PubMed

Radiol Imaging Cancer. 2024 Mar;6(2):e230056. doi: 10.1148/rycan.230056.ABSTRACTPurpose To characterize the metabolomic profiles of two hepatocellular carcinoma (HCC) rat models, track evolution of these profiles to a stimulated tumor state, and assess their effect on lactate flux with hyperpolarized (HP) carbon 13 (13C) MRI. Materials and Methods Forty-three female adult Fischer rats were implanted with N1S1 or McA-RH7777 HCC tumors. In vivo lactate-to-pyruvate ratio (LPR) was measured with HP 13C MRI at 9.4 T. Ex vivo mass spectrometry was used to measure intratumoral metabolites, and Ki67 labeling was used to quantify proliferation. Tumors were first compared with three normal liver controls. The tumors were then compared with stimulated variants via off-target hepatic thermal ablation treatment. All comparisons were made using the Mann-Whitney test. Results HP 13C pyruvate MRI showed greater LPR in N1S1 tumors compared with normal liver (mean [SD], 0.564 ± 0.194 vs 0.311 ± 0.057; P < .001 [n = 9]), but not for McA-RH7777 (P = .44 [n = 8]). Mass spectrometry confirmed that the glycolysis pathway was increased in N1S1 tumors and decreased in McA-RH7777 tumors. The pentose phosphate pathway was also decreased only in McA-RH7777 tumors. Increased proliferation in stimulated N1S1 tumors corresponded to a net increase in LPR (six stimulated vs six nonstimulated, 0.269 ± 0.148 vs 0.027 ± 0.08; P = .009), but not in McA-RH7777 (eight stimulated vs six nonstimulated, P = .13), despite increased proliferation and metastases. Mass spectrometry demonstrated relatively increased lactate production with stimulation in N1S1 tumors only. Conclusion Two HCC subtypes showed divergent glycolytic dependency at baseline and during transformation to a high proliferation state. This metabolic heterogeneity in HCC should be considered with use of HP 13C MRI for diagnosis and tracking. Keywords: Molecular Imaging-Probe Development, Liver, Abdomen/GI, Oncology, Hepatocellular Carcinoma © RSNA, 2024 See also commentary by Ohliger in this issue.PMID:38426887 | DOI:10.1148/rycan.230056

Microbiol Spectr. 2024 Mar 1:e0413823. doi: 10.1128/spectrum.04138-23. Online ahead of print.ABSTRACTChemistry in eukaryotic intercellular spaces is shaped by both hosts and symbiotic microorganisms such as bacteria. Pathogenic microorganisms like barley-associated Xanthomonas translucens (Xt) swiftly overtake the inner leaf tissue becoming the dominant microbial community member during disease development. The dynamic metabolic changes due to Xt pathogenesis in the mesophyll spaces remain unknown. Genomic group I of Xt consists of two barley-infecting lineages: pathovar translucens (Xtt) and pathovar undulosa (Xtu). Xtu and Xtt, although genomically distinct, cause similar water-soaked lesions. To define the metabolic signals associated with inner leaf colonization, we used untargeted metabolomics to characterize Xtu and Xtt metabolism signatures associated with mesophyll growth. We found that mesophyll apoplast fluid from infected tissue yielded a distinct metabolic profile and shift from catabolic to anabolic processes over time compared to water-infiltrated control. The pathways with the most differentially expressed metabolites by time were glycolysis, tricarboxylic acid cycle, sucrose metabolism, pentose interconversion, amino acids, galactose, and purine metabolism. Hierarchical clustering and principal component analysis showed that metabolic changes were more affected by the time point rather than the individual colonization of the inner leaves by Xtt compared to Xtu. Overall, in this study, we identified metabolic pathways that explain carbon and nitrogen usage during host-bacterial interactions over time for mesophyll tissue colonization. This foundational research provides initial insights into shared metabolic strategies of inner leaf colonization niche occupation by related but phylogenetically distinct phyllosphere bacteria.IMPORTANCE: The phyllosphere is a habitat for microorganisms including pathogenic bacteria. Metabolic shifts in the inner leaf spaces for most plant-microbe interactions are unknown, especially for Xanthomonas species in understudied plants like barley (Hordeum vulgare). Xanthomonas translucens pv. translucens (Xtt) and Xanthomonas translucens pv. undulosa (Xtu) are phylogenomically distinct, but both colonize barley leaves for pathogenesis. In this study, we used untargeted metabolomics to shed light on Xtu and Xtt metabolic signatures. Our findings revealed a dynamic metabolic landscape that changes over time, rather than exhibiting a pattern associated with individual pathovars. These results provide initial insights into the metabolic mechanisms of X. translucens inner leaf pathogenesis.PMID:38426767 | DOI:10.1128/spectrum.04138-23

Chem Biodivers. 2024 Mar 1:e202301779. doi: 10.1002/cbdv.202301779. Online ahead of print.ABSTRACTPlant-insect interactions are a driving force into ecosystem evolution and community dynamics. Many insect herbivores enter diapause, a developmental arrest stage in anticipation of adverse conditions, to survive and thrive through seasonal changes. Herein, we investigated the roles of medium- to non-polar metabolites during larval development and diapause in a specialist insect herbivore, Chlosyne lacinia, reared on Aldama robusta leaves. Varying metabolites were determined using gas chromatography-mass spectrometry (GC-MS)-based metabolomics. Sesquiterpenes and steroids were the main metabolites putatively identified in A. robusta leaves, whereas C. lacinia caterpillars were characterized by triterpenes, steroids, fatty acids, and long-chain alkanes. We found out that C. lacinia caterpillars biosynthesized most of the identified steroids and fatty acids from plant-derived ingested metabolites, as well as all triterpenes and long-chain alkanes. Steroids, fatty acids, and long-chain alkanes were detected across all C. lacinia instars and in diapausing caterpillars. Sesquiterpenes and triterpenes were also detected across larval development, yet they were not detected in diapausing caterpillars, which suggested that these metabolites were converted to other molecules prior to the diapause stage. Our findings shed light on the chemical content variation across C. lacinia development and diapause, providing insights into the roles of metabolites in plant-insect interactions.PMID:38426669 | DOI:10.1002/cbdv.202301779

Brief Bioinform. 2024 Jan 22;25(2):bbae056. doi: 10.1093/bib/bbae056.ABSTRACTAccurate metabolite annotation and false discovery rate (FDR) control remain challenging in large-scale metabolomics. Recent progress leveraging proteomics experiences and interdisciplinary inspirations has provided valuable insights. While target-decoy strategies have been introduced, generating reliable decoy libraries is difficult due to metabolite complexity. Moreover, continuous bioinformatics innovation is imperative to improve the utilization of expanding spectral resources while reducing false annotations. Here, we introduce the concept of ion entropy for metabolomics and propose two entropy-based decoy generation approaches. Assessment of public databases validates ion entropy as an effective metric to quantify ion information in massive metabolomics datasets. Our entropy-based decoy strategies outperform current representative methods in metabolomics and achieve superior FDR estimation accuracy. Analysis of 46 public datasets provides instructive recommendations for practical application.PMID:38426325 | DOI:10.1093/bib/bbae056

Circ Heart Fail. 2024 Mar 1:e010896. doi: 10.1161/CIRCHEARTFAILURE.123.010896. Online ahead of print.ABSTRACTBACKGROUND: Older adults have markedly increased risks of heart failure (HF), specifically HF with preserved ejection fraction (HFpEF). Identifying novel biomarkers can help in understanding HF pathogenesis and improve at-risk population identification. This study aimed to identify metabolites associated with incident HF, HFpEF, and HF with reduced ejection fraction and examine risk prediction in older adults.METHODS: Untargeted metabolomic profiling was performed in Black and White adults from the ARIC study (Atherosclerosis Risk in Communities) visit 5 (n=3719; mean age, 75 years). We applied Cox regressions to identify metabolites associated with incident HF and its subtypes. The metabolite risk score (MRS) was constructed and examined for associations with HF, echocardiographic measures, and HF risk prediction. Independent samples from visit 3 (n=1929; mean age, 58 years) were used for replication.RESULTS: Sixty metabolites (hazard ratios range, 0.79-1.49; false discovery rate, <0.05) were associated with incident HF after adjusting for clinical risk factors, eGFR, and NT-proBNP (N-terminal pro-B-type natriuretic peptide). Mannonate, a hydroxy acid, was replicated (hazard ratio, 1.36 [95% CI, 1.19-1.56]) with full adjustments. MRS was associated with an 80% increased risk of HF per SD increment, and the highest MRS quartile had 8.7× the risk of developing HFpEF than the lowest quartile. High MRS was also associated with unfavorable values of cardiac structure and function. Adding MRS over clinical risk factors and NT-proBNP improved 5-year HF risk prediction C statistics from 0.817 to 0.850 (∆C, 0.033 [95% CI, 0.017-0.047]). The association between MRS and incident HF was replicated after accounting for clinical risk factors (P<0.05).CONCLUSIONS: Novel metabolites associated with HF risk were identified, elucidating disease pathways, specifically HFpEF. An MRS was associated with HF risk and improved 5-year risk prediction in older adults, which may assist at at-risk population identification.PMID:38426319 | DOI:10.1161/CIRCHEARTFAILURE.123.010896

Circ Heart Fail. 2024 Mar 1:e011482. doi: 10.1161/CIRCHEARTFAILURE.124.011482. Online ahead of print.NO ABSTRACTPMID:38426300 | DOI:10.1161/CIRCHEARTFAILURE.124.011482

Obesity (Silver Spring). 2024 Mar 1. doi: 10.1002/oby.23989. Online ahead of print.ABSTRACTOBJECTIVE: Big Data are increasingly used in obesity and nutrition research to gain new insights and derive personalized guidance; however, this data in raw form are often not usable. Substantial preprocessing, which requires machine learning (ML), human judgment, and specialized software, is required to transform Big Data into artificial intelligence (AI)- and ML-ready data. These preprocessing steps are the most complex part of the entire modeling pipeline. Understanding the complexity of these steps by the end user is critical for reducing misunderstanding, faulty interpretation, and erroneous downstream conclusions.METHODS: We reviewed three popular obesity/nutrition Big Data sources: microbiome, metabolomics, and accelerometry. The preprocessing pipelines, specialized software, challenges, and how decisions impact final AI- and ML-ready products were detailed.RESULTS: Opportunities for advances to improve quality control, speed of preprocessing, and intelligent end user consumption were presented.CONCLUSIONS: Big Data have the exciting potential for identifying new modifiable factors that impact obesity research. However, to ensure accurate interpretation of conclusions arising from Big Data, the choices involved in preparing AI- and ML-ready data need to be transparent to investigators and clinicians relying on the conclusions.PMID:38426232 | DOI:10.1002/oby.23989

Front Neurol. 2024 Feb 15;15:1298385. doi: 10.3389/fneur.2024.1298385. eCollection 2024.ABSTRACTOBJECTIVE: Metabolomics has found extensive applications in the field of neurological diseases, significantly contributing to their diagnosis and treatment. However, there has been limited research applying metabolomics to moyamoya disease (MMD). This study aims to investigate and identify differential metabolites associated with MMD.METHODS: We employed a liquid chromatography coupled with mass spectrometry (LC-MS) approach, complemented by univariate and multivariate analyses, to discern metabolic biomarkers in cerebrospinal fluid samples. We then compared these biomarkers between MMD patients and healthy controls (Ctl).RESULTS: Sixteen patients diagnosed with MMD via cerebral angiography and eight healthy controls were enrolled in this study. Comparative analyses, including univariate and multivariate analyses, correlation studies, heatmaps, Volcano Plots, and KEGG pathway enrichment, were performed between MMD patients and controls. As a result, we identified 129 significant differential metabolites in the cerebrospinal fluid between MMD patients and controls. These metabolic biomarkers are associated with various pathways, with notable involvement in purine and pyrimidine metabolism.CONCLUSION: Utilizing an LC-MS-based metabolomics approach holds promise for enhancing the clinical diagnosis of MMD. The identified biomarkers offer potential avenues for the development of novel diagnostic methods for MMD and offer fresh insights into the pathogenesis of the disease.PMID:38426176 | PMC:PMC10902010 | DOI:10.3389/fneur.2024.1298385

Front Microbiol. 2024 Feb 15;15:1334045. doi: 10.3389/fmicb.2024.1334045. eCollection 2024.ABSTRACTThe purpose of this research was to investigate the impact of dietary supplementation of Caragana korshinskii tannin (CKT) on rumen fermentation, methane emission, methanogen community and metabolome in rumen of sheep. A total of 15 crossbred sheep of the Dumont breed with similar body conditions, were divided into three groups (n = 5), which were fed with CKT addition at 0, 2 and 4%/kg DM. The study spanned a total of 74 days, with a 14-day period dedicated to adaptation and a subsequent 60-day period for conducting treatments. The results indicated that the levels of ammonia nitrogen (NH3-N) and acetate were reduced (p < 0.05) in rumen sheep fed with 2 and 4% CKT; The crude protein (CP) digestibility of sheep in 2 and 4% CKT groups was decreased(p < 0.05); while the neutral detergent fiber (NDF) digestibility was increased (p < 0.05) in 4% CKT group. Furthermore, the supplementation of CKT resulted in a decrease (p < 0.05) in daily CH4 emissions from sheep by reducing the richness and diversity of ruminal methanogens community, meanwhile decreasing (p < 0.05) concentrations of tyramine that contribute to methane synthesis and increasing (p < 0.05) concentrations of N-methy-L-glutamic acid that do not contribute to CH4 synthesis. However, CH4 production of DMI, OMI, NDFI and metabolic weight did not differ significantly across the various treatments. To sum up, the addition of 4% CKT appeared to be a viable approach for reducing CH4 emissions from sheep without no negative effects. These findings suggest that CKT hold promise in mitigating methane emissions of ruminant. Further investigation is required to evaluate it effectiveness in practical feeding strategies for livestock.PMID:38426060 | PMC:PMC10902071 | DOI:10.3389/fmicb.2024.1334045

Front Microbiol. 2024 Feb 16;15:1382290. doi: 10.3389/fmicb.2024.1382290. eCollection 2024.ABSTRACT[This corrects the article DOI: 10.3389/fmicb.2023.1197970.].PMID:38426055 | PMC:PMC10904077 | DOI:10.3389/fmicb.2024.1382290

Front Pain Res (Lausanne). 2024 Feb 15;5:1343551. doi: 10.3389/fpain.2024.1343551. eCollection 2024.ABSTRACTNewborns admitted to the neonatal intensive care unit (NICU) regularly undergo painful procedures and may face various painful conditions such as postoperative pain. Optimal management of pain in these vulnerable preterm and term born neonates is crucial to ensure their comfort and prevent negative consequences of neonatal pain. This entails accurate and timely identification of pain, non-pharmacological pain treatment and if needed administration of analgesic therapy, evaluation of treatment effectiveness, and monitoring of adverse effects. Despite the widely recognized importance of pain management, pain assessment in neonates has thus far proven to be a challenge. As self-report, the gold standard for pain assessment, is not possible in neonates, other methods are needed. Several observational pain scales have been developed, but these often rely on snapshot and largely subjective observations and may fail to capture pain in certain conditions. Incorporation of biomarkers alongside observational pain scores holds promise in enhancing pain assessment and, by extension, optimizing pain treatment and neonatal outcomes. This review explores the possibilities of integrating biomarkers in pain assessment in the NICU.PMID:38426011 | PMC:PMC10902154 | DOI:10.3389/fpain.2024.1343551

Mol Genet Metab Rep. 2024 Feb 23;39:101066. doi: 10.1016/j.ymgmr.2024.101066. eCollection 2024 Jun.ABSTRACTMitochondrial malate dehydrogenase 2 (MDH2) is crucial to cellular energy generation through direct participation in the tricarboxylic acid (TCA) cycle and the malate aspartate shuttle (MAS). Inherited MDH2 deficiency is an ultra-rare metabolic disease caused by bi-allelic pathogenic variants in the MDH2 gene, resulting in early-onset encephalopathy, psychomotor delay, muscular hypotonia and frequent seizures. Currently, there is no cure for this devastating disease. We recently reported symptomatic improvement of a three-year-old girl with MDH2 deficiency following treatment with the triglyceride triheptanoin. Here, we aimed to better characterize this disease and improve our understanding of the potential utility of triheptanoin treatment. Using fibroblasts derived from this patient, we generated induced pluripotent stem cells (hiPSCs) and differentiated them into hepatocytes (hiPSC-Heps). Characterization of patient-derived hiPSCs and hiPSC-Heps revealed significantly reduced MDH2 protein expression. Untargeted proteotyping of hiPSC-Heps revealed global dysregulation of mitochondrial proteins, including upregulation of TCA cycle and fatty acid oxidation enzymes. Metabolomic profiling confirmed TCA cycle and MAS dysregulation, and demonstrated normalization of malate, fumarate and aspartate following treatment with the triheptanoin components glycerol and heptanoate. Taken together, our results provide the first patient-derived hiPSC-Hep-based model of MDH2 deficiency, confirm altered TCA cycle function, and provide further evidence for the implementation of triheptanoin therapy for this ultra-rare disease.SYNOPSIS: This study reveals altered expression of mitochondrial pathways including the tricarboxylic acid cycle and changes in metabolite profiles in malate dehydrogenase 2 deficiency and provides the molecular basis for triheptanoin treatment in this ultra-rare disease.PMID:38425868 | PMC:PMC10900122 | DOI:10.1016/j.ymgmr.2024.101066

Front Nutr. 2024 Feb 15;11:1340735. doi: 10.3389/fnut.2024.1340735. eCollection 2024.ABSTRACTINTRODUCTION: Obesity is prevalent with the adult population in the United States. Energy-dense diets and erratic eating behavior contribute to obesity. Time-restricted eating is a dietary strategy in humans that has been advanced to reduce the propensity for obesity. We hypothesized that time-restricted feeding (TRF) would improve metabolic flexibility and normalize metabolic function in adult mice with established excess adiposity.METHODS: Male C57BL/6NHsd mice were initially fed a high-fat diet (HFD) for 12 weeks to establish excess body adiposity, while control mice were fed a normal diet. Then, the HFD-fed mice were assigned to two groups, either ad libitum HFD or TRF of the HFD in the dark phase (12 h) for another 12 weeks.RESULTS AND DISCUSSION: Energy intake and body fat mass were similar in TRF and HFD-fed mice. TRF restored rhythmic oscillations of respiratory exchange ratio (RER), which had been flattened by the HFD, with greater RER amplitude in the dark phase. Insulin sensitivity was improved and plasma cholesterol and hepatic triacylglycerol were decreased by TRF. When compared to HFD, TRF decreased transcription of circadian genes Per1 and Per2 and genes encoding lipid metabolism (Acaca, Fads1, Fads2, Fasn, Scd1, and Srebf1) in liver. Metabolomic analysis showed that TRF created a profile that was distinct from those of mice fed the control diet or HFD, particularly in altered amino acid profiles. These included aminoacyl-tRNA-biosynthesis, glutathione metabolism, and phenylalanine, tyrosine, and tryptophan biosynthesis pathways. In conclusion, TRF improved metabolic function in adult mice with excess adiposity. This improvement was not through a reduction in body fat mass but through the restoration of metabolic flexibility.PMID:38425486 | PMC:PMC10902009 | DOI:10.3389/fnut.2024.1340735

Front Nutr. 2024 Feb 15;11:1335242. doi: 10.3389/fnut.2024.1335242. eCollection 2024.ABSTRACTTryptophan is an essential amino acid and is the precursor of many important metabolites and neurotransmitters. In malnutrition, the availability of tryptophan is reduced, potentially putting patients at increased risks. Herein, we investigated the prognostic implications of the tryptophan metabolism in a secondary analysis of the Effect of Early Nutritional Support on Frailty, Functional Outcomes, and Recovery of Malnourished Medical Inpatients Trial (EFFORT), a randomized, controlled trial comparing individualized nutritional support to usual care in patients at risk for malnutrition. Among 238 patients with available measurements, low plasma levels of metabolites were independently associated with 30-day mortality with adjusted hazard ratios (HR) of 1.77 [95% CI 1.05-2.99, p 0.034] for tryptophan, 3.49 [95% CI 1.81-6.74, p < 0.001] for kynurenine and 2.51 [95% CI 1.37-4.63, p 0.003] for serotonin. Nutritional support had more beneficial effects on mortality in patients with high tryptophan compared to patients with low tryptophan levels (adjusted HR 0.61 [95% CI 0.29-1.29] vs. HR 1.72 [95% CI 0.79-3.70], p for interaction 0.047). These results suggest that sufficient circulating levels of tryptophan might be a metabolic prerequisite for the beneficial effect of nutritional interventions in this highly vulnerable patient population.PMID:38425485 | PMC:PMC10902466 | DOI:10.3389/fnut.2024.1335242

Curr Dev Nutr. 2024 Feb 1;8(3):102087. doi: 10.1016/j.cdnut.2024.102087. eCollection 2024 Mar.ABSTRACTBACKGROUND: Water is vital for humans' survival and general health, which is involved in various metabolic activities.OBJECTIVES: The aim of this study was to investigate the variation in urine metabolome and associated metabolic pathways among people with different hydration states.METHODS: A metabolomic analysis was conducted using 24-h urine samples collected during a cross-sectional study on fluid intake behavior from December 9 to 11, 2021, in Hebei, China. Subjects were divided into the optimal hydration (OH, ≤500 mOsm/kg, n = 21), middle hydration (500-800 mOsm/kg, n = 33), and hypohydration groups (HH, >800 mOsm/kg, n = 13) based on the 3-d average 24-h urine osmolality. Collected 24-h urine samples from 67 subjects (43 males and 34 females) were analyzed for urine metabolome using liquid chromatography-MS.RESULTS: The untargeted metabolomic analysis yielded 1055 metabolites by peak intensities. Integrating the results of the orthogonal projections to latent structures discriminant analysis and fold change test, 115 differential metabolites between the OH and HH groups, including phospholipids (PLs) and lysophospholipids, were identified. Among the 115 metabolites identified as differential metabolites, 85 were recorded by the Human Metabolome Database and uploaded to the Kyoto Encyclopedia of Genes and Genomes databases for pathway analysis. Twenty-one metabolic pathways were recognized. Phenylalanine metabolism (0.50, P = 0.007), phenylalanine, tyrosine, and tryptophan biosynthesis (0.50, P = 0.051), glycerophospholipid metabolism (0.31, P < 0.001), sphingolipid metabolism (0.27, P = 0.029), and cysteine and methionine metabolism (0.10, P = 0.066) had the leading pathway impacts.CONCLUSIONS: We found variations in the urinary PLs and amino acids among subjects with different hydration states. Pathways associated with these differential metabolites could further impact various physiologic and pathologic functions. A more comprehensive and in-depth investigation of the physiologic and pathologic impact of the hydration state and the underlying mechanisms to elucidate and advocate optimal fluid intake habits is needed.This trial was registered at Chinese Clinical Trial Registry as ChiCTR2100045268.PMID:38425438 | PMC:PMC10904166 | DOI:10.1016/j.cdnut.2024.102087

J Ethnopharmacol. 2024 Feb 27:117990. doi: 10.1016/j.jep.2024.117990. Online ahead of print.ABSTRACTETHNOPHARMACOLOGICAL RELEVANCE: Banxia Xiexin decoction (BXD) is a classic traditional Chinese medicine prescription for treating ulcerative colitis (UC). However, its potential mechanism of action is still unclear.AIM OF THE STUDY: Reveal the correlation between the beneficial impacts of BXD on UC and the composition of the gut microbiota.MATERIALS AND METHODS: The major constituents of BXD were identified using the HPLC-DAD technique. An experimental model of UC was induced in male C57BL/6 mice by administering dextran sodium sulfate (DSS). A total of 48 mice were divided into different groups, including control, model, high-dose BXD treatment, medium-dose BXD treatment, low-dose BXD treatment, and a group treated with 5-amino acid salicylic acid (5-ASA). Body weight changes and disease activity index (DAI) scores were documented; colon length, colon index, spleen index, and thymus index scores were determined; myeloperoxidase (MPO) and tumor necrosis factor-α (TNF-α) activities were assessed; and histological staining with hematoxylin-eosin and alcian blue/phosphate Schiff was performed. The immunofluorescence technique was employed to examine the presence of ZO-1 and occludin in the colon tissue. 16S rRNA sequencing was employed to assess the gut microbiota's diversity and metabolomics was utilized to examine alterations in metabolites within the gut microbiota. The impact of BXD on the gut microbiota was confirmed through fecal microbiota transplantation (FMT).RESULTS: BXD exhibited a positive impact on UC mice, particularly in the high-dose BXD treatment group. The BXD group experienced weight recovery, decreased DAI scores, improved colon length, and restored of spleen and thymus index scores compared to the DSS group. Additionally, BXD alleviated colon damage and the inflammatory response while restoring intestinal barrier function. FMT in BXD-treated mice also showed therapeutic effects in UC mice. At the phylum level, the relative abundance of Desulfobacterota, Deferribacterota and Actinobacteriota increased; at the genus level, g__norank__f__Muribaculaceae, Dubosiella, Akkermansia, and Lactobacillus increased, whereas Faecalibaculum, Alloprevotella, Turicibacter, and g_Paraprevotella decreased. g__norank_f__Muribaculaceae was positively correlated with body weight and colon length and negatively with colon index scores, splenic index scores, and MPO levels; Alloprevotella was positively correlated with splenic index scores, histological scores, and TNF-α levels and negatively with thymus index scores and thymus index scores. Faecalibaculum was positively correlated with colon index scores and MPO levels. Metabolic investigations revealed 58 potential indicators, primarily associated with the metabolism of amino acids, purines, and lipids. Alloprevotella, g_Paraprevotella, and Bifidobacterium were strongly associated with metabolic pathways.CONCLUSION: BXD showed beneficial therapeutic effects in UC mice. The mechanism may be by promoting the balance and variety of gut microbiota, as well as regulating the metabolism of amino acids, purines, and lipids.PMID:38423412 | DOI:10.1016/j.jep.2024.117990

Cell Mol Gastroenterol Hepatol. 2024 Feb 27:S2352-345X(24)00042-0. doi: 10.1016/j.jcmgh.2024.02.014. Online ahead of print.ABSTRACTBACKGROUND AND AIMS: As the most abundant memory T cells and major source of tumor necrosis factor α (TNF-α) in the intestinal mucosa of Crohn's disease (CD) patients, CD4+ tissue-resident memory T (TRM) cells play a critical role in CD pathogenesis. We investigated the role of metabolic reprogramming in the regulation of proinflammatory and apoptosis-resistant phenotype for CD4+ TRM cells.METHODS: CD4+ TRM cells were collected from intestinal resection tissues from control and CD patients. Transcriptomic and metabolomic analysis were performed to identify metabolic characteristics of CD4+ TRM cells. ELISA and qPCR experiments were utilized to assess cytokines level in CD4+ TRM cells, activation-induced cell apoptosis (AICD) rate was evaluated by flow cytometry. Transwell assay and wound healing assay were performed to detect the effect of CD4+ TRM cells on the migration of normal intestinal epithelial cells.RESULTS: Transcriptomic data combined with unbiased metabolomic analysis revealed an increased fatty acid oxidation (FAO) phenotype existed in CD4+ TRM cells from CD patients. The lipidomic data and stable isotope tracer experiments demonstrated that CD4+ TRM cells upregulated their lipid lipolysis and fatty acid uptake to fuel FAO in CD patients. Mechanistically, the activated NF-κB signaling increased transcription of genes involved in lipid lipolysis, fatty acid uptake and oxidation in CD4+ TRM cells from CD patients. Targeting FAO of CD4+ TRM cells reversed their apoptosis-resistant and proinflammatory phenotype in CD Patients.CONCLUSION: CD4+ TRM cells process an accelerated FAO mediated by activated NF-κB signaling in CD patients, targeting FAO could reverse their apoptosis-resistant and proinflammatory phenotype. These findings shed a new light on the pathogenic mechanism investigation and novel therapy development in CD patients.PMID:38423357 | DOI:10.1016/j.jcmgh.2024.02.014

Sci Total Environ. 2024 Feb 27:171335. doi: 10.1016/j.scitotenv.2024.171335. Online ahead of print.ABSTRACTGiven the widespread presence of Pseudomonas aeruginosa in water and its threat to human health, the metabolic changes in Pseudomonas aeruginosa when exposed to polystyrene microplastics (PS-MPs) exposure were studied, focusing on molecular level. Through non-targeted metabolomics, a total of 64 differential metabolites were screened out under positive ion mode and 44 under negative ion mode. The content of bacterial metabolites changed significantly, primarily involving lipids, nucleotides, amino acids, and organic acids. Heightened intracellular oxidative damage led to a decrease in lipid molecules and nucleotide-related metabolites. The down-regulation of amino acid metabolites, such as L-Glutamic and L-Proline, highlighted disruptions in cellular energy metabolism and the impaired ability to synthesize proteins as a defense against oxidation. The impact of PS-MPs on organic acid metabolism was evident in the inhibition of pyruvate and citrate, thereby disrupting the cells' normal participation in energy cycles. The integration of Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis revealed that PS-MPs mainly caused changes in metabolic pathways, including ABC transporters, Aminoacyl-tRNA biosynthesis, Purine metabolism, Glycerophospholipid metabolism and TCA cycle in Pseudomonas aeruginosa. Most of the differential metabolites enriched in these pathways were down-regulated, demonstrating that PS-MPs hindered the expression of metabolic pathways, ultimately impairing the ability of cells to synthesize proteins, DNA, and RNA. This disruption affected cell proliferation and information transduction, thus hampering energy circulation and inhibiting cell growth. Findings of this study supplemented the toxic effects of microplastics and the defense mechanisms of microorganisms, in turn safeguarding drinking water safety and human health.PMID:38423332 | DOI:10.1016/j.scitotenv.2024.171335

Sci Total Environ. 2024 Feb 27:171287. doi: 10.1016/j.scitotenv.2024.171287. Online ahead of print.ABSTRACTIt remains challenging to establish reliable links between transformation products (TPs) of contaminants and corresponding microbes. This challenge arises due to the sophisticated experimental regime required for TP discovery and the compositional nature of 16S rRNA gene amplicon sequencing and mass spectrometry datasets, which can potentially confound statistical inference. In this study, we present a new strategy by combining the use of 2H-labeled Stable Isotope-Assisted Metabolomics (2H-SIAM) with a neural network-based algorithm (i.e., MMvec) to explore links between TPs of pyrene and the soil microbiome. The links established by this novel strategy were further validated using different approaches. Briefly, a metagenomic study provided indirect evidence for the established links, while the identification of pyrene degraders from soils, and a DNA-based stable isotope probing (DNA-SIP) study offered direct evidence. The comparison among different approaches, including Pearson's and Spearman's correlations, further confirmed the superior performance of our strategy. In conclusion, we summarize the unique features of the combined use of 2H-SIAM and MMvec. This study not only addresses the challenges in linking TPs to microbes but also introduces an innovative and effective approach for such investigations. Environmental Implication: Taxonomically diverse bacteria performing successive metabolic steps of the contaminant were firstly depicted in the environmental matrix.PMID:38423316 | DOI:10.1016/j.scitotenv.2024.171287

Chemosphere. 2024 Feb 27:141463. doi: 10.1016/j.chemosphere.2024.141463. Online ahead of print.ABSTRACTAmidst the global plastic pollution crisis, the gastrointestinal tract serves as the primary entry point for daily exposure to micro- and nanoplastics. We investigated the complex dynamics between polystyrene micro- and nanoplastics (PS-MNPs) and four distinct human colorectal cancer cell lines (HT29, HCT116, SW480, and SW620). Our findings revealed a significant size- and concentration dependent uptake of 0.25, 1, and 10 μm PS-MNPs across all cell lines, with HCT116 cells exhibiting the highest uptake rates. During cell division, particles were distributed between mother and daughter cells. Interestingly, we observed no signs of elimination from the cells. Short-term exposure to 0.25 μm particles significantly amplified cell migration, potentially leading to pro-metastatic effects. Particles demonstrated high persistence in 2D and 3D cultures, and accumulation in non-proliferating parts of spheroids, without interfering with cell proliferation or division. Our study unveils the disturbing fact of the persistence and bioaccumulation of MNPs in colorectal cancer cell lines, key toxicological traits under REACH (Regulation concerning the Registration, Evaluation, Authorisation and Restriction of Chemicals). Our observations underscore the potential of MNPs as hidden catalysts for tumor progression, particularly through enhancing cell migration and possibly fueling metastasis - a finding that sheds light on a significant and previously underexplored area of concern.PMID:38423146 | DOI:10.1016/j.chemosphere.2024.141463