PubMed

Appl Environ Microbiol. 2026 Sep 11:e0067426. doi: 10.1128/aem.00674-26. Online ahead of print.ABSTRACTBile acid (BA) transformation relies on gut microbiota and is vulnerable to Toxoplasma gondii infection, yet feline microbial BA-transforming capacity upon toxoplasmosis remains unclear. Here, we constructed a catalog of 2,474 nonredundant feline gut microbial genomes and integrated serum metabolomic data to verify BA transformation alterations. The results revealed that the feline gut microbiome harbored widespread genetic potential for BA transformation but lacked a complete 7α-dehydroxylation pathway due to the absence of the key gene baiE. The BA transformation-related genomes (2,045 in total) were predominantly from the phyla Bacillota_A and Actinomycetota, among which only 37 encoded baiB, all belonging to Bacillota_A. The distribution of BA transformation-related genes varied across intestinal regions: genes encoding 7α-HSDH were primarily enriched in the small intestine, whereas genes encoding 3α-HSDH, baiCD, and baiH were more abundant in the large intestine. Additionally, the abundance of genes encoding BSH and 3α-HSDH increased significantly in the small intestine on day 3 post-infection, accompanied by increases in the phylum Bacillota_C and genera such as Blautia_A, Enterococcus_E, and Ligilactobacillus. Serum metabolomics revealed a significant increase in cholesterol levels post-infection, supporting the impact of T. gondii infection on intestinal BA transformation. These findings illustrated that the feline gut microbiota played an important role in BA transformation and that T. gondii infection disrupted the microbial potential for secondary BA transformation. This study provided new insights into gut microbiota-associated metabolic perturbations during feline toxoplasmosis.IMPORTANCE: Bile acid (BA) transformation plays a critical role in host metabolism and immune regulation. Although studies on BA transformation are increasing, the capacity for BA transformation within the feline gut microbiota and the impact of Toxoplasma gondii infection on this capacity remain unclear. To bridge this gap, we constructed a catalog of 2,474 nonredundant feline gut microbial genomes and integrated serum metabolomic data to verify BA transformation alterations. Our findings revealed that the feline gut microbiome lacked a complete 7α-dehydroxylation pathway, and the specific functions involved in BA transformation may differ between the small and large intestines. Furthermore, integrated metagenomic and serum metabolomic analyses suggested that T. gondii infection disrupted BA transformation capacity in the small intestine. This study provided new insights into gut microbiota-associated metabolic perturbations during feline toxoplasmosis.PMID:42726488 | DOI:10.1128/aem.00674-26

Curr Atheroscler Rep. 2026 Sep 11;28(1):89. doi: 10.1007/s11883-026-01463-7.ABSTRACTPURPOSE OF REVIEW: This review critically summarizes evidence linking the Mediterranean diet, gut microbiome, microbial metabolites, and cardiovascular disease risk, with emphasis on the shift from microbial taxonomy to functional pathways, multiomic integration, and translation to precision nutrition.RECENT FINDINGS: Mediterranean diet adherence is associated with enrichment of fiber-degrading and short-chain fatty acid-producing taxa, greater microbial capacity for polysaccharide degradation, and more favorable bile acid, phenolic, lipid, and inflammatory profiles. Evidence from randomized trials and prospective cohort studies suggests that microbiome remodeling may partly mediate or modify the effects of the Mediterranean diet on adiposity, insulin resistance, lipid metabolism, inflammation, and cardiometabolic risk. However, effects are heterogeneous, global diversity metrics are inconsistent, and most studies rely on surrogate outcomes rather than incident cardiovascular events. The gut microbiome is a plausible mediator and modifier of Mediterranean diet-related cardiovascular protection, but it is not yet a validated clinical target. Future research should prioritize longitudinal multiomic studies with repeated measures, standardized analytical pipelines, externally validated biomarkers, and pragmatic trials testing whether microbiome-informed Mediterranean diet counseling improves adherence, cardiometabolic profiles, and cardiovascular outcomes.PMID:42726368 | DOI:10.1007/s11883-026-01463-7

Funct Integr Genomics. 2026 Sep 11;26(1):261. doi: 10.1007/s10142-026-02042-4.ABSTRACTLivestock reference genomes have transformed the discovery of variants associated with production, reproduction, health, and environmental adaptation. Nevertheless, a single linear reference represents only one mosaic haplotype and incompletely captures sequence diversity within a species, particularly structural variants, copy-number changes, repeat-rich regions, and breed-specific sequences. Pangenomes address this limitation by integrating multiple high-quality assemblies or population-scale variants into a unified sequence or graph representation. Concurrently, multi-omics approaches connect genomic variation with transcriptomic, epigenomic, manuscriptproteomic, metabolomic, and microbiome responses, thereby improving biological interpretation of genotype-phenotype relationships. This review synthesizes recent progress in livestock pangenomics and multi-omics, with emphasis on cattle, goats, sheep, water buffalo, and chickens. It describes advances in long-read and haplotype-resolved sequencing, graph construction, structural-variant discovery and genotyping, functional annotation, and integrative analysis. Recent pangenome studies have uncovered substantial non-reference sequence, reduced reference bias, identified breed- and population-specific structural variants, and resolved candidate variants underlying pigmentation, body size, tail morphology, cashmere production, altitude adaptation, and other economically relevant traits. However, translation into routine breeding remains constrained by uneven population representation, inconsistent structural-variant definitions, limited functional annotation, computational demands, and insufficient validation across environments. Future progress will depend on diverse near-complete assemblies, graph-aware imputation and genomic prediction, long-read transcriptomics, single-cell and spatial omics, rigorous causal validation, and open, interoperable resources. Together, these developments can support more accurate, resilient, and biologically informed livestock improvement. Importantly, current dairy-cattle evidence indicates that pangenome-derived structural variants can substantially improve variant discovery and functional interpretation while yielding only marginal average gains in routine genomic prediction, favoring targeted augmentation rather than wholesale replacement of established SNP-based evaluations.PMID:42726296 | DOI:10.1007/s10142-026-02042-4

Cardiovasc Toxicol. 2026 Sep 11;26(10):106. doi: 10.1007/s12012-026-10181-0.ABSTRACTMyocardial injury is a common pathological endpoint in conditions such as acute myocardial infarction, ischemia/reperfusion injury, myocarditis, and drug-induced cardiotoxicity, and remains a therapeutic challenge due to the irreversible loss of cardiomyocytes and subsequent ventricular remodeling. Current strategies lack effective interventions directly targeting regulated cell death pathways. This review centers on the dysregulation of the regulated cell death (RCD) and autophagic network. We comprehensively integrate the dual roles, and evidence-graded crosstalk among RCD modalities (apoptosis, pyroptosis, and ferroptosis) and autophagic responses, proposing a paradigm shift from isolated pathway inhibition to dynamic rebalancing of the RCD and autophagic network for cardioprotection. Within this framework, we consolidate and compare evidence illustrating how active metabolites, single botanical drugs, and compound formulations of traditional Chinese medicine regulate multiple forms of RCD-associated signaling and autophagic processes. The multi-metabolite, multi-target nature enables coordinated regulation at the cellular survival-death checkpoint. Mechanistically, TCM interventions can: (1) attenuate apoptotic marker expression and context-dependently modulate autophagic responses via axes such as PI3K/Akt/mTOR, AMPK/mTOR, MAPK, and JAK/STAT; (2) suppress NLRP3/caspase-1/GSDMD-mediated pyroptotic signaling markers; and (3) modulate lipid peroxidation-associated ferroptotic signaling through antioxidant pathways centered on the Nrf2/GPX4 and System xc⁻ axes. These actions collectively ameliorate upstream pathological loops involving oxidative stress, inflammatory amplification, and mitochondrial dysfunction. This review adopts a comprehensive cardiovascular toxicology perspective to integrate the regulatory mechanisms of RCD and autophagic networks in myocardial injury, encompassing both exogenous drug-induced cardiotoxicity (e.g., doxorubicin) and endogenous toxic stresses, including lipotoxicity, ROS-mediated toxicity, and ischemia-related metabolic injury. Notably, many TCM agents exhibit cross-RCD and autophagic synergistic effects supported by direct perturbation-and-rescue evidence (Level c crosstalk) as well as co-regulatory profiles, suggesting that cardioprotection at the network level may be achieved through shared hub nodes. This perspective provides a clearer mechanistic landscape for elucidating the action of TCM formulas and for screening novel therapeutic candidates. Ultimately, it advocates for advancing traditional Chinese medicine-based myocardial protection strategies into reproducible, quantifiable, and clinically verifiable pharmacological research systems oriented around RCD and autophagic network homeostasis.PMID:42726179 | DOI:10.1007/s12012-026-10181-0

Metabolomics. 2026 Sep 11;22(5):150. doi: 10.1007/s11306-026-02516-3.ABSTRACTBACKGROUND: Colorectal cancer (CRC) is a leading cause of cancer-related mortality. Prognosis is primarily guided by tumor stage despite substantial molecular heterogeneity. Urinary metabolomics may capture systemic and tumor-related biology beyond staging and could improve prognostic assessment. We hypothesized that incorporating urinary metabolomic profiles would improve overall survival (OS) prediction performance compared with a stage- and age-based reference model.METHOD: A total of n = 76 stage I-IV CRC patients recruited as part of the ColoCare Study in Heidelberg Germany with pre-surgery urinary metabolomics were included (23 deaths; median follow-up 3.03 years). Four metabolomics-based penalized Cox models adjusted for tumor stage and age at diagnosis were developed using LASSO, adaptive LASSO, spike-and-slab LASSO, and iterative sure independence screening (iSIS)-LASSO. Model discrimination was assessed using Harrell's C-index and time-dependent AUC based on the nested cross-validation.RESULTS: Compared with the reference model (Cox model including only tumor stage and age at diagnosis), all metabolomics-based models provided better discrimination. The spike-and-slab LASSO Cox model demonstrated the best performance, achieving a C-index of 0.75 (vs. 0.68) and consistently higher time-dependent AUCs at 1-5 years of follow-up, with a peak AUC of 0.76 at year 3 (vs. 0.68). Three urinary metabolites were consistently selected across all metabolomics-based models: indolelactate, 2-hydroxyisobutyrate and a uridine-like metabolite.CONCLUSIONS: Urinary metabolomics may improve CRC OS prediction beyond tumor stage and age at diagnosis, especially with the spike-and-slab LASSO Cox model. These results support urinary metabolomics as a promising noninvasive prognostic tool that merits external validation.PMID:42726173 | DOI:10.1007/s11306-026-02516-3

Adv Sci (Weinh). 2026 Sep 11:e77762. doi: 10.1002/advs.77762. Online ahead of print.ABSTRACTIsocitrate dehydrogenase 3 alpha (IDH3A) is a key rate-limiting enzyme in the tricarboxylic acid (TCA) cycle, traditionally associated with cellular energy metabolism. However, its role in cancer remains incompletely understood. Here, we demonstrate that IDH3A is significantly overexpressed in melanoma, primarily due to DNA copy number amplification. Metabolomic analysis revealed that IDH3A overexpression enhanced multiple biosynthetic intermediates, including G6P, F6P, DHAP, and 6-phosphogluconate, indicating metabolic reprogramming toward anabolic processes without significantly affecting ATP or lactate production. Intriguingly, IDH3A localizes to the nucleus in melanoma cells and promotes tumorigenesis independent of its dehydrogenase activity. Nuclear IDH3A interacts with transcription factor YBX1, enriching at promoter regions of oncogenes such as c-FOS and c-JUN, thereby suppressing apoptosis and promoting tumor growth. Furthermore, we identify NONO as a nuclear chaperone that facilitates the nuclear localization of IDH3A through direct interaction, primarily involving NONO amino acids Q166 and S207. Disruption of NONO impairs IDH3A nuclear translocation and mitigates its tumor-promoting function. Collectively, our findings uncover a noncanonical role of IDH3A as a nuclear regulator of transcription via YBX1, offering novel insight into metabolic enzyme reprogramming in melanoma.PMID:42725805 | DOI:10.1002/advs.77762

Virulence. 2026 Dec;17(1):2728766. doi: 10.1080/21505594.2026.2728766. Epub 2026 Sep 11.ABSTRACTAscaris roundworms impair human and swine health. While treatments using anthelmintic drugs are generally effective in eliminating worms, their effects on the gut microenvironment remain poorly understood. Here we applied integrated multi-omics to characterize infection- and treatment-associated alterations in the pig-Ascaris system. In vitro anaerobic cultures were conducted as supportive validation of selected observations. Ascaris suum infection altered microbial composition and dysregulated 182 serum and fecal metabolites, including histamine and p-cresol sulfate. Compared with time-matched uninfected controls, infected pigs treated with fenbendazole showed marked differences in gut microbial composition 13 days after confirmed worm clearance. Eleven microbial pathways were enriched in successfully treated pigs, including peptidoglycan biosynthesis and histidine metabolism, indicating that infection-associated alterations may persist after treatment. In vitro co-exposure of Lactobacillus reuteri to fenbendazole and A. suum proteins increased histamine production by approximately 79% at 48 h (p < 0.05), serving as supportive evidence of a microbiome contribution. Collectively, our in vivo findings support that host-microbiota-parasite interactions are multifaceted. Microbiota-derived metabolites were associated with regulation of host gene expression, such as TFF2 and IL8. Microbiota plasticity allows the exploitation of the niche differentiated upon infection, resulting in the proliferation of certain Lactobacillus strains in treated animals. Nevertheless, interpretations of treatment effects are made cautiously given the absence of an uninfected drug-only group and the cross-sectional design. Understanding these complex interactions will be important for the design of next-generation functional anthelmintics.PMID:42725788 | DOI:10.1080/21505594.2026.2728766

FASEB J. 2026 Sep 30;40(18):e72283. doi: 10.1096/fj.202600847RRRR.ABSTRACTDiminished ovarian reserve (DOR) is characterized by a decline in oocyte quantity and/or quality and represents a growing cause of female infertility, particularly among young women, yet its pathogenesis remains incompletely understood. Disordered lipid metabolism impairs folliculogenesis and steroidogenesis, thereby contributing to the pathological changes of DOR. Here, we identify hypoxia-inducible lipid droplet-associated protein (HILPDA), a regulator of lipid droplet biogenesis, as a potential contributor to DOR. We found that HILPDA was significantly upregulated in granulosa cells (GCs) from DOR patients and that its expression levels correlated with reduced ovarian reserve indicators and adverse assisted reproductive technology (ART) outcomes. Ovarian overexpression of HILPDA in mice promoted follicular atresia and disrupted the estrous cycle. In KGN cells, HILPDA overexpression suppressed proliferation and induced apoptosis. Mechanistically, HILPDA overexpression promoted excessive accumulation of triglyceride-rich lipid droplets, accompanied by depletion of phospholipids, cholesteryl esters, and mitochondrial cardiolipin species. This lipid remodeling was associated with impaired estradiol biosynthesis, mitochondrial dysfunction, and endoplasmic reticulum stress activation. Genetic restoration of lipolysis via adipose triglyceride lipase (ATGL) overexpression or pharmacological inhibition of excessive lipid droplet formation alleviated HILPDA-associated lipotoxicity and cellular dysfunction. Collectively, these findings suggest that HILPDA may play an important role in GC dysfunction in DOR through reprogramming lipid metabolism and indicate that targeting this pathway may represent a potential therapeutic strategy for DOR.PMID:42725586 | DOI:10.1096/fj.202600847RRRR

Alzheimers Dement. 2026 Sep;22(9):e71789. doi: 10.1002/alz.71789.ABSTRACTINTRODUCTION: Metabolic dysfunction, altered adenosine signaling, and white matter abnormalities are implicated in tauopathies, but their relationship to network disconnection remains unclear. Myelinating oligodendrocytes may represent a metabolically vulnerable hub linking these processes to circuit dysfunction.METHODS: We assessed human hippocampal tissue by immunofluorescence and profiled THY-Tau22 mice using diffusion tensor imaging, metabolomics, lipidomics, and single-nucleus RNA sequencing. Symptomatic mice were treated with the equilibrative nucleoside transporter 1 (ENT1) inhibitor J4 to evaluate therapeutic modulation.RESULTS: Hippocampal tissue from patients with tauopathy showed reduced oligodendrocyte- and myelin-associated CNPase signal. THY-Tau22 mice exhibited progressive reductions in hippocampal-prefrontal fractional anisotropy, myelin-associated alterations, purine and lipid metabolic remodeling, and oligodendrocyte-enriched lipid-associated transcriptional changes. J4 treatment selectively modulated purine and lipid metabolic pathways and improved myelin-associated markers and structural connectivity measures.DISCUSSION: ENT1 inhibition links adenosine homeostasis to oligodendrocyte-associated metabolic pathways and supports further investigation as a potential therapeutic approach for tauopathy-associated network dysfunction.PMID:42725558 | DOI:10.1002/alz.71789

Curr Hypertens Rev. 2026 Sep 4. doi: 10.2174/0115734021496393260828062926. Online ahead of print.ABSTRACTStillbirth remains a major global public health challenge, accounting for nearly two million deaths annually despite significant advances in antenatal and obstetric care. Reliable biomarkers for its early prediction are still lacking, highlighting the need to identify novel diagnostic strategies. Since preeclampsia and stillbirth share several underlying pathophysiological mechanisms, including placental insufficiency, impaired trophoblast invasion, endothelial dysfunction, angiogenic imbalance, oxidative stress, and systemic inflammation, biomarkers established for preeclampsia may also hold promise for stillbirth risk assessment. This tutorial review summarizes current evidence on protein- and metabolome-based biomarkers used for the early diagnosis of preeclampsia and evaluates their potential applicability for predicting stillbirth. A comprehensive literature search of Scopus, PubMed, and ScienceDirect was conducted for studies published between 2010 and 2024. Conventional fetal monitoring techniques such as ultrasonography, magnetic resonance imaging (MRI), and cardiotocography (CTG) remain valuable for assessing fetal well-being but offer limited predictive accuracy for stillbirth. Several biomarkers, including angiogenic factors (sFlt-1, PLGF, sEng), placental proteins (PP13, PAPP-A), cardiovascular markers (BNP, NT-proBNP), renal biomarkers (cystatin C), metabolic markers (uric acid), and emerging candidates such as growth differentiation factor- 15 (GDF-15), have demonstrated diagnostic value in preeclampsia. However, their clinical utility for stillbirth prediction remains insufficiently validated. Prospective studies involving dedicated stillbirth cohorts are essential to establish their predictive performance and facilitate translation into routine clinical practice.PMID:42725516 | DOI:10.2174/0115734021496393260828062926

Stroke. 2026 Sep 11. doi: 10.1161/STROKEAHA.125.053290. Online ahead of print.ABSTRACTBACKGROUND: Stratification of stroke risk remains challenging, but metabolomic profiling offers the potential to detect new biomarkers and to improve early risk assessment of incident stroke. The objective of this study was to evaluate the association between circulating metabolites and the incidence of stroke in a case-cohort study conducted across several large population-based European cohorts.METHODS: Following the case-cohort design, a subset of 10 299 individuals, including all individuals with incident stroke, was selected from the original cohort of >70 000 individuals. The case-cohort design used a random subsample of the selected population cohorts, supplemented with cases not sampled in this random subcohort. A total of 141 circulating metabolites were measured from serum samples of the selected individuals, and associations of these metabolites with risk of incident stroke were estimated and compared with those of classic risk factors (sex, age at examination, systolic blood pressure, total cholesterol, body mass index, diabetes, daily smoking status, and antihypertensive treatment). Associations with time to stroke were assessed using weighted Cox proportional hazards models adjusted for the classic risk factors. Hazard ratios (HRs) for the log-transformed metabolites were reported per 1 SD increase.RESULTS: Of the 70 195 individuals in the original cohort, 1516 (2.2%) experienced incident strokes during a median follow-up time of 8.9 years (interquartile range, 4.4-14.7). Median age was 56.8 years (interquartile range, 49.5-62.4), and 39.5% were female. Six of the 141 metabolites (2 diacyl-phosphatidylcholines, 2 lyso-phosphatidylcholines, 1 hydroxysphingomyelin, and glutamic acid) remained significantly associated with incident stroke after correction for multiple comparisons (adjusted HRs [95% CIs] per SD: lyso-phosphatidylcholines a C18:2 HR, 0.88 [95% CI, 0.82-0.93], lyso-phosphatidylcholines a C17:0 HR, 0.88 [95% CI, 0.83-0.94], hydroxysphingomyelin C14:1 HR, 0.90 [95% CI, 0.85-0.94], diacyl-phosphatidylcholines C34:1 HR, 1.10 [95% CI 1.05-1.16], diacyl-phosphatidylcholines C32:1 HR, 1.14 [95% CI, 1.08-1.21], glutamic acid HR, 1.23 [95% CI 1.11-1.37]). The strengths of these associations were similar to those for classic cardiovascular risk factors (C statistics for 10-year prediction ranging from 0.782 to 0.785 for metabolites compared with 0.781 to 0.792 for classic cardiovascular risk factors).CONCLUSIONS: Among 10 299 individuals from the general European population, we identified 6 metabolites from 4 different metabolite classes that were associated with future risk of stroke. The application of specific circulating metabolites may improve early stroke risk prediction before the onset of potentially irreversible cerebrovascular pathological processes.PMID:42725362 | DOI:10.1161/STROKEAHA.125.053290

Front Genet. 2026 Aug 28;17:1885466. doi: 10.3389/fgene.2026.1885466. eCollection 2026.ABSTRACTOBJECTIVE: This study aimed to characterize the clinical features and identify serum differential metabolites in children with left-to-right shunt congenital heart disease (CHD) complicated by neurodevelopmental abnormalities (NDA) and harboring CHD7 mutations, to elucidate potential pathogenic mechanisms.METHODS: A case-control study was conducted with three groups: seven children with CHD7-mutant CHD-NDA, 24 children with isolated CHD, and nine healthy controls. Serum metabolomic profiling was performed using untargeted liquid chromatography-tandem mass spectrometry (LC-MS/MS) in both positive and negative ion modes.RESULTS: The metabolomic profiles showed a tendency toward separation among the CHD7-mutant CHD-NDA, isolated CHD, and healthy control groups. Candidate differential metabolites were mainly enriched in steroid hormone biosynthesis, glyoxylate and dicarboxylate metabolism, ascorbate and aldarate metabolism, and glutathione metabolism in the CHD7-mutant group compared with the isolated CHD group. Compared with healthy controls, the CHD7-mutant group also showed candidate alterations related to steroid hormone biosynthesis, riboflavin metabolism, and folate biosynthesis. Two overlapping candidate metabolites, 11-deoxycortisol and 2-hydroxyestrone, were identified across pairwise comparisons and may represent potential metabolic markers related to steroid metabolism.CONCLUSION: The metabolic disturbances observed in children with CHD7-associated CHD-NDA may be related to steroid metabolism and hypothalamic-pituitary axis regulation. These preliminary findings suggest a potential metabolic link between CHD7 mutations, cardiac phenotypes, and neurodevelopmental abnormalities, warranting further validation in larger, sex-matched cohorts.PMID:42725350 | PMC:PMC13561501 | DOI:10.3389/fgene.2026.1885466

Transl Cancer Res. 2026 Aug 31;15(8):637. doi: 10.21037/tcr-2026-0836. Epub 2026 Jul 16.ABSTRACTBACKGROUND: Bone cancer pain (BCP) frequently develops following cancerous lesions in the bone, severely affecting patients' daily activities and long-term quality of life. However, effective therapeutic options remain limited. Therefore, it is essential to explore its underlying mechanisms to identify new therapeutic targets.METHODS: A mouse model of BCP was established to investigate pain development using the von Frey test. Immunofluorescence staining and Western blotting were performed to detect neuroinflammation and astrocyte activation. Transcriptome sequencing and targeted metabolomics were conducted to identify significantly altered genes and pathways in BCP mice, and the results were validated by Western blotting, enzyme-linked immunosorbent assay, and immunofluorescence staining. Small interfering RNA was used to examine the relationship between Arpc1b and ALDOA using the aforementioned methods.RESULTS: Neuroinflammation in the spinal cord of BCP mice was accompanied by activation of C3-positive reactive astrocytes. Sequencing analysis revealed that Arpc1b and glycolysis were associated with C3-positive astrocyte activation. Further experiments demonstrated that BCP-induced neuroinflammation downregulated Arpc1b and increased the expression of glycolytic enzymes in spinal cord astrocytes. Additionally, increased soluble ALDOA appeared to contribute to BCP-induced glycolysis in astrocytes, while Arpc1b-mediated cytoskeletal remodeling increased free ALDOA levels.CONCLUSIONS: The significant reduction of Arpc1b in C3-positive astrocytes within the spinal cord of BCP mice mediates cytoskeletal remodeling, causing dissociation of ALDOA from F-actin. This process promotes excessive glycolysis in astrocytes and persistent neuroinflammation, which may underlie BCP.PMID:42724891 | PMC:PMC13559645 | DOI:10.21037/tcr-2026-0836

Front Nutr. 2026 Aug 27;13:1938235. doi: 10.3389/fnut.2026.1938235. eCollection 2026.ABSTRACTBACKGROUND: Pueraria thomsonii is rich in isoflavonoids; however, its glycoside-dominated forms exhibit limited intestinal absorption and metabolism, and the material possesses undesirable sensory traits. This study employs a defined co-culture of Saccharomycopsis fibuligera and Bacillus velezensis to achieve coordinated starch hydrolysis, cell-wall degradation, and β-glucosidase-mediated deglycosylation. We investigate the resulting nutritional, metabolic, and volatile profiles through integrated multi-omics, establishing this consortium as a bioprocessing method for value-added P. thomsonii.METHODS: Solid-state fermentation (SSF) was conducted at 30 °C for 72 h under microaerophilic conditions across five treatments: raw P. thomsonii (Y), natural fermentation (K), single-strain fermentation with S. fibuligera YPD01 (S) or B. velezensis NA03 (B), and co-fermentation with both strains at a 1:1 ratio (M). Nutritional components, total flavonoids, and total phenolics were quantified. Activities of α-amylase, β-glucosidase, and cellulase were assayed. The microbial community structure and functional genes were characterized through metagenomic sequencing. Untargeted metabolomics was performed using UPLC-MS, and volatile compounds were analyzed by GC-MS.RESULTS: Co-fermentation achieved the highest nutritional quality, yielding reducing sugars (15.45 ± 0.26 mg/g), total flavonoids (9.30 ± 0.17 mg RUT/g), total phenolics (13.19 ± 0.25 mg GAE/g), total amino acids (52.11 ± 0.53 g/kg), and crude protein (12.56 ± 0.26%), all significantly surpassing other treatments. Both inoculated strains effectively colonized the substrate. Co-fermentation exhibited the highest activities of β-glucosidase (90.67 ± 2.66 U/g) and cellulase (343.77 ± 10.75 U/g). Metagenomic analysis generated approximately 659 million reads, identifying 7,737 KEGG entries, with enriched CAZy families in co-fermentation. Untargeted metabolomics identified 1,693 metabolites, with co-fermentation uniquely enriching isoflavone aglycones, peptides, and esterase-related compounds. GC-MS analysis revealed that co-fermentation produced the highest levels of fruity esters, including ethyl linoleate (1009.73 ± 32.51 μg/g) and ethyl palmitate (335.85 ± 9.76 μg/g), while hexanal was eliminated in all fermented groups.CONCLUSION: The S. fibuligera-B. velezensis consortium enhanced the nutritional, metabolic, and aromatic quality of P. thomsonii through enzymatic biotransformation and metabolic complementarity. Co-fermentation outperformed both natural and single-strain fermentations in the release of phenolic compounds and isoflavone aglycones, amino acid enrichment, and flavor development. These findings provide a theoretical basis and technical guidance for developing high-value fermented foods and offer a reference framework for the precision microbial transformation of medicinal and edible homologous materials.PMID:42724850 | PMC:PMC13559536 | DOI:10.3389/fnut.2026.1938235

J Thorac Dis. 2026 Aug 31;18(8):967. doi: 10.21037/jtd-2026-0628. Epub 2026 Aug 28.ABSTRACTBACKGROUND AND OBJECTIVE: The gut-lung axis is a bidirectional network through which intestinal microbial ecology, mucosal immunity, epithelial barrier function, microbial metabolites, and neurohumoral signalling influence pulmonary inflammation. This narrative review summarizes the mechanistic basis of gut-lung communication, compares the strength of evidence across major chronic respiratory diseases (CRDs), and evaluates emerging microbiome-targeted interventions.METHODS: PubMed, Embase, and Google Scholar were searched for peer-reviewed English-language literature published from January 2010 through June 2024 using combinations of terms related to the gut-lung axis, microbiome, asthma, chronic obstructive pulmonary disease (COPD), interstitial lung disease (ILD), short-chain fatty acids (SCFAs), intestinal permeability, bile acids, tryptophan metabolites, vagal signalling, and glucagon-like peptide-1 (GLP-1). Human and animal original studies, randomized trials, cohort studies, mechanistic studies, and relevant narrative or systematic reviews were considered; case reports, non-English articles, and studies without respiratory outcomes were excluded. Reference lists of key papers were also hand-searched.KEY CONTENT AND FINDINGS: Evidence is strongest for biologically plausible immune and metabolic pathways linking intestinal dysbiosis to pulmonary disease. In asthma, early-life depletion of SCFA-producing taxa may impair regulatory T-cell development and promote allergic sensitization. In COPD, gut dysbiosis, increased intestinal permeability, and systemic endotoxin exposure are more consistently associated with inflammatory phenotype and exacerbation burden. Evidence in ILD remains preliminary but supports a possible role for gut-derived pathogen-associated molecular patterns in profibrotic signalling. After lung transplantation (LT), antibiotic exposure, immunosuppression, and microbial loss may interact with allograft inflammation and chronic lung allograft dysfunction (CLAD). Dietary modulation, probiotics, prebiotics/synbiotics, post-biotics, and fecal microbiota transplantation (FMT) remain investigational, with heterogeneous and generally limited clinical evidence.CONCLUSIONS: Current data support mechanistic plausibility but do not justify routine microbiome-directed treatment of CRDs. Future trials should standardize microbiome profiling, incorporate metabolomic and disease-specific clinical endpoints, and stratify responders to define where gut-lung axis interventions can add clinically meaningful benefit.PMID:42724737 | PMC:PMC13559459 | DOI:10.21037/jtd-2026-0628

Int J Cardiol Heart Vasc. 2026 Aug 31;66:102004. doi: 10.1016/j.ijcha.2026.102004. eCollection 2026 Oct.ABSTRACTBACKGROUND: Atrial fibrillation (AF) is the most common heart rhythm disorder worldwide. Changes in metabolism and damage to mitochondria affect left atrial structure and electrical function. Few studies have applied multi-omics to plasma from AF patients.METHODS: We enrolled 37 patients with persistent AF and 36 with supraventricular tachycardia (SVT). Blood samples were drawn from the coronary sinus in all patients. Ten subjects from each group were randomly selected for 4D-DIA proteomics and untargeted metabolomics. ELISA validation was done on 35 patients per group. Four GEO atrial tissue datasets and one single-nucleus RNA-seq dataset were used for external support. Differentially expressed proteins (DEPs) were defined by |fold change| ≥ 1.5 and Benjamini-Hochberg adjusted P < 0.05. Protein-protein interaction networks were built with STRING and Cytoscape.RESULTS: We quantified 3268 plasma proteins and identified 217 DEPs in AF. Network analysis showed voltage-dependent anion channel 1 (VDAC1) as a central mitochondrial hub. It connected respiratory chain subunits and autophagy regulators. ELISA confirmed higher plasma VDAC1, citrate synthase(CS) and secreted frizzled-related protein 2(SFRP2) in AF patients (all P < 0.001). Metabolomics identified 505 differentially abundant compounds. Glycerophospholipid and fatty acid pathways were disrupted. Integrated analysis revealed eight shared dysregulated pathways linked to energy metabolism. Four GEO datasets showed higher atrial VDAC1 transcripts in AF (P < 0.05). Single-nucleus RNA-seq localized VDAC1 to cardiomyocytes.CONCLUSIONS: Plasma protein and metabolite profiles differ between persistent AF and SVT. Mitochondrial and lipid pathways are both affected. VDAC1 is elevated in plasma, atrial tissue. These findings are supported across multiple cohorts.PMID:42724651 | PMC:PMC13560034 | DOI:10.1016/j.ijcha.2026.102004

Transl Cancer Res. 2026 Aug 31;15(8):658. doi: 10.21037/tcr-2026-0096. Epub 2026 Aug 27.ABSTRACTBACKGROUND AND OBJECTIVE: Radiotherapy and radionuclide therapy are essential components of modern cancer treatment. Despite substantial advances in radiation delivery and treatment planning, considerable interindividual variability remains in therapeutic response and radiation-induced toxicity. Conventional monitoring approaches, including imaging and routine laboratory tests, often provide limited insight into early or systemic biological responses. Body fluid-based biomarkers may provide accessible molecular readouts of radiation-induced damage, host response, and treatment-related toxicity. This narrative review summarizes radiation biomarkers detectable in body fluids, with emphasis on oxidative stress and cellular damage markers, circulating RNAs and extracellular vesicles, and metabolomic and lipidomic signatures relevant to precision radiation medicine.METHODS: A targeted literature search was conducted using PubMed/MEDLINE and Web of Science. Priority was given to primary experimental and clinical studies reporting specific molecular findings, longitudinal biomarker changes, or associations with treatment response and radiation-induced toxicity.KEY CONTENT AND FINDINGS: Ionizing radiation induces oxidative stress, DNA damage, inflammatory signaling, metabolic reprogramming, and intercellular communication, generating measurable signals in blood, plasma, serum, and urine. Oxidative DNA damage products such as 8-hydroxy-2'-deoxyguanosine and γ-H2AX-related responses may reflect cellular injury and toxicity risk. Circulating microRNAs and extracellular vesicle-associated cargo may capture transcriptional responses, bystander signaling, and treatment-related systemic changes. Metabolomic and lipidomic studies have identified multimetabolite signatures associated with radiation exposure and normal tissue toxicity. However, most candidate biomarkers remain exploratory, and clinical implementation is limited by variability in sampling, analytical platforms, normalization, and external validation.CONCLUSIONS: Integrated longitudinal assessment of complementary biomarker classes, together with clinical and dosimetric information, may improve toxicity monitoring and treatment personalization. Prospective validation and methodological standardization are required before these biomarkers can support routine treatment adaptation.PMID:42724455 | PMC:PMC13559624 | DOI:10.21037/tcr-2026-0096

J Clin Transl Hepatol. 2026 Aug 28;14(8):771-784. doi: 10.14218/JCTH.2026.00384. Epub 2026 Aug 3.ABSTRACTBACKGROUND AND AIMS: Bacterial infection is a key cause of mortality in patients with acute-on-chronic liver failure (ACLF). In this study, we aimed to identify metabolite biomarkers and develop a novel machine learning model for early identification of bacterial infection in ACLF.METHODS: Based on a prospective multicenter cohort from 14 centers, 1,314 patients with acute-on-chronic liver disease were enrolled, including those with ACLF and non-ACLF. Plasma samples at admission were collected for metabolomics profiling. Patients were randomly divided into discovery (n = 921) and validation (n = 393) sets. Machine learning was used to develop diagnostic models. The win ratio method was employed to assess the risk stratification capability of the models.RESULTS: Bacterial infection occurred in 198 of the 451 ACLF patients and 132 of the 863 non-ACLF patients. Infection altered the plasma metabolome, especially in lipid, amino acid, and xenobiotic metabolic pathways. Models for bacterial infection in ACLF (five metabolites) and non-ACLF (six metabolites) demonstrated superior discrimination in the discovery (AUCs: 0.881 and 0.935, respectively) and validation sets (AUCs: 0.835 and 0.889, respectively) compared with C-reactive protein, white blood cell count, procalcitonin, and the best composite clinical model. Metabolic risk stratification based on the models effectively predicted 90-day outcomes (all-cause death, organ failure, sepsis, new-onset acute decompensation, and systemic inflammatory response syndrome).CONCLUSIONS: Our models based on novel metabolic biomarkers enable identification of patients at high risk of bacterial infection and support risk stratification of 90-day outcomes.PMID:42724154 | PMC:PMC13558248 | DOI:10.14218/JCTH.2026.00384

Compr Physiol. 2026 Oct;16(5):e70251. doi: 10.1002/cph4.70251. Epub 2026 Sep 9.ABSTRACTShort-chain fatty acids (SCFAs) have emerged as key molecular mediators of gut-eye communication, linking microbial metabolism to ocular physiology and disease. Produced through microbial fermentation of dietary fiber, SCFAs function as systemic signaling molecules that regulate immune homeostasis, metabolic function, vascular integrity, and neuroinflammatory pathways through activation of SCFA-responsive receptors and epigenetic mechanisms. Growing evidence indicates that SCFAs influence biological processes central to ocular health, including inflammation, oxidative stress, neurodegeneration, and pathological angiogenesis. Experimental, metabolomic, and emerging clinical studies suggest that disruptions in SCFA signaling may contribute to the pathogenesis of retinal and ocular surface diseases; however, the mechanisms governing ocular exposure, target engagement, and therapeutic efficacy remain incompletely understood, highlighting a critical gap between mechanistic insight and clinical translation. In this review, we integrate current evidence into a mechanistic and translational framework that positions SCFAs as central effectors of the gut-eye axis. We further evaluate the therapeutic potential of SCFA modulation and identify key barriers to clinical implementation, including bioavailability, pharmacokinetics, dosing, and long-term safety, thereby delineating a roadmap for the development of microbiome-derived precision therapeutics in ophthalmology.PMID:42724150 | PMC:PMC13559049 | DOI:10.1002/cph4.70251

J Clin Transl Hepatol. 2026 Aug 28;14(8):824-841. doi: 10.14218/JCTH.2026.00106. Epub 2026 Aug 7.ABSTRACTBACKGROUND AND AIMS: Despite the surging global prevalence of metabolic dysfunction-associated steatotic liver disease (MASLD) and related liver fibrosis, effective treatments remain limited. While the traditional Chinese medicine Juanyu-Xiaozhi Formula (JYXZF) is used against MASLD, its bioactive components and mechanisms are poorly understood. This study aimed to investigate the therapeutic effects of JYXZF and elucidate its underlying mechanisms of action.METHODS: The constituents of JYXZF were characterized using ultra-high-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). Its efficacy was evaluated in a rat model of metabolic dysfunction-associated steatohepatitis (MASH) induced by a high-fat/calorie diet with high-fructose/high-glucose water, utilizing serum biochemistry, histology, and glucose/insulin tolerance tests. Mechanistic validation was performed in free fatty acid-treated human hepatocellular carcinoma cell line HepG2 (HepG2) cells and HepG2/human hepatic stellate cell line LX-2 (LX-2) co-culture models using luciferase assays, chromatin immunoprecipitation-quantitative polymerase chain reaction (ChIP-qPCR), and activator protein 1 (AP-1) overexpression rescue experiments. The functional relevance of stearoyl-CoA desaturase 1 (SCD1) was further assessed in vivo through liver-targeted adeno-associated virus (AAV)-mediated Scd1 overexpression.RESULTS: Flavonoids were identified as the main bioactive constituents. JYXZF administration alleviated metabolic dysfunction, reduced hepatic lipid accumulation, and attenuated inflammation and fibrosis in MASH rats. Multi-omics integration and machine learning-assisted target prioritization identified lipid metabolic and inflammatory pathways. Among these pathways, we selected the AP-1/peroxisome proliferator-activated receptor gamma (PPARγ)/SCD1-related lipogenic pathway for functional validation. Target perturbation experiments supported the functional involvement of AP-1 in the regulation of the PPARγ/SCD1 pathway and its contribution to the anti-steatotic effects of JYXZF.CONCLUSIONS: JYXZF alleviates MASLD-associated steatosis and fibrosis via the AP-1/PPARγ/SCD1-related lipogenic axis, demonstrating its therapeutic potential for MASLD/MASH and providing a mechanistic basis for future clinical applications.PMID:42723998 | PMC:PMC13558244 | DOI:10.14218/JCTH.2026.00106