focus on their advantages, disadvantages, and scopes. Among them, various improved microscale extraction methods, combined with hyphenated instrumental analysis techniques and chemometric data processing tools, have broad application potential in honey authenticity research. The future of honey authenticity determination will involve the use of simplified and portable methods, which will enable on-site rapid detection and transfer detection technologies from the laboratory to the industry.PMID:37780275 | PMC:PMC10534224 | DOI:10.1016/j.fochx.2023.100850

Analytical strategies based on untargeted and targeted metabolomics for the accurate authentication of organic milk from Jersey and Yak

Mon, 02/10/2023 - 12:00
Food Chem X. 2023 Jul 8;19:100786. doi: 10.1016/j.fochx.2023.100786. eCollection 2023 Oct 30.ABSTRACTOrganic milk has a high risk of food fraud as it can easily be adulterated with non-organic milk. This study aimed to identify metabolite markers for assessing the authenticity of organic milk from Jersey and Yak. In the untargeted strategy, ultra-high performance liquid chromatography-Q Exactive HF-X mass spectrometer coupled with chemometrics analysis was used to screen and identify tentative markers of organic milk from Jersey and Yak. In the targeted strategy, a quick and easy method of ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) was developed to quantify three markers. The peptide of Thr-Ala-Val and D-biotin were determined to be metabolite markers for distinguishing organic and non-organic Jersey milk, whereas trimethylamine N-oxide was determined to be a metabolite marker for distinguishing organic and non-organic Yak milk. These findings provide critical information to facilitate assessments of organic milk authenticity.PMID:37780248 | PMC:PMC10534096 | DOI:10.1016/j.fochx.2023.100786

Insight into the differences of meat quality between Qinghai white Tibetan sheep and black Tibetan sheep from the perspective of metabolomics and rumen microbiota

Mon, 02/10/2023 - 12:00
Food Chem X. 2023 Aug 16;19:100843. doi: 10.1016/j.fochx.2023.100843. eCollection 2023 Oct 30.ABSTRACTThe purpose of this study was to investigate the differences in meat quality between two local breeds of Tibetan sheep, the White Tibetan sheep and the Black Tibetan sheep in Qinghai, and to search for metabolic mechanisms that produce meat quality differences by analyzing differential metabolites and key rumen microorganisms. The meat quality results showed that one breed, SG73, was superior to the other (WG). Further investigation identified differences in the composition of muscle metabolites and rumen microorganisms between the two Tibetan sheep breeds. It also regulates muscle tenderness, water retention, fat content and the composition and content of AA and FA through two major metabolic pathways, AA metabolism and carbohydrate metabolism. These findings could be beneficial for the development of breeding strategies for Tibetan sheep in Qinghai in the future.PMID:37780244 | PMC:PMC10534161 | DOI:10.1016/j.fochx.2023.100843

Metabolomic comparison of meat quality and metabolites of geese breast muscle at different ages

Mon, 02/10/2023 - 12:00
Food Chem X. 2023 Jun 27;19:100775. doi: 10.1016/j.fochx.2023.100775. eCollection 2023 Oct 30.ABSTRACTThe purpose of this study was to distinguish the effect of age on the meat quality and chemical composition of Yangzhou goose breast meat. Nontargeted metabolomics analysis (UHPLC-MS/MS) was used to distinguish the metabolic composition of goose meat at different ages, and Pearson's correlations between differential metabolites and key meat parameters were assessed. Compared with goslings, adult geese had lighter, redder and chewier meat (p < 0.05). Metabolite analysis revealed significant differences in nucleosides, organic acids, amino acids and sugars. Levels of IMP, xanthosine, pretyrosine and l-threonine were significantly higher in older meat (p < 0.05) and positively correlated with meat freshness indicators. However, pyruvic acid, l-cysteine and glucose 6-phosphate were up-regulated in gosling meat (p < 0.05), which were important flavor compounds. These results facilitate the further investigation of changes in goose meat composition and provide biomarkers for determining goose meat quality at different ages.PMID:37780242 | PMC:PMC10534087 | DOI:10.1016/j.fochx.2023.100775

Elucidating the molecular mechanisms of ozone therapy for neuropathic pain management by integrated transcriptomic and metabolomic approach

Mon, 02/10/2023 - 12:00
Front Genet. 2023 Sep 14;14:1231682. doi: 10.3389/fgene.2023.1231682. eCollection 2023.ABSTRACTIntroduction: Neuropathic pain remains a prevalent and challenging condition to treat, with current therapies often providing inadequate relief. Ozone therapy has emerged as a promising treatment option; however, its mechanisms of action in neuropathic pain remain poorly understood. Methods: In this study, we investigated the effects of ozone treatment on gene expression and metabolite levels in the brainstem and hypothalamus of a rat model, using a combined transcriptomic and metabolomic approach. Results: Our findings revealed significant alterations in key genes, including DCST1 and AIF1L, and metabolites such as Aconitic acid, L-Glutamic acid, UDP-glucose, and Tyrosine. These changes suggest a complex interplay of molecular pathways and region-specific mechanisms underlying the analgesic effects of ozone therapy. Discussion: Our study provides insights into the molecular targets of ozone treatment for neuropathic pain, laying the groundwork for future research on validating these targets and developing novel therapeutic strategies.PMID:37779912 | PMC:PMC10536237 | DOI:10.3389/fgene.2023.1231682

Metabolite profiles and DNA methylation in metabolic syndrome: a two-sample, bidirectional Mendelian randomization

Mon, 02/10/2023 - 12:00
Front Genet. 2023 Sep 15;14:1184661. doi: 10.3389/fgene.2023.1184661. eCollection 2023.ABSTRACTIntroduction: Metabolic syndrome (MetS) increases the risk of cardiovascular disease and death. Previous '-omics' studies have identified dysregulated serum metabolites and aberrant DNA methylation in the setting of MetS. However, the relationship between the metabolome and epigenome have not been elucidated. In this study, we identified serum metabolites associated with MetS and DNA methylation, and we conducted bidirectional Mendelian randomization (MR) to assess causal relationships between metabolites and methylation. Methods: We leveraged metabolomic and genomic data from a national United States cohort of older adults (REGARDS), as well as metabolomic, epigenomic, and genomic data from a family-based study of hypertension (HyperGEN). We conducted metabolite profiling for MetS in REGARDS using weighted logistic regression models and validated them in HyperGEN. Validated metabolites were selected for methylation studies which fit linear mixed models between metabolites and six CpG sites previously linked to MetS. Statistically significant metabolite-CpG pairs were selected for two-sample, bidirectional MR. Results: Forward MR indicated that glucose and serine metabolites were causal on CpG methylation near CPT1A [B(SE): -0.003 (0.002), p = 0.028 and B(SE): 0.029 (0.011), p = 0.030, respectively] and that serine metabolites were causal on ABCG1 [B(SE): -0.008(0.003), p = 0.006] and SREBF1 [B(SE): -0.009(0.004), p = 0.018] methylation, which suggested a protective effect of serine. Reverse MR showed a bidirectional relationship between cg06500161 (ABCG1) and serine [B(SE): -1.534 (0.668), p = 0.023]. Discussion: The metabolome may contribute to the relationship between MetS and epigenetic modifications.PMID:37779905 | PMC:PMC10540781 | DOI:10.3389/fgene.2023.1184661

Artificial Intelligence and Machine Learning in Pharmacological Research: Bridging the Gap Between Data and Drug Discovery

Mon, 02/10/2023 - 12:00
Cureus. 2023 Aug 30;15(8):e44359. doi: 10.7759/cureus.44359. eCollection 2023 Aug.ABSTRACTArtificial intelligence (AI) has transformed pharmacological research through machine learning, deep learning, and natural language processing. These advancements have greatly influenced drug discovery, development, and precision medicine. AI algorithms analyze vast biomedical data identifying potential drug targets, predicting efficacy, and optimizing lead compounds. AI has diverse applications in pharmacological research, including target identification, drug repurposing, virtual screening, de novo drug design, toxicity prediction, and personalized medicine. AI improves patient selection, trial design, and real-time data analysis in clinical trials, leading to enhanced safety and efficacy outcomes. Post-marketing surveillance utilizes AI-based systems to monitor adverse events, detect drug interactions, and support pharmacovigilance efforts. Machine learning models extract patterns from complex datasets, enabling accurate predictions and informed decision-making, thus accelerating drug discovery. Deep learning, specifically convolutional neural networks (CNN), excels in image analysis, aiding biomarker identification and optimizing drug formulation. Natural language processing facilitates the mining and analysis of scientific literature, unlocking valuable insights and information. However, the adoption of AI in pharmacological research raises ethical considerations. Ensuring data privacy and security, addressing algorithm bias and transparency, obtaining informed consent, and maintaining human oversight in decision-making are crucial ethical concerns. The responsible deployment of AI necessitates robust frameworks and regulations. The future of AI in pharmacological research is promising, with integration with emerging technologies like genomics, proteomics, and metabolomics offering the potential for personalized medicine and targeted therapies. Collaboration among academia, industry, and regulatory bodies is essential for the ethical implementation of AI in drug discovery and development. Continuous research and development in AI techniques and comprehensive training programs will empower scientists and healthcare professionals to fully exploit AI's potential, leading to improved patient outcomes and innovative pharmacological interventions.PMID:37779744 | PMC:PMC10539991 | DOI:10.7759/cureus.44359

Glutamate-pantothenate pathway promotes antibiotic resistance of <em>Edwardsiella tarda</em>

Mon, 02/10/2023 - 12:00
Front Microbiol. 2023 Sep 13;14:1264602. doi: 10.3389/fmicb.2023.1264602. eCollection 2023.ABSTRACTAlthough cellular metabolic states have been shown to modulate bacterial susceptibility to antibiotics, the interaction between glutamate (Glu) and chloramphenicol (CAP) resistance remains unclear because of the specificity of antibiotics and bacteria. We found that the level of Glu was upregulated in the CAP-resistant strain of Edwardsiella tarda according to a comparative metabolomics approach based on LC-MS/MS. Furthermore, we verified that exogenous metabolites related to Glu, the tricarboxylic acid (TCA) cycle, and glutathione (GSH) metabolism could promote CAP resistance in survival assays. If GSH metabolism or the TCA cycle is inhibited by L-buthionine sulfoximine or propanedioic acid, the promotion of CAP resistance by Glu in the corresponding pathway disappears. According to metabolomic analysis, exogenous Glu could change pantothenate metabolism, affecting GSH biosynthesis and the TCA cycle. These results showed that the glutamate-pantothenate pathway could promote CAP resistance by being involved in the synthesis of GSH, entering the TCA cycle by direct deamination, or indirectly affecting the metabolism of the two pathways by pantothenate. These results extend our knowledge of the effect of Glu on antibiotic resistance and suggest that the potential effect, which may aggravate antibiotic resistance, should be considered before Glu and GSH administration in the clinic.PMID:37779691 | PMC:PMC10533917 | DOI:10.3389/fmicb.2023.1264602

Exploring the potential mechanism of <em>Rubus corchorifolius</em> L. fruit polyphenol-rich extract in mitigating non-alcoholic fatty liver disease by integration of metabolomics and transcriptomics profiling

Mon, 02/10/2023 - 12:00
Food Funct. 2023 Oct 2. doi: 10.1039/d3fo02653a. Online ahead of print.ABSTRACTNonalcoholic fatty liver disease (NAFLD), as the commonest chronic liver disease, is accompanied by liver oxidative stress and inflammatory responses. Herein, the extract obtained from Rubus corchorifolius fruits was purified and characterized for its polyphenol composition. The liver protective effect of the purified R. corchorifolius fruit extract (RCE) on mice with high-fat-diet (HFD)-induced NAFLD were investigated, and the potential mechanisms were explored through the integration of transcriptomics and metabolomics. Results showed that the polyphenolic compounds in RCE mainly included (-)-epigallocatechin, procyanidin B2, keracyanin, vanillin, dihydromyricetin, and ellagic acid. In addition, RCE intervention ameliorated liver and mitochondrial damage, which was evidenced by decreased indices of oxidative stress, liver function markers, and lipid profile levels. The liver metabonomics research revealed that RCE intervention affected the metabolic pathways of metabolites, including linoleic acid metabolism, galactose metabolism, alanine, aspartate and glutamate metabolism, retinol metabolism, glycine, serine and threonine metabolism, tryptophan metabolism, aminoacyl-tRNA biosynthesis, riboflavin metabolism, starch and sucrose metabolism, and arachidonic acid metabolism. Additionally, liver transcriptomics research indicated that pathways like fatty acid degradation, circadian rhythm, valine, leucine and isoleucine degradation, primary bile acid biosynthesis, cytokine-cytokine receptor interaction, adipocytokine signaling pathway, glutathione metabolism, lipid and atherosclerosis were significantly enriched. The transcriptomics and metabolomics analysis demonstrated that RCE intervention had significant modulatory effects on the metabolic pathways associated with glycolipid metabolism. Moreover, RT-PCR results verified that RCE intervention regulated liver mRNA levels associated with the inflammatory response. Therefore, our findings suggest that the intake of RCE might be an effective strategy to alleviate liver damage.PMID:37779461 | DOI:10.1039/d3fo02653a

Metabolite profiling and antioxidant capacity of natural Ophiocordyceps gracilis and its cultures using LC-MS/MS-based metabolomics: Comparison with Ophiocordyceps sinensis

Mon, 02/10/2023 - 12:00
Phytochem Anal. 2023 Oct 1. doi: 10.1002/pca.3289. Online ahead of print.ABSTRACTINTRODUCTION: Ophiocordyceps gracilis is an entomopathogenic fungus and a precious traditional Chinese medicine with similar medicinal properties to Ophiocordyceps sinensis. However, information on the metabolite profiles of natural O. gracilis and its cultures is lacking, which limits their utilization.OBJECTIVE: The metabolic variations and antioxidant activities of O. gracilis cultures and natural O. gracilis were analyzed to evaluate the nutritional and medicinal value of O. gracilis and its cultures.METHOD: The metabolite profiles of O. gracilis cultures (fruiting bodies and aerial mycelia), natural O. gracilis, and natural O. sinensis were compared by LC-MS/MS coupled with multivariate data analysis. Furthermore, their antioxidant activities were evaluated based on their DPPH• , ABTS•+ , and • OH scavenging abilities.RESULTS: A total of 612 metabolites were identified, and the metabolic compositions of the four Cordyceps samples were similar, with differences observed in the levels of some metabolites. There were 126 differential metabolites between natural O. gracilis and natural O. sinensis, among which fatty acids, carbohydrates, and secondary metabolites are predominant in natural O. gracilis. Furthermore, 116 differential metabolites between O. gracilis cultures and natural Cordyceps were identified, with generally higher levels in O. gracilis cultures than in natural Cordyceps. O. gracilis cultivated fruiting bodies exhibited the strongest antioxidant capacity among Cordyceps samples. Additionally, 46 primary and 24 secondary differential metabolites contribute to antioxidant activities.CONCLUSION: This study provides a reference for the application of natural O. gracilis and its cultures in functional food and medicine from the perspective of metabolites and antioxidant capacity.PMID:37779226 | DOI:10.1002/pca.3289

Toxicity of the disinfectant benzalkonium chloride (C<sub>14</sub>) towards cyanobacterium Microcystis results from its impact on the photosynthetic apparatus and cell metabolism

Sun, 01/10/2023 - 12:00
J Environ Sci (China). 2024 Jan;135:198-209. doi: 10.1016/j.jes.2022.11.007. Epub 2022 Nov 17.ABSTRACTQuaternary ammonium compounds (QACs) are commonly used in a variety of consumer and commercial products, typically as a component of disinfectants. During the COVID-19 pandemic, QACs became one of the primary agents utilized to inactivate the SARS-CoV-2 virus on surfaces. However, the ecotoxicological effects of QACs upon aquatic organisms have not been fully assessed. In this study, we examined the effects of a widely used QAC (benzalkonium chloride-C14, BAC-14) on two toxigenic Microcystis strains and one non-toxigenic freshwater Microcystis strain and carried out an analysis focused on primary, adaptive and compensatory stress responses at apical (growth and photosynthesis) and metabolic levels. This analysis revealed that the two toxic Microcystis strains were more tolerant than the non-toxic strain, with 96 hr-EC50 values of 0.70, 0.76, and 0.38 mg/L BAC-14 for toxigenic M. aeruginosa FACHB-905, toxigenic M. aeruginosa FACHB-469, and non-toxigenic M. wesenbergii FACHB-908, respectively. The photosynthetic activities of the Microcystis, assessed via Fv/Fm values, were significantly suppressed under 0.4 mg/L BAC-14. Furthermore, this analysis revealed that BAC-14 altered 14, 12, and 8 metabolic pathways in M. aeruginosa FACHB-905, M. aeruginosa FACHB-469, and M. wesenbergii FACHB-908, respectively. It is noteworthy that BAC-14 enhanced the level of extracellular microcystin production in the toxigenic Microcystis strains, although cell growth was not significantly affected. Collectively, these data show that BAC-14 disrupted the physiological and metabolic status of Microcystis cells and stimulated the production and release of microcystin, which could result in damage to aquatic systems.PMID:37778795 | DOI:10.1016/j.jes.2022.11.007

Gut microbiome as a biomarker for predicting early recurrence of HBV-related hepatocellular carcinoma

Sun, 01/10/2023 - 12:00
Cancer Sci. 2023 Oct 1. doi: 10.1111/cas.15983. Online ahead of print.ABSTRACTTo investigate the potential of the gut microbiome as a biomarker for predicting the early recurrence of HBV-related hepatocellular carcinoma (HCC), we enrolled 124 patients diagnosed with HBV-associated HCC and 82 HBV-related hepatitis, and 86 healthy volunteers in our study, collecting 292 stool samples for 16S rRNA sequencing and 35 tumor tissue samples for targeted metabolomics. We performed an integrated bioinformatics analysis of gut microbiome and tissue metabolome data to explore the gut microbial-liver metabolite axis associated with the early recurrence of HCC. We constructed a predictive model based on the gut microbiota and validated its efficacy in the temporal validation cohort. Dialister, Veillonella, the Eubacterium coprostanoligenes group, and Lactobacillus genera, as well as the Streptococcus pneumoniae and Bifidobacterium faecale species, were associated with an early recurrence of HCC. We also found that 23 metabolites, including acetic acid, glutamate, and arachidonic acid, were associated with the early recurrence of HCC. A comprehensive analysis of the gut microbiome and tissue metabolome revealed that the entry of gut microbe-derived acetic acid into the liver to supply energy for tumor growth and proliferation may be a potential mechanism for the recurrence of HCC mediated by gut microbe. We constructed a nomogram to predict early recurrence by combining differential microbial species and clinical indicators, achieving an AUC of 78.0%. Our study suggested that gut microbes may serve as effective biomarkers for predicting early recurrence of HCC, and the gut microbial-tumor metabolite axis may explain the potential mechanism by which gut microbes promote the early recurrence of HCC.PMID:37778742 | DOI:10.1111/cas.15983

Influence of time-dependent sampling on the plasma metabolome and exposome of fish collected from an effluent-dependent pond

Sun, 01/10/2023 - 12:00
Sci Total Environ. 2023 Sep 29:167446. doi: 10.1016/j.scitotenv.2023.167446. Online ahead of print.ABSTRACTMetabolomics is increasingly recognized as a useful approach to characterize environmental pollution gradients. While the performance of analytical procedures must be validated and documented, many studies only briefly describe sampling and sample storage. Here we advance our recent study on the influences of sampling delay and holding media on two contaminants of emerging concern in fish plasma by targeted analysis. We specifically examined the metabolome and exposome of common carp under three conditions: plasma sampled immediately after field collection (t = 0 h) and then after 3 h (t = 3 h) or 20 h (t = 20 h) of holding fish in lab water. Plasma samples were analyzed using reversed-phase and HILIC chromatography with mass spectrometric detection. 6143 of the 12,904 compounds (after clustering features) varied among the groups. We observed different metabolite variations patterns depending on the sample collection time. We also identified several xenobiotics (2-Ethylhexyl sulfate, 6-Chloro-5-methyl-1H-benzotriazole) at concentrations generally found at the highest levels in plasma sampled immediately after field collection (t = 0 h). Both the metabolome and the exposome changed rapidly in fish plasma with a time lag, which indicates that obtaining relevant results is complicated by fish-holding conditions. We further identified that non-lethal, relatively low-volume blood sample collection was sufficient with this species, which presents ethical and practical advantages.PMID:37778561 | DOI:10.1016/j.scitotenv.2023.167446

Multi-omics analysis of Gwakhyangjeonggi-san for gastrointestinal complications in atopic dermatitis: A randomized, double-blinded, placebo-controlled, parallel-group clinical trial

Sun, 01/10/2023 - 12:00
J Ethnopharmacol. 2023 Sep 29:117256. doi: 10.1016/j.jep.2023.117256. Online ahead of print.ABSTRACTETHNOPHARMACOLOGICAL RELEVANCE: In traditional Chinese medicine (TCM) and traditional Korean medicine (TKM), Gwakhyangjeonggi-san (GJS) is an herbal decoction used to treat gastrointestinal disorders and allergic diseases. However, no randomized controlled trials have reported the efficacy and safety of GJS against atopic dermatitis (AD) or its comorbidities.AIM OF THE STUDY: This clinical trial investigated the clinical efficacy and safety of GJS for treating patients with AD who have gastrointestinal symptoms, using a multi-omics approach that included 16S rRNA sequencing and metabolomics.MATERIALS AND METHODS: This study was a randomized, double-blind, placebo-controlled, parallel-group clinical trial. Fifty-two patients with AD (age: 19-60) were randomly assigned to receive either the GJS (N = 27) or placebo (N = 25) granules thrice daily for 8 weeks. The primary outcome was measured as the change in the SCORing of Atopic Dermatitis index from baseline to 8 weeks. The secondary outcomes included the eczema area and severity index, dermatology life quality index, EuroQoL 5 dimensions 5 levels (EQ-5D-5L), immunological factors, gastrointestinal status, and safety evaluation. In addition, 16S rRNA sequencing on gut-microbiomes and non-targeted metabolomics approach using mass spectrometry on sera samples were applied to investigate the GJS therapeutic mechanism.RESULTS: After 8 weeks, AD symptoms were reduced in both the GJS and placebo groups without any serious adverse events, but the reduction was not significantly different between the two groups. However, the EQ-5D-5L scores and gastrointestinal symptom scores, such as bitter-tasting fluid presenting in the mouth, upper abdomen bloating, and nausea, only improved in the GJS group. To further elucidate the effect of GJS on patients with AD who have gastrointestinal symptoms, 16S rRNA sequencing and metabolomics were executed. The GJS group had lower gut microbiome diversity including observed OUT, Ace, Chao1 and Shannon index than the placebo group at enrollment time, while the difference in gut microbiome diversity between GJS and placebo group was eliminated by 8 weeks of treatment. Consistently, the metabolomics results showed that the gut microbiome-derived uremic toxins, including indoxyl sulfate and phenylacetylglutamine, significantly increased in the placebo group, while these in GJS group were maintained without any significant change.CONCLUSIONS: These results showed that the GJS had no significant effect on AD compared to the placebo but exerted a beneficial effect on improving the quality of life and gastrointestinal symptoms in patients with AD, and it acted by modulating gut microbiome diversity and gut microbiome-derived uremic toxins. Our findings support the use of GJS for AD comorbidities and also provide evidence that multi-omics approaches can be useful for understanding herbal decoctions in TCM and TKM comprehensively.PMID:37778520 | DOI:10.1016/j.jep.2023.117256

Fat from Hermetia illucens alters the cecal gut microbiome and lowers hepatic triglyceride concentration in comparison to palm oil in obese Zucker rats

Sun, 01/10/2023 - 12:00
J Nutr. 2023 Sep 29:S0022-3166(23)72614-X. doi: 10.1016/j.tjnut.2023.09.019. Online ahead of print.ABSTRACTBACKGROUND: Palm oil (PO) is the most widely utilized plant oil for food production. Owing to great ecological problems associated with PO production, sustainably produced fats, such as insect fat, might be a suitable alternative.OBJECTIVE: The hypothesis was tested that fat from Hermetia illucens larvae (HF) compared with PO and soybean oil (SO) has no adverse effects on hepatic lipid metabolism, plasma metabolome and cecal microbiome in obese Zucker rats.METHODS: 30 male obese Zucker rats were randomly assigned to three groups (SO, PO, HF; n = 10 rats/group), and fed three different semisynthetic diets containing either SO, PO or HF as the main fat source for 4 weeks. The effects were evaluated by measurement of liver and plasma lipid concentrations, liver transcriptomics, targeted plasma metabolomics, and cecal microbiomics.RESULTS: Supplementation of HF reduced hepatic triglyceride (TG) concentration and mRNA levels of selected genes involved in fatty acid and TG synthesis in comparison to PO (P < 0.05). Pairwise comparison of Simpson index and Jaccard index showed a higher cecal microbial α- and β-diversity in rats fed the HF diet compared to rats fed the PO diet (P = 0.015 and P = 0.027, respectively), but no difference between rats fed the diets with SO or PO. Taxonomic analysis of the cecal microbial community revealed a lower abundance of Clostridium_sensu_stricto_1 and a higher abundance of Blautia, Mucispirillum, Anaerotruncus, Harryflintia and Peptococcus in rats supplemented with HF than in rats supplemented with PO (P < 0.05).CONCLUSIONS: HF compared with PO has liver lipid lowering effects in obese Zucker rats, which may be caused by a shift in the gut microbial community. Thus, HF might serve as a sustainably produced fat alternative to PO for food production.PMID:37778509 | DOI:10.1016/j.tjnut.2023.09.019

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