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

Current Challenges and Future Directions in the Assessment of Glucocorticoid Status

Sat, 25/05/2024 - 12:00
Endocr Rev. 2024 May 25:bnae016. doi: 10.1210/endrev/bnae016. Online ahead of print.ABSTRACTGlucocorticoid hormones (GC) are secreted in a circadian and ultradian rhythm and play a critical role in maintaining physiological homeostasis, with both excess and insufficient GC associated with adverse effects on health. Current assessment of GC status is primarily clinical, often in conjunction with serum cortisol values, which may be stimulated or suppressed depending on the GC disturbance being assessed. In the setting of extreme perturbations in cortisol levels i.e. markedly low or high levels, symptoms and signs of GC dysfunction may be overt. However, when disturbances in cortisol GC status values are less extreme, such as when assessing optimization of a GC replacement regimen, signs and symptoms can be more subtle or non-specific. Current tools for assessing GC status, are best suited to identifying profound disturbances but may lack sensitivity for confirming optimal GC status. Moreover, single cortisol values do not necessarily reflect an individual's GC status, as they are subject to inter- and intra-individual variation, do not take into account the pulsatile nature of cortisol secretion, variation in binding proteins, or local tissue concentrations as dictated by 11βeta-hydroxysteroid dehydrogenase (11β-HSD) activity, as well as GC receptor sensitivity. In the present review, we evaluate possible alternative methods for the assessment of GC status that do not solely rely on measurement of circulating cortisol levels. We discuss the potential of changes in metabolomic profiles, miRNA, gene expression, epigenetic, and other novel biomarkers such as GDF-15 and osteocalcin, that could in future aid in the objective classification of GC status.PMID:38795365 | DOI:10.1210/endrev/bnae016

Aconitum coreanum and processed products on its base prevent stroke via the PI3K/Akt and KEAP1/NRF2 in the in vivo study

Sat, 25/05/2024 - 12:00
Metab Brain Dis. 2024 May 25. doi: 10.1007/s11011-024-01357-0. Online ahead of print.ABSTRACTAconitum coreanum (A. coreanum), a traditional Chinese medicine, has been proved to treat ischemic stroke (IS). However, the mechanisms of A. coreanum's anti-stroke is currently unknown. This study aimed to uncover the effect and mechanisms of A. coreanum. And study raw Aconitum coreanum (RA) and steamed Aconitum coreanum (SA) and Aconitum coreanum processed with ginger and Alumen (GA) on the mechanism of the pharmacological action of treating IS. Determining whether the efficacy is affected after processing. The right unilateral ligation of the carotid artery of gerbils was used to mimic IS. The neurological function score, infarct volume, oxidative stress level and inflammatory factor expression were measured in gerbils after IS. Western blot and immunofluorescence analyses were conducted to evaluate the expression of related proteins. Metabolomic analyzes IS-related metabolic pathways in urinary metabolites. RA, SA and GA significantly improved the infarct volume and behavioral score of IS gerbils, increased the expression of brain tissue superoxide dismutase (SOD), glutathione (GSH), nitric oxide (NO) and decreased the content of malondialdehyde (MDA), interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α). Western blot and immunofluorescence analysis results showed that RA, SA and GA significantly increased the expression of P-Akt, PI3K, HO-1 and KEAP1. Metabolomic studies identified 112 differential metabolites, including L-Proline, Riboflavin, Leukotriene D4, and 7-Methylxanthine, as potential biomarkers of stroke, involving 14 metabolic pathways including riboflavin metabolism, pyrimidine metabolism, and purine metabolism. Our findings indicated that A. coreanum protected against cerebral ischemia injury probably via the PI3K/Akt and KEAP1/NRF2 pathway. A. coreanum before and after processing both had a protective effect against IS brain injury in gerbils. The A. coreanum efficacy was not reduced after processing. Even compared to RA, SA had better efficacy.PMID:38795262 | DOI:10.1007/s11011-024-01357-0

Antifungal mechanisms investigation of lactic acid bacteria against Aspergillus flavus: through combining microbial metabolomics and co-culture system

Sat, 25/05/2024 - 12:00
J Appl Microbiol. 2024 May 24:lxae112. doi: 10.1093/jambio/lxae112. Online ahead of print.ABSTRACTAIMS: To develop antifungal lactic acid bacteria (LAB) and investigate their antifungal mechanisms against Aspergillus flavus in aflatoxin (AF) production.METHODS AND RESULTS: We isolated 179 LABs from cereal-based fermentation starters and investigated their antifungal mechanism against Aspergillus flavus through liquid chromatography-mass spectrometry and co-culture analysis techniques. Of the 179 isolates, antifungal activity was identified in Pediococcus pentosaceus, Lactobacillus crustorum, and Weissella paramesenteroides. These LABs reduced AF concentration by i) inhibiting mycelial growth, ii) binding AF to the cell wall, and iii) producing antifungal compounds. Species-specific activities were also observed, with P. pentosaceus inhibiting AF production and W. paramesenteroides showing AF B1 binding activity. In addition, crucial extracellular metabolites for selecting antifungal LAB were involved in the 2',3'-cAMP-adenosine and nucleoside pathways.CONCLUSIONS: This study demonstrates that P. pentosaceus, L. crustorum, and W. paramesenteroides are key LAB strains with distinct antifungal mechanisms against A. flavus, suggesting their potential as biological agents to reduce AF in food materials.PMID:38794887 | DOI:10.1093/jambio/lxae112

Exploration of circulating metabolic signature of erythrodermic psoriasis based on LC-MS metabolomics

Sat, 25/05/2024 - 12:00
Exp Dermatol. 2024 May;33(5):e15103. doi: 10.1111/exd.15103.ABSTRACTErythrodermic psoriasis (EP) is a rare and life-threatening disease, the pathogenesis of which remains to be largely unknown. Metabolomics analysis can provide global information on disease pathophysiology, candidate biomarkers, and potential intervention strategies. To gain a better understanding of the mechanisms of EP and explore the serum metabolic signature of EP, we conducted an untargeted metabolomics analysis from 20 EP patients and 20 healthy controls. Furthermore, targeted metabolomics for focused metabolites were identified in the serum samples of 30 EP patients and 30 psoriasis vulgaris (PsV) patients. In the untargeted analysis, a total of 2992 molecular features were extracted from each sample, and the peak intensity of each feature was obtained. Principal component analysis (PCA), orthogonal partial least squares-discriminant analysis (OPLS-DA) revealed significant difference between groups. After screening, 98 metabolites were found to be significantly dysregulated in EP, including 67 down-regulated and 31 up-regulated. EP patients had lower levels of L-tryptophan, L-isoleucine, retinol, lysophosphatidylcholine (LPC), and higher levels of betaine and uric acid. KEGG analysis showed differential metabolites were enriched in amino acid metabolism and glycerophospholipid metabolism. The targeted metabolomics showed lower L-tryptophan in EP than PsV with significant difference and L-tryptophan levels were negatively correlated with the PASI scores. The serum metabolic signature of EP was discovered. Amino acid and glycerophospholipid metabolism were dysregulated in EP. The metabolite differences provide clues for pathogenesis of EP and they may provide insights for therapeutic interventions.PMID:38794829 | DOI:10.1111/exd.15103

Pilot-Study to Explore Metabolic Signature of Type 2 Diabetes: A Pipeline of Tree-Based Machine Learning and Bioinformatics Techniques for Biomarkers Discovery

Sat, 25/05/2024 - 12:00
Nutrients. 2024 May 20;16(10):1537. doi: 10.3390/nu16101537.ABSTRACTBACKGROUND: This study aims to identify unique metabolomics biomarkers associated with Type 2 Diabetes (T2D) and develop an accurate diagnostics model using tree-based machine learning (ML) algorithms integrated with bioinformatics techniques.METHODS: Univariate and multivariate analyses such as fold change, a receiver operating characteristic curve (ROC), and Partial Least-Squares Discriminant Analysis (PLS-DA) were used to identify biomarker metabolites that showed significant concentration in T2D patients. Three tree-based algorithms [eXtreme Gradient Boosting (XGBoost), Light Gradient Boosting Machine (LightGBM), and Adaptive Boosting (AdaBoost)] that demonstrated robustness in high-dimensional data analysis were used to create a diagnostic model for T2D.RESULTS: As a result of the biomarker discovery process validated with three different approaches, Pyruvate, D-Rhamnose, AMP, pipecolate, Tetradecenoic acid, Tetradecanoic acid, Dodecanediothioic acid, Prostaglandin E3/D3 (isobars), ADP and Hexadecenoic acid were determined as potential biomarkers for T2D. Our results showed that the XGBoost model [accuracy = 0.831, F1-score = 0.845, sensitivity = 0.882, specificity = 0.774, positive predictive value (PPV) = 0.811, negative-PV (NPV) = 0.857 and Area under the ROC curve (AUC) = 0.887] had the slight highest performance measures.CONCLUSIONS: ML integrated with bioinformatics techniques offers accurate and positive T2D candidate biomarker discovery. The XGBoost model can successfully distinguish T2D based on metabolites.PMID:38794775 | DOI:10.3390/nu16101537

Lipidomic Assessment of the Inhibitory Effect of Standardized Water Extract of <em>Hydrangea serrata</em> (Thunb.) Ser. Leaves during Adipogenesis

Sat, 25/05/2024 - 12:00
Nutrients. 2024 May 16;16(10):1508. doi: 10.3390/nu16101508.ABSTRACTObesity is primarily exacerbated by excessive lipid accumulation during adipogenesis, with triacylglycerol (TG) as a major lipid marker. However, as the association between numerous lipid markers and various health conditions has recently been revealed, investigating the lipid metabolism in detail has become necessary. This study investigates the lipid metabolic effects of Hydrangea serrata (Thunb.) Ser. hot water leaf extract (WHS) on adipogenesis using LC-MS-based lipidomics analysis of undifferentiated, differentiated, and WHS-treated differentiated 3T3-L1 cells. WHS treatment effectively suppressed the elevation of glycerolipids, including TG and DG, and prevented a molecular shift in fatty acyl composition towards long-chain unsaturated fatty acids. This shift also impacted glycerophospholipid metabolism. Additionally, WHS stabilized significant lipid markers such as the PC/PE and LPC/PE ratios, SM, and Cer, which are associated with obesity and related comorbidities. This study suggests that WHS could reduce obesity-related risk factors by regulating lipid markers during adipogenesis. This study is the first to assess the underlying lipidomic mechanisms of the adipogenesis-inhibitory effect of WHS, highlighting its potential in developing natural products for treating obesity and related conditions. Our study provides a new strategy for the development of natural products for the treatment of obesity and related diseases.PMID:38794745 | DOI:10.3390/nu16101508

Do Precision and Personalised Nutrition Interventions Improve Risk Factors in Adults with Prediabetes or Metabolic Syndrome? A Systematic Review of Randomised Controlled Trials

Sat, 25/05/2024 - 12:00
Nutrients. 2024 May 14;16(10):1479. doi: 10.3390/nu16101479.ABSTRACTThis review aimed to synthesise existing literature on the efficacy of personalised or precision nutrition (PPN) interventions, including medical nutrition therapy (MNT), in improving outcomes related to glycaemic control (HbA1c, post-prandial glucose [PPG], and fasting blood glucose), anthropometry (weight, BMI, and waist circumference [WC]), blood lipids, blood pressure (BP), and dietary intake among adults with prediabetes or metabolic syndrome (MetS). Six databases were systematically searched (Scopus, Medline, Embase, CINAHL, PsycINFO, and Cochrane) for randomised controlled trials (RCTs) published from January 2000 to 16 April 2023. The Academy of Nutrition and Dietetics Quality Criteria were used to assess the risk of bias. Seven RCTs (n = 873), comprising five PPN and two MNT interventions, lasting 3-24 months were included. Consistent and significant improvements favouring PPN and MNT interventions were reported across studies that examined outcomes like HbA1c, PPG, and waist circumference. Results for other measures, including fasting blood glucose, HOMA-IR, blood lipids, BP, and diet, were inconsistent. Longer, more frequent interventions yielded greater improvements, especially for HbA1c and WC. However, more research in studies with larger sample sizes and standardised PPN definitions is needed. Future studies should also investigate combining MNT with contemporary PPN factors, including genetic, epigenetic, metabolomic, and metagenomic data.PMID:38794717 | DOI:10.3390/nu16101479

Transcriptome and Metabolome Analysis of Rice Cultivar CBB23 after Inoculation by Xanthomonas oryzae pv. oryzae Strains AH28 and PXO99(A)

Sat, 25/05/2024 - 12:00
Plants (Basel). 2024 May 18;13(10):1411. doi: 10.3390/plants13101411.ABSTRACTBacterial leaf blight (BLB), among the most serious diseases in rice production, is caused by Xanthomonas oryzae pv. oryzae (Xoo). Xa23, the broadest resistance gene against BLB in rice, is widely used in rice breeding. In this study, the rice variety CBB23 carrying the Xa23 resistance gene was inoculated with AH28 and PXO99A to identify differentially expressed genes (DEGs) associated with the resistance. Transcriptome sequencing of the infected leaves showed 7997 DEGs between the two strains at different time points, most of which were up-regulated, including cloned rice anti-blight, peroxidase, pathology-related, protein kinase, glucosidase, and other coding genes, as well as genes related to lignin synthesis, salicylic acid, jasmonic acid, and secondary metabolites. Additionally, the DEGs included 40 cloned, five NBS-LRR, nine SWEET family, and seven phenylalanine aminolyase genes, and 431 transcription factors were differentially expressed, the majority of which belonged to the WRKY, NAC, AP2/ERF, bHLH, and MYB families. Metabolomics analysis showed that a large amount of alkaloid and terpenoid metabolite content decreased significantly after inoculation with AH28 compared with inoculation with PXO99A, while the content of amino acids and their derivatives significantly increased. This study is helpful in further discovering the pathogenic mechanism of AH28 and PXO99A in CBB23 rice and provides a theoretical basis for cloning and molecular mechanism research related to BLB resistance in rice.PMID:38794481 | DOI:10.3390/plants13101411

Production of Polyphenolic Natural Products by Bract-Derived Tissue Cultures of Three Medicinal Tilia spp.: A Comparative Untargeted Metabolomics Study

Sat, 25/05/2024 - 12:00
Plants (Basel). 2024 May 7;13(10):1288. doi: 10.3390/plants13101288.ABSTRACTMedicinal plant tissue cultures are potential sources of bioactive compounds. In this study, we report the chemical characterization of the callus cultures of three medicinal Tilia spp. (Tilia cordata, Tilia vulgaris and Tilia tomentosa), along with the comparison to bracts and flowers of the same species. Our aim was to show that calli of Tilia spp. are good alternatives to the calli of T. americana for the production of polyphenols and are better sources of a subset of polyphenolic metabolites, compared to the original organs. Calli were initiated from young bracts and grown on woody plant medium containing 1 mg L-1 2,4-D and 0.1 mg L-1 BAP. For chemical characterization, a quality-controlled untargeted metabolomics approach and the quantification of several bioactive compounds was performed with the use of LC-ESI-MS/MS. While bracts and flowers contained flavonoid glycosides (astragalin, isoquercitrin) as major polyphenols, calli of all species contained catechins, coumarins (fraxin, esculin and scopoletin) and flavane aglyca. T. tomentosa calli contained 5397 µg g DW-1 catechin, 201 µg g DW-1 esculin, 218 µg g DW-1 taxifolin and 273 µg g DW-1 eriodictyol, while calli from other species contained lower amounts. T. cordata and T. tomentosa flowers were rich in isoquercitrin, containing 8134 and 6385 µg g DW-1, respectively. The currently tested species contained many of the bioactive metabolites described from T. americana. The production of catechin was shown to be comparable to the most efficient tissue cultures reported. Flowers and bracts contained flavonoid glycosides, including tiliroside, resembling bioactive fractions of T. americana. In addition, untargeted metabolomics has shown fingerprint-like differences among species, highlighting possible chemotaxonomic and quality control applications, especially for bracts.PMID:38794359 | DOI:10.3390/plants13101288

(1)H-NMR Metabolomic Study of the Mushroom Pleurotus djamor for the Identification of Nematocidal Compounds

Sat, 25/05/2024 - 12:00
Pharmaceuticals (Basel). 2024 Apr 30;17(5):580. doi: 10.3390/ph17050580.ABSTRACTDue to the increasing populations of anthelmintic-resistant gastrointestinal nematodes and as a consequence of the adverse effects of synthetic drugs, this study focuses on the search for secondary metabolites with nematocidal activity from the edible mushroom Pleurotus djamor using The proton nuclear magnetic resonance (1H-NMR) metabolomics. The highest activity was shown by the ethyl acetate fractions of mycelium (EC50 290.8 µg/mL) and basidiomes (EC50 282.7 µg/mL). Principal component analysis (PCA) and hierarchical data analysis (HCA) of the 1H-NMR metabolic profiles data showed that the ethanolic extracts, the ethyl acetate, butanol, and water fractions from mycelium have different metabolic profiles than those from basidiomes, while low polarity (hexane) fractions from both stages of fungal development show similar profiles. Orthogonal partial least squares discriminant analysis (OPLS-DA) allowed the identification of signals in the 1H-NMR metabolic profile associated with nematocidal activity. The signals yielded via OPLS-DA and bidimensional NMR analysis allowed the identification of uracil as a component in the ethyl acetate fraction from basidiomes, with an EC50 of 237.7 µg/mL. The results obtained showed that chemometric analyses of the 1H-NMR metabolic profiles represent a viable strategy for the identification of bioactive compounds from samples with complex chemical profiles.PMID:38794150 | DOI:10.3390/ph17050580

The Potential of Fecal Volatile Organic Compound Analysis for the Early Diagnosis of Late-Onset Sepsis in Preterm Infants: A Narrative Review

Sat, 25/05/2024 - 12:00
Sensors (Basel). 2024 May 16;24(10):3162. doi: 10.3390/s24103162.ABSTRACTEarly diagnosis and treatment of late-onset sepsis (LOS) is crucial for survival, but challenging. Intestinal microbiota and metabolome alterations precede the clinical onset of LOS, and the preterm gut is considered an important source of bacterial pathogens. Fecal volatile organic compounds (VOCs), formed by physiologic and pathophysiologic metabolic processes in the preterm gut, reflect a complex interplay between the human host, the environment, and microbiota. Disease-associated fecal VOCs can be detected with an array of devices with various potential for the development of a point-of-care test (POCT) for preclinical LOS detection. While characteristic VOCs for common LOS pathogens have been described, their VOC profiles often overlap with other pathogens due to similarities in metabolic pathways, hampering the construction of species-specific profiles. Clinical studies have, however, successfully discriminated LOS patients from healthy individuals using fecal VOC analysis with the highest predictive value for Gram-negative pathogens. This review discusses the current advancements in the development of a non-invasive fecal VOC-based POCT for early diagnosis of LOS, which may potentially provide opportunities for early intervention and targeted treatment and could improve clinical neonatal outcomes. Identification of confounding variables impacting VOC synthesis, selection of an optimal detection device, and development of standardized sampling protocols will allow for the development of a novel POCT in the near future.PMID:38794014 | DOI:10.3390/s24103162

The Causal Effect of Gut Microbiota and Plasma Metabolome on Lung Cancer and the Heterogeneity across Subtypes: A Mendelian Randomization Study

Sat, 25/05/2024 - 12:00
J Pers Med. 2024 Apr 25;14(5):453. doi: 10.3390/jpm14050453.ABSTRACTThe causal effect and pathways of gut microbiota and plasma metabolome on lung cancer have been important topics for personalized medicine; however, the heterogeneity of lung cancer subtypes has not gained enough attention in previous studies. This study sought to employ a Mendelian randomization analysis to screen the specific gut microbiota and plasma metabolome, which may have a causal effect on lung cancer. We further extended our analysis to estimate the effects of these exposures on various pathological subtypes of lung cancer. Furthermore, a mediation analysis was performed to identify the potential pathway underlying the influence of microbiota and metabolites. Our study identified 13 taxa and 15 metabolites with a causal association with the overall risk of lung cancer. Furthermore, we found 8 taxa and 14 plasma metabolites with a causal effect on lung adenocarcinoma, 4 taxa and 10 metabolites with a causal effect on squamous cell lung carcinoma, and 7 taxa and 16 metabolites with a causal effect on SCLC. We also identified seven mediation pathways that could potentially elucidate the influence of these microbiota and metabolites on overall lung cancer or special subtypes. Our study highlighted the heterogeneity of the gut microbiome and plasma metabolome in a lung cancer subtype and elucidated the potential underlying mechanisms. This could pave the way for more personalized lung cancer prevention and treatment.PMID:38793035 | DOI:10.3390/jpm14050453

Facial Skin Microbiome Composition and Functional Shift with Aging

Sat, 25/05/2024 - 12:00
Microorganisms. 2024 May 18;12(5):1021. doi: 10.3390/microorganisms12051021.ABSTRACTThe change in the skin microbiome as individuals age is only partially known. To provide a better understanding of the impact of aging, whole-genome sequencing analysis was performed on facial skin swabs of 100 healthy female Caucasian volunteers grouped by age and wrinkle grade. Volunteers' metadata were collected through questionnaires and non-invasive biophysical measurements. A simple model and a biological statistical model were used to show the difference in skin microbiota composition between the two age groups. Taxonomic and non-metric multidimensional scaling analysis showed that the skin microbiome was more diverse in the older group (≥55 yo). There was also a significant decrease in Actinobacteria, namely in Cutibacterium acnes, and an increase in Corynebacterium kroppenstedtii. Some Streptococcus and Staphylococcus species belonging to the Firmicutes phylum and species belonging to the Proteobacteria phylum increased. In the 18-35 yo younger group, the microbiome was characterized by a significantly higher proportion of Cutibacterium acnes and Lactobacillus, most strikingly, Lactobacillus crispatus. The functional analysis using GO terms revealed that the young group has a higher significant expression of genes involved in biological and metabolic processes and in innate skin microbiome protection. The better comprehension of age-related impacts observed will later support the investigation of skin microbiome implications in antiaging protection.PMID:38792850 | DOI:10.3390/microorganisms12051021

Role of Probiotics in Gut Microbiome and Metabolome in Non-Alcoholic Fatty Liver Disease Mouse Model: A Comparative Study

Sat, 25/05/2024 - 12:00
Microorganisms. 2024 May 17;12(5):1020. doi: 10.3390/microorganisms12051020.ABSTRACTNon-alcoholic fatty liver disease (NAFLD) is the most prevalent chronic liver condition worldwide. Numerous studies conducted recently have demonstrated a connection between the dysbiosis of the development of NAFLD and gut microbiota. Rebuilding a healthy gut ecology has been proposed as a strategy involving the use of probiotics. The purpose of this work is to investigate and compare the function of probiotics Akkermansia muciniphila (A. muciniphila) and VSL#3 in NAFLD mice. Rodent NAFLD was modeled using a methionine choline-deficient diet (MCD) with/without oral probiotic delivery. Subsequently, qPCR, histological staining, and liver function tests were conducted. Mass spectrometry-based analysis and 16S rDNA gene sequencing were used to investigate the liver metabolome and gut microbiota. We found that while both A. muciniphila and VSL#3 reduced hepatic fat content, A. muciniphila outperformed VSL#3. Furthermore, probiotic treatment restored the β diversity of the gut flora and A. muciniphila decreased the abundance of pathogenic bacteria such as Ileibacterium valens. These probiotics altered the metabolism in MCD mice, especially the glycerophospholipid metabolism. In conclusion, our findings distinguished the role of A. muciniphila and VSL#3 in NAFLD and indicated that oral-gavage probiotics remodel gut microbiota and improve metabolism, raising the possibility of using probiotics in the cure of NAFLD.PMID:38792849 | DOI:10.3390/microorganisms12051020

Innovative Biomarkers for Obesity and Type 1 Diabetes Based on Bifidobacterium and Metabolomic Profiling

Sat, 25/05/2024 - 12:00
Microorganisms. 2024 May 3;12(5):931. doi: 10.3390/microorganisms12050931.ABSTRACTThe role of Bifidobacterium species and microbial metabolites such as short-chain fatty acids (SCFAs) and human milk oligosaccharides in controlling intestinal inflammation and the pathogenesis of obesity and type 1 diabetes (T1D) has been largely studied in recent years. This paper discusses the discovery of signature biomarkers for obesity and T1D based on data from a novel test for profiling several Bifidobacterium species, combined with metabolomic analysis. Through the NUTRISHIELD clinical study, a total of 98 children were recruited: 40 healthy controls, 40 type 1 diabetics, and 18 obese children. Bifidobacterium profiles were assessed in stool samples through an innovative test allowing high taxonomic resolution and precise quantification, while SCFAs and branched amino acids were measured in urine samples through gas chromatography-mass spectrometry (GC-MS). KIDMED questionnaires were used to evaluate the children's dietary habits and correlate them with the Bifidobacterium and metabolomic profiles. We found that B. longum subs. infantis and B. breve were higher in individuals with obesity, while B. bifidum and B. longum subs. longum were lower compared to healthy individuals. In individuals with T1D, alterations were found at the metabolic level, with an overall increase in the level of the most measured metabolites. The high taxonomic resolution of the Bifidobacterium test used meant strong correlations between the concentrations of valine and isoleucine, and the relative abundance of some Bifidobacterium species such as B. longum subs. infantis, B. breve, and B. bifidum could be observed.PMID:38792760 | DOI:10.3390/microorganisms12050931

Microbial Community and Metabolome Analysis of the Porcine Intestinal Damage Model Induced by the IPEC-J2 Cell Culture-Adapted Porcine Deltacoronavirus (PDCoV) Infection

Sat, 25/05/2024 - 12:00
Microorganisms. 2024 Apr 27;12(5):874. doi: 10.3390/microorganisms12050874.ABSTRACTThis study was conducted to elucidate the intestinal damage induced by the IPEC-J2 cell culture-passaged PDCoV. The results showed that PDCoV disrupted the intestinal structure and increased intestinal permeability, causing abnormalities in mucosal pathology. Additionally, PDCoV induced an imbalance in the intestinal flora and disturbed its stability. Microbial community profiling revealed bacterial enrichment (e.g., Proteobacteria) and reduction (e.g., Firmicutes and Bacteroidetes) in the PDCoV-inoculated piglet model. In addition, metabolomics analysis indicated that 82 named differential metabolites were successfully quantified, including 37 up-regulated and 45 down-regulated metabolites. Chenodeoxycholic acid, sphingosine, and oleanolic aldehyde levels were reduced in PDCoV-inoculated piglets, while phenylacetylglycine and geranylgeranyl-PP levels were elevated. Correlation analysis indicated a negative correlation between Escherichia-Shigella and choline, succinic acid, creatine, phenyllactate, and hippuric acid. Meanwhile, Escherichia-Shigella was positively correlated with acetylcholine, L-Glutamicacid, and N-Acetylmuramate. Roseburia, Lachnospiraceae_UCG-010, Blautia, and Limosilactobacillus were negatively and positively correlated with sphingosine, respectively. These data suggested PDCoV-inoculated piglets exhibited significant taxonomic perturbations in the gut microbiome, which may result in a significantly altered metabolomic profile.PMID:38792704 | DOI:10.3390/microorganisms12050874

Plant Growth-Promoting Bacteria Influence Microbial Community Composition and Metabolic Function to Enhance the Efficiency of <em>Hybrid pennisetum</em> Remediation in Cadmium-Contaminated Soil

Sat, 25/05/2024 - 12:00
Microorganisms. 2024 Apr 26;12(5):870. doi: 10.3390/microorganisms12050870.ABSTRACTThe green and efficient remediation of soil cadmium (Cd) is an urgent task, and plant-microbial joint remediation has become a research hotspot due to its advantages. High-throughput sequencing and metabolomics have technical advantages in analyzing the microbiological mechanism of plant growth-promoting bacteria in improving phytoremediation of soil heavy metal pollution. In this experiment, a pot trial was conducted to investigate the effects of inoculating the plant growth-promoting bacterium Enterobacter sp. VY on the growth and Cd remediation efficiency of the energy plant Hybrid pennisetum. The test strain VY-1 was analyzed using high-throughput sequencing and metabolomics to assess its effects on microbial community composition and metabolic function. The results demonstrated that Enterobacter sp. VY-1 effectively mitigated Cd stress on Hybrid pennisetum, resulting in increased plant biomass, Cd accumulation, and translocation factor, thereby enhancing phytoremediation efficiency. Analysis of soil physical-chemical properties revealed that strain VY-1 could increase soil total nitrogen, total phosphorus, available phosphorus, and available potassium content. Principal coordinate analysis (PCoA) indicated that strain VY-1 significantly influenced bacterial community composition, with Proteobacteria, Firmicutes, Chloroflexi, among others, being the main differential taxa. Redundancy analysis (RDA) revealed that available phosphorus, available potassium, and pH were the primary factors affecting bacterial communities. Partial Least Squares Discriminant Analysis (PLS-DA) demonstrated that strain VY-1 modulated the metabolite profile of Hybrid pennisetum rhizosphere soil, with 27 differential metabolites showing significant differences, including 19 up-regulated and eight down-regulated expressions. These differentially expressed metabolites were primarily involved in metabolism and environmental information processing, encompassing pathways such as glutamine and glutamate metabolism, α-linolenic acid metabolism, pyrimidine metabolism, and purine metabolism. This study utilized 16S rRNA high-throughput sequencing and metabolomics technology to investigate the impact of the plant growth-promoting bacterium Enterobacter sp. VY-1 on the growth and Cd enrichment of Hybrid pennisetum, providing insights into the regulatory role of plant growth-promoting bacteria in microbial community structure and metabolic function, thereby improving the microbiological mechanisms of phytoremediation.PMID:38792702 | DOI:10.3390/microorganisms12050870

Multi-Omics of <em>Campylobacter jejuni</em> Growth in Chicken Exudate Reveals Molecular Remodelling Associated with Altered Virulence and Survival Phenotypes

Sat, 25/05/2024 - 12:00
Microorganisms. 2024 Apr 25;12(5):860. doi: 10.3390/microorganisms12050860.ABSTRACTCampylobacter jejuni is the leading cause of foodborne human gastroenteritis in the developed world. Infections are largely acquired from poultry produced for human consumption and poor food handling is thus a major risk factor. Chicken exudate (CE) is a liquid produced from defrosted commercial chicken products that facilitates C. jejuni growth. We examined the response of C. jejuni to growth in CE using a multi-omics approach. Changes in the C. jejuni proteome were assessed by label-based liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS). We quantified 1328 and 1304 proteins, respectively, in experiments comparing 5% CE in Mueller-Hinton (MH) medium and 100% CE with MH-only controls. These proteins represent 81.8% and 80.3% of the predicted C. jejuni NCTC11168 proteome. Growth in CE induced profound remodelling of the proteome. These changes were typically conserved between 5% and 100% CE, with a greater magnitude of change observed in 100% CE. We confirmed that CE induced C. jejuni biofilm formation, as well as increasing motility and resistance against oxidative stress, consistent with changes to proteins representing those functions. Assessment of the C. jejuni metabolome showed CE also led to increased intracellular abundances of serine, proline, and lactate that were correlated with the elevated abundances of their respective transporters. Analysis of carbon source uptake showed prolonged culture supernatant retention of proline and succinate in CE-supplemented medium. Metabolomics data provided preliminary evidence for the uptake of chicken-meat-associated dipeptides. C. jejuni exposed to CE showed increased resistance to several antibiotics, including polymyxin B, consistent with changes to tripartite efflux system proteins and those involved in the synthesis of lipid A. The C. jejuni CE proteome was also characterised by very large increases in proteins associated with iron acquisition, while a decrease in proteins containing iron-sulphur clusters was also observed. Our data suggest CE is both oxygen- and iron-limiting and provide evidence of factors required for phenotypic remodelling to enable C. jejuni survival on poultry products.PMID:38792690 | DOI:10.3390/microorganisms12050860

Effects of Different Carbon and Nitrogen Ratios on Yield, Nutritional Value, and Amino Acid Contents of <em>Flammulina velutipes</em>

Sat, 25/05/2024 - 12:00
Life (Basel). 2024 May 8;14(5):598. doi: 10.3390/life14050598.ABSTRACTThe carbon-to-nitrogen (C/N) ratio in the cultivation medium significantly influences the growth rate, vigor of mycelium, yield of fruiting bodies, and their nutritional composition. Recently, agricultural and forestry wastes have been increasingly used in cultivating Flammulina velutipes. However, systematic research on how these materials affect the nutritional and functional properties of the fruiting bodies is lacking. This study investigated the effects of different C/N ratios on F. velutipes cultivation. We evaluated the agronomic traits, nutritional composition, and flavor compounds of the fruiting bodies. Our findings reveal that an optimal C/N ratio of 27:1 in the composted substrates enhances the total yield of fruiting bodies, with 25.1% soybean straw as the primary raw material. This ratio also significantly increases the levels of crude protein, total amino acids, and essential amino acids in the fruiting bodies (p < 0.05). Fruiting bodies from the high-nitrogen (HN) treatment showed the highest content of umami amino acids and equivalent umami concentration value. Additionally, we employed an untargeted liquid chromatography-mass spectrometry (LC-MS)-based metabolomics approach to analyze the metabolite profiles of fruiting bodies cultivated in high-nitrogen (HN), medium-nitrogen (MN), and low-nitrogen (LN) substrates. We found that the carbon-nitrogen ratio can affect the flavor and quality of fruiting bodies by regulating amino acid biosynthesis and metabolism and other related pathways. Our results suggest that a C/N ratio of 27:1 offers numerous benefits for the cultivation of F. velutipes with comprehensive analyses and has promising application prospects.PMID:38792619 | DOI:10.3390/life14050598

Characteristics of the Follicular Fluid Extracellular Vesicle Molecular Profile in Women in Different Age Groups in ART Programs

Sat, 25/05/2024 - 12:00
Life (Basel). 2024 Apr 24;14(5):541. doi: 10.3390/life14050541.ABSTRACTThe aim of this study was to investigate the molecular composition of follicular fluid (FF) extracellular vesicles (EVs) in women of different reproductive ages and its possible relationship to sperm fertilizing ability. FF EVs were obtained by differential centrifugation. The concentration and size distribution of FF EVs were analyzed by nanoparticle tracking analysis. The lipidome and proteome were analyzed by liquid chromatography-mass spectrometry. The isolated FF EVs had a variety of shapes and sizes; their concentration and size distribution did not differ significantly between the age groups. In women younger than 35 years, the concentration of vesicular progesterone was 6.6 times higher than in women older than 35 years, and the total levels of the main lipid classes were increased in younger women. A proteomic analysis revealed that not only FF EV-specific proteins, but also proteins involved in sperm activation were present. New data were obtained on the composition of FF EVs, confirming their importance as molecular indicators of age-related changes in the female reproductive system. In addition, these results shed light on the possible interaction between the FF EVs of women in different age groups and male germ cells. Therefore, studying the transcriptomic and metabolomic profile of FF EVs may be a crucial approach to evaluate the efficacy of ART.PMID:38792563 | DOI:10.3390/life14050541

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