In biology, cytokinins were long considered regulators exclusive to the plant kingdom, where they control, among other things, growth and responses to stress. Until now, little researches have been conducted into whether these substances might also play a significant role in the human organism. A research team from the Bio Centre at the University of Würzburg has now demonstrated, however, that cytokinins are distributed throughout multiple mammalian organs and thus also in humans.

The team published its findings in the journal Gut Microbes. The study was led by biochemist PD Dr. Eman M. Othman-Sholkamy and bioinformatician Professor Thomas Dandekar.

Across five different species, ranging from carnivores to omnivores, the team demonstrated that cytokinins are an integral part of mammalian physiology. Furthermore, the scientists were able to show that these signaling molecules are not confined to specific locations but are distributed throughout the body via bloodstream.

However, there are significant differences in cytokinin concentrations between plants and mammals: In plants, concentrations are roughly four to ten times higher than in animal or human blood serum. Nevertheless, these molecules are unlikely to be mere byproducts. The research findings suggest that they may perform important functions, such as in muscle growth, cellular aging processes, or the protection of nerve cells.

To identify the origin of cytokinins, the scientists conducted controlled feeding experiments and subsequently examined the animals’ microbiome in detail. Microbiome: This term describes the totality of all microorganisms such as bacteria, viruses, and fungi that colonize the body. To understand the genetic basis, they analyzed a massive dataset of 2.3 billion gene sequences from the Global Microbial Gene Catalog. The key findings are as follows:

• Influence of diet: After eight hours of fasting, cytokinin levels in blood serum and urine of mice declined significantly. This demonstrates that daily dietary intake is a primary source of the cytokinin pool.
• Importance of the gut microbiota: Significantly lower levels of these signaling molecules were detected in so-called “germ-free” mice, which lack a natural microbiome. However, metagenomic analyses identified specific genes involved in cytokinin production in various bacterial strains.
• Endogenous cytokinin producers: The body’s own TRIT1 gene may play a special role. This gene is associated with the synthesis of specific types of cytokinin. Its presence suggests that mammals do not rely solely on external sources but possess the genetic machinery needed to produce small amounts of these compounds themselves.
• Inactive hormone stores: During their biochemical analysis, the researchers discovered what is known as cytokinin O-glucoside. This compound functions in the body as an inactive storage form of the hormone, which can be converted into its active form as needed.

The distribution of cytokinins is by no means limited to the blood. The researchers detected these substances in the kidneys, heart, and liver. According to them, this widespread presence in vital organs underscores their potential biological relevance. “If these substances are systemically stored in peripheral tissues, their widespread presence raises the possibility that they may influence fundamental processes such as cellular aging or the immune response,” says first author Eman M. Othman-Sholkamy. Accordingly, the findings could have important implications for understanding how long-term health is maintained.

“The presence of these botanical hormones in the human body may open up new avenues for medicine,” adds Thomas Dandekar. Future studies should therefore clarify the extent to which cytokinins can be used therapeutically for inflammation or neurodegenerative diseases such as Huntington’s disease.

Eman M. Othman-Sholkamy, Muhammed Naseem and Thomas Dandekar were among the first groups who have been conducting research on cytokinins in infection (Naseem et al., 2012), in cross-kingdom communication (Naseem et al., 2015) and their presence in humans, mammals and redox stress protection (Othman-Sholkamy et al., 2016).

Together, the three authors have published twenty scientific studies on this topic. In parallel with the study presented here, they also published a review article in *Gut Microbes*. In it, they provide a comprehensive overview of cytokinins and the human microbiome as an indispensable biological partner that significantly influences metabolism, the immune system, and the efficacy of medications.