Integrative Molecular Phenotyping
INTEGRATIVE MOLECULAR
PHENOTYPING
WHEELOCK LABORATORY
DEPARTMENT OF MEDICAL
BIOCHEMISTRY AND BIOPHYSICS
WHEELOCK LABORATORY
DEPARTMENT OF MEDICAL
BIOCHEMISTRY AND BIOPHYSICS
WHEELOCK LABORATORY
DEPARTMENT OF MEDICAL
BIOCHEMISTRY AND BIOPHYSICS
WHEELOCK LABORATORY
DEPARTMENT OF MEDICAL
BIOCHEMISTRY AND BIOPHYSICS
WHEELOCK LABORATORY
DEPARTMENT OF MEDICAL
BIOCHEMISTRY AND BIOPHYSICS
WHEELOCK LABORATORY

PubMed

Amur linden honey and its principal polyphenols alleviate obesity and regulate gut microbiota in high-fat diet-induced mice

Fri, 11/04/2025 - 12:00
Food Chem X. 2025 Mar 14;27:102368. doi: 10.1016/j.fochx.2025.102368. eCollection 2025 Apr.ABSTRACTObesity has emerged as a critical global health challenge in recent decades, driving increased scientific interest in honey as a sugar alternative. Despite its perceived nutritional benefits, the inherent high fructose-glucose ratio in honey continues to raise concerns regarding metabolic implications for overweight individuals. In this study, Amur linden honey (LH) was evaluated as a low-glycemic-index (GI) dietary intervention, demonstrating significant anti-obesity effects through murine model. Subsequently, nine principal polyphenols (PC) were identified by metabolomics and proven anti-obesity activity in cellular assays, suggesting their potential role in mediating the biological effects of LH. Notably, the anti-obesity effects of LH were more pronounced as compared to the equivalent amount of glucose and fructose, and this effect was further facilitated by addition of the PC. Furthermore, LH and HP (LH with the addition of PC) attenuate obesity by modulating gut microbiota, promoting production of SCFA especially acetate and propionate etc., and activating the AMPK/PI3K/AKT pathways. The present study revealed that LH, enriched with diverse bioactive compounds, presents the potential to be a healthy and safe sugar substitutes due to its positive effects on the obesity.PMID:40213330 | PMC:PMC11985147 | DOI:10.1016/j.fochx.2025.102368

Taste characteristics and symbolic metabolites of Rougui tea with different grades in China

Fri, 11/04/2025 - 12:00
Food Chem X. 2025 Mar 21;27:102405. doi: 10.1016/j.fochx.2025.102405. eCollection 2025 Apr.ABSTRACTThe national tea standard sample is an important reference for the evaluation of tea grades. Clarifying the taste characteristics of different grades of Rougui tea (RGT) and its characteristic metabolites is of great significance for the standardization and scientificization of national standard samples. In this study, metabolites of different grades of RGT were analyzed by sensory evaluation and metabolomics, and symbolic metabolites were obtained and verified. The results showed that the higher the RGT grade, the stronger the mellowness and fresh and brisk taste, and the weaker the bitterness and astringency. Cyclo-glycyl-L-phenylalanine and calyxanthone can be used as the main symbolic metabolites to evaluate the quality of RGT, and their contents in 15 different grades of RGT verified the conclusion. This study lays an important foundation for the production of national tea standards and the measurement of commercial tea quality.PMID:40213328 | PMC:PMC11984596 | DOI:10.1016/j.fochx.2025.102405

Longitudinal multi-omics analysis of the gut-liver axis: Unraveling the molecular mechanisms of metabolic homeostasis regulation by Pd@Pt nanozymes

Fri, 11/04/2025 - 12:00
Mater Today Bio. 2025 Mar 19;32:101685. doi: 10.1016/j.mtbio.2025.101685. eCollection 2025 Jun.ABSTRACTRecently, the nanozyme Pd@Pt has garnered attention due to its notable specific surface area and superior enzyme-like catalytic activity, leading to extensive examination and application in previous studies. However, the comprehensive impact of Pd@Pt nanozyme on treating metabolic disorders, such as diabetes and its associated conditions, remains largely unexplored. This research aimed to clarify how Pd@Pt influences metabolic balance at both the transcriptome and microbiome levels and to explore the interactions between microbiota and genes. We conducted an examination of mice subjected to a high-fat diet (HFD) following treatment with Pd@Pt. Transcriptome analysis was performed to identify differentially expressed genes (DEGs), and microbiome analysis was conducted to identify significant bacterial correlations associated with Pd@Pt exposure. The results indicated enhancements in glucose metabolism dysfunctions in the treated mice. Transcriptome analysis revealed that DEGs after Pd@Pt administration were enriched in the PI3K-Akt, NF-κB, and MAPK signaling pathways in the liver. Microbiome analysis identified four significant bacteria that exhibited a strong negative correlation with Pd@Pt exposure, while ten bacteria showed a positive correlation. Furthermore, a correlation network established among the gut microbiota, metabolites, and DEGs demonstrated a robust association. This research enhances our understanding of the mechanisms by which Pd@Pt affects the regulation of metabolic diseases in HFD-exposed environments and proposes a novel strategy for utilizing nanozymes in human health management.PMID:40213158 | PMC:PMC11984605 | DOI:10.1016/j.mtbio.2025.101685

Characterization of metabolic features derived from the non-polar metabolite UHPLC-QTOF dataset of <em>Jaspis sp.</em> Collected from the waters off Pulau Banggi, Sabah, Malaysia

Fri, 11/04/2025 - 12:00
Data Brief. 2025 Mar 22;60:111474. doi: 10.1016/j.dib.2025.111474. eCollection 2025 Jun.ABSTRACTThe marine biome is a rich source of bioactive compounds. The discovery of anti-cancer compounds in Cryptotheca crypta in 1950 initiated a wave of bioprospecting efforts focused on marine sponges. Jaspis sp., a marine sponge, has been reported to exhibit anti-cancer activity against human colorectal cancer. A sample of Jaspis sp., collected from the waters off Pulau Banggi, Sabah, Malaysia, was analyzed through a non-polar metabolite survey. The non-polar crude extract was profiled using UHPLC-QTOF in both positive and negative modes. The detected metabolic features were clustered, and representative features were tentatively identified through a combination of spectral database searches (using various MS2 spectral databases) and in silico compound identification. This dataset provides a valuable foundation for future bioprospecting endeavors involving Jaspis sp.PMID:40213043 | PMC:PMC11985046 | DOI:10.1016/j.dib.2025.111474

Metabolomics for the Identification of Biomarkers in Kidney Diseases

Fri, 11/04/2025 - 12:00
Nanotheranostics. 2025 Mar 24;9(2):110-120. doi: 10.7150/ntno.108320. eCollection 2025.ABSTRACTWith the apparent rise in lifestyle-related changes, there has been a significant decline in renal health. Metabolomics plays a crucial role in the prognosis, diagnosis, and treatment of various renal conditions, including chronic kidney disease, acute kidney injury, diabetic kidney disease, kidney cancer, and post-transplant complications. Metabolomics has identified novel biomarkers, providing insights into altered pathways and potential therapeutic targets for kidney diseases. Kidney diseases and metabolomics keywords were searched in correspondence with the assigned keywords, including chronic kidney diseases, acute kidney injury, kidney carcinoma, kidney transplant, and diabetic kidney diseases on literature search engines. The applicable studies from this search were extracted and included in the study. This review is focused on the biomarkers identified in different kidney diseases such as chronic kidney diseases, acute kidney injury, diabetic kidney disease, kidney carcinoma and kidney transplant.PMID:40212952 | PMC:PMC11980039 | DOI:10.7150/ntno.108320

Multi-Omics Analysis of Gut Microbiome and Host Metabolism in Different Populations of Chinese Alligators (<em>alligator sinensis</em>) During Various Reintroduction Phases

Fri, 11/04/2025 - 12:00
Ecol Evol. 2025 Apr 9;15(4):e71221. doi: 10.1002/ece3.71221. eCollection 2025 Apr.ABSTRACTReintroduction plays a significant role in the self-maintenance and reconstruction of wild animal populations, serving as a communication bridge between captive and wild animals. The Chinese alligator (Alligator sinensis) is a distinct and endangered reptile species found in China. The mechanisms by which artificially bred Chinese alligators adapt following their release into the wild remain poorly understood. This study aims to elucidate the alterations in gut microbiomes and metabolic phenotypes of Chinese alligators during their reintroduction. During the Chinese alligator's reintroduction, Fusobacterium and Cetobacterium became more abundant, while typical pathogens declined significantly. The gut type of the Chinese alligator changed from Acinetobacter to Cetobacterium. The construction of the gut microbial community was dominated by neutral (random) processes and shifted towards deterministic processes with the progression of reintroduction. In terms of species function, reintroduction significantly upregulated the expression of host immune-related genes and significantly decreased the expression of gut bacterial pathogenic genes and antibiotic resistance genes. Metagenomic and metabolomic KEGG enrichment analyses indicate that glucoside hydrolase families 13 and 23-alongside glycolysis and gluconeogenesis pathways-may play pivotal roles in energy metabolism, host-pathogen interactions, and homeostasis maintenance for Chinese alligators. Differential metabolite analysis identified significant upregulation of metabolites related to neuroendocrine immune modulation and significant down-regulation of anti-inflammatory metabolites during Chinese alligator reintroduction. Association analysis showed that there were significant co-metabolic effects between microorganisms and metabolites, which coordinated host adaptive interaction. This study provides insights into the synergistic mechanisms of host adaptation and wild environment adaptation for Chinese alligators.PMID:40212922 | PMC:PMC11981878 | DOI:10.1002/ece3.71221

Multi-omics assessment of gut microbiota in circadian rhythm disorders: a cross-sectional clinical study

Fri, 11/04/2025 - 12:00
Front Cell Infect Microbiol. 2025 Mar 27;15:1524987. doi: 10.3389/fcimb.2025.1524987. eCollection 2025.ABSTRACTBACKGROUND: The interaction between the host and microbiota is influenced by host circadian rhythm. However, it is unknown what the changes of gut microbiota and metabolites.METHODS: We conducted a cross-sectional study (n=72) in which participants' fecal DNA was detected by macrogenomic sequencing analysis. The feces, urine and blood were analyzed by widely targeted metabolomics analysis.RESULTS: Pearson correlation analysis showed that most of the clinical symptoms of people with circadian rhythm disorders were moderately positively correlated with gastrointestinal symptoms. By distilling the results of multinomic analysis, we reported a variety of different species (19 species in the gut) and metabolites. In our results, the correlation of multiomics is mostly concentrated in Lachnospiraceae bacterium and Streptococcus mitis oralis pneumoniae. Bile acid-related metabolites are the most significant metabolites associated with these species.DISCUSSION: Our study demonstrates the severity of clinical manifestations caused by circadian rhythm disorder is closely related to microbiota and metabolism. In the future, personalized interventions targeting specific microbial species or metabolites may help alleviate the physical and psychological discomfort induced by circadian rhythm disturbances.PMID:40212846 | PMC:PMC11983646 | DOI:10.3389/fcimb.2025.1524987

Investigation of Urinary Exosome Metabolic Patterns in Membranous Nephropathy by Titania-Assisted Intact Exosome Mass Spectrometry

Fri, 11/04/2025 - 12:00
Small Sci. 2022 Feb 9;2(5):2100118. doi: 10.1002/smsc.202100118. eCollection 2022 May.ABSTRACTExosomes are regarded as the emerging potential targets for liquid biopsy and bioprocess study owing to their abundant inclusive cargos that carry significant disease information. In addition, metabolites have been promising biomarkers for diagnosis. However, little metabolic research on exosomes is carried out by now. Herein, the mix-crystal titania-assisted laser desorption/ionization mass spectrometry (LDI-MS) method is established, which features fast speed, high throughput, and efficiency, to directly extract urinary exosome metabolic patterns of healthy controls (HC) and membrane nephropathy (MN) patients. Besides, this method is also adopted to acquire the primitive urinary metabolic patterns from the same samples for comparison. By taking advantage of principal component analysis, unpaired parametric t-test, and orthogonal partial least squares discriminant analysis on the exosome metabolic patterns, 27 significant m/z signals are filtrated, which possess more prominent differentiation capacity toward HC and MN patients (AUC = 0.942), and hold greater potential in MN diagnosis, compared to primitive urine (AUC = 0.801). The work reveals the important clinical value of exosome metabolic analysis, and paves a way to exosome-based diagnosis at metabolomic level toward large-scale clinical use.PMID:40212598 | PMC:PMC11935978 | DOI:10.1002/smsc.202100118

Perfluorocarbon Nanoparticles Loaded with Oxygen Alleviate Acute Kidney Injury via Ameliorating Renal Oxygenation Level

Fri, 11/04/2025 - 12:00
Biomater Res. 2025 Apr 10;29:0181. doi: 10.34133/bmr.0181. eCollection 2025.ABSTRACTRenal microcirculatory disturbances and tissue hypoxia play a pivotal role in acute kidney injury (AKI) initiation and progression, and addressing renal hypoxia during the acute phase presents a promising therapeutic strategy for preventing AKI or protecting kidney function. In this study, we explored the renal protective potential of perfluorocarbon nanoparticles (PFPs), engineered for superior oxygen-carrying and delivery capacities, in an AKI mouse. Specifically, PFP-treated mice exhibited significant reductions in tubular dilation, necrosis, and brush border loss in renal tubules. Additionally, PFP pretreatment reduced tissue inflammation and fibrosis, as indicated by decreased nuclear factor-kappa B, α-smooth muscle actin, fibronectin, and collagen I expression. Serum creatinine and blood urea nitrogen levels improved, decreasing by 26.9% and 41.7%, respectively. Flow cytometry further showed controlled levels of f4/80+ macrophages and CD45+ inflammatory markers, with f4/80+ macrophages reduced by approximately 31.2% and CD45+ inflammatory factors reduced by 40.5%. Metabolomic analyses highlighted PFP's modulation of key metabolic pathways linked to renal recovery, notably up-regulating slc22a19 by 48.3%, a gene encoding a short-chain fatty acid transporter, and down-regulating hyaluronic acid synthesis in renal tissue. These findings are the first to demonstrate that PFPs, as an oxygen carrier, can enhance renal resilience against IR (ischemia-reperfusion)-induced AKI, offering compelling evidence of PFP's clinical potential in AKI management.PMID:40212394 | PMC:PMC11982615 | DOI:10.34133/bmr.0181

Combined microbiome and metabolomics analysis of yupingfeng san fermented by Bacillus coagulans: insights into probiotic and herbal interactions

Fri, 11/04/2025 - 12:00
PeerJ. 2025 Apr 7;13:e19206. doi: 10.7717/peerj.19206. eCollection 2025.ABSTRACTBACKGROUND: Yupingfeng san is a traditional Chinese medicine formula composed of siler, atractylodes, and astragalus. The herbal medicine fermentation process relies on the role of probiotics. Bacillus coagulans is a probiotic commonly used to ferment food and drugs. It produces a variety of beneficial metabolites during fermentation. However, the study on the interaction between B. coagulans and yupingfeng san is still blank.METHODS: During solid-state fermentation of yupingfeng san, we used metabolomics technology and 16S rDNA sequencing to analyze the differential metabolites and microbial flora of B. coagulans at 0, 3, 7, 11, and 15 d, which corresponded to groups A0, B3, B7, B11, and B15, respectively. This research explored the correlation between microorganisms and metabolites in fermented compound Chinese medicine.RESULTS: The results revealed a significant difference in species β diversity between group A0 and the B groups (P < 0.01). At the phylum level, in fermentation groups B3, B7, B11, and B15, the Cyanobacteria relative abundance decreased by 6.69%, 9.09%, 5.74%, and 2.24%, respectively (P < 0.05). The Firmicutes relative abundance increased by 39.73%, 35.65%, 49.09%, and 68.66% (P < 0.05), respectively. The Proteobacteria relative abundance decreased by 39.86% and 26.70%, respectively, in groups B11 and B15 (P < 0.05). The relative abundance of Actinobacteria increased initially with extended fermentation time, and then gradually decreased after reaching its peak in group B7. At the genus level, compared with group A0, the relative abundance of Actinobacteria increased to its highest level of 21.12% in fermentation group B3 and decreased to 9.51% after a fermentation time of 15 d. The abundance of Leuconostoc in fermentation groups B3, B7, and B11 was significantly higher than in group A0 (20.93%, 20.73%, and 21.00%, respectively, P < 0.05). Pediococcus in fermentation groups B3, B7, B11, and B15 was also significantly higher than in group A0 (4.20%, 2.35%, 18.84%, and 52.01%, P < 0.05). Both Pediococcus and Leuconostoc, which belong to lactic acid bacteria, increased fivefold, accounting for a total abundance of 62%. After yupingfeng san fermentation, using nontargeted metabolomics, we identified 315 differential metabolites. This results showed a decrease in the content of alkene and an increase in the contents of acids, lipids, ketones, and amino acids. In addition, in group B3, the contents of quercetin, paeoniflorin-3-O-glucoside, netin, iristin, anthocyanin, caffeic acid, rosmarinic acid, liquiritin, and isoliquiritin were significantly upregulated.CONCLUSION: In this study, the composition and metabolic profile of yupingfeng san after the fermentation of B. coagulans were studied, and it was found that the fermentation group showed rich species diversity, in which the abundance of Leuconostoc and Weisseria increased significantly, while the opportunistic pathogens such as Pseudomonas aeruginosa and Enterobacter decreased significantly. The analysis of metabolic products showed that the contents of acids, lipids and ketones were significantly increased, rich in a variety of beneficial microorganisms and small molecular compounds with antibacterial effects, and these changes worked together to inhibit the growth of pathogens and maintain intestinal health. The study not only helps to elucidate the assembly mechanism and functional expression of microorganisms after Chinese traditional medicine fermentation, but also provides a solid scientific basis for the development of efficient and safe micro-ecological feed additives.PMID:40212372 | PMC:PMC11984470 | DOI:10.7717/peerj.19206

Integrated metabolomics and network pharmacology to investigate the effects of Yi-Qi-Xuan-Fei-Hua-Tan decoction for treating acute respiratory distress syndrome

Fri, 11/04/2025 - 12:00
Ann Med Surg (Lond). 2025 Feb 28;87(4):1969-1981. doi: 10.1097/MS9.0000000000003130. eCollection 2025 Apr.ABSTRACTBACKGROUND: Acute respiratory distress syndrome (ARDS) is a common severe lung disease with high morbidity and mortality. Yi-Qi-Xuan-Fei-Hua-Tan decoction (YQXFHT) is based on the classical formula of Ma-Xing-Shi-Gan decoction with flavor addition.METHODS: First, a global view of the potential compound-target-pathway network based on network pharmacology was constructed to provide a preliminary understanding of active compounds. Subsequently, the in vivo efficacy of YQXFHT was verified in a mouse model. Meanwhile, the metabolic mechanism of YQXFHT in the treatment of ARDS was explored using the corresponding metabolomic profiles.RESULTS: Five active components of YQXFHT and 10 core targets for the treatment of ARDS were obtained through network pharmacological studies. Potential activities include isorhamnetin, jaranol, medicarpin, quercetin, and mandneol, and core targets include STAT3, PIK3CA, PIK3CD, NRAS, AKT1, PTPN11, JAK1, EGFR, IL-6, and CTNNB1. Besides, 10 pathways were analyzed by Kyoto Gene and Genome Encyclopedia enrichment analysis, mainly including estrogen, IL-17, TNF, FoxO, PI3k-Akt, and HIF-1 signaling pathways, etc. It was shown that the docking model between the core target and its corresponding components was stable by molecular docking. Finally, in metabolomics, it was concluded that YQXFHT can be activated by unsaturated fatty acid synthesis, linoleic acid metabolism, lysine degradation, arginine proline metabolism, and drug metabolism-cytochrome P450 metabolic pathways to exert effects on ARDS.CONCLUSION: This study highlighted the reliability and validity of the metabolomics and network pharmacology-based approach that identified and validated complexes of natural components in YQXFHT to elucidate the therapeutic mechanisms of ARDS.PMID:40212228 | PMC:PMC11981420 | DOI:10.1097/MS9.0000000000003130

Gut Microbiota Regulate Saturated Free Fatty Acid Metabolism in Heart Failure

Fri, 11/04/2025 - 12:00
Small Sci. 2024 Jul 8;4(9):2300337. doi: 10.1002/smsc.202300337. eCollection 2024 Sep.ABSTRACTAIMS: Heart failure (HF) is associated with profound changes in cardiac metabolism. At present, there is still a lack of relevant research to explore the key microbiome and their metabolites affecting the progression of HF. Herein, the interaction of gut microbiota and circulating free fatty acid (FFA) in HF patients and mice is investigated.METHODS AND RESULTS: In HF patients, by applying metagenomics analysis and targeted FFA metabolomics, enriched abundance of Clostridium sporogenes (C.sp) in early and late stage of HF patients, which negatively correlated to saturated free fatty acid (SFA) levels, is identified. KEGG analysis further indicates microbiota gene enrichment in FFA degradation in early HF, and decreased gene expression in FFA synthesis in late HF. In HF mice (C57BL/6J) induced by isoproterenol (ISO), impaired intestinal permeability is observed, and decreased fecal C.sp and increased SFA are further validated. At last, by supplementing C.sp to ISO-induced HF mice, the cardiac function, fibrosis, and myocardial size are partially rescued, together with decreased circulating SFA levels.CONCLUSIONS: Clostridium abundance is increased in HF, compensating cardiac function deterioration via downregulation of circulating SFA levels. The results demonstrate that the gut microbiota-SFA axis plays an important role in HF protection, which may provide a strategic advantage for the probiotic therapy development in HF.PMID:40212081 | PMC:PMC11935106 | DOI:10.1002/smsc.202300337

Heart Has Intrinsic Ketogenic Capacity that Mediates NAD<sup>+</sup> Therapy in HFpEF

Fri, 11/04/2025 - 12:00
Circ Res. 2025 Apr 11. doi: 10.1161/CIRCRESAHA.124.325550. Online ahead of print.ABSTRACTBACKGROUND: Heart failure with preserved ejection fraction (HFpEF) has overtaken heart failure with reduced ejection fraction as the leading type of heart failure globally and is marked by high morbidity and mortality rates, yet with only a single approved pharmacotherapy: SGLT2i (sodium-glucose co-transporter 2 inhibitor). A prevailing theory for the mechanism underlying SGLT2i is nutrient deprivation signaling, of which ketogenesis is a hallmark. However, it is unclear whether the canonical ketogenic enzyme, HMGCS2 (3-hydroxy-3-methylglutaryl-coenzyme A synthase 2), plays any cardiac role in HFpEF pathogenesis or therapeutic response.METHODS: We used human myocardium, human HFpEF and heart failure with reduced ejection fraction transcardiac blood sampling, an established murine model of HFpEF, ex vivo Langendorff perfusion, stable isotope tracing in isolated cardiomyocytes, targeted metabolomics, proteomics, lipidomics, and a novel cardiomyocyte-specific conditional HMGCS2-deficient model that we generated.RESULTS: We demonstrate, for the first time, the intrinsic capacity of the human heart to produce ketones via HMGCS2. We found that increased acetylation of HMGCS2 led to a decrease in the enzyme's specific activity. However, this was overcome by an increase in the steady-state levels of protein. Oxidized form of nicotinamide adenine dinucleotide repletion restored HMGCS2 function via deacetylation, increased fatty acid oxidation, and rescued cardiac function in HFpEF. Critically, using a conditional, cardiomyocyte-specific HMGCS2 knockdown murine model, we revealed that the oxidized form of nicotinamide adenine dinucleotide is unable to rescue HFpEF in the absence of cardiomyocyte HMGCS2.CONCLUSIONS: The canonical ketogenic enzyme, HMGCS2, mediates the therapeutic effects of the oxidized form of nicotinamide adenine dinucleotide repletion in HFpEF by restoring normal lipid metabolism and mitochondrial function.PMID:40211954 | DOI:10.1161/CIRCRESAHA.124.325550

Metabolomic Profiling of Three Body Fluids Differentiates UWS and MCS in Disorders of Consciousness

Fri, 11/04/2025 - 12:00
Biomed Chromatogr. 2025 May;39(5):e70079. doi: 10.1002/bmc.70079.ABSTRACTDisorders of consciousness (DOC), including unresponsive wakefulness syndrome (UWS) and minimally conscious state (MCS), are complex brain dysfunctions with various causes. Misdiagnosis is common when relying solely on neurological exams, highlighting the need for accurate differentiation to guide clinical rehabilitation. This study explores metabolomic differences between UWS and MCS across cerebrospinal fluid (CSF), serum, and urine samples to identify biomarkers and metabolic pathways. Fifty-one subjects were categorized into UWS (n = 35) and MCS (n = 16) based on coma recovery scale-revised (CRS-R) scores. Ultraperformance liquid chromatography tandem mass spectrometry (UPLC-MS/MS) was used to analyze samples, and statistical methods identified 14, 24, and 22 differential metabolites in CSF, serum, and urine, respectively. CSF metabolites were linked to necrosis, apoptosis, and neuroprotection; serum metabolites to lipid metabolism and immune response; and urine metabolites to cell signaling and neural function. Metabolomic panels showed AUC values of 0.85 (95% CI: 0.73-0.96) for CSF (95% CI: 0.86-1.00), 0.94 for serum, and 0.93 (95% CI: 0.79-1.00) for urine in distinguishing UWS from MCS. This profiling offers valuable insights into DOC pathophysiology and aids in accurate differentiation of these states.PMID:40211935 | DOI:10.1002/bmc.70079

Heated drinking water in winter improves growth performance of male Hu sheep by modulating rumen quorum sensing and metabolites, and enhancing serum antioxidant capacity

Fri, 11/04/2025 - 12:00
Anim Biosci. 2025 Apr 4. doi: 10.5713/ab.24.0821. Online ahead of print.ABSTRACTOBJECTIVE: This study aimed to explore the mechanism by which increasing the temperature of drinking water in winter promotes sheep growth from a microbial perspective.METHODS: A total of 12 healthy male Hu sheep were evenly divided into two groups: one with drinking water at 12°C (WT12) and the other at 25°C (WT25), and they were raised for 60 days in the cold winter.RESULTS: The WT25 group exhibited higher average daily gain, serum immunoglobulin G, total antioxidant capacity, glutathione peroxidase, and superoxide dismutase, along with lower feed-to-gain ratio, serum cortisol, malondialdehyde, reactive oxygen species, and oxidative stress index when compared to the WT12 group (p<0.05). The concentrations of microbial crude protein, microbial density, autoinducer-2 (AI-2) signaling molecule concentration, and biofilm formation were higher in the WT25 group, while the ammonia nitrogen concentration was lower (p<0.05). The relative abundances of Muribaculum and Clostridia UCG-014, as well as the predicted metabolic pathways related to lipid metabolism, were lower in the WT25 group, whereas the metabolism of other amino acids showed increased abundances (p<0.05). Both principal coordinates analysis (PCoA) and analysis of similarities (ANOSIM) revealed no significant differences in rumen microbial communities between the WT12 and WT25 groups (p>0.05). Metabolomics analysis identified 12 differential metabolites, four of which were correlated with Muribaculum, Raoultibacter, and Coriobacteriales Incertae Sedis.CONCLUSION: These results indicate that heated drinking water in winter could improve growth performance by increasing rumen bacterial biofilm formation and enhancing serum antioxidant capacity in Hu sheep. This study establishes correlations between rumen microbial quorum sensing and key factors such as animal growth phenotypes, rumen metabolic characteristics, and specific bacterial genera. It offers innovative perspectives on enhancing animal feed efficiency through the modulation of rumen bacterial quorum sensing.PMID:40211844 | DOI:10.5713/ab.24.0821

Mitochondrial fusion reduces T cell susceptibility to HIV infection through citrate modulation

Fri, 11/04/2025 - 12:00
J Leukoc Biol. 2025 Apr 11:qiaf042. doi: 10.1093/jleuko/qiaf042. Online ahead of print.ABSTRACTInhibiting the metabolic activity of CD4+ T cells can effectively reduce HIV infection. Mitochondria, as critical organelles in eukaryotic metabolism, play a significant role in the progression of many diseases. The change of mitochondrial dynamics is an important process of mitochondrial regulation of cell metabolic activity. However, it remains uncertain whether regulating mitochondrial dynamics is a viable approach to reducing HIV infection. In this study, we demonstrated that promoting mitochondrial fusion in Jurkat cells through treatment with the mitochondrial fusion promoter M1 and the dynamin-related protein 1 (Drp1) inhibitor Mdivi1 conferred resistance to single-round VSVG-HIVNL4-3-GFP viral infection. Targeted metabolomics analysis revealed and subsequently confirmed the potential involvement of citrate in reducing HIV infection, which has been subsequently verified. And we found that plasma citrate level was negatively associated with HIV disease progression. Multi-omics results showed that citric acid leads to a decrease in the level of nucleotide metabolism in Jurkat cells. In conclusion, increased citrate levels resulting from mitochondrial fusion significantly impair the ability of HIV to infect cells, which may due to regulate nucleotide metabolism.PMID:40211578 | DOI:10.1093/jleuko/qiaf042

Regulating Effects of Three Polysaccharides on Gut Microbiota in Felines and Canines: Insights from <em>In Vitro</em> Digestion, Fecal Fermentation, and Lactic Acid Bacterial Fermentation

Fri, 11/04/2025 - 12:00
J Agric Food Chem. 2025 Apr 10. doi: 10.1021/acs.jafc.4c12847. Online ahead of print.ABSTRACTThis study evaluated the effects of laminaria polysaccharide (FU), aloe polysaccharide (AL), and yeast β-glucan (YG) on in vitro digestion, fecal fermentation, and lactic acid bacterial fermentation in felines and canines. FU (Mw 27 713 g/mol), AL (44 425 g/mol), and YG (29 296 g/mol) were primarily composed of glucose, galacturonic acid, and glucuronic acid. The FU strongly promoted the fermentation of Bifidobacterium, Lactobacillus, and Pediococcus. The AL slightly supported Lactobacillus. The YG showed minimal activity. Molecular weights decreased after digestion with negligible monosaccharide release. The FU and AL were almost completely metabolized during fecal fermentation, while YG had ∼50% utilization. The FU produced the highest lactate concentration. The YG significantly increased SCFA levels, especially in canines, surpassing fructooligosaccharides. The FU:AL:YG mixture (0.8:0.2:1, FAY) achieved the best overall effects. 16S rRNA analysis revealed the enrichment of SCFA-producing genera (e.g., Megamonas, Parabacteroides) and suppression of odor-related bacteria (e.g., Fusobacterium, Desulfovibrio). Metabolomics showed reduced levels of odor compounds (e.g., 2-oxindole, 5-hydroxyindole) and increased secondary bile acids (e.g., deoxycholic acid, glycocholic acid). The FU, AL, and FAY upregulated bile secretion, neuroactive pathways, and arachidonic acid metabolism, while YG activated the ABC transporter pathway.PMID:40211571 | DOI:10.1021/acs.jafc.4c12847

Dissecting Causal Relationships Between Gut Microbiota, 1400 Blood Metabolites, and Intervertebral Disc Degeneration

Fri, 11/04/2025 - 12:00
Neurospine. 2025 Mar;22(1):211-221. doi: 10.14245/ns.2449172.586. Epub 2025 Mar 31.ABSTRACTOBJECTIVE: The precise mechanisms driving intervertebral disc degeneration (IVDD) development remain unclear, but evidence suggests a significant involvement of gut microbiota (GM) and blood metabolites. We aimed to investigate the causal relationships between GM, IVDD, and blood metabolites using Mendelian randomization (MR) analysis.METHODS: We utilized the summary statistics of GM from the MiBioGen consortium, 1400 blood metabolites from the genome-wide association studies (GWAS) Catalog, and IVDD data from the FinnGen repository, which are sourced from the largest GWAS conducted to date. Employing bidirectional MR analyses, we investigated the causal relationships between GM and IVDD. Additionally, we conducted 2 mediation analyses, 2-step MR and multivariable MR (MVMR), to identify potential mediating metabolites.RESULTS: Five bacterial genera were causally associated with IVDD, while IVDD did not show a significant causal effect on GM. In the 2-step MR analysis, Eubacteriumfissicatenagroup, RuminococcaceaeUCG003, Lachnoclostridium, and Marvinbryantia genera, along with metabolites X-24949, Pimeloylcarnitine/3-methyladipoylcarnitine (C7-DC), X-24456, histidine, 2-methylserine, Phosphocholine, and N-delta-acetylornithine, were all significantly associated with IVDD (all p < 0.05). MVMR analysis revealed that the associations between Eubacteriumfissicatenagroup genus and IVDD were mediated by X-24949 (8.1%, p = 0.024); Lachnoclostridium genus and IVDD were mediated by histidine (18.1%, p = 0.013); and RuminococcaceaeUCG003 genus and IVDD were mediated by C7-DC (-7.5%, p = 0.041).CONCLUSION: The present MR study offers evidence supporting the causal relationships between several specific GM taxa and IVDD, as well as identifying potential mediating metabolites.PMID:40211528 | DOI:10.14245/ns.2449172.586

Fate and Toxicity of Carbon Black to Phytoplankton in Natural Lakes: Insight into the Role of Phototransformation

Fri, 11/04/2025 - 12:00
Environ Sci Technol. 2025 Apr 10. doi: 10.1021/acs.est.4c13895. Online ahead of print.ABSTRACTConcern over the contamination of freshwater ecosystems with carbon black (CB) is increasing. Here, the toxicity of CB to phytoplankton (Chlorella pyrenoidosa) was evaluated; upon exposure, the median effective concentration for 72 h was 23.4 mg/L. CB underwent significant photooxidation during 15 days of light irradiation, although phototransformation was generally completed by day 7. Algal growth inhibition induced by phototransformed CB (TCB) at 1 mg/L was 64.1% greater than that induced by parent CB. Mechanistically, 1) phototransformation triggered the release of highly toxic byproducts, which inhibited algal growth by 18.9%; 2) metabolomic results demonstrate that the suppression of carbon and nitrogen assimilation in algal cells induced by TCB was 13.2-53.7% greater than that induced by CB; 3) TCB exhibited reactive oxygen species production ability, which triggered more significant algal membrane damage. A full-factorial experiment (26+1 runs) showed that the combined effect of temperature and suspended mineral particles, as well as electrical conductivity, was the primary environmental factor that mediated CB and TCB toxicity, respectively. The predicted toxicity of CB and TCB in Taihu Lake exhibited significant regional distribution, and TCB posed a greater environmental risk in aquatic ecosystems than CB. These findings highlight the importance of particulate contaminant transformation and environmental factors when evaluating their environmental risk.PMID:40211440 | DOI:10.1021/acs.est.4c13895

Characterization of gut microbiota and metabolites in renal transplant recipients during COVID-19 and prediction of one-year allograft function

Fri, 11/04/2025 - 12:00
J Transl Med. 2025 Apr 10;23(1):420. doi: 10.1186/s12967-025-06090-5.ABSTRACTBACKGROUND: The gut-lung-kidney axis is pivotal in immune-related kidney diseases, with gut dysbiosis potentially exacerbating the severity of Coronavirus disease 2019 (COVID-19) in recipients of kidney transplant. This study aimed to characterize the gut microbiome and metabolome in renal transplant recipients with COVID-19 pneumonia over a one-year follow-up period.METHODS: A total of 30 renal transplant recipients were enrolled, comprising 17 with COVID-19 pneumonia, six with mild COVID-19, and seven without COVID-19. Fecal samples were collected at the onset of infection for gut microbiome and metabolome analysis. Generalized Estimating Equations (GEE) model and Latent Class Growth Mixed Model (LCGMM) were employed to dissect the relationships among clinical characteristics, laboratory tests, and gut microbiota and metabolites.RESULTS: Four microbial phyla (Deferribacteres, TM7, Fusobacteria, and Gemmatimonadetes) and 13 genera were significantly enriched across three recipients groups, correlating with baseline inflammatory response and allograft function. Additionally, 52 differentially expressed metabolites were identified, with seven significantly correlating with eight altered microbiota genera. LCGMM revealed two distinct classes of recipients, with those suffering from COVID-19 pneumonia exhibiting significantly elevated serum creatinine (Scr) trajectories over the one-year period. GEE further identified 12 genera and 181 metabolites closely associated with these trajectories; a multivariable model incorporating gut metabolites of 1-Caffeoylquinic Acid and PMK was found to effectively predict one-year allograft function.CONCLUSIONS: Our study indicates a possible interaction between the composition of the gut microbiota and metabolites community and COVID-19 in renal transplant recipients, particularly in relation to disease severity and the prediction of one-year allograft function.PMID:40211390 | DOI:10.1186/s12967-025-06090-5

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