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

Human gut microbiome and metabolite dynamics under simulated microgravity

Tue, 26/09/2023 - 12:00
Gut Microbes. 2023 Dec;15(2):2259033. doi: 10.1080/19490976.2023.2259033. Epub 2023 Sep 25.ABSTRACTThe Artificial Gravity Bed Rest - European Space Agency (AGBRESA) study was the first joint bed rest study by ESA, DLR, and NASA that examined the effect of simulated weightlessness on the human body and assessed the potential benefits of artificial gravity as a countermeasure in an analog of long-duration spaceflight. In this study, we investigated the impact of simulated microgravity on the gut microbiome of 12 participants during a 60-day head-down tilt bed rest at the :envihab facilities. Over 60 days of simulated microgravity resulted in a mild change in the gut microbiome, with distinct microbial patterns and pathway expression in the feces of the countermeasure group compared to the microgravity simulation-only group. Additionally, we found that the countermeasure protocols selectively increased the abundance of beneficial short-chain fatty acids in the gut, such as acetate, butyrate, and propionate. Some physiological signatures also included the modulation of taxa reported to be either beneficial or opportunistic, indicating a mild adaptation in the microbiome network balance. Our results suggest that monitoring the gut microbial catalog along with pathway clustering and metabolite profiling is an informative synergistic strategy to determine health disturbances and the outcome of countermeasure protocols for future space missions.PMID:37749878 | DOI:10.1080/19490976.2023.2259033

Dietary branched-chain amino acids intake, glycemic markers, metabolic profile, and anthropometric features in a community-based sample of overweight and obese adults

Mon, 25/09/2023 - 12:00
BMC Endocr Disord. 2023 Sep 25;23(1):205. doi: 10.1186/s12902-023-01459-3.ABSTRACTBACKGROUND: Existing research provides conflicting evidence regarding the relationship between estimated branched-chain amino acid (BCAA) intake and metabolic, glycemic markers, and anthropometric characteristics. This research seeks to examine the association between estimated dietary BCAA consumption and glycemic, and metabolic markers, as well as anthropometric parameters in adults classified as overweight or obese.METHODS: In this cross-sectional analysis, we gathered data from 465 overweight and obese individuals aged between 18 and 37 years. To evaluate dietary data, we employed the food frequency questionnaire, and the BCAA content in foods was determined via the United States Department of Agriculture website. We utilized ELISA kits to measure fasting blood glucose (FBS) and lipid profile markers, and additionally calculated low-density lipoprotein (LDL) and insulin sensitivity markers. We assessed sociodemographic status, physical activity (PA), and anthropometric attributes through a method recognized as both valid and reliable. For statistical analysis, we conducted analyses of covariance (ANCOVA), making adjustments for variables including sex, PA, age, energy, and body mass index (BMI).RESULTS: Upon adjusting for confounders, those in the highest tertiles of BCAA intake exhibited an increase in weight, BMI, waist circumference (WC), waist-to-hip ratio (WHR), and fat-free mass (FFM). Conversely, they demonstrated reduced fat mass (FM) (%) and FM (kg) compared to their counterparts in the lowest tertiles (P < 0.05). Additionally, there was a noted association between greater estimated BCAA intake and reduced LDL levels. Nonetheless, our findings did not reveal a significant relationship between dietary BCAA and glycemic indices.CONCLUSIONS: From our findings, an increased estimated intake of BCAA seems to correlate with diminished serum LDL concentrations. To gain a more comprehensive understanding of this association, it is imperative that further experimental and longitudinal studies be conducted.PMID:37749544 | PMC:PMC10518913 | DOI:10.1186/s12902-023-01459-3

Bioactive compounds from Vellozia pyrantha A.A.Conc: A metabolomics and multivariate statistical analysis approach

Mon, 25/09/2023 - 12:00
Fitoterapia. 2023 Sep 23:105686. doi: 10.1016/j.fitote.2023.105686. Online ahead of print.ABSTRACTThe chemical composition of V. pyrantha resin (VpR) and fractions (VpFr1-7 and VpWS) were assessed by LC-MS and NMR. Twenty-eight metabolites were identified, including 16 diterpenoids, seven nor-diterpenoids, one fatty acid, one bis-diterpenoid, one steroid, one flavonoid, and one triterpenoid. The pharmacological potential of VpR, VpFr1-7, and isolated compounds was assessed by determining their antioxidant, antimicrobial, and cytotoxic activities. VpFr4 (IC50 = 205.48 ± 3.37 μg.mL-1) had the highest antioxidant activity, whereas VpFr6 (IC50 = 842.79 ± 10.23 μg.mL-1) had the lowest. The resin was only active against Staphylococcus aureus (MIC 62.5 μg.mL-1) and Salmonella choleraesius (MIC and MFC 500 μg.mL-1), but fractions were enriched with antibacterial compounds. V. pyrantha resin and fractions showed great cytotoxic activity against HCT116 (IC50 = 20.08 μg.mL-1), HepG2 (IC50 = 20.50 μg.mL-1), and B16-F10 (12.17 μg.mL-1) cell lines. Multivariate statistical analysis was used as a powerful tool to pinpoint possible metabolites responsible for the observed activities.PMID:37748714 | DOI:10.1016/j.fitote.2023.105686

Exploring the Interplay Between Metabolomics and Genetics in Parkinson's Disease: Insights From Ongoing Research And Future Avenues

Mon, 25/09/2023 - 12:00
Mech Ageing Dev. 2023 Sep 23:111875. doi: 10.1016/j.mad.2023.111875. Online ahead of print.ABSTRACTParkinson's disease (PD) is a widespread neurodegenerative disorder, whose complex aetiology remains under construction. While rare variants have been associated with the monogenic PD form, most PD cases are influenced by multiple genetic and environmental aspects. Nonetheless, the pathophysiological pathways and molecular networks involved in monogenic/idiopathic PD overlap, and genetic variants are decisive in elucidating the convergent underlying mechanisms of PD. In this scenario, metabolomics has furnished a dynamic and systematic picture of the synergy between the genetic background and environmental influences that impact PD, making it a valuable tool for investigating PD-related metabolic dysfunctions. In this review, we performed a brief overview of metabolomics current research in PD, focusing on significant metabolic alterations observed in idiopathic PD from different biofluids and strata and exploring how they relate to genetic factors associated with monogenic PD. Dysregulated amino acid metabolism, lipid metabolism, and oxidative stress are the critical metabolic pathways implicated in both genetic and idiopathic PD. By merging metabolomics and genetics data, it is possible to distinguish metabolic signatures of specific genetic backgrounds and to pinpoint subgroups of PD patients who could derive personalized therapeutic benefits. This approach holds great promise for advancing PD research and developing innovative, cost-effective treatments.PMID:37748695 | DOI:10.1016/j.mad.2023.111875

F6P/G6P-mediated ChREBP activation promotes the insulin resistance-driven hepatic lipid deposition in zebrafish

Mon, 25/09/2023 - 12:00
J Nutr Biochem. 2023 Sep 23:109452. doi: 10.1016/j.jnutbio.2023.109452. Online ahead of print.ABSTRACTInsulin-sensitive lipogenesis dominates the body lipid deposition; however, nonalcoholic fatty liver disease (NAFLD) develops in the insulin-resistant state. The regulation mechanism of insulin resistance-driven NAFLD remains elusive. Using zebrafish model of insulin resistance (ZIR, insrb-/-) and mouse hepatocytes (NCTC 1469), we explored the regulation mechanism of insulin resistance-driven hepatic lipid deposition under the stimulation of carbohydrate diet (CHD). In ZIR model, insulin resistance induced hyperlipidemia and elevated hepatic lipid deposition via elevating the gene/protein expressions of lipogenic enzymes, that was activated by carbohydrate response element binding protein (ChREBP), rather than sterol regulatory element binding proteins 1c (SREBP-1c). The metabolomic analysis in zebrafish and silencing of chrebp in mouse hepatocytes revealed that the increased hepatic frucotose-6-phosphate (F6P) and glucose-6-phosphate (G6P) promoted the ChREBP-mediated lipid deposition. We further identified that F6P alone was sufficient to activate ChREBP-mediated lipid deposition by a SREBP-1c-independent manner. Moreover, we clarified the suppressed hepatic phosphofructokinase/glucose-6-phosphatase functions and the normal glucokinase function preserved by glucose transporter 2 (GLUT2) manipulated the increased F6P/G6P content in ZIR. In conclusion, the present study revealed that insulin resistance promoted hepatic lipid deposition via the F6P/G6P-mediated ChREBP activation. Our findings deciphered the main regulation pathway for the liver lipid deposition in the insulin-resistant state and identified F6P as a new potential regulator for ChREBP.PMID:37748621 | DOI:10.1016/j.jnutbio.2023.109452

An integrated analysis of the fecal metabolome and metagenome reveals the distinct effects of differentially charged nanoplastics on the gut microbiota-associated metabolites in mice

Mon, 25/09/2023 - 12:00
Sci Total Environ. 2023 Sep 23:167287. doi: 10.1016/j.scitotenv.2023.167287. Online ahead of print.ABSTRACTWhether nanoplastics with differential charges cause intestinal impairment via distinct mechanisms remains unclear. We investigated the relationship between fecal metabolites and the gut microbiome, and potential biomarkers thereof, in mice following exposure to differentially charged polystyrene nanoplastics (PS-NPs). Metagenomic analysis revealed that exposure to differentially charged PS-NPs resulted in alterations in the abundances of Bilophila_wadsworthia, Helicobacter apodemus, and Helicobacter typhlonius. A total of 237 fecal metabolites were significantly altered in mice that exhibited intestinal impairment, and these included 10 gut microbiota-related fecal metabolites that accurately discriminated impaired intestinal samples from the control. Additionally, the specific gut microbiome-related fecal metabolite-based model approach for the prediction of intestinal impairment in mice had an area under the curve (AUC) of 1.0 in the PS (without charge) group, an AUC of 0.94 in the PS-NH2 (positive charge) group, and an AUC of 0.86 in the PS-COOH (negative charge) group. Thus, the model showed promising evaluable accuracy for the prediction of intestinal impairment induced by nanoplastics in a charge-specific manner. Our study demonstrates that the fecal metabolome of mice with intestinal impairment following exposure to differentially charged nanoplastics is associated with changes in the gut microbiome. The identified biomarkers have potential application for the detection of intestinal impairment after exposure to negative, positive, or noncharged nanomaterials.PMID:37748599 | DOI:10.1016/j.scitotenv.2023.167287

Identification of phenolic compounds from inflorescences of non-psychoactive Cannabis sativa L. by UHPLC-HRMS and in vitro assessment of the antiproliferative activity against colorectal cancer

Mon, 25/09/2023 - 12:00
J Pharm Biomed Anal. 2023 Sep 14;236:115723. doi: 10.1016/j.jpba.2023.115723. Online ahead of print.ABSTRACTPhenolic compounds from Cannabis sativa L. (Cannabaceae family), in particular cannflavins, are known to possess several biological properties. However, their antiproliferative activity, being of great interest from a medicinal chemistry point of view, has not been deeply investigated so far in the literature. In the light of this, the aim of this study was to obtain an enriched fraction of polyphenols (namely PEF) from inflorescences of a non-psychoactive C. sativa (hemp) variety and to evaluate its antiproliferative activity against cancer cells, capitalizing on a new and selective extraction method for hemp polyphenols, followed by preparative flash column chromatography. Untargeted metabolomics, using a new method based on ultra-high-performance liquid chromatography coupled with high-resolution mass spectrometry (UHPLC-HRMS), was applied here for the first time to fully characterize PEF. Then, the main phenolic compounds were quantified by HPLC-UV. The antiproliferative activity of PEF and of the isolated compounds was assessed in vitro for the first time against Caco-2 and SW480 human colon adenocarcinoma cell lines providing promising IC50 values, in comparison with the reference drug used in therapy for this cancer type. Based on these results, PEF can be considered as a new highly potential therapeutic product to be further investigated against colorectal cancer, thanks to the possible synergistic interaction of its compounds.PMID:37748359 | DOI:10.1016/j.jpba.2023.115723

Exposure to PM<sub>2.5</sub>, seminal plasma metabolome, and semen quality among Chinese adult men: Association and potential mediation analyses

Mon, 25/09/2023 - 12:00
J Hazard Mater. 2023 Sep 21;461:132602. doi: 10.1016/j.jhazmat.2023.132602. Online ahead of print.ABSTRACTExposure to ambient fine particulate matter (PM2.5) has been linked to a decline in semen quality, but the underlying mechanisms for this association remain unclear. We aimed to examine whether specific metabolites act as mediators in the association between PM2.5 exposure and changes in semen quality. We conducted untargeted metabolomics analysis using LC-MS/MS platforms to identified seminal plasma metabolites associated with various semen quality parameters among 200 Chinese adult men. Additionally, we performed mediation analyses to examine the effects of the seminal plasma metabolites on the association between PM2.5 exposure and semen quality. We identified 140 differential metabolites between the normal and abnormal semen groups, involving two metabolic pathways: Alanine, aspartate and glutamate metabolism, and Aminoacyl-tRNA biosynthesis. We additionally identified 7 specific seminal plasma metabolites that were associated with discrepant metabolic networks related to semen quality. The mediation analysis revealed that D-Aspartate might play a mediating role in the adverse effects of ambient PM2.5 exposure on both total and progressive motility during spermatogenesis period (70-90 days before ejaculation), with a proportion of mediation up to 16% and 17%, respectively. Exposure to PM2.5 was associated with alterations in D-Aspartate levels, which might partially mediate the association between PM2.5 and reduced sperm motility.PMID:37748305 | DOI:10.1016/j.jhazmat.2023.132602

CHSY1 promotes CD8<sup>+</sup> T cell exhaustion through activation of succinate metabolism pathway leading to colorectal cancer liver metastasis based on CRISPR/Cas9 screening

Mon, 25/09/2023 - 12:00
J Exp Clin Cancer Res. 2023 Sep 25;42(1):248. doi: 10.1186/s13046-023-02803-0.ABSTRACTBACKGROUND: The most common site of metastasis in colorectal cancer (CRC) is the liver and liver metastases occur in more than 50% of patients during diagnosis or treatment. The occurrence of metastasis depends on a series of events known as the invasive-metastasis cascade. Currently, the underlying genes and pathways regulating metastasis initiation in the liver microenvironment are unknown.METHODS: We performed systematic CRISPR/Cas9 screening using an in vivo mouse model of CRC liver metastasis to identify key regulators of CRC metastasis. We present the full results of this screen,which included a list of genes that promote or repress CRC liver colonization. By silencing these genes individually, we found that chondroitin sulfate synthase 1 (CHSY1) may be involved in CRC metastasis. We verified the function of CHSY1 and its involvement in liver metastasis of CRC through in vivo and in vitro experiments.RESULT: The results of TCGA and CRISPR/Cas9 showed that CHSY1 was overexpressed in CRC primary and liver metastasis tissues and indicated a worse clinical prognosis. In vitro and in vivo experiments confirmed that CHSY1 facilitated the liver metastasis of CRC and CHSY1 induced CD8+ T cell exhaustion and upregulated PD-L1 expression. The metabolomic analysis indicated that CHSY1 promoted CD8+ T cell exhaustion by activating the succinate metabolism pathway leading to liver metastasis of CRC. Artemisinin as a CHSY1 inhibitor reduced liver metastasis and enhanced the effect of anti-PD1 in CRC. PLGA-loaded Artemisinin and ICG probe reduced liver metastasis and increased the efficiency of anti-PD1 treatment in CRC.CONCLUSION: CHSY1 could promote CD8+ T cell exhaustion through activation of the succinate metabolic and PI3K/AKT/HIF1A pathway, leading to CRC liver metastasis. The combination of CHSY1 knockdown and anti-PD1 contributes to synergistic resistance to CRC liver metastasis. Artemisinin significantly inhibits CHSY1 activity and in combination with anti-PD1 could synergistically treat CRC liver metastases. This study provides new targets and specific strategies for the treatment of CRC liver metastases, bringing new hope and benefits to patients.PMID:37749638 | DOI:10.1186/s13046-023-02803-0

Human umbilical cord mesenchymal stem cells ameliorate colon inflammation via modulation of gut microbiota-SCFAs-immune axis

Mon, 25/09/2023 - 12:00
Stem Cell Res Ther. 2023 Sep 25;14(1):271. doi: 10.1186/s13287-023-03471-9.ABSTRACTBACKGROUND: Inflammatory bowel disease (IBD) is a global health problem in which gut microbiota dysbiosis plays a pivotal pathogenic role. Mesenchymal stem cells (MSCs) therapy has emerged as a prospective novel tool for managing IBD, and which can also regulate the composition of gut microbiota. However, the functional significance of MSCs-induced changes in gut microbiome is poorly understood.METHODS: Here, we investigated for the first time the role of gut microbiota in mediating the protective effect of human umbilical cord MSCs (HUMSCs) on DSS-induced colitis. Gut microbiota alteration and short-chain fatty acids (SCFAs) production were analyzed through 16S rRNA sequencing and targeted metabolomics. Spectrum antibiotic cocktail (ABX), fecal microbiota transplantation (FMT) and sterile fecal filtrate (SFF) were employed to evaluate the protective effect of intestinal flora and its metabolites. Cytokine microarray, Enzyme-linked immunosorbent assay (ELISA), and flow cytometry were conducted to assess the effect on CD4+T homeostasis.RESULTS: Here, we investigated for the first time the role of gut microbiota in mediating the protective effect of MSCs on DSS-induced colitis. By performing gut microbiota depletion and fecal microbiota transplantation (FMT) experiments, we revealed that MSCs derived from human umbilical cord ameliorated colon inflammation and reshaped T-cells immune homeostasis via remodeling the composition and diversity of gut flora, especially up-regulated SCFAs-producing bacterial abundance, such as Akkermansia, Faecalibaculum, and Clostridia_UCG_014. Consistently, targeted metabolomics manifested the increased SCFAs production with MSCs administration, and there was also a significant positive correlation between differential bacteria and SCFAs. Meanwhile, combined with sterile fecal filtrate (SFF) gavage experiments, the underlying protective mechanism was further associated with the improved Treg/Th2/Th17 balance in intestinal mucosa mediated via the increased microbiota-derived SCFAs production.CONCLUSION: The present study advances understanding of MSCs in the protective effects on colitis, providing evidence for the new role of the microbiome-metabolite-immune axis in the recovery of colitis by MSCs.PMID:37749611 | DOI:10.1186/s13287-023-03471-9

Recent Progress on Microtubule Degradation Agents

Mon, 25/09/2023 - 12:00
J Med Chem. 2023 Sep 25. doi: 10.1021/acs.jmedchem.3c00517. Online ahead of print.ABSTRACTTargeted protein degradation (TPD) has emerged as the most promising approach for the specific knockdown of disease-associated proteins and is achieved by exploiting the cellular quality control machinery. TPD technologies are highly advantageous in overcoming drug resistance as they degrade the whole target protein. Microtubules play important roles in many cellular processes and are among the oldest and most well-established targets for tumor chemotherapy. However, the development of drug resistance, risk of hypersensitivity reactions, and intolerable toxicities severely restrict the clinical applications of microtubule-targeting agents (MTAs). Microtubule degradation agents (MDgAs) operate via completely different mechanisms compared with traditional MTAs and are capable of overcoming drug resistance. The emergence of MDgAs has expanded the scope of TPD and provided new avenues for the discovery of tubulin-targeted drugs. Herein, we summarized the development of MDgAs, and discussed their degradation mechanisms, mechanisms of action on the binding sites, potential opportunities, and challenges.PMID:37748178 | DOI:10.1021/acs.jmedchem.3c00517

October Literature Synopsis

Mon, 25/09/2023 - 12:00
Stroke. 2023 Oct;54(10):e442-e443. doi: 10.1161/STROKEAHA.123.044481. Epub 2023 Sep 25.NO ABSTRACTPMID:37747967 | DOI:10.1161/STROKEAHA.123.044481

Comprehensive metabolomics and transcriptomics analysis reveals protein and amino acid metabolic characteristics in liver tissue under chronic hypoxia

Mon, 25/09/2023 - 12:00
PLoS One. 2023 Sep 25;18(9):e0291798. doi: 10.1371/journal.pone.0291798. eCollection 2023.ABSTRACTAt high altitudes, oxygen deprivation can cause pathophysiological changes. Liver tissue function is known to impact whole-body energy metabolism; however, how these functions are affected by chronic hypoxia remains unclear. We aimed to elucidate changing characteristics underlying the effect of chronic hypoxia on protein and amino acid metabolism in mouse livers. Mice were maintained in a hypobaric chamber simulating high altitude for 4 weeks. Livers were collected for metabolomic analysis via ultra-high performance liquid chromatography-quadrupole time-of-flight mass spectrometry. For transcriptomics analysis, we conducted RNA sequencing of hepatic tissues followed by Gene Ontology and KEGG pathway enrichment analyses. Chronic hypoxic exposure caused metabolic disorders of amino acids and their derivatives in liver tissue. We identified a number of metabolites with significantly altered profiles (including amino acids, peptides, and analogues), of which serine, phenylalanine, leucine, proline, aspartic acid, L-glutamate, creatine, 5-aminovaleric acid, L-hydroxyarginin, and g-guanidinobutyrate showed great potential as biomarkers of chronic hypoxia. A total of 2124 genes with significantly different expression levels were identified in hypoxic liver tissue, of which 1244 were upregulated and 880 were downregulated. We found pathways for protein digestion and absorption, arginine and proline metabolism, and mineral absorption related to amino acid metabolism were affected by hypoxia. Our findings surrounding the regulation of key metabolites and differentially expressed genes provide new insights into changes in protein and amino acid metabolism in the liver that result from chronic hypoxia.PMID:37747892 | DOI:10.1371/journal.pone.0291798

Metabolomics revealed alterations in serum lipid metabolite levels in childhood atopic dermatitis

Mon, 25/09/2023 - 12:00
Pediatr Allergy Immunol. 2023 Sep;34(9):e14021. doi: 10.1111/pai.14021.NO ABSTRACTPMID:37747754 | DOI:10.1111/pai.14021

The role of the host-microbiome and metabolomics in sarcoidosis

Mon, 25/09/2023 - 12:00
Am J Physiol Cell Physiol. 2023 Sep 25. doi: 10.1152/ajpcell.00316.2023. Online ahead of print.ABSTRACTSarcoidosis is a complex inflammatory fibrotic disease that affects multiple organ systems. It is characterised by the infiltration of lymphocytes and mononuclear phagocytes, which form non-caseating granulomas in affected organs. The lungs and intrathoracic lymph nodes are the most commonly affected organs. The underlying cause of sarcoidosis is unknown, but it is believed to occur in genetically predisposed individuals who are exposed to pathogenic organisms, environmental contaminants, or self and non-self-antigens. Recent research has suggested that the microbiome may play a role in the development of respiratory conditions, including sarcoidosis. Additionally, metabolomic studies have identified potential biomarkers for monitoring sarcoidosis progression. This review will focus on recent microbiome and metabolomic findings in sarcoidosis, with the goal of shedding light on the pathogenesis and possible diagnostic and therapeutic approaches.PMID:37746695 | DOI:10.1152/ajpcell.00316.2023

Transcriptomic and metabolomic insights into the roles of exogenous β-hydroxybutyrate acid for the development of rumen epithelium in young goats

Mon, 25/09/2023 - 12:00
Anim Nutr. 2023 Jul 15;15:10-21. doi: 10.1016/j.aninu.2023.02.012. eCollection 2023 Dec.ABSTRACTBeta-hydroxybutyric acid (BHBA), as one of the main metabolic ketones in the rumen epithelium, plays critical roles in cellular growth and metabolism. The ketogenic capacity is associated with the maturation of rumen in young ruminants, and the exogenous BHBA in diet may promote the rumen development. However, the effects of exogenous BHBA on rumen remain unknown. This is the first study to investigate the mechanisms of BHBA on gene expression and metabolism of rumen epithelium using young goats as a model through multi-omics techniques. Thirty-two young goats were divided into control, low dose, middle dose, and high dose groups by supplementation of BHBA in starter (0, 3, 6, and 9 g/day, respectively). Results demonstrated the dietary of BHBA promoted the growth performance of young goats and increased width and length of the rumen papilla (P < 0.05). Hub genes in host transcriptome that were positively related to rumen characteristics and BHBA concentration were identified. Several upregulated hub genes including NDUFC1, NDUFB4, NDUFB10, NDUFA11 and NDUFA1 were enriched in the gene ontology (GO) pathway of nicotinamide adenine dinucleotide (NADH) dehydrogenase (ubiquinone) activity, while ATP5ME, ATP5PO and ATP5PF were associated with ATP synthesis. RT-PCR revealed the expression of genes (HMGCS2, BDH1, SLC16A3, etc.) associated with lipolysis increased significantly by BHBA supplementation (P < 0.05). Metabolomics indicated that some metabolites such as glucose, palmitic acid, cortisol and capric acid were also increased (P < 0.05). This study revealed that BHBA promoted rumen development through altering NADH balance and accelerating lipid metabolism, which provides a theoretical guidance for the strategies of gastrointestinal health and development of young ruminants.PMID:37746660 | PMC:PMC10514413 | DOI:10.1016/j.aninu.2023.02.012

Expanding the Biological Role of Lipo-Chitooligosaccharides and Chitooligosaccharides in <em>Laccaria bicolor</em> Growth and Development

Mon, 25/09/2023 - 12:00
Front Fungal Biol. 2022 Feb 14;3:808578. doi: 10.3389/ffunb.2022.808578. eCollection 2022.ABSTRACTThe role of lipo-chitooligosaccharides (LCOs) as signaling molecules that mediate the establishment of symbiotic relationships between fungi and plants is being redefined. New evidence suggests that the production of these molecular signals may be more of a common trait in fungi than what was previously thought. LCOs affect different aspects of growth and development in fungi. For the ectomycorrhizal forming fungi, Laccaria bicolor, the production and effects of LCOs have always been studied with a symbiotic plant partner; however, there is still no scientific evidence describing the effects that these molecules have on this organism. Here, we explored the physiological, molecular, and metabolomic changes in L. bicolor when grown in the presence of exogenous sulfated and non-sulfated LCOs, as well as the chitooligomers, chitotetraose (CO4), and chitooctaose (CO8). Physiological data from 21 days post-induction showed reduced fungal growth in response to CO and LCO treatments compared to solvent controls. The underlying molecular changes were interrogated by proteomics, which revealed substantial alterations to biological processes related to growth and development. Moreover, metabolite data showed that LCOs and COs caused a downregulation of organic acids, sugars, and fatty acids. At the same time, exposure to LCOs resulted in the overproduction of lactic acid in L. bicolor. Altogether, these results suggest that these signals might be fungistatic compounds and contribute to current research efforts investigating the emerging impacts of these molecules on fungal growth and development.PMID:37746234 | PMC:PMC10512320 | DOI:10.3389/ffunb.2022.808578

Assessing the intracellular primary metabolic profile of <em>Trichoderma reesei and Aspergillus niger</em> grown on different carbon sources

Mon, 25/09/2023 - 12:00
Front Fungal Biol. 2022 Sep 27;3:998361. doi: 10.3389/ffunb.2022.998361. eCollection 2022.ABSTRACTTrichoderma reesei and Aspergillus niger are efficient biological platforms for the production of various industrial products, including cellulases and organic acids. Nevertheless, despite the extensive research on these fungi, integrated analyses of omics-driven approaches are still missing. In this study, the intracellular metabolic profile of T. reesei RUT-C30 and A. niger N402 strains grown on glucose, lactose, carboxymethylcellulose (CMC), and steam-exploded sugarcane bagasse (SEB) as carbon sources for 48 h was analysed by proton nuclear magnetic resonance. The aim was to verify the changes in the primary metabolism triggered by these substrates and use transcriptomics data from the literature to better understand the dynamics of the observed alterations. Glucose and CMC induced higher fungal growth whereas fungi grown on lactose showed the lowest dry weight. Metabolic profile analysis revealed that mannitol, trehalose, glutamate, glutamine, and alanine were the most abundant metabolites in both fungi regardless of the carbon source. These metabolites are of particular interest for the mobilization of carbon and nitrogen, and stress tolerance inside the cell. Their concomitant presence indicates conserved mechanisms adopted by both fungi to assimilate carbon sources of different levels of recalcitrance. Moreover, the higher levels of galactose intermediates in T. reesei suggest its better adaptation in lactose, whereas glycolate and malate in CMC might indicate activation of the glyoxylate shunt. Glycerol and 4-aminobutyrate accumulated in A. niger grown on CMC and lactose, suggesting their relevant role in these carbon sources. In SEB, a lower quantity and diversity of metabolites were identified compared to the other carbon sources, and the metabolic changes and higher xylanase and pNPGase activities indicated a better utilization of bagasse by A. niger. Transcriptomic analysis supported the observed metabolic changes and pathways identified in this work. Taken together, we have advanced the knowledge about how fungal primary metabolism is affected by different carbon sources, and have drawn attention to metabolites still unexplored. These findings might ultimately be considered for developing more robust and efficient microbial factories.PMID:37746225 | PMC:PMC10512294 | DOI:10.3389/ffunb.2022.998361

AM fungal-bacterial relationships: what can they tell us about ecosystem sustainability and soil functioning?

Mon, 25/09/2023 - 12:00
Front Fungal Biol. 2023 Aug 1;4:1141963. doi: 10.3389/ffunb.2023.1141963. eCollection 2023.ABSTRACTConsidering our growing population and our continuous degradation of soil environments, understanding the fundamental ecology of soil biota and plant microbiomes will be imperative to sustaining soil systems. Arbuscular mycorrhizal (AM) fungi extend their hyphae beyond plant root zones, creating microhabitats with bacterial symbionts for nutrient acquisition through a tripartite symbiotic relationship along with plants. Nonetheless, it is unclear what drives these AM fungal-bacterial relationships and how AM fungal functional traits contribute to these relationships. By delving into the literature, we look at the drivers and complexity behind AM fungal-bacterial relationships, describe the shift needed in AM fungal research towards the inclusion of interdisciplinary tools, and discuss the utilization of bacterial datasets to provide contextual evidence behind these complex relationships, bringing insights and new hypotheses to AM fungal functional traits. From this synthesis, we gather that interdependent microbial relationships are at the foundation of understanding microbiome functionality and deciphering microbial functional traits. We suggest using pattern-based inference tools along with machine learning to elucidate AM fungal-bacterial relationship trends, along with the utilization of synthetic communities, functional gene analyses, and metabolomics to understand how AM fungal and bacterial communities facilitate communication for the survival of host plant communities. These suggestions could result in improving microbial inocula and products, as well as a better understanding of complex relationships in terrestrial ecosystems that contribute to plant-soil feedbacks.PMID:37746131 | PMC:PMC10512368 | DOI:10.3389/ffunb.2023.1141963

Study on the effect of magnesium on leaf metabolites, growth and quality of tea tree

Mon, 25/09/2023 - 12:00
Front Plant Sci. 2023 Sep 8;14:1192151. doi: 10.3389/fpls.2023.1192151. eCollection 2023.ABSTRACTMagnesium (Mg) is one of the essential elements for the growth of tea trees. In this study, we investigated changes in metabolites, photosynthetic fluorescence parameters and quality indexes of tea leaves under different concentrations of magnesium treatment, and the results showed that there were no significant differences in the quantity and total content of metabolites in tea leaves under different Mg concentrations. The results of volcano map analysis showed that the content of 235 metabolites in tea leaves showed an increasing trend and the content of 243 metabolites showed a decreasing trend with the increase of Mg concentration. The results of the combined analysis of the OPLS-DA model and bubble map showed that 45 characteristic metabolites were screened at different concentrations of Mg. Among these, the content of 24 characteristic metabolites showed an increasing trend and 21 characteristic metabolites showed a decreasing trend with the increase of Mg concentrations. The results of KEEG pathway enrichment showed that 24 characteristic metabolites with a upward trend were significantly enriched in saccharides metabolism, nucleic acid metabolism and vitamin metabolism, while the 21 characteristic metabolites with a downward trend were enriched in the synthesis of plant secondary metabolites, phenylpropanoid biosynthesis, biosynthesis of terpenoids, synthesis and metabolism of alkaloids, and synthesis and metabolism of amino acids. It can be inferred that Mg regulation was beneficial to enhance the photosynthetic capacity of tea trees, improve the accumulation and metabolism of carbohydrate substances in tea trees, and thus promoted the growth of tea trees, but was not conducive to the synthesis of secondary metabolites and amino acids related to tea quality. The results of photosynthetic fluorescence parameters and quality indexes of the tea tree confirmed the conclusion predicted by metabolomics. This study provided a reference for regulating of the growth and quality of tea trees with Mg fertilizer in tea plantations.PMID:37746019 | PMC:PMC10514580 | DOI:10.3389/fpls.2023.1192151

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