Diet and microbiome shape small-molecule cytokinin pools in mammals

Author First name, Last name, Institution

• Eman M. Othman, Faculty of Pharmacy
• Elena Bencurova, Biozentrum der Universität Würzburg
• Pamela Ferretti, European Molecular Biology Laboratory Heidelberg
• Peer Bork, European Molecular Biology Laboratory Heidelberg
• Alvaro Rodriguez del Rio, CSIC - Centro de Biotecnología y Genómica de Plantas (CBGP-INIA)
• Jaime Huerta-Cepas, CSIC - Centro de Biotecnología y Genómica de Plantas (CBGP-INIA)
• Ignazio Caruana, Universitätsklinikum Würzburg
• Rania Abdel-latif, Faculty of Pharmacy
• Aman Akash, Biozentrum der Universität Würzburg
• Alfonso Albacete, Instituto Murciano de Investigacion y Desarrollo Agrario y Alimentario
• Feras Lafi, Zayed University, Abu Dhabi CampusFollow
• Thomas Dandekar, Biozentrum der Universität Würzburg
• Muhammad Naseem, Biozentrum der Universität WürzburgFollow

Document Type

Article

Source of Publication

Gut Microbes

Publication Date

6-12-2026

Abstract

Cytokinins (CKs) are adenine-derived metabolites traditionally characterized as plant hormones, yet their origin, distribution, and functions in mammalian systems remain largely undefined. Using integrated metabolomics, microbiome, and metagenomics approaches, we provide a systematic characterization of CK occurrence and potential sources in mammals. Serum profiling across five animal species revealed consistent detection of multiple CK derivatives, with concentrations markedly lower than in plant tissue. The CK storage form, zeatin-O-glucoside, predominated in mammalian sera, followed by trans-zeatin and kinetin, indicating a CK composition distinct from that in plants. Species-specific differences, such as reduced trans-zeatin in mice and lower kinetin in humans, further suggest divergent regulatory patterns. In mice, CKs were present in vascular tissues of the kidney, heart, and liver, demonstrating systemic distribution. Dietary manipulation showed that starvation significantly reduced CK abundance in serum, colon, feces, and urine, confirming that diet is a major contributor to the mammalian CK pool. Meta-omics analysis of gut microbiomes identified CK-related genes across multiple microbial taxa, with the highest representation in human microbiomes, followed by those of mouse and pig. Germ-free mouse experiments showed substantially lower CK levels than conventionally raised counterparts, establishing a microbiome-dependent contribution. Collectively, our findings identify CKs as diet and microbiome modulated metabolites in mammals, warranting future investigation to elucidate their physiological significance in mammalian biology.

DOI Link

10.1080/19490976.2026.2679497

ISSN

1949-0976

Publisher

Informa UK Limited

Volume

18

Issue

1

Disciplines

Life Sciences

Keywords

Cytokinins, diet-gut nexus, kinetin, plant hormone, t-zeatin

Scopus ID

105041959575

Creative Commons License

This work is licensed under a Creative Commons Attribution 4.0 International License.

Recommended Citation

Othman, Eman M.; Bencurova, Elena; Ferretti, Pamela; Bork, Peer; Rodriguez del Rio, Alvaro; Huerta-Cepas, Jaime; Caruana, Ignazio; Abdel-latif, Rania; Akash, Aman; Albacete, Alfonso; Lafi, Feras; Dandekar, Thomas; and Naseem, Muhammad, "Diet and microbiome shape small-molecule cytokinin pools in mammals" (2026). All Works. 8149.
https://zuscholars.zu.ac.ae/works/8149

Indexed in Scopus

yes

Open Access

yes

Open Access Type

Gold: This publication is openly available in an open access journal/series