Going with your gut

It’s a fact that’s hard to stomach: you are more bacteria than human. The approximately 39 trillion cells in these tiny organisms just outnumber the 30 trillion human ones in an adult body. Scientists are now beginning to understand how these billions of bacteria and other microbes, collectively known as the microbiome, work together to affect functions as diverse as digestion, heart function, mental health, and even the development – or treatment – of cancer.

Dr Erin Shanahan (BSc(Adv)(Hons) ’07, PhD ’14) has a personal stake in beating bowel cancer, also known as colorectal cancer: it has affected her family throughout her lifetime, with three grandparents and an aunt all having suffered through the disease. But it is her warmth and humour that shine through as she discusses her work on the microbiome, acknowledging it’s “not necessarily dinner-time conversation.”

“The surface area of the gut is absolutely enormous – flattened out, it could cover a studio apartment. This creates a massive area for microbes to grow in.”

The organisms living in our guts are not innately harmful, but issues can arise when the hundreds of species become imbalanced. Our diet has an important role to play in managing these microbial hitchhikers: over time, the wrong diet can encourage a proliferation of species which impact surrounding gut cells, pushing them towards becoming cancerous.

As Shanahan quips, “what we eat is what they eat! We already know some risk factors, like diets which are low in fibre and high in processed meats. But we don’t understand why, if you put 100 people on that ‘bad’ diet, they won’t all develop bowel cancer. And the answer to that might lie in the microbiome.”

A microbiologist and à Beckett Fellow, Shanahan conducts her research from the Charles Perkins Centre at the University of Sydney.

The fellowship was created when Emma Elwin “Ellie” à Beckett left a $15 million bequest to the University following her death in 2013. Named after Ellie’s brother, the William Arthur Martin à Beckett Cancer Research Trust has supported four Fellows and the establishment of a germ-free facility – a space completely free of microbes, critical for studying the relationship between the microbiome and disease.

With work spanning preclinical studies through to patient-led care interventions for bowel cancer, the à Beckett Fellows stand as an extraordinary monument both to Ellie’s love for her brother, and to the profound impact of endowed giving.

Bowel cancer is the third most diagnosed in Australia, with 15,000 new cases every year. When Martin à Beckett died in 1986, the five-year survival rate for bowel cancer stood at 55 percent with treatment largely focused on surgery, and chemoradiation just beginning to gain traction. 

Today the five-year survival rate is 70 percent due to an increase in colonoscopies and screening, and the growing number of treatment options, including more targeted therapies.

Using personalised nutrition to treat cancer is central to Shanahan’s two-pronged research. The first element of her study uses pre-clinical models and clinical data analysis to investigate what constitutes a healthy microbiome, including which dietary elements can encourage gut health, or affect tumour development.

Shanahan hopes this knowledge will help patients lower their risk of bowel cancer. For example, following a colonoscopy where polyps are discovered, doctors in future might advise a patient on specific dietary changes or supplements that could reduce the chances of developing a tumour.

“If we can inform an individual that eating red meat is particularly risky for them based on their unique microbiome, that’s more powerful than generic advice to eat a healthy, high-fibre diet.”

But it’s the second component of her work which Shanahan seems most passionate about.

“In terms of a ‘breakthrough’, I’m really excited about my work in immunotherapy, and reactivating the immune system to try to target and kill cancer cells. Immunotherapy has been revolutionary in cancer treatment in recent years, and we’re interested in the emerging evidence that the gut microbiome has a role to play.”

The gut microbiome interacts with our immune system, and can stimulate the right types of immune responses to potentially eliminate a tumour – even one located nowhere near the gut.

However, many immunotherapy patients suffer prohibitive side effects, or are unresponsive to treatment.

Shanahan is researching whether biological signatures in the microbiome can predict which patients are likely to respond positively to immunotherapy. Longer term, the aim is to help more patients become part of this responsive group, through diet and other interventions.

“Although we are still designing clinical trials, I feel there is a direct pathway to change ahead. One clinician I work with has already begun talking to her patients about what might be possible for them in future.”

For Shanahan, the à Beckett Fellowship has provided the stability to build a comprehensive research program, in a field not traditionally associated with microbiology.

“Without Ellie’s gift, I wouldn’t be bringing my knowledge of microbiology to colorectal cancer – she has enabled me to apply my expertise to a new, emerging area.

“It’s an incredibly generous thing to do,” says Shanahan, beaming. “This gift will keep on giving, beyond its original scope. As researchers, we are always building on what has come before. The knowledge and ideas generated by the Fellowship will be informing studies, and helping patients, long after the money has been spent.”