Effects of apple phenolics on the human metabolome: modulation of key metabolic pathways.

Niklas Roeder; Antje Geiken; Stefan Dussling; Louise Holtmann; Tim Hollstein; Svea Gluesing; Fynn Brix; Julia Jensen-Kroll; Vivian Schaarschmidt; Louisa Pannenbeckers; Thomas Stegemann; Anja Bosy-Westphal; Svenja Fedde; Dominik M Schulte; Mario Hasler; Ralf Schweiggert; Christof D&#xf6;rfer; Karin Schwarz; Tobias Demetrowitsch

doi:10.1016/j.foodchem.2026.150382

PubMed · 42462304

Effects of apple phenolics on the human metabolome: modulation of key metabolic pathways.

Niklas Roeder·Antje Geiken·Stefan Dussling·Louise Holtmann·Tim Hollstein·Svea Gluesing·Fynn Brix·Julia Jensen-Kroll·Vivian Schaarschmidt·Louisa Pannenbeckers·Thomas Stegemann·Anja Bosy-Westphal·Svenja Fedde·Dominik M Schulte·Mario Hasler·Ralf Schweiggert·Christof Dörfer·Karin Schwarz·Tobias Demetrowitsch

View original source ↗Export metadata ↓

Abstract

Apples are widely recognized for their potential health benefits, partly attributed to their phenolic compounds. However, their impact on human metabolism remains incompletely understood. This study investigated metabolic effects of apple-derived phenolic compounds using untargeted metabolomics approach across multiple biofluids. In a crossover intervention study, 30 healthy men consumed a phenolic-rich apple juice or a placebo for two weeks. Blood, urine and saliva samples were collected before and after each intervention and analyzed by direct infusion ultra-high resolution mass spectrometry. Consumption of apple phenolic compounds resulted in significant alterations of the human metabolome, including increased levels of phenolic-derived degradation products and microbial-associated metabolites across all biofluids. Pathway enrichment analysis revealed pronounced effects on phenylalanine and tyrosine metabolism, as well as linoleic and arachidonic acid metabolism, Overall, these findings demonstrate that apple phenolic compounds induce measurable, microbiota-associated and systemic metabolic changes, providing new insights into their metabolic fate and biological relevance.

Explore related subjects

Humans Malus Male Phenols Metabolome Metabolic Networks and Pathways Adult Young Adult Cross-Over Studies Fruit and Vegetable Juices Fruit Chlorogenic acid Double-blinded crossover study Pathway analysis Phenylalanine metabolism Tyrosine metabolism Untargeted metabolomics Journal Article Randomized Controlled Trial

Keep this discovery

BibTeX RIS

Niklas Roeder, Antje Geiken, Stefan Dussling, Louise Holtmann, Tim Hollstein, Svea Gluesing, Fynn Brix, Julia Jensen-Kroll, Vivian Schaarschmidt, Louisa Pannenbeckers, Thomas Stegemann, Anja Bosy-Westphal, Svenja Fedde, Dominik M Schulte, Mario Hasler, Ralf Schweiggert, Christof Dörfer, Karin Schwarz, Tobias Demetrowitsch. 2026-07-12. Effects of apple phenolics on the human metabolome: modulation of key metabolic pathways.. https://doi.org/10.1016/j.foodchem.2026.150382

Cite the original work for its findings. Save a collection to share your selection of sources.

Discover connections

Journal Article; Randomized Controlled Trial resource Adult subject Cross-Over Studies subject Fruit subject Fruit and Vegetable Juices subject Humans subject Journal Article subject Male subject Metabolome subject Randomized controlled trials study

Connections use source metadata and explicit phrase matches, not verified experimental comparisons.

KEEP EXPLORING

Related citations

PubMed2026

Introgression shapes the genomic conflict landscape of Malus, providing evidence for a reticulate backbone in a woody crop lineage.

Phylogenomic discordance is widespread across plants, but its evolutionary significance is often obscured when conflict is treated primarily as analytical noise rather than as evidence of underlying processes. In woody lineages in particular, incomplete lineage sorting, introgression, and genome duplication can interact over long timescales to produce complex genomic histories that are not adequately summarized by a strictly bifurcating tree. Here, we use Malus as a model woody genus to investigate how these processes structure conflict across a genus-scale, accession-based phylogenomic framework. Using broad taxon sampling, hundreds of nuclear loci, plastid genomes, and genome-wide SNP summaries, we reconstruct a robust nuclear backbone for sampled Malus lineages and evaluate where discordance is concentrated and which processes best explain it. Nuclear analyses resolve eight major clades, whereas conflict is non-random and localized to recurrent hotspots rather than evenly distributed across the tree. Cytonuclear discordance is similarly concentrated, especially around Clade H, represented by sampled accessions of M. tschonoskii, where localized plastid-nuclear disagreement is consistent with candidate plastid capture or organellar introgression. Multiple complementary analyses further indicate that the strongest conflict is not explained by ILS alone, but instead reflects lineage-structured introgression, while polyploid complexes represent additional localized sources of evolutionary complexity. Together, these results provide evidence for a reticulate genomic backbone in Malus and show how integrating nuclear, plastid, and genome-wide conflict analyses can help distinguish background discordance from process-specific signals in woody plant radiations. Several lineage-level reticulation hypotheses identified here should now be tested with broader population-level sampling and curated reference accessions.

Malus↗

PubMed2026

Cis-regulatory variation in the MdCKX6 promoter is associated with allele-specific expression and fruit size in apple.

Fruit size is a key determinant of apple fruit quality and market value and is strongly influenced by phytohormone-regulated cell proliferation and expansion during early fruit development. Cytokinin oxidase/dehydrogenase (CKX) enzymes regulate cytokinin homeostasis by irreversibly degrading active cytokinins, but the contribution of natural variation in CKX genes to fruit size remains poorly understood. Here, we identified MdCKX6 as a candidate regulator of fruit growth in apple (Malus domestica). MdCKX6 exhibited pronounced allele-specific expression during fruit development in the cultivar 'Royal Gala'. Sequence analysis identified a promoter SNP associated with differential promoter activity and allele-specific expression. Genotyping of diverse apple cultivars and wild Malus accessions revealed a significant association between MdCKX6 promoter genotype and fruit size. Cultivars carrying low-expression alleles produced larger fruits, whereas high-expression alleles were associated with smaller fruits. To investigate gene function, MdCKX6 was overexpressed in tomato, resulting in reduced fruit size. Histological analyses of the transgenic tomato fruit revealed smaller pericarp cells. Transcriptome analysis of transgenic fruits revealed widespread changes in genes associated with cell-cycle regulation, cell wall modification, hormone-related processes, and transcriptional regulation. Together, these results identify MdCKX6 as a potential negative regulator of apple fruit growth and reveal an association between cis-regulatory variants, gene expression, and fruit size. This study provides new insights into the role of cytokinin metabolism in fruit development and highlights regulatory variation in MdCKX6 as a potential target for apple breeding.

Malus↗

PubMed2026

Functional characterization of the MdFLZ2 gene in drought and salt stress tolerance in apple.

Drought and salt stress are significant environmental limitations that severely constrain plant growth and productivity, therefore, enhancing stress tolerance is a key goal in crop improvement. The plant-specific FCS-like zinc finger (FLZ) proteins have been identified as important regulators of stress adaptation. In this study, we conducted a genome-wide characterization of the FLZ gene family in apple and functionally characterized MdFLZ2. qRT-PCR analysis revealed that MdFLZ2 was differentially expressed across various tissues and transcriptionally induced by both drought and salt stress. Subcellular localization assays demonstrated that the MdFLZ2 protein is localized to both the nucleus and the cytoplasm. The overexpression of MdFLZ2 in apple calli, Arabidopsis and tomato conferred increased resistance to drought and salt stress. In addition, yeast two-hybrid (Y2H) assays confirmed that MdFLZ2 interacted with MdSnRK1.1, and similar interactions were also detected between other MdFLZ family members and MdSnRK1.1. Collectively, our findings suggest MdFLZ2 as a positive regulator of drought and salt tolerance and highlight its potential to serve as a genetic resource for abiotic stress improvement.

Malus↗