PubMed

J Nutr Biochem. 2025 Feb 6:109845. doi: 10.1016/j.jnutbio.2025.109845. Online ahead of print.ABSTRACTThe disturbance of gut microbiota and its metabolites are considered to be the causes of ulcerative colitis (UC), which leads to immune abnormalities. Diet is the most important regulator of gut microbiota; therefore, it has a beneficial impact on UC. A novel food ingredient, L-theanine, alters the gut microbiota, thereby regulating gut immunity. However, whether L-theanine prevents UC by altering the gut microbiota, as well as the underlying mechanisms, remains unknown. Here, L-theanine was used to optimize the gut microbiota and its metabolites. Furthermore, to explore the mechanism by which L-theanine prevents UC, an L-theanine fecal microbiota solution was used to prevent dextran sulfate sodium-induced UC via fecal microbiota transplantation. Improvements in the colonic structure, colon histology scores, immune factors (IL-10), and inflammatory factors (IL-1β) demonstrated the preventive effect of L-theanine on UC. The 16S rDNA and metabolomic results showed that tryptophan-, short chain fatty acid-, and bile acid-related microbiota, such as Muribaculaceae, Lachnospiraceae, Alloprevotella, and Prevotellaceae were the dominant. Flow cytometry results showed that L-theanine decreased helper T (Th)1 and Th17 immune responses, and increased Th2 and T-regulatory immune responses via regulation of antigen-presenting cell responses, such as dendritic cells and macrophages. Therefore, L-theanine regulated the immune response of colon CD4 + T cells to dendritic cell and macrophage antigen presentation via tryptophan-, short chain fatty acid-, and bile acid-related microbiota, thereby preventing dextran sulfate sodium-induced UC.PMID:39922394 | DOI:10.1016/j.jnutbio.2025.109845

J Ethnopharmacol. 2025 Feb 6:119456. doi: 10.1016/j.jep.2025.119456. Online ahead of print.ABSTRACTETHNOPHARMACOLOGICAL RELEVANCE: The hypothalamic-pituitary-adrenal (HPA) axis plays a vital role in the protection against sepsis. Sini decoction (SND) could improve HPA axis function.AIM OF THE STUDY: This work aimed to explore the effective mechanism of SND against lipopolysaccharide (LPS)-induced sepsis in rats from the metabolic regulation of the HPA axis microenvironment.MATERIALS AND METHODS: We evaluated the multiorgan injury-associated enzymatic indicators and histopathological changes as well as the ultrastructural changes in the hypothalamus, pituitary gland, and adrenal gland associated with LPS-induced sepsis. Serum inflammatory cytokines, corticotropin-releasing hormone (CRH), adrenocorticotropic hormone (ACTH) and corticosterone (CORT) were determined by ELISA. The target tissues metabolomics of the HPA axis (hypothalamus, pituitary gland, and adrenal gland), based on ultra-high performance liquid chromatography coupled with quadrupole-time-of-flight mass spectrometry (UHPLC-Q-TOFMS), were conducted to dissect the metabolic network regulated by SND. Western blotting was further used to validate the key metabolic pathways. In addition, the absorbed chemical constituents in serum and cerebrospinal fluid were identified by UHPLC-Q-TOFMS combined with solid-phase extraction.RESULTS: Forty and twenty-three components of SND were absorbed into the serum and cerebrospinal fluid, respectively. SND could decrease multiorgan injury-associated indicators, including serum creatine kinase, urea nitrogen, creatinine, lactate dehydrogenase, alanine aminotransferase, and aspartate aminotransferase, inhibit inflammatory cytokines IL-6 and TNF-α, regulate the serum levels of CRH, ACTH and CORT in LPS-induced septic rats, and alleviate the sepsis-induced morphological changes in the heart, liver, spleen, lung, and kidney and HPA tissues. SND had the ability to regulate the unbalanced glycerophospholipid metabolism, fatty acid β-oxidation, fatty acid amide metabolism, tryptophan metabolism and arachidonic acid metabolism to improve the LPS-induced sepsis. The results of western blotting analysis demonstrated that SND could decrease the expressions of LPCAT1 and IDO1 and increase the expressions of CPT1A and FAAH1 to regulate the above metabolic disorders.CONCLUSION: SND could alleviate LPS-induced sepsis partly via restoration of metabolic impairments in the HPA axis microenvironment, which provided important insights to future work to ascertain the mechanisms undergoing the HPA axis response to SND against sepsis.PMID:39922328 | DOI:10.1016/j.jep.2025.119456

J Ethnopharmacol. 2025 Feb 6:119452. doi: 10.1016/j.jep.2025.119452. Online ahead of print.ABSTRACTETHNOPHARMACOLOGICAL RELEVANCE: Gaultheria leucocarpa var. yunnanensis, a distinguished member of the Gaultheria Kalm ex L. in the Ericaceae family, has been traditionally employed in the southwestern regions of China for the efficacious treatment of rheumatoid arthritis (RA). The anti-RA fraction (ARF) derived from Gaultheria leucocarpa var. yunnanensis has been previously demonstrated to effectively alleviate RA in vivo and in vitro.AIM OF THE STUDY: This research endeavor is dedicated to surveying the pharmacokinetic (PK) processes of ARF within plasma and tissues, profiling its metabolites in vivo, discerning the material foundation of its therapeutic efficacy, and delineating its anti-RA mechanisms.MATERIALS AND METHODS: The prototype components and metabolites of ARF in plasma and seven tissues of RA rats were analyzed by LC-MSn. Advanced LC-MS/MS and HPLC-DAD methodologies were developed to investigate the plasma PK profiles and tissue distribution characteristics of MSTG-A, MSTG-B, and Gaultherin in both RA model rats and healthy controls. A panel of four cytokines (TNF-α, IL-1, IL-6, and IL-2) was selected as pharmacodynamic (PD) biomarkers and quantified using ELISA. The PK, PD, and PK-PD modeling of ARF were skillfully constructed by combining WinNonlin with Matlab software, enabling a comprehensive analysis of the interrelationships between components and effect markers. A non-targeted plasma metabolomics approach employing LC-QE-MS was utilized to insight into the underlying mechanisms of ARF alleviating RA.RESULTS: The quantity and diversity of identified prototypical components and metabolites of ARF in model rat plasma increased over time. The spleen exhibited the highest number of metabolites and prototypical compounds of ARF. The UPLC-QQQ-MS/MS and HPLC-DAD method were developed and validated for the quantification of three chemical markers in rat plasma and tissues, respectively. Three effective components (MSTG-B, MSTG-A, and Gautherin) demonstrated linear dynamics in plasma and tissues at an oral dosage of 3 g/kg ARF. The PK-PD models involving three components and four inflammatory cytokines aligned with the one company model, demonstrating a linear correlation through compartmental modeling and curve fitting analysis. Significant variations were identified in the concentrations of various amino acids and lipid metabolites among the CON, ARF, and MTX groups in comparison to the MOD group, which are intricately linked to the inflammation-immunity response.CONCLUSIONS: The three components displayed favorable bioavailability and were rapidly eliminated in RA rats, collectively exerting an anti-RA effect. The mechanism by which ARF mitigates RA is associated with the modulation of inflammation-immunity related metabolic pathways. The spleen may serve as the target tissue for ARF attenuating RA. These findings provide a robust foundation for rationalizing intervention strategies, elucidating biological mechanisms, and advancing the clinical application of ARF in the amelioration of RA.PMID:39922327 | DOI:10.1016/j.jep.2025.119452

Biochem Pharmacol. 2025 Feb 6:116793. doi: 10.1016/j.bcp.2025.116793. Online ahead of print.ABSTRACTNatural products are known to be a rich source of potential compounds for metabolic diseases. In this study, we aim to identify the lead compounds with anti-adipogenic and anti-obesity effects in Cimicifuga foetida L. (CF). Five high-content chemicals from ethyl acetate-(EtOAc) extract of CF (ECF) were isolated to investigate their effects on adipogenesis in 3 T3-L1 preadipocytes. Actein is identified to possess substantial anti-adipogenic activity in 3 T3-L1 adipocytes, which exerts its anti-adipogenic effect throughout the entire adipocyte differentiation stages. Dietary actein ameliorates diet-induced obesity, improves the disturbed serum lipid levels, and enhances white fat browning in diet-induced obese mice. Metabolomic analysis using urine and serum samples from mice revealed that actein treatment reverses the dysregulation of γ-linolenic acid and lecithin in obese mice, thus ameliorating the disturbance of linoleic acid metabolism induced by high-fat diet, suggesting that actein can be used as a lead compound with the potential to develop new therapies for obesity and related metabolic disorders.PMID:39922317 | DOI:10.1016/j.bcp.2025.116793

Environ Res. 2025 Feb 6:121074. doi: 10.1016/j.envres.2025.121074. Online ahead of print.ABSTRACTMaternal exposure to per- and polyfluoroalkyl substances (PFAS) has been associated with offspring adiposity; however, underlying mechanisms remain unclear. In this study, we quantified 11 PFAS in maternal plasma collected between 12 and 16 gestational weeks and 104 lipid metabolites in the cord blood of 525 mother-infant pairs. Principal components of multiple PFAS compounds, extracted by principal component analysis, were employed to investigate the effect of the PFAS mixture. Infant anthropometric indicators included weight, length, waist/arm circumference, and abdominal/triceps/subscapular skinfold thickness at birth and 6 and 12 months old. Multiple linear regression showed that maternal PFAS exposure was primarily associated with increased glycerophospholipids and decreased fatty acyls and bile acids in cord blood. Four glycerophospholipids (16:0 PI, 16:0-18:1 PI, 18:0-20:4 PI, and 18:0-18:1 PS), fatty acyls (5(S)-HETE, 15(S)-HETE, 13-HDoHE, and dhkPGF2), and bile acids (GCA, TCA, TCDA, and TDCA) partially mediated the positive associations of the first principle component of PFAS compounds (with positive loadings for all PFAS compounds), PFNA, and PFUdA with infant skinfold thickness with mediating proportions ranging from 7.58-33.39%. Our findings provide novel insights into mechanisms underlying the effects of maternal PFAS exposure on infant growth.PMID:39922253 | DOI:10.1016/j.envres.2025.121074

Fish Shellfish Immunol. 2025 Feb 6:110165. doi: 10.1016/j.fsi.2025.110165. Online ahead of print.ABSTRACTDensity is an important aquaculture parameter. When the pearl gentian grouper (Epinephelus fuscoguttatus♀×E. lanceolatus♂) is farmed intensively, it could lead to a degradation in genetic resources and an increase in disease outbreaks. The composition of the intestinal microbiota plays a key role in creating a specific intestinal microecosystem, which is essential for the survival, growth, and immune response of the host under environmental stress like overcrowding. This study utilized 16S rRNA sequencing and metabolomics analysis techniques to investigate the differences in intestinal microbial community stability of grouper under different stocking time and density pressure conditions. The research results showed that compared to the low-density group, the high-density group of groupers experienced an increase in mortality rate and feed coefficient in the early stages of culture, while the weight gain rate decreased. Differential analysis of intestinal microbial communities revealed significant differences in the gut microbiota of grouper between different density groups after 10 days of culture, but no significant differences were observed after 20 days of culture. At the same time, intestinal histopathology showed that the high-density group of groupers exhibited a reduction in intestinal villi length and thickness of the intestinal wall after 10 days of culture. However, the intergroup differences had reduced after 20 days of culture. Furthermore, high density cultivation upregulated the expression of inflammatory factors like IL-1β, TNF-α, IL-8, and IL-6 in the intestinal tract of groupers after 10 days of culture. However, after 20 days of culture, the expression levels of intestinal inflammatory factors in both the high-density and low-density groups of groupers were significantly reduced, and the differences between the intergroup diminished. Through correlation analysis of differential metabolites and species in the intestine, multiple metabolites significantly upregulated and associated with the upregulation of the Staphylococcus genus were identified in the intestinal tract of groupers after 20 days of high-density cultivation. The selected four associated metabolites (including creatine, fosinopril, 4-aminobutyric acid, and guanidinopropanoic acid) were validated to significantly reduce the expression of cellular inflammatory factors using the self-established grouper head kidney (HK) cell line. In conclusion, density pressure in the early culture period could affect the stability of the intestinal microbial environment of grouper. As aquaculture time increases, the intestinal microbial community of grouper drives the body's anti-inflammatory response and enhanced its adaptation to density pressure by regulating own structure and secretion of metabolites.PMID:39922247 | DOI:10.1016/j.fsi.2025.110165

Phytomedicine. 2025 Feb 2;139:156445. doi: 10.1016/j.phymed.2025.156445. Online ahead of print.ABSTRACTBACKGROUND: Although probiotics-based therapies and postbiotics derived from Lactobacillus reuteri (L. reuteri) hold promising potential in mitigating alcohol-associated liver disease (ALD), the role of L. reuteri's metabolite, 3-Hydroxypropionaldehyde (3-HPA, reuterin), remains elusive.PURPOSE: The objective of this study is to examine the influence of 3-HPA on the attenuation of alcohol-induced hepatic steatosis and its underlying mechanisms.METHODS: The study utilizes network pharmacology to identify potential targets for 3-HPA in treating ALD. Comprehensive analytical methods, including histological and biochemical assessments, coupled with metabolomics techniques, are employed to evaluate the protective mechanisms and actions of 3-HPA in ALD. Additionally, the therapeutic potential of hepatic aryl hydrocarbon receptor (AhR) activation is explored through using both an AhR agonist and inhibitor, in order to assess the potential of 3-HPA as an AhR ligand in treating ALD.RESULTS: Chronic alcohol consumption stimulates AhR activation in hepatocytes, both in vivo and in vitro, leading to the disruption of hepatic tryptophan metabolism. Our observations indicate that 3-HPA has the potential to regulate this process by activating AhR signaling through modulating tryptophan metabolism, specifically affecting indole acetaldehyde, indole, and 5‑hydroxy-l-tryptophan (5-HTP) levels. Mechanistically, 3-HPA demonstrates potential as an effective AhR agonist in mitigating ethanol-induced liver injury by regulating AhR-CD36 signaling, thereby exerting protective effects against hepatic steatosis.CONCLUSION: Ultimately, the study identifies a previously uncharacterized role of 3-HPA in alleviating alcohol-associated liver injury and hepatic steatosis. It further elucidates that 3-HPA serves as a mediator in tryptophan metabolism, activating the AhR signaling, thereby suggesting its potential as a promising candidate for the treatment of ALD.PMID:39922148 | DOI:10.1016/j.phymed.2025.156445

Phytomedicine. 2025 Feb 6;139:156462. doi: 10.1016/j.phymed.2025.156462. Online ahead of print.ABSTRACTBACKGROUND: Parkinson's disease (PD) is a neurodegenerative disease, and neuroinflammation is an important factor in its pathogenesis. Therefore, improving neuroinflammation has become a key direction in PD research. Cycloastragenol (CAG) is one of the active ingredients in Astragalus membranaceus, which has pharmacological activities such as anti-inflammatory, antioxidant, and neuroprotective effects. However, there are few reports on its pharmacological effects on PD. Therefore, it is necessary to comprehensively evaluate the pharmacological effects of CAG on PD and elucidate the potential mechanisms of action, providing new ideas for drug development in PD.OBJECTIVE: To comprehensively and systematically evaluate the pharmacological effects of CAG on PD and reveal its potential mechanisms of action.RESEARCH DESIGN AND METHODS: Firstly, the pharmacological effects of CAG on cell viability, cytotoxicity, behavior, and pathology were evaluated using PD in vitro (MPP+ induced SH-SY5Y cells) and in vivo models (MPTP induced mouse model). Furthermore, potential targets and signaling pathways will be screened based on metabolomics and transcriptomics. Ultimately, the connection between the target and the signaling pathway will be validated to elucidate the potential mechanism by which CAG exerts its effects.RESULT: CAG can significantly improve the behavioral indicators of PD mice, enhance neuronal vitality, and improve neuroinflammatory levels by inhibiting the expression of inflammatory factors. In addition, CAG can target and activate the expression of Fpr2, thereby regulating the TLR4/NF-κB signaling pathway and promoting the resolution of inflammation.PMID:39922145 | DOI:10.1016/j.phymed.2025.156462

Food Chem. 2025 Feb 1;474:143079. doi: 10.1016/j.foodchem.2025.143079. Online ahead of print.ABSTRACTAs the primary raw material for Baijiu brewing, sorghum variety exerts an intricate influence on the taste profile of strong-flavor Baijiu. However, how sorghum variety comprehensively affects Baijiu flavor formation through fermentation by microorganisms and metabolites remains largely unknown. Using 16S&ITS rRNA gene sequencing and non-targeted metabolomics, in this study we comprehensively analyzed the changes in microbial communities and metabolites during fermentation of a glutinous and non-glutinous sorghum variety. The results showed that these varieties significantly affected microbial diversity and community structure, and their interactions, among which, there were particularly complex interactions among bacterial communities, while the effects of "functional differentiation" and "community aggregation" of fungal communities were prominent. Furthermore, three bacterial and nine fungal genera were identified as core microorganisms related to changes in glycerophospholipids during fermentation, that led to a change in ester content, ultimately improving Baijiu quality. These findings provide reference for the selection of brewing materials.PMID:39921974 | DOI:10.1016/j.foodchem.2025.143079

Cell Rep. 2025 Feb 7;44(2):115278. doi: 10.1016/j.celrep.2025.115278. Online ahead of print.ABSTRACTThe transcription factor carbohydrate response element binding protein (ChREBP) activates genes of glucose, fructose, and lipid metabolism in response to carbohydrate feeding. Integrated transcriptomic and metabolomic analyses in rats with GalNac-siRNA-mediated suppression of ChREBP expression in liver reveal other ChREBP functions. GalNac-siChREBP treatment reduces expression of genes involved in coenzyme A (CoA) biosynthesis, with lowering of CoA and short-chain acyl-CoA levels. Despite suppression of pyruvate kinase, pyruvate levels are maintained, possibly via increased expression of pyruvate and amino acid transporters. In addition, expression of multiple anaplerotic enzymes is decreased by GalNac-siChREBP treatment, affecting TCA cycle intermediates. Finally, GalNAc-siChREBP treatment suppresses late steps in purine and NAD synthesis, with increases in precursors and lowering of end products in both pathways. In sum, our study reveals functions of ChREBP beyond its canonical roles in carbohydrate and lipid metabolism to include regulation of substrate transport, mitochondrial function, and energy balance.PMID:39921857 | DOI:10.1016/j.celrep.2025.115278

Cell Biol Toxicol. 2025 Feb 8;41(1):41. doi: 10.1007/s10565-024-09972-4.ABSTRACTSojae semen praeparatum is a traditional Chinese medicine, and its active component, Glycitin, has shown potential in the treatment of non-small cell lung cancer (NSCLC). The purpose of this investigation is to examine the mechanism of action of the effective components of sojae semen praeparatum in the treatment of NSCLC, with a special emphasis on Glycitin, and to explore the integration of nanotechnology in delivering pharmaceutical agents. Key effective components were selected through network pharmacology analysis and functional analysis, and protein-protein interaction analysis and functional enrichment were performed using transcriptomics and metabolomics data to identify the key NSCLC-related target genes and regulatory mechanisms of action of the active components of sojae semen praeparatum. Glycitin-loaded NPs encapsulated in tumor-associated fibroblast membranes were developed to verify their characterization and safety, and their therapeutic effects in inhibiting the malignant phenotype of NSCLC cells through targeting the DNA topoisomerase II alpha (TOP2A) protein were validated. The results indicate that Glycitin exhibits significant anti-tumor activity by affecting the function of the TOP2A protein, thereby inhibiting tumor proliferation and metastasis. This research presents proof of the crucial function of Glycitin in managing NSCLC using sojae semen praeparatum, and sheds light on the possibilities of nanotechnology in drug delivery mechanisms, offering a novel avenue for NSCLC therapy research.PMID:39921782 | DOI:10.1007/s10565-024-09972-4

Vet Q. 2025 Dec;45(1):1-14. doi: 10.1080/01652176.2025.2463338. Epub 2025 Feb 8.ABSTRACTBovine mammosphere-derived epithelial cell (MDEC) cultures are heterogeneous and enriched for stem and progenitor cells. We previously reported that the bovine MDEC secretome, comprised of all bioactive factors secreted by the cells, displays regenerative properties, exerts antimicrobial effects, and modulates neutrophil activity, positioning it as a promising non-antibiotic biologic therapy for infectious diseases important to the dairy industry, like mastitis. Mastitis is defined as inflammation of the udder, and it is typically caused by bacterial infection. The effect of the MDEC secretome on macrophages, a first line of defense against bacterial infections in the udder, is unknown and could impact the utility of the secretome as a therapy for mastitis. To address this, we isolated bovine monocytes from peripheral blood and maintained them as an unpolarized (M0) population or polarized them into M1 or M2 phenotypes. Macrophages cultured with the secretome of bovine MDECs were assessed for their ability to phagocytose labeled bacterial particles and accumulate reactive oxygen species (ROS). We used single-cell RNA sequencing (scRNA-seq) and fluorescence-activated cell sorting (FACS) to isolate a subpopulation of MDECs that exert enhanced effects on macrophages. We found that the secretome of MDECs that do not express cluster of differentiation (CD) 73, a cell surface enzyme used as a marker for mesenchymal stromal cells, most strongly increased macrophage phagocytosis and ROS accumulation. These findings will help optimize the generation of the bovine MDEC secretome as a suitable treatment option for mastitis.PMID:39921381 | DOI:10.1080/01652176.2025.2463338

Am J Clin Nutr. 2025 Feb 5:S0002-9165(25)00070-X. doi: 10.1016/j.ajcnut.2025.02.002. Online ahead of print.ABSTRACTBACKGROUND: Human milk offers significant health benefits for infants; however, when not feasible, infant formula serves as an alternative. The higher protein content in infant formula is thought to contribute to the distinct metabolic profiles observed in formula-fed infants compared to those fed human milk.OBJECTIVES: This study investigates the impact of formula protein quantity and whey protein types on the serum, urine, and fecal metabolomes of infants.METHODS: A secondary analysis was performed on a random subset of 200 well-characterized per-protocol infants who completed a prospective, randomized, double-blind controlled trial. Infants were randomly assigned to one of three groups: standard formula, protein-reduced formula with α-lactalbumin-enriched whey, or protein-reduced formula with casein glycomacropeptide-reduced whey, along with an observational reference group of exclusively human milk-fed infants. Serum, urine, and fecal metabolites were quantified using 1H NMR spectroscopy at baseline (1-2 months), 4, and 6 months of age. Dietary intake was assessed monthly up to 6 months of age.RESULTS: Formula protein content and type of whey protein used significantly influenced the amino acid profile and associated catabolic markers in serum and urine but had minimal impact on the fecal metabolome. Reduced protein formulas yielded metabolome profiles closer to those of human milk-fed infants compared to standard formula. Despite these improvements, infants fed human milk still demonstrated enhanced branched-chain amino acid (BCAA) oxidation and a greater capacity to eliminate catabolic waste products from BCAA metabolism over infants consuming protein-reduced formulas.CONCLUSIONS: Comprehensive metabolomics profiling of serum, urine and feces captures molecular-level changes and informs potential strategies for formula optimization. Both the quantity and source of protein significantly influenced the metabolic profiles of formula-fed infants. However, modifications in protein alone cannot fully resolve the metabolic differences between formula-fed and human milk-fed infants, highlighting the complexity of mimicking the human milk feeding-associated metabolic profile.CLINICAL TRIAL REGISTRATION: This study was registered at ClinicalTrials.gov as NCT02410057.PMID:39921093 | DOI:10.1016/j.ajcnut.2025.02.002

Mol Metab. 2025 Feb 5:102109. doi: 10.1016/j.molmet.2025.102109. Online ahead of print.ABSTRACTOBJECTIVE: There is growing evidence that sleep deprivation promotes cancer progression. In addition, colon cancer patients often experience sleep deprivation due to factors such as cancer pain and side effects of treatment. The occurrence of liver metastases is an important factor in the mortality of colon cancer patients. However, the relationship between sleep deprivation and liver metastases from colon cancer has not been elucidated.METHODS: A sleep deprivation liver metastasis model was constructed to evaluate the effect of sleep deprivation on liver metastasis of colon cancer. Subsequently, mice feces were collected for untargeted metabolomics to screen and identify the key mediator, Kynurenic acid (KynA). Furthermore, HILPDA was screened by transcriptomics, and its potential mechanism was explored through ChIP, co-IP, ubiquitination experiments, phenotyping experiments, etc. RESULTS: Sleep deprivation promotes liver metastases in colon cancer. Functionally, sleep deprivation aggravates lipid accumulation and decreases the production of the microbiota metabolite KynA. In contrast, KynA inhibited colon cancer progression in vitro. In vivo, KynA supplementation reversed the promoting effects of sleep deprivation on liver metastases from colon cancer. Mechanistically, KynA downregulates the expression of P4HA2 to promote the ubiquitination and degradation of HIF-1α, which leads to a decrease in the transcription of HILPDA, and ultimately leads to an increase in lipolysis of colon cancer cells.CONCLUSION: Our findings reveal that sleep deprivation impairs intracellular lipolysis by KynA, leading to lipid droplets accumulation in colon cancer cells. This process ultimately promotes colon cancer liver metastasis. This suggests a promising strategy for colon cancer treatment.PMID:39920992 | DOI:10.1016/j.molmet.2025.102109

Microbiome. 2025 Feb 7;13(1):47. doi: 10.1186/s40168-025-02040-x.NO ABSTRACTPMID:39920859 | DOI:10.1186/s40168-025-02040-x

Microbiome. 2025 Feb 7;13(1):45. doi: 10.1186/s40168-025-02042-9.ABSTRACTBACKGROUND: Weaning-associated enteric diseases are a major concern in the swine industry. This study investigates the effects of fecal microbiota transplantation (FMT) on the jejunum of weanling piglets, a segment of bowel less studied in terms of microbiomic changes despite its primary involvement in major post-weaning enteric diseases, including postweaning diarrhea (PWD). Thirty-two 3-week-old piglets were divided equally into two groups: Control and FMT. The FMT group received fecal microbiota preparation from 3-month-old healthy pigs on the 1st and 3rd day after weaning. Half of each group was inoculated with an enterotoxigenic E. coli (ETEC) isolate 10 days post-FMT. Piglets were euthanized in the third week (14th and 18th days post-FMT) after weaning to collect intestinal tissues and contents for microbiomic, metabolomic, and transcriptomic analyses.RESULTS: The jejunal microbiota showed a significant increase in alpha diversity in the third week post-FMT compared with the ileum and colon. FMT significantly enriched the jejunal microbiota composition, while multiple bacterial genera were specifically lacking in control weanling piglets. FMT was strongly associated with the enrichment of the genus Pseudoscardovia of the Bifidobacteriaceae family, which was found lacking in the jejunum of weanling control piglets and inversely associated with the abundance of the genus Bifidobacterium within the same family. Other genera associated with FMT included Solobacterium, Shuttleworthia, and Pseudoraminibacter, whereas bacteria such as Erysipelotrichaceae and Acidaminococcus were identified as most abundant in the control piglets. Metabolomic analysis revealed a significant modulatory effect of FMT on carbohydrate, amino acid, nucleotide, vitamin, and xenobiotic metabolisms, suggesting improved nutrient utilization. Transcriptomic analyses further confirmed the regulatory effects of FMT on gene expression associated with immune, metabolic, barrier, and neuroendocrine functions. Prior FMT treatment in the context of ETEC infection indicated a potential protective role, as evidenced by a significant shift in microbial diversity and metabolomic compositions and decreased diarrhea severity even though no effect on pathogen shedding was evident.CONCLUSIONS: This study underscores the promise of FMT in enhancing jejunal health. In addition, the results suggest that FMT could be considered a potential strategy to address conditions associated with small intestinal dysbiosis in swine and other monogastric species with similar gut anatomy and physiology, such as humans. Video Abstract.PMID:39920804 | DOI:10.1186/s40168-025-02042-9

Microbiome. 2025 Feb 7;13(1):44. doi: 10.1186/s40168-025-02034-9.ABSTRACTBACKGROUND: Synthetic human milk oligosaccharides (HMOs) are used to supplement infant formula despite limited understanding of their impact on the post-weaned developing gut microbiota. Here, we assess the influence of 0.5 g/L 2-fucosyllactose (2'FL) and 4.0 g/L pooled HMOs (pHMOs) on the composition and activity of cultured fecal-derived microbial communities from seven healthy young children.RESULTS: Exposure to pHMOs induced significant shifts in both the microbial community composition and metabolic output, including an increased abundance of several genera, notably Bacteroides, and the production of health-associated metabolites. In contrast, 2'FL alone did not lead to substantial changes in the communities. A total of 330 bacterial isolates, spanning 157 species, were cultured from these communities and individually evaluated for their responses to HMOs. Over 100 non-Bifidobacterium species showed enhanced growth upon pHMOs treatment and a high degree of intraspecies variation in HMO metabolism was observed.CONCLUSION: Our study provides valuable insight into the health-enhancing properties of HMOs while highlighting the need for future research into the efficacy of incorporating individual structures into infant formula, particularly when aiming to modulate the gut microbiota. Video Abstract.PMID:39920790 | DOI:10.1186/s40168-025-02034-9

BMC Endocr Disord. 2025 Feb 7;25(1):32. doi: 10.1186/s12902-025-01861-z.ABSTRACTBACKGROUND: Type 2 diabetes mellitus (T2DM) is the fastest-growing metabolic disease in the world. The gut microbiota is linked to T2DM. Recent studies have showed that the metabolism of gut microbiota can trigger T2DM. Low dose radiation (LDR) has been proved to activate various protective bioeffects on diabetes. However, the underlying mechanisms remain unclear.METHODS: In this study, T2DM model was established using high fat diet combined with streptozocin (STZ) injection in C57BL/6 mice, and then exposed to multiple 75 mGy LDR every other day for one month. The changes of blood glucose levels, body weight, and the damage of pancreas were measured. In addition, 16 S rDNA amplicon sequencing was used to detect gut microbiota alteration. Metabolic profiling was carried out using the liquid mass spectrometry system, followed by the combinative analysis of gut microbiota alteration. Furthermore, the inflammatory factors and related pathways were detected.RESULTS: We found that LDR attenuate blood glucose levels and the weights of body in T2DM mice, and reduce pancreas impairment. In addition, in the gut, LDR regulated the relative abundance of Bacilli, Desulfobacterota, Verrucomicrobiota, and Proteobacteria. The non-target metabolomics analysis found that LDR significantly improve the metabolic abnormalities in T2DM, which is closely related to the gut microbiota abundance. Furthermore, the inflammatory effects activated by TLR4/MyD88/NF-κB pathways in T2DM were ameliorated by LDR.CONCLUSION: These results suggest that LDR may exert a beneficial role in T2DM by modulating gut microbiota and metabolites, especially in TLR4/MyD88/NF-κB pathway.PMID:39920713 | DOI:10.1186/s12902-025-01861-z

Metabolomics. 2025 Feb 7;21(1):24. doi: 10.1007/s11306-024-02220-0.ABSTRACTBACKGROUND: Chronic periodontitis is a condition impacting approximately 50% of the world's population. As chronic periodontitis progresses, the bacteria in the oral cavity change resulting in new microbial interactions which in turn influence metabolite production. Chronic periodontitis manifests with inflammation of the periodontal tissues, which is progressively developed due to bacterial infection and prolonged bacterial interaction with the host immune response. The bi-directional relationship between periodontitis and systemic diseases has been reported in many previous studies. Traditional diagnostic methods for chronic periodontitis and systemic diseases such as chronic kidney diseases (CKD) have limitations due to their invasiveness, requiring practised individuals for sample collection, frequent blood collection, and long waiting times for the results. More rapid methods are required to detect such systemic diseases, however, the metabolic profiles of the oral cavity first need to be determined.AIM OF REVIEW: In this review, we explored metabolomics studies that have investigated salivary metabolic profiles associated with chronic periodontitis and systemic illnesses including CKD, oral cancer, Alzheimer's disease, Parkinsons's disease, and diabetes to highlight the most recent methodologies that have been applied in this field.KEY SCIENTIFIC CONCEPTS OF THE REVIEW: Of the rapid, high throughput techniques for metabolite profiling, Nuclear magnetic resonance (NMR) spectroscopy was the most applied technique, followed by liquid chromatography-mass spectrometry (LC-MS) and gas chromatography-mass spectrometry (GC-MS). Furthermore, Raman spectroscopy was the most used vibrational spectroscopic technique for comparison of the saliva from periodontitis patients to healthy individuals, whilst Fourier Transform Infra-Red Spectroscopy (FT-IR) was not utilised as much in this field. A recommendation for cultivating periodontal bacteria in a synthetic medium designed to replicate the conditions and composition of saliva in the oral environment is suggested to facilitate the identification of their metabolites. This approach is instrumental in assessing the potential of these metabolites as biomarkers for systemic illnesses.PMID:39920480 | DOI:10.1007/s11306-024-02220-0

Metabolomics. 2025 Feb 7;21(1):25. doi: 10.1007/s11306-024-02217-9.ABSTRACTINTRODUCTION: The diagnosis of Growth Hormone Deficiency (GHD) during childhood has been the subject of much controversy over the last few years. Aiming to accurate medical treatment, there is a need for biomarker discovery.OBJECTIVE: To characterize the metabolic profile of GHD children, examine the effect of GH administration on the metabolic signature, and investigate the correlations between metabolites and IGF-1.METHODS: Nuclear Magnetic Resonance (NMR)-based untargeted and targeted metabolomic approach applied to study the metabolic profiles of children with GHD. Plasma, serum, and urine samples were collected from twenty-two children diagnosed with GHD and forty-eight age matched controls from the Pediatric Endocrinology Unit of the University Hospital of Patras. Experimental data were examined by both multivariate and univariate statistical analysis.RESULTS: The results of this pilot study revealed a different metabolic fingerprint of children with GHD in comparison to age-matched healthy individuals. However, the detected alterations in the metabolite patterns before and after GH treatment were subtle and of minor discriminative statistical power.CONCLUSIONS: This study provides evidence that metabolome plays a pivotal role in GHD, but large-scale multicenter studies are warranted to validate the results.PMID:39920379 | DOI:10.1007/s11306-024-02217-9