PubMed

Semin Nephrol. 2025 Apr 21:151583. doi: 10.1016/j.semnephrol.2025.151583. Online ahead of print.ABSTRACTIn the last decade, advanced developments of mass spectrometry-based assays have made spatial measurements of hundreds of metabolites and thousands of proteins not only possible, but routine. The information obtained from such mass spectrometry imaging experiments traces metabolic events and helps decipher feedback loops across anatomical regions, connecting genetic and metabolic networks that define phenotypes. Herein we overview developments in the field over the past decade, highlighting several case studies demonstrating direct measurement of metabolites, proteins, and proteoforms from thinly sliced tissues at the level of functional tissue units, approaching single-cell levels. Much of this work is feasible due to multidisciplinary team science, and we offer brief perspectives on paths forward and the challenges that persist with adoption and application of these spatial omics techniques at the single-cell level on mammalian kidneys. Data analysis and reanalysis still pose issues that plague spatial omics, but many mass spectrometry imaging platforms are commercially available. With greater harmonization across platforms and rigorous quality control, greater adoption of these platforms will undoubtedly provide major insights in complex diseases. Semin Nephrol 36:x-xx © 20xx Elsevier Inc. All rights reserved.PMID:40263091 | DOI:10.1016/j.semnephrol.2025.151583

BMJ Open. 2025 Apr 22;15(4):e099108. doi: 10.1136/bmjopen-2025-099108.ABSTRACTINTRODUCTION: The prevalence of type 2 diabetes (T2D) within sub-Saharan Africa (SSA) is increasing. Despite the pathophysiology of T2D differing by ethnicity and sex, risk stratification and guidelines for the prevention of T2D are generic, relying on evidence from studies including predominantly Europeans. Accordingly, this study aims to develop ethnic-specific and sex-specific risk prediction models for the early detection of dysglycaemia (impaired glucose tolerance and T2D) to inform clinically feasible, culturally acceptable and cost-effective risk management and prevention strategies using dietary modification in SSA and European populations.METHODS AND ANALYSIS: This multinational collaboration will include the prospective cohort data from two African cohorts, the Middle-Aged Soweto Cohort from South Africa and the Research on Obesity and Diabetes among African Migrants Prospective cohort from Ghana and migrants living in Europe, and a Swedish cohort, the Pre-Swedish CArdioPulmonary bioImage Study. Targeted proteomics, as well as targeted and untargeted metabolomics, will be performed at baseline to discover known and novel ethnic-specific and sex-specific biomarkers that predict incident dysglycaemia in the different longitudinal cohorts. Dietary patterns that explain maximum variation in the biomarker profiles and that associate with dysglycaemia will be identified in the SSA and European cohorts and used to build the prototypes for dietary interventions to prevent T2D. A comparative cost-effectiveness analysis of the dietary interventions will be estimated in the different populations. Finally, the perceptions of at-risk participants and healthcare providers regarding ethnic-specific and sex-specific dietary recommendations for the prevention of T2D will be assessed using focus group discussions and in-depth interviews in South Africa, Ghana, Germany (Ghanaian migrants) and Sweden.ETHICS AND DISSEMINATION: Ethical clearance has been obtained from all participating sites. The study results will be disseminated at scientific conferences and in journal publications, and through community engagement events and diabetes organisations in the respective countries.PMID:40262963 | DOI:10.1136/bmjopen-2025-099108

Am J Trop Med Hyg. 2025 Apr 22:tpmd230395. doi: 10.4269/ajtmh.23-0395. Online ahead of print.ABSTRACTRecent omics studies (cytogenomics, genomics, and transcriptomics) have provided extensive information on Chagas disease (CD) vectors. Here, we conduct a review of proteomic and metabolomic studies on these insect vectors. We address proteomic studies in triatomines, focusing on the identification and characterization of proteins in their saliva, midgut, and salivary glands, emphasizing their role in blood feeding by providing vasodilatory and anticoagulant substances, along with anti-inflammatory and antiplatelet activities. In addition, the review investigates protein diversity in different triatomine species, highlighting the importance of proteomic analysis in understanding adaptation to hematophagy, genetic evolution, and vector defense mechanisms. Metabolomic studies on CD vectors have revealed crucial information about their biology because metabolites correlate with the presence of Trypanosoma cruzi (T. cruzi), suggesting roles in the parasite-vector interaction. Additionally, some studies have predicted T. cruzi infection and observed altered metabolomes after feeding on infected blood, providing information about vector exposure to the parasite.PMID:40262606 | DOI:10.4269/ajtmh.23-0395

J Environ Manage. 2025 Apr 21;383:125430. doi: 10.1016/j.jenvman.2025.125430. Online ahead of print.ABSTRACTThe knowledge on earthworm gut metabolomic variations in metal-enriched green waste (GW)-based vermicomposting systems is scarce. Earthworm's gut metabolite-metal accumulation interactions have also not been studied earlier. Therefore, GW-based Eisenia fetida-mediated vermicomposting and aerobic composting systems were spiked with Pb-Cr-Cu (1:1:1)-mixed solutions. While earthworm reproduction, body weight, and gut microbial growth were slightly lower in metal-spiked GW-vermibeds compared to unspiked vermibeds, the temporal increase in N-P-K enrichment, feedstock microbial counts, and microbial biomass-C&N were significantly more in metal-spiked vermicomposts than in metal-spiked composts. Interestingly, the metal removal efficiency was ∼1.2-3.0 times higher in metal-spiked vermibeds than in unspiked vermibeds and composting beds. Furthermore, the degree of bioaccumulation for Pb (spiked - 1.64 mg kg-1 versus unspiked - 0.22 mg kg-1), Cr (spiked - 0.92 mg kg-1 versus unspiked - 0.40 mg kg-1), and Cu (spiked - 1.54 mg kg-1 versus unspiked - 0.79 mg kg-1) was significantly higher in earthworms grown in spiked than in unspiked GW feedstocks. The LC-QTOF-MS-mediated earthworm-gut metabolomic profiling revealed that 655 biomolecules were significantly up or down-regulated due to metal spiking. Interestingly, compounds known for stress-ameliorating roles (e.g., methylcitisine and trans-anethole) have increased most dramatically in metal-spiked vermibed-borne earthworms. A KEGG-database analysis revealed that the phenylpropanoid pathway metabolites augment in metal-rich feedstock-borne earthworms. Finally, the correlation statistics clarified that earthworm gut metabolite distribution meaningfully alters to enhance the detoxification of non-essential toxic metals (Pb and Cr) more than essential micronutrient metals (Cu) in waste-based vermicomposting systems.PMID:40262501 | DOI:10.1016/j.jenvman.2025.125430

J Environ Manage. 2025 Apr 21;383:125423. doi: 10.1016/j.jenvman.2025.125423. Online ahead of print.ABSTRACTAs emerging pollutants, microplastics (MPs) pose serious threats to the terrestrial ecosystems, and the long-term presence of aged MPs in soil results in toxic effects on plant growth. However, the phytotoxicity mechanisms of aged MPs remain unclear. To understand the toxic effects of aged MPs and the response mechanism of lettuce plants, we selected polyethylene (PE) and polypropylene (PP) (commonly found in soil), and then studied the effects of the two phytotoxins on the soil-plant system before and after aging of the MPs. We found that aging enhanced the toxicity of the MPs to the plants. Compared with the original MPs-treatment group, aged PE and PP particles reduced plant biomasses by 26.19%-28.44% and 25.58%-26.13%, respectively, potentially due to the effects of aged MPs on the rhizosphere soil, which further inhibited nutrient absorption in lettuce. The metabolic response of lettuce to MPs was also different. Aged PE significantly attenuated malic acid and proline concentrations in lettuce, and the reduction in these two products inhibited photosynthesis, energy metabolism, and cellular homeostasis, thereby aggravating the damage caused by aged PE. Aged PP principally affected the metabolic pathways of phenylalanine, tyrosine and tryptophan, which was postulated to be the reason why aging enhanced the phytotoxicity of PP. This study provides new insights into the assessment of the toxic effects of MPs, as well as the environmental behavior and ecological risks of aged MPs.PMID:40262494 | DOI:10.1016/j.jenvman.2025.125423

J Environ Manage. 2025 Apr 21;383:125474. doi: 10.1016/j.jenvman.2025.125474. Online ahead of print.ABSTRACTInnovative technology to address iron deficiency in agriculture while reducing environmental burden is needed because of increasing food demand for the rapidly rising global population. The impact of foliar application of ferroferric oxide nanomaterials (Fe3O4 NMs) at different concentrations (1-50 mg/L) on soybean growth were investigated in the whole life cycle. The beneficial effects of Fe3O4 NMs on soybean were concentration-dependent and exhibited nano-effect. Foliar application with 10 mg/L Fe3O4 NMs exhibited the best performance, notably improving fresh shoot biomass by 9.7-36.2 % among three stages, and increasing root/shoot ratio by 39.1-78.2 %, which are higher than commercial iron fertilizer. Transcriptomic and metabolomic analyses revealed that Fe3O4 NMs: (1) increased soybean photosynthesis to supply more sucrose in soybean leaves; (2) upregulated sucrose transporter genes expression, enhanced auxin and abscisic acid content, and augmented stage-specific sucrose-related metabolites (including tricarboxylic acid cycle and amino acids at seedling stage, the antioxidants at flowering and mature stage) in leaves, thereby enhancing the ability of sucrose transport from source to sink, and finally improving the developments of soybean different sinks among different stages. Our findings highlight the considerable potential of Fe3O4 NMs as a sustainable and high-efficiency crop fertilizer strategy.PMID:40262492 | DOI:10.1016/j.jenvman.2025.125474

J Psychiatr Res. 2025 Mar 11;186:252-262. doi: 10.1016/j.jpsychires.2025.03.016. Online ahead of print.ABSTRACTBACKGROUND: Autism spectrum disorder (ASD) involves challenges in social interaction and communication and repetitive behaviours. CNTNAP4 is implicated in neuronal signalling, and its deficiency plays a role in ASD. Transcriptomic analyses revealed similar gene expression between the brain and in humans as well as in mice. However, the relationships between the brain and testicular gene expression profiles and metabolism in ASD remain unclear. In this study, the effects of Cntnap4 deletion on gene expression and metabolic profiles in the cerebral cortex and testes were investigated to better understand ASD pathogenesis.METHODS: Cntnap4 knockout mice were used to explore transcriptomic and metabolomic alterations. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were employed to identify significantly altered pathways.RESULTS: Cntnap4 deletion caused significant changes in both tissues. In the cerebral cortex, GO and KEGG analyses revealed differentially expressed genes (DEGs) related to mitochondrial energy production and synaptic signalling. Metabolomic analysis revealed altered levels of metabolites such as glutamic acid and glutamine. In the testes, 482 DEGs were linked to mitochondrial function and steroid biosynthesis. Additionally, commonly downregulated genes in both tissues highlighted disruptions in antioxidant activity and glutathione metabolism.CONCLUSIONS: These findings suggest that Cntnap4 deletion impacts mitochondrial function, synaptic signalling, and metabolic processes, contributing to the ASD phenotype. By highlighting these mechanisms, this study provides insights into ASD pathogenesis and potential molecular targets for treatment and highlights the importance of the mitochondrial and synaptic pathways in the development of ASD associated with Cntnap4 deficiency.PMID:40262286 | DOI:10.1016/j.jpsychires.2025.03.016

J Agric Food Chem. 2025 Apr 22. doi: 10.1021/acs.jafc.4c12810. Online ahead of print.ABSTRACTThe fruit peel serves as the frontline defense of grapes against pathogens like Botrytis cinerea, yet its defense mechanisms remain poorly understood. This study reveals novel resistance mechanisms underlying peel immunity through comparative transcriptomic and metabolomic analysis of Vitis amurensis "Bei Binghong" (BH) and V. vinifera "Red Globe" (RG). The analysis identified 1277 differentially expressed genes (DEGs) and 38 differentially accumulated metabolites (DAMs), primarily associated with secondary metabolic processes and plant hormone signaling pathways. Weighted gene coexpression network analysis (WGCNA) uncovered three key modules and several novel hub genes. Crucially, transcriptomic profiling identified VaWRKY20 as a central regulator. Postinfection, upregulated genes and metabolites were involved in salicylic acid (SA), lignin, and stilbene biosynthesis in BH, as well as enhanced resistance through overexpression of VaWRKY20. A conceptual model for V. amurensis defense against B. cinerea was proposed, providing novel insights into grapevine defense mechanisms.PMID:40262121 | DOI:10.1021/acs.jafc.4c12810

Environ Sci Technol. 2025 Apr 22. doi: 10.1021/acs.est.4c13689. Online ahead of print.ABSTRACTNontargeted high-resolution mass spectrometry (HRMS) allows for the characterization of a large fraction of the exposome, i.e., the entirety of chemicals an organism is exposed to, and helps detect important exogenous chemical compounds that could be key drivers of toxicological impact. Along with these chemical compounds occur endogenous metabolites that are essential for the health of the host organism. Chemical compounds derived from the biotransformation of xenobiotics present in the exposome are referred to as the xenometabolome, while endogenous metabolites derived from the host organism are referred to as the endometabolome. Recent advancements in HRMS technology allow for the detection of chemical features of biological and ecological importance in the context of chemical safety assessments with unprecedented sensitivity and resolution. In this perspective, we highlight the application of HRMS-based metabolomics of organisms in the context of ecotoxicology, the complexity of comprehensively characterizing the endometabolome, and distinguishing chemical compounds of the xenometabolome.PMID:40261989 | DOI:10.1021/acs.est.4c13689

Sci Signal. 2025 Apr 22;18(883):eads2547. doi: 10.1126/scisignal.ads2547. Epub 2025 Apr 22.ABSTRACTAdaptation to starvation is a multimolecular and temporally ordered process. We sought to elucidate how the healthy liver regulates various molecules in a temporally ordered manner during starvation and how obesity disrupts this process. We used multiomic data collected from the plasma and livers of wild-type and leptin-deficient obese (ob/ob) mice at multiple time points during starvation to construct a starvation-responsive metabolic network that included responsive molecules and their regulatory relationships. Analysis of the network structure showed that in wild-type mice, the key molecules for energy homeostasis, ATP and AMP, acted as hub molecules to regulate various metabolic reactions in the network. Although neither ATP nor AMP was responsive to starvation in ob/ob mice, the structural properties of the network were maintained. In wild-type mice, the molecules in the network were temporally ordered through metabolic processes coordinated by hub molecules, including ATP and AMP, and were positively or negatively coregulated. By contrast, both temporal order and coregulation were disrupted in ob/ob mice. These results suggest that the metabolic network that responds to starvation was structurally robust but temporally disrupted by the obesity-associated loss of responsiveness of the hub molecules. In addition, we propose how obesity alters the response to intermittent fasting.PMID:40261956 | DOI:10.1126/scisignal.ads2547

J Appl Microbiol. 2025 Apr 1;136(4):lxaf089. doi: 10.1093/jambio/lxaf089.ABSTRACTAIMS: Phenoxyethanol is a broad-spectrum antimicrobial agent widely used in cosmetic formulations. However, its antibacterial effects on different skin bacteria, particularly the predominant Cutibacterium acnes and its various phylotypes, remain unclear. The objective of this study was to examine the antimicrobial effects of phenoxyethanol on C. acnes and explore the mechanism.METHODS AND RESULTS: Phenoxyethanol exhibited strong antimicrobial effects against both C. acnes ATCC6919 (phylotype IA1) and CCSM0331 (phylotype II), achieving a minimum inhibitory concentration (MIC) of 0.5% (v/v). Sub-MIC concentrations showed a stronger inhibitory effect on CCSM0331. RNA-seq and metabolomic analyses revealed that phenoxyethanol disrupted cell membrane integrity and influenced essential metabolic pathways, such as energy metabolism, amino acid metabolism, and pyrimidine metabolism. Additionally, glycolysis and the Wood-Werkman cycle were inhibited in CCSM0331 but enhanced in ATCC6919. The expression of genes involved in porphyrin metabolism, associated with inflammation, was significantly reduced.CONCLUSIONS: Phenoxyethanol exhibits the antimicrobial activity against C. acnes, with differential effects on phylotypes, targeting critical metabolic pathways and cellular processes. These findings indicate its potential for acne treatment.PMID:40261688 | DOI:10.1093/jambio/lxaf089

Biol Trace Elem Res. 2025 Apr 22. doi: 10.1007/s12011-025-04627-9. Online ahead of print.ABSTRACTLead is a common environmental pollutant. It can affect several body systems including the central nervous system (CNS). Lead can disrupt the nervous system by different mechanisms including oxidative stress, inflammation, disruption of neurotransmission, and aberrant autophagy. Apiaceous species have been used traditionally as food flavoring and medicine, representing a rich source of bioactive compounds. In the current study, the antioxidant power of four Apiaceous extracts (Foeniculum vulgare L., Pimpinella anisum L., Coriandrum sativum L., and Cuminum cyminum L.) was evaluated. Additionally, the metabolite profiles of the selected species were comprehensively investigated by untargeted liquid chromatography electrospray ionization tandem mass spectrometry (LC/ESI-MS/MS) coupled to chemometry. Coriander (Coriandrum sativum L.) extract showed the highest radical scavenging activity and reducing power. Coriander was further subjected to in vivo evaluation of its protective effect against Lead (Pb)-induced neurotoxicity. Administration of coriander extracts improved the short- and long-term memory performance and decreased hippocampal Pb content in Pb-intoxicated rats. Moreover, it attenuated hippocampal oxidative stress, neurochemical changes, and exhibited anti-inflammatory effect in the hippocampal tissue. Further, coriander extracts attenuated Pb inhibitory effect on the mammalian target of Rapamycin (mTORC1) pathway resulting in upregulation of Phospho-p70 S6 Kinase (P-P70S6K) and Phospho-S6 Ribosomal Protein (PS6) and downregulation of Beclin-1. Additionally, some selected coriander ingredients were subjected to molecular docking to examine their regulatory effect on mTORC-1 and IκB kinase complex (Ikk-β). The present findings highlight the future pharmaceutical utilization of coriander extract as valuable source of phenolic compounds that can be used as antioxidant, anti-inflammatory, and neuroprotective agents against Pb-induced neurotoxicity.PMID:40261543 | DOI:10.1007/s12011-025-04627-9

J Cardiovasc Transl Res. 2025 Apr 22. doi: 10.1007/s12265-025-10616-z. Online ahead of print.ABSTRACTThis study investigated the association between serum small peptides and arteriosclerosis (AS) in hypertensive patients. Sixty hypertensive patients (with and without AS) and 30 healthy individuals were enrolled. Untargeted metabolomics identified 120 peptides in AS patients, 136 in hypertensive patients, and 59 shared peptides. LASSO regression identified key peptides differentiating hypertensive patients with AS from those without. Peptides like Thr-Ile, Phe-Asp-Lys, and Lys-Ile-Val-Lys were upregulated in AS, while others like Gln-Glu and Lys-Lys were higher in non-AS patients. The diagnostic model showed AUCs of 0.896 for AS and 0.909 for non-AS. Elevated levels of Lys-Ile-Val-Lys and Phe-Asp-Lys were linked to increased carotid intima-media thickness, indicating higher AS risk.PMID:40261542 | DOI:10.1007/s12265-025-10616-z

Funct Integr Genomics. 2025 Apr 22;25(1):94. doi: 10.1007/s10142-025-01603-3.ABSTRACTAcute respiratory distress syndrome (ARDS) is a life-threatening condition characterized by severe hypoxemia and high mortality. Ferroptosis, a form of regulated cell death driven by iron accumulation and lipid peroxidation, has emerged as a critical mechanism in ARDS pathogenesis. However, the molecular regulators of ferroptosis in ARDS remain unclear. This study integrates multi-omics analysis and experimental validation to identify ferroptosis-related targets in ARDS. Bronchoalveolar lavage fluid (BALF) samples from ARDS patients and healthy controls were subjected to proteomics and metabolomics analysis. Transcriptomic data from the GSE243066 dataset and ferroptosis-related gene databases were integrated to identify key genes. Functional enrichment analyses were performed using Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways. An LPS-induced ARDS mouse model was established for experimental validation, including Western blotting, histopathology, and ferroptosis-related biochemical assays. Multi-omics analysis identified YWHAE as a ferroptosis-associated gene significantly upregulated in ARDS. Functional enrichment revealed key pathways, including ferroptosis, hypoxia-inducible factor-1 signaling, and oxidative stress responses. Proteomic and transcriptomic integration highlighted 51 overlapping differentially expressed genes, with YWHAE emerging as a central hub in the protein-protein interaction network. Metabolomics analysis further revealed glutathione and cysteine metabolism as critical pathways linked to ferroptosis. In the ARDS mouse model, ferroptosis inhibitor ferrostatin-1 (Fer-1) attenuated LPS-induced lung injury, reduced oxidative stress markers, and downregulated YWHAE expression. This study identifies YWHAE as a novel ferroptosis-related target in ARDS through multi-omics analysis and experimental validation. These findings provide new insights into the molecular mechanisms of ferroptosis in ARDS and highlight YWHAE as a potential therapeutic target for future interventions.PMID:40261442 | DOI:10.1007/s10142-025-01603-3

Eur J Nucl Med Mol Imaging. 2025 Apr 22. doi: 10.1007/s00259-025-07280-5. Online ahead of print.ABSTRACTBACKGROUND: PSMA-targeted radioligand therapies (PSMA RLT) are an effective and safe option for metastatic castration-resistant prostate cancer, but responsive subtypes and their biomarkers are not fully defined.METHODS: Plasma samples for cell-free DNA (cfDNA) analysis were collected from 17 patients undergoing [¹⁷⁷Lu]Lu-PSMA-I&T. CfDNA underwent whole-genome sequencing to establish copy number variation (CNV) profiles and circulating-tumor DNA (ctDNA) levels and compared between prostate-specific antigen (PSA) response- and 1-year overall survival (1YOS) groups.RESULTS: Non-responders exhibited higher degrees of cfDNA CNV burden (P = 0.048) and higher ctDNA levels (P = 0.036) than responders. Both markers allowed for the differentiation of responses (AUC: 0.792, 0.806) and 1YOS (AUC: 0.778, 0.847).CONCLUSION: Unresponsive patients exhibited higher levels of cfDNA genomic instability and ctDNA levels, warranting genome-wide CNV profiling studies next to targeted approaches for mechanistic radiobiological insights and their value as response biomarkers for PSMA RLTs.PMID:40261406 | DOI:10.1007/s00259-025-07280-5

Food Funct. 2025 Apr 22. doi: 10.1039/d5fo00900f. Online ahead of print.ABSTRACTIn this rat feeding study, it was hypothesized that the impact of red (vs. white) meat consumption on gut health is more pronounced in fiber-deprived diets, whereas fiber-rich diets may attenuate meat-related differences. For this purpose, rats were fed a red (beef) or white (chicken) meat diet with and without fructo-oligosaccharides (FOS) for three weeks. Gut health was assessed through colonic microbiota, fermentation metabolites, oxidative stress, inflammation, DNA adducts and histology. In rats on the fiber-deprived diets, beef consumption resulted in higher abundance of mucin-degrading bacteria Akkermansia and lower blood glutathione levels compared to chicken-fed rats. Adding FOS to the meat diets modulated the gut microbiota and fermentation metabolites, affected oxidative stress and inflammation markers in tissues and blood, increased colon length, and reduced fat deposition and liver weight. Thus, results showed that the dietary context should be considered when evaluating the impact of red meat consumption on gut health.PMID:40261136 | DOI:10.1039/d5fo00900f

mSystems. 2025 Apr 22:e0020225. doi: 10.1128/msystems.00202-25. Online ahead of print.ABSTRACTEndometriosis (EM) and adenomyosis (AM) are interrelated gynecological disorders characterized by the aberrant presence of endometrial tissue and are frequently linked with chronic pelvic pain and infertility, yet their pathogenetic mechanisms remain largely unclear. In this cross-sectional study, we analyzed endometrial samples from 244 participants, split into 91 EM patients, 56 AM patients, and 97 healthy controls (HC). We conducted untargeted liquid chromatography-mass spectrometry (LC-MS) and 5R 16S rRNA sequencing to examine endometrial metabolome and microbiome profiles. Additionally, we integrated transcriptomic analysis using nine transcriptomic data sets to investigate the biological basis of these conditions. Metabolomic profiling and 16S rRNA sequencing revealed distinct metabolic and microbial signatures. Specific pathways, including linoleic acid and glycerophospholipid metabolism, show significant alterations in both conditions. Notably, four metabolites, including phosphatidylcholine 40:8 [PC(40:8)], exhibited marked changes in both EM and AM, suggesting shared pathological features. Furthermore, taxonomic analysis identified unique bacterial species associated with each condition, particularly those belonging to the phylum Proteobacteria, which correlated with altered metabolic signatures. Machine learning models demonstrated high predictive accuracy for differentiating between AM, EM, and HC based on metabolic and microbial signatures. Integrative analysis with transcriptomic data highlighted distinct pathways related to immune response and signaling transduction for each condition. Our study provides fresh insights into the pathogenesis of AM and EM through a multi-omic approach, suggesting potential inconsistencies in the underlying pathogenetic mechanisms.IMPORTANCE: Existing research highlighted a connection between endometriosis (EM) and adenomyosis (AM), underscoring their overlapping symptoms and potential shared pathophysiological mechanisms. Although the role of microbiota in inflammatory conditions has been acknowledged, comprehensive investigations into the endometrial microbiota in cases of EM and AM have been limited. Previous studies identified distinct microbial communities associated with these conditions; however, they were constrained by small sample sizes and a lack of integrated analyses of microbiota and metabolomics. Furthermore, the ongoing debate over whether EM and AM should be classified as separate diseases or related phenotypes emphasizes the necessity for further exploration of their molecular interactions. Our study uncovers distinct microbial and metabolic signatures associated with each condition, revealing both shared and unique pathways that may contribute to their pathogenesis. Furthermore, the integration of transcriptomic data offers valuable insights into the complex interactions underlying these disorders.PMID:40261026 | DOI:10.1128/msystems.00202-25

Microbiol Spectr. 2025 Apr 22:e0246724. doi: 10.1128/spectrum.02467-24. Online ahead of print.ABSTRACTMany studies indicate the gut microbiome is associated with diseases caused by administering high-dose glucocorticoids (GCs), such as hypertension, hyperglycemia, and osteoporosis. However, the association between intestinal flora and the use of high-dose GCs remains elusive. We aimed to characterize gut microbiome in Graves' ophthalmopathy (GO) patients after administering high-dose GCs. In this study, 20 primary GO patients were recruited. The differences in gut microbiota of GO patients before and after administering high-dose GCs were analyzed by 16S rDNA sequencing technology. Untargeted metabolomic analysis was used to examine the differences in gut metabolites between two groups. There were significant differences in α and β diversities of gut microbiota in GO patients before and after administering high-dose GCs. The random forest analysis indicated that three intestinal bacteria (Faecalibacterium, Streptococcus, and Prevotella) could distinguish the two groups with the highest accuracy, which was proven by receiver operator characteristic curve and linear discriminant analysis effect size analysis. The short-chain fatty acid-producing ability in GO patients' gut after high-dose GC administration was significantly decreased. The 5-hydroxytryptamine levels significantly increased in the gut of GO patients after administering high-dose GCs. Our study suggests that high-dose GC administration causes the changes in gut microbiome and metabolites. Moreover, the altered flora and metabolites are related to hypertension, hyperglycemia, and osteoporosis. These findings can help understand the development of side effects caused by high-dose GCs and can be further used to develop potential probiotics to facilitate the prevention for those side effects.IMPORTANCEFor the first time, we revealed that gut microbiome and metabolome in Graves' ophthalmopathy patients after high-dose glucocorticoid (GC) administration significantly changed, and the altered flora and metabolites are related to hypertension, hyperglycemia, and osteoporosis. These findings can help understand the development of side effects caused by high-dose GCs and can be further used to develop potential probiotics to facilitate the prevention for those side effects.PMID:40261021 | DOI:10.1128/spectrum.02467-24

Mol Nutr Food Res. 2025 Apr 22:e70046. doi: 10.1002/mnfr.70046. Online ahead of print.ABSTRACTAcute coronary syndrome (ACS) is a leading cause of global mortality, largely due to atherosclerosis influenced by lifestyle factors like diet. Gut microbiota impacts lipid metabolism, inflammation, and endothelial function, all vital in atherosclerosis. Dysbiosis increases intestinal permeability, causing inflammation and plaque instability, elevating cardiac event risk. This study investigates the impact of dietary improvements on gut microbiota and metabolite release in recent ACS patients versus healthy individuals. A cohort of 29 recent ACS patients receiving lipid-lowering therapy and dietary advice was analyzed alongside 56 healthy controls. Dietary habits, serum, and stool samples were collected at admission and after 3 months. Metagenomic analysis of stool and metabolomic analysis of serum were conducted. The results showed bacterial dysbiosis in ACS patients, characterized by a reduction in beneficial genera and an increase in potentially pro-inflammatory bacteria. After 3 months of dietary improvements, three metabolites with anti-inflammatory properties were significantly upregulated. The findings highlight the association between gut microbiota dysbiosis, fatty diets, and inflammation in ACS patients. The observed increase in anti-inflammatory metabolites following dietary changes underscore the following dietary interventions in modulating gut microbiota and improving cardiovascular and metabolic health.PMID:40260991 | DOI:10.1002/mnfr.70046

CNS Neurosci Ther. 2025 Apr;31(4):e70381. doi: 10.1111/cns.70381.ABSTRACTAIMS: Post-cardiac arrest brain injury (PCABI) is a leading cause of death in cardiac arrest/cardiopulmonary resuscitation (CA/CPR) victims and long-term disability in CA/CPR survivors. Despite previous evidence indicating that the microbiota-gut-brain axis is critically involved in many neurological disorders, no research has hitherto established a connection between the gut microbiota and PCABI through this axis. This study aims to explore the biological roles of microbial tryptophan metabolites in the progression of PCABI.METHODS: To achieve this, we pretreated rats with a cocktail of broad-spectrum antibiotics (Abx) to eradicate the gut microbiota before establishing a 7-min asphyxia-CA/CPR model.RESULTS: Remarkably, the 24-h survival rate and neurological outcomes improved in Abx/CPR rats. Fecal 16s rDNA sequencing and PICRUSt2 analysis revealed that Abx reshaped the microbial community and elevated the proportion of microbial tryptophan metabolism in rats. Metabolomic profiling suggested that Abx shifted the phenotype of microbial tryptophan metabolism from the indole pathway to the kynurenine pathway, thereby increasing the levels of the neuroprotective metabolite kynurenine in the feces, circulation, and ultimately the brain. Furthermore, the hippocampal expression of aryl hydrocarbon receptor (AhR), an endogenous receptor of kynurenine, was upregulated in Abx/CPR rats. In vitro experiments further demonstrated that the neuroprotective effects of kynurenine are AhR-dependent and that AhR activation could negatively regulate the NLRP3 protein expression. Supporting this, results from qRT-PCR, immunohistochemistry, and immunofluorescence in the rat cerebral cortex exhibited that L-kynurenine inhibited NLRP3-induced pyroptosis.CONCLUSIONS: Our study provides a direct clue to the essential participation of the microbiota-gut-brain axis in the progression of PCABI. It demonstrates that kynurenine might attenuate PCABI by inhibiting NLRP3-induced pyroptosis.PMID:40260682 | DOI:10.1111/cns.70381