The role of gut bacteria in colorectal cancer

The role of gut bacteria in colorectal cancer

A large and increasing volume of convincing evidence links the loss of specific, friendly gut bacteria and the increased presence of known pathogens to heightened Colorectal Cancer, or CRC, risk; in this overview - written by Dr. Linda Thomas, (PhD, FIFST, FRSB), Science Director at Yakult UK with updates by Chris Woollams (M.Biochem Oxon) - we explain the findings and ways you can help protect yourself where possible.

Specific bacteria implicated in Colorectal Cancer

Two important reports came from the EU funded SYNCAN study, which began in 2005 to study the role of foods in Colorectal Cancer or bowel cancer. One area of SYNCAN research evolved into the role of prebiotic foods, and from there into the bacteria those foods promoted. 

In the first study, researchers identified that people with CRC had a completely different gut flora to healthy people, with less diversity of bacteria in their gut, and some important strains missing, but those bacteria that are present include higher numbers of harmful strains.

In The Journal of the National Cancer Institute, December 2013, the researchers reported that people with colorectal cancer had higher levels of Fusobacterium nucleatum (chemicals from which are known to stimulate two receptors that lead to cancer), along with lower levels of a particular strain of Clostridium (a particular strain known to aid glucose metabolism and removal in the gut).

Go to:  SYNCAN research study

This was confirmed in studies with Bowel Cancer patients by Professor Wendy Garrett and Professor Mathew Meyerson of TH Chan School of Public Health, Harvard. This group believe the F. nucleatum can stick to emerging CRC cells hiding them from immune attack.

Both studies followed a multi-centre study in 2012 led by researchers at North Carolina University, showing that E coli levels could increase inflammation in the gut, and were themselves increased by gut inflammation - it was a two-way process.

In 2017 research from the Dept. of Surgery, University of Otago, New Zealand(1) had identified clear subtypes of CRC, and linked these to different pathogenic bacteria and their mRNA.

   * Some subtypes had more Fusobacterium and Bacteroidetes, and decreased levels of Firmicutes and Proteobacteria;

   * Some more Fusobacterium hwasookii and Porphyromonas gingivalis (common in gum disease)

   * Some more Selenomas and Prevotella species, and so on.

Each species and pathogen strain sends out mRNA and the belief is that this is what lies behind CRC.

In 2018, research from Bloomberg-Kimmel in Baltimore, Maryland concluded there were two ever-present bacteria in CRC in their mice samples: E coli and Bacteroides fragilis, which together cause DNA damage. 

In fact, rather that CRC being a single disease, researchers in Otago stated that it was increasingly clear (2) that CRC is actually a number of heterogeneous diseases. And different pathogenic bacteria maybe behind each! It would seem that almost always Fusobacterium is the 'gang leader', but its lieutenants can be various from E.coli to gingivalis.

In 2018 research by Dr. Blekhman at the University of Minnesota, microRNA produced by pathogens was shown able to control the microRNA of your healthy gut lining cells. It's not just the chemicals, the proteins and enzymes the gut pathogens make, it's their microRNA that can trump your own RNA.

Go to: Messages from pathogens crucial in colorectal cancer

A 2019 study from Osaka Genomics Center has shown that Colorectal cancer builds in stages. It seems in adnocarcinoma, Fusobacterium nucleatum is present throughout, while in intramucosal cancers, Atoobiumparvulum and Actinoyces odontolyticus co-existed.

Otago have also shown that the pathogens 'cluster' - further along the gut they may not be present and the gut can be healthy. The implications for CRC surgery are enormous. How could a surgeon remove a tumour and then state that you are 'All clear'?

In summary, 'Microbiome Otago', as the centre is now called, has stated that 'the intestinal microbiota play a key role in inflammatory and malignant gastrointestinal diseases.'

Diet and probiotics in Colorectal cancer

The team at TH Chan, Harvard are now looking at human CRC patients. It is known that certain gut bacteria can help chemotherapy treatments while others can block them. They are looking at whether rebuilding a healthy gut can promote better chemotherapy outcomes.

Certainly, the gut bacteria in your microbiome can be highly protective. Professor Emma Allen-Vercoe from the University of Guelph in Canada has spent her life's work studying them. She is linking up with Profs Garrett and Meyerson to try to discover which ones best protect you and how to increase their numbers.

The second SYNCAN reported results that showed people consuming a mix of probiotic bacteria and the correct prebiotic foods that feed them, have less DNA damage, lower rates of cell proliferation and lowered risk of colorectal cancer.

So does taking a probiotic help?

In the short-term, we know that taking a quality probiotic can produce rapid results - in breast cancer there are often low levels of Lactobacillus acidophilus in the breast. A probiotic supplement can rectify this in 24 hours according to research. So can the right diet. Lactobacillus strains change gut acidity for the better. L. rhamnosus helps heal the gut wall. Bifidobacterium infantis helps correct IBS in research. We've covered all this and more before on this Website and Linda Thomas produces more evidence below.. 

Do you need help sorting out gut problems or even a plan to fight Colorectal cancer? Read what people have to say about a one to one chat with Chris Woollams.

But probiotic supplements have just a few strains compared to the 800 or more species (families) in the gut, and 20+ strains of each. The 'Contains Billions' is only valid to a point. If you take 20 billion, you need to convert them to 3-5 trillion in the next few days to get the job done. This means eating the right foods - prebiotic foods - mainly soluble fibre foods.  

Ultimately, you should be eating probiotic foods - raw apple cider vinegar, sauerkraut, unpasteurised cheese, Kefir, Kombucha, Tempeh. Although, be clear, it is now known that taking an antibiotic can render certain strains extinct. You are unlikely to be able to re-colonise them.

Fish oils, extra virgin olive oil and vitamin D all help reduce inflammation in the gut.

Go to: The best foods for gut health

Remember the golden rules of probiotics - Buy a reputable brand; never keep it in the 'fridge; never take with hot foods or hot drink; never use a probiotic that contains glutamine or glutamate if you have cancer; always take the probiotic with soluble fibre foods.

Go to: Practitioner strength probiotic designed specifically by Chris Woollams to help 'heal your gut’ 

 

The finding on Clostridium and sugar metabolism is very interesting because previously Johns Hopkins Cancer Center in Seattle had done several studies with colorectal cancer, showing that people on metformin had better outcomes and even people on restricted sugar diets. A study "Colorectal Cancer may yield to sugar starvation' looking at colon cancer tumours showed that they even had a sugar pump!

Other studies have shown similar results for both the diabetes drug Metformin and the herb Berberine in CRC. Both lower blood sugar levels, and Berberine limits invasion and metastasis of CRC cells.

What is actually unclear is whether the sugar is feeding the pathogens, yeasts or cancer cells; maybe all of them!

All illness starts in the gut - especially Colorectal Cancer!

By 2012, a large scale American study, the Human Microbiome Project, had told us a number of important things in connection with colorectal cancer. For example, your gut gets ill first then you get ill. And then you cannot get better until your microbiome gets better. This may have seemed a revelation to the researchers, but a chap called Hippocrates said much the same thing 2500 years or so ago, when he said ’All illness begins in the gut’. No cancer could be more linked to the effects of the bacteria within it than colorectal or bowel cancer, surely?

Research also showed that gut bacteria MADE (note - made, not released, from your food) your B vitamins and vitamin K. They MADE short-chain esters which controlled bad cholesterol in your blood stream, they MADE anti-inflammatory molecules, and one in particular - sodium butyrate - can protect healthy cells yet kill colorectal cancer cells!

But now we also know that the higher your levels of LDL and triglyceride fats the more metastases and lowered survival in cancer patients. We know that colorectal cancer is linked to localized inflammation in the gut, and that this can make polyps worse, or denature bile acids, and turn on Cox-2, a driver of colorectal cancer.

What damages your gut microbiome in Colorectal Cancer? 

How does your gut get damaged? Research had confirmed that there were three general ways your microbiome could be damaged:

      i) By drugs - particularly, Proton Pump inhibitors and antibiotics

      ii) Self-inflicted: You don’t eat enough of your commensal bacteria’s favourite food - soluble fibre (like whole oats, pulses, vegetables, nut and seeds). But you do eat too much of the food the yeasts and microbes love (like sugar). You can also change the pH of the gut - with too much salt, binge drinking, smoking, or stress.

      iii) You get food poisoning. And you pick up a parasite on your holidays or eating out. Maryland Medical School have shown that even though you got over the food poisoning, the parasite and/or its effects can stay with you for 20 years or more. A second study showed that the food poisoning 'knocked out' friendly bacteria that kept E coli in check, with the result that years later you were more likely to get Crohn's or Colorectal Cancer. 

Let's look at the research on this:

A number of studies have confirmed the above causes of gut ’damage’. 

     i) Parasites, food poisoning and the gut

For example, Brian Coombes and his team at McMaster University presented research in October 2016, showing that people who had suffered from food poisoning once in their lives (Salmonella, Listeria, or something you picked up on an exotic holiday), still showed adherent-invasive E. coli (AIEC) growth even after the original causal bacteria was cleared from the body. This could be because the original pathogen damaged a commensal bacterium, which also keeps E.coli incheck, or the drugs taken did. Either way, E. coli could slowly take hold over the next 10 to 20 years.

As a result,there was then a much higher risk of Crohn’s disease (abdominal pain,diarrhoea, cramps) and, subsequently, a greater risk of colorectal cancer plusa reduced life expectancy.

     ii) Antibiotics and gut bacteria damage

For example, a number of studies have provided links between antibiotic taking and an increased risk of gut damage and even colorectal cancer. In 2017 Colby Zaph, head of Biomedical studies at Monash in Australia showed the dangers of giving antibiotics to young children and how this resulted in more inflammation, gut damage and IBS, Crohn’s and worse later in life.

Dr. Ben Boursi of the Tel Aviv Integrated Cancer Prevention Centre showed that the more antibiotics you take, the greater your risk of colorectal cancer. This was confirmed by Dr. Andrew Chan of Harvard Medical School, who showed that taking antibiotics for more than 15 days in one treatment raised the risk of pre-cancerous polyps by 36 per cent in 20-39 year-old women, and overall colorectal cancer risk by 69 per cent in women aged 40-59, and by 73 per cent in all women.

Antibiotics have now been shown to have a devastating short-term and long-term effect. A meta-review of these effects, talked of the emergence of pathogens, a fall of good bacteria by 30%, and the inability of certain strains to ever recover. Most damaging is when infants are given antibiotics in the first months of their lives. The effects can be life-long.

Go to: Colorectal or Bowel cancer - symptoms, causes and alternative treatments; overview

Research on gut bacteria and Colorectal cancer gathers momentum

Maybe, just maybe, oncologists are treating the wrong body. Perhaps they should be treating the gut microbiome, not the human host and the cancer?

Go to: Article - How to Heal your gut

Other factors are at work. When you damage levels of your good bacteria, the pathogens they normally control then come out to play. But so do yeasts. You take in yeasts with every mouthful of food and drink. At night time, your commensal bacteria eat 2.2 pounds of them; but if they are not there?

Yeast excess in the gut can cause leaky gut syndrome, and gluten consumption can make the holes bigger leading to yeasts in the blood stream. Yeasts are known to sit on cells preventing messages going in or out; they also colonies area and, being anaerobes, they reduce the oxygen. This leads to all manner of problems.

The commensal bacteria normally

   1. Keep bad bacteria in check, and 

   2. Eat up to 2.2 lbs of yeasts at night, and also 

   3. Constantly heal the gut lining.

That all stops if you have been on antibiotics!

Furthermore, without the control of good bacteria, bad bacteria and yeasts produce toxins, some of which are inflammatory, and some can even produce an immune reaction. And they produce messages from their own DNA. And the messages are known to alter yours.

The Human Microbiome Project

Since the $173 million American Gut Project was completed there have been a large number of quality research studies looking into gut bacteria with many illnesses. Shortfalls of good bacteria has shown up in breast cancer, prostate cancer, pancreatic cancer and liver cancer. Pathogens (even pathogens from the mouth) have been linked to cancer. Women with breast cancer have high levels of E Coli and so on. 

Text book thinking is that the human body is an organism of 7 trillion cells and 25,000 genes. The very latest thinking is that in fact we are, in fact, ’Super-organisms’ of 100 trillion cells and 100,000 genes. The ’extra’ cells and DNA come from your gut bacteria - and their genes make messages, proteins, enzymes and more. So much so that at any time 38 per cent of the small molecules in your blood stream come from them, not you. They control your physical biochemistry, and your mental biochemistry.

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We know, gut bacteria produce messenger RNA. Could this actually cause colorectal cancer? Worryingly, it seems the answer is ’Yes’. Research with mice showed that giving them bacteria from a microbiome of a colorectal cancer patient prompted colorectal cancer of a vigorous nature. 

20 per cent of people are believed to carry a parasite infection, up to 75% if you include excessive yeast colonies (have you had thrush, yellow toe nails, cystitis, flatulence?). A bad stomach on holiday, an infection, eating raw fish (sushi). Many doctors resort to weeks of antibiotics. But American and Australian research on faecal enemas used to cure gut problems showed that drugs actually make matters worse.

If you want to read more on fecal enemas or fecal transplants, go here.

                             
                                                                        * * * * * * * * * * * * *

The original article from over a decade ago ...

Colorectal cancer (CRC)

In the UK, colorectal cancer (CRC or bowel cancer) is the third most common cancer for men and the second most common cancer for women. Globally, the picture is similar. Although there were some claims in a CRUK report that a better diet is producing a reduction in this cancer in the UK, we can find little evidence of that in the figures. In fact, the truth is that Colorectal Cancer is increasing and it is becoming ever younger. A modern diet, (along with modern lifestyle factors such as smoking, obesity, stress, inactivity and even increasing diabetes levels), is probably making this cancer a great deal more prevalent. But then so is the widespread use of antibiotics, Proton Pump Inhibitors an food-poisoning through foreign travel. Even more depressing is the fact that mortality from this cancer is rising (Boyle & Langman 2000).  Western Europeans may be particularly susceptible due to the combination of inherited risk and a diet often high in fat and low in fibre (de Ferlay et al 2001; Gill & Rowland 2002).

Treatments are now expanding; not necessarily all ’orthodox’. Vitamin D is known to reduce inflammation and an aggressive bile acid, curcumin is used by some American Cancer hospitals, and an old drug cimetidine (an anti-histamine) has been shown to double survival rates if taken prior to, during and shortly after surgery.

Read more in our Colorectal Cancer overview - here.

Diet and colorectal cancer

There is probably no cancer more logically attributable to diet; and problems with the gut bacteria. Research (carried in icon Cancer Watch) from Japan indicated that a doubling of salt consumption doubled risk; other research we have carried indicates red meat consumption and animal fat consumption go hand in hand with risk, as does alcohol intake. But then salt, alcohol, stress and other factors will change the pH (acidity) of your gut. Thus upsetting the environment of the helpful bacteria, allowing the pathogens more freedom.

The prime group of sufferers is concentrated in the 60+ age group but then 85 per cent of all cancers are. However, a growing number of pregnant women seem to be succumbing and research amongst sufferers has indicated a higher prior incidence of irregular bowel movements and that prior (often chronic) bowel inflammation, Crohn’s disease, severe ulcerative colitis and IBS may be precursors.

Some foods are known to reduce risk.  A diet high in natural fibre is shown as a benefit in research, as is a good level of garlic intake (Boston Nurses Study). And here the clues become interesting via two routes.

Firstly, since John Vane won his Nobel Prize in 1982 for the finding that aspirin could reduce the level of harmful eicosanoids, (localised hormones produced at the cellular level and lasting barely one and a half seconds), a great number of studies have shown that garlic, ginger, curcumin and long-chain omega 3 (fish oils) also have this effect,  not merely salicylin. All seem to reduce bad eicosanoids and reduce the effect of a negative enzyme, named Cox-2 in making the inflammatory eicosanoids. For example, you may have heard of prostaglandins, which can cause arthritis. In the gut, ’bad’ eicosanoids can cause inflammation directly or via a carcinogenic bile acid. And inflammation, especially via the formation of polyps, is a precursor to CRC. (Aloe Vera would also be a good source of natural anti-inflammatories and is known to be very calming). New research in the SYNCAN project indicates that certain beneficial bacteria can bind to these bile fats and prevent DNA damage and inflammation.

Also, Lactic Acid Bacteria like acidophilus, and bifidobacteria can change the pH of the gut, making it more acid and preventing damaging bacteria having their evil way. Both seem able to minimise DNA damage and inflammation. One route is by producing short-chain esters which prevent inflammation, and one (sodium butyrate) even corrects DNA damage and ’kills’ cancer cells.

Also, omega-3 from fish oils and vitamin D have both been shown to directly reduce the production of the carcinogenic bile acid (produced most frequently by the excesses of animal fats and alcohol). Clinical Trials from Leeds University showed a reduction in polyps and recurrent CRC. The vitamin D factor may explain why there is some research indicating that dairy, milk and calcium products can reduce risk. Vitamin D and calcium have a strong biochemical inter-relationship in the body. It is more likely that the calcium is having an effect through altering levels of vitamin D. (You can get your vitamin D  through sunshine, fish oils or supplementation - see icon issue 2 2006 for a complete review on this essential cancer-fighting vitamin)

Secondly, as we have reported before, one theory of CRC is the negative presence of yeasts. In icon Cancer Watch we have covered recent US research about microbes as the cause of CRC. Microbes, yeasts, viruses are all parasites and can produce toxins whilst draining you of key nourishment.

We have covered Gerald Green’s theories and anti-yeast diets before (Click here for full details). Garlic can act as a natural killer to a number of yeasts and harmful microbes and Gerald suggests garlic along with a number of other natural foodstuffs from Artemisinin, Caprylic acid, Oregano oil and Pau D’Arco along with the use of Probiotics.

Which takes us full circle.  And so here, in Part II of our in-depth look into the serious use of Probiotics, we asked Linda Thomas, PhD FIFST (Science Manager at Yakult UK Ltd.) to tell us about this vital element that seems so often to be overlooked in the prevention of cancer and especially Colorectal Cancer.

Risks for Colorectal cancer

Everything we eat passes through our digestive systems, so it is no surprise that diet can affect our risk of developing any type of gut cancer.  However, this is very hard to prove. There is no one cause for cancer, and it is particularly difficult to prove any relationship between diet (consisting of many foods) and cancer. In 1992, a large, long term European prospective study (EPIC: the European Prospective Investigation of Cancer) was set up, involving 10 countries and 521,486 people who will each be followed for at least 10 years.  So far, this has reported that a diet high in fibre reduces CRC risk, whereas a diet high in red or processed meat increases CRC risk. The EPIC study has also concluded that a high intake of fish may reduce risk, but this trend was less clear and seemed to vary between countries. A further finding was that a diet high in milk and cheese and high levels of calcium in the diet may reduce risk? but it was also shown that a diet high in fat was a general cancer risk. Similar conclusions have been drawn from epidemiological data (see below Gonzalez 2006)

Controllable factors for Bowel Cancer

Associated with increased risk                                  Level of evidence

Obesity                                                                                       Sufficient

Red and processed meat                                                           Sufficient/probable

Alcohol                                                                                        Sufficient/probable

Animal fat                                                                                    Possible

Food with high glycaemic load                                                    Possible

 

Controllable factors associated with decreased risk

Total vegetables                                                                        Probable

Dairy products                                                                          Probable

Total fruit                                                                                  Possible

 

Dr Tony Leeds, a principal investigator and senior lecturer in nutritional sciences at Kings College London, comments: Most of the changes needed to reduce colorectal cancer risk are changes that reduce risks of other major degenerative problems such as cardiovascular disease.  The risk reduction approach includes controlling overweight and obesity, moderating alcohol and red meat intake, and increasing intake of fruit and vegetable consumption.  There is evidence too for regularisation of bowel function by increasing intake of cereal foods and physical activity.  Most healthy diet and lifestyle advice given by health professionals now includes these recommendations.

What are probiotics again?

Probiotics and prebiotics were recently reviewed in icon. Before we look at their particular relevance to CRC, perhaps we should refresh our memories.

The general concept of probiotics is a very old one. In Genesis 18:8 we are told: Abraham owed his longevity to the consumption of sour milk. In 1907, Eli Metchnikoff (the Russian Nobel prize winner) attributed the healthy longevity of Bulgarian peasants to their consumption of naturally fermented yogurts containing many Lactobacillus species. Yogurts we eat today are not necessarily probiotic unless labelled as such, since they are normally made with just two species of bacteria (Lactobacillus bulgaricus and Streptococcus thermophilus) and the particular strains may not survive the digestive process. In 1996, the first probiotic food appeared in the UK: a fermented milk drink (Yakult). This was developed over 70 years ago in Japan. Now an almost bewildering array of probiotic products is available drinks, yogurts, capsules, powders, etc. Many published research papers have increased the body of evidence supporting the health benefits associated with certain probiotic strains. 

So, what exactly is a probiotic?

Probiotics are live microbial food ingredients that, when administered in adequate amounts, confer a health benefit on a host (WHO/FAO 2002).

Most probiotics are species of lactobacilli and bifidobacteria, but importantly probiotics must:


  • Grow and be active in the lower intestines (even for just a few days). To do this they must survive and pass through the stomach (the acidity of which kills most bacteria)

  • Have a proven health effect (i.e. one that has been shown in clinical trials)

  • Improve the balance of bacteria in the gut, so that the activities of beneficial bacteria outweigh those that may be harmful

  • Be properly identified and named strains (i.e. not just a species, which consists of many strains). These strains must be safe to eat, and the probiotics must stay alive and remain stable before being eaten or drunk.

Prebiotics are food ingredients that stimulate the growth of beneficial bacteria, including probiotics. Prebiotics are not digested in the stomach or upper intestines, so they reach the large intestine (or colon) to feed the beneficial bacteria there. Harmful bacteria that may also be in the colon cannot use prebiotics as an energy source, so a diet high in prebiotics will favour the growth of beneficial bacteria in the colon. Prebiotics are available naturally in certain foods: the Allium group of plants (onions, garlic, shallots, leeks), asparagus, chicory, and Jerusalem artichokes, and to a lesser extent in beans and pulses and some cereals such as oats. Inulin is a pure form of the sugar fructose, that is the basis of many prebiotic carbohydrates, and is often used as a prebiotic supplement in certain food products.

To confuse things further, the combination of both is called a synbiotic.

Why should probiotics/prebiotics influence cancer risk? 

It has been thought for some time that the gut microflora could be involved in causing CRC. Certain bacterial species in the colon produce harmful substances that are almost certainly linked to cancer.  Beneficial bacteria may prevent the growth of these organisms, and some beneficial species even produce anti-carcinogenic substances. Since probiotics modify the balance of gut bacteria in favour of beneficial bacteria, it seems more than a possibility that probiotics might help reduce CRC risk.  Experts think this is probably due to a combination of several different mechanisms (as shown in the table).

What are the probiotic effects that may reduce cancer risk?

Preventing damage to the chromosomes of the gut cells


  1. Preventing harmful enzyme activity in the gut

  2. Controlling the growth of potentially harmful bacteria

  3. Beneficial interactions with the cells of the colon

  4. Stimulation of the immune system

  5. Producing products that have a beneficial effect on the cells of the colon (e.g. short chain fatty acids)

Probiotic bacteria grow and are active in the colon, and so compete with harmful bacteria for food and space and help suppress them. Some probiotics also produce antibacterial agents. Species of Lactobacillus and Bifidobacterium produce lactic acid and similar short chain fatty acids; this makes the gut lumen more acidic and unfavourable to the growth of harmful bacteria. Dietary fibre, including prebiotics, supports the growth of lactobacilli and bifidobacteria. This will increase levels of butyric acid in the gut - a compound important for the growth and regulation (including programmed death) of colon cells.

Epidemiological studies show a link between CRC risk and high fat diets and this is thought to be due to raised levels of bile acids (which help digest the fat) in the colon. These salts are released into the small intestine, and also re-absorbed there, but some may pass into the colon. The breakdown products of bile may have a cytotoxic effect on the cells lining the colon, increasing cell proliferation and possibly cancer. Probiotic modulation of the intestinal microflora may affect the activity of one of the enzymes (7a-dehydroxylase) forming these toxic products, but probiotics may also reduce the toxicity of bile salts by binding to them.

To summarise, at the molecular level, probiotics may help by:

  • suppressing the activities of enzymes associated with carcinogen formation (e.g. glucuronidase, nitroreductase)

  • binding to mutagens

  • stimulating the activity of beneficial enzymes that inactivate carcinogens (e.g. glutathione S transferase).

  • forming conjugated linoleic acid, a compound with anti-inflammatory properties that may inhibit development of cancer.

  • Increasing levels of butyric acid in the colon: an important energy source and growth regulator for colon cells.

Probiotics can also help support and stimulate the immune system indirectly and directly. This may partly explain the results of a study in Japan, which reported anti-cancer effects outside the colon. The particular probiotic helped prevent the recurrence of bladder tumours, a protective effect that was thought to be due to the combination of the probiotic reducing levels of toxic substances excreted via the bladder but also by stimulation of the immune system, in particular the activity of natural killer (NK) cells (innate immune cells that are thought to be involved in cancer protection) (Aso et al 1995).

How do scientists show probiotic involvement in helping to reduce cancer risk?

Professor Ian Rowland, (Professor of Human Nutrition at the University of Ulster), is one of the worlds leading experts on diet and cancer prevention, with a particular interest in probiotics.  This is what he has to say:

Studies using cultures of human colon cells grown in flasks show that probiotics can interfere with the action of cancer forming substances. When probiotics have been given to laboratory rats, they have decreased the level of gene damage (an important event in cancer) and reduced the numbers of tumours induced in the colon. There are only a few studies in humans because of the difficulties in studying the effects of diet on human cancer. However, in the few studies that have been done, probiotics - sometimes in combination with prebiotics - have shown effects suggesting that they may reduce the risk of colon cancer.

Real proof of probiotic benefit must come from double-blind, placebo-controlled, human volunteer studies. These are trials in which one set of people consumes the probiotic and another set of patients consumes a placebo: a product looking and tasting exactly the same as the probiotic but with no activity because it has no bacteria. None of the volunteers know which they are taking. Even better, neither do the doctors and nurses involved in the trial. Someone else de-codes the results after the trial has finished. This is all to ensure the trial is completely objective and the results can be trusted. This can be done relatively easily in probiotic trials.

The main problem with all cancer trials is that they involve high numbers of patients over many years.  Another problem is there is no generally accepted scientific way of measuring the risk of developing cancer or the progression of carcinogenesis. Biomarkers are used instead, but these may not necessarily be a true indication of cancer risk or progression. The following biomarkers have been used:


  • those relating to the health, correct growth and division of the cells lining the colon

  • those that measure levels of carcinogenic or other harmful substances in the faeces (a marker for colon levels)

  • those that are markers of the immune system, the bulk of which is located in the gut.

To give one example the work of Belgian scientists who used biomarkers to measure levels of two toxic metabolites (p-cresol and ammonia) in the faeces of healthy volunteers. These are compounds formed by microbial fermentation of protein in the colon. The results showed that consuming either a probiotic (species of Lactobacillus and Bifidobacterium) or a prebiotic (oligofructose-enriched inulin), resulted in reduced levels of these compounds (de Preter et al 2006). 

What evidence is there?

CRC progresses along a well-defined adenoma-carcinoma sequence, with histological changes associated with alterations in various genes. Different strains may act at different stages before or during cancer development and the extent of any protection may vary according to the probiotic (Commane et al 2005). There is, as yet, no concrete evidence for probiotics in prevention of cancer - but there are some encouraging results for specific probiotic strains particularly for Lactobacillus or Bifidobacterium.

Studies have shown probiotics may:

  • prevent DNA damage for cells in test tube studies and in animals

  • prevent early changes in the colon tissue

  • suppress tumours in animals

  • may have some protection in humans

More human trials need to be done but here are two examples of the few studies published: 

An unusually large study over 4 years followed 400 patients who had previously had colorectal tumours. Their diet was supplemented with either wheat bran, a Lactobacillus casei probiotic powder, both, or neither. The most positive results from the study were for the group taking the probiotic. Although the incidence of new tumours in this group was no less compared to the control group, the rate of development of the tumours was significantly slower (Ishikawa et al 2005).

Studies have looked at people eating a diet high in fried ground beef, which is known to increase levels of mutagenic amines. Lower mutagen levels in the urine and the faeces were found to be associated with consumption of Lactobacillus probiotic species (Hayatsu & Hayatsu 1993; Lidbeck et al 1992).

At the moment, a large EU-funded project (SYNCAN) is running. This is looking at the effects of probiotics (Lactobacillus and Bifidobacterium) and/or inulin-based prebiotics in various experimental models as well as human volunteers. In a trial conducted at the University of Ulster, 80 volunteers were recruited. Half had been treated for CRC and half had been diagnosed with intestinal polyps: intestinal growths that can become cancerous if left untreated (http://www.synca.be/; van Loo et al 2006). During the study, biopsies were taken before and after a course of a drink containing probiotic bacteria and a prebiotic. The effects of this synbiotic intervention were determined by comparing the extent of cell damage and cell proliferation (how rapidly the cells grow). The results showed no difference for the group of patients who had previously been treated for cancer but there was evidence of some benefit for patients with intestinal polyps.

Professor Rowland again:

There is a lot of evidence from studies on cell cultures and in animals that probiotics, prebiotics and combinations of the two can exert anticancer effects. Until recently, there has been little work conducted in humans. However a paper soon to be published reports a study conducted as part of the European Union funded SYNCAN Project. In this experiment volunteers were fed a mixture of pro and prebiotics, or placebo, for 8 weeks and a wide range of indicators of colon cancer risk were measured. Those subjects on the pro and prebiotics had less DNA damage and a lower rate of cell proliferation in biopsies taken from their colons. Additionally pro/prebiotic feeding resulted in improvements in certain characteristics of stool samples that may be indicative of reduced cancer risk.

Lower levels of chemical associated with cancer were found in the faeces. Professor Rowland concluded:

Whilst this evidence is not definitive, the study does suggest that the extensive data showing anticancer activity from experiments in animals and isolated cells may be applicable to humans, and that more studies in human volunteers are warranted.

Cancer killing chemicals

A final twist came in research covered in Cancer Watch in Autumn 2009, where researchers have shown that beneficial bacteria in the gut can actually cause the release of a cancer cell killing chemical from foodstuffs. That chemical is Sodium Butyrate. You could replicate it’s effects by taking ’Biotin’. But why bother. Beneficial bacteria will also help release biotin from the whole grains you eat.

You really should ensure that your beneficial bacteria are fully represented and part of your cancer prevention, and cancer fightinmg team.

If you are thinking of buying a probiotic, you might like to look at the Natural Selection Product of Choice. You can do this by  clicking here

REFERENCES


  1. Preventive effect of a Lactobacillus casei preparation on the recurrence of superficial bladder cancer in a double blind trial. Eur Urol 27: 104-109.

  2. Boyle, P & Langman, JS (2000) ABS of colorectal cancer epidemiology. British Medical Journal 321: 805-808.

  3. Cappocaccia, R et al (2002) Measuring cancer prevalence in Europe the EUROPREVAL project. Ann Oncol 13: 831-839

  4. Commane et al (2005) The potential mechanisms involved in the anti-carcinogenic action of probiotics. Mutation Res 1-2:276-289p

  5. De Preter, V et al (2006) Effects of Lactobacillus casei Shirota, Bifidobacterium breve, and oligofructose-enriched inulin on the colonic nitrogen-protein metabolism in healthy humans. Am J Physiol Gastrointest Liver Physiol. Sept 21 (Epublication)

  6. Ferlay, J et al (2001) Globocan 2000: Cancer incidence, mortality and prevalence worldwide. Versio 1.0 IARC Cancer Base No 5 Lyon, IARC Press

  7. Gill, CIR & Rowland, IR (2002) Diet and cancer: assessing the risk. British J Nutrition 88, S73-S87

  8. Gonzalez, CA (2006) Nutrition and cancer: the current epidemiological evidence. British J Nutrition 96, Suppl 1: S42-S45.

  9. Hayatsu, H & Hayatsu, T (1993) Suppressing effect of Lactobacillus casei administration on the urinary mutagenicity arising from ingestion of fried ground beef in urine. Cancer Lett 73: 173-179.

  10. Ishikawa, H et al (2005) Randomized trial of dietary fiber and Lactobacillus casei administration for prevention of colorectal tumours. Int J Cancer 116, 762-767.

  11. Lidbeck, A et al (1992) Effect of Lactobacillus acidophilus supplements on mutagen excretion in feces and urine in humans. Microb Ecol Health Dis 5: 59-67

  12. Van Loo, J et al (2006) The SYNCAN project: goals, set-up, first results and settings of the human intervention study. Br J Nutr 1: S91-S98.

WHO/FAO Joint Working Group (2002) Guidelines for the evaluation of probiotics in food.

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