Metabolites最新文献

{"title":"Differences in Serum Cytokine Profiles Between Vegetarians and Omnivores: Exploratory Assessment of Dietary Factors.","authors":"Ivana Šarac, Slavko Mojsilović, Marta Despotović, Milan Ivanov, Marija Paunović, Jelena Milešević, Marija Takić","doi":"10.3390/metabo16100793","DOIUrl":"https://doi.org/10.3390/metabo16100793","url":null,"abstract":"<p><p><b>Background/Objectives:</b> Evidence suggests that plant-based diets are associated with reduced risk of chronic inflammatory diseases and lower circulating C-reactive protein (CRP) levels. However, associations with other inflammatory biomarkers, including interleukins (ILs), tumor necrosis factors (TNFs), interferons (IFNs), and chemokines, remain limited and inconclusive. This study compared multiple serum cytokine and chemokine levels between healthy vegetarians and omnivores. <b>Methods:</b> 160 apparently healthy, normal-weight participants aged 25-50 years, without acute and chronic illnesses or allergies, were included: 80 omnivores and 80 vegetarians (67 vegans and 13 lacto-ovo vegetarians). Serum concentrations of 13 cytokines/chemokines were measured using flow cytometry with a LEGENDplex™ bead-based multiplex immunoassay kit. Anthropometry, standard clinical hematological and biochemistry parameters, CRP, and dietary intakes were also analyzed. <b>Results:</b> The groups did not differ by sex (50% women), age, smoking, physical activity, or anthropometrics. Vegetarians had lower levels of TNF-α, IL-6, IL-8, IL-10, IL-12p70, IL-17A, IFN-γ, and IFN-α2, as well as lower leukocyte and lymphocyte counts, with no difference in IL-1β, IL-18, IL-33, IL-23, MCP-1, or CRP. The differences persisted after adjustment for potential confounders (although fewer remained significant after multiple-testing correction), and were principally present in both vegetarian subgroups, alongside substantial differences in multiple dietary factors. Regression analyses further confirmed the association of vegetarian dietary patterns with cytokine levels that differed. <b>Conclusions:</b> Vegetarian dietary patterns were associated with lower circulating concentrations of selected cytokines/chemokines in this cohort. However, the number of associations remaining after multiple-testing correction was limited; there was high multicollinearity between dietary factors, and causality could not be established. Further research is needed to elucidate causal relationships, specific dietary factors, underlying mechanisms, and clinical implications.</p>","PeriodicalId":18496,"journal":{"name":"Metabolites","volume":"16 10","pages":""},"PeriodicalIF":4.5,"publicationDate":"2026-10-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149270015","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Detection of Sulfur Mustard Adducts in Eye Compartments Following Ocular Exposure in Rabbits.","authors":"Fanny Gros-Désormeaux, Fanny Caffin, Alexandre Igert, Jade Boudard, Sylvain Caillat, Jihéne Bouhlel, François Fenaille, Thierry Douki","doi":"10.3390/metabo16100792","DOIUrl":"https://doi.org/10.3390/metabo16100792","url":null,"abstract":"<p><p><b>Background/Objectives</b>: Sulfur mustard (SM) is an old warfare agent that remains a threat to both military personnel and civilians. SM contamination occurs through three main routes: dermal contact, inhalation, and ocular exposure. The clinical consequences of ocular exposure range from conjunctivitis and ulcerations to blindness. While these pathophysiological consequences are well-established, the mechanisms of action of SM in the eyes are not fully understood. <b>Methods</b>: The present study, which was conducted in rabbits, aimed at quantifying a series of biomarkers resulting from the electrophilic addition of SM to glutathione and nucleic acids in multiple biological matrices. This allowed us to investigate the distribution of SM within the ocular sphere and its diffusion to distant organs. <b>Results</b>: SM biomarkers were detected in large amounts in tears and aqueous humor but at substantially lower levels in the vitreous humor. No evidence of diffusion was observed from the exposed eye to plasma and distant organs, including the brain, liver, and lungs. <b>Conclusions</b>: These results are in agreement with a role for the cornea as a major sink for SM, thereby preventing damage to other ocular compartments and systemic diffusion.</p>","PeriodicalId":18496,"journal":{"name":"Metabolites","volume":"16 10","pages":""},"PeriodicalIF":4.5,"publicationDate":"2026-10-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149270042","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Metabolite Profiles in Inflammatory Diseases.","authors":"Rodica Pădureanu, Ionuț Donoiu","doi":"10.3390/metabo16100789","DOIUrl":"https://doi.org/10.3390/metabo16100789","url":null,"abstract":"<p><p>Inflammation and intermediary metabolism are closely interconnected [...].</p>","PeriodicalId":18496,"journal":{"name":"Metabolites","volume":"16 10","pages":""},"PeriodicalIF":4.5,"publicationDate":"2026-10-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149270090","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Untargeted Plasma Metabolomics Reveals Metabolic Differences Associated with Job Stress in Manufacturing Workers: A Cross-Sectional Study.","authors":"Guofeng Li, Jing Liao, Peifang Liu, Yifei Liu, Yulan Chen, Chuancheng Wu, Jing Li, Bo Shen, Yu Jiang","doi":"10.3390/metabo16100790","DOIUrl":"https://doi.org/10.3390/metabo16100790","url":null,"abstract":"<p><p><b>Background</b>: Job stress is a common occupational hazard and has been linked to adverse mental and cardiometabolic outcomes; however, the metabolic responses to job stress remain incompletely understood. This study aimed to characterize plasma metabolic alterations associated with job stress and identify the potential metabolic pathways involved. <b>Methods</b>: A total of 195 male manufacturing workers aged 20-60 years were recruited in Fuzhou, China. After applying the inclusion and exclusion criteria and screening for outliers, 143 participants were included in the final analysis, comprising 78 workers in the job stress group and 65 in the non-job stress group. Job stress was assessed using the revised Chinese Job Content Questionnaire on the basis of the demand-control model, with a demand-to-control ratio > 1.0 warranting inclusion in the stress group. Fasting plasma samples were analyzed through untargeted liquid chromatography-mass spectrometry (LC-MS). Differentially abundant metabolites were identified using univariate and multivariate statistical approaches, and pathway enrichment analyses were conducted using MetaboAnalyst 6.0. <b>Results</b>: Twelve plasma metabolite features, predominantly lipid species such as phosphatidylethanolamine (PE), diacylglycerol (DG), and free fatty acids, were significantly associated with job stress after adjustment for covariates. Five features (M573T1, M264T3, M673T5, M686T27 and M569T1) showed moderate discriminative ability (AUC > 0.7) for job stress exposure. Pathway analysis revealed enrichment of seven metabolic pathways, among which glycerophospholipid metabolism was significantly enriched (FDR_<i>P</i> < 0.05). <b>Conclusions</b>: Untargeted plasma metabolomics revealed distinct metabolic differences associated with job stress, particularly in relation to lipid metabolism and membrane remodeling pathways. These findings provide preliminary evidence supporting the utility of metabolomics in exploring occupational stress-related metabolic signatures and identifying exploratory candidate markers for further validation.</p>","PeriodicalId":18496,"journal":{"name":"Metabolites","volume":"16 10","pages":""},"PeriodicalIF":4.5,"publicationDate":"2026-10-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149270066","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Integrated Serum and Spatial Metabolomics Reveals Compartmentalized Metabolic Reprogramming and Ferroptosis Susceptibility in Nasopharyngeal Carcinoma.","authors":"Huiling Hong, Yusong Zhang, Linhui Yan, Ting Xu, Yiying Xu, Zhaodong Fei, Jiyang Dong, Chuanben Chen","doi":"10.3390/metabo16100783","DOIUrl":"https://doi.org/10.3390/metabo16100783","url":null,"abstract":"<p><strong>Background: </strong>Nasopharyngeal carcinoma (NPC) is a malignancy highly prevalent in southern China. Metabolic reprogramming is a hallmark of cancer, yet the interplay between the systemic and local metabolic landscapes of NPC remains poorly characterized. This study aimed to identify serum metabolic biomarkers and characterize local tissue metabolic alterations through integrated metabolomics.</p><p><strong>Methods: </strong>We conducted a dual-compartment metabolomic investigation. Untargeted serum metabolomics was performed on 80 NPC patients and 35 healthy controls. Air flow-assisted desorption electrospray ionization mass spectrometry imaging (AFADESI-MSI) was applied to nasopharyngeal tissues (3 NPC vs. 3 chronically inflamed tissues). Cross-platform integration was performed to identify overlapping metabolic signatures, followed by least absolute shrinkage and selection operator (LASSO) regression for feature selection and logistic regression for biomarker panel construction.</p><p><strong>Results: </strong>Serum metabolomics revealed systemic perturbations involving amino acid and propanoate metabolism. Spatial metabolomics identified glycerophospholipid metabolism as the most significantly altered pathway in NPC tissues, with markedly reduced phosphatidylserine in tumor regions, and the ferroptosis pathway was significantly enriched. Cross-omics integration identified 8 overlapping metabolites, of which 5 were mapped to the biosynthesis of unsaturated fatty acids. Cysteine demonstrated excellent diagnostic performance (area under the receiver operating characteristic curve (AUC) = 0.903). A 5-metabolite combined model achieved an AUC of 0.904 (95% confidence interval (CI): 0.892-0.916).</p><p><strong>Conclusions: </strong>NPC exhibits compartmentalized metabolic reprogramming characterized by systemic amino acid and propanoate perturbations alongside local glycerophospholipid remodeling and ferroptosis susceptibility. The identified 5-metabolite serum panel shows considerable potential as a non-invasive diagnostic tool for NPC.</p>","PeriodicalId":18496,"journal":{"name":"Metabolites","volume":"16 10","pages":""},"PeriodicalIF":4.5,"publicationDate":"2026-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149270098","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Systemic Inflammatory Markers, Thyroid Autoimmunity, and Neuroretinal Structure in Graves' Disease: A Comparative OCT Study According to Ophthalmopathy Status.","authors":"Sinem Keser, Aykut Bulu","doi":"10.3390/metabo16100782","DOIUrl":"https://doi.org/10.3390/metabo16100782","url":null,"abstract":"&lt;p&gt;&lt;p&gt;&lt;b&gt;Background:&lt;/b&gt; Graves' disease is a systemic autoimmune disorder that may affect ocular structures even in the absence of clinically apparent ophthalmopathy. Optical coherence tomography (OCT) enables objective assessment of neuroretinal structures, but the relationships between OCT findings, systemic inflammatory indices, thyroid hormone levels, and thyroid autoimmunity markers in Graves' disease remain incompletely defined. This study aimed to evaluate the associations between OCT-derived neuroretinal measurements and systemic inflammatory, hormonal, and autoimmune markers according to ophthalmopathy status. &lt;b&gt;Methods:&lt;/b&gt; This retrospective cross-sectional study included 161 participants: 60 healthy controls, 50 Graves' disease patients with ophthalmopathy (GO+), and 51 Graves' disease patients without ophthalmopathy (GO-). Central macular thickness (CMT) and circumpapillary retinal nerve fiber layer (cpRNFL) thickness measurements were obtained using spectral-domain OCT. Macular RNFL (mRNFL) thickness was not evaluated. Laboratory evaluation included complete blood count, glucose, urea, creatinine, aspartate aminotransferase (AST), alanine aminotransferase (ALT), total cholesterol, high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), triglycerides, C-reactive protein (CRP), thyroid-stimulating hormone (TSH), free triiodothyronine (fT3), free thyroxine (fT4), anti-thyroid peroxidase (anti-TPO), and anti-thyroglobulin (anti-Tg) antibodies. &lt;b&gt;Results:&lt;/b&gt; In the primary three-group OCT analysis, significant differences were observed for superior (&lt;i&gt;p&lt;/i&gt; = 0.010, &lt;i&gt;q&lt;/i&gt; = 0.0125), inferior (&lt;i&gt;p&lt;/i&gt; &lt; 0.001, &lt;i&gt;q&lt;/i&gt; = 0.0024), temporal (&lt;i&gt;p&lt;/i&gt; = 0.002, &lt;i&gt;q&lt;/i&gt; = 0.0050), and nasal cpRNFL thickness (&lt;i&gt;p&lt;/i&gt; = 0.006, &lt;i&gt;q&lt;/i&gt; = 0.0092), and all remained significant after FDR correction; CMT did not differ among the groups (&lt;i&gt;p&lt;/i&gt; = 0.925, &lt;i&gt;q&lt;/i&gt; = 0.925). The lowest cpRNFL thickness values were observed in the GO- subgroup, particularly in the inferior quadrant (116.39 ± 27.52 vs. 136.65 ± 20.01 µm, post hoc &lt;i&gt;p&lt;/i&gt; &lt; 0.001); however, this finding should be interpreted cautiously because standardized GO activity and severity staging was not consistently available. Systemic inflammatory indices were largely similar between groups, whereas CRP levels were higher in Graves' disease in the exploratory analysis (3.87 ± 3.40 vs. 1.86 ± 1.11 mg/L, nominal p &lt; 0.001). Several weak correlations between cpRNFL parameters and fT4, CRP, and anti-TPO reached nominal significance; however, none remained statistically significant after FDR correction. In multivariable analysis restricted to patients with Graves' disease, GO+ status remained associated with greater inferior cpRNFL thickness compared with GO- status, whereas anti-TPO was not associated with inferior cpRNFL thickness after adjustment. &lt;b&gt;Conclusion:&lt;/b&gt; Sectoral cpRNFL differences were observed among the control, GO+, and GO- groups, wh","PeriodicalId":18496,"journal":{"name":"Metabolites","volume":"16 10","pages":""},"PeriodicalIF":4.5,"publicationDate":"2026-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149270101","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Caffeine Intake and Performance Outcomes in Taekwondo Athletes: A Systematic Review and Meta-Analysis.","authors":"Limin Cai, Jintao Guo, Si Chen","doi":"10.3390/metabo16100784","DOIUrl":"https://doi.org/10.3390/metabo16100784","url":null,"abstract":"<p><p><b>Background:</b> The ergogenic role of caffeine in taekwondo-specific performance has not been comprehensively synthesized. This study aimed to evaluate the effects of caffeine supplementation on performance outcomes in taekwondo athletes. <b>Methods:</b> PubMed, Web of Science, Cochrane Library, and SPORTDiscus were searched up to April 2026. Randomized controlled trials comparing caffeine supplementation with placebo in taekwondo athletes were included, including both acute and longer/repeated intervention protocols where eligible. Effect sizes were pooled as Hedges' g, a small-sample-corrected standardized mean difference, using random-effects models. Evidence certainty was assessed using the GRADE approach. <b>Results:</b> Caffeine supplementation was associated with favorable pooled effects for explosive performance (Hedges' g = 0.40; 95% CI 0.07-0.72; moderate-certainty evidence), reaction agility (g = 1.43; 95% CI 0.79-2.08; low-certainty evidence), technical accuracy (g = 1.05; 95% CI 0.32-1.77; low-certainty evidence), FSKT-10s performance (g = 3.31; 95% CI 1.42-5.19; very-low-certainty evidence), and FSKT-mult performance (g = 4.29; 95% CI 1.88-6.70; very-low-certainty evidence). No significant pooled effect was observed for endurance performance (g = 0.10; 95% CI -0.19-0.39; low-certainty evidence). <b>Conclusions:</b> Across the clinically heterogeneous acute and longer/repeated protocols included in this review, caffeine supplementation was associated with favorable pooled effects for explosive performance, reaction agility, and technical accuracy, whereas no significant pooled effect was observed for endurance outcomes. These estimates represent averages across different intervention protocols and should not be interpreted as a uniform effect of either acute or repeated supplementation. FSKT-based effects were large but should be interpreted cautiously given high heterogeneity. Observed dose-related patterns should be considered hypothesis-generating because formal subgroup or dose-response analyses were not conducted; independent replication is needed.</p>","PeriodicalId":18496,"journal":{"name":"Metabolites","volume":"16 10","pages":""},"PeriodicalIF":4.5,"publicationDate":"2026-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149270162","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Lactate-Driven Biphasic Reprogramming of Macrophage Immune Responses.","authors":"Qingshuang Guo, Pan Ren, Lanqi He, Jiaying Gao, Ruiqi Lu, Yitian Wang, Zhiheng Zhang, Xiaohui Han, Xi Zhang, Chao Fang","doi":"10.3390/metabo16100788","DOIUrl":"https://doi.org/10.3390/metabo16100788","url":null,"abstract":"<p><p>Lactate is a metabolic substrate, an extracellular signaling molecule, and a precursor for protein lactylation, with diverse effects on macrophage immunity. Evidence from infection, tissue injury, efferocytosis, and cancer indicates that lactate-associated pathways can amplify inflammation, support resolution and tissue repair, or sustain immune suppression. These outcomes depend on the timing, cellular source and compartment, chemical formulation and pH, transport and receptor engagement, and the chemistry and targets of lactylation. In this narrative review, we critically synthesize the biochemical foundations of lactate metabolism and lactyl-group donation and examine the mechanisms underlying these distinct macrophage responses. We distinguish model-specific biphasic responses from a universal sequence of early inflammation followed by resolution, and separate reparative programs from impaired antimicrobial or antitumor immunity. We also evaluate evidence for histone and non-histone lactylation, emphasizing the limits of metabolic perturbations and chromatin associations for establishing site-specific causality. This framework identifies experimental variables that should be controlled and supports context-selective investigation of lactate-related therapeutic targets in inflammatory diseases and cancer.</p>","PeriodicalId":18496,"journal":{"name":"Metabolites","volume":"16 10","pages":""},"PeriodicalIF":4.5,"publicationDate":"2026-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149269981","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Integrated Microbiome and Metabolomics Reveal Mechanism of Saline-Alkali Stress in <i>Avena sativa</i> L.","authors":"Guoling Ren, Beibei Yang, Zitong Chen, Rixin Wang, Yajie Yin, Anqi Xia","doi":"10.3390/metabo16100785","DOIUrl":"https://doi.org/10.3390/metabo16100785","url":null,"abstract":"<p><strong>Background/objectives: </strong>This study subjected four-week-old oats (<i>Avena sativa</i> L. cv. Qinqiong and <i>Avena sativa</i> L. cv. Menglong) to saline-alkali stress for 6, 12, 24, and 48 h, and non-targeted metabolomics was used to analyse root metabolites under stress. Differential metabolites in oat roots after saline-alkali stress were primarily concentrated in substances such as carbohydrates, amino acids, acids, purines, and pyrimidines.</p><p><strong>Methods: </strong>In addition, 16S rRNA high-throughput sequencing was used to analyse changes in the rhizosphere microbial community structure of oats under saline-alkali stress. The abundance of some taxa, such as <i>Nocardioides</i>, <i>Bacillus</i>, and <i>Proteobacteria</i>, increased. Spearman's correlation analysis was used to determine correlations between differential microorganisms and metabolites.</p><p><strong>Results: </strong>Oats can secrete carbohydrate substances into the rhizosphere to recruit strains such as <i>Saccharothrix</i>, <i>Kineococcus</i>, and <i>Streptomyces</i>; aliphatic and heterocyclic amino acid substances to recruit <i>Arthrobacter</i>, <i>Bacillus</i>, and <i>Nostoc</i>; and acid substances to recruit <i>Accumulibacter</i>, thereby alleviating saline-alkali stress.</p><p><strong>Conclusions: </strong>These findings are significant for further studies on saline-alkali resistance in oats and for exploring the potential of oats' inherent saline-alkali resistance. They also provide basic data and theoretical and practical support for promoting the sustainable development of agriculture in saline-alkali soils through the utilisation of microorganisms and metabolites.</p>","PeriodicalId":18496,"journal":{"name":"Metabolites","volume":"16 10","pages":""},"PeriodicalIF":4.5,"publicationDate":"2026-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149270114","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Nutrition, T-2 Toxin, and Gut Microbiota in Kashin-Beck Disease: Current Evidence and Proposed Links Within the Microbiota-Gut-Osteochondral Framework.","authors":"Yang Liu, Chaowei Wang, Liangyu Cui, Xiong Guo, Xi Wang, Yujie Ning","doi":"10.3390/metabo16100787","DOIUrl":"https://doi.org/10.3390/metabo16100787","url":null,"abstract":"<p><p>Kashin-Beck disease (KBD) is an endemic osteoarthropathy characterized by the degeneration and necrosis of articular cartilage and epiphyseal growth plate cartilage, with disease onset occurring predominantly during childhood. Its etiology has long been associated with environmental and nutritional factors, particularly selenium deficiency, T-2 toxin exposure, and dietary imbalance. Recent studies have also reported alterations in gut microbial composition and metabolic profiles in patients with KBD, raising the possibility that the gut microbiota may represent an additional component of its multifactorial etiology. This narrative review critically evaluates current evidence linking nutritional factors, T-2 toxin exposure, gut microbial alterations, and osteochondral injury in KBD, with particular attention to the level of evidence supporting these relationships. Direct human evidence is currently limited to a small number of predominantly cross-sectional microbiome and metabolomic studies, largely involving adults with established KBD. KBD-related experimental models provide evidence that selenium deficiency and T-2 toxin exposure can induce osteochondral injury, including combined-exposure effects, and experimental studies also indicate that these exposures can be associated with alterations in gut microbial composition. However, these findings do not demonstrate that gut microbial changes mediate exposure-related osteochondral injury. Proposed pathways involving short-chain fatty acids (SCFAs), intestinal-barrier dysfunction, lipopolysaccharide (LPS)-related inflammatory signaling, immune regulation, and bone remodeling are supported mainly by experimental or mechanistic evidence from non-KBD settings and have not been validated as an integrated causal pathway in KBD. The microbiota-gut-osteochondral framework should therefore be regarded as an evidence-stratified, hypothesis-generating model. Prospective studies in children and adolescents from endemic areas, together with factorial exposure models, direct measurement of proposed intermediate mediators, and functional microbiota-manipulation experiments, are needed to determine whether gut microbial alterations contribute causally to KBD development.</p>","PeriodicalId":18496,"journal":{"name":"Metabolites","volume":"16 10","pages":""},"PeriodicalIF":4.5,"publicationDate":"2026-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149270148","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}