Gut microbiota and nutrition in cancer care

THE microbiome has recently become a focus of medical research activity and popular conversations about nutrition.

Dr Michael Mosley, a renowned science communicator, has helped popularise diverse research findings about the microbiome and its role in human health and disease. His latest Australian media work has focused specifically on gut health.

While the topic of nutrition has always been popular (and undoubtedly controversial), new discoveries about the myriad links between the gut microbiota and health and disease have further piqued researchers’ interest in nutrition, and increased public expectations regarding evidence-based dietary advice.

Yet another nutritional controversy

But navigating the complex field of nutrition science can be difficult.

An important study published in 2013 that is frequently used to support now-popular dietary recommendations found itself at the centre of a notable and interesting controversy. While this controversy does not necessarily diminish the validity of the advice that is proffered based on the study, it does illuminate some challenges associated with conducting rigorous large scale longitudinal studies focused on nutrition and health.

The reason I mention it here is to highlight that it is not always easy to develop rigorous studies that may be used to provide definitive nutritional advice.

The Prevención con Dieta Mediterránea (PREDIMED) trial was once deemed a keystone of nutritional epidemiology. It was a Spanish randomised controlled trial (RCT) that sought to examine the health benefits of the Mediterranean diet. The study involved 7447 participants who were assessed as being at high risk of cardiovascular disease.

It found that the two intervention groups – comprising people who received advice about following a Mediterranean diet supplemented with either extra virgin olive oil or nuts – were less likely (hazard ratio, 0.70 [95% CI, 0.54–0.92] and 0.72 [95% CI, 0.54 –0.96], respectively) to experience a cardiovascular event (myocardial infarction, stroke or cardiovascular disease-related death) than others who received advice about following a low fat diet (the control group).

The trial was closed prematurely (5 years after commencement) because the benefits observed among participants in the intervention groups (those who followed the Mediterranean diet) in an interim analysis were deemed highly significant. A Mediterranean diet supplemented with extra virgin olive oil or nuts, the study found, reduced the incidence of major cardiovascular events. The benefits of the intervention were obvious, it was argued, and the control group needed to receive the same advice. This dramatic announcement and the early closure of the trial certainly added to its aura.

However, upon publication of the results, reviews of the data, prompted by an article that criticised poor randomisation practices in RCTs, found inconsistencies in the randomisation of participants. These inconsistencies meant that the results of 21% of the study participants had to be discounted. The PREDIMED authors re-analysed the data and published a revised version of the article, which maintained that, even without these now-expunged results, the original conclusions remained valid.

Primarily predicated on methodological concerns, debates around the trial highlighted some of the significant challenges that routinely constrain studies (particularly RCTs) in nutritional epidemiology (a field that has traditionally relied on observational studies). The (sometimes needlessly acrimonious) controversy around this trial did also contribute to some confusion about the suitability of dietary advice recommending the Mediterranean diet.

Gut microbiota and nutrition in cancer care

As general awareness of the significance of the microbiome grows, general practitioners and other clinicians are likely to encounter more questions about diet, nutrition and gut microbiota health.

For cancer patients, understanding how their diet and gut health may affect (and be affected by) cancer treatments can be quite crucial. Earlier this year, the National Centre for Infections in Cancer at the Peter MacCallum Cancer Centre in Melbourne organised a consumers’ information forum on the microbiome. The aim of this event was to present a summary of information about the microbiome that addressed some of the questions that patients themselves had raised with clinicians at the hospital. Nutrition was among the topics that were discussed at the forum. The information presented was tailored to primarily address concerns raised by cancer patients.

Rose Rocca, a dietitian who works at the hospital, helped distil and clarify some of the nutrition-related implications of what we know so far about the microbiome.

Rocca noted that different bacteria in the gut microbiota feed off different food sources, so eating a variety of foods will support a healthy gut microbiota. She said her key message was that eating fibre is important.

“Most of us eat about 15 to 20 grams of fibre a day, but the recommended daily intake is 25 to 30 grams,” Rocca said.

“We need different types of fibres. Different fibres affect the gut in different ways. Greens, tomatoes, artichokes, asparagus, onions, garlic, leeks, certain types of berries, bananas, legumes and flax seed are examples of foods that are rich in prebiotics. Prebiotics are important because they promote healthy gut bacteria and support the production of short-chain fatty acids. Short-chain fatty acids help maintain the health of our intestines.”

Prebiotics are food substances that support the growth and activity of probiotics (bacteria that support gut health). Rocca added that resistant starch – found in oats, legumes, pasta, rice and potatoes – also has a role to play in maintaining a healthy gut microbiota.

As a dietician in a cancer hospital, Rocca said that she emphasised to patients that improving nutritional intake and having a healthy body weight before cancer treatment were important.

“We want you to come into treatment having the best nutritional state that you can have. We want you to have a good, healthy weight.”

While there isn’t enough evidence to suggest that having a healthy gut microbiota before treatment will influence outcomes or affect whether and how patients experience side effects from treatments, there is some emerging literature that suggests that people who have a healthy gut microbiota respond better to immunotherapy. Therefore, for some patients, the health of their gut microbiota (the absence of dysbiosis) may be a factor that contributes to the trajectory of their treatment and treatment outcomes. This speaks to the need for maintaining good nutritional intake before treatment (and more generally). However, the focus of dietary care may change after the commencement of therapy.

“Once we start treatment, things change because a lot of treatments can affect your weight. You can lose your appetite quite quickly, and experience nausea, vomiting, taste changes and difficulty swallowing,” Rocca said.

“This can then lead to weight loss, and that in turn can lead to worse outcomes. The evidence is quite clear – if you lose weight and become malnourished, you are more likely to experience fatigue and loss of muscle mass, and face the prospect of prolonged recovery time post-treatment and longer hospital stays. The body does not have what it needs to heal and recover.”

Rocca said that, in the cancer setting, when patients experience weight loss and malnourishment during treatment, the dietician’s focus may shift to encouraging consumption of high energy, high protein foods. The aim of this strategy is to promote the maintenance of a reasonably good body weight and reverse weight loss during treatment.

Every cancer patient will have a unique set of circumstances and health concerns that will shape their experiences of treatment. Getting expert and tailored dietary advice about maintaining good nutritional intake throughout the treatment journey can certainly help.

Dr Arjun Rajkhowa is the centre manager of the National Centre for Antimicrobial Stewardship at the Department of Medicine, University of Melbourne, Doherty Institute, and Royal Melbourne Hospital.

The statements or opinions expressed in this article reflect the views of the authors and do not represent the official policy of the AMA, the MJA or InSight+ unless so stated.