PubMed
The regulatory effect of PI3K/Akt/HIF-1α glycolytic signaling pathway on the metabolites in urine of mice with bleomycin-induced pulmonary fibrosis model
Zhonghua Lao Dong Wei Sheng Zhi Ye Bing Za Zhi. 2026 Aug 20;44(8):633-641. doi: 10.3760/cma.j.cn121094-20240814-00379.ABSTRACTObjective: To investigate the regulatory effects of the phosphatidylinositol-4, 5-bisphosphate 3-kinase (PI3K)/protein kinase B (Akt)/hypoxia-inducible factor 1α (HIF-1α) glycolytic signaling pathway on urinary metabolites in a mouse model of bleomycin-induced pulmonary fibrosis. Methods: From May to October 2023, 36 C57BL/6 mice were randomly divided into six groups (n=6 each): control (BD) group, bleomycin model (BM) group, early PI3K inhibitor (LY294002) intervention (BZLY) group, late PI3K inhibitor intervention (BWLY) group, early HIF-1α inhibitor[2-methoxyestradiol(2-ME2) ] intervention (BZ2M) group, and late HIF-1α inhibitor intervention (BW2M) group. Idiopathic pulmonary fibrosis model was established in mice by a single non-exposed intratracheal instillation of 4 mg/kg bleomycin. Mice in the intervention groups received intraperitoneal injections of 1.0 mg/kg LY294002 or 16 mg/kg 2-ME2 starting on day 2 or day 22 post-exposure, lasting 41 or 21 days, respectively. On day 42 post-exposure, urine of each group of mice was collected, the mice were sacrificed and the lung tissues were collected. Lung histopathology of mice was assessed by HE staining. Urine metabolomics was performed, and differential metabolites were identified using principal component analysis (PCA) and orthogonal partial least squares discriminant analysis (OPLS-DA), followed by pathway enrichment analysis. Results: At 42 days post-exposure, the mice in BM group showed inflammatory cell infiltration in the pulmonary interstitium and alveolar spaces, along with pulmonary interstitial fibrosis. The degrees of inflammatory cell infiltration and fibrosis in the lung tissues of the mice in each intervention groups were all alleviated. Compared with the BD group, 5 differential metabolites were identified in the urine of mice in the BM group. Compared with the BM group, the BZLY, BWLY, BZ2M, and BW2M groups exhibited 5, 3, 4, and 6 differential urinary metabolites in mice, respectively. Pathway enrichment analysis revealed 6 significantly altered metabolic pathways: purine metabolism, linoleic acid metabolism, α-linolenic acid metabolism, riboflavin metabolism, sphingolipid metabolism, and tyrosine metabolism (P<0.05) . Conclusion: The PI3K/Akt/HIF-1α glycolytic signaling pathway may regulate the development and progression of idiopathic pulmonary fibrosis through purine metabolism, linoleic acid metabolism, α-linolenic acid metabolism, riboflavin metabolism, sphingolipid metabolism, and tyrosine metabolism pathways.PMID:42706012 | DOI:10.3760/cma.j.cn121094-20240814-00379
A multi-herb botanical formula ameliorates diet-induced non-alcoholic fatty liver disease associated with microbiota-dependent metabolic remodeling in mice
Food Res Int. 2026 Nov 1;243(Pt 2):120383. doi: 10.1016/j.foodres.2026.120383. Epub 2026 Aug 21.ABSTRACTNon-alcoholic fatty liver disease (NAFLD) is closely associated with gut microbial dysbiosis and metabolic dysfunction, yet effective and sustainable therapeutic options remain limited. Wuqing Decoction (WQT), a multi-herb botanical formula containing Pueraria lobata and other medicinal and edible components, has shown metabolic regulatory potential, but its mechanistic basis in NAFLD remains unclear. Here, we evaluated the preventive and therapeutic effects of WQT in high-fat diet (HFD)-induced NAFLD mice and examined its microbiota-dependent mechanisms. WQT significantly alleviated hepatic steatosis, improved serum lipid profiles and liver injury markers, and reduced systemic inflammation, with more pronounced effects observed under preventive administration. Multi-omics analyses showed that WQT increased gut microbial diversity, altered community composition, and enriched beneficial taxa such as Akkermansia, Lactobacillus, and Ligilactobacillus. These changes were accompanied by coordinated shifts in fecal metabolites, including short-chain fatty acids, bile acid-related metabolites, and microbiota-derived phytochemical metabolites such as ginsenoside C-K. Hepatic transcriptomic profiling further demonstrated significant enrichment of fatty acid degradation and PPAR signaling pathways, indicating enhanced lipid catabolism and metabolic reprogramming. Importantly, antibiotic-mediated microbiota depletion markedly attenuated the metabolic, metabolomic, and transcriptional responses to WQT, whereas fecal microbiota transplantation partially restored these effects, supporting a microbiota-dependent mechanism. Collectively, these findings suggest that WQT ameliorates NAFLD through microbiota-dependent metabolic remodeling, which is associated with activation of the hepatic PPAR signaling network, highlighting its potential as a microbiota-targeted botanical intervention for metabolic liver disease.PMID:42705792 | DOI:10.1016/j.foodres.2026.120383
Unravelling the role of lipid molecules in odor-active compound formation during beef roasting
Food Res Int. 2026 Nov 1;243(Pt 2):120452. doi: 10.1016/j.foodres.2026.120452. Epub 2026 Aug 19.ABSTRACTLipids greatly influence beef aroma, but their role in forming odor-active compounds during roasting remains unclear. In this study, changes in aroma compounds, lipid profiles, and their correlations during roasting were investigated by integrating volatilomics and lipidomics. Aroma profiles varied across roasting stages. Twenty odor-active compounds, including 1-octen-3-one, hexanal, (E, E)-2,4-decadienal, dimethyl trisulfide, 1-octen-3-ol, trimethylpyrazine, and 2-acetyl-2-thiazoline, were critical for differentiating the aroma profile during roasting. Lipidomic profiling altered during roasting, particularly in the 0-2.5 min period. Six molecules, namely TG(16:1/18:0/20:4), TG(18:3/16:0/18:3), TG(16:1/18:1/18:2), TG(18:1/18:1/20:4), PC(P-16:0/18:1) and PC(16:0/18:1), were identified as potential key lipids. Correlation analysis revealed that triglyceride and phosphatidylcholine molecules with C16:1, C18:1, C18:2, C18:3, and C20:4 fatty acyl chains showed negative correlation with odor-active compounds such as 2-pentylfuran, γ-hexalactone, and (E, E)-2,4-decadienal. This indicates triglyceride and phosphatidylcholine molecules' involvement in beef odorant formation. The study provided a detailed elucidation of lipids' role in aroma generation in roasted beef.PMID:42705791 | DOI:10.1016/j.foodres.2026.120452
Integrated rumen microbiome and lipidomic analyses reveal the effects of feeding-regimes on fat deposition and mutton odor formation in Bashbay sheep
Food Res Int. 2026 Nov 1;243(Pt 2):120443. doi: 10.1016/j.foodres.2026.120443. Epub 2026 Aug 20.ABSTRACTThis study investigated how natural grazing and concentrate-based feeding regime regulate mutton odor-related compound deposition through the rumen microbiota-fermentation-lipid metabolism axis in Bashbay sheep. Sixteen healthy 6-month-old uncastrated Bashbay rams were assigned to the natural grazing group (FM) and the concentrate-based feeding group (SS), with eight animals per group. Mutton odor-related compounds, rumen fermentation parameters, rumen microbiota, and lipidomic profiles of subcutaneous adipose tissue (SAT), perirenal adipose tissue (PAT), and tail fat tissue (TFT) were analyzed using gas chromatography-mass spectrometry (GC-MS), full-length 16S rRNA gene sequencing, and untargeted lipidomics. The results showed that, among the three adipose depots, SAT contained the highest concentrations of 4-methyloctanoic acid (MOA), 4-ethyloctanoic acid (EOA), and 4-methylnonanoic acid (MNA), and the overall deposition of mutton odor-related branched-chain fatty acids followed the order SAT > TFT > PAT. Compared with the FM group, SS group significantly increased MNA levels and was associated with higher ruminal isobutyrate concentration and greater relative abundance of Selenomonas, whereas FM group was associated with enrichment of Saccharofermentans. Lipidomic analysis identified 2592 lipid species, mainly triglycerides (TG) and glycerophospholipids (GP). Phosphatidylcholine (PC) and phosphatidylethanolamine (PE) abundance were higher in the FM group, whereas SS group promoted TG accumulation, indicating marked remodeling of adipose tissue lipid composition in Bashbay sheep under different feeding regimes. Notably, PC 37:5 was identified as a shared exploratory candidate biomarker across SAT, PAT, and TFT, suggesting that it may reflect phospholipid remodeling characteristics in adipose tissues under natural grazing and concentrate-based feeding conditions. Partial Spearman correlation analysis showed that, after controlling for feeding regime, the associations between PC 37:5 and rumen fermentation parameters, differential microbial taxa, and mutton odor-related branched-chain fatty acids were no longer significant, indicating that PC 37:5 may be more appropriately interpreted as a candidate lipid marker. In conclusion, FM group and SS group were closely associated with differences in rumen fermentation characteristics, microbial composition, adipose tissue lipid profiles, and the deposition of mutton odor-related branched-chain fatty acids in Bashbay sheep. The lower MNA deposition under natural grazing conditions, together with changes in membrane-related phospholipid composition, suggests that natural grazing may influence mutton odor-related characteristics. This study provides insight into the formation of mutton odor-related compounds in Bashbay sheep under different feeding regimes from the perspective of the "rumen microbiota-fermentation metabolism-lipid remodeling-mutton odor-related precursor deposition" axis.PMID:42705789 | DOI:10.1016/j.foodres.2026.120443
Indirubin attenuates DSS-induced colitis in mice and is associated with partial gut microbiota shifts and altered intestinal metabolic profiles
Food Res Int. 2026 Nov 1;243(Pt 2):120412. doi: 10.1016/j.foodres.2026.120412. Epub 2026 Aug 16.ABSTRACTBACKGROUND: Ulcerative colitis (UC) is a chronic, relapsing inflammatory bowel disease for which safe and durable treatment options remain limited. Indirubin (IDB) is a natural bisindole constituent of Indigo naturalis, Folium Isatidis, and Radix Isatidis with reported anti-inflammatory activity, but the contribution of gut microbiota-host metabolic interactions to its effects in colitis remains unclear.METHODS: Male C57BL/6 mice with dextran sulfate sodium (DSS)-induced colitis received IDB at 10, 20, or 40 mg/kg, with 5-aminosalicylic acid as a positive control. Disease activity, colon histopathology, intestinal barrier proteins, inflammatory mediators, and oxidative stress indices were evaluated. 16S rRNA sequencing and untargeted metabolomics of cecal contents and colon tissue were performed in the control, DSS, and medium-dose IDB groups. Absolute bacterial-load qPCR, antibiotic treatment and fecal microbiota transplantation (FMT) were used to assess microbiota dependence. Network pharmacology, molecular docking and dynamics, and Western blotting were used to explore candidate host pathways.RESULTS: IDB attenuated body-weight loss, disease activity index and colonic mucosal damage index scores, colon shortening, histological injury, inflammatory cytokine production, and oxidative stress, while preserving ZO-1, Occludin, and Claudin-3. IDB treatment was associated with partial shifts in DSS-disrupted microbial community structure and enrichment of taxa including Bacteroidia, Muribaculaceae, Bifidobacterium and Actinomycetales. Absolute qPCR confirmed a marked reduction in total bacterial load after antibiotic treatment. The protective phenotype was markedly attenuated in antibiotic-treated mice and was partially transferred by fecal material from IDB-treated donors. Untargeted metabolomics identified candidate changes in bile acid, fatty acid, amino acid, purine, and tricarboxylic acid cycle-related pathways in cecal contents and colon tissue. These metabolic features were correlated with selected microbial taxa and disease indices. IDB also increased AMPKα and ACC1 phosphorylation in colon tissue.CONCLUSIONS: IDB alleviated DSS-induced colitis through anti-inflammatory, antioxidant, and barrier-preserving effects. The integrated functional and multi-omics findings support a microbiota-associated working model linking IDB treatment with partial gut-community shifts, altered intestinal metabolic profiles, and AMPK pathway activation.PMID:42705768 | DOI:10.1016/j.foodres.2026.120412
Atmospheric steam outperforms other thermal treatments in elevating the storage stability of oat flour: Revealed via enzyme inactivation, volatile profiles, and lipidomics
Food Res Int. 2026 Nov 1;243(Pt 2):120408. doi: 10.1016/j.foodres.2026.120408. Epub 2026 Aug 18.ABSTRACTOats, as a representative nutritious grain, are rich in various bioactive compounds, but the high endogenous lipid-related enzymes make their flour highly susceptible to hydrolytic and oxidative rancidity during storage, thus affecting nutrition and sensory quality. In this study, four thermal stabilization technologies, including microwave (MW), stir-frying (SF), far-infrared (FIR), and atmospheric steam (AS), were used to improve the storage stability of oat flour. The results showed that all treatments reduced initial lipase (LA) activity by more than 91% and delayed lipid deterioration to varying degrees. However, AS provided the strongest stabilization effect, as evidenced by the lowest measured residual enzyme activity and the highest total phenolic retention during storage. Compared with the untreated control at the end of storage, AS-treated oat flour showed only a 1.3-fold increase in fatty acid value, while peroxide value and malondialdehyde content were reduced by 38.8% and 19.9%, respectively. Furthermore, volatile profiling showed that AS restrained the accumulation of lipid-derived volatile compounds associated with oxidation, particularly aldehydes. Lipidomic analysis showed that AS markedly reduced storage-induced lipid remodeling mainly by limiting triglyceride hydrolysis, free fatty acid release, and the oxidation of unsaturated fatty acid. These findings indicated that AS outperformed other thermal treatments in elevating the storage stability of oat flour, which provided basic support for improving the shelf-life quality of whole-grain oat products.PMID:42705764 | DOI:10.1016/j.foodres.2026.120408
Flavour signatures of Duolang lamb from arid-desert and temperate regions: precursor chemistry, aroma validation and metabolomic links
Food Res Int. 2026 Nov 1;243(Pt 2):120406. doi: 10.1016/j.foodres.2026.120406. Epub 2026 Aug 17.ABSTRACTThis study investigated flavour precursor chemistry, lipid oxidation status and aroma-active compounds in Duolang lamb produced in two contrasting ecological regions of Xinjiang: the temperate continental region of northern Xinjiang (BDL) and the arid-desert region of southern Xinjiang (NDL). Fatty acid, free amino acid, nucleotide and metabolomic profiles, together with TBARS values, were determined in raw longissimus dorsi muscle, whereas electronic-tongue responses were measured in cooking broth and volatile and aroma-active compounds were analysed in meat after standardised boiling. BDL meat contained higher total fatty acids (1976.03 vs. 879.10 mg/100 g), saturated fatty acids and monounsaturated fatty acids, whereas NDL meat showed a more unsaturated lipid profile, with higher polyunsaturated fatty acids (152.76 vs. 96.56 mg/100 g), particularly C20:3n-6 and C20:4n-6. NDL also had a higher mean TBARS value than BDL, although the difference was not significant. NDL raw meat contained higher sweet amino acids, IMP, GMP, AMP and equivalent umami concentration, while its cooking broth showed higher instrumental responses associated with sweetness, umami and richness. Aldehydes dominated the volatile fraction in both groups. Aroma validation confirmed hexanal, 1-octen-3-ol and (E,E)-2,4-decadienal as common contributors to cooked lamb aroma, while (Z)-6-nonenal, 3,5-octadien-2-one and (E,E)-2,4-nonadienal were more relevant to the NDL aroma profile, and (E)-2-nonenal to BDL. Metabolomic profiling linked these differences to glycerophospholipid, linoleic acid, arachidonic acid, histidine and beta-alanine metabolism. Overall, the two regional-origin groups differed in raw-meat flavour precursors and cooked aroma profiles under their respective production environments.PMID:42705763 | DOI:10.1016/j.foodres.2026.120406
Nontargeted metabolomics of Korean and Chinese Platycodon grandiflorum using GC-TOF-MS: geographical-origin discrimination and metabolic pathway analysis via chemometrics
Food Res Int. 2026 Nov 1;243(Pt 2):120405. doi: 10.1016/j.foodres.2026.120405. Epub 2026 Aug 17.ABSTRACTPlatycodon grandiflorum is an economically significant medicinal and edible plant in East Asia, whose chemical composition varies with cultivation location. In this study, a nontargeted metabolomics approach based on gas chromatography-time-of-flight mass spectrometry was combined with multivariate chemometrics to differentiate P. grandiflorum roots from Korea and China. Following sample derivatization, 53 primary metabolites, including amino acids, organic acids, sugars, and fatty acids, were putatively annotated. Principal component analysis showed origin-related clustering, and orthogonal partial least squares discriminant analysis (OPLS-DA) showed strong discrimination (R2, Q2 > 0.8). Chinese samples showed higher relative abundances of 1-monopalmitin, 4-hydroxybutanoic acid, hexose, formic acid, and linoleic acid, whereas Korean samples showed higher L-threonine. Metabolic pathway analysis identified linoleic acid metabolism as the pathway with the highest impact, and chemical-structure-based metabolite set enrichment analysis highlighted glycerolipids as a major differential chemical class. These findings provide a promising exploratory approach for geographical-origin discrimination of P. grandiflorum.PMID:42705762 | DOI:10.1016/j.foodres.2026.120405
Spatially resolved multi-omics analysis of indigenous Bacillus-fortified high-temperature Daqu
Food Res Int. 2026 Nov 1;243(Pt 2):120404. doi: 10.1016/j.foodres.2026.120404. Epub 2026 Aug 16.ABSTRACTLayer-dependent patterns associated with indigenous Bacillus fortification on high-temperature Daqu remain unclear. Here, six indigenous functional Bacillus strains were combined to fortify Daqu at three inoculation levels (QH4, QH5, QH6), with non-fortified as the control (CK). Upper, middle, and lower shelf-layer samples were profiled by physicochemical measurements, volatilomics, organic acid analysis, untargeted metabolomics, 16S/ITS amplicon sequencing, and metagenomics. PERMANOVA showed significant effects of treatment, spatial layer, and their interaction on physicochemical, volatile, bacterial, and fungal profiles (P = 0.001). Among the three inoculation levels, QH5 showed the most balanced performance: QH5_M exhibited the highest observed mean peak temperature (63.3 °C; +4.5 °C relative to CK_M), and its group-mean temperature remained ≥ 60 °C for seven consecutive days. Multi-omics analyses indicated coordinated, non-linear, and layer-dependent differences associated with indigenous Bacillus fortification, with QH5_M showing the most pronounced combined thermal, pyrazine, substrate, microbial, and predicted functional profile. These findings indicate that moderate indigenous Bacillus fortification was associated with distinct layer-dependent thermal and flavor profiles and coordinated microbial, metabolic, and predicted functional differences.PMID:42705761 | DOI:10.1016/j.foodres.2026.120404
Mechanistic insights into flavor deterioration in bitter sturgeon caviar: Evidence from lipidomics and metagenomics
Food Res Int. 2026 Nov 1;243(Pt 2):120381. doi: 10.1016/j.foodres.2026.120381. Epub 2026 Aug 14.ABSTRACTThis study systematically compared the flavor and multi-omics differences between normal caviar and bitter caviar based on quantitative descriptive analysis (QDA), volatile compounds (VOCs) analysis, untargeted lipidomics, and metagenomics. The results showed that bitter caviar was characterized not only by increased bitterness, but also by decreased positive sensory attributes, including buttery, nutty, and marine fresh. VOCs analysis indicated that the volatile profile of bitter caviar was reorganized. Compounds such as 3-hydroxy-2-butanone, 1-octen-3-ol, and (E, Z)-2,6-nonadienal showed higher relative odor activity values (rOAVs); however, these changes did not improve its overall sensory experience. Untargeted lipidomics identified 492 differential lipids. These changes were mainly characterized by decreased PC and increased DG and LPC in bitter caviar. KEGG pathways analysis showed that these differential lipids were mainly associated with glycerophospholipid metabolism, choline metabolism in cancer, and retrograde endocannabinoid signaling. Metagenomic analysis showed that bacteria dominated the microbial community of caviar. Among them, Bacillus and Micromonospora showed relatively high abundance in the caviar microbiota. They were also closely associated with lipid metabolic changes involving PC, DG, and LPC, suggesting their potential as candidate targets for future microbiota-directed regulation of caviar quality. These findings provide new insights into the mechanisms underlying sensory deterioration and flavor formation in bitter caviar, and offer a theoretical basis for improving caviar quality in industrial production.PMID:42705742 | DOI:10.1016/j.foodres.2026.120381
Intestinal content accelerates muscle protein degradation in red shrimp (Solenocera crassicornis) during refrigeration: Insights from metagenomics and metabolomics
Food Res Int. 2026 Nov 1;243(Pt 2):120377. doi: 10.1016/j.foodres.2026.120377. Epub 2026 Aug 14.ABSTRACTThis study systematically explored the effects of intestinal components on muscle quality deterioration and protein degradation of red shrimp during refrigerated storage. The results demonstrated that refrigeration induced continuous quality degradation and muscle protein breakdown in red shrimp, whereas eliminating intestinal tissues effectively retarded muscle spoilage and protein degradation, and optimized muscle texture. The intestinal microorganisms could secrete extracellular proteases to promote muscle protein degradation were primarily Vibrio, Bacillus, Pseudomonas, Photobacterium, and Shewanella. These microorganisms promote protein degradation by secreting zinc proteases, serine proteases, and aspartyl proteases. This study elucidates the molecular mechanisms of intestinal microbial metabolism influences the muscle protein degradation of red shrimp during refrigeration. The findings provide a theoretical foundation for precise regulation of intestinal-targeted microorganisms, thereby maintaining optimal quality of shrimps during refrigeration.PMID:42705740 | DOI:10.1016/j.foodres.2026.120377
Oxidation patterns and stability mechanisms of marine oils revealed by oxidized triglyceride and phospholipid analysis using RPLC-Q-TOF
Food Res Int. 2026 Nov 1;243(Pt 2):120369. doi: 10.1016/j.foodres.2026.120369. Epub 2026 Aug 17.ABSTRACTMarine oils are rich in polyunsaturated fatty acids and are highly susceptible to oxidation, resulting in complex oxidized lipids that deteriorate their quality. This study aims to explore the dynamic profiles of these oxidized species and elucidate the molecular mechanisms governing their oxidative stability. By utilizing RPLC-Q-TOF oxidized lipidomics combined with molecular dynamics (MD) simulations, this work provided a pioneering molecular-level analysis of oxidized marine oils, identifying 47 oxidized triacylglycerol (oxTG) and 45 oxidized phospholipid (oxPL) molecular species, including 14 oxTG and 6 oxPL isomers. Temporal tracking revealed divergent oxidation kinetics among the samples. In highly unsaturated TG-type oils, multi‑oxygenated TGs exhibited a dramatic "rise-then-fall" cleavage pattern, characterized by a rapid peak of 4.5 mg/g as early as day 2. Conversely, phospholipid (PL)-rich oil demonstrated remarkable macroscopic stability via preferential PL oxidation, suppressing oxTG accumulation to below 0.6 mg/g. At 40% PL addition, MD simulations confirmed that PC provides a better physical barrier against O2 than PE due to its bulkier headgroup and lower free volume. When applied at trace PL level (0.5%), a crucial acyl-chain trade-off emerged. While marine PUFA-PLs autoxidized and compromised their physical barrier, fully saturated PC (16:0_16:0) effectively blocked radical initiation, restricting specific deep oxidation products (TG (22:6_22:6_22:6 < +3O>)) to 0.86 mg/g. By profiling oxidized molecular species and bridging PL spatial conformation to oxidation trajectories, this study provides precision theoretical strategies for stabilizing marine oil systems.PMID:42705732 | DOI:10.1016/j.foodres.2026.120369
Multi-omics integration elucidates molecular mechanisms underlying distinctive meat quality in Liping cattle versus Angus hybrid and Simmental breeds
Food Res Int. 2026 Nov 1;243(Pt 2):120368. doi: 10.1016/j.foodres.2026.120368. Epub 2026 Aug 11.ABSTRACTLiping cattle, an indigenous Chinese breed, may possess unique meat quality characteristics, yet systematic comparisons with commercial breeds remain limited. This study systematically compared nutritional composition, amino acids, fatty acids, volatile flavor-related substances of longissimus dorsi muscle among Liping cattle (LP), Angus hybrid cattle (AG) and Simmental cattle (XM), and further adopted untargeted metabolomics and transcriptome sequencing to reveal the molecular basis for excellent meat quality of LP cattle. Nutritional detection demonstrated LP beef possessed typical advantages of high crude protein, low crude fat and low cholesterol. LP cattle accumulated higher contents of most essential and non-essential amino acids, accompanied by elevated functional n-3 polyunsaturated fatty acids and lower harmful trans fatty acids, which endows LP beef superior nutritional value and healthy fatty acid profile. Untargeted metabolomics identified numerous differential metabolites between LP and the two control breeds. Shared differential metabolites in LP cattle were mainly enriched in fructose and mannose metabolism, ferroptosis and carbohydrate metabolism pathways; characteristic metabolites related to nutrition, flavor and antioxidant capacity were significantly accumulated in LP muscle. Transcriptome screening uncovered a series of core differentially expressed genes. Consistently upregulated genes including MYH3, MSTN and PAX3 participated in skeletal muscle development, myofibril construction and lipid metabolism, while downregulated genes were mainly involved in inflammation and cell adhesion processes. Transcriptome-metabolome integrated analysis confirmed strong coordinated positive regulation between differential genes and metabolites. Fructose and mannose metabolism was identified as the shared critical pathway participating in forming the unique flavor traits of LP beef. In conclusion, the distinctive nutrient profile, abundant flavor precursors and coordinated transcription-metabolite regulation jointly shape the superior meat quality of LP cattle.PMID:42705731 | DOI:10.1016/j.foodres.2026.120368
Phocaeicola vulgatus alleviates obesity through cross-species arginine production and hepatic retinoic acid signaling
Food Res Int. 2026 Nov 1;243(Pt 2):120365. doi: 10.1016/j.foodres.2026.120365. Epub 2026 Aug 11.ABSTRACTFecal microbiota transplantation (FMT) shows inconsistent clinical efficacy in treating obesity, and the specific microbial determinants dictating its success remain poorly characterized. Our previous clinical FMT trial identified Phocaeicola vulgatus as a key microbe contributing to the therapeutic efficacy of obesity treatment. Here, to investigate its role in obesity, we established an independent clinical cohort comprising obese and lean individuals, revealing that the P. vulgatus-centered network and ornithine synthesis are impaired in the obese group. We then confirmed causality by utilizing a humanized rat model carrying microbiota from a P. vulgatus-deficient obese patient, demonstrating that P. vulgatus supplementation significantly mitigates HFD-induced obesity, including reductions in body weight and serum total cholesterol levels, as well as the alleviation of hepatic steatosis. To further explore the functional mechanisms of P. vulgatus, integrated metagenomic and metabolomic analyses revealed a potential functional association between P. vulgatus and Phascolarctobacterium faecium that is associated with enhanced intestinal arginine biosynthesis and systemic availability. Furthermore, hepatic transcriptomics linked these elevated circulating arginine levels to the upregulation of retinoic acid (RA) signaling. Taken together, our findings outline a potential microbial-host network wherein P. vulgatus mitigates obesity via the arginine-RA axis, providing a valuable scientific basis for exploring this strain as a probiotic candidate for metabolic health.PMID:42705729 | DOI:10.1016/j.foodres.2026.120365
Increased levels of long-chain acylcarnitines and polyunsaturated fatty acids in girls with premature adrenarche: an exploratory longitudinal metabolomics study
J Steroid Biochem Mol Biol. 2026 Sep 7:107115. doi: 10.1016/j.jsbmb.2026.107115. Online ahead of print.ABSTRACTPremature adrenarche (PA) has been associated with accelerated growth, increased adiposity, and reduced insulin sensitivity traceable to early life, yet the mechanisms underlying these metabolic traits remain unclear. This study investigated whether PA is associated with distinct circulating metabolite signatures. Untargeted metabolomics was used to analyze fasting serum samples from a community-based cohort. Sixteen girls with PA at age 7 were compared with 27 age-matched controls before adrenarche at the same age ("age-matched" comparison) and again when controls developed adrenarche at age 9 ("event-matched" comparison). The groups were comparable in body composition, dietary intake, and standard biomarkers, including insulin and lipids. PA associated with significant differences in 93 and 128 metabolite features in the age- and event-matched comparisons, respectively. Twenty-three identified metabolites were consistently altered in both comparisons, with 22 elevated and one reduced in PA girls. Elevated metabolites included long-chain acylcarnitines, polyunsaturated fatty acids, and sulfated steroid derivatives, whereas the microbiota-derived p-cresol-sulfate was reduced. In PA girls, acylcarnitines were inversely associated with leptin and triglycerides, whereas polyunsaturated fatty acids correlated negatively with birth size and body fat percentage, and positively with lean mass, tumor necrosis factor alpha, and dietary intake of protein, fat, and sodium. PA is associated with metabolic alterations that extend beyond androgen excess, raising hypotheses regarding fatty acid oxidation and gut microbiota-derived metabolism. While these findings provide insights into the pathophysiology of PA and may inform future research on biomarkers relevant to long-term outcomes, they warrant confirmation in larger studies.PMID:42705555 | DOI:10.1016/j.jsbmb.2026.107115
Association of Limb Fat Distribution and Plasma Metabolites With the Risk of Venous Thromboembolism
J Thromb Haemost. 2026 Sep 7:S1538-7836(26)00555-6. doi: 10.1016/j.jtha.2026.08.030. Online ahead of print.ABSTRACTBACKGROUND: Venous thromboembolism (VTE) is a potentially life-threatening cardiovascular condition. However, the role of limb-specific fat distribution and related metabolic signatures in VTE remains unclear.OBJECTIVE: To assess associations of upper- and lower-limb fat distribution with VTE risk and evaluate whether circulating metabolites mediate these relationships.METHODS: This retrospective cohort study analyzed UK Biobank data, in which arm and leg fat mass was measured by bioelectrical impedance. Cox proportional hazards models and restricted cubic splines assessed its sex-specific associations with incident VTE, deep vein thrombosis (DVT), and pulmonary embolism (PE). Least absolute shrinkage and selection operator regression identified metabolites related to the arm-to-leg fat mass percentage, followed by mediation analysis.RESULTS: Over a median follow-up of 13.6 years, 14,593 VTE events occurred among 458,651 participants. Higher arm-to-leg fat mass percentage was associated with increased VTE risk, with hazard ratios (HRs) of 1.81 (95% CI, 1.63-2.00) in women and 1.55 (95% CI, 1.47-1.64) in men when comparing the highest with lowest tertile. A total of 138 metabolites in women and 38 in men were associated with arm-to-leg fat distribution. In women, the metabolic signature mediated 15.2% (95% CI, 6.8-21.9) of the association between arm-to-leg fat and VTE, and 21.1% (95% CI, 12.8-28.4) of the corresponding association for PE; no significant mediation was observed in men.CONCLUSIONS: Upper-predominant peripheral fat distribution is associated with high risk of VTE. Sex-specific metabolic signatures partially mediate these associations in women, underscoring the importance of integrating limb fat distribution and metabolomics for improved VTE risk assessment.PMID:42705545 | DOI:10.1016/j.jtha.2026.08.030
Metabolomics of in vivo inflammation identifies soluble sialic acid as a conserved myeloid-cell metabolite
J Biol Chem. 2026 Sep 7:113519. doi: 10.1016/j.jbc.2026.113519. Online ahead of print.ABSTRACTDuring an immune response, metabolism changes dramatically. Metabolites are oxidized to power immune cell functions, serve as building blocks for proliferation, and act as effectors to regulate pathogen or host cells. Though metabolic changes in cultured cells have been studied extensively, metabolism changes in vivo are less understood. Here, we measured metabolomic changes across six mouse tissues in three models of immune activation: CpG-DNA cytokine storm, lymphocytic choriomeningitis virus infection, and polyI:C viral mimetic injection; and carried out metabolomics in cultured macrophages activated with different stimuli. We found most metabolomic changes were exclusive to either inflamed tissues or cultured macrophages, although itaconate was strongly induced in both contexts. We then mechanistically dissected the role of the soluble sialic acid N-glycolylneuraminic acid, which is highly induced in inflamed tissues yet only modestly in cultured macrophages. This metabolite increases in tissues in different models of inflammation, and the analogous human metabolite, N-acetylneuraminic acid, rises in human patients experiencing inflammation. We found that N-glycolylneuraminic acid is produced in CD11b+ myeloid cells by cleavage of protein-bound sialic acid. However, blocking its production did not affect CpG-DNA liver inflammation or LCMV infection in mice. Therefore, these experiments identify soluble sialic acid as a conserved biomarker of inflammation in mice and humans and highlight the differences in metabolism between in vitro and in vivo models of inflammation.PMID:42705538 | DOI:10.1016/j.jbc.2026.113519
Vegetable trimming pellets in laying hen diets drive cecal remodeling and dose-dependent plasma-egg metabolomic dissociation
Poult Sci. 2026 Aug 16;105(11):107637. doi: 10.1016/j.psj.2026.107637. Online ahead of print.ABSTRACTVegetable trimming pellets (TVP) provide a potential route for recovering plant biomass as poultry feed, but their dose-dependent effects across production and biological compartments remain unclear. We evaluated diets containing 0% (A), 3% (B), 6% (C), or 9% (D) TVP (80% lettuce and 20% cabbage trimmings) in 240 17-wk-old Hy-Line Grey hens (6 pens of 10 hens per diet) for 12 wk. Diets had similar calculated crude protein, while calculated metabolizable energy decreased from 2.854 to 2.659 Mcal/kg. We assessed production, egg quality, serum, intestine, cecal microbiota and metagenome, and plasma and egg metabolomes. Full-period feed conversion ratio increased from 2.74 in A to 2.88 in D (P = 0.026), and average daily feed intake differed (P = 0.001), while egg production, egg weight, and egg mass remained similar (P > 0.05). At wk 12, shell breaking strength was lower in D than in A to C (3.55 vs. 3.92 to 4.02 kgf/cm²; P = 0.030), and yolk color differed among diets (P = 0.007). Serum hormones, several biochemical indices, catalase, and malondialdehyde differed at wk 12 (P < 0.05; marker-specific n = 3 to 6). Cecal community composition differed (permutational multivariate analysis of variance: R² = 0.571, P = 0.0006; dispersion P = 0.229), while Shannon diversity remained similar (P = 0.582). Five A-vs.-D metagenomic pathways met a false discovery rate (FDR) < 0.05. In D vs. A, exploratory screening identified 254 annotated plasma and 338 annotated egg candidates, of which 62 and 80, respectively, also met FDR < 0.05; exact annotation matching identified one shared candidate. Graded TVP inclusion maintained major egg-output traits while producing dose-related shifts in feed use, cecal microbial features, and compartment-specific molecular profiles. At the higher inclusion levels, less favorable feed conversion and the lower late-period shell strength at 9% were the principal practical responses.PMID:42705201 | DOI:10.1016/j.psj.2026.107637
Revealing the cytokine-mediated embryo-maternal crosstalk during extended in vitro culture in the Arabian camel (Camelus dromedarius)
Anim Reprod Sci. 2026 Sep 2;294:108319. doi: 10.1016/j.anireprosci.2026.108319. Online ahead of print.ABSTRACTThis study reports, for the first time, the establishment of endometrial organoids (EOs) from the Arabian camel (Camelus dromedarius) and evaluates their suitability as an in vitro model for embryo-maternal interactions during implantation. Endometrial tissues were collected from non-pregnant she-camels and cultured in Matrigel with a defined growth medium. By Day 7, organoids displayed a spherical morphology (200-250 µm), remained viable for up to 20 days, and expanded to approximately 1 mm. They exhibited epithelial characteristics and high proliferative activity, confirmed by expression of mucin-1, pan-cytokeratin, vimentin, and Ki67. Day 7 in vitro-produced embryos co-cultured with EOs showed significant improvements in development and trophoblast outgrowth. This was accompanied by upregulation of key developmental genes (OCT4, c-MYC, KLF4, CDX2). Cytokine profiling revealed enhanced bidirectional signaling: embryos increased secretion of CCL2, CCL4, IGF-1, IFNG, IL1α, IL12b, IL-8, LIF, IL-10, and NTF3, while EOs upregulated VEGFA, IL-8, CCL2, and TIMP1. Co-culture uniquely induced additional cytokines and amplified signaling intensity. Metabolomic analysis of embryo-conditioned medium identified 108 metabolites, including steroids associated with immunomodulation. Notably, embryos cultured in EO-conditioned medium developed up to Day 21 post-cleavage, reaching a mean diameter of 2.4 mm. Overall, camel EOs provide a physiologically relevant platform that supports embryo development and enables detailed investigation of cytokine-mediated embryo-maternal communication and implantation processes in the dromedary camel.PMID:42705161 | DOI:10.1016/j.anireprosci.2026.108319
Unraveling lung cancer complexity: Spatial omics in tumor microenvironment characterization and precision medicine
Curr Probl Cancer. 2026 Sep 7;65:101333. doi: 10.1016/j.currproblcancer.2026.101333. Online ahead of print.ABSTRACTHeterogeneous tumor microenvironment (TME) in lung cancer plays a crucial role in disease progression and resistance to therapy. Despite advances in single-cell and bulk omics profiling, these methods often overlook spatial context, which is vital for understanding cell-cell interactions and regional heterogeneity. In recent years, spatial omics technologies-including spatial genomics, transcriptomics, proteomics, and metabolomics-have revolutionized the ability to map molecular landscapes while maintaining tissue architecture. These advancements have become essential components of next-generation lung cancer management. By providing unprecedented resolution in characterizing the lung cancer TME, spatial omics could reveal prognostic and predictive biomarkers and identify new therapeutic vulnerabilities. This review will provide the first critical evaluation of spatial multi-omics approaches for lung cancer prognosis. It will also assess various integration strategies for multi-omics data to explore the clinical translational potential of these tools for therapy selection and patient stratification. Therefore, a deeper understanding of spatial omics technologies and their application in lung cancer can significantly improve precision diagnostics and therapeutic decision-making.PMID:42705130 | DOI:10.1016/j.currproblcancer.2026.101333










