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

Key metabolites and regulatory network mechanisms in co-culture of fungi and microalgae based on metabolomics analysis

Thu, 07/09/2023 - 12:00
Bioresour Technol. 2023 Sep 5:129718. doi: 10.1016/j.biortech.2023.129718. Online ahead of print.NO ABSTRACTPMID:37678649 | DOI:10.1016/j.biortech.2023.129718

Integration approach of transcriptomics and metabolomics reveals the toxicity of Anthracene and its chlorinated derivatives on human hepatic cells

Thu, 07/09/2023 - 12:00
Sci Total Environ. 2023 Sep 5:166886. doi: 10.1016/j.scitotenv.2023.166886. Online ahead of print.ABSTRACTPolycyclic aromatic hydrocarbons (PAHs) and Chlorinated PAHs (Cl-PAHs) are ubiquitous environmental contaminants. The toxicological information of anthracene (Ant) and its chlorinated derivatives is quite limited. In this study, an integrated metabolomic and transcriptomic analysis approach was adopted to assess the toxic effects triggered by Ant and its chlorinated derivatives, 2-chloroanthracene (2-ClAnt) and 9,10-dichloroanthracen (9,10-Cl2Ant), at human-relevant levels on human normal hepatocyte L02 cells. The cell viability test showed no significant effects on the viability of L02 cells exposed to Ant, 2-ClAnt and 9,10-Cl2Ant at doses of 5-500 nM for 24 h. However, based on transcriptomic analysis, Ant, 2-ClAnt and 9,10-Cl2Ant exposure at human-relevant levels obviously perturbed global gene expression in L02 cells and induced the differential expression of several genes related to cancer development. As the number of genes related to cancer development altered by 9,10-Cl2Ant is the largest, 9,10-Cl2Ant posed greater risks of tumor development than Ant and 2-ClAnt did. Metabolomics analysis demonstrated that Ant, 2-ClAnt and 9,10-Cl2Ant caused significant metabolic perturbation in L02 cells. Pathway enrichment analysis indicated that Ant, 2-ClAnt and 9,10-Cl2Ant mainly perturbed the lipid metabolism and nucleotide metabolism pathway. However, 9,10-Cl2Ant caused a wider perturbation to metabolic pathways than Ant and 2-ClAnt did. In addition, dysregulation of nucleotide metabolism perturbed by Ant, 2-ClAnt and 9,10-Cl2Ant may be associated with the genomic instability and further carcinogenesis.PMID:37678537 | DOI:10.1016/j.scitotenv.2023.166886

Paeoniflorin recued hepatotoxicity under zinc oxide nanoparticles exposure via regulation on gut-liver axis and reversal of pyroptosis

Thu, 07/09/2023 - 12:00
Sci Total Environ. 2023 Sep 5:166885. doi: 10.1016/j.scitotenv.2023.166885. Online ahead of print.ABSTRACTThe risks of Zinc oxide nanoparticles (ZnO NPs) applications in biological medicine, food processing industry, agricultural production and the biotoxicity brought by environmental invasion of ZnO NPs both gradually troubled the public due to the lack of research on detoxification strategies. TFEB-regulated autophagy-pyroptosis pathways were found as the crux of the hepatotoxicity induced by ZnO NPs in our latest study. Here, our study served as a connecting link between preceding toxic target and the following protection mechanism of Paeoniflorin (PF). According to a combined analysis of network pharmacology/molecular docking-intestinal microbiota-metabolomics first developed in our study, PF alleviated the hepatotoxicity of ZnO NPs from multiple aspects. The hepatic inflammatory injury and hepatocyte pyroptosis in mice liver exposed to ZnO NPs was significantly inhibited by PF. And the intestinal microbiota disorder and liver metabolic disturbance were rescued. The targets predicted by bioinformatics and the signal trend in subacute toxicological model exhibited the protectiveness of PF related to the SIRT1-mTOR-TFEB pathway. These evidences clarified multiple protective mechanisms of PF which provided a novel detoxification approach against ZnO NPs, and further provided a strategy for the medicinal value development of PF.PMID:37678520 | DOI:10.1016/j.scitotenv.2023.166885

Phytochemical characterisation and aromatic potential for brewing of wild hops (Humulus lupulus L.) from Northern France: Towards a lead for local hop varieties

Thu, 07/09/2023 - 12:00
Food Chem. 2023 Aug 26;433:137302. doi: 10.1016/j.foodchem.2023.137302. Online ahead of print.ABSTRACTIn the current context of developing aromatic beers, our study aims at deciphering the chemical characterisation of cones from 39 wild hop genotypes collected in the North of France and replanted in an experimental hop farm, as well as 10 commercial and 3 heirloom varieties, using HS-SPME/GC-MS for the volatile compounds, UHPLC-UV for phenolic compound quantification, and UHPLC-IMS-HRMS for untargeted metabolomics. These analyses revealed a strong opposition between wild accessions and reference varieties, and an original chemical composition of some genotypes. 27 beers were produced with the same recipe, analysed by SBSE-GC-MS and evaluated by panellists. The unique difference relates to the hops to be assessed in order to determine their sensory profile. The different datasets were compared by OPLS-DA analysis in order to identify chemical markers which may influence the hop aromatic potential. Our results highlight the aromatic potential of some wild accessions, close to the commercial variety Cascade.PMID:37678125 | DOI:10.1016/j.foodchem.2023.137302

Ootheca mantidis mitigates renal fibrosis in mice by the suppression of apoptosis via increasing the gut microbe Akkermansia muciniphila and modulating glutamine metabolism

Thu, 07/09/2023 - 12:00
Biomed Pharmacother. 2023 Sep 5;166:115434. doi: 10.1016/j.biopha.2023.115434. Online ahead of print.ABSTRACTRenal interstitial fibrosis (RIF), a progressive process affecting the kidneys in chronic kidney disease (CKD), currently lacks an effective therapeutic intervention. Traditional Chinese medicine (TCM) has shown promise in reducing RIF and slowing CKD progression. In this study, we demonstrated the dose-dependent attenuation of RIF by Ootheca mantidis (SPX), a commonly prescribed TCM for CKD, in a mouse model of unilateral ureteral obstruction (UUO). RNA-sequencing analysis suggested that SPX treatment prominently downregulated apoptosis and inflammation-associated pathways, thereby inhibiting the fibrogenic signaling in the kidney. We further found that transplantation of fecal microbiota from SPX-treated mice conferred protection against renal injury and fibrosis through suppressing apoptosis in UUO mice, indicating that SPX ameliorated RIF via remodeling the gut microbiota and reducing apoptosis in the kidneys. Further functional exploration of the gut microbiota combined with fecal metabolomics revealed increased levels of some probiotics, including Akkermansia muciniphila (A. muciniphila), and modulations in glutamine-related amino acid metabolism in UUO mice treated with SPX. Subsequent colonization of A. muciniphila and supplementation with glutamine effectively mitigated cell apoptosis and RIF in UUO mice. Collectively, these findings unveil a functionally A. muciniphila- and glutamine-involved gut-renal axis that contributes to the action of SPX, and provide important clue for the therapeutic potential of SPX, A. muciniphila, and glutamine in combatting RIF.PMID:37677965 | DOI:10.1016/j.biopha.2023.115434

Identifications of metabolic differences between Hedysari Radix Praeparata Cum Melle and Astragali Radix Praeparata Cum Melle for spleen-qi deficiency rats: A comparative study

Thu, 07/09/2023 - 12:00
J Pharm Biomed Anal. 2023 Aug 29;236:115689. doi: 10.1016/j.jpba.2023.115689. Online ahead of print.ABSTRACTHedysari Radix Praeparata Cum Melle (HRPCM) and Astragali Radix Praeparata Cum Melle (ARPCM) are capable of improving spleen-qi deficiency (SQD) syndrome especially in the gastrointestinal dysfunction and decreased immunity in traditional Chinese medicine clinically. This study aims to compare and reveal the metabolic differences between HRPCM and ARPCM for SQD rats. Firstly, HRPCM (12.6 g/kg) and ARPCM (12.6 g/kg) were used to intervene SQD rats to further evaluate the effect. The results showed that HRPCM and ARPCM were able to improve the spleen pathology, increase the body weight, the rectal temperature, the spleen index, the thymus index, the levels of GAS and D-xylose in serum, and decrease the levels of IL-2, IL-6 and TNF-α in serum for SQD rats. Then, the studies of metabolic differences in serum and spleen were carried out using UPLC-Q-TOF-MS. The findings emphasized that HRPCM and ARPCM not only regulated metabolic profiling of serum and spleen in SQD rats, but also existed differences. HRPCM and ARPCM regulated metabolic pathways mainly including lipid metabolism, energy metabolism, amino acid metabolism, nucleotide metabolism, sugar metabolism and other types of metabolism for SQD rats. However, the metabolite profiles in SQD rats changed significantly, mainly involving abnormal glycine synthesis occurred in SQD rats. The expression trends of metabolites in HRPCM and ARPCM intervention for SQD rats were partly the same. Interestingly, there are similarities and differences in metabolic profiling between HRPCM and ARPCM for SQD rats. The differences were mainly in the synthesis of L-glutamine in amino acid metabolism.PMID:37677887 | DOI:10.1016/j.jpba.2023.115689

The QseB response regulator imparts tolerance to positively charged antibiotics by controlling metabolism and minor changes to LPS

Thu, 07/09/2023 - 12:00
mSphere. 2023 Sep 7:e0005923. doi: 10.1128/msphere.00059-23. Online ahead of print.ABSTRACTThe modification of lipopolysaccharide (LPS) in Escherichia coli and Salmonella spp. is primarily controlled by the two-component system PmrAB. LPS modification allows bacteria to avoid killing by positively charged antibiotics like polymyxin B (PMB). We previously demonstrated that in uropathogenic E. coli (UPEC), the sensor histidine kinase PmrB also activates a non-cognate transcription factor, QseB, and this activation somehow augments PMB tolerance in UPEC. Here, we demonstrate-for the first time-that in the absence of the canonical LPS transcriptional regulator, PmrA, QseB can direct some modifications on the LPS. In agreement with this observation, transcriptional profiling analyses demonstrate regulatory overlaps between PmrA and QseB in terms of regulating LPS modification genes. However, both PmrA and QseB must be present for UPEC to mount robust tolerance to PMB. Transcriptional and metabolomic analyses also reveal that QseB transcriptionally regulates the metabolism of glutamate and 2-oxoglutarate, which are consumed and produced during the modification of lipid A. We show that deletion of qseB alters glutamate levels in the bacterial cells. The qseB deletion mutant, which is susceptible to positively charged antibiotics, is rescued by exogenous addition of 2-oxoglutarate. These findings uncover a previously unknown mechanism of metabolic control of antibiotic tolerance that may be contributing to antibiotic treatment failure in the clinic. IMPORTANCE Although antibiotic prescriptions are guided by well-established susceptibility testing methods, antibiotic treatments oftentimes fail. The presented work is significant because it uncovers a mechanism by which bacteria transiently avoid killing by antibiotics. This mechanism involves two closely related transcription factors, PmrA and QseB, which are conserved across Enterobacterales. We demonstrate that PmrA and QseB share regulatory targets in lipid A modification pathway and prove that QseB can orchestrate modifications of lipid A in Escherichia coli in the absence of PmrA. Finally, we show that QseB controls glutamate metabolism during the antibiotic response. These results suggest that rewiring of QseB-mediated metabolic genes could lead to stable antibiotic resistance in subpopulations within the host, thereby contributing to antibiotic treatment failure.PMID:37676915 | DOI:10.1128/msphere.00059-23

Mitapivat reprograms red cell metabolome and improves anemia in a mouse model of hereditary spherocytosis

Thu, 07/09/2023 - 12:00
JCI Insight. 2023 Sep 7:e172656. doi: 10.1172/jci.insight.172656. Online ahead of print.ABSTRACTHereditary spherocytosis (HS) is the most common non-immune hereditary chronic hemolytic anemia after hemoglobinopathies. The genetic defects in membrane function causing HS leads to perturbation of red cell metabolome, with altered glycolysis. In mice genetically lacking protein 4.2 (4.2-/-, Epb42), a murine model of HS, we show increased expression of pyruvate kinase (Pk) isoforms in whole and fractioned red cells in conjunction with abnormalities in the glycolytic pathway and in GSH system. Mitapivat, a PKs activator, metabolically re-programs 4.2-/- mouse red cells with amelioration of glycolysis and GSH cycle. This results in improved osmotic fragility, reduced phosphatidyl-serine (PS) positivity and decrease in erythroid vesicles release in vitro. Mitapivat treatment significantly decreases erythrophagocytosis and beneficially impacts iron homeostasis. In mild/moderate HS, the beneficial effect of splenectomy is still controversial. Here, we show that splenectomy improves anemia in 4.2-/- mice and that mitapivat is non-inferior to splenectomy. An additional benefit of mitapivat treatment is lower expression of markers of inflammatory vasculopathy in 4.2-/- mice with or without splenectomy, indicating a multi-systemic action of mitapivat. These findings support the notion that mitapivat treatment should be considered for symptomatic HS.PMID:37676741 | DOI:10.1172/jci.insight.172656

Effects of perinatal stress on the metabolites and lipids in plasma of dairy goats

Thu, 07/09/2023 - 12:00
Stress Biol. 2023 May 12;3(1):11. doi: 10.1007/s44154-023-00088-z.ABSTRACTDairy goats experience metabolic stress during the peripartal period, and their ability to navigate this stage of lactation is related to the occurrence and development of metabolic diseases. Unlike dairy cows, there is a lack of comprehensive analysis of changes in the plasma profiles of peripartal dairy goats, particularly using high-throughput techniques. A subset of 9 clinically-healthy dairy goats were used from a cohort of 96 primiparous Guanzhong dairy goats (BCS, 2.75 ± 0.15). Blood samples were collected at seven time points around parturition (d 21, 14, 7 before parturition, the day of kidding, and d 7, 14, 21 postpartum), were analyzed using untargeted metabolomics and targeted lipidomics. The orthogonal partial least squares discriminant analysis model revealed a total of 31 differential metabolites including p-cresol sulfate, pyruvic acid, cholic acid, and oxoglutaric acid. The pathway enrichment analysis identified phenylalanine metabolism, aminoacyl-tRNA biosynthesis, and citrate cycle as the top three significantly-altered pathways. The Limma package identified a total of 123 differentially expressed lipids. Phosphatidylserine (PS), free fatty acids (FFA), and acylcarnitines (ACs) were significantly increased on the day of kidding, while diacylglycerols (DAG) and triacylglycerols (TAG) decreased. Ceramides (Cer) and lyso-phosphatidylinositols (LPI) were significantly increased during postpartum period, while PS, FFA, and ACs decreased postpartum and gradually returned to antepartum levels. Individual species of FFA and phosphatidylcholines (PC) were segregated based on the differences in the saturation and length of the carbon chain. Overall, this work generated the largest repository of the plasma lipidome and metabolome in dairy goats across the peripartal period, which contributed to our understanding of the multifaceted adaptations of transition dairy goats.PMID:37676623 | DOI:10.1007/s44154-023-00088-z

Herbicide 2,4-dichlorophenoxyacetic acid interferes with MAP kinase signaling in Fusarium graminearum and is inhibitory to fungal growth and pathogenesis

Thu, 07/09/2023 - 12:00
Stress Biol. 2023 Aug 15;3(1):31. doi: 10.1007/s44154-023-00109-x.ABSTRACTPlant hormones are important for regulating growth, development, and plant-pathogen interactions. Some of them are inhibitory to growth of fungal pathogens but the underlying mechanism is not clear. In this study, we found that hyphal growth of Fusarium graminearum was significantly reduced by high concentrations of IAA and its metabolically stable analogue 2,4-dichlorophenoxyacetic acid (2,4-D). Besides inhibitory effects on growth rate, treatments with 2,4-D also caused significant reduction in conidiation, conidium germination, and germ tube growth. Treatments with 2,4-D had no obvious effect on sexual reproduction but significantly reduced TRI gene expression, toxisome formation, and DON production. More importantly, treatments with 2,4-D were inhibitory to infection structure formation and pathogenesis at concentrations higher than 100 µM. The presence of 1000 µM 2,4-D almost completely inhibited plant infection and invasive growth. In F. graminearum, 2,4-D induced ROS accumulation and FgHog1 activation but reduced the phosphorylation level of Gpmk1 MAP kinase. Metabolomics analysis showed that the accumulation of a number of metabolites such as glycerol and arabitol was increased by 2,4-D treatment in the wild type but not in the Fghog1 mutant. Transformants expressing the dominant active FgPBS2S451D T455D allele were less sensitive to 2,4-D and had elevated levels of intracellular glycerol and arabitol induced by 2,4-D in PH-1. Taken together, our results showed that treatments with 2,4-D interfere with two important MAP kinase pathways and are inhibitory to hyphal growth, DON biosynthesis, and plant infection in F. graminearum.PMID:37676555 | DOI:10.1007/s44154-023-00109-x

Collaborative impact of bacterial exometabolites governing root microbiota formation

Thu, 07/09/2023 - 12:00
Stress Biol. 2023 Sep 7;3(1):38. doi: 10.1007/s44154-023-00121-1.ABSTRACTThe majority of the root microbiota formation derives from soil-dwelling microorganisms. The limited extent of thorough investigation leads to a dearth of knowledge concerning the intricate mechanisms of microbe-microbe interaction implicated in the establishment of root microbiota. Therefore, the taxonomic signatures in bacterial inhibition profiles were determined by in vitro testing of 39,204 binary interbacterial interactions. However, findings from genetic and metabolomic studies elucidated that co-functioning of the antimicrobial 2,4-d iacetylphloroglucinol (DAPG) and the iron chelator pyoverdine as exometabolites has significantly contributed to the potent inhibitory activities of the highly antagonistic Pseudomonas brassicacearum R401. Microbiota restoration with a core of Arabidopsis thaliana root commensals showed that these exometabolites possess a root niche-specific function in establishing root competence and inducing anticipated changes in root surroundings. Both biosynthetic operons are abundant in roots in natural habitats, indicating that these exometabolites co-functioning is an adaptive feature that helps Pseudomonad dominate the root microbiota.PMID:37676462 | DOI:10.1007/s44154-023-00121-1

Metabolic signatures of Arabidopsis thaliana abiotic stress responses elucidate patterns in stress priming, acclimation, and recovery

Thu, 07/09/2023 - 12:00
Stress Biol. 2022 Feb 15;2(1):11. doi: 10.1007/s44154-022-00034-5.ABSTRACTTemperature, water, and light are three abiotic stress factors that have major influences on plant growth, development, and reproduction. Plants can be primed by a prior mild stress to enhance their resistance to future stress. We used an untargeted metabolomics approach to examine Arabidopsis thaliana 11-day-old seedling's abiotic stress responses including heat (with and without priming), cold (with and without priming), water-deficit and high-light before and after a 2-day-recovery period. Analysis of the physiological phenotypes showed that seedlings with stress treatment resulted in a reduction in fresh weight, hypocotyl and root length but remained viable. Several stress responsive metabolites were identified, confirmed with reference standards, quantified, and clustered. We identified shared and specific stress signatures for cold, heat, water-deficit, and high-light treatments. Central metabolism including amino acid metabolism, sugar metabolism, glycolysis, TCA cycle, GABA shunt, glutathione metabolism, purine metabolism, and urea cycle were found to undergo changes that are fundamentally different, although some shared commonalities in response to different treatments. Large increases in cysteine abundance and decreases in reduced glutathione were observed following multiple stress treatments highlighting the importance of oxidative stress as a general phenomenon in abiotic stress. Large fold increases in low-turnover amino acids and maltose demonstrate the critical role of protein and starch autolysis in early abiotic stress responses.PMID:37676384 | DOI:10.1007/s44154-022-00034-5

Deletion of all three MAP kinase genes results in severe defects in stress responses and pathogenesis in Fusarium graminearum

Thu, 07/09/2023 - 12:00
Stress Biol. 2022 Jan 17;2(1):6. doi: 10.1007/s44154-021-00025-y.ABSTRACTMitogen-activated protein kinase (MAPK) cascades are activated by external stimuli and convert signals to cellular changes. Individual MAPKs have been characterized in a number of plant pathogenic fungi for their roles in pathogenesis and responses to biotic or abiotic stresses. However, mutants deleted of all the MAPK genes have not been reported in filamentous fungi. To determine the MAPK-less effects in a fungal pathogen, in this study we generated and characterized mutants deleted of all three MAPK genes in the wheat scab fungus Fusarium graminearum. The Gpmk1 mgv1 Fghog1 triple mutants had severe growth defects and was non-pathogenic. It was defective in infection cushion formation and DON production. Conidiation was reduced in the triple mutant, which often produced elongated conidia with more septa than the wild-type conidia. The triple mutant was blocked in sexual reproduction due to the loss of female fertility. Lack of any MAPKs resulted in an increased sensitivity to various abiotic stress including cell wall, osmotic, oxidative stresses, and phytoalexins, which are likely related to the defects of the triple mutant in environmental adaptation and plant infection. The triple mutant also had increased sensitivity to the biocontrol bacterium Bacillus velezensis and fungus Clonostachys rosea. In co-incubation assays with B. velezensis, the Gpmk1 mgv1 Fghog1 mutant had more severe growth limitation than the wild type and was defective in conidium germination and germ tube growth. In confrontation assays, the triple mutant was defective in defending against mycoparasitic activities of C. rosea and the latter could grow over the mutant but not wild-type F. graminearum. RNA-seq and metabolomics analyses showed that the MAPK triple mutant was altered in the expression of many ATP-binding cassette (ABC) and major facilitator superfamily (MFS) transporter genes and the accumulation of metabolites related to arachidonic acid, linoleic acid, and alpha-linolenic acid metabolisms. Overall, as the first study on mutants deleted of all three MAPKs in fungal pathogens, our results showed that although MAPKs are not essential for growth and asexual reproduction, the Gpmk1 mgv1 Fghog1 triple mutant was blocked in plant infection and sexual reproductions. It also had severe defects in responses to various abiotic stresses and bacterial- or fungal-fungal interactions.PMID:37676362 | DOI:10.1007/s44154-021-00025-y

Plant immune inducer ZNC promotes rutin accumulation and enhances resistance to Botrytis cinerea in tomato

Thu, 07/09/2023 - 12:00
Stress Biol. 2023 Aug 22;3(1):36. doi: 10.1007/s44154-023-00106-0.ABSTRACTGray mold is a destructive disease caused by Botrytis cinerea, a pervasive plant pathogen, which poses a threat to both tomato growth and postharvest storage. The utilization of induced resistance presents a potential strategy for combating plant pathogenic attacks. ZNC (zhinengcong), an extract derived from the endophytic fungus Paecilomyces variotii, has been discovered to play a vital role in preventing diverse forms of bacterial infections. Nevertheless, the precise mechanism behind its ability to enhance tomato resistance to fungi remains unclear. In this study, we found that the exogenous spraying of ZNC could significantly improve the resistance of tomato plants to B. cinerea. The results of both the metabolomic analysis and high-performance liquid chromatography (HPLC) demonstrated that tomato plants responded to ZNC treatment by accumulating high levels of rutin. Additional transcriptome analysis uncovered that rutin enhances tomato resistance possible by initiating the generation of reactive oxygen species (ROS) and phosphorylation of mitogen-activated protein kinases (MPKs) related genes expression during the initial phase of invasion by B. cinerea. In addition, we also found that rutin might activate plant immunity by eliciting ethylene (ET) and jasmonic acid (JA)-mediated pathways. Therefore, plant immune inducer ZNC and rutin has bright application prospects and high utilization value to control gray mold.PMID:37676331 | DOI:10.1007/s44154-023-00106-0

Morphogenesis and metabolomics reveal the compatible relationship among <em>Suillus bovinus</em>, <em>Phialocephala fortinii</em>, and their co-host, <em>Pinus massoniana</em>

Thu, 07/09/2023 - 12:00
Microbiol Spectr. 2023 Sep 7:e0145323. doi: 10.1128/spectrum.01453-23. Online ahead of print.ABSTRACTEctomycorrhizal (ECM) fungi and dark septate endophytes (DSEs) can both form a symbiotic relationship with the same host plant. However, the interactions that occur among these two types of fungi and their co-hosts are largely unknown. Here, we investigated interactions that occur among the ECM fungus Suillus bovinus, the DSE Phialocephala fortinii, and their co-host Pinus massoniana. We used both scanning electron microscopy and optical microscopy to characterize the morphogenesis of the two symbionts and employed the ultra-high-performance liquid chromatography-tandem mass spectrometry technique to assess the effects of fungal inoculation on the root metabolome. Under pure culture conditions, no synergistic or antagonistic effects were observed between Phi. fortinii and S. bovinus. Generally, S. bovinus and Phi. fortinii can simultaneously colonize P. massoniana roots without affecting each other's symbiotic processes. S. bovinus can colonize the root locus where Phi. fortinii has already invaded but not vice versa, which may be due to the physical barrier effect of the mantle. Both fungi can significantly promote the growth of P. massoniana, and they have a synergistic effect on host N and K uptake. Metabolite accumulation patterns in roots inoculated with Phi. fortinii and/or S. bovinus were greatly altered, especially with respect to organic acids, flavonoids, lipids, and phenolic acids. S. bovinus inoculation significantly enhanced root flavonoid biosynthesis, whereas Phi. fortinii and dual-inoculation treatments mainly induced phenylpropanoid biosynthesis. These findings reveal compatible relationships among P. massoniana, S. bovinus, and Phi. fortinii, and suggest a theoretical basis for ECM fungi and DSE co-application when cultivating seedlings. IMPORTANCE The prevalence of both ectomycorrhizal fungi and dark septate endophytes in the roots of a wide spectrum of tree species is well recognized. In this study, we investigated the interactions that occur among the ECM fungus S. bovinus, the DSE Phi. fortinii, and their co-host, P. massoniana. The two fungi can simultaneously colonize P. massoniana roots without affecting each other's symbiotic processes. S. bovinus appears to be superior to Phi. fortinii in microniche competition, which may be due to the physical barrier effect of the mantle. The two fungi have different effects on root metabolite accumulation patterns. S. bovinus inoculation significantly enhanced root flavonoid biosynthesis, whereas Phi. fortinii and dual-inoculation treatments mainly induced phenylpropanoid biosynthesis. This is the first study revealing the morphological and metabolic mechanisms that contribute to the compatible relationship among ECM fungi, DSEs, and their co-host.PMID:37676026 | DOI:10.1128/spectrum.01453-23

Analysis of the alleviating effect of modified Huangqi Chifeng decoction on rats with focal segmental glomerulosclerosis based on gut microbiota and fecal metabolomics

Thu, 07/09/2023 - 12:00
J Appl Microbiol. 2023 Sep 7:lxad205. doi: 10.1093/jambio/lxad205. Online ahead of print.ABSTRACTAIMS: To investigate the reno-protective effects of modified Huangqi Chifeng decoction (MHCD) on focal segmental glomerulosclerosis (FSGS) rats, and the underlying mechanisms of systemic regulation of gut microbiota and metabolite profiles.METHODS AND RESULTS: A rat FSGS model was established via unilateral nephrectomy plus doxorubicin injections. Rats were divided into sham, FSGS, and MHCD groups from which urine, blood, and histological tests were conducted. Fecal microbiotas were identified via 16S rRNA gene sequencing. Fecal metabolomics allowed for metabolic pathways analysis. Biochemical indices and pathological examination revealed that MHCD treatment improved the symptoms of FSGS, and corrected dysbiosis of gut microbiota, enriched the abundance of Bifidobacterium, Odoribacter, Christensella, Oscillospira, and reduced that of harmful bacteria such as Collinsella and Coprobacterilus at the genus level. Fecal metabolomic profiles revealed 152 different metabolites between the FSGS and sham groups, which are mainly enriched in signaling pathways like arachidonic acid, serotonergic synapse, and oxytocin. Besides, 93 differential metabolites between MHCD and FSGS groups were identified, which are mainly enriched in signaling pathways like steroid hormone biosynthesis, prostate cancer, and linoleic acid metabolism. Spearman's correlation analysis showed a correlation between differential fecal metabolites and enriched gut microbiota or serum biochemical parameters.CONCLUSIONS: MHCD may exert a reno-protective effect by regulating the gut microbiome and metabolite profiles in FSGS rats.PMID:37675978 | DOI:10.1093/jambio/lxad205

Functionally discrete fine roots differ in microbial assembly, microbial functional potential, and produced metabolites

Thu, 07/09/2023 - 12:00
Plant Cell Environ. 2023 Sep 7. doi: 10.1111/pce.14705. Online ahead of print.ABSTRACTTraditionally, fine roots were grouped using arbitrary size categories, rarely capturing the heterogeneity in physiology, morphology and functionality among different fine root orders. Fine roots with different functional roles are rarely separated in microbiome-focused studies and may result in confounding microbial signals and host-filtering across different root microbiome compartments. Using a 26-year-old common garden, we sampled fine roots from four temperate tree species that varied in root morphology and sorted them into absorptive and transportive fine roots. The rhizoplane and rhizosphere were characterized using 16S rRNA gene and internal transcribed spacer region amplicon sequencing and shotgun metagenomics for the rhizoplane to identify potential microbial functions. Fine roots were subject to metabolomics to spatially characterize resource availability. Both fungi and bacteria differed according to root functional type. We observed additional differences between the bacterial rhizoplane and rhizosphere compartments for absorptive but not transportive fine roots. Rhizoplane bacteria, as well as the root metabolome and potential microbial functions, differed between absorptive and transportive fine roots, but not the rhizosphere bacteria. Functional differences were driven by sugar transport, peptidases and urea transport. Our data highlights the importance of root function when examining root-microbial relationships, emphasizing different host selective pressures imparted on different root microbiome compartments.PMID:37675977 | DOI:10.1111/pce.14705

Tricaprylin, a medium-chain triglyceride, aggravates high-fat diet-induced fat deposition but improves intestinal health

Thu, 07/09/2023 - 12:00
Food Funct. 2023 Sep 7. doi: 10.1039/d3fo01749d. Online ahead of print.ABSTRACTMedium-chain triglycerides (MCTs) are absorbed and metabolized more rapidly than long-chain triglycerides (LCTs) and therefore are considered to have obesity-prevention potential in foods. The effect of adding tricaprylin, an MCT, to food on fat deposition and intestinal health is uncharted. In this study, mice were randomly divided into four groups and fed a normal diet (ND), ND with tricaprylin, a high-fat diet (HFD), or HFD with tricaprylin. Supplementation of 2% tricaprylin in HFD significantly increased the body weight, fat mass, liver weight, adipocyte size in adipose tissue and liver, and upregulated genes related to fat deposition. Metabolomic analysis of serum and adipose tissue revealed that tricaprylin significantly increased the contents of metabolites related to lipid metabolism, triglyceride storage, and fat deposition related signaling pathways. In vitro experiments and molecular docking analysis suggest that octanoic acid, a primary decomposition product of tricaprylin, may promote adipogenic differentiation of preadipocytes by acting as a PPARγ ligand to activate the expression of lipogenesis-related genes. Although supplementation with 2% tricaprylin in HFD cannot reduce fat deposition, it has a beneficial effect on intestinal health. Tricaprylin improved intestinal morphology, digestive enzyme activity, short-chain fatty acid concentration, and intestinal barrier function-related protein expression, while reducing inflammatory factor levels and the abundance of harmful intestinal microorganisms.PMID:37675852 | DOI:10.1039/d3fo01749d

Protocol for the safety and efficacy of fecal microbiota transplantation liquid in children with autism spectrum disorder: a randomized controlled study

Thu, 07/09/2023 - 12:00
Front Microbiol. 2023 Aug 22;14:1236904. doi: 10.3389/fmicb.2023.1236904. eCollection 2023.ABSTRACTBACKGROUND: Autism Spectrum Disorder (ASD) is a neurodevelopmental disorder characterized by deficits in social interaction, repetitive behavior and language impairment, and its worldwide prevalence has been found to be increasing annually in recent years. Till now, ASD is uncurable as its pathogenesis remains unknown. However, studies on both animals and humans have demonstrated that fecal microbiota transplantation (FMT) may ameliorate the symptoms of ASD, as well as gastrointestinal symptoms. Nonetheless, there is still no agreement regarding the optimal dosage or duration of FMT treatment for individuals with ASD.METHODS: This clinical study is a double-blind, randomized, interventional trial conducted at a single center. The aim is to investigate the safety and efficacy of a pediatric formulation of FMT for ASD. A total of 42 children between the ages of 3-9 with ASD will be randomly assigned in a 2:1 ratio to either an FMT treatment group (n = 28) or a placebo group (n = 14), forming cohort 1. Additionally, 30 healthy children of similar age and gender will be recruited as the control group (cohort 2). Cohort 1 will be assessed using a variety of scales, including the Autism Behavior Checklist, Childhood Autism Rating Scale, Social Responsiveness Scale, Gastrointestinal Symptom Rating Scale, Children's Sleep Habits Questionnaire, and Psychoeducational Profile (Third Edition). These assessments will evaluate the effectiveness of FMT in reducing core symptoms and comorbidities (such as gastrointestinal symptoms and sleep disturbances) in children with ASD. The study will use metagenomic and metabolomic sequencing to assess changes in the composition and structure of the intestinal flora and its metabolites in blood, urine, and feces following treatment. Furthermore, the study will evaluate the acceptability of the FMT formulation by participants' legal guardians and investigate differences in the intestinal flora and metabolism in the FMT group before and after treatment compared to 30 healthy children.CLINICAL TRIAL REGISTRATION: https://www.chictr.org.cn/, identifier ChiCTR2200058459.PMID:37675433 | PMC:PMC10477363 | DOI:10.3389/fmicb.2023.1236904

Erratum to associations between the exposure to organophosphate flame retardants during early pregnancy and the risk of spontaneous abortion based on metabolomics combined with tandem mass spectrometry

Thu, 07/09/2023 - 12:00
Ann Transl Med. 2023 Aug 30;11(10):377. doi: 10.21037/atm-2023-17. Epub 2023 Jul 27.ABSTRACT[This corrects the article DOI: 10.21037/atm-21-3109.].PMID:37675327 | PMC:PMC10477615 | DOI:10.21037/atm-2023-17

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