Personalising cancer treatment using the gut microbiome

Listen to this blog story:

Listen to "Personalising cancer treatment using the gut microbiome" on Spreaker.

Over three million people in the UK live with cancer, and this is set to rise to 3.5 million by 2025¹. The past decade saw an increase in cancer patients undergoing immunotherapy, which activates the immune system to fight cancer. Unlike chemotherapy and radiotherapy, immunotherapy specifically targets cancer cells and often minimises collateral damage to healthy cells. However, immunotherapy can be expensive, slower and less effective. It can also trigger negative side effects, including autoimmunity.

But immunotherapy research may have hit a turning point. Scientists have discovered a link between the gut microbiome – the complex community of microorganisms living along the digestive tract – and a person’s response to immunotherapy. Dr Ashray Gunjur, a Clinical Research Training Fellow at the Wellcome Sanger Institute, investigates whether microbiome-based treatments can increase the effectiveness of immunotherapy for various cancers. I recently met with Ashray to learn about his valuable research, hospital work, and vision for the future of personalised cancer treatments.

An invisible community of microbes, including bacteria, viruses and fungi, lives on and in our bodies. This microbiome supports our health and bodily functions, including strengthening the immune system and digesting food. These bugs form distinct microbiomes in areas as diverse as the skin, gut and lungs. The gut microbiome is the best studied because microbe-rich stool samples are easy to collect.

“When looking at potential cancer treatments, there are many strategies that microbiome therapeutics can take. It could involve removing certain microbe species using targeted antibiotics, or encouraging beneficial species with probiotics. The aim is to leverage the microbiome to prevent or treat cancer.”

Dr Ashray Gunjur,
Clinical Research Training Fellow, Wellcome Sanger Institute

Immunotherapy is any treatment that uses the body's immune system to fight diseases, including cancer. Nineteenth-century scientists knew that tumours may shrink after an infection and Dr William Coley² administered dead bacteria to treat cancer. Later, monoclonal antibodies³ became the mainstay of immunotherapy until the arrival of immune checkpoint inhibitors, also known as immune checkpoint blockade (ICB).

The discovery of immune checkpoint inhibitors won the Nobel Prize for Medicine in 2018⁴. Research showed the immune system can identify cancer cells as distinct from other bodily cells. However, cancer cells may evolve proteins that prevent immune cells from detecting them. ICB drugs block these evasive proteins and unleash a wave of anti-cancer immune responses.

Two approved ICB drugs are ipilimumab and pembrolizumab, which target the immune checkpoints CTLA4 and PD1 respectively. These drugs are often effective in melanoma treatment and increase survival rates. For example, one study showed that pembrolizumab reduced the relative risk of cancer progression or death by 42 per cent⁵. The medicines also work against other types of cancer, including lung cancer, kidney cancer and bladder cancer.

CAR T-cell therapy⁶, another type of immunotherapy, was approved in 2017. This involves improving the ability of a patient's T cells, an immune cell, to identify and attack cancer.

Recent research supports a link between the gut microbiome and the effectiveness of immunotherapy. For example, a large study confirmed a connection between gut microbiome composition and how patients with advanced melanoma respond to ICB⁷.

This progressive research inspired Ashray’s career.

Ashray qualified as a medical oncologist in Melbourne, Australia. As a junior doctor, he chose to pursue medicine because he wanted to diagnose and understand diseases within a hospital setting.

“I chose oncology as my sub-specialty because immunotherapy was revolutionary. I watched the science unfold, increasing our understanding of cancers and how to treat them. You could see the scientific community’s enthusiasm - we could positively impact patients and improve treatments. Another research area exploding with knowledge was genomics combined with microbiome science. That’s what got me hooked and set my career trajectory.”

Dr Ashray Gunjur

Ashray pursued a career as a hospital doctor, so his first research project was purely serendipitous. His Australian colleagues invited him to collaborate on a clinical trial. The trial offered immunotherapy to patients with rare cancers, diagnosed in fewer than six in 100,000 people each year⁸. Patients with rare cancers seldom access clinical trials because it is difficult to find enough participants and there are few specialist clinicians. This study, likely the largest of its kind, was a multicentre trial, combining over 100 patients from five different hospitals⁹.

Flying to the UK, Ashray joined collaborators at the Sanger Institute as a PhD student to sequence and analyse these samples. Here, Ashray is co-supervised by two research group leaders: Dr Dave Adams, experimental cancer group, and Dr Trevor Lawley, host-microbiota interactions. This cross-disciplinary teamwork underpins Ashray’s innovative research. The Sanger Institute’s large-scale genetic sequencing capabilities enable scientists to explore vast microbial datasets and the labs provide specialist equipment to automate some of the analyses.

“It was a nice ‘bedside to bench’ transition – I had extensive knowledge about the clinical trial and patients, which helped guide our analysis. My work at the Sanger Institute has included wet lab research (sequencing the microbial genomes) and dry lab (data analysis). This rich experience influenced my new career direction. I want to be a cancer clinician who works with patients, alongside being a gut microbiome researcher. It’s really inspiring working in the clinic and having that patient contact – it helps me learn from patients and develop more effective treatments.”

Dr Ashray Gunjur

During Ashray’s research project, the team in Australia collected stool samples to see how the patients’ gut microbiomes responded to combination immunotherapy with ipilimumab and nivolumab. They discovered 22 microbial strains associated with a response to ICB treatment: 7 positive and 15 negative. Excitingly, these associations were consistent across different cancer types.

Researchers are interested in finding predictive biomarkers that work across multiple cancers to assess how a patient might respond to treatment. So far this has proved challenging. Focusing on individual gut microbial strains, Ashray’s group identified gut-microbiome biomarkers specific to varying immunotherapy treatments, but valid across cancers. They also showed the effectiveness of ICB is reflected by differences in gut microbiomes. The findings suggest that gut microbiome diagnostics or therapeutics should be tailored to the ICB treatment, rather than cancer type.

“This is the holy grail in personalised medicine research – to find “tumour-agnostic” biomarkers. For traditional treatments, you're not just fighting cancer directly, you have to attack normal cells. Each type of cancer is different – and so are the drugs. But with immunotherapy we’re unleashing human immune systems, so it's the same recipe for each microbe-assisted treatment. There are specific responses for specific immunotherapy types, but these remain consistent across cancers. This allows one drug to target numerous cancers.”

Dr Ashray Gunjur

Immunotherapy and microbiome-based treatments are promising cancer therapeutics. These techniques will help clinicians tailor cancer therapies to a person’s unique gut microbiome, increasing their effectiveness. Connecting microbiome data to genetic information will create highly personalised treatments.

The microbiome could also be used to predict treatment outcomes. By understanding how groups of microbes link to successful treatment responses, clinicians can predict how a patient might respond to a therapy before it starts. Clinicians could also monitor the microbiome during treatment to assess its effectiveness and make adjustments.

Another advantage is reducing the side effects of cancer treatments. Chemotherapy and radiotherapy often disrupt the gut microbiome, leading to gastrointestinal issues and other side effects. By maintaining or restoring a healthy microbiome, patients can experience fewer side effects and a better quality of life.

Whilst microbial-based treatments are less invasive, and can even mitigate side effects, it is important to remember they are used alongside immunotherapy. Unfortunately, a major side effect of ICB is long-term autoimmune disease, and the most common is hypothyroidism, where the body does not produce enough thyroid hormone. This can be managed through existing medication, but a smaller number of people risk more serious conditions including type one diabetes, colitis, and inflammatory bowel disease.

So clinicians may want to alter a patient’s gut microbiome to support their cancer treatment and reduce side effects. Here are some techniques for manipulating the microbiome:

Faecal Microbiota Transplants (FMT)

In FMT, a clinician will take a stool sample from someone with a healthy microbiome and implant this stool into the gut of a patient with an unhealthy microbiome. In the UK, FMT is already used to treat Clostridioides difficile infections that are unresponsive to other treatments. It shows promise in clinical trials for cancer patients, for instance to relieve some of the side effects of chemotherapy¹⁰. However, a recent Nature article suggested that whilst FMT provides a useful proof-of-concept tool, it is likely to be superseded by more precise treatments¹¹.

Probiotics and Prebiotics

Probiotics are collections of live bacteria and yeast that aim to restore the healthy microbial balance in the gut. Prebiotics are fermentable, but non-digestible, fibres that stimulate the growth of specific beneficial microbes living in the colon.

Whilst certain studies show they may reduce the side effects of some cancer treatments and can support anti-cancer therapies¹², there is a risk that live microbes may cause infection because some cancer treatments lower the number of white blood cells.

Personalised Nutrition Plans

Several recent studies have shown that personalised nutrition plans are more effective for overall health, and researchers are particularly interested in tailoring nutrition based on individual genetics¹³.

Similarly, cancer treatments could include nutrition plans that support gut health and enhance treatment effects by incorporating specific diets and supplements tailored to the patient's microbiome​.

Targeted antibiotics

In theory, if certain microbes are associated with a specific cancer, then using antibiotics that target these species may help treat that particular cancer. Several antibiotics are already used in cancer treatment, although there is some uncertainty about their mode of action¹⁴.

However, use of antibiotics comes with associated risks of antibiotic resistance and some may even affect the reproductive system. They may also reduce the effectiveness of immunotherapy by disrupting the intestinal microbiota¹⁵.

While microbiome-based treatments have a lot of potential, they are largely in the early stages of research and clinical trials. They are not yet widely available as standard care in hospitals. But as research progresses and there are more data, these approaches may become more integrated into standard cancer care.

For Ashray, in 2025 he has his mind set on developing microbiome-based treatments for pancreatic cancer. Globally, pancreatic cancer is one of the leading causes of cancer death and is set to become the UK's second leading cause by 2030¹⁶. Unfortunately, over the past 50 years, scientists have made very little progress in improving patient outcomes.

The gut microbiome appears to be closely linked to the development of pancreatic cancer and severe complications like cachexia (muscle wasting and weight loss despite adequate diet). This means the microbiome could pose a suitable target for pancreatic cancer detection, early interception, or mitigating its severity. Though cachexia is a common and distressing syndrome in pancreatic cancer, there is currently a lack of treatments to reduce or reverse it. Scientists also do not know which specific microorganisms may contribute to, or protect against cachexia.

Ashray aims to address this by curating the largest international collection of stool samples from pancreatic cancer patients. He will identify the specific microbial strains associated with cachexia and explore how these microbes impact the condition. Importantly, this may lay the groundwork for new microbe-based cachexia treatments for pancreatic cancer patients.

In this new study, the team will take a novel approach: rather than predicting immunotherapy responses, they aim to predict who might develop cancer. Ashray explains that the exciting question is whether it is possible to reduce a patient’s cancer risk. But the first step is finding strong, consistent associations between gut bugs and pancreatic cancer.

Before researchers develop personalised microbiome treatments, they need to address technical challenges. For example, studies must focus on larger, more geographically diverse populations, ideally with standardised, best-practice approaches to faecal collection and DNA extraction.

Ashray shared his vision for the microbiome in cancer care:

“I see a future where clinicians, who already run routine blood tests etc., also regularly provide gut microbiome tests. For example, newly diagnosed cancer patients, or people at a high risk of cancer, could be offered rapid and accurate stool profiling to get a ‘gut microbiome readout’.

Patients with a gut microbiome that may predispose them to cancer or other negative outcomes – such as not responding to treatment or cachexia – could be given tailored preventative microbiome-based treatments. This is analogous to correcting electrolyte or vitamin deficiencies detected by blood tests. Eventually, we hope to offer ‘precision microbiome medicine’, providing the right interventions, to the right patient, at the right time.”

Dr Ashray Gunjur

Microbiome-supported immunotherapies are here to stay and several pharmaceutical companies are investing in this area. For example, Sanger Institute spin-out Microbiotica  has developed a microbe-based co-therapy (MB097) for melanoma that is entering clinical trials.

Ashray envisions a future where cancer treatment is highly personalised, leveraging microbiome data to tailor therapies. His work on the microbiome's role in cancer prevention and early detection, particularly for hard-to-treat cancers like pancreatic cancer, heralds significant improvements in cancer therapy.