PubMed

Drug Chem Toxicol. 2023 Aug 7:1-16. doi: 10.1080/01480545.2023.2242005. Online ahead of print.ABSTRACTSodium taurocholate (NaT) is a hydrophobic bile salt that exhibits varying toxicity and antimicrobial activity. The accumulation of BSs during their entero-hepatic cycle causes cytotoxicity in the liver and intestine and could also alter the intestinal microbiome leading to various diseases. In this research, the acute toxicity of sodium taurocholate in different concentrations (3000 mg/L, 1500 mg/L, 750 mg/L, 375 mg/L, and 0 mg/L) was investigated on four months old zebrafish by immersion in water for 96 h. The results were determined based on the fish mortality, behavioral response, and NMR metabolomics analysis which revealed LC50 of 1760.32 mg/L and 1050.42 mg/L after 72 and 96 h treatment, respectively. However, the non-lethal NaT concentrations of 750 mg/L and 375 mg/L at 96 h exposure significantly (p ≤ 0.05) decreased the total distance traveled and the activity duration, also caused surface respiration on the zebrafish. Orthogonal Projections to Latent Structures Discriminant Analysis (OPLS-DA) revealed that the metabolome of the fish treated with 750 mg/L was discriminated from that of the control by PC1. Major significantly downregulated metabolites by NaT-induction include valine, isoleucine, 2-hydroxyvalerate, glycine, glycerol, choline, glucose, pyruvate, anserine, threonine, carnitine and homoserine. On the contrary, taurine, creatine, lactate, acetate and 3-hydroxybutyrate were upregulated suggesting cellular consumption of lipids, glucose and amino acids for adenosine triphosphate (ATP) generation during immune and inflammatory response. whereby these metabolites were released in the process. In conclusion, the research revealed the toxic effect of NaT and its potential to trigger changes in zebrafish metabolism.PMID:37548163 | DOI:10.1080/01480545.2023.2242005

New Phytol. 2023 Aug 7. doi: 10.1111/nph.19160. Online ahead of print.ABSTRACTThe ascorbate-glutathione (ASC-GSH) cycle is at the heart of redox metabolism, linking the major redox buffers with central metabolism through the processing of reactive oxygen species (ROS) and pyridine nucleotide metabolism. Tomato fruit development is underpinned by changes in redox buffer contents and their associated enzyme capacities, but interactions between them remain unclear. Based on quantitative data obtained for the core redox metabolism, we built an enzyme-based kinetic model to calculate redox metabolite concentrations with their corresponding fluxes and control coefficients. Dynamic and associated regulations of the ASC-GSH cycle throughout the whole fruit development were analysed and pointed to a sequential metabolic control of redox fluxes by ASC synthesis, NAD(P)H and ROS availability depending on the developmental phase. Furthermore, we highlighted that monodehydroascorbate reductase and the availability of reducing power were found to be the main regulators of the redox state of ASC and GSH during fruit growth under optimal conditions. Our kinetic modelling approach indicated that tomato fruit development displayed growth phase-dependent redox metabolism linked with central metabolism via pyridine nucleotides and H2 O2 availability, while providing a new tool to the scientific community to investigate redox metabolism in fruits.PMID:37548068 | DOI:10.1111/nph.19160

Nanoscale. 2023 Aug 7. doi: 10.1039/d3nr02322b. Online ahead of print.ABSTRACTCrops are constantly challenged by different environmental conditions. Seed treatment using nanomaterials is a cost-effective and environmentally friendly solution for environmental stress mitigation in crop plants. Here, 56 seed nanopriming treatments are used to alleviate environmental stresses in maize. Seven selected nanopriming treatments significantly increase the stress resistance index (SRI) by 13.9% and 12.6% under salinity stress and combined heat-drought stress, respectively. Metabolomics data reveal that ZnO nanopriming treatment, with the highest SRI value, mainly regulates the pathways of amino acid metabolism, secondary metabolite synthesis, carbohydrate metabolism, and translation. Understanding the mechanism of seed nanopriming is still difficult due to the variety of nanomaterials and the complexity of interactions between nanomaterials and plants. Using the nanopriming data, we present an interpretable structure-activity relationship (ISAR) approach based on interpretable machine learning for predicting and understanding its stress mitigation effects. The post hoc and model-based interpretation approaches of machine learning are integrated to provide complementary advantages and may yield more illuminating or trustworthy results for researchers or policymakers. The concentration, size, and zeta potential of nanoparticles are identified as dominant factors for correlating root dry weight under salinity stress, and their effects and interactions are explained. Additionally, a web-based interactive tool is developed for offering prediction-level interpretation and gathering more details about a specific nanopriming treatment. This work offers a promising framework for accelerating the agricultural applications of nanomaterials and may contribute to nanosafety assessment.PMID:37548042 | DOI:10.1039/d3nr02322b

Analyst. 2023 Aug 7. doi: 10.1039/d3an01051a. Online ahead of print.ABSTRACTThere is a wide variety of autoimmune diseases (ADs) with complex pathogenesis and their accurate diagnosis is difficult to achieve because of their vague symptoms. Metabolomics has been proven to be an efficient tool in the analysis of metabolic disorders to provide clues about the mechanism and diagnosis of diseases. Previous studies of the metabolomics analysis of ADs were not competent in their discrimination. Herein, a liquid chromatography tandem mass spectrometry (LC-MS) strategy combined with machine learning is proposed for the discrimination and classification of ADs. Urine and serum samples were collected from 267 subjects consisting of 127 healthy controls (HC) and 140 AD patients, including those with rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), sicca syndrome (SS), ankylosing spondylitis (AS), systemic scleroderma (SSc) and connective tissue disease (CTD). Machine learning algorithms were encoded for the discrimination and classification of ADs with metabolomic patterns obtained by LC-MS, and satisfactory results were achieved. Notably, urine samples exhibited higher accuracy for disease differentiation and triage than serum samples. Apart from that, differential metabolites were selected and metabolite panels were evaluated to demonstrate their representativeness. Metabolic dysregulations were also investigated to gain more knowledge about the pathogenesis of ADs. This research provides a promising method for the application of metabolomics combined with machine learning in precision medicine.PMID:37547947 | DOI:10.1039/d3an01051a

Front Microbiol. 2023 Jul 20;14:1188649. doi: 10.3389/fmicb.2023.1188649. eCollection 2023.ABSTRACTOphiocordyceps is a species-rich genus in the order Hypocreales (Sordariomycetes, Ascomycota) depicting a fascinating relationship between microbes and insects. In the present study, a new species, Ophiocordyceps indica sp. nov., is discovered infecting lepidopteran larvae from tree line locations (2,202-2,653 m AMSL) of the Kullu District, Himachal Pradesh, Indian Western Himalayan region, using combinations of morphological and molecular phylogenetic analyses. A phylogeny for Ophiocordyceps based on a combined multigene (nrSSU, nrLSU, tef-1α, and RPB1) dataset is provided, and its taxonomic status within Ophiocordycipitaceae is briefly discussed. Its genome size (~59 Mb) revealed 94% genetic similarity with O. sinensis; however, it differs from other extant Ophiocordyceps species based on morphological characteristics, molecular phylogenetic relationships, and genetic distance. O. indica is identified as the second homothallic species in the family Ophiocordycipitaceae, after O. sinensis. The presence of targeted marker components, viz. nucleosides (2,303.25 μg/g), amino acids (6.15%), mannitol (10.13%), and biological activity data, suggests it to be a new potential source of nutraceutical importance. Data generated around this economically important species will expand our understanding regarding the diversity of Ophiocordyceps-like taxa from new locations, thus providing new research avenues.PMID:37547690 | PMC:PMC10399244 | DOI:10.3389/fmicb.2023.1188649

Front Microbiol. 2023 Jul 20;14:1217449. doi: 10.3389/fmicb.2023.1217449. eCollection 2023.ABSTRACTOxidative stress, inflammatory response, and gut-liver axis dysbiosis have been suggested as the primarily involved in the pathogenesis of alcoholic liver injury. Previous research established that yeast extract (YE) has antioxidant, immune-boosting or microbiota-regulating properties. However, there is currently lack of information regarding the efficacy of YE on alcoholic liver injury. This study seeks to obtain data that will help to address this research gap using a Wistar male rat experimental model. Histologic and biochemical analysis results showed that the groups treated with both low-dose yeast extract (YEL) and high-dose yeast extract (YEH) had lower degrees of alcohol-induced liver injury. The abundance of Peptococcus and Ruminococcus reduced in the low-dose yeast extract (YEL) group, while that of Peptococcus, Romboutsia, Parasutterella, and Faecalibaculum reduced in the high-dose (YEH) group. Furthermore, Spearman analysis showed that the gut microbes were significantly associated with several liver-related indicators. For the analysis of differential metabolites and enriched pathways in the YEL group, the abundance of lysophosphatidylcholine (16:0/0:0) significantly increased, and then the levels of histamine, adenosine and 5' -adenine nucleotide were remarkedly elevated in the YEH group. These findings suggest that both high and low doses of YE can have different protective effects on liver injury in alcoholic liver disease (ALD) rats, in addition to improving gut microbiota disorder. Besides, high-dose YE has been found to be more effective than low-dose YE in metabolic regulation, as well as in dealing with oxidative stress and inflammatory responses.PMID:37547679 | PMC:PMC10399763 | DOI:10.3389/fmicb.2023.1217449

Comput Struct Biotechnol J. 2023 Jul 22;21:3705-3714. doi: 10.1016/j.csbj.2023.07.023. eCollection 2023.ABSTRACTLarge-scale multidimensional cancer genomic and pharmacological profiles have been created by several large consortium projects, including NCI-60, GDSC and DepMap, providing novel opportunities for data mining and further understanding of intrinsic therapeutic response mechanisms. However, it is increasingly challenging for experimental biologists, especially those without a bioinformatic background, to integrate, explore, and analyse these tremendous pharmacogenomics. To address this gap, IMOPAC, an interactive and easy-to-use web-based tool, was introduced to provide rapid visualizations and customizable functionalities on the basis of these three publicly available databases, which may reduce pharmacogenomic profiles from cell lines into readily understandable genetic, epigenetic, transcriptionomic, proteomic, metabolomic, and pharmacological events. The user-friendly query interface together with customized data storage enables users to interactively investigate and visualize multiomics alterations across genes and pathways and to link these alterations with drug responses across cell lines from diverse cancer types. The analyses in our portal include pancancer expression, drug-omics/pathway correlation, cancer subtypes, omics-omics (cis-/trans-regulation) correlation, fusion query analysis, and drug response prediction analysis. The comprehensive multiomics and pharmacogenomic analyses with simple clicking through IMOPAC will significantly benefit cancer precision medicine, contribute to the discoveries of potential biological mechanisms and facilitate pharmacogenomics mining in the identification of clinically actionable biomarkers for both basic researchers and clinical practitioners. IMOPAC is freely available at http://www.hbpding.com/IMOPAC.PMID:37547083 | PMC:PMC10400808 | DOI:10.1016/j.csbj.2023.07.023

bioRxiv. 2023 Jul 25:2023.07.25.550588. doi: 10.1101/2023.07.25.550588. Preprint.ABSTRACTUropathogenic E. coli (UPEC) secrete multiple siderophore types to scavenge extracellular iron(III) ions during clinical urinary tract infections, despite the metabolic costs of biosynthesis. Here we find the siderophore enterobactin and its related products to be prominent components of the iron-responsive extracellular metabolome of a model UPEC strain. Using defined enterobactin biosynthesis and import mutants, we identify lower molecular weight, dimeric exometabolites as products of incomplete siderophore catabolism, rather than prematurely released biosynthetic intermediates. In E. coli, iron acquisition from iron(III)-enterobactin complexes requires intracellular esterases that hydrolyze the siderophore. Although UPEC are equipped to consume the products of completely hydrolyzed enterobactin, we find that enterobactin and its derivatives may be incompletely hydrolyzed to yield products with retained siderophore activity. These results are consistent with catabolic inefficiency as means to obtain more than one iron ion per siderophore molecule. This is compatible with an evolved UPEC strategy to maximize the nutritional returns from metabolic investments in siderophore biosynthesis.PMID:37546885 | PMC:PMC10402112 | DOI:10.1101/2023.07.25.550588

medRxiv. 2023 Jul 27:2023.07.25.23293055. doi: 10.1101/2023.07.25.23293055. Preprint.ABSTRACTMetabolic dysregulation is a hallmark of neurodegenerative diseases, including Alzheimer's disease (AD) and progressive supranuclear palsy (PSP). While metabolic dysregulation is a common link between these two tauopathies, a comprehensive brain metabolic comparison of the diseases has not yet been performed. We analyzed 342 postmortem brain samples from the Mayo Clinic Brain Bank and examined 658 metabolites in the cerebellar cortex and the temporal cortex between the two tauopathies. Our findings indicate that both diseases display oxidative stress associated with lipid metabolism, mitochondrial dysfunction linked to lysine metabolism, and an indication of tau-induced polyamine stress response. However, specific to AD, we detected glutathione-related neuroinflammation, deregulations of enzymes tied to purines, and cognitive deficits associated with vitamin B. Taken together, our findings underscore vast alterations in the brain's metabolome, illuminating shared neurodegenerative pathways and disease-specific traits in AD and PSP.PMID:37546878 | PMC:PMC10402214 | DOI:10.1101/2023.07.25.23293055

bioRxiv. 2023 Jul 25:2023.07.22.550155. doi: 10.1101/2023.07.22.550155. Preprint.ABSTRACTMetabolites, lipids, and glycans are fundamental biomolecules involved in complex biological systems. They are metabolically channeled through a myriad of pathways and molecular processes that define the physiology and pathology of an organism. Here, we present a blueprint for the simultaneous analysis of spatial metabolome, lipidome, and glycome from a single tissue section using mass spectrometry imaging. Complimenting an original experimental protocol, our workflow includes a computational framework called Spatial Augmented Multiomics Interface (Sami) that offers multiomics integration, high dimensionality clustering, spatial anatomical mapping with matched multiomics features, and metabolic pathway enrichment to providing unprecedented insights into the spatial distribution and interaction of these biomolecules in mammalian tissue biology.PMID:37546843 | PMC:PMC10401929 | DOI:10.1101/2023.07.22.550155

Res Sq. 2023 Jul 25:rs.3.rs-2276903. doi: 10.21203/rs.3.rs-2276903/v1. Preprint.ABSTRACTNeuronal activity creates an intense energy demand that must be met by rapid metabolic responses. To investigate metabolic adaptations in the neuron-enriched dentate granule cell (DGC) layer within its native tissue environment, we employed murine acute hippocampal brain slices coupled with fast metabolite preservation, followed by mass spectrometry imaging (MALDI-MSI) to generate spatially resolved metabolomics and isotope tracing data. Here we show that membrane depolarization induces broad metabolic changes, including increased glycolytic activity in DGCs. Increased glucose metabolism in response to stimulation is accompanied by mobilization of endogenous inosine into pentose phosphates, via the action of purine nucleotide phosphorylase (PNP). The PNP reaction is an integral part of the neuronal response to stimulation, as inhibiting PNP leaves DGCs energetically impaired during recovery from strong activation. Performing MSI on brain slices bridges the gap between live cell physiology and the deep chemical analysis enabled by mass spectrometry.PMID:37546759 | PMC:PMC10402263 | DOI:10.21203/rs.3.rs-2276903/v1

bioRxiv. 2023 Jul 24:2023.07.22.550177. doi: 10.1101/2023.07.22.550177. Preprint.ABSTRACTThe impact of temperature on growth is typically considered under heat- or cold-shock conditions that elicit specific regulation. In between, cellular growth rate varies according to the Arrhenius law of thermodynamics. Here, we use growth-rate dynamics during transitions between temperatures to discover how this behavior arises and what determines the temperature sensitivity of growth. Using a device that enables single-cell tracking across a wide range of temperatures, we show that bacteria exhibit a highly conserved, slow response to temperatures upshifts with a time scale of ∼1.5 doublings at the higher temperature, regardless of initial/final temperature or nutrient source. We rule out transcriptional, translational, and membrane reconfiguration as potential mechanisms. Instead, we demonstrate that an autocatalytic enzyme network incorporating temperature-sensitive Michaelis-Menten kinetics recapitulates all temperature-shift dynamics, reveals that import dictates steady-state Arrhenius growth behavior, and successfully predicts alterations in the upshift response observed under simple-sugar or low-nutrient conditions or in fungi. These findings indicate that metabolome rearrangement dictates how temperature affects microbial growth.PMID:37546722 | PMC:PMC10401945 | DOI:10.1101/2023.07.22.550177

Oncoimmunology. 2023 Aug 3;12(1):2240613. doi: 10.1080/2162402X.2023.2240613. eCollection 2023.ABSTRACTAs long as breast cancer (BC) stays under immunosurveillance, it can be controlled by treatments eliciting anticancer immune responses. However, once BC escapes immunosurveillance, it becomes therapeutically uncontrollable. A paper in the Journal for ImmunoTherapy of Cancer describes a new hormone receptor-positive BC cell line generating incurable tumors in C57BL/6 mice.PMID:37546695 | PMC:PMC10402843 | DOI:10.1080/2162402X.2023.2240613

Ecol Evol. 2023 Aug 2;13(8):e10363. doi: 10.1002/ece3.10363. eCollection 2023 Aug.ABSTRACTSeasonal dietary shifts in animals are important strategies for ecological adaptation. An increasing number of studies have shown that seasonal dietary shifts can influence or even determine the composition of gut microbiota. The Turpan wonder gecko, Teratoscincus roborowskii, lives in extreme desert environments and has a flexible dietary shift to fruit-eating in warm seasons. However, the effect of such shifts on the gut microbiota is poorly understood. In this study, 16S rRNA sequencing and LC-MS metabolomics were used to examine changes in the gut microbiota composition and metabolic patterns of T. roborowskii. The results demonstrated that the gut microbes of T. roborowskii underwent significant seasonal changes, and the abundance of phylum level in autumn was significantly higher than spring, but meanwhile, the diversity was lower. At the family level, the abundance and diversity of the gut microbiota were both higher in autumn. Firmicutes, Bacteroidetes, and Proteobacteria were the dominant gut microbes of T. roborowskii. Verrucomicrobia and Proteobacteria exhibited dynamic ebb and flow patterns between spring and autumn. Metabolomic profiling also revealed differences mainly related to the formation of secondary bile acids. The pantothenate and CoA biosynthesis, and lysine degradation pathways identified by KEGG enrichment symbolize the exuberant metabolic capacity of T. roborowskii. Furthermore, strong correlations were detected between metabolite types and bacteria, and this correlation may be an important adaptation of T. roborowskii to cope with dietary shifts and improve energy acquisition. Our study provides a theoretical basis for exploring the adaptive evolution of the special frugivorous behavior of T. roborowskii, which is an important progress in the study of gut microbes in desert lizards.PMID:37546566 | PMC:PMC10396791 | DOI:10.1002/ece3.10363

Front Oncol. 2023 Jul 21;13:1175707. doi: 10.3389/fonc.2023.1175707. eCollection 2023.ABSTRACTIntrahepatic mucinous cholangiocarcinoma (IMCC) is a rare subtype of intrahepatic cholangiocarcinoma (IHCC). Limited data describe the genetic characteristics of IMCC and insights on its pathogenesis are lacking. Here, we employed a multi-omics approach to analyze somatic mutations, transcriptome, proteome and metabolome of tumor tissue obtained from a case of IMCC in order to clarify the pathogenesis of IMCC. A total of 54 somatic mutations were detected, including a G12D mutation in KRAS that is likely to be involved in the onset of IMCC. The genes consistently up-regulated at the transcription level and in the proteome were enriched for mucin and mucopolysaccharide biosynthesis, for cell cycle functions and for inflammatory signaling pathways. The consistently down-regulated genes were enriched in bile synthesis and fatty acid metabolism pathways. Further multi-omics analysis found that mucin synthesis by MUC4 and MUC16 was elevated by up-regulated expression of mesothelin (MSLN). Moreover, transcription factor ONECUT3 was identified that possibly activates the transcription of mucin and mucopolysaccharide biosynthesis in IMCC.PMID:37546424 | PMC:PMC10401833 | DOI:10.3389/fonc.2023.1175707

Front Vet Sci. 2023 Jul 21;10:1212422. doi: 10.3389/fvets.2023.1212422. eCollection 2023.ABSTRACTTo date, no research has been done on energy requirements for yaks in Tibetan cold weather. The findings of the current study provide proper energy requirements for yaks would facilitate scientific feeding of fattening yaks in cold weather. The metabolomics and 16s rRNA sequencing technologies were used to explore the underlying mechanism that affects the growth performance of yaks fed with different energy levels of diet in cold weather. Three groups of yaks (141.7 ± 3.34 kg) were fed with diets containing metabolizable energy 7.20, 7.89, and 8.58 MJ/kg DM (dry matter) and named the low-, medium-, and high-energy groups, respectively. The results showed that the average daily feed intake of the high-energy group was higher than that of the low-energy group (p = 0.006). Plasma aspartate aminotransferase (p = 0.004), alanine aminotransferase (p < 0.001), and interferon-γ (p < 0.001) in the high-energy group were lower than in the low-energy group. In contrast, superoxide dismutase (p < 0.001), immunoglobulin G (p < 0.001), and interleukin 2 (p = 0.002) were higher than the low-energy group. The rumen microbial protein (p = 0.025), total volatile fatty acids (p = 0.029), and neutral detergent fiber digestibility (p = 0.050) in the high-energy group were higher than in the low-energy group, whereas the acetate: propionate ratio (p = 0.001) and ammonium nitrogen (p = 0.001) were lower than in the low-energy group. The plasma metabolomics results displayed that yaks fed with a high-energy diet augmented the metabolism of arginine, proline, purine, taste transduction, pyrimidine, and glutathione pathways. The relative abundance of Methanobrevibacter in the high-energy group was lower (p < 0.001), whereas the relative abundance of Methanosphaera (p < 0.001) was higher than in the low-energy group. The results of the current study suggest that a high-energy diet in growing yaks during the cold season can improve growth performance, rumen microbial protein synthesis, antioxidants, and immunity.PMID:37546339 | PMC:PMC10402921 | DOI:10.3389/fvets.2023.1212422

Front Plant Sci. 2023 Jul 21;14:1210146. doi: 10.3389/fpls.2023.1210146. eCollection 2023.ABSTRACTMetabolite genome-wide association studies (mGWASs) are increasingly used to discover the genetic basis of target phenotypes in plants such as Populus trichocarpa, a biofuel feedstock and model woody plant species. Despite their growing importance in plant genetics and metabolomics, few mGWASs are experimentally validated. Here, we present a functional genomics workflow for validating mGWAS-predicted enzyme-substrate relationships. We focus on uridine diphosphate-glycosyltransferases (UGTs), a large family of enzymes that catalyze sugar transfer to a variety of plant secondary metabolites involved in defense, signaling, and lignification. Glycosylation influences physiological roles, localization within cells and tissues, and metabolic fates of these metabolites. UGTs have substantially expanded in P. trichocarpa, presenting a challenge for large-scale characterization. Using a high-throughput assay, we produced substrate acceptance profiles for 40 previously uncharacterized candidate enzymes. Assays confirmed 10 of 13 leaf mGWAS associations, and a focused metabolite screen demonstrated varying levels of substrate specificity among UGTs. A substrate binding model case study of UGT-23 rationalized observed enzyme activities and mGWAS associations, including glycosylation of trichocarpinene to produce trichocarpin, a major higher-order salicylate in P. trichocarpa. We identified UGTs putatively involved in lignan, flavonoid, salicylate, and phytohormone metabolism, with potential implications for cell wall biosynthesis, nitrogen uptake, and biotic and abiotic stress response that determine sustainable biomass crop production. Our results provide new support for in silico analyses and evidence-based guidance for in vivo functional characterization.PMID:37546246 | PMC:PMC10402742 | DOI:10.3389/fpls.2023.1210146

World J Gastroenterol. 2023 Jul 21;29(27):4252-4270. doi: 10.3748/wjg.v29.i27.4252.ABSTRACTChronic and recurrent inflammatory disorders of the gastrointestinal tract caused by a complex interplay between genetics and intestinal dysbiosis are called inflammatory bowel disease. As a result of the interaction between the liver and the gut microbiota, bile acids are an atypical class of steroids produced in mammals and traditionally known for their function in food absorption. With the development of genomics and metabolomics, more and more data suggest that the pathophysiological mechanisms of inflammatory bowel disease are regulated by bile acids and their receptors. Bile acids operate as signalling molecules by activating a variety of bile acid receptors that impact intestinal flora, epithelial barrier function, and intestinal immunology. Inflammatory bowel disease can be treated in new ways by using these potential molecules. This paper mainly discusses the increasing function of bile acids and their receptors in inflammatory bowel disease and their prospective therapeutic applications. In addition, we explore bile acid metabolism and the interaction of bile acids and the gut microbiota.PMID:37545642 | PMC:PMC10401658 | DOI:10.3748/wjg.v29.i27.4252

Oncol Lett. 2023 Jul 4;26(2):358. doi: 10.3892/ol.2023.13944. eCollection 2023 Aug.ABSTRACTColorectal cancer (CRC) is one of the leading global malignancies with low 5-year survival and high mortality rates. Despite extensive research, the precise role of gut metabolites in CRC development and clinical outcomes remains unclear, while its elucidation may aid the development of improved clinical diagnosis and treatment options. In the present study, targeted metabolomic analysis was conducted on fecal samples from 35 patients with CRC, 37 patients with colorectal adenoma and 30 healthy controls (HC) to identify metabolite biomarkers. Using orthogonal partial least squares discriminant analysis, metabolomic features distinguishing the three groups were identified. Receiver operating characteristic (ROC) curve analysis was used to assess diagnostic utility for distinguishing CRC from HC. The association of gut metabolites with survival in patients with CRC was also analyzed by comparing short-term survivors (STS) and long-term survivors (LTS), and the prognostic ability of metabolites was predicted using Cox regression and Kaplan-Meier analysis. The results of the current study showed that the enriched pathways in CRC included 'caffeine metabolism', 'thiamine metabolism', 'phenylalanine, tyrosine and tryptophan biosynthesis' and 'phenylalanine metabolism'. ROC analysis found that 9,10-dihydroxy-12-octadecenoic acid, cholesterol ester (18:2) and lipoxinA4 distinguished CRC from HC. Joint quantification of these three metabolites resulted in an area under the ROC curve of 0.969 in the diagnosis of CRC. The analysis of the current study also showed that the expression of metabolites involved in 'sphingolipid metabolism' was mainly dysregulated in LTS and STS, while N-acetylmannosamine and 2,5-dihydroxybenzaldehyde were associated with better overall survival. In conclusion, the present study provided preliminary insight into the metabolic changes associated with CRC and may have important implications for the development of future diagnostic and treatment strategies.PMID:37545617 | PMC:PMC10398631 | DOI:10.3892/ol.2023.13944

Front Nutr. 2023 Jul 20;10:1121203. doi: 10.3389/fnut.2023.1121203. eCollection 2023.ABSTRACTBACKGROUND/AIMS: Some studies showed that probiotics could improve the composition and structure of gut microbiota. Changes in the gut microbiota may alter bile acid (BAs) composition and kinetics, improving non-alcoholic fatty liver disease (NAFLD). However, it still needs to be clarified how probiotics improve both the metabolism of BAs and NAFLD. This study aimed to reveal the regulatory mechanisms of cholesterol-lowering (CL) probiotics on NAFLD from aspects involved in BA metabolism in FXR gene knockout (FXR-/-) mice.METHODS: FXR-/- male mice were randomly divided into three groups based on different interventions for 16 weeks, including normal diet (ND), high-fat diet (HFD), and probiotic intervention in the HFD (HFD+P) group. 16s rDNA sequencing and ultrahigh performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) were utilized to analyze the changes in gut microbiota and fecal bile acids in mice.RESULTS: We found that the intervention of the CL probiotics improved liver lipid deposition and function in HFD-induced NAFLD mice by decreasing the levels of total cholesterol (TC; p = 0.002) and triglyceride (TG; p = 0.001) in serum, as well as suppressing liver inflammation, such as interleukin-1 beta (IL-1β; p = 0.002) and tumor necrosis factor-alpha (TNF-α; p < 0.0001). 16S rDNA sequencing and metabolomic analyses showed that probiotics effectively reduced the abundance of harmful gut microbiota, such as Firmicutes (p = 0.005), while concomitantly increasing the abundance of beneficial gut microbiota in NAFLD mice, such as Actinobacteriota (p = 0.378), to improve NAFLD. Compared with the ND group, consuming an HFD elevated the levels of total BAs (p = 0.0002), primary BAs (p = 0.017), and secondary BAs (p = 0.0001) in mice feces, while the intervention with probiotics significantly reduced the increase in the levels of fecal total bile acids (p = 0.013) and secondary bile acids (p = 0.017) induced by HFD.CONCLUSION: The CL probiotics were found to improve liver function, restore microbiota balance, correct an abnormal change in the composition and content of fecal bile acids, and repair the damaged intestinal mucosal barrier in mice with NAFLD, ultimately ameliorating the condition. These results suggested that CL probiotics may be a promising and health-friendly treatment option for NAFLD.PMID:37545590 | PMC:PMC10397539 | DOI:10.3389/fnut.2023.1121203