PubMed

Chin Med. 2023 Feb 16;18(1):17. doi: 10.1186/s13020-023-00716-w.ABSTRACTBACKGROUND: TongFengTangSan (TFTS) is a commonly used Tibetan prescription for gout treatment. Previously, TFTS (CF) was confirmed to have a significant uric acid-lowering effect. However, the anti-hyperuricemia mechanisms and the main active fractions remain unclear. The current study aimed to investigate the anti-hyperuricemia mechanism using metabolomics and confirm the active CF fraction.METHODS: The hyperuricemia model was established through intraperitoneal injection containing 100 mg/kg potassium oxonate and 150 mg/kg hypoxanthine by gavage. We used serum uric acid (sUA), creatinine (CRE), blood urea nitrogen (BUN), xanthine oxidase (XOD) activity, interleukin-6 (IL-6) and interleukin-1β (IL-1β) as indicators to evaluate the efficacy of CF and the four fractions (SX, CF30, CF60, and CF90). The anti-hyperuricemia mechanism of CF was considered through non-targeted metabolomics depending on the UPLC-Q-TOF-MS technology. Principle component analysis (PCA) and orthogonal partial least squares-discriminant analysis (OPLS-DA) helped explore the potential biomarkers in hyperuricemia. Moreover, the differential metabolites and metabolic pathways regulated by CF and four fractions were also assessed.RESULTS: CF revealed a significant anti-hyperuricemia effect by down-regulating the level of sUA, sCRE, sIL-1β, and XOD. SX, CF30, CF60, and CF90 differed in the anti-hyperuricemia effect. Only CF60 significantly lowered the sUA level among the four fractions, and it could be the main efficacy fraction of TFTS. Forty-three differential metabolites were identified in hyperuricemia rats from plasma and kidney. Pathway analysis demonstrated that seven pathways were disrupted among hyperuricemia rats. CF reversed 19 metabolites in hyperuricemia rats and exerted an anti-hyperuricemia effect by regulating purine metabolism. CF60 was the main active fraction of TFTS and exerted a similar effect of CF by regulating purine metabolism.CONCLUSIONS: CF and CF60 could exert an anti-hyperuricemia effect by regulating the abnormal purine metabolism because of hyperuricemia while improving intestinal and renal function. CF60 could be the main active fraction of TFTS.PMID:36797795 | DOI:10.1186/s13020-023-00716-w

Discov Oncol. 2023 Feb 17;14(1):20. doi: 10.1007/s12672-023-00628-z.ABSTRACTBACKGROUND: Carbohydrate antigen 19-9 (CA19-9) is the most widely used biomarker for pancreatic cancer. Since CA19-9 closely correlates with patient outcome and tumor stage in pancreatic cancer, the deciphering of CA19-9 biosynthesis provides a potential clue for treatment.METHODS: Concentration of amino acids was detected by ultrahigh-performance liquid chromatography tandem mass spectrometry. Metabolic flux of glutamine was examined by isotope tracing untargeted metabolomics. Label-free quantitative N-glycosylation proteomics was used to examine N-glycosylation alterations.RESULTS: Among all amino acids, glutamine was higher in CA19-9-high pancreatic cancers (> 37 U/mL, 66 cases) than in CA19-9-normal clinical specimens (≤ 37 U/mL, 37 cases). The glutamine concentration in clinical specimens was positively correlated with liver metastasis or lymphovascular invasion. Glutamine blockade using diazooxonorleucine suppressed pancreatic cancer growth and intraperitoneal and lymphatic metastasis. Glutamine promotes O-GlcNAcylation, protein glycosylation, and CA19-9 biosynthesis through the hexosamine biosynthetic pathway. UDP-N-acetylglucosamine (UDP-GlcNAc) levels correlated with the glutamine influx through hexosamine biosynthetic pathway and supported CA19-9 biosynthesis.CONCLUSIONS: Glutamine is a substrate for CA19-9 biosynthesis in pancreatic cancer. Glutamine blockade may be a potential therapeutic strategy for pancreatic cancer.PMID:36797531 | DOI:10.1007/s12672-023-00628-z

Drug Metab Dispos. 2023 Feb 16:DMD-AR-2022-001234. doi: 10.1124/dmd.122.001234. Online ahead of print.ABSTRACTUncaria rhynchophylla (Gou Teng) and Uncaria tomentosa (Cat's Claw) are frequently used herbal supplements in Asia and America, respectively. Despite their common usage, information is limited regarding potential herb-drug interactions associated with Gou Teng and Cat's Claw. The pregnane X receptor (PXR) is a ligand-dependent transcription factor that regulates Cytochrome P450 3A4 (CYP3A4) expression and contributes to some known herb-drug interactions. A recent study found that Gou Teng induces CYP3A4 expression, but its mechanism is unknown. Cat's Claw has been determined as a PXR-activating herb, but the PXR activators in Cat's Claw have not been identified. Using a genetically engineered PXR cell line, we found that the extracts of Gou Teng and Cat's Claw can dose-dependently activate PXR and induce CYP3A4 expression. We next used a metabolomic approach to profile the chemical components in the extracts of Gou Teng and Cat's Claw followed by screening for PXR activators. Four compounds, isocorynoxeine, rhynchophylline, isorhynchophylline, and corynoxeine, were identified as PXR activators from both Gou Teng and Cat's Claw extracts. In addition, three more PXR activators were identified from the extracts of Cat's Claw including isopteropodine, pteropodine, and mitraphylline. All these seven compounds showed the half maximal effective concentration < 10 µM for PXR activation. In summary, our work determined Gou Teng as a PXR-activating herb and discovered novel PXR activators from Gou Teng as well as Cat's Claw. Significance Statement Our data can be used to guide the safe use of Gou Teng and Cat's Claw by avoiding PXR-mediated herb-drug interactions.PMID:36797057 | DOI:10.1124/dmd.122.001234

J Therm Biol. 2023 Feb;112:103406. doi: 10.1016/j.jtherbio.2022.103406. Epub 2022 Dec 9.ABSTRACTIn order to investigate the influence of gradient cooling acclimation on body mass regulation in tree shrews (Tupaia belangeri), white adipose tissue (WAT) and brown adipose tissue (BAT) in T. belangeri between the control group and gradient cooling acclimation group on day 56 were collected, body mass, food intake, thermogenic capacity, differential metabolites, and related metabolic pathways in WAT and BAT were measured, the changes of differential metabolites were analyzed by non-targeted metabolomics method based on liquid chromatography-mass spectrometry. The results shown that gradient cooling acclimation significantly increased body mass, food intake, resting metabolic rate (RMR), non-shivering thermogenesis (NST), and masses of WAT and BAT. 23 significant differential metabolites in WAT between the gradient cooling acclimation group and the control group, of which the relative contents of 13 differential metabolites were up-regulated and 10 differential metabolites were down-regulated. 27 significant differential metabolites in BAT, of which 18 differential metabolites decreased and 9 differential metabolites increased. 15 differential metabolic pathways in WAT, 8 differential metabolic pathways in BAT, and 4 differential metabolic pathways involved in both WAT and BAT, including Purine metabolism, Pyrimidine metabolism, Glycerol phosphate metabolism, Arginine and proline metabolism, respectively. All of the above results suggested that T. belangeri could use different metabolites of adipose tissue to withstand low temperature environments and enhance their survival.PMID:36796882 | DOI:10.1016/j.jtherbio.2022.103406

Biotechnol J. 2023 Feb 16:e2200444. doi: 10.1002/biot.202200444. Online ahead of print.ABSTRACTMetabolic reprogramming has been coined as a hallmark of cancer, accompanied by which the alterations in metabolite levels have profound effects on gene expression, cellular differentiation and the tumor environment. Yet a systematic evaluation of quenching and extraction procedures for quantitative metabolome profiling of tumor cells is currently lacking. To achieve this, this study is aimed at establishing an unbiased and leakage-free metabolome preparation protocol for Hela carcinoma cell. We evaluated 12 combinations of quenching and extraction methods from three quenchers (liquid nitrogen, -40°C 50% methanol, 0.5°C normal saline) and four extractants (-80°C 80% methanol, 0.5°C methanol: chloroform: water (1:1:1, v/v/v), 0.5°C 50% acetonitrile, 75°C 70% ethanol) for global metabolite profiling of adherent Hela carcinoma cells. Based on the isotope dilution mass spectrometry (IDMS) method, gas/liquid chromatography in tandem with mass spectrometry was used to quantitatively determine 43 metabolites including sugar phosphates, organic acids, amino acids, adenosine nucleotides and coenzymes involved in central carbon metabolism. The results showed that the total amount of the intracellular metabolites in cell extracts obtained using different sample preparation procedures with the IDMS method ranged from 21.51 to 295.33 nmol/million cells. Among 12 combinations, cells that washed twice with phosphate buffered saline (PBS), quenched with liquid nitrogen, and then extracted with 50% acetonitrile was found to be the most optimal method to acquire intracellular metabolites with high efficiency of metabolic arrest and minimal loss during sample preparation. In addition, the same conclusion was drawn as these 12 combinations were applied to obtain quantitative metabolome data from three-dimensional (3D) tumor spheroids. Furthermore, a case study was carried out to evaluate the effect of doxorubicin (DOX) on both adherent cells and 3D tumor spheroids using quantitative metabolite profiling. Pathway enrichment analysis using targeted metabolomics data showed that DOX exposure would significantly affect amino acid metabolism-related pathways, which might be related to the mitigation of redox stress. Strikingly, our data suggested that compared to 2D cells the increased intracellular glutamine level in 3D cells benefited replenishing the tricarboxylic acid (TCA) cycle when the glycolysis was limited after dosing with DOX. Taken together, this study provides a well-established quenching and extraction protocol for quantitative metabolome profiling of Hela carcinoma cell under 2D and 3D cell culture conditions. Based on this, quantitative time-resolved metabolite data can serve to the generation of hypotheses on metabolic reprogramming to reveal its important role in tumor development and treatment. This article is protected by copyright. All rights reserved.PMID:36796787 | DOI:10.1002/biot.202200444

Genomics. 2023 Feb 14:110586. doi: 10.1016/j.ygeno.2023.110586. Online ahead of print.ABSTRACTControlling eutrophication with algicidal bacteria is widely recognized as an effective solution. Here, an integrated transcriptomic and metabolomic approach was used to elucidate the algicidal process of Enterobacter hormaechei F2, which exhibits substantial algicidal activity. At the transcriptome level, RNA sequencing (RNA-seq) identified 1104 differentially expressed genes in the algicidal process of the strain, thus indicating that amino acids, energy metabolism, and signaling-related genes were significantly activated during the algicidal process according to the Kyoto Encyclopedia of Genes and Genomes enrichment analysis. By analyzing the enriched amino acid and energy metabolism pathways using metabolomics, we identified 38 upregulated and 255 downregulated significantly changed metabolites in the algicidal process and an accumulation of B vitamins, peptides, and energy substances. The integrated analysis demonstrated that energy and amino acid metabolism, co-enzymes and vitamins, and bacterial chemotaxis are the most important pathways for the algicidal process of this strain, and metabolites from these pathways, such as thiomethyladenosine, isopentenyl diphosphate, hypoxanthine, xanthine, nicotinamide, and thiamine, all exhibited algicidal activity.PMID:36796656 | DOI:10.1016/j.ygeno.2023.110586

Genomics. 2023 Feb 14:110581. doi: 10.1016/j.ygeno.2023.110581. Online ahead of print.ABSTRACTFish farms are prone to disease outbreaks and stress due to high-density rearing conditions in tanks and sea cages, adversely affecting growth, reproduction, and metabolism. To understand the molecular mechanisms affected in the gonads of breeder fish after an immune challenge, we investigated the metabolome and the transcriptome profiles in zebrafish testes after inducing an immune response. After 48 h of the immune challenge, ultra-high-performance liquid chromatography (LC-MS) and transcriptomic analysis by RNA-seq (Illumina) resulted in 20 different released metabolites and 80 differentially expressed genes. Among these, glutamine and succinic acid were the most abundant metabolites released and 27,5% of the genes belong to either the immune or reproduction systems. Pathway analysis based on metabolomic and transcriptomic crosstalk identified cad and iars genes that act simultaneously with succinate metabolite. This study deciphers interactions between reproduction and immune systems and provides a basis to improve protocols in generating more resistant broodstock.PMID:36796654 | DOI:10.1016/j.ygeno.2023.110581

Environ Pollut. 2023 Feb 14;323:121280. doi: 10.1016/j.envpol.2023.121280. Online ahead of print.NO ABSTRACTPMID:36796308 | DOI:10.1016/j.envpol.2023.121280

J Pharm Biomed Anal. 2022 Nov 29;227:115187. doi: 10.1016/j.jpba.2022.115187. Online ahead of print.ABSTRACTThe differentiation of raw herbal products from similar species have been achieved by plant metabolomics. However, the distinguishment on various processed products with improved activities and wide clinical utilization from similar species is still tricky due to obscure composition variations during processing. In this study, a comprehensive analysis of phytoecdysteroids in Achyranthes bidentata Blume (AB) and its three analogous species, which were all called Niuxi in Chinese, was conducted on UPLC-HRMS by integrating dynamic exclusion acquisition with data post-processing of targeted multilateral mass defect filter. Two most frequently used species, AB and Cyathula officinalis Kuan (CO) were systematically compared with plant metabolomics methods. And the differential components from the raw materials were evaluated on the ability of distinguishing processed products. The substitution of hydroxyl groups on C-21, C-20, C-22 and C-25 were determined by characteristic mass differences, leading to systematical characterization of 281 phytoecdysteroids. In plant metabolomics studies of raw AB and CO, 16 potential markers were filtered by VIP value > 1, and displayed satisfactory differentiation on the processed AB and CO. The results facilitated the quality control of the four species, especially the processed products of AB and CO, also provided a reference method for the quality control of other processed products.PMID:36796274 | DOI:10.1016/j.jpba.2022.115187

J Chromatogr B Analyt Technol Biomed Life Sci. 2023 Feb 2;1217:123627. doi: 10.1016/j.jchromb.2023.123627. Online ahead of print.ABSTRACTBACKGROUND: The herbal pair of Salvia miltiorrhiza Bunge and Pueraria montana var. lobata (Willd.) Sanjappa & Pradeep (DG) is commonly used in the treatment of type 2 diabetes (T2DM) in traditional Chinese medicine (TCM). The drug pair DG was designed by Dr. Zhu chenyu to improve the treatment of T2DM.AIM: This study combined with systematic pharmacology and urine metabonomics to explore the mechanism of DG in the treatment of T2DM.METHODS: The therapeutic effect of DG on T2DM was evaluated by fasting blood glucose (FBG) and biochemical indexes. Systematic pharmacology was used to screen the active components and targets that may be related to DG. Metabonomics was established to find urinary metabolites and pathways that may be induced by DG. Finally, integrate the results of these two parts for mutual verification.RESULTS: FBG and biochemical indexes showed that DG could reduce FBG and adjust the related biochemical indexes. Metabolomics analysis indicated that 39 metabolites were related to DG for T2DM treatment. In addition, systematic pharmacology showed compounds and potential targets which were associated with DG. Finally, 12 promising targets were selected as targets for T2DM therapy by integrating the results.CONCLUSION: The combination of metabonomics and systematic pharmacology based on LC-MS is feasible and effective, which provides strong support for exploring the effective components and pharmacological mechanism of TCM.PMID:36796216 | DOI:10.1016/j.jchromb.2023.123627

Ecotoxicol Environ Saf. 2023 Feb 14;253:114616. doi: 10.1016/j.ecoenv.2023.114616. Online ahead of print.ABSTRACTManganese (Mn) accumulates in the central nervous system and can cause neurotoxicity, but the mechanisms of Mn-induced neurotoxicity remain unclear. We performed single-cell RNA sequencing (scRNA-seq) of zebrafish brain after Mn exposure and identified 10 cell types by marker genes: cholinergic neurons, dopaminergic (DA) neurons, glutaminergic neurons, GABAergic neurons, neuronal precursors, other neurons, microglia, oligodendrocyte, radial glia, and undefined cells. Each cell type has its distinct transcriptome profile. Pseudotime analysis revealed that DA neurons had a critical role in Mn-induced neurological damage. Combined with metabolomic data, chronic Mn exposure significantly impaired amino acid and lipid metabolic processes in the brain. Furthermore, we found that Mn exposure disrupted the ferroptosis signaling pathway in the DA neurons in zebrafish. Overall, our study employed joint analysis of multi-omics and revealed ferroptosis signaling pathway is a novel potential mechanism of Mn neurotoxicity.PMID:36796209 | DOI:10.1016/j.ecoenv.2023.114616

Comp Biochem Physiol Part D Genomics Proteomics. 2023 Feb 9;46:101061. doi: 10.1016/j.cbd.2023.101061. Online ahead of print.ABSTRACTWhether in aquaculture or in nature, starvation stress limits the growth of fish. The purpose of the study was to clarify the detailed molecular mechanisms underlying starvation stress in Korean rockfish (Sebastes schlegelii) through liver transcriptome and metabolome analysis. Transcriptome results showed that liver genes associated with cell cycle and fatty acid synthesis were down-regulated, whereas those related to fatty acid decomposition were up-regulated in the experimental group (EG; starved for 72 days) compared to the control group (CG; feeding). Metabolomic results showed that there were significant differences in the levels of metabolites related to nucleotide metabolism and energy metabolism, such as purine metabolism, histidine metabolism and oxidative phosphorylation. Five fatty acids (C22:6n-3; C22:5n-3; C20:5n-3; C20:4n-3; C18:3n-6) were selected as possible biomarkers of starvation stress from the differential metabolites of metabolome. Subsequently, correlation between these differential genes of lipid metabolism and cell cycle and differential metabolites were analyzed, and observed that these five fatty acids were significantly correlated with the differential genes. These results provide new clues for understanding the role of fatty acid metabolism and cell cycle in fish under starvation stress. It also provides a reference for promoting the biomarker identification of starvation stress and stress tolerance breeding research.PMID:36796184 | DOI:10.1016/j.cbd.2023.101061

Pediatr Endocrinol Diabetes Metab. 2022;28(1):35-45. doi: 10.5114/pedm.2022.112857.ABSTRACTINTRODUCTION: Endocrine-disruptors are exogenous compounds that interfere with the human biological system. Bisphenol-A and toxic ele-mental mixtures (e.g. As, Pb, Hg, Cd, and U) are major endocrine-disruptive chemicals documented by the USEPA. Globally obesi-ty is a major health problem with increasing fast-food intake among children. The use of food packaging material is rising global-ly, becoming a primary source of chemical migration from food contact materials.MATERIAL AND METHODS: This protocol is a cross-sectional study, and the primary outcome is to assess the various dietary and non-dietary exposure sources of endocrine-disruptive chemicals (bisphenol A and heavy metals) through a questionnaire, and quantification of urinary bisphenol A and heavy metals using LC-MS/MS and ICP-MS, respectively, among children. In this study, anthropometric assess-ment, socio-demographic characteristics, and laboratory investigations will be performed. Exposure pathway assessment will be done using questions about household characteristics, surroundings, food and water sources, physical/dietary habits, and nutri-tional assessment.RESULTS: An exposure pathway model will be developed based on the questions on source, pathway/exposure, and receptor (child), of those exposed to or potentially exposed to the endocrine-disruptive chemicals.CONCLUSIONS: The children who are exposed or potentially exposed to the chemical migration sources need intervention through local bodies, school curriculum, and training programs. Also, methodological points of view implication of regression models and the LASSO approach will be assessed to identify the emerging risk factors of childhood obesity and even reverse causality through multi-pathway exposure sources. The feasibility of the current study outcome can be implicated in developing countries.PMID:36795968 | DOI:10.5114/pedm.2022.112857

J Clin Invest. 2023 Feb 16:e164596. doi: 10.1172/JCI164596. Online ahead of print.ABSTRACTLysosomal inhibition elicited by palmitoyl protein transferase 1 (PPT1) inhibitors such as DC661 can produce cell death, but the mechanism is not completely understood. Programmed cell death pathways (autophagy, apoptosis, necroptosis, ferroptosis, and pyroptosis) were not required to achieve the cytotoxic effect of DC661. Inhibition of cathepsins, or iron or calcium chelation, did not rescue DC661-induced cytotoxicity. PPT1 inhibition induced lysosomal lipid peroxidation (LLP), which led to lysosomal membrane permeabilization and cell death that could be reversed by the antioxidant N-acetylcysteine (NAC), but not by other lipid peroxidation antioxidants. The lysosomal cysteine transporter MFSD12, was required for intralysosomal transport of NAC and rescue of LLP. PPT1 inhibition produced cell-intrinsic immunogenicity with surface expression of calreticulin that could only be reversed with NAC. DC661-treated cells primed naïve T cells, and enhanced T cell-mediated toxicity. Mice vaccinated with DC661-treated cells, engendered adaptive immunity and tumor rejection in "immune hot" tumors but not in "immune cold" tumors. These findings demonstrate LLP drives lysosomal cell death, a unique immunogenic form of cell death, pointing the way to rational combinations of immunotherapy and lysosomal inhibition that can be tested in clinical trials.PMID:36795483 | DOI:10.1172/JCI164596

Inflamm Res. 2023 Feb 16. doi: 10.1007/s00011-023-01706-2. Online ahead of print.NO ABSTRACTPMID:36795337 | DOI:10.1007/s00011-023-01706-2

Sci China Life Sci. 2023 Feb 10. doi: 10.1007/s11427-022-2226-1. Online ahead of print.ABSTRACTBroiler chicks are fast-growing and susceptible to dietary selenium (Se) deficiency. This study sought to reveal the underlying mechanisms of how Se deficiency induces key organ dysfunctions in broilers. Day-old male chicks (n=6 cages/diet, 6 chicks/cage) were fed with a Se-deficient diet (Se-Def, 0.047 mg Se/kg) or the Se-Def+0.3 mg Se/kg (Control, 0.345 mg Se/kg) for 6 weeks. The serum, liver, pancreas, spleen, heart, and pectoral muscle of the broilers were collected at week 6 to assay for Se concentration, histopathology, serum metabolome, and tissue transcriptome. Compared with the Control group, Se deficiency induced growth retardation and histopathological lesions and reduced Se concentration in the five organs. Integrated transcriptomics and metabolomics analysis revealed that dysregulation of immune and redox homeostasis related biological processes and pathways contributed to Se deficiency-induced multiple tissue damage in the broilers. Meanwhile, four metabolites in the serum, daidzein, epinephrine, L-aspartic acid and 5-hydroxyindoleacetic acid, interacted with differentially expressed genes with antioxidative effects and immunity among all the five organs, which contributed to the metabolic diseases induced by Se deficiency. Overall, this study systematically elucidated the underlying molecular mechanisms in the pathogenesis of Se deficiency-related diseases, which provides a better understanding of the significance of Se-mediated heath in animals.PMID:36795182 | DOI:10.1007/s11427-022-2226-1

Appl Microbiol Biotechnol. 2023 Feb 16. doi: 10.1007/s00253-023-12435-1. Online ahead of print.ABSTRACTVibrio alginolyticus is an important foodborne pathogen that can infect both humans and marine animals and cause massive economic losses in aquaculture. Small noncoding RNAs (sRNAs) are emerging posttranscriptional regulators that affect bacterial physiology and pathological processes. In the present work, a new cell density-dependent sRNA, Qrr4, was characterized in V. alginolyticus based on a previously reported RNA-seq analysis and bioinformatics approach. The effects of Qrr4 actions on the physiology, virulence, and metabolism of V. alginolyticus were comprehensively investigated based on molecular biology and metabolomics approaches. The results showed that qrr4 deletion markedly inhibited growth, motility and extracellular protease activities. Additionally, nontargeted metabolism and lipidomics analyses revealed that qrr4 deletion induced significant disturbance of multiple metabolic pathways. The key metabolic remodelling that occurred in response to qrr4 deletion was found to involve phospholipid, nucleotide, carbohydrate and amino acid metabolic pathways, providing novel clues about a potential mechanism via which mutation of qrr4 could interfere with cellular energy homeostasis, modulate membrane phospholipid composition and inhibit nucleic acid and protein syntheses to regulate the motility, growth and virulence characteristics of V. alginolyticus. Overall, this study provides a comprehensive understanding of the regulatory roles of the new cell density-dependent sRNA Qrr4 in V. alginolyticus. KEY POINTS: • A novel cell density-dependent sRNA, Qrr4, was cloned in V. alginolyticus. •Qrr4 regulated growth and virulence factors of V. alginolyticus. • Phospholipid, nucleotide and energy metabolisms were modulated obviously by Qrr4.PMID:36795140 | DOI:10.1007/s00253-023-12435-1

J Dig Dis. 2023 Feb 16. doi: 10.1111/1751-2980.13162. Online ahead of print.ABSTRACTAIM: Gut bacteria facilitate nutrient metabolism and generate small molecules that form part of the broader "metabolome." It is unclear whether these metabolites are disturbed during chronic pancreatitis. This study aimed to evaluate the gut microbial-host co-metabolites and the relationship between them in patients with chronic pancreatitis.METHODS: We collected fecal samples from 40 patients with chronic pancreatitis and 38 healthy family members with each sample undergoing 16S rRNA gene profiling and gas chromatography time-of-flight mass spectrometry , to estimate the relative abundance of specific bacterial taxa between the two groups and to profile any changes in the metabolome, respectively. Correlation analysis was used to evaluate differences in metabolites and bacteria between the two groups.RESULTS: The abundance of Actinobacteria was lower at the phylum level, and that of Bifidobacterium was lower at the genus level in the chronic pancreatitis group metabolites had a significantly different. Oxoadipic acid and citric acid levels were positively correlated with Bifidobacterium abundance (Spearman's r = 0.306, and r = 0.33, respectively, p < 0.05),and the 3-methylindole concentration was negatively correlated with Bifidobacterium abundance (r = -0.252, p = 0.026).CONCLUSIONS: Gut microbiome and host microbiome metabolic products might be altered in patients with chronic pancreatitis. Evaluating gastrointestinal tract metabolite levels in this regard may further enhance our understanding of the pathogenesis and/or progression of chronic pancreatitis.PMID:36795087 | DOI:10.1111/1751-2980.13162

Microbiol Spectr. 2023 Feb 16:e0377122. doi: 10.1128/spectrum.03771-22. Online ahead of print.ABSTRACTThe pathogenesis of gut microbiota and their metabolites in the development of metabolic syndrome (MS) remains unclear. This study aimed to evaluate the signatures of gut microbiota and metabolites as well as their functions in obese children with MS. A case-control study was conducted based on 23 MS children and 31 obese controls. The gut microbiome and metabolome were measured using 16S rRNA gene amplicon sequencing and liquid chromatography-mass spectrometry. An integrative analysis was conducted, combining the results of the gut microbiome and metabolome with extensive clinical indicators. The biological functions of the candidate microbial metabolites were validated in vitro. We identified 9 microbiota and 26 metabolites that were significantly different from the MS and the control group. The clinical indicators of MS were correlated with the altered microbiota Lachnoclostridium, Dialister, and Bacteroides, as well as with the altered metabolites all-trans-13,14-dihydroretinol, DL-dipalmitoylphosphatidylcholine (DPPC), LPC 24: 1, PC (14:1e/10:0), and 4-phenyl-3-buten-2-one, etc. The association network analysis further identified three MS-linked metabolites, including all-trans-13,14-dihydroretinol, DPPC, and 4-phenyl-3-buten-2-one, that were significantly correlated with the altered microbiota. Bio-functional validation showed that all-trans-13, 14-dihydroretinol could significantly upregulate the expression of lipid synthesis genes and inflammatory genes. This study identified a new biomarker that may contribute to MS development. These findings provided new insights regarding the development of efficient therapeutic strategies for MS. IMPORTANCE Metabolic syndrome (MS) has become a health concern worldwide. Gut microbiota and metabolites play an important role in human health. We first endeavored to comprehensively analyze the microbiome and metabolome signatures in obese children and found the novel microbial metabolites in MS. We further validated the biological functions of the metabolites in vitro and illustrated the effects of the microbial metabolites on lipid synthesis and inflammation. The microbial metabolite all-trans-13, 14-dihydroretinol may be a new biomarker in the pathogenesis of MS, especially in obese children. These findings were not available in previous studies, and they provide new insights regarding the management of metabolic syndrome.PMID:36794949 | DOI:10.1128/spectrum.03771-22

Elife. 2023 Feb 16;12:e82785. doi: 10.7554/eLife.82785. Online ahead of print.ABSTRACTMultiomics technologies improve the biological understanding of health status in people living with HIV on antiretroviral therapy (PLWH). Still, a systematic and in-depth characterization of metabolic risk profile during successful long-term treatment is lacking. Here, we used multi-omics (plasma lipidomic, metabolomic, and fecal 16S microbiome) data-driven stratification and characterization to identify the metabolic at-risk profile within PLWH. Through network analysis and similarity network fusion (SNF), we identified three groups of PLWH (SNF-1 to 3): healthy (HC)-like (SNF-1), mild at-risk (SNF-3), and severe at-risk (SNF-2). The PLWH in the SNF-2 (45%) had a severe at-risk metabolic profile with increased visceral adipose tissue, BMI, higher incidence of metabolic syndrome (MetS), and increased di- and triglycerides despite having higher CD4+ T-cell counts than the other two clusters. However, the HC-like and the severe at-risk group had a similar metabolic profile differing from HIV-negative controls (HNC), with dysregulation of amino acid metabolism. At the microbiome profile, the HC-like group had a lower α-diversity, a lower proportion of men having sex with men (MSM) and was enriched in Bacteroides. In contrast, in at-risk groups, there was an increase in Prevotella, with a high proportion of MSM, which could potentially lead to higher systemic inflammation and increased cardiometabolic risk profile. The multi-omics integrative analysis also revealed a complex microbial interplay of the microbiome-derived metabolites in PLWH. Those severely at-risk clusters may benefit from personalized medicine and lifestyle intervention to improve their dysregulated metabolic traits, aiming to achieve healthier aging.PMID:36794912 | DOI:10.7554/eLife.82785