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Metabolites

Metabolites is an international, peer-reviewed, open access journal of metabolism and metabolomics, published monthly online by MDPI.
  • Open Access— free for readers, with article processing charges (APC) paid by authors or their institutions.
  • High Visibility: indexed within Scopus, SCIE (Web of Science), PubMed, PMC, Embase, CAPlus / SciFinder, and other databases.
  • Journal Rank: JCR - Q2 (Biochemistry and Molecular Biology) / CiteScore - Q1 (Endocrinology, Diabetes and Metabolism)
  • Rapid Publication: manuscripts are peer-reviewed and a first decision is provided to authors approximately 12.6 days after submission; acceptance to publication is undertaken in 3.7 days (median values for papers published in this journal in the first half of 2026).
  • Recognition of Reviewers: Reviewers whose reports are timely and of high quality receive an APC discount voucher for a future publication in an MDPI journal. Become a reviewer.

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All Articles (6,962)

  • Review
  • Open Access

Lactate-Driven Biphasic Reprogramming of Macrophage Immune Responses

  • Qingshuang Guo,
  • Pan Ren and
  • Chao Fang
  • + 7 authors

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.

Metabolites

16 October 2026

Lactate-related inflammatory pathways in defined macrophage models. (a) SPNS2/S1P disruption links lactate accumulation to mitochondrial ROS and sepsis-associated injury. (b) Lactate-associated HMGB1 modifications accompany exosomal signaling. (c) GLO2 loss alters lactoyl-donor metabolism, histone signals and inflammatory responsiveness. (d) PKM2/LDH-dependent fermentation supports PKR and inflammasome responses. Red upward arrows and blue downward arrows denote upregulation and downregulation, respectively. Created with BioGDP (https://biogdp.com/), accessed on 9 October 2026.
  • Article
  • Open Access

Background/Objectives: This study subjected four-week-old oats (Avena sativa L. cv. Qinqiong and Avena sativa 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. Methods: 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 Nocardioides, Bacillus, and Proteobacteria, increased. Spearman’s correlation analysis was used to determine correlations between differential microorganisms and metabolites. Results: Oats can secrete carbohydrate substances into the rhizosphere to recruit strains such as Saccharothrix, Kineococcus, and Streptomyces; aliphatic and heterocyclic amino acid substances to recruit Arthrobacter, Bacillus, and Nostoc; and acid substances to recruit Accumulibacter, thereby alleviating saline–alkali stress. Conclusions: 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.

Metabolites

16 October 2026

Root zone enzyme activity of oat under salt stress. Different lowercase letters denote significant differences between groups (p < 0.05). Q-0 h, Q-6 h, Q-12 h, Q-24 h, and Q-48 h indicate plants of saline–alkali-tolerant oat cv. Qinqiong under saline–alkali stress for 0, 6, 12, 24, and 48 h. M-0 h, M-6 h, M-12 h, M-24 h, and M-48 h indicate plants of saline–alkali-sensitive oat cv. Menglong under saline–alkali stress for 0, 6, 12, 24, and 48 h.
  • Systematic Review
  • Open Access

Background: 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. Methods: 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. Results: 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). Conclusions: 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.

Metabolites

16 October 2026

PRISMA flowchart.
  • Article
  • Open Access

Background: 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. Methods: 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. Results: 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). Conclusions: 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.

Metabolites

16 October 2026

Spatial metabolomics reveals local metabolic reprogramming in nasopharyngeal carcinoma (NPC). (A,B) UMAP projections of MSI data in positive-ion (POS) and negative-ion (NEG) modes. (C,D) Volcano plots from the exploratory pixel-level spatial screen (FDR < 0.05; FC > 1.2 or FC < 0.83); red, higher pixel-level mean intensity in NPC; blue, lower pixel-level mean intensity in NPC. Dashed vertical lines indicate the fold-change thresholds (log2 FC = +0.26 for FC > 1.2, and log2 FC = −0.27 for FC < 0.83), and the dashed horizontal line indicates the significance threshold (FDR = 0.05; −log10(0.05) = 1.30).These thresholds do not denote biological specimen-level significance. (E,F) GSEA of pathways in POS and NEG modes; bars, normalized enrichment scores (NES). (G–I) Over-representation analysis (ORA); bubble size, number of hits; color intensity, FDR. (J) H&E staining (top) and corresponding AFADESI-MSI ion images of PS(18:1/20:2), betaine, DPA, and AdA (below); color scale, normalized ion intensity (blue, low; red, high). Panel (J) shows illustrative images from one NPC and one chronic-inflammation specimen, rather than a display of all six biological specimens. The quantitative sensitivity analysis used all six biological specimens as described in Section 2.4; none of the four metabolites was significant after BH correction. AFADESI-MSI, air flow-assisted desorption electrospray ionization mass spectrometry imaging; MSI, mass spectrometry imaging; UMAP, uniform manifold approximation and projection; FDR, false discovery rate; GSEA, gene set enrichment analysis; ORA, over-representation analysis; H&E, hematoxylin and eosin.

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Metabolites - ISSN 2218-1989