What's new in cancer?: Microbiome

Last week I popped some poo in the post. Not something I necessarily thought I’d be sharing with you all. But this blog is all about the power in poo and how we need to understand it better.

As an early birthday present I was invited to a pilot extension of a NHS colon cancer screening to submit a Faecal Immunochemical Test (FIT).

The FIT test is a screening test for colorectal cancer that is available throughout the UK. It is offered every 2 years to men and women aged 60 to 74. A pilot scheme is now offering the test to some people in their fifties.

The UK has 3 screening programmes. There are regular screening tests to help find breast or colorectal cancer early. There is also a regular screening to prevent cervical cancer.

The FIT looks for the tiniest traces of blood in poo as an early sign of bowel cancer. If any is found then a colonoscopy is recommended.

GPs can use a FIT test to help determine which people might need a colonoscopy. This is helpful as there is a shortage of capacity for these specialist examinations. 

A recent study in Scotland has shown that two tests may better than one. Lorna Porteous, Macmillan Regional Clinical Advisor, co-authored the study which suggests that 2 sequential tests improved sensitivity from 84.1% to 96.6%.

The test is only helpful if the public are happy to sample their poo. Studies so far show they are, particularly if it helps avoid a colonoscopy.

I’ve been deliberately using the word ‘poo’ rather than more medicalised jargon e.g. ‘faeces’ or ‘stool’. In communicating with the public it’s important that we use language that is understood and accepted by the majority.

We need to know that people might refer to their oesophagus as their ‘gullet’ and their endometrium as their ‘womb’. ‘Gut’ could mean anything from the mouth all the way down to the anus.

Various words have been tested for understanding and acceptability, and ‘poo’ is an NHS approved term.

Examining poo for blood has been done in various ways for decades as a screening test. There is now interest in what poo might tell us about causes of cancer. Specifically in improving responses to cancer treatment and even dealing with side effects. The main focus is on the microbiome.

Our bodies are host to trillions of microorganisms. These include bacteria, fungi, parasites and viruses.

Collectively they are referred to as microbiota or microbes. Where they collect in an organism is called a microbiome.

Microbiomes exist in different systems (niches) within our bodies, for example the skin or vagina. The largest microbiome is in the gut and it is where there is currently a lot of scientific attention.

Bacteria can make up to half the dry weight of poo. Microbiota are vital for health and:

• help digest food
• make certain vitamins and proteins
• have an important role in immunity.

There are 10 times the number of microbial cells in the human gut than in the whole human body. This equates to roughly 100 trillion microbes, weighing approximately 2kg.

Some of these organisms have a role in the development of certain cancers. The best understood is the h.plyori which is known to be a risk factor for stomach cancer.

There is data which demonstrates higher presence of some microbiota in other cancers. This includes colorectal, breast and ovary and suggests that the microbiome may have a role in cancer risk more generally.

An individual’s microbiome begins to form from birth and is influenced through life by diet and environment. Your height may even influence the content of your microbiome.

There are large projects in place to better understand the gut microbiome, including the US-based ‘Gut Project’. It is hoped that the project will have eventually have a UK roll out.

The microbiome fluctuates massively throughout the day, influenced by feeding. Measuring fluctuation is difficult. The best way to capture the microbiome only appears as poo once a day or less. However, scientists publishing this summer in Nature are developing dynamic models.

These projects require skills in metagenomics and bioinformatics. The projects will require experts who can crunch the massive amounts of biological data to be found in a single poo.

Immunotherapy has been revolutionary in the treatment of multiple cancers. We are still unsure why some immunotherapies have fantastic disease responses and why some have no response at all.

A clue may lie in the microbiome. Gut microbiota can modulate  immune cells including  CD8+ T cells and  T helper cells. Early studies in mice showed that the response to immunotherapy might differ according to microbiome. There are now human studies showing that some bacteria are more commonly found in the microbiome of people with melanoma who respond to immunotherapy than those who don’t. We don’t know if this is due effects on the immune cells or the other proteins or chemicals (metabolites) produced by the microbiota. 

Immunotherapies are treatments that use the immune system to find and attack cancer cells.
What has also not yet been proven is whether changing a microbiome can influence a positive response. If this proves true it may impact on the role of diet and use of antibiotics. Both of which can alter the microbiota (antibiotics quickly, diet more slowly). Trials are underway, including a study on the prescription of probiotic drinks.

It has been recognised for many years that responses to some cancer therapies vary according to the time of day. Older studies have suggested that radiotherapy may be more effective in the morning. There are theories based on cyclical changes in body hormones and T cells. 

More recently there has been interest in improved responses to immunotherapy according to time of day. One theory is that this could in part be due to shifts in the microbiome caused by feeding.

One way to alter a microbiome is to replace it by faecal microbiota transplantation (FMT). FMT involves taking the microbiota from one person. This is then placed in the gut of another person using pills or by a colonoscopy or gastroscopy. The technique has been used successfully to overcome severe bowel infection caused by the bug clostridium dificile. It is being tested for inflammatory bowel conditions like ulcerative colitis and Chron's disease.

A difficult problem caused by immunotherapy is an inflammation of the bowel (colitis). This is usually managed by using steroids to counter the inflammation.

In rare cases the colitis does not settle. FMT was trialled with immunotherapy related colitis that had not settled with standard treatment. A study published in June this year showed benefits in 10 out of 12 people treated with this intriguing technique.

There are currently a large number of companies selling commercial ‘at home’ testing kits for the microbiome. It reminds me of the expression “where there’s muck there’s brass”. My children used to be delighted by a book about animal poo called The Story of the Little Mole Who Knew it Was None of His Business.

It now seems that poo is now potentially big business and certainly a very fertile area for future research.

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