PubMed

Front Pharmacol. 2022 Oct 20;13:990307. doi: 10.3389/fphar.2022.990307. eCollection 2022.ABSTRACTBackground: Bushen Tiansui Formula (BSTSF) is a traditional formulation of Chinese medicine that has been used to treat Alzheimer's disease (AD) for decades; however, the underlying mechanisms by which this formula achieves such therapeutic effects have yet to be elucidated. Prupose: To investigate the neuroprotective mechanisms of BSTSF against AD by analyzing metabolite profiles in the hippocampus and cortex of AD rats. Methods: The rat models of AD were established by the injection of Aβ25-35. The Morris water maze (MWM) test was performed to evaluate the effect of BSTSF treatment on cognitive dysfunction. Hematoxylin and eosin (HE) staining was used to assess the effect of BSTSF on typical AD pathologies. Underlying mechanisms were investigated using LC-MS/MS-based untargeted metabolomics analysis of the cerebral cortex and hippocampus. Results: BSTSF significantly improved memory deficits and the typical histopathological changes of AD rats. Untargeted metabolomics analysis showed that 145 and 184 endogenous metabolites in the cerebral cortex and hippocampus, respectively, were significantly different in the BSTSF group when compared with the AD group. The differential metabolites in the cerebral cortex were primarily involved in cysteine and methionine metabolism, while those in the hippocampus were mainly involved in d-Glutamine and d-glutamate metabolism. Conclusion: In the present study, we confirmed the neuroprotective effects of BSTSF treatment against AD using a rat model. Our findings indicate that the BSTSF-mediated protective effects were associated with amelioration of metabolic disorders in the hippocampus and cerebral cortex.PMID:36339577 | PMC:PMC9630565 | DOI:10.3389/fphar.2022.990307

Front Pharmacol. 2022 Oct 21;13:1011608. doi: 10.3389/fphar.2022.1011608. eCollection 2022.ABSTRACTThe 9-(R)-HODE is an active compound isolated from cortex lycii that showed significant hypoglycemic effects in our previous in vitro study. In this study, 9-(R)-HODE's in vivo hypoglycemic activity and effect on alleviating diabetic complications, together with its molecular mechanism, was investigated using a metabolomics approach. The monitored regulation on dynamic fasting blood glucose, postprandial glucose, body weight, biochemical parameters and histopathological analysis confirmed the hypoglycemic activity and attenuation effect, i.e., renal lesions, of 9-(R)-HODE. Subsequent metabolomic studies indicated that 9-(R)-HODE induced metabolomic alterations primarily by affecting the levels of amino acids, organic acids, alcohols and amines related to amino acid metabolism, glucose metabolism and energy metabolism. By mediating the related metabolism or single molecules related to insulin resistance, e.g., kynurenine, myo-inositol and the branched chain amino acids leucine, isoleucine and valine, 9-(R)-HODE achieved its therapeutic effect. Moreover, the mediation of kynurenine displayed a systematic effect on the liver, kidney, muscle, plasma and faeces. Lipidomic studies revealed that 9-(R)-HODE could reverse the lipid metabolism disorder in diabetic mice mainly by regulating phosphatidylinositols, lysophosphatidylcholines, lysophosphatidylcholines, phosphatidylserine, phosphatidylglycerols, lysophosphatidylglycerols and triglycerides in both tissues and plasma. Treatment with 9-(R)-HODE significantly modified the structure and composition of the gut microbiota. The SCFA-producing bacteria, including Rikenellaceae and Lactobacillaceae at the family level and Ruminiclostridium 6, Ruminococcaceae UCG 014, Mucispirillum, Lactobacillus, Alistipes and Roseburia at the genus level, were increased by 9-(R)-HODE treatment. These results were consistent with the increased SCFA levels in both the colon content and plasma of diabetic mice treated with 9-(R)-HODE. The tissue DESI‒MSI analysis strongly confirmed the validity of the metabolomics approach in illustrating the hypoglycemic and diabetic complications-alleviation effect of 9-(R)-HODE. The significant upregulation of liver glycogen in diabetic mice by 9-(R)-HODE treatment validated the interpretation of the metabolic pathways related to glycogen synthesis in the integrated pathway network. Altogether, 9-(R)-HODE has the potential to be further developed as a promising candidate for the treatment of diabetes.PMID:36339561 | PMC:PMC9633664 | DOI:10.3389/fphar.2022.1011608

Front Pharmacol. 2022 Oct 20;13:961087. doi: 10.3389/fphar.2022.961087. eCollection 2022.ABSTRACTTraditional Chinese medicine (TCM) has been used to treat infectious diseases and could offer potential drug leads. This study evaluates the in vitro antimicrobial activities from commercially sourced Dryopteris crassirhizoma Nakai (Polypodiaceae) whose authenticity was confirmed by DNA barcoding based on the ribulose bisphosphate carboxylase (rbcL) gene. Powdered rhizomes were sequentially extracted using n-hexane, dichloromethane, ethyl acetate, and methanol at ambient temperature. The dried extracts at different concentrations were tested for antimicrobial activities against Escherichia coli, Pseudomonas aeruginosa, Staphylococcus aureus, methicillin-resistant Staphylococcus aureus (MRSA), and Mycobacterium smegmatis. D. crassirhizoma extracts exhibited significant antimicrobial activities only against MRSA (minimum inhibitory concentration: 3.125 μg/ml n-hexane extract). Activity-led fractionations of D. crassirhizoma and characterization by ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) targeted a fraction (A3), with two anti-MRSA phloroglucinol derivatives, flavaspidic acid AB and norflavaspidic acid AB-being greatly enriched in the latter. The impact of A3 on MRSA cells was examined using untargeted metabolomic analysis and compared to that of other established antibiotics (all treatments normalized to MIC50 at 6 h). This suggested that norflavaspidic acid AB had distinctive effects, one of which involved targeting bioenergetic transformation, metabolism, and particularly acetyl-CoA, on MRSA cells. No cytotoxicity was observed for the norflavaspidic acid AB-enriched fraction against murine HepG2 cells. This study requires further experimental validation but can have indicated a naturally available compound that could help counter the threat of clinically relevant strains with antibiotic resistance.PMID:36339560 | PMC:PMC9630833 | DOI:10.3389/fphar.2022.961087

Front Pharmacol. 2022 Oct 21;13:947512. doi: 10.3389/fphar.2022.947512. eCollection 2022.ABSTRACTEthnopharmacological relevance: The past couple of decades have witnessed the global resurgence of medicinal plants in the field of herbal-based health care. Increased consumption of medicinal plants and their derivative products is the major cause of the adulteration issues in herbal industries. As a result, the quality of herbal products is affected by spurious and unauthorized raw materials. Recent development in molecular plant identification using DNA barcodes has become a robust methodology to identify and authenticate the adulterants in herbal samples. Hence, rapid and accurate identification of medicinal plants is the key to success for the herbal industry. Aim of the study: This paper provides a comprehensive review of the application of DNA barcoding and advanced technologies that have emerged over the past 10 years related to medicinal plant identification and authentication and the future prospects of this technology. Materials and methods: Information on DNA barcodes was compiled from scientific databases (Google Scholar, Web of Science, SciFinder and PubMed). Additional information was obtained from books, Ph.D. thesis and MSc. Dissertations. Results: Working out an appropriate DNA barcode for plants is challenging; the single locus-based DNA barcodes (rbcL, ITS, ITS2, matK, rpoB, rpoC, trnH-psbA) to multi-locus DNA barcodes have become the successful species-level identification among herbal plants. Additionally, multi-loci have become efficient in the authentication of herbal products. Emerging advances in DNA barcoding and related technologies such as next-generation sequencing, high-resolution melting curve analysis, meta barcodes and mini barcodes have paved the way for successful herbal plant/samples identification. Conclusion: DNA barcoding needs to be employed together with other techniques to check and rationally and effectively quality control the herbal drugs. It is suggested that DNA barcoding techniques combined with metabolomics, transcriptomics, and proteomics could authenticate the herbal products. The invention of simple, cost-effective and improved DNA barcoding techniques to identify herbal drugs and their associated products of medicinal value in a fool-proof manner will be the future thrust of Pharmacopoeial monograph development for herbal drugs.PMID:36339543 | PMC:PMC9635000 | DOI:10.3389/fphar.2022.947512

Front Pharmacol. 2022 Oct 21;13:1058587. doi: 10.3389/fphar.2022.1058587. eCollection 2022.ABSTRACTPatrinia villosa (Thunb.) Juss (P.V) is widely used in the treatment of chronic diseases, such as appendicitis, enteritis and gynecological inflammation. Modern research indicated that the herb has pharmacological effect on liver injury caused by inflammation, but the metabolomics mechanism is not clear. For the purpose of discovering the therapeutic effect and metabolomic mechanism of P.V on liver injury, 40 Sprague-Dawley (SD) rats were divided into normal group, model group, and P.V groups (0.98, 1.97, and 2.96 g/kg). The model group and P.V groups were injected intraperitoneally with 40% CCl4 (v/v, olive oil) to establish liver injury model. After administration of P.V for seven consecutive days. Therapeutic effect of P.V on liver injury rats were analyzed. P.V could decrease serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels of liver injury rats as a dose-dependent manner. Compared with the model group, the pathological analysis of liver tissue of P.V groups exhibit significant decrease tendency of hepatic tissue structure destruction, cytoplasmic vacuolation, cellular swelling, and inflammatory cell infiltration as a dose-dependent manner. 82 endogenous metabolites in rat serum and liver were analyzed by Ultra-high performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS). 14 metabolites in serum and 26 metabolites in liver were significantly different between the P.V group (2.96 g/kg) and the model group. Metabolic pathway analysis revealed that the main pathway including alanine, aspartate and glutamate metabolism, and TCA cycle were significantly altered. It is suggested that P.V can alleviate CCl4 induced liver injury, and its effect on metabolites may be an important mechanism of action.PMID:36339542 | PMC:PMC9633866 | DOI:10.3389/fphar.2022.1058587

Front Pharmacol. 2022 Oct 20;13:1025540. doi: 10.3389/fphar.2022.1025540. eCollection 2022.ABSTRACTObjective: Network pharmacology provides new methods and references for the research of traditional Chinese medicine, but some problems remain, such as single evaluation components and index methods, imperfect relevant databases, unscientific prediction results, and lack of verification of results. Herein, we used a modified network pharmacology research method to explore the potential network analysis mechanism of Huoxue Qingre decoction in the treatment of coronary heart disease and utilized clinical trials for assessment. Methods: Based on literature research, the targets corresponding to the drug were obtained with the assistance of the TCMSP database and Swiss Target Prediction, and the target proteins were corrected using the UniProt database. The targets related to coronary heart disease was obtained through the GeneCards database. A protein-protein interaction network diagram was constructed, and a "component-intersection target" network diagram was drawn based on Cytoscape 3.6.2 software. The mapped targets were imported into the DAVID bioinformatics platform, which underwent Gene Ontology (GO) function and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis, and the network pharmacology prediction results were evaluated through clinical trials. Results: We obtained 151 compounds related to Huoxue Qingre decoction, 286 genes after evaluation and deduplication, and 426 genes related to coronary heart disease. Finally, 81 common target genes were obtained with 32 pathways according to the KEGG pathway enrichment analysis. The validation results of the clinical trials showed that a total of 98 differential metabolites were found in the treatment of coronary heart disease with Huoxue Qingre decoction, involving a total of 16 metabolic pathways. Compared with the network pharmacology prediction results, it was found that only the pathways in cancer (hsa05200) were the common pathways in the top 32 signaling pathways predicted by network pharmacology. The expanded network pharmacology prediction results revealed that the sphingolipid signaling pathway (hsa04071) and prostate cancer pathway (hsa05215) matched the predicted metabolic pathways, with differential metabolites of N-oleoyl-D-sphingomyelin and 1-methyl-6-phenyl-1h-imidazole[4,5-b]pyridine-2-amine. Conclusion: Through the network analysis and metabolomic evaluation, there may be three signaling pathways that involve the Huoxue Qingre decoction in the treatment of coronary heart disease: pathways in cancer (hsa05200), sphingolipid signaling pathway (hsa04071), and prostate cancer pathway (hsa05215).PMID:36339536 | PMC:PMC9631828 | DOI:10.3389/fphar.2022.1025540

Front Public Health. 2022 Oct 19;10:1035301. doi: 10.3389/fpubh.2022.1035301. eCollection 2022.ABSTRACTDrinking water contaminated by Cd2+ is one of the main pathways for Cd to enter the body. The skin barrier is destroyed when the skin is contaminated by environmental Cd2+, however, the detailed mechanism by which Cd2+ induces skin metabolic disorder, and senescence and affects hair regeneration is not completely understood. In this study, 18 C57BL/6 mice were randomly divided into a Control group, a Low-dose group, and a High-dose group with 6 mice in each group, and intragastrically administered with different concentrations of cadmium chloride once a day, respectively. After 1 month of intervention, the skin tissues on the back of mice were collected for non-targeted metabolomics analysis, and the related proteins were detected by immunofluorescence assay. Non-targeted metabolomics analysis result showed that compared with the Control group, there were 29 different metabolites, mainly including lysophospholipids, fatty acids, and bile acids, in the Low-dose group, and 39 differential metabolites in the High-dose group, in addition to the above compounds, there were more amino acid compounds, and most of the metabolites had a reduced response after administration. Immunofluorescence assay result showed that the higher the concentration of cadmium chloride led to the more obvious the proliferation inhibition and apoptosis promotion effects of skin cells, and the more significant damage to hair follicle stem cells. Thus, our findings demonstrate that cadmium chloride pollution can accelerate skin metabolism disorder, and aging and impair hair regeneration.PMID:36339210 | PMC:PMC9627278 | DOI:10.3389/fpubh.2022.1035301

Front Chem. 2022 Oct 19;10:1005843. doi: 10.3389/fchem.2022.1005843. eCollection 2022.ABSTRACTAnimal bile is an important component of natural medicine and is widely used in clinical treatment. However, it is easy to cause mixed applications during processing, resulting in uneven quality, which seriously affects and harms the interests and health of consumers. Bile acids are the major bioactive constituents of bile and contain a variety of isomeric constituents. Although the components are structurally similar, they exhibit different pharmacological activities. Identifying the characteristics of each animal bile is particularly important for processing and reuse. It is necessary to establish an accurate analysis method to distinguish different types of animal bile. We evaluated the biological activity of key feature markers from various animal bile samples. In this study, a strategy combining metabolomics and machine learning was used to compare the bile of three different animals, and four key markers were screened. Quantitative analysis of the key markers showed that the levels of Glycochenodeoxycholic acid (GCDCA) and Taurodeoxycholic acid (TDCA) were highest in pig bile; Glycocholic acid (GCA) and Cholic acid (CA) were the most abundant in bovine and sheep bile, respectively. In addition, four key feature markers significantly inhibited the production of NO in LPS-stimulated RAW264.7 macrophage cells. These findings will contribute to the targeted development of bile in various animals and provide a basis for its rational application.PMID:36339047 | PMC:PMC9627196 | DOI:10.3389/fchem.2022.1005843

World J Gastroenterol. 2022 Oct 21;28(39):5764-5783. doi: 10.3748/wjg.v28.i39.5764.ABSTRACTBACKGROUND: Primary biliary cholangitis (PBC) and autoimmune hepatitis (AIH) are two unexplained immune diseases. The golden standard for diagnosis of these diseases requires a liver biopsy. Liver biopsy is not widely accepted by patients because of its invasive nature, and atypical liver histology can confuse diagnosis. In view of the lack of effective diagnostic markers for PBC and AIH, combined with the increasingly mature metabolomics technologies, including full-contour metabolomics and target.AIM: To determine non-invasive, reliable, and sensitive biochemical markers for the differential diagnosis of PBC and AIH.METHODS: Serum samples from 54 patients with PBC, 26 patients with AIH and 30 healthy controls were analyzed by Ultra-high performance liquid chromatography-tandem mass spectrometry serum metabolomics. The metabolites and metabolic pathways were identified, and the metabolic changes, metabolic pathways and inter-group differences between PBC and AIH were analyzed. Fifteen kinds of target metabolites of bile acids (BAs) were quantitatively analyzed by SRM, and the differential metabolites related to the diagnosis of PBC were screened by receiver operating characteristic curve analysis.RESULTS: We found the changes in the levels of amino acids, BAs, organic acids, phospholipids, choline, sugar, and sugar alcohols in patients with PBC and AIH. Furthermore, the SRM assay of BAs revealed the increased levels of chenodeoxycholic acid, lithocholic acid (LCA), taurolithocholic acid (TLCA), and LCA + TLCA in the PBC group compared with those in the AIH group. The levels of BAs may be used as biomarkers to differentiate PBC from AIH diseases. The levels of glycochenodeoxycholic acid, glycochenodeoxycholic sulfate, and taurodeoxycholic acid were gradually elevated with the increase of Child-Pugh class, which was correlated with the severity of disease.CONCLUSION: The results demonstrated that the levels of BAs could serve as potential biomarkers for the early diagnosis and assessment of the severity of PBC and AIH.PMID:36338890 | PMC:PMC9627419 | DOI:10.3748/wjg.v28.i39.5764

Hortic Res. 2022 Aug 25;9:uhac189. doi: 10.1093/hr/uhac189. eCollection 2022.ABSTRACTThe Actinidia (kiwifruit) is an emerging fruit plant that is severely affected by salt stress in northern China. Plants have evolved several signaling network mechanisms to cope with the detrimental effects of salt stress. To date, no reported work is available on metabolic and molecular mechanisms involved in kiwifruit salt tolerance. Therefore, the present study aims to decipher intricate adaptive responses of two contrasting salt tolerance kiwifruit species Actinidia valvata [ZMH (an important genotype), hereafter referred to as R] and Actinidia deliciosa ['Hayward' (an important green-fleshed cultivar), hereafter referred to as H] under 0.4% (w/w) salt stress for time courses of 0, 12, 24, and 72 hours (hereafter refered to as h) by combined transcriptome and metabolome analysis. Data revealed that kiwifruit displayed specific enrichment of differentially expressed genes (DEGs) under salt stress. Interestingly, roots of R plants showed a differential expression pattern for up-regulated genes. The KEGG pathway analysis revealed the enrichment of DEGs related to plant hormone signal transduction, glycine metabolism, serine and threonine metabolism, glutathione metabolism, and pyruvate metabolism in the roots of R under salt stress. The WGCNA resulted in the identification of five candidate genes related to glycine betaine (GB), pyruvate, total soluble sugars (TSS), and glutathione biosynthesis in kiwifruit. An integrated study of transcriptome and metabolome identified several genes encoding metabolites involved in pyruvate metabolism. Furthermore, several genes encoding transcription factors were mainly induced in R under salt stress. Functional validation results for overexpression of a candidate gene betaine aldehyde dehydrogenase (AvBADH, R_transcript_80484) from R showed significantly improved salt tolerance in Arabidopsis thaliana (hereafter referred to as At) and Actinidia chinensis ['Hongyang' (an important red-fleshed cultivar), hereafter referred to as Ac] transgenic plants than in WT plants. All in all, salt stress tolerance in kiwifruit roots is an intricate regulatory mechanism that consists of several genes encoding specific metabolites.PMID:36338850 | PMC:PMC9630968 | DOI:10.1093/hr/uhac189

Front Physiol. 2022 Oct 20;13:1037758. doi: 10.3389/fphys.2022.1037758. eCollection 2022.ABSTRACTMacropinocytosis is a unique type of endocytosis accompanied by membrane ruffle formation. Closure of membrane ruffles leads to the uptake of large volumes of fluid phase and, subsequently, the formation of large vacuoles termed macropinosomes. Immune cells, such as dendritic cells, T cells, and macrophages, endocytose the surrounding amino acids and pathogens via macropinocytosis either constitutively or in a stimulus-dependent fashion. This process is critical for cell migration, mammalian target of rapamycin complex 1 (mTORC1) activation, and antigen presentation. Large vacuoles are fragmented into tubules and smaller vesicles during the progression and maturation of macropinosomes in immune cells. This process is called "macropinosome resolution" and requires osmotically driven shrinkage of macropinosomes, which is controlled by ion channels present in them. The crenation of membranes on shrunken macropinosomes is recognized by curvature-sensing proteins and results in intracellular membrane trafficking. In this mini review, we highlight the recent progress in research on macropinosome resolution in macrophages, with a focus on ion channels (TPC1/2 for Na+ and TMEM206 for Cl-) that is required for macropinosome resolution. We also discuss the potential contribution of membrane lipids to this process.PMID:36338503 | PMC:PMC9630563 | DOI:10.3389/fphys.2022.1037758

Front Physiol. 2022 Oct 21;13:989105. doi: 10.3389/fphys.2022.989105. eCollection 2022.ABSTRACTCoronary heart disease (CHD) is caused by coronary atherosclerosis and has a high morbidity and mortality rate worldwide. There are challenges in both early screening and treatment of CHD. The appearance and development of CHD is a complex metabolic disorder process. Therefore, to search for new biomarkers of CHD, we analyzed the peripheral blood metabolome in patients with CHD. In the study, a plasma metabolite, 4'-Phosphopantetheine (4-PPanSH), which was discovered by HPLC-MS/MS, as peripheral blood 4-PPanSH decreases, the degree of coronary blockage gradually aggravates. In addition, the 4-PPanSH supplement limited atherosclerotic plaque formation and endothelial injury in mice. Further, in vascular endothelial cells, 4-PPanSH effectively inhibited ROS generation and ox-LDL accumulation. In summary, 4-PPanSH was associated with the degree of coronary stenosis, and the 4-PPanSH supplement reduced atherosclerotic plaque generation, which could be associated with 4-PPanSH acting as a potent antioxidant that inhibits ROS generation and alleviates vascular endothelial injury.PMID:36338497 | PMC:PMC9634529 | DOI:10.3389/fphys.2022.989105

Breathe (Sheff). 2022 Mar;18(1):210161. doi: 10.1183/20734735.0161-2021. Epub 2022 Apr 5.ABSTRACTThe respiratory microbiome and its impact in health and disease is now well characterised. With the development of next-generation sequencing and the use of other techniques such as metabolomics, the functional impact of microorganisms in different host environments can be elucidated. It is now clear that the respiratory microbiome plays an important role in respiratory disease. In some diseases, such as bronchiectasis, examination of the microbiome can even be used to identify patients at higher risk of poor outcomes. Furthermore, the microbiome can aid in phenotyping. Finally, development of multi-omic analysis has revealed interactions between the host and microbiome in some conditions. This review, although not exhaustive, aims to outline how the microbiome is investigated, the healthy respiratory microbiome and its role in respiratory disease.EDUCATIONAL AIMS: To define the respiratory microbiome and describe its analysis.To outline the respiratory microbiome in health and disease.To describe future directions for microbiome research.PMID:36338247 | PMC:PMC9584600 | DOI:10.1183/20734735.0161-2021

Front Microbiol. 2022 Oct 20;13:984654. doi: 10.3389/fmicb.2022.984654. eCollection 2022.ABSTRACTCecal microflora plays a key role in the production performance and immune function of chickens. White Leghorn (WL) is a well-known commercial layer line chicken with high egg production rate. In contrast, Silky Fowl (SF), a Chinese native chicken variety, has a low egg production rate, but good immune performance. This study analyzed the composition of cecal microbiota, metabolism, and gene expression in intestinal tissue of these varieties and the correlations among them. Significant differences were observed in the cecal microbes: Bacteroides was significantly enriched in WL, whereas Veillonellaceae and Parabacteroides were significantly enriched in SF. Carbohydrate biosynthesis and metabolism pathways were significantly upregulated in WL cecum, which might provide more energy to the host, leading to persistently high levels of egg production. The higher Parabacteroides abundance in SF increased volicitin content, enhanced α-linolenic acid metabolism, and significantly negatively correlated with metabolites of propanoate metabolism and carbohydrate metabolism. Genes related to lipid metabolism, immunity, and melanogenesis were significantly upregulated in the SF cecum, regulating lipid metabolism, and participating in the immune response, while genes related to glucose metabolism and bile acid metabolism were expressed at higher levels in WL, benefiting energy support. This study provided a mechanism for intestinal microorganisms and metabolic pathways to regulate chicken egg-laying performance and immunity.PMID:36338096 | PMC:PMC9633115 | DOI:10.3389/fmicb.2022.984654

Front Microbiol. 2022 Oct 19;13:1017147. doi: 10.3389/fmicb.2022.1017147. eCollection 2022.ABSTRACTOBJECTIVE: The purpose of this study was to investigate the specific alterations in gut microbiome and serum metabolome and their interactions in patients with polycystic ovary syndrome (PCOS).METHODS: The stool samples from 32 PCOS patients and 18 healthy controls underwent the intestinal microbiome analysis using shotgun metagenomics sequencing approach. Serum metabolome was analyzed by ultrahigh performance liquid chromatography quadrupole time-of-flight mass spectrometry. An integrative network by combining metagenomics and metabolomics datasets was constructed to explore the possible interactions between gut microbiota and circulating metabolites in PCOS, which was further assessed by fecal microbiota transplantation (FMT) in a rat trial.RESULTS: Fecal metagenomics identified 64 microbial strains significantly differing between PCOS and healthy subjects, half of which were enriched in patients. These changed species showed an ability to perturb host metabolic homeostasis (including insulin resistance and fatty acid metabolism) and inflammatory levels (such as PI3K/Akt/mTOR signaling pathways) by expressing sterol regulatory element-binding transcription factor-1, serine/threonine-protein kinase mTOR, and 3-oxoacyl-[acyl-cattier-protein] synthase III, possibly suggesting the potential mechanisms of gut microbiota underlying PCOS. By integrating multi-omics datasets, the panel comprising seven strains (Achromobacter xylosoxidans, Pseudomonas sp. M1, Aquitalea pelogenes, Porphyrobacter sp. HL-46, Vibrio fortis, Leisingera sp. ANG-Vp, and Sinorhizobium meliloti) and three metabolites [ganglioside GM3 (d18:0/16:0), ceramide (d16:2/22:0), and 3Z,6Z,9Z-pentacosatriene] showed the highest predictivity of PCOS (AUC: 1.0) with sensitivity of 0.97 and specificity of 1.0. Moreover, the intestinal microbiome modifications by FMT were demonstrated to regulate PCOS phenotypes including metabolic variables and reproductive hormones.CONCLUSION: Our findings revealed key microbial and metabolite features and their interactions underlying PCOS by integrating multi-omics approaches, which may provide novel insights into discovering clinical diagnostic biomarkers and developing efficient therapeutic strategies for PCOS.PMID:36338055 | PMC:PMC9627625 | DOI:10.3389/fmicb.2022.1017147

Front Nutr. 2022 Oct 20;9:1025511. doi: 10.3389/fnut.2022.1025511. eCollection 2022.ABSTRACTThe gut microbiota and related metabolites are positively regulated by soluble dietary fiber (SDF). In this study, we explored the effects of SDF from pear pomace (PP) on the regulation of gut microbiota and metabolism in high-fat-diet-fed (HFD-fed) C57BL/6J male mice. The results showed that PP-SDF was able to maintain the HFD disrupted gut microbiota diversity with a significant increase in Lachnospiraceae_UCG-006, Akkermansia, and Bifidobacterium spp. The negative effects of high-fat diet were ameliorated by PP-SDF by regulating lipid metabolisms with a significant increase in metabolites like isobutyryl carnitine and dioscoretine. Correlation analysis revealed that gut microbiota, such as Akkermansia and Lachnospiraceae_UCG-006 in the PP-SDF intervention groups had strong positive correlations with isobutyryl carnitine and dioscoretin. These findings demonstrated that PP-SDF interfered with the host's gut microbiota and related metabolites to reduce the negative effects caused by a high-fat diet.PMID:36337664 | PMC:PMC9633104 | DOI:10.3389/fnut.2022.1025511

Front Nutr. 2022 Oct 19;9:984094. doi: 10.3389/fnut.2022.984094. eCollection 2022.ABSTRACTYeasts are reported to be rich in folates, a group of vitamers known to be involved in several biosynthetic reactions such as methylation reactions, oxidation and reduction processes, and nucleotide synthesis. Not being able to synthesize folates, humans rely on external folate supply. Here, we show the application of LC/MS-MS methods using SIDA (stable isotope dilution analysis) assays for the quantitative analysis of different folate mono- and polyglutamates during growth of Saccharomyces cerevisiae. Molecular networking (MN) was applied for detailed analysis of further folate metabolites. Highest folate contents of 13,120 μg/100 g were observed after 20 h of cultivation. The main vitamers 5-CH3-H4folate and H4folate decreased during cultivation, while 5-CHO-H4folate increased during cultivation. The hexa- and heptaglutamate of 5-CH3-H4folate accounted for >96% of the total 5-CH3-H4folate content. A shift of the major polyglutamate from hexa- to heptaglutamate was observed after 29 h. MN unraveled two groups of novel folates which could be assigned to a potentially existing C2-metabolism in yeast. In detail, 5,10-ethenyl-tetrahydrofolate and a further CO-substituted 5-CH3-H4folate were identified as hexa- and heptaglutamates. The latter was neither identified as 5-acetyl-tetrahydrofolate nor as EthylFox, the oxidation product of 5-ethyl-tetrahydrofolate. The structure needs to be elucidated in future studies.PMID:36337654 | PMC:PMC9626864 | DOI:10.3389/fnut.2022.984094

Front Nutr. 2022 Oct 13;9:934294. doi: 10.3389/fnut.2022.934294. eCollection 2022.ABSTRACTObesity and atherosclerosis are the most prevalent metabolic diseases. ApoE-/- and ob/ob mice are widely used as models to study the pathogenesis of these diseases. However, how gut microbes, gut bacteriophages, and metabolites change in these two disease models is unclear. Here, we used wild-type C57BL/6J (Wt) mice as normal controls to analyze the intestinal archaea, bacteria, bacteriophages, and microbial metabolites of ob/ob and ApoE-/- mice through metagenomics and metabolomics. Analysis of the intestinal archaea showed that the abundances of Methanobrevibacter and Halolamina were significantly increased and decreased, respectively, in the ob/ob group compared with those in the Wt and ApoE-/- groups (p < 0.05). Compared with those of the Wt group, the relative abundances of the bacterial genera Enterorhabdus, Alistipes, Bacteroides, Prevotella, Rikenella, Barnesiella, Porphyromonas, Riemerella, and Bifidobacterium were significantly decreased (p < 0.05) in the ob/ob mice, and the relative abundance of Akkermansia was significantly decreased in the ApoE-/- group. The relative abundances of A. muciniphila and L. murinus were significantly decreased and increased, respectively, in the ob/ob and ApoE-/- groups compared with those of the Wt group (p < 0.05). Lactobacillus_ prophage_ Lj965 and Lactobacillus _ prophage _ Lj771 were significantly more abundant in the ob/ob mice than in the Wt mice. Analysis of the aminoacyl-tRNA biosynthesis metabolic pathway revealed that the enriched compounds of phenylalanine, glutamine, glycine, serine, methionine, valine, alanine, lysine, isoleucine, leucine, threonine, tryptophan, and tyrosine were downregulated in the ApoE-/- mice compared with those of the ob/ob mice. Aminoacyl-tRNA synthetases are considered manifestations of metabolic diseases and are closely associated with obesity, atherosclerosis, and type 2 diabetes. These data offer new insight regarding possible causes of these diseases and provide a foundation for studying the regulation of various food nutrients in metabolic disease models.PMID:36337626 | PMC:PMC9634818 | DOI:10.3389/fnut.2022.934294

Front Nutr. 2022 Oct 20;9:930414. doi: 10.3389/fnut.2022.930414. eCollection 2022.ABSTRACTBACKGROUND: Resistant starch (RS) type 4 (RS4) is a type of RS, a class of non-digestible prebiotic dietary fibers with a range of demonstrated metabolic health benefits to the host. On the other hand, bile acids (BA) have recently emerged as an important class of metabolic function mediators that involve host-microbiota interactions. RS consumption alters fecal and cecal BA in humans and rodents, respectively. The effect of RS intake on circulating BA concentrations remains unexplored in humans.METHODS AND RESULTS: Using available plasma and stool samples from our previously reported double-blind, controlled, 2-arm crossover nutrition intervention trial (Clinicaltrials.gov: NCT01887964), a liquid-chromatography/mass-spectrometry-based targeted multiple reaction monitoring, and absolute quantifications, we assessed BA changes after 12 weeks of an average 12 g/day RS4-intake. Stool BA concentrations were lower post RS4 compared to the control, the two groups consuming similar macronutrients (n = 14/group). Partial least squares-discriminant analysis revealed distinct BA signatures in stool and plasma post interventions. The increased circulating BA concentrations were further investigated using linear mixed-effect modeling that controlled for potential confounders. A higher plasma abundance of several BA species post RS4 was observed (fold increase compared to control in parenthesis): taurocholic acid (1.92), taurodeoxycholic acid (1.60), glycochenodeoxycholic acid (1.58), glycodeoxycholic acid (1.79), and deoxycholic acid (1.77) (all, p < 0.05). Distinct microbiome ortholog-signatures were observed between RS4 and control groups (95% CI), derived using the Piphillin function-prediction algorithm and principal component analysis (PCA) of pre-existing 16S rRNA gene sequences. Association of Bifidobacterium adolescentis with secondary BA such as, deoxycholic acid (rho = 0.55, p = 0.05), glycodeoxycholic acid (rho = 0.65, p = 0.02), and taurodeoxycholic acid (rho = 0.56, p = 0.04) were observed in the RS4-group, but not in the control group (all, p > 0.05).CONCLUSION: Our observations indicate a previously unknown in humans- RS4-associated systemic alteration of microbiota-derived secondary BA. Follow-up investigations of BA biosynthesis in the context of RS4 may provide molecular targets to understand and manipulate microbiome-host interactions.PMID:36337613 | PMC:PMC9631925 | DOI:10.3389/fnut.2022.930414

Biomed Chromatogr. 2022 Nov 6:e5523. doi: 10.1002/bmc.5523. Online ahead of print.ABSTRACTOccupational chronic cadmium poisoning (OCCP) can cause irreversible organ damage. Currently, no effective treatment is available for OCCP, and effective and sensitive biomarkers for treatment evaluation are still lacking. In this study, metabolomics techniques were used to analyze changes in endogenous metabolites in the urine of patients with OCCP after 15 years of treatment. Thirty urine samples from female patients with OCCP and healthy female controls (n = 15 per group) were assessed using gas chromatography-time-of-flight mass spectrometry and ultra-high-performance liquid chromatography-Q-Exactive mass spectrometry. The OCCP group had higher concentrations of blood urea nitrogen and urinary cadmium but near-normal urinary concentrations of β2 -microglobulin and retinol-binding protein. Compared to the control group, the OCCP group had 66 significantly different metabolites with a variable importance in projection score greater than 1 and P < 0.05. These differential metabolites were involved in various metabolic pathways, such as creatine metabolism, nicotinate and nicotinamide metabolism, the pentose phosphate pathway, d-glutamine and d-glutamate metabolism, and amino acid metabolism. Compared to the control group, the OCCP group had significantly higher urinary concentrations of creatine, glutamic acid, quinolinic acid, and nicotinic acid. In a receiver operator characteristic analysis, the area under the curve (AUC) of creatine was higher than the AUCs for glutamic acid, quinolinic acid, and nicotinic acid, indicating that urinary concentrations of creatine could be used as a sensitive biomarker for the diagnosis and prognosis of OCCP and for monitoring its treatment.PMID:36336973 | DOI:10.1002/bmc.5523