Cancer, chemotherapy and the microbiome
Cancer is a central health issue in our society: although new cases and mortality risk are tending to decline, cancer is still one of the most common causes of death and is expected to affect 4.9% of Austrians by 2030 due to the increasing aging of our society. Anita Frauwallner discusses with Prof. Christoph Castellani to what extent tumor diseases change the microbiome and what influence pro- and prebiotics can have as an accompanying therapy, including identifying the best probiotics for chemo patients.
Anita Frauwallner: Cancer is affecting more and more people, so that almost everyone comes into contact with it. In your research, you deal with metabolic disorders that occur in cancer patients – in children as well as in adults – and also investigate the connection with intestinal bacteria. Which functions of the microbiome are particularly relevant for cancer patients?
Prof. Christoph Castellani: Our microbiome can influence health in many ways, for example, intestinal bacteria metabolize non-digestible carbohydrates into short-chain fatty acids (SCFAs). These SCFAs reduce inflammation in the body, improve the intestinal barrier, and are an important source of energy for epithelial cells, the innermost layer of our gut.
However, when bacteria break down, toxins can be released that cause severe inflammation. This can damage the intestinal wall. However, this is one of the most important barriers of our body, because it prevents harmful substances from being absorbed from the intestinal contents. At the same time, the intestinal wall is very capable of allowing water and nutrients to pass through and be made available to the organism. For this selective barrier to function, it is important that the epithelial cells are very tightly connected: They are glued together, so to speak, by means of the so-called tight junctions, and in a healthy intestine these glued junctions can open and close in a targeted manner, precisely to let nutrients through and “lock out” pathogens.
However, if there is dysbiosis in the intestine, i.e. an altered composition of the intestinal flora that has a detrimental effect on us, then the important short-chain fatty acids are missing. The cells of the intestinal wall are undersupplied and the intestinal barrier is damaged. In this way, bacterial toxins and toxins from food can then pass through the intestinal wall into the body, activating immune cells and causing inflammatory reactions. This creates a vicious cycle: the inflammation causes the intestinal wall to leak, the leaky intestinal wall increases the inflammation, and the increased inflammation causes the intestinal wall to become even more “holey.”
Anita Frauwallner: We already know from patients with various inflammatory diseases such as dementia, multiple sclerosis or liver disease that the microbiome is altered. Can this also be observed in cancer patients? Or is an altered intestinal flora even causally involved in the development of cancer?
Prof. Christoph Castellani: It may well be that dysbiosis is partly responsible for triggering tumor development: the composition of the microbiome changes, the pathogenic germs produce toxins, and these trigger colon cancer. This harmful change in the intestinal bacteria occurs as a result of taking medication and, in particular, as a result of an incorrect diet: Our Western diet with plenty of meat, fast food, soft drinks and sugar is particularly bad for the microbiome; in addition, we also consume cancer-causing substances (note: e.g. alcohol; heavy metals; cadmium from cigarette smoke) with our food. Studies that have investigated the influence of food on the development of colorectal cancer show how harmful our diet is: Consumption of red meat, sausages, ham and alcohol is considered to be particularly risky – and obesity, which affects 55% of Europeans, is also a key factor. Animal fats, cheese and sugar also seem to favor the development of colon carcinomas.
What is also known is that patients with colorectal cancer show a marked decrease in lactobacilli, i.e. lactic acid bacteria, and faecalibacteria, which incidentally are important producers of SCFAs. A close connection between the microbiome and tumors is therefore clearly given.
Anita Frauwallner: One of your research areas is cachexia in tumor diseases. What do you mean by this? Is there also a connection with the microbiome that can be supported with study results?
Prof. Christoph Castellani: Cachexia is a deficiency disease in which fat and muscle tissue is lost. It occurs particularly frequently in cancer patients: Approximately 50% of adults with a malignant tumor have to struggle – sometimes only temporarily – with such emaciation. In 20-50% of tumor patients, cachexia is even the cause of death. The problem is that patients not only lose fat and muscle due to various metabolic disorders, but also suffer from inappetence at the same time: They no longer feel hungry. Although the loss of the feeling of hunger can be attributed in part to the side effects of chemotherapy, an important reason is also cachexia itself, which leads to this reduction in the feeling of hunger via inflammatory reactions and modulations in the brain. The situation is similar in children, where 46% of young patients with malignancies exhibit tumor-associated malnutrition.
Cachexia not only makes patients weaker – it also increases their susceptibility to infections and delays wound healing, which poses further risks, especially after surgical interventions. The effectiveness of chemotherapy deteriorates, and this also has negative consequences for the prognosis of patients.
In tumor therapy, we should aim to keep the patients’ microbiome intact in order to deliver more effective chemotherapy.
We have conducted two experimental studies ourselves: In both models, the cancerous mice became cachectic, losing fat and muscle mass, and it was clearly seen in the stool that several Lactobacillus species were significantly reduced. Obviously, cachexia leads to a change in the microbiome and in particular to a decrease in lactic acid bacteria.
Anita Frauwallner: You just mentioned that chemotherapeutic agents – as necessary as they undoubtedly are – have an additional negative impact on the microbiome. Are there side effects which may even drastically limit the course of treatment?
Prof. Christoph Castellani: Chemotherapy serves to destroy the tumor. However, a side effect of this treatment is an (additional) increase in intestinal permeability: chemotherapeutic agents are designed to attack all those cells that divide rapidly. These include precisely the tumor cells, but also hair follicles (which explains the hair loss in cancer patients) – and the cells of the intestinal mucosa. The permeability of the intestine is increased by changing the tight junctions and destroying the epithelial cells of the intestine. Thus, as mentioned at the outset, increased bacterial toxins can enter the body and exacerbate existing inflammation.
However, the most serious side effect of chemotherapy is mucositis, an inflammation of the mucous membrane of the entire gastrointestinal tract, which manifests itself as abdominal pain, nausea, vomiting, (bloody) diarrhea or constipation. These are quite common complaints, occurring in 40% of adults and even in 60% of children. The big problem here is again the permeability of the intestines, which allows bacterial toxins to enter the body and lead to life-threatening infections. But even worse, when mucositis is present, we have to reduce the dose of drugs – and thus reduce the effectiveness of chemotherapy. So the gut forces us to use less effective therapy.
The connection with the microbiome is that the administration of chemotherapeutic agents alone leads to dysbiosis in the gut. In addition, experimental groups show that animals with a tumor generally have fewer bacteria in their gut than healthy ones. A combination of tumor and chemotherapeutic agents is particularly severe for the intestine – here the drop in the important lactobacilli in particular is especially high. However, what is also known from a very recent study is that an intact, healthy microbiome is essential for the function of chemotherapy. Therefore, in tumor therapy we should aim to keep the patient’s microbiome intact in order to be able to administer more effective chemotherapy.
Anita Frauwallner discusses with Prof. Christoph Castellani to what extent tumor diseases change the microbiome and what influence probiotics and prebiotics can have as an accompanying therapy. Anita Frauwallner: We know from our research at the AllergoSan Institute that pre- and probiotics have an essential influence on intestinal health. What experience do you have with this in the field of chemotherapy and tumor therapy?
Prof. Christoph Castellani: We know from study data that an increased consumption of natural fibers, e.g. pectin, inulin or maltodextrin, reduces the risk of colon cancer. All that is needed is a change in diet from the Western diet to a high-fiber diet. The potential of specifically combined prebiotic and probiotic supplements is even greater: prebiotics, i.e. fiber substances that promote bacteria resident in the intestine, have the great advantage that they transport the food pulp through the digestive tract more quickly. Thus, we are exposed to cancer-causing substances for a shorter period of time. In addition, experimental studies show that inulin, for example, promotes the growth of lactobacilli and bifidobacteria so that more short-chain fatty acids are available and inflammatory parameters are reduced. Pectin administration was even shown to reduce fat loss, lipolysis, and restore feelings of hunger.
Probiotics have positive effects in several ways, including inhibiting the adhesion of pathogenic germs in the intestine, creating a better environment for beneficial bacteria by influencing pH, and stimulating the immune system. Here, too, an experimental study shows success: after administration of lactobacilli, inflammation parameters were also reduced and muscle wasting improved. A combined administration of pre- and probiotics could thus positively influence cachexia, and thus be an important concomitant therapy.
Clearly positive data exist for the use of probiotics to reduce mucositis. Here, several studies – the largest with almost 500 patients – show that the use of probiotics can significantly reduce mucositis and chemotherapy-associated diarrhea, both in adults and children. Thus, probiotics are important in the adjunct of chemotherapy to reduce severe side effects and thus enable effective treatment.
Anita Frauwallner: Thank you very much for the interview – we are looking forward to new research results!
*Christoph Castellani is a specialist in pediatric and adolescent surgery at MedUni Graz and his research focuses on inflammatory reactions, disorders of the intestinal wall barrier and metabolic disorders associated with cancer, which also originate in the microbiome.
We highly recommend our unique probiotic colon drink, which contains trillions of good bacteria and as many as 27 strains. One bottle (34oz) lasts up to a week and COLONDRINK can be used by adults and children. It is a unique product with a very high concentration of good bacteria, nothing like Yakult or similar popular products with only a few billion good bacteria. Colondrink+ is plant based, especially important for those who are lactose intolerant, or simply concerned about their health to avoid unnecessary substances such as sugar or flavour enhancers or food colours. This is a very high quality product that you won’t find in popular supermarkets like Kroger, Walmart, Costco, etc. Wow, we are thrilled to share that our product has received an abundance of positive reviews from satisfied customers! They rave about the delicious taste and unique tangy flavor that is sure to please even the most discerning palates. Don’t miss out on this mouthwatering experience!
