PubMed

Food Res Int. 2025 May;208:116061. doi: 10.1016/j.foodres.2025.116061. Epub 2025 Feb 27.ABSTRACTThe coexistence and coevolution of viruses and fermenting microbes have a significant impact on the structure and function of microbial communities. Although the presence of viruses in Daqu, the fermentation starter for Chinese Baijiu, has been documented, their specific effects on the community composition and metabolic functions of low, medium, and high-temperature Daqu remain unclear. In this study, we employed multi-omics technology to explore the distribution of viruses and active bacteria and fungi in various Daqu and their potential metabolic roles. Viral metagenomic sequencing showed a predominance of Parvoviridae in High-Temperature Daqu (HTQ), while Genomoviridae were dominant in Medium-Temperature Daqu (MTQ) and Low- Temperature Daqu (LTQ). Phages belonging to the Siphoviridae, Podoviridae, Herelleviridae, and Myoviridae families showed significantly different abundances across three Daqu groups. Metatranscriptomic analysis showed that fungal communities were most active in LTQ, whereas bacterial communities were dominant in MTQ and HTQ. By employing the CRISPR-Cas spacer, a higher predicted number of phage-host linkages was identified in LTQ, particularly with hosts including Lactobacillus, Staphylococcus, Acinetobacter, Enterobacter, and Bacillus. Correlation analysis showed that bacteria like Acinetobacter, Lactobacillus, and Streptococcus exhibited the strongest associations with metabolites, particularly amino acids and organic acids. The potential phage-induced metabolic differences in the three Daqu groups were mainly linked to pathways involved in the metabolism of amino acids, sugars, and organic acids. Overall, our study elucidates the impact of viruses on shaping microbial composition and influencing metabolic functions in Daqu. These results improve our comprehension of viruses and microbes in Daqu microbial communities and provide valuable insights for enhancing quality control in Daqu production.PMID:40263874 | DOI:10.1016/j.foodres.2025.116061

Food Res Int. 2025 May;208:116060. doi: 10.1016/j.foodres.2025.116060. Epub 2025 Mar 8.ABSTRACTThis study systematically examined the effects of processing techniques on the flavor profiles and functional attributes of tea derived from fresh leaves (Camellia sinensis) of identical origin. Pu-erh raw tea (PRT), white tea (WT), and black tea (BT) were produced through distinct processing protocols (non-fermented, lightly fermented, and fully fermented, respectively). Antioxidant activity and sensory characteristics were evaluated alongside comprehensive metabolomic analyses using GC-IMS, GC-MS, and UHPLC-QTOF-MS. PRT exhibited superior antioxidant capacity with pronounced bitterness and astringency, whereas WT displayed fruity-sweet notes and BT demonstrated a mellow profile linked to fermentation. Metabolomic profiling identified six discriminative biomarkers and two pivotal compounds differentiating tea types, alongside six key metabolic pathways (e.g., secondary metabolite biosynthesis) driving compositional variations. These findings elucidate processing-induced biochemical transformations, offering insights for quality optimization and consumer-oriented tea selection.PMID:40263873 | DOI:10.1016/j.foodres.2025.116060

Food Res Int. 2025 May;208:116043. doi: 10.1016/j.foodres.2025.116043. Epub 2025 Feb 24.ABSTRACTVolatolomics - branch of metabolomics focused on volatile organic compounds (VOCs) - provides a wealth of information for characterizing foodborne pathogens and their behavior. But there is no knowledge relating on how to sample microbial VOCs. The aim of the present study was to determine the most informative sampling mode for further volatolomics. Taking Listeria monocytogenes (L.monocytogenes) as a model pathogen and using case-control experiments based on 0-24 h cultures on liquid synthetic growth medium, bacteria volatolomics was performed by headspace solid phase microextraction - gas chromatography - Q Exactive - Orbitrap ™ mass spectrometry on three types of samples: (i) the whole culture, which contains global information diluted by the growth medium, (ii) the pellet collected after centrifugation of the whole culture, which concentrates bacterial cells; and (iii) the related supernatant which includes what the bacteria released into the growth medium. Compound Discoverer ™ software was used for automatic peak deconvolution of VOCs. The three sampling modes resulted in different and complementary L.monocytogenes candidate VOC markers: whole culture and pellet together cover 83 % of the candidate markers, while supernatant and supernatant-pellet combination reveal only 59 % and 74 %, respectively. The robustness of the candidate VOC markers identified together with the relevance of combining the different sampling modes are discussed.PMID:40263872 | DOI:10.1016/j.foodres.2025.116043

Food Res Int. 2025 May;208:116218. doi: 10.1016/j.foodres.2025.116218. Epub 2025 Mar 14.ABSTRACTChitosan, is a natural bio-based polymer with known prebiotic properties. However, its potential in the management of spermatogenic disorders remains largely unexplored. By utilizing a busulfan-treated mouse model and integrated multi-omics analysis, this study explored the potential mechanisms through which chitosan improves impaired spermatogenesis. The results showed that chitosan treatment can improve testicular function and significantly reshape the gut microbiota composition in busulfan-treated mice. Metabolomics revealed that docosahexaenoic acid (DHA) transport was significantly dysregulated in busulfan-treated mice, but chitosan reversed this dysfunction by modulating tight junction proteins and fatty acid transporters in the intestine. Fecal microbiota transplantation experiments further highlighted the critical role of gut microbiota in DHA transport and spermatogenesis. Additionally, DHA supplementation alleviated busulfan-induced ferroptosis in testicular tissues. Hence, owing to its prebiotic effects chitosan could serve as a novel therapeutic strategy for improving busulfan-induced spermatogenic disorders by restoring the homeostasis of the gut-testis axis.PMID:40263850 | DOI:10.1016/j.foodres.2025.116218

Food Res Int. 2025 May;208:116202. doi: 10.1016/j.foodres.2025.116202. Epub 2025 Mar 15.ABSTRACTPerturbations in intestinal homeostasis can significantly influence the pathophysiology of metabolic disorders through the gut-liver axis, with nonalcoholic fatty liver disease (NAFLD) being a prime example. Our previous study demonstrated that Akebia trifoliata extracts (APE) exhibit significant anti-inflammatory activity; however, their protective effect on the intestinal barrier and liver remain unclear. In this study, we established a TNF-α-induced Caco-2 cell monolayer model and a mouse model of NAFLD with DSS-induced low grade colitis. Serum, intestinal tissue, and liver samples were used to assess the effects of APE effects on inflammation, gut barrier integrity, and hepatic lipid metabolism. 16S rRNA sequencing, targeted metabolomics, and RNA sequencing were employed to examine gut microbiota composition, short-chain fatty acid metabolism, and liver gene expression profiles. Results indicated that APE effectively alleviates hepatic steatosis induced by HFD and DSS reducing by hepatocellular lipid accumulation. APE treatment also reduced inflammatory cytokine levels, including TNF-α, IL-6, and IL-1β. Additionally, APE restored the impaired intestinal barrier by reducing intestinal permeability, enhancing tight junction protein expression, and modulating gut microbiota composition. Notably, APE reduced the abundance of Verrucomicrobia and Prevotellaceae, while increasing the abundance of Proteobacteria, Lachnospiraceae, Ruminococcaceae, and Bifidobacterium. Correlation analysis indicated that the abundance of Ruminococcaceae was negatively correlated with levels of d-mannitol, liver LPS, and IL-6, while it was positively correlated with butyrate concentration. Furthermore, liver inflammatory factors, TG, TC, IL-6 and LPS levels were positively correlated with serum d-mannitol levels, but negatively correlated with intestinal ZO-1 expression and acetic and propionic acid levels. This study is the first to explore the hepatoprotective effects of bioactives from Akebia trifoliata via the gut-liver axis, thereby broadening the application value of Akebia trifoliata.PMID:40263842 | DOI:10.1016/j.foodres.2025.116202

Food Res Int. 2025 May;208:116187. doi: 10.1016/j.foodres.2025.116187. Epub 2025 Mar 13.ABSTRACTThe metabolites of green coffee beans can be influenced by various factors, including species, variety, geographical origin, and post-harvest processing methods. However, previous studies often focused on limited factors separately and were not comprehensive in scope, utilizing only green coffee beans from a restricted area. To fill the gap, we simultaneously analyzed 176 global green coffee beans (C. arabica) from various continents, altitudes, post-harvest processing methods, and varieties to comprehensively investigate the primary factors influencing coffee quality, using metabolomics approach with GC-MS, and machine learning analysis. Partial least squares-discriminant analysis (PLS-DA) revealed that coffee bean characteristics were differently affected by each factor, highlighting 56 key metabolites that varied by each factor, while simultaneously identifying metabolites associated with sub-level variables within each factor. According to the F1 score of the Random Forest model (continent: 91.5 %, altitude: 74.2 %, processing method: 81.4 %, variety: 64.7 %), the continent had the greatest effect on coffee metabolite profiles, followed by the post-harvest processing, altitude, and variety. Additionally, comprehensive heatmap visualizations, incorporating the four factors, are presented, which can be utilized as valuable information for manufacturing customized coffee beans aligned with consumer preferences. These findings provide comprehensive insights into the association between various factors affecting coffee quality and coffee metabolites.PMID:40263838 | DOI:10.1016/j.foodres.2025.116187

Food Res Int. 2025 May;208:116170. doi: 10.1016/j.foodres.2025.116170. Epub 2025 Mar 22.NO ABSTRACTPMID:40263834 | DOI:10.1016/j.foodres.2025.116170

Food Res Int. 2025 May;208:116168. doi: 10.1016/j.foodres.2025.116168. Epub 2025 Mar 13.ABSTRACTFruits, vegetables, and plant-based foods contain several bioactive substances such as phenolic compounds (PCs), that are plant secondary metabolites with attributed health properties. The study of the metabolic pathways of PCs, including those related with their synthesis, transport, accumulation, and degradation are essential to advance in this field of research. In this regard, omics tools such as foodomics are gaining relevance due to their versatility and their tremendous potential to generate significant advances in PC research. In this review, we present a comprehensive overview of the applications of omics technologies in PC analysis, including transcriptomics, micromics, proteomics and metabolomics, highlighting their role in metabolic pathways, current limitations, and emerging insights. Omics techniques as well as data analyses are continuously progressing, emerging new opportunities with onset of artificial intelligence and machine learning. However, significant limitations and challenges still remain. The immense diversity of PC chemical structures and their variability across plant species, varieties, and impact of agronomic factors complicate the analyses and limit the extrapolation of findings. Additionally, high data dimensionality, strong correlations among measured variables, and general lack of standardization in the different omics techniques can impact in the results. Addressing these limitations requires integrating multi-omics approaches and developing standardized protocols to enhance comparability and interpretation in PC research. In summary, foodomics approaches arise as essential for the complete mapping of PC biosynthesis.PMID:40263832 | DOI:10.1016/j.foodres.2025.116168

Food Res Int. 2025 May;208:116181. doi: 10.1016/j.foodres.2025.116181. Epub 2025 Mar 14.ABSTRACTBlack tea flavor is predominantly shaped by the internal composition of the materials utilized, and black teas produced from high-polyphenol varieties is typically characterized by a stronger, bitter, astringent taste with a low aroma intensity. Therefore, understanding the flavor profile and material basis of black tea produced from high-amino acids tea plants may be helpful to enhance flavor and innovate black tea products. Here, by sensory evaluation and metabolomics analysis, it was found that the typical flavor of 'Baiye 1' black tea (BYBT) was orange-red solution color, a sweet potato-like or sweet honey-like aroma, and a sweet, umami, and light taste. A total of 110 characteristic volatiles of BYBT were identified, among which 29 metabolites, including β-ionone with a sweet aroma, may be considered the key compounds responsible for the sweet aroma. The geraniol, cis-3-hexenyl isovalerate, and n-valeric acid cis-3-hexenyl were key volatiles that distinguish different seasons. Additionally, 7 volatiles, including β-ocimene, geraniol, citral, were the crucial metabolites responsible for the stronger sweet or honey aroma of BYBT in spring. The lower tea polyphenols and the higher amino acids and sugars shaped the BYBT profile with distinct umami and sweetness, as well as a light taste. Amino acids, catechins and their derivatives were the most significantly affected by seasonal variations in BYBT, and were also responsible for the differences in taste and color quality observed between samples with different seasons. The findings of this study provided a scientific foundation for the development of novel black tea products or derivatives thereof.PMID:40263789 | DOI:10.1016/j.foodres.2025.116181

Food Res Int. 2025 May;208:116114. doi: 10.1016/j.foodres.2025.116114. Epub 2025 Mar 4.ABSTRACTComprehensive 2D gas chromatography-mass spectrometry (GC × GC-MS) and non-targeted metabolomics were used in this study to systematically investigate the effects of various fermentation agent combinations on the quality characteristics of Sichuan-style fermented sausages. The results indicate that the inoculation of the combined starter culture significantly improves the sensory score and texture characteristics of Sichuan-style sausages, with the overall acceptability score increasing from 77.6 to 79.9-82.9. Furthermore, substantial improvements were observed in key texture parameters, particularly in hardness (increased from 9050.34 g to 10,625.40-16,633.95 g) and chewiness (elevated from 2231.33 g to 2327.23-4505.71 g). Additionally, it reduces both pH values (from 5.86 to 5.83-5.71) and moisture content (from 31.84 % to 31.72-28.99 %). The combined starter culture facilitates the degradation, transformation, and metabolism of proteins and lipids in the sausages, resulting in the production of more metabolites and volatile flavor compounds. In addition, the combined starter culture may promote the release of flavor substances in the sausage spices, thereby enhancing the overall flavor quality. Compared to the control group, the combined starter culture F, comprising Debaryomyces hansenii, Lactobacillus curvatus, Staphylococcus carnosus, and Staphylococcus vitulinus, significantly increased the levels of 60 volatile flavor substances, such as linalool, β-myrcene, and 3-methyl-1-butanol, in the sausages. The combined starter culture F enhanced the levels of 73 secondary metabolites, including beneficial amino acids, organic acids, fatty acids, and others, demonstrating its superior effectiveness in improving the quality characteristics of Sichuan-style fermented sausages.PMID:40263780 | DOI:10.1016/j.foodres.2025.116114

Food Res Int. 2025 May;208:116111. doi: 10.1016/j.foodres.2025.116111. Epub 2025 Mar 4.ABSTRACTPrevious studies imply that dark tea has more advantages in facilitating the growth of Akkermansia which may be beneficial to anti-obesity. However, whether those benefits are affected by the unique processing (microbial fermentation) of dark tea remains unclear. Moreover, although there are many reports regarding the comparison of anti-obesity effects among different types of tea, the insights into the relationship between tea pharmacological component and the therapeutic effects are still limited due to the ununified tea raw material. In our study, the anti-obesity effects of non-microbial fermentation tea (NFT) and microbial fermentation tea (FT) are investigated and compared. By controlling for the raw material source, the effects of microbial fermentation on tea in alleviating obesity symptoms are effectively isolated. Our results suggested that even though NFT and FT showed distinctive differences in terms of ingredients, they exerted similar properties in attenuating overweight, regulating glucolipid metabolism, and alleviating hepatic dysfunction. The underlying mechanisms could be that NFT and FT displayed similar effects in promoting the proliferation of Akkermansia as well as enhancing the production of short-chain fatty acids. Furthermore, tea chemical constituent analyses exhibited that although microbial fermentation caused differences in polyphenol profiling between NFT and FT, it didn't remarkably influence the polyphenol content in tea which is strongly associated with the growth of Akkermansia. This might be root cause of the comparable effects on alleviating obesity symptoms between NFT and FT groups. Together, the current data supplied valuable information on the relationship among the microbial fermentation of tea, tea bioactivities, and obesity symptoms for mankind to understand.PMID:40263778 | DOI:10.1016/j.foodres.2025.116111

Thorac Cancer. 2025 Apr;16(8):e70068. doi: 10.1111/1759-7714.70068.ABSTRACTBACKGROUND: Brain metastasis is a common and severe complication in non-small cell lung cancer (NSCLC) patients, significantly affecting prognosis. However, the role of gut microbiota and its metabolites in NSCLC brain metastasis remains poorly understood. This study aims to explore the relationship between gut microbiota, metabolites, and the development of brain metastasis in NSCLC.METHODS: We conducted an integrative analysis combining metagenomics and non-targeted metabolomics on baseline fecal samples from NSCLC patients with brain metastasis (n = 18) and those without distant metastasis (n = 12). Gut microbiota composition and metabolite profiles were detected and analyzed, and statistical methods, including machine learning models, were applied to identify differences and potential biomarkers.RESULTS: Significant differences in gut microbiota composition were found between the two groups, with higher microbial diversity observed in patients with brain metastasis. Specific genera, such as Paenibacillus, Fournierella, and Adlercreutzia, were enriched in the brain metastasis group. Metabolomic analysis revealed altered levels of short-chain fatty acids and other metabolites associated with immune modulation and vascular permeability, including angiotensin (1-7). These changes were linked to the metastatic process and may influence brain metastasis development. Furthermore, machine learning models identified key biomarkers, such as Raoultibacter, Mobilibacterium, and N-acetyl-L-glutamic acid, which could serve as valuable indicators for brain metastasis.CONCLUSIONS: Our findings suggest that gut microbiota dysbiosis and its metabolic products may contribute to the development of brain metastasis in NSCLC. The identification of microbiota-derived biomarkers holds potential for early detection and therapeutic intervention in NSCLC brain metastasis.PMID:40263747 | DOI:10.1111/1759-7714.70068

Sci Rep. 2025 Apr 22;15(1):13963. doi: 10.1038/s41598-025-98547-2.ABSTRACTThe present research aimed to assess the metabolomic responses of wheat to olive mill wastewater (OMWW) and drought stress treatments. Wheat plants were cultivated under controlled conditions with the following treatments: control (75% field capacity, FC), OMWW (75 ml L-1), drought stress (40% FC, applied 30 days after sowing), and a combined treatment of OMWW and drought stress. Drought stress alone reduced grain yield by 67%, while the OMWW-treated plants resulted in a 29% reduction under stress relative to the control. OMWW application improved soil properties, enhancing organic matter and nutrient levels. Wheat grains from OMWW-treated plants exhibited higher sugar content and related enzyme activities, indicating improved metabolism, with significant increases in starch, fructose, and glucose levels alongside stable invertase and sucrose phosphate synthase activities. The study also noted substantial changes in amino acids, fatty acids, and phenolic acids in plants subjected to OMWW and drought stress. These modifications indicate OMWW's capability to influence vital biochemical pathways and boost antioxidant capacities in wheat. In conclusion, OMWW proves to be an effective soil amendment that mitigates drought stress and contributes to the production of nutrient-rich, resilient wheat, underscoring its potential as a sustainable agricultural practice in water-scarce areas.PMID:40263511 | DOI:10.1038/s41598-025-98547-2

Eur J Clin Nutr. 2025 Apr 22. doi: 10.1038/s41430-025-01625-x. Online ahead of print.ABSTRACTBACKGROUND: Objective biomarkers of diet, such as metabolomics, may improve dietary assessment and provide additional insight into how diet influences disease risk. The portfolio diet, a cholesterol-lowering plant-based diet, is recommended for lowering low-density lipoprotein cholesterol (LDL-C). This diet is low in saturated fat and includes nuts, plant protein (legumes), viscous fiber, and phytosterols.OBJECTIVE: We examined metabolomic profiles in response to the portfolio diet in two randomized controlled trials (RCTs), where all foods were provided to the participants, compared to a control vegetarian diet and the same control diet with a statin.METHODS: The first RCT included 34 adults (age 58.4 ± 8.6 y) and the second RCT included 25 adults (age 61.0 ± 9.6 y), all with high LDL-C (>4.1 mmol/L). Plasma samples were obtained at baseline, week 2, and week 4 in both RCTs for metabolomics analysis using liquid chromatography-tandem mass spectrometry. Linear mixed models were used to examine effects of the interventions on the metabolites in each RCT, applying a Bonferroni correction.RESULTS: Of 496 known metabolites, 145 and 63 metabolites significantly changed within the portfolio diet interventions in the first and second RCT, respectively. The majority were glycerophosphocholines (32%), triacylglycerols (20%), glycerophosphoethanolamines (14%), sphingomyelins (8%), and amino acids and peptides (8%) in the first RCT, and glycerophosphocholines (48%), glycerophosphoethanolamines (17%), and amino acids and peptides (8%) in the second RCT. Fifty-two metabolites were consistently changed in the same direction with the portfolio diet intervention across both RCTs, after Bonferroni correction.CONCLUSIONS: Many of these metabolites likely reflect the plant-based nature, low saturated fat content, and cholesterol-lowering effects of the diet, such as increased N2-acetylornithine, L-pipecolic acid, lenticin, and decreased C18:0 lipids and cholesteryl esters. Further research is needed to validate these metabolites as biomarkers of a plant-based dietary pattern.PMID:40263496 | DOI:10.1038/s41430-025-01625-x

Sci Rep. 2025 Apr 22;15(1):13903. doi: 10.1038/s41598-025-90859-7.ABSTRACTAlthough positive effects of microwave irradiation on plants have been reported, their underlying mechanisms remain unknown. In this study, we investigated the effects of low microwave irradiation on Arabidopsis thaliana. Interestingly, we found low output (23 W) with oscillating condition (not continuous irradiation) promoted plant growth. The microwave irradiation neither raised the plants' temperature nor induced heat responsive gene expression. Furthermore, overall transcriptome profile in microwave irradiation treated plants were significantly different from heat treated plants, suggesting that growth promotion might be attributed to non-thermal effects of microwave. Transcriptome and metabolome analysis indicated that microwave irradiation altered circadian clock as well as hormonal response especially in auxin and gibberellin, which promoted plant growth by inducing amino acid biosynthesis and stress tolerance, and reducing cell wall thickness. This finding potentially contributes to develop new approach to increase food production through accelerating crop yield in environmentally friendly way.PMID:40263396 | DOI:10.1038/s41598-025-90859-7

Sci Rep. 2025 Apr 22;15(1):13822. doi: 10.1038/s41598-025-97710-z.ABSTRACTPsilocybin-producing fungi have garnered attention due to accumulating evidence regarding the therapeutic potential of their principal component psilocybin. This diverse group of fungi harbors a wealth of less-studied metabolites, however, thus far most research has addressed them as a cohesive group. By optimizing an approach for extraction and analysis, we examined the metabolomes of 42 distinct fungi strains and show that the breadth and diversity of metabolites within and between 9 species. We integrated and validated the reproducible and reliable extraction of fruiting bodies followed by chromatographic separation, quantification and identification of their known and yet to be identified secondary metabolites. The optimal extraction of fruiting bodies for high yield of indole alkaloids was achieved using a 1:20 tissue:solvent ratio, 25:75 H2O:MeOH (pH = 9), for 1.5 h, followed by the quantification of 8 tryptophan-derived indolamines by HPLC-DAD and the identification of putative metabolite hydroxypsilocybin by HPLC-MS/MS. The metabolomic analysis revealed the diversity of metabolites within and between species. Finally, we developed and present a method that mimics the in vivo process of dephosphorylation that occurs upon ingestion for in vitro setups. Overall, our study summarizes a standardized approach for both in vitro and in vivo studies involving psilocybin-producing fungi, showcasing the unique metabolome of each strain and the rich diversity of these fungi, encompassing promising pharmaceutical potential.PMID:40263354 | DOI:10.1038/s41598-025-97710-z

Nat Commun. 2025 Apr 22;16(1):3750. doi: 10.1038/s41467-025-58972-3.ABSTRACTType 1 diabetes is a chronic, autoimmune disease characterized by the destruction of insulin-producing β-cells in the pancreas. Early detection can facilitate timely intervention, potentially delaying or preventing disease onset. Circulating proteins reflect dysregulated biological processes and offer insights into early disease mechanisms. Here, we construct a genome-wide pQTL map of 1985 proteins in 695 newborn babies (median age 2 days) at increased genetic risk of developing Type 1 diabetes. We identify 535 pQTLs (352 cis-pQTLs, 183 trans-pQTLs), 62 of which characteristic of newborns. We show colocalization of pQTLs for CTRB1, APOBR, IL7R, CPA1, and PNLIPRP1 with Type 1 diabetes GWAS signals, and Mendelian randomization causally implicates each of these five proteins in the aetiology of Type 1 diabetes. Our study illustrates the utility of newborn molecular profiles for discovering potential drug targets for childhood diseases of significant concern.PMID:40263317 | DOI:10.1038/s41467-025-58972-3

Cell Death Dis. 2025 Apr 22;16(1):327. doi: 10.1038/s41419-025-07661-6.ABSTRACTFMS-like tyrosine kinase 3-internal tandem duplication (FLT3/ITD) is a common driver mutation that presents with a high leukemic burden and its impact on metabolic homeostasis remains to be further investigated. Here, we revealed that the oncogenic activation of FLT3/ITD induced upregulation of target genes of sterol regulatory element-binding proteins (SREBPs) in vivo and in acute myeloid leukemia patients. Quizartinib is a second-generation FLT3 inhibitor that selectively inhibits the activating FLT3 mutations. We demonstrated the critical role of SREBP1 degradation in conferring the response of FLT3/ITD cells to quizartinib. Mechanistically, quizartinib facilitated degradation of the precursor form of SREBP1 via the FLT3/AKT/GSK3 axis and reduced protein levels of its target gene fatty acid synthase (FASN). Lipidomics analysis by Liquid Chromatography Mass Spectrometry (LC-MS) demonstrated that inhibition of FLT3 altered global levels of phospholipids including reduction of cardiolipin, leading to subsequent loss of mitochondrial membrane potential. Pharmacological inhibition of SREBP1 or FASN sensitized FLT3/ITD leukemia cells to quizartinib. Quizartinib combined with SREBP inhibitor fatostatin or FASN inhibitor orlistat provided substantial therapeutic benefit over monotherapies in the murine FLT3/ITD leukemia model. Our results indicated the mechanistic link between FLT3/ITD and SREBP degradation and suggested the combination therapy via targeting FLT3/SREBP/FASN axis.PMID:40263296 | DOI:10.1038/s41419-025-07661-6

NPJ Biofilms Microbiomes. 2025 Apr 22;11(1):61. doi: 10.1038/s41522-025-00698-7.ABSTRACTAn imbalance between oxidative and antioxidant processes in the host can lead to excessive oxidation, a condition known as oxidative stress (OS). Although changes in the hindgut microbiota have been frequently linked to OS, the specific microbial and metabolic underpinnings of this association remain unclear. In this study, we enrolled 81 postpartum Holstein cows and stratified them into high oxidative stress (HOS, n = 9) and low oxidative stress (LOS, n = 9) groups based on the oxidative stress index (OSi). Using a multi-omics approach, we performed 16S rRNA gene sequencing to evaluate microbial diversity, conducted metagenomic analysis to identify functional bacteria, and utilized untargeted metabolomics to profile serum metabolites. Our analyses revealed elevated levels of kynurenine, formyl-5-hydroxykynurenamine, and 5-hydroxyindole-3-acetic acid in LOS dairy cows. Additionally, the LOS cows had a higher abundance of short-chain fatty acids (SCFAs)-producing bacteria, including Bacteroidetes bacterium, Paludibacter propionicigenes, and Phascolarctobacterium succinatutens (P. succinatutens), which were negatively correlated with OSi. To explore the potential role of these bacteria in mitigating OS, we administered P. succinatutens (108 cfu/day for 14 days) to C57BL/6 J mice (n = 10). Oral administration of P. succinatutens significantly increased serum total antioxidant capacity, decreased total oxidants, and reduced OSi in mice. Moreover, this treatment promoted activation of the Nrf2-Keap1 antioxidant pathway, significantly enhancing the enzymatic activities of GSH-Px and SOD, as well as the concentrations of acetate and propionate in the colon. In conclusion, our findings suggest that systemic tryptophan metabolism and disordered SCFAs production are concurrent factors influenced by hindgut microbiota and associated with OS development. Modulating the hindgut microbiota, particularly by introducing specific SCFAs-producing bacteria, could be a promising strategy for combating OS.PMID:40263287 | DOI:10.1038/s41522-025-00698-7

Nat Commun. 2025 Apr 22;16(1):3749. doi: 10.1038/s41467-025-58762-x.ABSTRACTDespite extensive studies at the genomic, transcriptomic and metabolomic levels, the underlying mechanisms regulating longevity are incompletely understood. Post-translational protein acetylation is suggested to regulate aspects of longevity. To further explore the role of acetylation, we develop the PHARAOH computational tool based on the 100-fold differences in longevity within the mammalian class. Analyzing acetylome and proteome data across 107 mammalian species identifies 482 and 695 significant longevity-associated acetylated lysine residues in mice and humans, respectively. These sites include acetylated lysines in short-lived mammals that are replaced by permanent acetylation or deacetylation mimickers, glutamine or arginine, respectively, in long-lived mammals. Conversely, glutamine or arginine residues in short-lived mammals are replaced by reversibly acetylated lysine in long-lived mammals. Pathway analyses highlight the involvement of mitochondrial translation, cell cycle, fatty acid oxidation, transsulfuration, DNA repair and others in longevity. A validation assay shows that substituting lysine 386 with arginine in mouse cystathionine beta synthase, to attain the human sequence, increases the pro-longevity activity of this enzyme. Likewise, replacing the human ubiquitin-specific peptidase 10 acetylated lysine 714 with arginine as in short-lived mammals, reduces its anti-neoplastic function. Overall, in this work we propose a link between the conservation of protein acetylation and mammalian longevity.PMID:40263264 | DOI:10.1038/s41467-025-58762-x