PubMed

Ultrason Sonochem. 2023 Feb 21;94:106339. doi: 10.1016/j.ultsonch.2023.106339. Online ahead of print.ABSTRACTThe current work combines headspace solid phase microextraction-gas chromatography-mass spectrometry (HS-SPME-GC/MS) with multivariate analysis fusion metabonomics for examining metabolite profile changes. The correlation with metabolic pathways during the fermentation of kombucha tea were comprehensively explored. For optimizing the fermentation process, ultrasound-assisted factors were explored. A total of 132 metabolites released by fermented kombucha were detected by HS-SPME-GC/MS. We employed the principal component analysis (PCA) and partial least squares-discriminant analysis (PLS-DA) to present the relationship between aroma components and fermentation time, of which the first two principal components respectively accounted for 60.3% and 6.5% of the total variance. Multivariate statistical analysis showed that during the fermentation of kombucha tea, there were significant differences in the phenotypes of metabolites in the samples, and 25 characteristic metabolites were selected as biomarkers. Leaf alcohol was first proposed as the characteristic volatile in the fermentation process of kombucha. Furthermore, we addressed the generation pathways of characteristic volatiles, their formation mechanisms, and the transformational correlation among them. Our findings provide a roadmap for future kombucha fermentation processing to enhance kombucha flavor and aroma.PMID:36842214 | DOI:10.1016/j.ultsonch.2023.106339

Andrology. 2023 Feb 26. doi: 10.1111/andr.13412. Online ahead of print.ABSTRACTBACKGROUND: Asthenozoospermia is one of the essential causes of male infertility, and its incidence is significantly higher in obese men. Due to its complex etiology and unknown pathomechanism, the diagnosis and treatment of obesity-induced asthenozoospermia is a prevalent problem in reproductive medicine.OBJECTIVE: To explore major differential metabolites and metabolic pathways in seminal plasma and pathological mechanisms for obesity-induced asthenozoospermia.MATERIALS AND METHODS: We performed nontarget metabolomic studies on the seminal plasma of healthy with normal semen parameters men (HN group, n = 20), obese with normal semen parameters men (ON group, n = 20) and obesity-induced asthenozoospermia men (OA group, n = 20) based on gas chromatography-mass spectrometry (GC-MS). Metabolic profilings and related pathway analyses were conducted to discriminate differential metabolites and metabolic pathways.RESULTS: A total of 20 differential metabolites including fructose, succinic acid, aconitic acid, methylmaleic acid, glucopyranose, serine, valine, leucine, phenylalanine, glycine, glutamic acid, alanine, proline and threonine were identified in HN group and ON group, 24 differential metabolites including glucose, fructose, pyruvic acid, citric acid, succinic acid, aconitic acid, glucopyranose, glutamic acid, valine, leucine, glycine, phenylalanine, lysine, citrulline, proline and alanine were produced in OA group and ON group, and 28 differential metabolites including glucose, fructose, citric acid, succinic acid, glucopyranose, valine, glycine, serine, leucine, phenylalanine, alanine, threonine, proline, glutamic acid, citrulline, lysine and tyrosine were produced in OA group and HN group. In addition, abnormal energy metabolism including carbohydrate metabolism (TCA cycle, glycolysis/gluconeogenesis and pyruvate metabolism) and amino acid metabolism (phenylalanine, tyrosine and tryptophan biosynthesis, D-glutamine and D-glutamate metabolism; phenylalanine metabolism, etc.) were found in ON group and OA group.CONCLUSION: Obesity could affect the metabolite composition in seminal plasma and abnormal energy metabolism in seminal plasma mainly including carbohydrate metabolism and amino acid metabolism was closely related to obesity-induced asthenozoospermia. This article is protected by copyright. All rights reserved.PMID:36841993 | DOI:10.1111/andr.13412

J Sep Sci. 2023 Feb 26:e2201004. doi: 10.1002/jssc.202201004. Online ahead of print.ABSTRACTEpilepsy is a complex neurological disease characterized by spontaneous recurrent seizures that affects around 1% of the global population. Despite the significant progress in the mechanisms of epileptogenesis, there is still about 60% of cases in which the cause is unknown. Thus, revealing the molecular mechanisms of epileptogenesis will greatly improve the development of epilepsy treatment. Since comprehensive characterization of amino acids and water-soluble vitamins is important in understanding the underlying mechanisms of epilepsy or seizures, we developed two liquid chromatography-tandem mass spectrometry methods to quantify 17 water-soluble vitamins and 46 amino acids and applied them to our pentylenetetrazole-induced kindling rat model. All water-soluble vitamins were detected with a linearity of r > 0.992 and limits of quantitation between 0.1 and 5 ng/ml except for nicotinic acid. For amino acids, the linearities obtained were good with correlation coefficients higher than 0.99, and matrix effects were between 85.3 and 110%. To handle the multidimensional data more effectively, multivariate statistical analysis approaches used in non-targeted metabolomics were creatively exploited in the visualization, interpretation, and exploration of the results. This article is protected by copyright. All rights reserved.PMID:36841992 | DOI:10.1002/jssc.202201004

Eye (Lond). 2023 Feb 25. doi: 10.1038/s41433-023-02457-4. Online ahead of print.ABSTRACTBACKGROUND: Pathological myopia (PM) is closely associated with blinding ocular morbidities. Identifying biomarkers can provide clues on pathogeneses. This study aimed to identify metabolic biomarkers and underlying mechanisms in the vitreous humour (VH) of PM patients with complications.METHODS: VH samples were collected from 39 PM patients with rhegmatogenous retinal detachment (RRD) (n = 23) or macular hole (MH)/myopic retinoschisis (MRS) (n = 16) and 23 controls (MH with axial length < 26 mm) who underwent surgical treatment. VH metabolomic profiles were investigated using ultra-performance liquid chromatography‒mass spectrometry. The area under the receiver operating characteristic curve (AUC) was computed to identify potential biomarkers for PM diagnosis.RESULTS: Bioinformatics analysis identified nineteen and four metabolites altered in positive and negative modes, respectively, and these metabolites were involved in tryptophan metabolism. Receiver operating characteristic analysis showed that seventeen metabolites (AUC > 0.6) in the positive mode and uric acid in the negative mode represent potential biomarkers for PM with complications (AUC = 0.894). Pairwise and pathway analyses among the RRD-PM, MH/MRS-PM and control groups showed that tryptophan metabolism and uric acid were closely correlated with PM. Altered metabolites and pathways in our study were characterized by increased oxidative stress and altered energy metabolism. These results contribute to a better understanding of myopia progression with or without related complications.CONCLUSIONS: Our study provides metabolomic signatures and related immunopathological features in the VH of PM patients, revealing new insight into the prevention and treatment of PM and related complications.PMID:36841867 | DOI:10.1038/s41433-023-02457-4

Sci Rep. 2023 Feb 25;13(1):3296. doi: 10.1038/s41598-023-30231-9.ABSTRACTMetabolomics-derived metabolites (henceforth metabolites) may mediate the relationship between modifiable risk factors and clinical biomarkers of metabolic health (henceforth clinical biomarkers). We set out to study the associations of metabolites with clinical biomarkers and a potential mediation effect in a population of young adults. First, we conducted a systematic literature review searching for metabolites associated with 11 clinical biomarkers (inflammation markers, glucose, blood pressure or blood lipids). Second, we replicated the identified associations in a study population of n = 218 (88 males and 130 females, average age of 18 years) participants of the DONALD Study. Sex-stratified linear regression models adjusted for age and BMI and corrected for multiple testing were calculated. Third, we investigated our previously reported metabolites associated with anthropometric and dietary factors mediators in sex-stratified causal mediation analysis. For all steps, both urine and blood metabolites were considered. We found 41 metabolites in the literature associated with clinical biomarkers meeting our inclusion criteria. We were able to replicate an inverse association of betaine with CRP in women, between body mass index and C-reactive protein (CRP) and between body fat and leptin. There was no evidence of mediation by lifestyle-related metabolites after correction for multiple testing. We were only able to partially replicate previous findings in our age group and did not find evidence of mediation. The complex interactions between lifestyle factors, the metabolome, and clinical biomarkers warrant further investigation.PMID:36841863 | DOI:10.1038/s41598-023-30231-9

Oncogenesis. 2023 Feb 25;12(1):10. doi: 10.1038/s41389-023-00456-4.ABSTRACTHead and neck paragangliomas (HNPGLs), rare chemoresistant tumors curable only with surgery, are strongly influenced by genetic predisposition, hence patients and relatives require lifetime follow-up with MRI and/or PET-CT because of de novo disease risk. This entails exposure to electromagnetic/ionizing radiation, costs, and organizational challenges, because patients and relatives are scattered far from reference centers. Simplified first-line screening strategies are needed. We employed flow injection analysis tandem mass spectrometry, as used in newborn metabolic screening, to compare the plasma metabolic profile of HNPGL patients (59 samples, 56 cases) and healthy controls (24 samples, 24 cases). Principal Component Analysis (PCA) and Partial Least Discriminant Analysis (PLS-DA) highlighted a distinctive HNPGL signature, likely reflecting the anaplerotic conversion of the TCA cycle to glutaminolysis and catabolism of branched amino acids, DNA damage and deoxyadenosine (dAdo) accumulation, impairment of fatty acid oxidation, switch towards the Warburg effect and proinflammatory lysophosphatidylcholines (LPCs) signaling. Statistical analysis of the metabolites that most impacted on PLS-DA was extended to 10 acoustic neuroma and 2 cholesteatoma patients, confirming significant differences relative to the HNPGL plasma metabolomic profile. The best confusion matrix from the ROC curve built on 2 metabolites, dAdo and C26:0-LPC, provided specificity of 94.29% and sensitivity of 89.29%, with positive and negative predictive values of 96.2% and 84.6%, respectively. Analysis of dAdo and C26:0-LPC levels in dried venous and capillary blood confirmed that dAdo, likely deriving from 2'-deoxy-ATP accumulated in HNPGL cells following endogenous genotoxic damage, efficiently discriminated HNPGL patients from healthy controls and acoustic neuroma/cholesteatoma patients on easily manageable dried blood spots.PMID:36841802 | DOI:10.1038/s41389-023-00456-4

Gastroenterology. 2023 Feb 23:S0016-5085(23)00161-0. doi: 10.1053/j.gastro.2023.02.022. Online ahead of print.ABSTRACTThe human gut microbiome has been linked to numerous digestive disorders, but its metabolic products have been much less well characterized, in part due to the expense of untargeted metabolomics and in part to the lack of ability to process the data. In this Review, we focus on the rapidly expanding information about the bile acid repertoire produced by the gut microbiome, including the impacts of bile acids on a wide range of host physiological processes and diseases, while also discussing the role of short-chain fatty acids and other important gut microbiome-derived metabolites. Of particular note is the action of gut microbiome-derived metabolites throughout the body, impacting processes ranging from obesity to aging to disorders traditionally thought of as diseases of the nervous system but now being recognized as being strongly influenced by the gut microbiome and the metabolites it produces. We also highlight the emerging role for modifying the gut microbiome to improve health or to treat disease, including the "engineered native bacteria'' approach that takes bacterial strains from a patient, modifies them to alter metabolism, and re-introduces them. Taken together, study of the metabolites derived from the gut microbiome will provide insights into a wide range of physiological and pathophysiological processes, and has substantial potential for new approaches to diagnostics and therapeutics of disease of or involving the gastrointestinal tract.PMID:36841488 | DOI:10.1053/j.gastro.2023.02.022

Environ Pollut. 2023 Feb 23:121352. doi: 10.1016/j.envpol.2023.121352. Online ahead of print.ABSTRACTRecently, sodium percarbonate (SPC) as a solid substitute for H2O2 has aroused extensive attention in advanced oxidation processes. In current work, the degradation kinetics and mechanisms of antibiotic sulfamethoxazole (SMX) by ultraviolet (UV) driven SPC system were explored. The removal efficiency of SMX was enhanced as the increasing dosage of SPC. Moreover, hydroxyl radical (•OH), carbonate radical (CO3•-) and superoxide radical (O2•-) were verified to be presented by scavenger experiments and •OH, CO3•- exhibited a significant role in SMX degradation. Reactions mediated by these radicals were affected by anions and natural organic matters, implying that an incomplete mineralization of SMX would be ubiquitous. The screening four intermediates and transformation patterns of SMX were verified by DFT analysis. Metabolomic analysis demonstrated that a decreasing negative effect in E. coli after 24 h exposure was induced by intermediates products. In detail, SMX interfered in some key functional metabolic pathways including carbohydrate metabolism, pentose and glucuronate metabolism, nucleotide metabolism, arginine and proline metabolism, sphingolipid metabolism, which were mitigated after UV/SPC oxidation treatment, suggesting a declining environmental risk of SMX. This work provided new insights into biological impacts of SMX and its transformation products and vital guidance for SMX pollution control using UV/SPC technology.PMID:36841421 | DOI:10.1016/j.envpol.2023.121352

Eur J Pharmacol. 2023 Feb 23:175618. doi: 10.1016/j.ejphar.2023.175618. Online ahead of print.ABSTRACTNon-alcoholic steatohepatitis (NASH) is the hepatic manifestation of metabolic syndrome. Non-resolving inflammation, triggered by sustained accumulation of lipids, is an important driving force of NASH. Thus, unveiling metabolic immune regulation could help better understand the pathology and intervention of NASH. In this study, we found the recruitment of neutrophils is an early inflammatory event in NASH mice, following the formation of neutrophil extracellular traps (NETs). NET is an initiating factor which exacerbates inflammatory responses in macrophages. Inhibition of NETs using DNase I significantly alleviated inflammation in NASH mice. We further carried out a metabolomic study to identify possible metabolic triggers of NETs, and linoleic acid (LA) metabolic pathway was the most altered pathway. We re-analyzed published clinical data and validated that LA metabolism was highly correlated with NASH. Consistently, both LA and γ-linolenic acid (GLA) were active in triggering NETs formation by oxidative burst. Furthermore, we identified silybin, a hepatoprotective agent, as a potent NETosis inhibitor, which effectively blocked NETs formation both in vitro and in vivo. Together, this study not only provide new insights into metabolism-immune causal link in NASH progression, but also demonstrate silybin as an important inhibitor of NETs and its therapeutical potential in treating NETosis-related diseases.PMID:36841284 | DOI:10.1016/j.ejphar.2023.175618

J Appl Microbiol. 2023 Feb 25:lxad036. doi: 10.1093/jambio/lxad036. Online ahead of print.ABSTRACTAIM: The objective of the work was to assess the effect of biostimulation with selected plant growth-promoting bacteria on growth and metabolite profile of Salicornia europaea.METHODS AND RESULTS: S. europaea seeds were inoculated with different combinations of plant growth-promoting bacteria Brevibacterium casei EB3, Pseudomonas oryzihabitans RL18 and Bacillus aryabhattai SP20. Plants germinated from inoculated seeds were grown either in laboratory conditions or in a saline crop field. Fresh and dry weight were determined at the end of the experiment, for biomass quantification. The microbiological quality of fresh shoots for human consumption as salad greens was assessed, and the persistence of the inoculated strains in the plant rhizosphere was confirmed by next-generation sequencing (Illumina) of the 16S rDNA gene. The primary metabolite profile of biostimulated plants was characterized by GC-TOF-MS.In laboratory conditions, inoculation with the two strains B. casei EB3 and P. oryzihabitans RL18 caused the most significant increase in biomass production (fresh and dry weight), and caused a shift in the central metabolic pathways of inoculated plants towards amino acid biosynthesis. In the field experiment, no significant biostimulation effect was detected with any of the tested inoculants. Seed inoculation had no significant effect on the microbiological quality of the edible parts. The persistence of inoculants was confirmed in both experiments.CONCLUSIONS: Manipulation of the plant microbiome can trigger primary metabolic reconfiguration and modulate the plant metabolism while promoting plant growth.PMID:36841232 | DOI:10.1093/jambio/lxad036

Water Res. 2023 Feb 21;233:119762. doi: 10.1016/j.watres.2023.119762. Online ahead of print.ABSTRACTMicroplastics (MPs, diameter <5 mm) are widely distributed on Earth, especially in the oceans. Diatoms account for ∼40% of marine primary productivity and affect the global biogeochemical cycles of macroelements. However, the effects of MPs on marine nitrogen cycling remain poorly understood, particularly comparisons between nitrogen-replete and nitrogen-limited conditions. We found that MPs trigger the Matthew effect on nitrogen assimilation in diatoms, where MPs inhibited nitrogen assimilation under nitrogen-limited conditions while enhancing nitrogen metabolism under nitrogen-replete conditions in Phaeodactylum tricornutum. Nitrate reductase (NR) and nitrite reductase (NIR) are upregulated, but nitrate transporter (NRT) and glutamine synthetase (GS) are downregulated by MPs under nitrogen-limited conditions. In contrast, NR, NIR, and GS are all upregulated by MPs under nitrogen-replete conditions. MPs accelerate nitrogen anabolic processes with an increase in the accumulation of carbohydrates by 80.7 ± 7.9% and enhance the activities of key nitrogen-metabolizing enzymes (8.20-44.90%) under nitrogen-replete conditions. In contrast, the abundance of carbohydrates decreases by 22.0-34.4%, and NRT activity is inhibited by 79.0-86.5% in nitrogen-limited algae exposed to MPs. Metabolomic and transcriptomic analyses were performed to further explore the molecular mechanisms of reprogrammed nitrogen assimilation, including carbon metabolism, nitrogen transport and ammonia assimilation. The aforementioned spatial redistribution (e.g., the Matthew effect between nitrogen-replete and -limited conditions) of nitrogen assimilation highlights the potential risks of MP contamination in the ocean.PMID:36841163 | DOI:10.1016/j.watres.2023.119762

Aquat Toxicol. 2023 Feb 23;257:106432. doi: 10.1016/j.aquatox.2023.106432. Online ahead of print.ABSTRACTPhthalic acid esters (PAEs) are a class of chemicals that are usually incorporated as additives in the manufacturing of plastics. PAEs are not covalently bound to the material matrix and can, consequently, be leached into the environment. PAEs have been reported to act as endocrine disruptors, neurotoxins, metabolic stressors, and immunotoxins to aquatic organisms but there is a lack of information regarding the impact of sub-lethal concentrations to target organisms. The freshwater crustacean Daphnia magna, a commonly used model organism in aquatic toxicity, was exposed to four phthalate pollutants: dimethyl phthalate (DMP), diethyl phthalate (DEP), monomethyl phthalate (MMP), and monoethyl phthalate (MEP). Liquid chromatography-tandem mass spectrometry (LC-MS/MS) was employed in a targeted metabolomic approach to quantify polar metabolites extracted from a single Daphnia body. Individual metabolite percent changes and hierarchical clustering heatmap analysis showed unique metabolic profiles for each phthalate pollutant. Metabolite percent changes were mostly downregulated or presented opposing responses for the low and high concentrations tested. Meanwhile, pathway analyses suggest the disruption of related and unique pathways, mostly connected with amino acid and energy metabolism. The pathways aminoacyl-tRNA biosynthesis, arginine biosynthesis, and glutathione metabolism were disrupted by most selected PAEs. Overall, this study indicates that although phthalate pollutants can elicit distinct metabolic perturbations to each PAE, they still impacted related biochemical pathways. These chemical-class based responses could be associated with a common toxic mechanism of action. The reported findings show how targeted metabolomic approaches can lead to a better understanding of sub-lethal exposure to pollutants, revealing metabolomic endpoints do not hold a close relationship with traditional acute toxicity endpoints.PMID:36841068 | DOI:10.1016/j.aquatox.2023.106432

Int J Hyg Environ Health. 2023 Feb 23;249:114140. doi: 10.1016/j.ijheh.2023.114140. Online ahead of print.ABSTRACTHuman biomonitoring (HBM) studies have highlighted widespread daily exposure to environmental chemicals. Some of these are suspected to contribute to adverse health outcomes such as reproductive, neurological, and metabolic disorders, among other developmental and chronic impairments. One of the objectives of the H2020 European Human Biomonitoring Initiative (HBM4EU) was the development of informative effect biomarkers for application in a more systematic and harmonized way in large-scale European HBM studies. The inclusion of effect biomarkers would complement exposure data with mechanistically-based information on early and late adverse effects. For this purpose, a stepwise strategy was developed to identify and implement a panel of validated effect biomarkers in European HBM studies. This work offers an overview of the complete procedure followed, from comprehensive literature search strategies, selection of criteria for effect biomarkers and their classification and prioritization, based on toxicological data and adverse outcomes, to pilot studies for their analytical, physiological, and epidemiological validation. We present the example of one study that demonstrated the mediating role of the effect biomarker status of brain-derived neurotrophic factor BDNF in the longitudinal association between infant bisphenol A (BPA) exposure and behavioral function in adolescence. A panel of effect biomarkers has been implemented in the HBM4EU Aligned Studies as main outcomes, including traditional oxidative stress, reproductive, and thyroid hormone biomarkers. Novel biomarkers of effect, such as DNA methylation status of BDNF and kisspeptin (KISS) genes were also evaluated as molecular markers of neurological and reproductive health, respectively. A panel of effect biomarkers has also been applied in HBM4EU occupational studies, such as micronucleus analysis in lymphocytes and reticulocytes, whole blood comet assay, and malondialdehyde, 8-oxo-2'-deoxyguanosine and untargeted metabolomic profile in urine, to investigate, for example, biological changes in response to hexavalent chromium Cr(VI) exposure. The use of effect biomarkers in HBM4EU has demonstrated their ability to detect early biological effects of chemical exposure and to identify subgroups that are at higher risk. The roadmap developed in HBM4EU confirms the utility of effect biomarkers, and support one of the main objectives of HBM research, which is to link exposure biomarkers to mechanistically validated effect and susceptibility biomarkers in order to better understand the public health implications of human exposure to environmental chemicals.PMID:36841007 | DOI:10.1016/j.ijheh.2023.114140

J Hazard Mater. 2023 Feb 23;449:131070. doi: 10.1016/j.jhazmat.2023.131070. Online ahead of print.ABSTRACTMicro/nanoplastics (MPs/NPs) have attracted global attention for their potential adverse impacts on marine ecosystems. This study investigated the impacts of MPs/NPs (70 nm, 500 nm, and 2 µm) on population growth and life-history traits of marine rotifer (Brachionus plicatilis), and further explored the differences from the aspects of nutrient accumulation and metabolomic profiles. The results showed that 200 and 2000 µg/L 70 nm NPs significantly suppressed population growth, and negatively affected life span, the first spawning and breeding time, and fecundity in F0-F2 generation rotifers. Whereas 500 nm NPs and 2 µm MPs showed no effect on population growth 200 µg/L and only changed the life-history traits at the highest concentration. Moreover, 70 nm NPs were more easily accumulated in the rotifers and reduced food ingestion and nutrient accumulation, which caused more severe disruption on purine-pyrimidine metabolism, tricarboxylic acid cycle, and protein synthesis pathway compared to 500 nm NPs. Thus, the smaller the size of the plastic particles, the stronger the toxicity to the rotifers. This study provided new insights into the toxicity of MPs/NPs on marine zooplankton and proposed that metabolomics was powerful to explore the toxicity mechanisms of MPs/NPs.PMID:36840989 | DOI:10.1016/j.jhazmat.2023.131070

Microbiol Spectr. 2023 Feb 22:e0479522. doi: 10.1128/spectrum.04795-22. Online ahead of print.ABSTRACTEnrofloxacin is an important antibiotic for the treatment of Salmonella infections in livestock and poultry. However, the effects of different concentrations of enrofloxacin on the bacterial and metabolite compositions of the chicken gut and changes in the abundance of resistance genes in cecum contents remain unclear. To investigate the effects of enrofloxacin on chickens, we orally administered different concentrations of enrofloxacin to 1-day-old chickens and performed 16S rRNA gene sequencing to assess changes in the gut microbiomes of chickens after treatment. The abundance of fluoroquinolone (FQ) resistance genes was measured using quantitative PCR. Metabolomics techniques were used to examine the cecal metabolite composition. We found that different concentrations of enrofloxacin had different effects on cecum microorganisms, with the greatest effect on cecum microbial diversity in the low-concentration enrofloxacin group at day 7. Enrofloxacin use reduced the abundance of beneficial bacteria such as Lactobacillaceae and Oscillospira. Furthermore, cecum microbial diversity was gradually restored as the chickens grew. In addition, enrofloxacin increased the abundance of resistance genes, and there were differences in the changes in abundance among different antibiotic resistance genes. Moreover, enrofloxacin significantly affected linoleic acid metabolism, amino acid metabolism, and signaling pathways. This study helps improve our understanding of how antibiotics affect host physiological activities and provides new insights into the rational use of drugs in poultry farming. The probiotics and metabolites that we identified could be used to modulate the negative effects of antibiotics on the host, which requires further study. IMPORTANCE In this study, we investigated changes in the cecum flora, metabolites, and abundances of fluoroquinolone antibiotic resistance genes in chickens following the use of different concentrations of enrofloxacin. These results were used to determine the effects of enrofloxacin on chick physiology and the important flora and metabolites that might contribute to these effects. In addition, these results could help in assessing the effect of enrofloxacin concentrations on host metabolism. Our findings could help guide the rational use of antibiotics and mitigate the negative effects of antibiotics on the host.PMID:36840593 | DOI:10.1128/spectrum.04795-22

Appl Environ Microbiol. 2023 Feb 22:e0188022. doi: 10.1128/aem.01880-22. Online ahead of print.ABSTRACTThe human gut microbiome contributes crucial bioactive metabolites that support human health and is sensitive to perturbations from the ingestion of alcohol and antibiotics. We interrogated the response and recovery of human gut microbes after acute alcohol or broad-spectrum antibiotic administration in a gut model simulating the luminal and mucosal colonic environment with an inoculated human microbiome. Both alcohol and antibiotic treatments reduced the production of major short-chain fatty acids (SCFAs) (acetate, propionate, and butyrate), which are established modulators of human health. Treatment with a microbial synbiotic restored and enhanced gut function. Butyrate and acetate production increased by up to 29.7% and 18.6%, respectively, relative to untreated, dysbiotic samples. In parallel, treatment led to increases in the relative abundances of beneficial commensal organisms not found in the synbiotic (e.g., Faecalibacterium prausnitzii and the urolithin-producing organism Gordonibacter pamelaeae) as well as species present in the synbiotic (e.g., Bifidobacterium infantis), suggesting synergistic interactions between supplemented and native microorganisms. These results lead us to conclude that functional shifts in the microbiome, evaluated by both metabolite production and specific taxonomic compositional changes, are an appropriate metric to assess microbiome "recovery" following a dysbiosis-inducing disruption. Overall, these findings support the execution of randomized clinical studies to determine whether a microbial synbiotic can help restore microbiome function after a disruption. IMPORTANCE The human gut microbiome is sensitive to disruptions by common stressors such as alcohol consumption and antibiotic treatment. In this study, we used an in vitro system modeling the gut microbiome to investigate whether treatment with a microbial synbiotic can help restore microbiome function after stress. We find that a complex gut community treated with alcohol or antibiotics showed reduced levels of production of short-chain fatty acids, which are critical beneficial molecules produced by a healthy gut microbiota. Treatment of stressed communities with a microbial synbiotic resulted in the recovery of SCFA production as well as an increase in the abundance of beneficial commensal organisms. Our results suggest that treatment with a microbial synbiotic has the potential to restore healthy gut microbiome function after stress and merits further investigation in clinical studies.PMID:36840551 | DOI:10.1128/aem.01880-22

J Clin Endocrinol Metab. 2023 Feb 24:dgad090. doi: 10.1210/clinem/dgad090. Online ahead of print.ABSTRACTCONTEXT: Puberty timing, which is vital for adult well-being, has been suggested to be linked to specific gut taxa recently. However, the impact of comprehensive gut microbiome structure assessed by enterotype on puberty timing remains unknown.OBJECTIVE: Investigate the prospective association of gut microbial enterotype with puberty timing and the potential interaction of age and body composition.METHODS: This study included 1826 children from the Chinese Adolescent Cohort Study, a cohort that collects information on sociodemographics, dietary intake, physical activity, anthropometry, and pubertal development of children aged 6 to 8 since 2013 and follows up annually until their age of 15. Fecal samples were collected annually since 2019 and analyzed for 16S rRNA sequencing and targeted fecal metabolomics. Cox proportional hazard regression models were used to investigate the prospective association of enterotype with puberty timing and the impact of age and body mass index (BMI) sex- and age-independent standard deviation scores (SDS).RESULTS: 592 (32.4%) and 1234 (67.6%) children belonged to the Prevotella-rich enterotype and the Bacteroides-rich enterotype, respectively. Children with the Bacteroides-rich enterotype experienced their menarche/voice break later than those with the Prevotella-enterotype (hazard ratio 0.53 (95%CI, 0.28-0.98), P = 0.02). Moreover, this association was more pronounced among younger children with higher BMI SDS (P for-interaction = 0.006).CONCLUSION: Our findings supported a role for gut microbial communities in pubertal development, in which younger children with higher body mass seems more sensitive.PMID:36840481 | DOI:10.1210/clinem/dgad090

Plants (Basel). 2023 Feb 19;12(4):942. doi: 10.3390/plants12040942.ABSTRACTVigna unguiculata is a vital vegetable crop in Southeast Asia, and Megalurothrips usitatus can cause huge damage to this crop. Enhancing the resistance of V. unguiculata against M. usitatus is a promising way to protect this crop; however, there is limited information regarding the mechanism underlying the resistance of V. unguiculata against M. usitatus. Here, a behavior assay was performed to explore the resistance of V. unguiculata against M. usitatus after insect damage or treatment by jasmonic acid (JA). Furthermore, transcriptome and metabonomics analysis was used to detect the putative mechanism underlying the resistance of V. unguiculata against M. usitatus. The pre-treatment of Vigna unguiculata with JA or infestation with Megalurothrips usitatus alleviated the damage resulting from the pest insect. We further identified differentially expressed genes and different metabolites involved in flavonoid biosynthesis and alpha-linolenic acid metabolism. Genes of chalcone reductase and shikimate O-hydroxycinnamoyltransferase involved in flavonoid biosynthesis, as well as lipoxygenase and acyl-CoA oxidase involved in alpha-linolenic acid metabolism, were upregulated in plants after herbivory or JA supplementation. The upregulation of these genes contributed to the high accumulation of metabolites involved in flavonoid biosynthesis and the alpha-linolenic acid metabolism pathway. These transcriptional and metabolite changes are potentially responsible for plant defense and a putative regulatory model is thus proposed to illustrate the cowpea defense mechanism against insect attack. Our study provides candidate targets for the breeding of varieties with resistance to insect herbivory by molecular technology.PMID:36840292 | DOI:10.3390/plants12040942

Plants (Basel). 2023 Feb 17;12(4):911. doi: 10.3390/plants12040911.ABSTRACTFusarium head blight (FHB) is one of the most dangerous diseases of winter wheat, resulting in reduced grain yield and quality, and production of mycotoxins by the Fusarium fungi. In the present study, changes in the grain metabolomics of winter wheat samples infected with Fusarium spp. and corresponding non-infected samples from two locations in Croatia were investigated by GC-MS. A Mann-Whitney test revealed that 24 metabolites detected were significantly separated between Fusarium-inoculated and non-infected samples during the variety by treatment interactions. The results confirmed that in grains of six FHB-resistant varieties, ten metabolites were identified as possible resistance-related metabolites. These metabolites included heptadecanoic acid, 9-(Z)-hexadecenoic acid, sophorose, and secolaganin in grains of FHB-resistant varieties at the Osijek location, as well as 2-methylaminomethyltartronic acid, maleamic acid, 4-hydroxyphenylacetonitrile, 1,4-lactonearabinonic acid, secolaganin, and alanine in grains of FHB-resistant varieties at the Tovarnik location. Moreover, on the PCA bi-plot, FHB-susceptible wheat varieties were closer to glycyl proline, decanoic acid, and lactic acid dimer that could have affected other metabolites, and thus, suppressed resistance to FHB. Although defense reactions were genetically conditioned and variety specific, resulting metabolomics changes may give insight into defense-related pathways that could be manipulated to engineer plants with improved resistance to the pathogen.PMID:36840259 | DOI:10.3390/plants12040911

Plants (Basel). 2023 Feb 17;12(4):908. doi: 10.3390/plants12040908.ABSTRACTVicia faba L. (faba bean) is one of the most promising pulse crops due to its nutritional value and high nitrogen fixation capacity. The aim of the present study was to compare the genetic diversity and the seed metabolite profiles of five genetic materials of faba bean. Specifically, three newly developed advanced lines (KK18, KK14 and KK10) and two commercial cultivars (POLIKARPI and TANAGRA), were evaluated for this purpose. Genetic diversity among populations was assessed by SCoT molecular markers. Through UPGMA dendrogram, genetic distances between populations were estimated. Untargeted metabolomics analysis of the seeds was performed employing GC/EI/MS. The cultivar POLYKARPI exhibited the highest polymorphism. All varieties showed a higher within-cultivars and advanced lines variability than between. POLYKARPI and KK14 had the lowest genetic distances, while KK18 and TANAGRA presented the highest ones. The advanced line KK18 displayed the best nutritional profile, the highest concentration of desirable metabolites (lactic acid and trehalose), the lowest concentration of anti-nutritional factors (oxalic acid) and the lowest concentration of saturated fatty acids (palmitic and stearic acid). According to the results of the present study, KK18 line is a very promising material for further exploration and utilization in breeding programs.PMID:36840256 | DOI:10.3390/plants12040908