PubMed

bioRxiv. 2023 Mar 30:2023.03.29.534718. doi: 10.1101/2023.03.29.534718. Preprint.ABSTRACTIschemic stroke results in a loss of tissue homeostasis and integrity, the underlying pathobiology of which stems primarily from the depletion of cellular energy stores and perturbation of available metabolites 1 . Hibernation in thirteen-lined ground squirrels (TLGS), Ictidomys tridecemlineatus , provides a natural model of ischemic tolerance as these mammals undergo prolonged periods of critically low cerebral blood flow without evidence of central nervous system (CNS) damage 2 . Studying the complex interplay of genes and metabolites that unfolds during hibernation may provide novel insights into key regulators of cellular homeostasis during brain ischemia. Herein, we interrogated the molecular profiles of TLGS brains at different time points within the hibernation cycle via RNA sequencing coupled with untargeted metabolomics. We demonstrate that hibernation in TLGS leads to major changes in the expression of genes involved in oxidative phosphorylation and this is correlated with an accumulation of the tricarboxylic acid (TCA) cycle intermediates citrate, cis-aconitate, and α-ketoglutarate-αKG. Integration of the gene expression and metabolomics datasets led to the identification of succinate dehydrogenase (SDH) as the critical enzyme during hibernation, uncovering a break in the TCA cycle at that level. Accordingly, the SDH inhibitor dimethyl malonate (DMM) was able to rescue the effects of hypoxia on human neuronal cells in vitro and in mice subjected to permanent ischemic stroke in vivo . Our findings indicate that studying the regulation of the controlled metabolic depression that occurs in hibernating mammals may lead to novel therapeutic approaches capable of increasing ischemic tolerance in the CNS.PMID:37205496 | PMC:PMC10187245 | DOI:10.1101/2023.03.29.534718

bioRxiv. 2023 May 3:2023.05.02.539172. doi: 10.1101/2023.05.02.539172. Preprint.ABSTRACTExercise modulates vascular plasticity in multiple organ systems; however, the metabolomic transducers underlying exercise and vascular protection in the disturbed flow-prone vasculature remain under-investigated. We simulated exercise-augmented pulsatile shear stress (PSS) to mitigate flow recirculation in the lesser curvature of the aortic arch. When human aortic endothelial cells (HAECs) were subjected to PSS ( τ ave = 50 dyne·cm -2 , ∂τ/∂t = 71 dyne·cm -2 ·s -1 , 1 Hz), untargeted metabolomic analysis revealed that Stearoyl-CoA Desaturase (SCD1) in the endoplasmic reticulum (ER) catalyzed the fatty acid metabolite, oleic acid (OA), to mitigate inflammatory mediators. Following 24 hours of exercise, wild-type C57BL/6J mice developed elevated SCD1-catalyzed lipid metabolites in the plasma, including OA and palmitoleic acid (PA). Exercise over a 2-week period increased endothelial SCD1 in the ER. Exercise further modulated the time-averaged wall shear stress (TAWSS or τ ave) and oscillatory shear index (OSI ave ), upregulated Scd1 and attenuated VCAM1 expression in the disturbed flow-prone aortic arch in Ldlr -/- mice on high-fat diet but not in Ldlr -/- Scd1 EC-/- mice. Scd1 overexpression via recombinant adenovirus also mitigated ER stress. Single cell transcriptomic analysis of the mouse aorta revealed interconnection of Scd1 with mechanosensitive genes, namely Irs2 , Acox1 and Adipor2 that modulate lipid metabolism pathways. Taken together, exercise modulates PSS ( τ ave and OSI ave ) to activate SCD1 as a metabolomic transducer to ameliorate inflammation in the disturbed flow-prone vasculature.PMID:37205360 | PMC:PMC10187200 | DOI:10.1101/2023.05.02.539172

Nanoscale Adv. 2023 Jan 30;5(10):2674-2723. doi: 10.1039/d2na00534d. eCollection 2023 May 16.ABSTRACTNowadays, nanomaterials (NMs) are widely present in daily life due to their significant benefits, as demonstrated by their application in many fields such as biomedicine, engineering, food, cosmetics, sensing, and energy. However, the increasing production of NMs multiplies the chances of their release into the surrounding environment, making human exposure to NMs inevitable. Currently, nanotoxicology is a crucial field, which focuses on studying the toxicity of NMs. The toxicity or effects of nanoparticles (NPs) on the environment and humans can be preliminary assessed in vitro using cell models. However, the conventional cytotoxicity assays, such as the MTT assay, have some drawbacks including the possibility of interference with the studied NPs. Therefore, it is necessary to employ more advanced techniques that provide high throughput analysis and avoid interferences. In this case, metabolomics is one of the most powerful bioanalytical strategies to assess the toxicity of different materials. By measuring the metabolic change upon the introduction of a stimulus, this technique can reveal the molecular information of the toxicity induced by NPs. This provides the opportunity to design novel and efficient nanodrugs and minimizes the risks of NPs used in industry and other fields. Initially, this review summarizes the ways that NPs and cells interact and the NP parameters that play a role in this interaction, and then the assessment of these interactions using conventional assays and the challenges encountered are discussed. Subsequently, in the main part, we introduce the recent studies employing metabolomics for the assessment of these interactions in vitro.PMID:37205285 | PMC:PMC10186990 | DOI:10.1039/d2na00534d

Front Immunol. 2023 Apr 27;14:1134747. doi: 10.3389/fimmu.2023.1134747. eCollection 2023.ABSTRACTINTRODUCTION: New early low-invasive biomarkers are demanded for the management of Oligoarticular Juvenile Idiopathic Arthritis (OJIA), the most common chronic pediatric rheumatic disease in Western countries and a leading cause of disability. A deeper understanding of the molecular basis of OJIA pathophysiology is essential for identifying new biomarkers for earlier disease diagnosis and patient stratification and to guide targeted therapeutic intervention. Proteomic profiling of extracellular vesicles (EVs) released in biological fluids has recently emerged as a minimally invasive approach to elucidate adult arthritis pathogenic mechanisms and identify new biomarkers. However, EV-prot expression and potential as biomarkers in OJIA have not been explored. This study represents the first detailed longitudinal characterization of the EV-proteome in OJIA patients.METHODS: Fourty-five OJIA patients were recruited at disease onset and followed up for 24 months, and protein expression profiling was carried out by liquid chromatography-tandem mass spectrometry in EVs isolated from plasma (PL) and synovial fluid (SF) samples.RESULTS: We first compared the EV-proteome of SF vs paired PL and identified a panel of EV-prots whose expression was significantly deregulated in SF. Interaction network and GO enrichment analyses performed on deregulated EV-prots through STRING database and ShinyGO webserver revealed enrichment in processes related to cartilage/bone metabolism and inflammation, suggesting their role in OJIA pathogenesis and potential value as early molecular indicators of OJIA development. Comparative analysis of the EV-proteome in PL and SF from OJIA patients vs PL from age/gender-matched control children was then carried out. We detected altered expression of a panel of EV-prots able to differentiate new-onset OJIA patients from control children, potentially representing a disease-associated signature measurable at both the systemic and local levels with diagnostic potential. Deregulated EV-prots were significantly associated with biological processes related to innate immunity, antigen processing and presentation, and cytoskeleton organization. Finally, we ran WGCNA on the SF- and PL-derived EV-prot datasets and identified a few EV-prot modules associated with different clinical parameters stratifying OJIA patients in distinct subgroups.DISCUSSION: These data provide novel mechanistic insights into OJIA pathophysiology and an important contribution in the search of new candidate molecular biomarkers for the disease.PMID:37205098 | PMC:PMC10186353 | DOI:10.3389/fimmu.2023.1134747

Front Immunol. 2023 May 2;14:1127785. doi: 10.3389/fimmu.2023.1127785. eCollection 2023.ABSTRACTBACKGROUND: Atractylodes macrocephala Koidz. (AM) is a functional food with strong ant-colitis activity. AM volatile oil (AVO) is the main active ingredient of AM. However, no study has investigated the improvement effect of AVO on ulcerative colitis (UC) and the bioactivity mechanism also remains unknown. Here, we investigated whether AVO has ameliorative activity on acute colitis mice and its mechanism from the perspective of gut microbiota.METHODS: Acute UC was induced in C57BL/6 mice by dextran sulfate sodium and treated with the AVO. Body weight, colon length, colon tissue pathology, and so on were assessed. The gut microbiota composition was profiled using 16s rRNA sequencing and global metabolomic profiling of the feces was performed. The results showed that AVO can alleviate bloody diarrhea, colon damage, and colon inflammation in colitis mice. In addition, AVO decreased potentially harmful bacteria (Turicibacter, Parasutterella, and Erysipelatoclostridium) and enriched potentially beneficial bacteria (Enterorhabdus, Parvibacter, and Akkermansia). Metabolomics disclosed that AVO altered gut microbiota metabolism by regulating 56 gut microbiota metabolites involved in 102 KEGG pathways. Among these KEGG pathways, many metabolism pathways play an important role in maintaining intestine homeostasis, such as amino acid metabolism (especially tryptophan metabolism), bile acids metabolism, and retinol metabolism.CONCLUSION: In conclusion, our study indicated that AVO can be expected as novel prebiotics to treat ulcerative colitis, and modulating the composition and metabolism of gut microbiota may be its pharmacological mechanism.PMID:37205093 | PMC:PMC10187138 | DOI:10.3389/fimmu.2023.1127785

Mol Omics. 2023 May 19. doi: 10.1039/d2mo00256f. Online ahead of print.ABSTRACTSarcopenia has garnered considerable interest in recent years as ageing-associated diseases constitute a significant worldwide public health burden. Nutritional supplements have received much attention as potential tools for managing sarcopenia. However, the specific nutrients responsible are still under-investigated. In the current study, we first determined the levels of short chain fatty acids (SCFAs) and intestinal flora in the feces of elderly sarcopenia subjects and elderly healthy individuals by ultra-performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS). Then cell viability detection, flow cytometry and transcriptome analysis were adopted to experimentally evaluate the effect and the underlying mechanism of SCFA on C2C12 cells proliferation in vitro. The results suggested that patients with sarcopenia exhibited decreased levels of butyrate. And butyrate may stimulate C2C12 myocyte proliferation via promoting G1/S cell cycle transition. Transcriptomic analyses pointed to upregulation of the Mitogen-activated protein kinase (MAPK) signaling pathway in butyrate-treated cells. In addition, the above proliferative phenotypes could be suppressed by the combination of ERK/MAPK inhibitor. A combined transcriptomic and metabolomic approach was applied in our study to investigate the potential effect of microbiota-derived butyrate yield on muscular proliferation which may indicate a protective effect of nutritional supplements.PMID:37204279 | DOI:10.1039/d2mo00256f

Lett Appl Microbiol. 2023 May 18:ovad061. doi: 10.1093/lambio/ovad061. Online ahead of print.ABSTRACTB. adolescentis is a probiotic. This research aimed to investigate the mechanism of antibiotics led to decrease in the number of B. adolescentis. The metabolomics approach was employed to explore the effects of amoxicillin on metabolism of B.adolescentis, while MTT assay and scanning electron microscopy were applied to analyze changes in viability and morphology of bacteria. Molecular docking was used to illuminate the mechanism by which amoxicillin acts on a complex molecular network. The results showed that increasing the concentration of amoxicillin led to a gradual decrease in the number of live bacteria. Untargeted metabolomics analysis identified eleven metabolites that change as a result of amoxicillin exposure. Many of these metabolites are involved in arginine and proline metabolism, glutathione metabolism, arginine biosynthesis, cysteine and methionine metabolism, and tyrosine and phenylalanine metabolism. Molecular docking revealed that amoxicillin had a good binding effect on the proteins AGR1, ODC1, GPX1, GSH, MAT2A and CBS. Overall, this research provides potential targets for screening probiotic regulatory factors and lays a theoretical foundation for the elucidation of its mechanisms.PMID:37204035 | DOI:10.1093/lambio/ovad061

Eur J Neurosci. 2023 May 18. doi: 10.1111/ejn.16047. Online ahead of print.ABSTRACTEarly life stress (ELS) is associated with metabolic-, cognitive-, and psychiatric diseases and has a very high prevalence, highlighting the urgent need for a better understanding of the versatile physiological changes and identification of predictive biomarkers. In addition to programming the hypothalamic-pituitary-axis (HPA), ELS may also affect the gut microbiota and metabolome, opening up a promising research direction for identifying early biomarkers of ELS-induced (mal)adaptation. Other factors affecting these parameters include maternal metabolic status and diet, with maternal obesity shown to predispose offspring to later metabolic disease. The aim of the present study was to investigate the long-term effects of ELS and maternal obesity on the metabolic- and stress phenotype of rodent offspring. To this end, offspring of both sexes were subjected to an adverse early-life experience, and their metabolic and stress phenotypes were examined. In addition, we assessed whether a prenatal maternal and an adult high-fat diet (HFD) stressor further shape observed ELS-induced phenotypes. We show that ELS has long-term effects on male body weight (BW) across the lifespan, whereas females more successfully counteract ELS-induced weight loss, possibly by adapting their microbiota, thereby stabilizing a balanced metabolome. Furthermore, the metabolic effects of a maternal HFD on BW are exclusively triggered by a dietary challenge in adult offspring and are more pronounced in males than in females. Overall, our study suggests that the female microbiota protects against an ELS challenge, rendering them more resilient to additional maternal- and adult nutritional stressors than males.PMID:37203224 | DOI:10.1111/ejn.16047

Animal Model Exp Med. 2023 May 18. doi: 10.1002/ame2.12327. Online ahead of print.ABSTRACTBACKGROUND: Nonalcoholic fatty liver disease (NAFLD) is one of the most common chronic liver diseases globally. Hepatic stellate cells (HSCs) are the major effector cells of liver fibrosis. HSCs contain abundant lipid droplets (LDs) in their cytoplasm during quiescence. Perilipin 5 (PLIN 5) is a LD surface-associated protein that plays a crucial role in lipid homeostasis. However, little is known about the role of PLIN 5 in HSC activation.METHODS: PLIN 5 was overexpressed in HSCs of Sprague-Dawley rats by lentivirus transfection. At the same time, PLIN 5 gene knockout mice were constructed and fed with a high-fat diet (HFD) for 20 weeks to study the role of PLIN 5 in NAFLD. The corresponding reagent kits were used to measure TG, GSH, Caspase 3 activity, ATP level, and mitochondrial DNA copy number. Metabolomic analysis of mice liver tissue metabolism was performed based on UPLC-MS/MS. AMPK, mitochondrial function, cell proliferation, and apoptosis-related genes and proteins were detected by western blotting and qPCR.RESULTS: Overexpression of PLIN 5 in activated HSCs led to a decrease in ATP levels in mitochondria, inhibition of cell proliferation, and a significant increase in cell apoptosis through AMPK activation. In addition, compared with the HFD-fed C57BL/6J mice, PLIN 5 knockout mice fed with HFD showed reduced liver fat deposition, decreased LD abundance and size, and reduced liver fibrosis.CONCLUSION: These findings highlight the unique regulatory role of PLIN 5 in HSCs and the role of PLIN 5 in the fibrosis process of NAFLD.PMID:37202925 | DOI:10.1002/ame2.12327

Diabetes Obes Metab. 2023 May 18. doi: 10.1111/dom.15118. Online ahead of print.ABSTRACTBACKGROUND: Composition of high-density lipoproteins (HDL) is emerging as an important determinant in the development of microvascular complications in type 2 diabetes mellitus (T2DM). Dutch South Asian (DSA) individuals with T2DM display an increased risk of microvascular complications compared with Dutch white Caucasian (DwC) individuals with T2DM. In this study, we aimed to investigate whether changes in HDL composition associate with increased microvascular risk in this ethnic group and lead to new lipoprotein biomarkers.MATERIALS AND METHODS: Using 1 H nuclear magnetic resonance spectroscopy and Bruker IVDr Lipoprotein Subclass Analysis (B.I.LISA) software, plasma lipoprotein changes were determined in 51 healthy individuals (30 DwC, 21 DSA) and 92 individuals with T2DM (45 DwC, 47 DSA) in a cross-sectional, case-control study. Differential HDL subfractions were investigated using multinomial logistic regression analyses, adjusting for possible confounders including BMI and diabetes duration.RESULTS: We identified HDL compositional differences between healthy and diabetic individuals in both ethnic groups. Specifically, levels of apolipoprotein A2 and HDL-4 subfractions were lower in DSA compared with DwC with T2DM. Apolipoprotein A2 and HDL-4 subfractions also negatively correlated with waist circumference, waist-to-hip ratio, haemoglobin A1c, glucose levels and disease duration in DSA with T2DM, and associated with increased incidence of microvascular complications.CONCLUSION: While HDL composition differed between controls and T2DM in both ethnic groups, the lower levels of lipid content in the smallest HDL subclass (HDL-4) in DSA with T2DM appeared to be more clinically relevant, with higher odds of having diabetes-related pan-microvascular complications such as retinopathy and neuropathy. These typical differences in HDL could be used as ethnicity-specific T2DM biomarkers.PMID:37202875 | DOI:10.1111/dom.15118

Life Sci Alliance. 2023 May 18;6(8):e202301900. doi: 10.26508/lsa.202301900. Print 2023 Aug.ABSTRACTMicrobial symbionts frequently localize within specific body structures or cell types of their multicellular hosts. This spatiotemporal niche is critical to host health, nutrient exchange, and fitness. Measuring host-microbe metabolite exchange has conventionally relied on tissue homogenates, eliminating dimensionality and dampening analytical sensitivity. We have developed a mass spectrometry imaging workflow for a soft- and hard-bodied cnidarian animal capable of revealing the host and symbiont metabolome in situ, without the need for a priori isotopic labelling or skeleton decalcification. The mass spectrometry imaging method provides critical functional insights that cannot be gleaned from bulk tissue analyses or other presently available spatial methods. We show that cnidarian hosts may regulate microalgal symbiont acquisition and rejection through specific ceramides distributed throughout the tissue lining the gastrovascular cavity. The distribution pattern of betaine lipids showed that once resident, symbionts primarily reside in light-exposed tentacles to generate photosynthate. Spatial patterns of these metabolites also revealed that symbiont identity can drive host metabolism.PMID:37202120 | DOI:10.26508/lsa.202301900

Clin Nutr ESPEN. 2023 Jun;55:1-9. doi: 10.1016/j.clnesp.2023.02.017. Epub 2023 Feb 21.ABSTRACTThe most well-grounded dietary pattern involved in nutrigenenic studies investigating non -communicable diseases is the Mediterranean diet. This dietary regime is inspired by the nutritional habits of people residing near Mediterranean Sea. The fundamental elements of this diet can vary based on ethnicity, culture, economic status and religious properties and are associated with lowercases of all-cause mortality rates. Mediterranean diet is most studied dietary pattern at the level of evidence-based medicine. Nutritional based studies are dependent on combined data analysis from the multi-omics technique which delineates systematic alternations taking place fallowing exposure to a stimulant. Comprehending the physiological mechanisms of plant metabolites in cellular processes, in combination of Nutri-genetic and nutrigenomics association with multi omics approaches is a necessary step for developing personalized nutrition regime for a stronger management, treatment and prevention of chronic diseases. The advanced lifestyle is marked by abundant access to food and an accelerating trend of physical inactivity, the latter of which contribute to a variety of health problems. In light of the importance of excellent food habits in the prevention of chronic diseases, health policy should promote the adoption of healthy diets that sustain traditional dietary patterns in the face of commercial pressures.PMID:37202031 | DOI:10.1016/j.clnesp.2023.02.017

J Ethnopharmacol. 2023 May 16:116571. doi: 10.1016/j.jep.2023.116571. Online ahead of print.ABSTRACTETHNOPHARMACOLOGICAL RELEVANCE: Platycladi Semen was recorded in Shen Nong's Herbal Classic and was considered a herbal medicine with low toxicity after long-term medication. Multiple traditional Chinese medicine prescriptions containing Platycladi Semen have been used to treat insomnia. Modern clinical practitioners commonly use Platycladi Semen to treat anxiety disorders, but there are few studies on its composition and anxiolytic mechanisms.AIM OF THE STUDY: To describe the main components of Platycladi Semen and investigate its anxiolytic effects and mechanisms.MATERIALS AND METHODS: The main components of Platycladi Semen were characterized by liquid chromatography-mass spectrometry (LC-MS) and gas chromatography-mass spectrometry (GC-MS). The anxiolytic effects of oral Platycladi Semen were evaluated in chronic unpredictable mild stress (CUMS) induced mice. To explore the anxiolytic mechanisms of Platycladi Semen, serum non-targeted metabolomics combined with network pharmacology and molecular docking was performed.RESULTS: Fourteen compounds were identified in the 50% methanol extract and 11 fatty acid derivatives were identified in the methyl-esterified fatty oil of Platycladi Semen. In CUMS mice, both the aqueous extract and fatty oil of Platycladi Semen had anxiolytic effects, which were shown by the increase in the time and frequency of mice entering the open arm in the elevated plus maze (EPM) experiment. Through serum non-targeted metabolomics, 34 differential metabolites were identified, and lipid metabolic pathways such as sphingolipid metabolism, steroidogenesis, alpha-linoleic acid, and linoleic acid metabolism were enriched. Through network pharmacology, 109 targets of the main components in Platycladi Semen were identified, and the 'neuroactive ligand-receptor interaction' and 'lipid metabolism' were enriched. The molecular docking results showed that the main components in Platycladi Semen could bind to the key targets such as peroxisome proliferator-activated receptor delta (PPARD), peroxisome proliferator-activated receptor alpha (PPARA), fatty acid binding protein 5 (FABP5), fatty acid binding protein 3 (FABP3), peroxisome proliferator-activated receptor gamma (PPARG), arachidonate 5-lipoxygenase (ALOX5) and fatty acid amide hydrolase (FAAH).CONCLUSION: This study indicated that Platycladi Semen has anxiolytic effects, and the anxiolytic mechanisms may be the regulation of lipid metabolism and the neuroactive ligand-receptor interaction.PMID:37201666 | DOI:10.1016/j.jep.2023.116571

Free Radic Biol Med. 2023 May 16:S0891-5849(23)00422-7. doi: 10.1016/j.freeradbiomed.2023.05.009. Online ahead of print.ABSTRACTAristolochic acids are widely distributed in the plants of Aristolochiaceae family and Asarum species. Aristolochic acid I (AAI) is the most frequent compound of aristolochic acids, which can accumulate in the soil, and then contaminates crops and water and enters the human body. Research has shown that AAI affects the reproductive system. However, the mechanism of AAI's effects on the ovaries at the tissue level still needs to be clarified. In this research, we found AAI exposure reduced the body and ovarian growth in mice, decreased the ovarian coefficient, prevented follicular development, and increased atretic follicles. Further experiments showed that AAI upregulated nuclear factor-κB and tumor necrosis factor-α expression, activated the NOD-like receptor protein 3 inflammasome, and led to ovarian inflammation and fibrosis. AAI also affected mitochondrial complex function and the balance between mitochondrial fusion and division. Metabolomic results also showed ovarian inflammation and mitochondrial dysfunction due to AAI exposure. These disruptions reduced the oocyte developmental potential by forming abnormal microtubule organizing centers and expressing abnormal BubR1 to destroy spindle assembly. In summary, AAI exposure triggers ovarian inflammation and fibrosis, affecting the oocyte developmental potential.PMID:37201634 | DOI:10.1016/j.freeradbiomed.2023.05.009

Metab Eng. 2023 May 16:S1096-7176(23)00075-7. doi: 10.1016/j.ymben.2023.05.001. Online ahead of print.ABSTRACTMicrobial production of valuable bioproducts is a promising route towards green and sustainable manufacturing. The oleaginous yeast, Rhodosporidium toruloides, has emerged as an attractive host for the production of biofuels and bioproducts from lignocellulosic hydrolysates. 3-hydroxypropionic acid (3HP) is an attractive platform molecule that can be used to produce a wide range of commodity chemicals. This study focuses on establishing and optimizing the production of 3HP in R. toruloides. As R. toruloides naturally has a high metabolic flux towards malonyl-CoA, we exploited this pathway to produce 3HP. Upon finding the yeast capable of catabolizing 3HP, we then implemented functional genomics and metabolomic analysis to identify the catabolic pathways. Deletion of a putative malonate semialdehyde dehydrogenase gene encoding an oxidative 3HP pathway was found to significantly reduce 3HP degradation. We further explored monocarboxylate transporters to promote 3HP transport and identified a novel 3HP transporter in Aspergillus pseudoterreus by RNA-seq and proteomics. Combining these engineering efforts with media optimization in a fed-batch fermentation resulted in 45.4 g/L 3HP production. This represents one of the highest 3HP titers reported in yeast from lignocellulosic feedstocks. This work establishes R. toruloides as a host for 3HP production from lignocellulosic hydrolysate at high titers, and paves the way for further strain and process optimization towards enabling industrial production of 3HP in the future.PMID:37201565 | DOI:10.1016/j.ymben.2023.05.001

Water Res. 2023 May 13;239:120061. doi: 10.1016/j.watres.2023.120061. Online ahead of print.ABSTRACTThe widespread use of antibiotics has created an antibiotic resistance genes (ARGs)-enriched environment, which causes high risks on human and animal health. Although antibiotics can be partially adsorbed and degraded in wastewater treatment processes, striving for a complete understanding of the microbial adaptive mechanism to antibiotic stress remains urgent. Combined with metagenomics and metabolomics, this study revealed that anammox consortia could adapt to lincomycin by spontaneously changing the preference for metabolite utilization and establishing interactions with eukaryotes, such as Ascomycota and Basidiomycota. Specifically, quorum sensing (QS) based microbial regulation and the ARGs transfer mediated by clustered regularly interspaced short palindromic repeats (CRISPR) system and global regulatory genes were the principal adaptive strategies. Western blotting results validated that Cas9 and TrfA were mainly responsible for the alteration of ARGs transfer pathway. These findings highlight the potential adaptative mechanism of microbes to antibiotic stress and fill gaps in horizontal gene transfer pathways in the anammox process, further facilitating the ARGs control through molecular and synthetic biology techniques.PMID:37201375 | DOI:10.1016/j.watres.2023.120061

Chin Med. 2023 May 18;18(1):57. doi: 10.1186/s13020-023-00752-6.ABSTRACTBACKGROUND: In recent decades, the prevalence of metabolic diseases, particularly diabetes, hyperlipidemia, obesity, and non-alcoholic fatty liver disease (NAFLD), has increased dramatically, causing great public health and economic burdens worldwide. Traditional Chinese medicine (TCM) serves as an effective therapeutic choice. Xiao-Ke-Yin (XKY) is a medicine and food homology TCM formula consisting of nine "medicine and food homology" herbs and is used to ameliorate metabolic diseases, such as insulin resistance, diabetes, hyperlipidemia and NAFLD. However, despite its therapeutic potential in metabolic disorders, the underlying mechanisms of this TCM remain unclear. This study aimed to evaluate the therapeutic effectiveness of XKY on glucolipid metabolism dysfunction and explore the potential mechanisms in db/db mice.METHODS: To verify the effects of XKY, db/db mice were treated with different concentrations of XKY (5.2, 2.6 and 1.3 g/kg/d) and metformin (0.2 g/kg/d, a hypoglycemic positive control) for 6 weeks, respectively. During this study, we detected the body weight (BW) and fasting blood glucose (FBG), oral glucose tolerance test (OGTT), insulin tolerance test (ITT), daily food intake and water intake. At the end of the animal experiment, blood samples, feces, liver and intestinal tissue of mice in all groups were collected. The potential mechanisms were investigated by using hepatic RNA sequencing, 16 S rRNA sequencing of the gut microbiota and metabolomics analysis.RESULTS: XKY efficiently mitigated hyperglycemia, IR, hyperlipidemia, inflammation and hepatic pathological injury in a dose dependent manner. Mechanistically, hepatic transcriptomic analysis showed that XKY treatment significantly reversed the upregulated cholesterol biosynthesis which was further confirmed by RT-qPCR. Additionally, XKY administration maintained intestinal epithelial homeostasis, modulated gut microbiota dysbiosis, and regulated its metabolites. In particular, XKY decreased secondary bile acid producing bacteria (Clostridia and Lachnospircaeae) and lowered fecal secondary bile acid (lithocholic acid (LCA) and deoxycholic acid (DCA)) levels to promote hepatic bile acid synthesis by inhibiting the LCA/DCA-FXR-FGF15 signalling pathway. Furthermore, XKY regulated amino acid metabolism including arginine biosynthesis, alanine, aspartate and glutamate metabolism, phenylalanine, tyrosine and tryptophan biosynthesis, and tryptophan metabolism likely by increasing Bacilli, Lactobacillaceae and Lactobacillus, and decreasing Clostridia, Lachnospircaeae, Tannerellaceae and Parabacteroides abundances.CONCLUSION: Taken together, our findings demonstrate that XKY is a promising "medicine food homology" formula for ameliorating glucolipid metabolism and reveal that the therapeutic effects of XKY may due to its downregulation of hepatic cholesterol biosynthesis and modulation of the dysbiosis of the gut microbiota and metabolites.PMID:37202792 | DOI:10.1186/s13020-023-00752-6

BMC Microbiol. 2023 May 18;23(1):139. doi: 10.1186/s12866-023-02863-4.ABSTRACTBACKGROUND: Acute viral myocarditis (AVMC) is an inflammatory disease of the myocardium. Evidence indicates that dysbiosis of gut microbiome and related metabolites intimately associated with cardiovascular diseases through the gut-heart axis.METHODS: We built mouse models of AVMC, then applied 16 S rDNA gene sequencing and UPLC-MS/MS metabolomics to explore variations of gut microbiome and disturbances of cardiac metabolic profiles.RESULTS: Compared with Control group, analysis of gut microbiota showed lower diversity in AVMC, decreased relative abundance of genera mainly belonging to the phyla Bacteroidetes, and increased of phyla Proteobacteria. Metabolomics analysis showed disturbances of cardiac metabolomics, including 62 increased and 84 decreased metabolites, and mainly assigned to lipid, amino acid, carbohydrate and nucleotide metabolism. The steroid hormone biosynthesis, cortisol synthesis and secretion pathway were particularly enriched in AVMC. Among them, such as estrone 3-sulfate, desoxycortone positively correlated with disturbed gut microbiome.CONCLUSION: In summary, both the structure of the gut microbiome community and the cardiac metabolome were significantly changed in AVMC. Our findings suggest that gut microbiome may participate in the development of AVMC, the mechanism may be related to its role in dysregulated metabolites such as steroid hormone biosynthesis.PMID:37202726 | DOI:10.1186/s12866-023-02863-4

BMC Plant Biol. 2023 May 19;23(1):264. doi: 10.1186/s12870-023-04264-1.ABSTRACTBACKGROUND: Flavor contributes to the sensory quality of fruits, including taste and aroma aspects. The quality of foods is related to their flavor-associated compounds. Pear fruits have a fruity sense of smell, and esters are the main contributor of the aroma. Korla pear are well known due to its unique aroma, but the mechanism and genes related to volatile synthesis have not been fully investigated.RESULTS: Flavor-associated compounds, including 18 primary metabolites and 144 volatiles, were characterized in maturity fruits of ten pear cultivars from five species, respectively. Based on the varied metabolites profiles, the cultivars could be grouped into species, respectively, by using orthogonal partial least squares discrimination analysis (OPLS-DA). Simultaneously, 14 volatiles were selected as biomarkers to discriminate Korla pear (Pyrus sinkiangensis) from others. Correlation network analysis further revealed the biosynthetic pathways of the compounds in pear cultivars. Furthermore, the volatile profile in Korla pear throughout fruit development was investigated. Aldehydes were the most abundant volatiles, while numerous esters consistently accumulated especially at the maturity stages. Combined with transcriptomic and metabolic analysis, Ps5LOXL, PsADHL, and PsAATL were screened out as the key genes in ester synthesis.CONCLUSION: Pear species can be distinguished by their metabolic profiles. The most diversified volatiles as well as esters was found in Korla pear, in which the enhancement of lipoxygenase pathway may lead to the high level of volatile esters at maturity stages. The study will benefit the fully usage of pear germplasm resources to serve fruit flavor breeding goals.PMID:37202722 | DOI:10.1186/s12870-023-04264-1

MedComm (2020). 2023 May 16;4(3):e268. doi: 10.1002/mco2.268. eCollection 2023 Jun.ABSTRACTThe ketogenic diet (KD) is a low-carbohydrate, high-fat regime that is protective against neurodegenerative diseases. However, the impact of KD on Parkinson's disease (PD) and its mechanisms remains unclear. 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced mouse model of PD was fed with KD for 8 weeks. Motor function and dopaminergic neurons were evaluated. Inflammation in the brain, plasma, and colon tissue were also measured. Fecal samples were assessed by 16S rDNA gene sequencing and untargeted metabolomics. We found that KD protected motor dysfunction, dopaminergic neuron loss, and inflammation in an MPTP mouse model of PD. 16S rDNA sequencing revealed that MPTP administration significantly increased Citrobacter, Desulfovibrio, and Ruminococcus, and decreased Dubosiella, whereas KD treatment reversed the dysbiosis. Meanwhile, KD regulated the MPTP-induced histamine, N-acetylputrescine, d-aspartic acid, and other metabolites. Fecal microbiota transplantation using feces from the KD-treated mice attenuated the motor function impairment and dopaminergic neuron loss in antibiotic-pretreated PD mice. Our current study demonstrates that KD played a neuroprotective role in the MPTP mouse model of PD through the diet-gut microbiota-brain axis, which may involve inflammation in the brain and colon. However, future research is warranted to explore the explicit anti-inflammatory mechanisms of the gut-brain axis in PD models fed with KD.PMID:37200942 | PMC:PMC10186339 | DOI:10.1002/mco2.268