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Secondary bile acids are produced by bacteria in the gut from primary bile acids through various chemical modifications. Secondary bile acids are reabsorbed from the gut into the bloodstream, where they can exert systemic effects similar to those of hormones. Secondary bile acids are continuously produced in the body. While bile acids are most commonly associated with the digestion of fats, they also play a prominent role in the functioning of the female reproductive system.
- The ovary itself is capable of producing bile acids, which is why the level of bile acids in ovarian follicular fluid is twice as high as in normal blood serum. In patients with ovarian cancer, bile acids can be detected not only in the blood but also in the fluid accumulating in the abdominal cavity. According to research, the receptors in our bodies that detect bile acids directly influence the characteristics of ovarian cancer, and thus presumably also play a role in determining how aggressively the cancer grows or spreads- explained Adrienn Sipos, an assistant professor at the Deparment of Medical Chemistry, Faculty of Medicine, University of Debrecen.
The researcher added that it is now known that bacterial metabolites, such as secondary bile acids, exhibit “bioactivity” in various tumors, which means they can have either carcinogenic or anticancer effects. Ursodeoxycholic acid (UDCA) is one such bacterial metabolite; from a biochemical standpoint, it is a secondary bile acid that has primarily been attributed with anticancer effects to date. This led researchers to investigate the effect of UDCA on ovarian cancer.
In their studies, they concluded that this secondary bile acid, which occurs naturally in the body, induced characteristics of cancer progression and metastasis in ovarian cancer cell models.
- According to our results, when administered at physiological concentrations, UDCA affects the function of ovarian cancer cells by influencing and altering their morphological characteristics, metabolism, and motility. The changes observed are processes that facilitate the spread and worsening of cancer—that is, progression and metastasis. We identified the molecular mechanisms underlying these processes: an increase in the levels of a protein called NRF2 and a phenomenon known as reductive stress. Using a database that allows for the comparison of human gene expression data from healthy and cancerous cells, we found that the genes induced by UDCA in our experiments are associated with poorer survival- emphasized Adrienn Sipos.
The assistant professor at the University of Debrecen emphasized that previous studies have shown that secondary bile acids, such as lithocholic acid or deoxycholic acid, can have both carcinogenic and anticancer effects depending on the type of tumor; however, in the case of UDCA, only anticancer effects have been demonstrated so far.
The findings of the Debrecen researchers once again highlight that bacterial metabolites—including, as it turns out, UDCA—can have opposing effects in different types of tumors. These findings are important for planning the practical application of bacterial metabolites. If substances of bacterial origin—such as bile acids—are to be used for therapeutic purposes in the future, it is important to take into account that the same substance may even have opposite effects in different tumors.
The research was a true team effort; PhD students (Szandra Schwarcz, Dóra Szeőcs, Gyula Ujlaki), postdocs (Éva Kerekes, Emese Tóth), and a TDK student (Fanni Szarvas) all contributed to the results, and Adrienn Sipos was able to rely on the professional guidance of Edit Mikó and Péter Bay throughout the project. An article presenting the study’s findings was published in an international scientific journal, and the study has won the Publication Award from the University of Debrecen and the Count István Tisza Foundation for the University of Debrecen.
- This recognition means a great deal to me. Day-to-day scientific research often takes place quietly and invisibly in the background, so any objective feedback or recognition related to it is particularly gratifying. The recognition from the university and the foundation reaffirms that the energy I’ve invested and the work I’ve devoted to international publications are visible and valuable; the award provides further motivation to continue-said the researcher.
Adrienn Sipos is currently working with chemists from the Department of Organic Chemistry to develop newly synthesized metal complex compounds. These compounds have dual potential, as they have proven effective against both cancer cells and multidrug-resistant bacteria that do not respond to most currently known antibiotics. Due to the bacterial studies, researchers from the Institute of One Health have also joined the research effort in recent years. Members of this molecular family could become promising drug candidates for the treatment of both cancer and infections caused by multidrug-resistant bacteria.
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