The Gut Microbiome, Cancer And Immunotherapy - by Dr Lauren MacDonald

This week we have another insightful piece from Lauren, a 29 year old junior doctor when she was diagnosed with stage IV cancer, who is now celebrating one year NED. Here she discusses her obsession with gut health and why it is so important...

I thought I’d write another post on my favourite subject, “Gut Health”, but this time I’ve gone into the science behind why I’ve been banging on about the importance of looking after your gut microbiome for the past few years. I hope it’s helpful for anyone not yet up-to-speed on this fascinating area of research. 

Over the past few months several human studies have supported the idea that our intestinal bacteria (the gut microbiome) plays a significant role in determining whether cancer patients respond to certain treatments. In the latest research study, Dr. Wargo (a doctor and research scientist in the USA), revealed that the composition of a patient’s gut can significantly influence whether someone responds to the type of cancer immunotherapy I’ve been receiving for the past 22 months (pembrolizumab, an anti-PD1). Interestingly, what seemed to matter most in the studies wasn’t the level of a specific gut microbe, but rather the overall diversity of the gut microbiome. Let’s take a look at the evidence so far…

Where My Obsession With My Gut Health Began

Prior to 2015 I’d never considered the state of my gut microbiome. I hadn’t tried kefir, I didn’t take a regular probiotic and I’d never experienced the joys of eating Jerusalem artichokes (you’ll know what I mean if you’ve tried them!). Then in October 2015 I was diagnosed with stage IV melanoma, a cancer which is notoriously chemotherapy and radiotherapy resistant, and which previously had a 5-year survival rate of around 15%. Fortunately, a new immunotherapy drug was approved by the NHS at the beginning of 2016, just six weeks after I’d received the stage IV diagnosis. Although this was incredible news – and the idea of a “game-changing cancer drug” made for sensational headlines – it transpired that only a small group of patients had responded to the treatment during the clinical trials. The drug I was about to start had a response rate of around 30-40% (meaning patients had their tumours stabilise or shrink) with only 15% having a complete response (achieving no evidence of disease). I was determined to find myself in the latter group so I began researching how I could swing the odds in my favour.

My research began by examining the gut-brain axis, specifically the gut microbiome and its impact on health. I then looked at the way in which stress and anxiety could be impacting on my immune system. This lead me to further explore the growing field of psychoneuroimmunology and the research highlighting the value of mind-body therapies. It soon became apparent that there was a huge area of medicine that had been largely ignored during my medical degree. I felt relatively knowledgeable about “the mind” due to my Psychology degree and “the body” due to my medical degree, but there was a gap in my knowledge at the interface between the body and mind. I became fascinated by the gut-brain axis and, specifically, the impact the gut microbiome has on both mental and physical health.

Prior to becoming a stage IV patient, I’d already had four operations over the past 18 months in an attempt to “cure” me and prevent the cancer from spreading. Along with conventional surgery, I’d also addressed my diet, started juicing, added in supplements and began a regular yoga practice. But nothing seemed to be helping. The cancer kept coming back, again and again. Over Christmas 2015 I could visibly see new tumours growing above my right breast and a scan had already confirmed I had tumours in my lung and adrenal gland. Consequently I started looking for other ways in which I could support my body to either fight cancer cells directly or slow down/prevent angiogenesis (the formation of new blood vessels – which helps “feed” tumours).

The Initial Gut Microbiome And Immunotherapy Research (2015)

Shortly after I started looking at the the gut-brain axis I came across some research which had just been published by the University of Chicago (back in November 2015). They’d found that by introducing a particular strain of bacteria into the gut of mice with melanoma, they were able to boost the ability of the animal’s immune system to attack tumour cells. The combination of oral doses of “good bacteria” and infusions with anti-PD-L1 immunotherapy nearly abolished tumour growth. Around the same time another group of researchers compared the effects of bacterial transfer (via fecal transplant) against immunotherapy (anti-PD-L1). They found that introducing the bacteria was just as effective as treating mice with anti-PD-L1 alone – resulting in significantly slower tumor growth. Furthermore, combining the benefits associated with the “good bacteria” with anti-PD-L1 treatment dramatically improved tumour control.

Turning My Attention To My Gut Health Before Starting Immunotherapy

Given these two fascinating studies I decided to do everything I could to get my gut in the best possible shape before starting immunotherapy. During one of my appointments I mentioned the research to my Oncologist (and explained my intention to diversify my microbiome) but, understandably, he was hesitant to support my plan. The microbiome is, of course, inordinately complex – with trillions of bacteria working in tandem to produce multivariate responses. Although the research in the initial mouse studies had been promising, it might have been the case that altering the gut microbiome in humans would have a different outcome – an idea that has recently been supported by a study which found that certain chemotherapies used to treat colorectal cancer actually become toxic to patients in the presence of certain gut bacteria.

Despite my Oncologist’s reservations, I set about diversifying my gut bacteria in the hope that I might help to push myself into the “complete responder” group. Along with having a diverse microbiome, I knew it was also important to have the right cocktail of bacteria. I didn’t have much to go on – just those two initial mouse studies – so I purchased probiotics which contained the specific bacteria which had helped the mice to survive (Bifidobacterium – although the probiotic I took actually contained several other strains too). I also changed my diet to include as many pre- and probiotics as possible.

Key Diet Changes

I know I’ve shared lots of blog posts about this subject during the past two years, but just to remind you once again…

• The best way to keep your gut microbiome healthy is to make sure you’re getting a healthy mix of probiotics and prebiotics in your diet.
• Although taking a probiotic supplement is also helpful, there are plenty of studies that suggest oral probiotics struggle to make a huge difference to the microbiome (compared to the impact of fecal transplants).
• Simply changing our diets to include plenty of fibre, reducing refined sugars and not eating processed foods, can help improve the balance of bacteria in the gut.
• You can easily load up on probiotics by eating certain foods (e.g. sauerkraut, kefir, miso, apple cider vinegar, sourdough bread).
• Prebiotics are things like garlic, leeks, chicory root, Jerusalem artichokes, asparagus and under-ripe bananas.
• Research also suggests that omega-3 fats (found in oily fish) affect the microbiome in positive ways.
• It’s a great idea to try and fast for at least 12 hours overnight too. There’s lots of evidence to suggest this helps support a healthy gut microbiome.

The Latest Research (2017)

Dr Wargo teamed up with Gopalakrishnan and other researchers to collect faecal samples from more than 100 people with advanced melanoma before they began treatment with anti-PD-1 immunotherapy drugs. The scientists found that those who had the most diverse gut microbes were most likely to respond to the immunotherapy. The type of microbe was also linked to differences in responses to treatment. For example, people whose guts contained a lot of bacteria from a group called Clostridiales were more likely to respond to treatment. A second study showed that people who received antibiotics to treat infections shortly before or after starting immunotherapy did not respond as well to PD-1-blocking therapies. The researchers also found that the presence of the bacterium Akkermansia muciniphila was linked to better responses to immunotherapy. Responders had a far greater density of killer T cells – which are largely responsible for attacking cancer. The researchers found that the presence of the Faecalibacterium and Clostridiales bacteria seemed to account for the difference in T cell density. When these bacteria were given to cancer patients via a fecal matter transplant, they were more likely to respond to treatment and live longer without their tumour recurring or worsening.

The Microbiome: The Future Of Cancer Treatment?

I am under no illusion that the only reason I’m sitting here writing this post is because I’ve been on the receiving end of cutting-edge cancer treatment. I started immunotherapy in January 2016 and by August 2016 my scans revealed “no evidence of disease”. During the previous 10 months I’d become *OBSESSED* with looking after my gut but, of course, I have no way of knowing whether this made any difference to how I responded to immunotherapy. It might have been that I would have responded in exactly the same way, whether or not I’d changed my diet and started taking a daily probiotic supplement. Having said that, the 2015 studies and the new 2017 human studies suggest a big role for gut microbes in determining the cancer-killing potential of immunotherapies. Yet there are still plenty of questions, namely how, exactly, certain bacteria may help the immune system to fight cancer and if there are side-effects or potential dangers of manipulating the microbiomes of cancer patients. It will be fascinating to follow this research in the future. WATCH THIS SPACE!

I hope I’ve inspired you to look after your gut health – whether you are a fellow cancer patient or just someone looking to support their health and wellbeing.

Sending you lots of love and good health.

Lauren x

You can read more inspirational and informative posts on Lauren's blog, www.laurencara.com.

Please make sure you tell your own doctor before you start taking a daily probiotic – especially if you are undergoing cancer treatment.