In her hand, Janine Ziemons (30) holds a mint green thesis, taken care of down to the last detail. In no fewer than 332 pages, she writes about her research into the role of intestinal bacteria in cancer patients. But it is plants that adorn the cover of her book. “These plants symbolize the ecosystem in the intestines. Just like in a healthy forest, the ecosystem in our intestines must also be in balance.”
About 100 billion bacteria live in our intestines. They form a complex ecosystem and constantly communicate with each other and with the intestinal environment, an entity known as the intestinal microbiota. Every person has a unique mix of such bacteria. Ziemons explains: “In a ‘healthy’ ecosystem, beneficial and less beneficial bacteria live together harmoniously. That balance is essential for our health, from digestion to the immune system. I think of it as ‘the power of balance’.”
For example, there are beneficial intestinal bacteria that break down nutrients, releasing substances that combat inflammation. Bacterial species also make contact with cells in the intestinal wall, which in turn release signaling substances to the nervous system, with the brain as their final destination.
“Unhealthy diet and antibiotics are factors that can disrupt this balance,” says Ziemons. If the less good bacteria increase, irritating substances can be released. These substances can damage the protective layer of the intestinal wall or end up in the bloodstream. “That can not only cause inflammation in your intestines, but also cause problems elsewhere in your body, such as more inflammation or a disturbance in metabolism.”
Chemotherapy can also throw the microbiota out of balance, Ziemons suspected at the start of her PhD research. “Chemotherapy is a major treatment. The toxins not only inhibit the division of cancer cells, they also unintentionally attack other rapidly dividing cells, such as those of the intestinal wall.”
Ziemons analyzed poop samples for five years. “It may sound strange, but I was actually busy with bowel movements day in and day out. Analyzes of fecal samples allow you to identify the bacteria present and substances produced in the intestines.”
In February, Ziemons obtained her doctorate at Maastricht University in the department of surgery. For her research, she followed patients with colon or breast cancer who underwent chemotherapy for several years, including at Maastricht UMC+. Ziemons was looking for answers to questions such as: which bacterial species respond sensitively to the treatment? And are there species that actually thrive?
Breakdown of fiber in the intestine
She collected three stool samples from each patient: before, during and after treatment. “By analyzing the bacterial DNA in these samples, we determined which bacterial species were present and in what quantity. We also measured the concentration of substances that come from bacteria.” For example, short-chain fatty acids, healthy substances that produce beneficial bacteria when breaking down fiber in the intestine. These substances, among other things, combat inflammation. “We prefer to see a high concentration of these short-chain fatty acids.”
Ziemons also conducted experiments in the laboratory. “It is important to also demonstrate in a controlled environment which bacterial species respond to chemotherapy. For this we used an artificial intestinal model, in which a patient’s environment and lifestyle do not influence the results.” This model accurately simulates the intestinal environment: it has the correct pH value, temperature and various tubes constantly transport intestinal substances in and out.
Ziemons initially had no experience with genetic data analysis. “It was quite exciting at first, but I was determined to learn the computer language,” she says. After watching numerous YouTube videos and taking courses, she finally managed to perform all her analyzes herself. “I was especially proud when I saw my first coded figure.”
Her hypothesis turned out to be correct: some beneficial bacteria appear to thrive less well during chemotherapy, while other less beneficial bacteria grow faster. This causes an imbalance in some patients, which increases the risk of inflammation. “And these inflammations may contribute to the side effects of chemotherapy, such as diarrhea.”
Food for beneficial bacteria
But there is hope, says Ziemons: “The intestinal microbiota is relatively easy to influence.” An example of this is the administration of prebiotics. These are indigestible fibers that serve as food for beneficial bacteria, causing them to grow faster at the expense of the less beneficial species. “This may restore the balance and keep side effects to a minimum.” Ziemons emphasizes that this is still a hypothesis: “The effect of prebiotics has not yet been studied in patients. Large-scale studies will have to reveal this in the coming years.”
Ziemons does not let go of the subject. She recently started as a postdoc at the same research group. “My dissertation was just the beginning,” she says. “There are still many questions I want answers to.”
Ziemons hopes to discover whether intestinal bacteria can help predict who will respond well to chemotherapy and who will benefit more from modulation of the microbiota or other treatments. Ziemons: “I want to make our research as practical as possible for hospitals, so that it really benefits doctors and benefits the patient. My goal is to make the intestinal microbiota an integral part of cancer treatment. In this way we can achieve increasingly personalized care.”
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Tags: Chemotherapy disrupt balance intestines
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