PubMed

Front Immunol. 2024 Nov 6;15:1443440. doi: 10.3389/fimmu.2024.1443440. eCollection 2024.ABSTRACTSystemic lupus erythematosus (SLE) is a multifaceted autoimmune disease affecting various body organs and systems. The diagnosis of SLE and its complications is based on evident clinical symptoms, serological marker levels, and pathological findings. Some serological markers have a low sensitivity and specificity, and biopsy procedures are invasive in nature. Hence, metabolomics has emerged as a valuable tool for SLE screening and categorization. Its application has contributed significantly to identifying SLE pathogenesis, improving clinical diagnosis, and developing treatment approaches. This review provides an overview of the utilization of metabolomics in the study of SLE, focusing on advancements in understanding the disease's pathogenesis, aiding in diagnosis, and monitoring treatment efficacy.PMID:39569194 | PMC:PMC11576423 | DOI:10.3389/fimmu.2024.1443440

Front Cell Neurosci. 2024 Nov 6;18:1430448. doi: 10.3389/fncel.2024.1430448. eCollection 2024.ABSTRACTMicroglia are non-electrogenic immune cells that respond rapidly to protect the central nervous system (CNS) from infections, injuries, or other forms of damage. Microglia mitochondria are essential for providing the requisite energy resources for immune regulation. While fluctuations in energy metabolism are regulated by mitochondria and are reflected in the mitochondrial membrane potential (ΔΨm), there remains a lack of innovation in microglia-centric tools that capitalize on this. In this study, live imaging of microglia in acute slices from EGFP reporter mice expressing EGFP under the control of the fractalkine receptor (CX3CR1) promoter is combined with loading a fluorescent reporter of ΔΨm. Depolarizations in the ΔΨm were recorded after administering the well-characterized immune stimulant lipopolysaccharide (LPS). Microglia ΔΨm increased in distinctive phases with a relatively steep slope following LPS exposure. Conversely, the ΔΨm of neurons showed minimal regulation, highlighting a distinct microglia ΔΨm response to immune stimuli. Analysis of the depolarization of the microglia ΔΨm in the soma, branches, and endfeet revealed progressive changes in each subcellular domain originating in the soma and progressing outward. The inverse agonist emapunil attenuated the depolarization of the ΔΨm across states in a domain-specific manner. These findings emphasize the contribution of mitochondrial membrane dynamics in regulating microglial responses to immune stimuli. Further, this work advances a novel drug screening strategy for the therapeutic regulation of metabolic activity in inflammatory conditions of the brain.PMID:39569069 | PMC:PMC11576292 | DOI:10.3389/fncel.2024.1430448

Int J Nanomedicine. 2024 Nov 15;19:11941-11956. doi: 10.2147/IJN.S483091. eCollection 2024.ABSTRACTPURPOSE: Periodontitis is a chronic inflammatory oral disease that causes defects in periodontal tissue. Conventional therapies are limited, and often lead to high recurrence rates. The emerging concept of medicinal food homology has shed light on the potential of ginger as a therapeutic adjuvant for periodontitis, given its antioxidant and anti-inflammatory properties. However, fresh ginger exhibits poor stability and bioavailability. Ginger exosome-like nanoparticles (GELNs), a derivative of ginger, have not been reported to exert therapeutic effects in periodontitis. This study aimed to explore the therapeutic effects of GELNs on tissue damage caused by periodontitis and their underlying mechanisms of action.METHODS: The GELNs composition was analyzed using a widely targeted metabolome. Stability was assessed using nanoparticle tracking analysis (NTA) and zeta potential measurements, flavor was evaluated using an electronic nose, and membrane penetration was studied using confocal microscopy. A periodontitis model was established in SD rats, periodontal clinical indicators were monitored, and histological changes were assessed using H&E and TRAP staining. Co-culture experiments investigate the antioxidant and reparative abilities of GELNs on periodontal ligament fibroblasts (PDLFs) in inflammatory environment. NF-κB protein expression was examined by immunofluorescence and immunohistochemistry.RESULTS: The findings revealed that GELNs demonstrated good stability in different environments and mitigated the pungent taste of the raw ginger. In vivo experiments showed that GELNs improved periodontal clinical parameters and pathology compared with ginger juice. In vitro data suggested that GELNs enhanced the proliferation and migration of PDLFs while reducing the reactive oxygen species (ROS) levels by inhibiting the NF-κB signaling pathway in an inflammatory setting.CONCLUSION: This study is the first to demonstrate that GELNs have a potential therapeutic effect on periodontitis. GELNs can alleviate oxidative stress (OS) and inflammatory reactions by inhibiting the NF-κB signaling pathway. These findings provide a promising method for the treatment of periodontitis by regulating an unbalanced OS state.PMID:39569064 | PMC:PMC11577593 | DOI:10.2147/IJN.S483091

Curr Res Food Sci. 2024 Oct 28;9:100898. doi: 10.1016/j.crfs.2024.100898. eCollection 2024.ABSTRACTInflammatory bowel disease (IBD), encompassing ulcerative colitis (UC) and Crohn's disease, entails chronic inflammation of the gastrointestinal tract. The pathogenesis of IBD implicates genetic factors, gut microbiome alterations, and immune dysregulation, contributing to its increasing global prevalence. The sturgeon-derived peptide, which exhibits promising anti-inflammatory effects, provides potential therapeutic insights for managing IBD symptoms. This study aims to elucidate the therapeutic mechanisms of novel sturgeon-derived peptide (LLLE, Leu-Leu-Leu-Glu) by investigating their effects on intestinal inflammation, gut microbiota composition, and fecal metabolites in a mouse model of IBD. LLLE administration alleviated weight loss and disease activity index (DAI) scores in dextran sulfate sodium salt (DSS)-induced colitis in mice. Histopathological examination showed LLLE pretreatment improved colon morphology and histopathological condition and decreased serum interleukin-6 (IL-6) levels. 16S rRNA sequencing indicated LLLE-modulation of gut microbiota, especially alleviated DSS-elevated Bacteroidetes. Fecal metabolomic analysis unveiled that LLLE restores critical metabolites such as indole-3-propionic acid, which is pivotal in anti-inflammatory responses. Altogether, sturgeon peptide exhibits considerable promise as a therapeutic agent for colitis, owing to its anti-inflammatory effects, modulation of gut microbiota, and restoration of essential fecal metabolites.PMID:39569007 | PMC:PMC11577126 | DOI:10.1016/j.crfs.2024.100898

Chem Sci. 2024 Nov 4. doi: 10.1039/d4sc04174g. Online ahead of print.ABSTRACTBioinformatics-guided metabolomics is a powerful means for the discovery of novel natural products. However, the application of such metabologenomics approaches on microbial polyketides, a prominent class of natural products with diverse bioactivities, remains largely hindered due to our limited understanding on the mass spectrometry behaviors of these metabolites. Here, we present a metabologenomics approach for the targeted discovery of polyketides biosynthesized by modular type I polyketide synthases. We developed the NegMDF workflow, which uses mass defect filtering (MDF) supported by bioinformatic structural prediction, to connect the biosynthetic gene clusters to corresponding metabolite ions obtained under negative ionization mode. The efficiency of the NegMDF workflow is illustrated by rapid characterization of 22 polyketides synthesized by three gene clusters from a well-characterized strain Streptomyces cattleya NRRL 8057, including cattleyatetronates, new members of polyketides containing a rare tetronate moiety. Our results showcase the effectiveness of the MDF-based metabologenomics workflow for analyzing microbial natural products, and will accelerate the genome mining of microbial polyketides.PMID:39568943 | PMC:PMC11575545 | DOI:10.1039/d4sc04174g

MedComm (2020). 2024 Nov 20;5(12):e70012. doi: 10.1002/mco2.70012. eCollection 2024 Dec.ABSTRACTThe gut microbiota plays a critical role in maintaining human health, influencing a wide range of physiological processes, including immune regulation, metabolism, and neurological function. Recent studies have shown that imbalances in gut microbiota composition can contribute to the onset and progression of various diseases, such as metabolic disorders (e.g., obesity and diabetes) and neurodegenerative conditions (e.g., Alzheimer's and Parkinson's). These conditions are often accompanied by chronic inflammation and dysregulated immune responses, which are closely linked to specific forms of cell death, including pyroptosis and ferroptosis. Pathogenic bacteria in the gut can trigger these cell death pathways through toxin release, while probiotics have been found to mitigate these effects by modulating immune responses. Despite these insights, the precise mechanisms through which the gut microbiota influences these diseases remain insufficiently understood. This review consolidates recent findings on the impact of gut microbiota in these immune-mediated and inflammation-associated conditions. It also identifies gaps in current research and explores the potential of advanced technologies, such as organ-on-chip models and the microbiome-gut-organ axis, for deepening our understanding. Emerging tools, including single-bacterium omics and spatial metabolomics, are discussed for their promise in elucidating the microbiota's role in disease development.PMID:39568773 | PMC:PMC11577303 | DOI:10.1002/mco2.70012

Front Nutr. 2024 Nov 6;11:1498605. doi: 10.3389/fnut.2024.1498605. eCollection 2024.ABSTRACTFermentation significantly influences the chemical composition of black tea, yet the effects of different fermentation temperatures on non-volatile components and their in vitro hypoglycemic activity are insufficiently studied. This research investigates how varying temperatures (20, 25, and 30°C) affect the bioactive profile and the inhibitory activity of Jinxuan black tea against α-glucosidase and α-amylase. Our results show that lower fermentation temperatures (20°C) lead to elevated levels of key bioactive compounds, including tea polyphenols (9.24%), soluble sugars (8.24%), thearubigins (7.17%), and theasinesin A (0.15%). These compounds correlate strongly with enhanced α-glucosidase inhibition (R = 0.76-0.97). Non-targeted metabolomic analysis revealed that 36 differential metabolites, including catechins, exhibited altered levels with increasing fermentation temperature. Notably, tea fermented at 20°C exhibited superior hypoglycemic activity, with α-glucosidase inhibition (IC50 = 14.00 ± 1.00 μg/ml) significantly outperforming α-amylase inhibition (IC50 = 2.48 ± 0.28 mg/ml). The findings of this research underscore the importance of fermentation temperature in optimizing the bioactive profile of black tea. It is proposed that recommendations for future processing or formulation should emphasize the use of lower fermentation temperatures, aimed at augmenting the health benefits linked to higher polyphenol content and stronger hypoglycemic activity.PMID:39568725 | PMC:PMC11576308 | DOI:10.3389/fnut.2024.1498605

Nutr Metab Insights. 2024 Nov 19;17:11786388241297143. doi: 10.1177/11786388241297143. eCollection 2024.ABSTRACTIncreasing dietary intake of fish oil is frequently recommended for decreasing the risk for cardiovascular diseases and improving metabolic health. We hypothesised that dietary intake of chromista oil (a marine food product and a rich source of long-chain n-3 polyunsaturated fatty acids) ameliorates metabolic impairments in mice with established excess adiposity. Three-to 4-week-old mice (male) were fed a control (n = 12) or a high-fat diet (HFD, n = 24) for 12 weeks to establish body fat mass. Then, mice on the HFD were assigned to 2 groups (n = 12 each) with 1 continuing being fed the HFD and the other fed the HFD with chromista oil for an additional 12 weeks. Intake of chromista oil did not affect body weight and body adiposity of the mice fed the HFD; mice fed the HFD had significantly more body weight and fat mass than control mice. The flattened daily oscillations of respiratory exchange ratio induced by the HFD were not changed by chromista oil intake. Intake of chromista oil significantly increased plasma concentration of insulin, the calculated value of HOMA-IR, and plasma concentration of adiponectin in the mice fed the HFD. However, blood glucose was unaffected by chromista oil. Transcription of genes encoding circadian rhythm and fatty acid metabolism of the 2 HFD-fed groups were similar. Untargeted metabolomic analysis showed that intake of chromista oil altered the hepatic metabolomic profile with substantial alterations in amino acid metabolism. Findings from this study indicate that dietary intake of chromista oil does not improve glucose homeostasis or alter the diminished metabolic flexibility in mice with excess adiposity induced by the HFD. argeted metabolomic analysis is warranted to investigate the effects of dietary chromista oil, as a source of n-3 poly unsaturated fatty acids, on metabolism in models of obesity.PMID:39568657 | PMC:PMC11577470 | DOI:10.1177/11786388241297143

Front Pharmacol. 2024 Nov 6;15:1491321. doi: 10.3389/fphar.2024.1491321. eCollection 2024.ABSTRACTINTRODUCTION: With the onset of the COVID-19 pandemic, the incidence and prevalence of acute pharyngitis (AP) have increased significantly. Tinosporae Radix (TR) is a vital medication utilized in the treatment of pharyngeal and laryngeal ailments, especially AP. The study endeavors to explore unclear molecular mechanisms of TR in addressing AP.METHODS: Network pharmacology and metabolomics analyses of effect of TR on AP were conducted, and apossible pathway was validated both in vivo using the acute pharyngitis rat model and in vitro using the LPS-induced RAW264.7 cells model, through techniques such as histopathological examinations, immunohistochemical technology, ELISA, RT-qPCR, and Western blotting to systematically explore the possible mechanisms underlying the inhibition of AP by TR.RESULTS AND DISCUSSION: Network pharmacology analysis identified several key targets, including PIK3CA, IL6, AKT1, TNF, and PTGS2, alongside pivotal signaling pathways such as IL-17, TNF, Hepatitis B, nuclear factor kappa B (NF-κB), Influenza A, and the PI3K-Akt pathway. Most of them are closely associated with inflammation. Then, wide-target metabolomics analysis showed that TR downregulated substances within the glycerophospholipid metabolic pathway, and modulated the PI3K-Akt pathway. The integrated findings from network pharmacology and metabolomics underscored the pivotal role of the PI3K-Akt signaling pathway and the attenuation of inflammatory responses. Finally, in vitro and in vivo experiments have shown that TR can inhibit inflammatory factors such as IL-6, TNF - α, and COX-2, downregulate targets such as PI3K and AKT on the PI3K-Akt signaling pathway, and thereby alleviate the inflammatory response of AP. Our study demonstrated that TR exerts an anti-AP effect through suppression of release of inflammatory factors and modulation of glycerophospholipid metabolism via suppressing the PI3K-Akt signaling pathway.PMID:39568590 | PMC:PMC11576305 | DOI:10.3389/fphar.2024.1491321

Front Pharmacol. 2024 Nov 6;15:1396825. doi: 10.3389/fphar.2024.1396825. eCollection 2024.ABSTRACTBACKGROUND: Gastrodiae rhizoma (GR) refers to the dried tuber of Gastrodia elata Bl. and has been used for many centuries to treat brain diseases, such as Alzheimer's disease, major depressive disorder, and cerebral ischemia. However, the processing of GR is complex and varied, resulting in unstable clinical treatment effects. The processing protocols significantly affect the active ingredients and curative effects of GR. We can optimize the processing of GR by identifying quality markers to treat brain diseases.METHODS: Fresh tubers of G. elata Bl. were processed under eight different protocols, and their resulting contents of potentially bioactive compounds were compared using liquid chromatography mass spectrometry to screen the potential quality markers of GR through stoichiometric analysis. The potential quality markers of GR targeting Alzheimer's disease, major depressive disorder, and cerebral ischemia were identified by network pharmacology, and the potentially neuroprotective effects of these components were validated through simulated docking to likely protein targets. Finally, a fit degree analysis was carried out using different composition ratios and proportions of the disease component degree value, and the therapeutic effects of different processing methods on Alzheimer's disease, major depressive disorder, and cerebral ischemia were outlined clearly.RESULTS: We identified 32 potential therapeutic components and screened 13 quality markers in GR, of which five quality markers (galactinol, glucosyringic acid, parishins C and E, and S-(4-hydroxybenzyl)-glutathione) showed efficacy against all three brain diseases. Furthermore, steaming and microwave-drying during processing can optimize the components of these quality markers for treating the three diseases.CONCLUSION: Processing protocols significantly affect the therapeutic components of GR and may also impact its effectiveness in treating brain diseases. Accordingly, optimizing the processing methods of GR to correspond to different therapeutic purposes may improve its efficacy against brain diseases.PMID:39568583 | PMC:PMC11576197 | DOI:10.3389/fphar.2024.1396825

Front Physiol. 2024 Nov 6;15:1492202. doi: 10.3389/fphys.2024.1492202. eCollection 2024.ABSTRACTPURPOSE: In recent years, ischemic preconditioning (IPC) has emerged as an effective strategy to increase tissue resistance against long-term ischemic damage and has been increasingly integrated into exercise regimens. However, further research is needed to explore the impact of IPC-mediated metabolic alterations from an exercise standpoint to conduct a comprehensive exploration of metabolic alterations and their exercise-related mechanisms during acute IPC.METHODS: Nontarget metabolomics was performed on blood samples obtained from 8 male athletes both before and after IPC. The studies included the identification of differentially abundant metabolites, analysis of receiver operating characteristic (ROC) curves, Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis for differentially abundant metabolites, and metabolite set enrichment analysis (MSEA).RESULTS: Nineteen differentially abundant metabolites were identified, with increasing levels of five metabolites, such as O-desmethyltramadol and D-gluconate, whereas 14 metabolites, including 9-hydroxy-10e, 12z-octadecadienoic acid (9-HODE), tetradione, 2-hexenal, (2,4-dichlorophenoxy)acetic acid (2,4-D), and phosphatidylserine (PS), decreased. ROC curve analysis revealed an AUC of 0.9375 for D-gluconate. Both KEGG enrichment analysis and MSEA revealed enrichment in the pentose phosphate pathway (PPP).CONCLUSION: This study revealed that PPP, D-gluconate, O-desmethyltramadol, and D-2-aminobutyric acid could be upregulated within 5 min after acute IPC, whereas 2,4-D, PS, 9-HODE, 2-hexenal, and tetradinone could be downregulated. These identified metabolites show promise for improving physical functional status and could be harnessed to enhance athletic performance.PMID:39568544 | PMC:PMC11576439 | DOI:10.3389/fphys.2024.1492202

Front Plant Sci. 2024 Nov 6;15:1448060. doi: 10.3389/fpls.2024.1448060. eCollection 2024.ABSTRACTFruit color is a crucial attribute of fruit quality in peppers (Capsicum spp.). However, few studies have focused on the mechanism of color formation in immature pepper fruits. In this study, the light-yellow color observed in immature CSJ009 fruits compared to CSJ010 could be attributed to decreased chlorophyll and carotenoid pigments. Through integrated analysis of the transcriptome and metabolome of CSJ009 and CSJ010, we identified 23,930 differentially expressed genes (DEGs) and 345 differentially accumulated metabolites (DAMs). Furthermore, integrated analysis revealed a strong correlation between the HCT-like gene and metabolite MWS0178 (chlorogenic acid). Paraffin section assay revealed that the epidermal cells of immature CSJ010 fruits exhibited a more compact arrangement with significantly greater length than those of CSJ009. Quantitative determination of carotenoids showed that lutein emerged as the predominant carotenoid in immature pepper fruits. Additionally, missense mutation of LCYB2 is likely to lead to a decrease in β-carotene content in immature CSJ009 fruits, whereas CCS may directly catalyze the conversion of lycopene to β-carotene in mature fruits. The null mutation in CCS promoted the biosynthesis of β,ϵ-branch carotenoids leading to lutein being the most abundant carotenoid found in orange CSJ010 fruits. These findings provide important insights into the mechanism underlying color formation in pepper fruits and establish a foundation for the further exploration of color-related genes.PMID:39568454 | PMC:PMC11576296 | DOI:10.3389/fpls.2024.1448060

Tumori. 2024 Nov 21:3008916241287719. doi: 10.1177/03008916241287719. Online ahead of print.ABSTRACTBACKGROUND: The management of individuals with familial adenomatous polyposis (FAP) includes invasive prophylactic surgery and intensive endoscopic surveillance to reduce their risk of colorectal cancer. FAP patients frequently ask for dietary recommendations to alleviate bowel disturbances after prophylactic colectomy, and to prevent the formation and growth of new adenomas. We have enriched the multidisciplinary outpatient clinic for FAP with nutritional support. This paper presents the results of the first six months of this nutritional activity.METHODS: Sixty-eight individuals with FAP, >18 years of age, who underwent a prophylactic total colectomy, entered in this observational study. At the baseline visit, participants underwent anthropometric measurements, answered the Mediterranean Diet Adherence Screener (MEDAS), the Faecal Incontinence Quality of Life (FIQL) questionnaire, and reported the number of their diarrhoeal discharges per day. They received dietary recommendations including specific information about the inflammatory food to reduce (red/processed meat, sugar, sweets), and the Mediterranean food to increase (vegetables, fruits, whole grain cereal in cream and legumes' hummus).RESULTS: After six months, participants repeated the same baseline measurements. Fifty-three individuals with FAP completed the six-month follow-up. The before-after analysis showed significant improvements in patients' body composition measurements and MEDAS score. Participants significantly reduced the number of diarrhoeal discharges per day. FIQL results showed improvements in lifestyle, behaviour, and depression scores.CONCLUSIONS: These results suggest that targeted low-inflammatory Mediterranean dietary recommendations are effective in improving anthropometric parameters, diet quality, and various aspects of quality of life related to bowel function in individuals with FAP.PMID:39568398 | DOI:10.1177/03008916241287719

Phytother Res. 2024 Nov 21. doi: 10.1002/ptr.8392. Online ahead of print.ABSTRACTThe activation of neural stem cells (NSCs) residing in the subventricular zone (SVZ) and dentate gyrus (DG) has been shown to promote the restoration of damaged brain tissues. Ginsenoside Rb3 (Rb3) is a bioactive substance known for its pharmacological properties in treating neurological disorders. This study investigated the effects of Rb3 on neural regeneration following ischaemic stroke (IS) and the underlying mechanisms involved. Male C57BL/6 mice were utilized and were subjected to middle cerebral artery occlusion/reperfusion (MCAO/R). Post-ischemia, Rb3 was administered through intraperitoneal (i.p.) injection for either 7 or 28 days. The promotion of Rb3 on regenerative neurogenesis was detected by immunofluorescence staining. NSCs were pretreated with different concentrations of Rb3 for 24 h before oxygen-glucose deprivation/reoxygenation (OGD/R) exposure. Afterward, immunofluorescence staining and flow cytometry were used to detect the migration and proliferation of Rb3 in OGD/R-induced NSCs. Furthermore, Adeno-associated virus (AAV) transduction experiments, siRNA transfection experiments, gene knockout experiments, targeted metabolomics analysis, molecular dynamics simulation, cellular thermal shift assay (CETSA), and drug affinity responsive target stability (DARTS) assays were used to explore the promotion and mechanism of Rb3 on regenerative neurogenesis following IS. Rb3 promoted Opa1-mediated NSCs migration and proliferation. Knockdown of Opa1 blunted the above-promoting effects of Rb3 in both the brains of ischemia-reperfusion (I/R)-treated mice and OGD/R-treated NSCs. Mechanistically, targeted metabolomics, molecular dynamics, molecular docking, CETAS, and DARTS experiments showed that Rb3 promoted Opa1-mediated neural regeneration required the activation of Ido1 and that Ido1 served as a direct target of Rb3 to repair I/R injury. Moreover, studies in siRNA-mediated knockdown and KO mice revealed that inhibition of Ido1 attenuated the enhancing effect of Rb3 on mitochondrial fusion. Our study provides novel evidence that Rb3 promotes neurogenesis through an Ido1/Opa1-mediated pathway involving the interaction between Rb3 and Ido1, leading to improved long-term neurological function. These results indicate that Rb3 or other mitochondrial fusion promoters could be a potential neurorestorative strategy for regenerative neurogenesis following IS.PMID:39568396 | DOI:10.1002/ptr.8392

Clin Transl Med. 2024 Nov;14(11):e70093. doi: 10.1002/ctm2.70093.ABSTRACTThe profound impact of the microbiota on the initiation and progression of cancer has been a focus of attention. In recent years, many studies have shown that microbial metabolites serve as key hubs that connect the microbiome and cancer progression, but the underlying molecular mechanisms have not been fully elucidated. Multiple mechanisms that influence tumour development and therapy resistance, including disrupting cellular signalling pathways, triggering oxidative stress, inducing metabolic reprogramming and reshaping tumour immune microenvironment, are reviewed. Focusing on recent advancements in this field, this review also summarises the methodological framework of studies regarding microbial metabolites. In this review, we outline the current state of research on tumour-associated microbial metabolites and describe the challenges in future scientific research and clinical applications. KEY POINTS: Metabolites derived from both gut and intratumoural microbiota play important roles in cancer initiation and progression. The dual roles of microbial metabolites pose an obstacle for clinical translations. Absolute quantification and tracing techniques of microbial metabolites are essential for addressing the gaps in studies on microbial metabolites. Integrating microbial metabolomics with multi-omics transcends current research paradigms.PMID:39568157 | DOI:10.1002/ctm2.70093

Gut Microbes. 2024 Jan-Dec;16(1):2428425. doi: 10.1080/19490976.2024.2428425. Epub 2024 Nov 20.ABSTRACTRotavirus (RV) accounts for 19.11% of global diarrheal deaths. Though GAVI assisted vaccine introduction has curtailed RV induced mortality, factors like RV strain diversity, differential infantile gut microbiome, malnutrition, interference from maternal antibodies and other administered vaccines, etc. often compromise vaccine efficacy. Herein emerges the need of antivirals which can be administered adjunct to vaccination to curb the socio-economic burden stemming from frequent RV infection. Cognisance of pathogen-perturbed host cellular physiology has revolutionized translational research and aided precision-based therapy, particularly for viruses, with no metabolic machinery of their own. To date there has been limited exploration of the host cellular metabolome in context of RV infection. In this study, we explored the endometabolomic landscape of human intestinal epithelial cells (HT-29) on RV-SA11 infection. Significant alteration of host cellular metabolic pathways like the nucleotide biosynthesis pathway, alanine, aspartate and glutamate metabolism pathway, the host citric acid cycle was observed in RV-SA11 infection scenario. Detailed study further revealed that RV replication is exclusively dependent on glutamine metabolism for their propagation in host cells. Glutamine metabolism generates glutamate, aspartate, and asparagine which facilitates virus infection. Abrogation of aspartate biogenesis from glutamine by use of Aminooxyacetic acid (AOAA), significantly curbed RV-SA11 infection in-vitro and in-vivo. Overall, the study improves our understanding of host-rotavirus interactome and recognizes host glutamine metabolism pathway as a suitable target for effective therapeutic intervention against RV infection.PMID:39567865 | DOI:10.1080/19490976.2024.2428425

Nat Microbiol. 2024 Nov 20. doi: 10.1038/s41564-024-01862-z. Online ahead of print.ABSTRACTThe liver makes bile, an aqueous solution critical for fat absorption, which is secreted into the duodenum. Despite extensive studies on bile salts, other components of bile are less well characterized. Here we used global metabolomic analysis on bile from specific-pathogen-free, germ-free, Citrobacter rodentium-infected or Listeria monocytogenes-infected mice and identified a metabolome of 812 metabolites that were altered by both microbiota and enteric infection. Hepatic transcriptomics identified enteric-infection-triggered pathways that probably underlie bile remodelling. Enteric infection increased levels of four dicarboxylates in bile, including itaconate. Analysis of Acod1-/- mice indicated that increased itaconate also increased tuft cell abundance, altered microbiota composition and function as detected by metagenomic analysis, and modulated host defence, leading to reduced Vibrio cholerae colonization. Our data suggest that enteric-infection-associated signals are relayed between the intestine and liver and induce transcriptional programmes that shape the bile metabolome, modifying the immunomodulatory and host defence functions of bile.PMID:39567665 | DOI:10.1038/s41564-024-01862-z

Sci Rep. 2024 Nov 20;14(1):28747. doi: 10.1038/s41598-024-79150-3.ABSTRACTNeurotoxic effects of general anesthetics, particularly sevoflurane, on pediatric neurodevelopment are a global concern. This study investigated the molecular and metabolic impacts of repeated short exposures to sevoflurane in neonatal rats. Metabolomics analysis revealed significant changes in fatty acid and mitochondrial energy metabolism. Transcriptomic analysis identified altered gene expression related to neurodevelopment and mitochondrial function. Various analyses emphasized upregulation in oxidative phosphorylation and DNA repair pathways. Weighted gene co-expression network analysis (WGCNA) identified key gene modules associated with sevoflurane exposure. Despite these acute changes, no significant long-term memory impairments were detected. These findings highlight the impact of sevoflurane on mitochondrial energy metabolism, oxidative stress, and neuroinflammation, emphasizing its relevance to pediatric neurodevelopment. The absence of substantial long-term memory impairments provides insights into the safety and implications of sevoflurane use in pediatric anesthesia, calling for further research.PMID:39567567 | DOI:10.1038/s41598-024-79150-3

Nat Commun. 2024 Nov 20;15(1):10068. doi: 10.1038/s41467-024-54417-5.ABSTRACTDrought is one of the most serious abiotic stresses, and emerging evidence suggest plant microbiome affects plant drought tolerance. However, there is a lack of genetic evidence regarding whether and how plants orchestrate the dynamic assembly of the microbiome upon drought. By utilizing mutants with enhanced or decreased root hair densities, we find that root hair regulators also affect drought induced root microbiome changes. Rhizobiaceae is a key biomarker taxa affected by root hair related mutants. We isolated and sequenced 1479 root associated microbes, and confirmed that several Rhizobium strains presented stress-alleviating activities. Metagenome, root transcriptome and root metabolome studies further reveal the multi-omic changes upon drought stress. We knocked out an ornithine cyclodeaminase (ocd) gene in Rhizobium sp. 4F10, which significantly dampens its stress alleviating ability. Our genetic and integrated multi-omics studies confirm the involvement of host genetic effects in reshaping a stress-alleviating root microbiome during drought, and provide mechanistic insights into Rhizobiaceae mediated abiotic stress protection.PMID:39567534 | DOI:10.1038/s41467-024-54417-5

Eur J Nutr. 2024 Nov 21;64(1):13. doi: 10.1007/s00394-024-03527-3.ABSTRACTBACKGROUND: Multiple diet patterns play a crucial role in the development of colorectal cancer and its precursor, colorectal adenoma, but mediating effect of plasma metabolite profiles is unclear.METHODS: A total of 95,275 participants from UK Biobank with plasma metabolomics and dietary information were analyzed. Metabolite profile scores for 14 dietary patterns were estimated through elastic net regression. Cox regression analysis assessed the associations of dietary patterns and their metabolite profile scores with colorectal tumor risk. Mediating effects of identified metabolite profile scores were estimated in the associations.RESULTS: Fourteen metabolite profile scores, including a range of 28 to 205 signatures, were weak to moderate correlation with dietary patterns (all p < 0.001). Multivariable Cox regression analyses revealed that five dietary patterns were significantly correlated with a decreased risk of colorectal tumor after FDR correction and adjustment for covariates. HRs (95% CIs) per 1 SD for these diet patterns were as follows: WCRF (0.93, 0.90-0.96), CRC score (0.94, 0.92-0.97), AHEI-2010 (0.95, 0.92-0.97), DASH (0.94, 0.91-0.97), and hPDI (0.95, 0.93-0.98). Similarly, metabolite profile scores for these five dietary patterns were inversely associated with colorectal tumor risk, with HRs (95% CIs) per 1 SD as follows: WCRF (0.59, 0.49-0.70), CRC score (0.67, 0.58-0.77), AHEI-2010 (0.73, 0.65-0.80), DASH (0.75, 0.66-0.84), and hPDI (0.56, 0.47-0.67). The mediation proportions of five metabolite profile scores between dietary patterns and colorectal tumor risk ranged from 6.37 to 27.23% (all p < 0.001).CONCLUSIONS: Five dietary patterns and their metabolite profile scores, were inversely correlated with colorectal tumor risk. These findings highlight the potential of metabolite profiles as mediators in the association between dietary patterns and the risk of colorectal tumor, further contributing to the prevention of colorectal cancer or adenoma and providing new insights for future research.PMID:39567382 | DOI:10.1007/s00394-024-03527-3