Colon Cancer and Beneficial Bacteria
Gut bacteria and colorectal cancer |
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Colon cancer, Rectal cancer and Colorectal cancer are now understood to be definitely linked to microbial problems in the gut.
The new EU-funded SYNCAN project is expected to confirm that taking beneficial bacteria and certain probiotics can lower DNA damage and reduce rates of colorectal cancer.
Previous research studies have shown that the disease is linked with less numbers and diversity in the gut microbiome, and with the increased presence of more harmful strains. The Journal of the National Cancer Institute , December 2013, reports that higher levels of Fusobacteriumwere found (which can lead to cancer) and lower levels ofclostridia, a bacterial class known to aid glucose metabolism in people with colorectal cancer (Click here for SYNCAN research study).
Under normal conditions a healthy flora contains a fully diverse range of bacteria. Due to age, drugs, antibiotics and/or infection the gut microbiome loses both volume and diversity. To put this in context - a healthy young person probably has about 90 trillion bacteria in his/her gut exhibiting some 800 types. If that person takes antibiotics, the strains of bacteria are not all killed equally. The helpful or commensal bacteria tend to be more fragile; the pathogens more hardy. This is why one hears reports of people having 8 weeks of antibiotics in an attempt to kill off ´a problem I picked up on holiday´.
Go to: How to Heal your gut
The initial infection becomes a triple problem. The wholesale destruction of the good bacteria, which normally ...
1. Keep bad bacteria in check, and
2. Eat yeasts at night, and also
3. Constantly heal the gut lining.
needs addressing urgently.
Furthermore, without the control of good bacteria, bad bacteria produce toxins, some of which are inflammatory, and some can even produce an immune reaction.
A surge in research
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.
For more on this subject read the brilliant new book by Chris Woollams ´The Secret Source of Your Good Health´. Click here to read about it.
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 come from your friendly bacteria - and their genes make a good number of compounds you simply cannot make for yourself. Over thousands of years we have grown interdependently with the bacteria that live in and around us. We give them food and shelter; they provide us with compounds we cannot make for ourselves. But when they start to suffer, we become ill. Worse, it seems we cannot become well until they do.
Research with mice showed that giving them bacteria from a microbiome of a colorectal cancer patient prompted colorectal cancer of a vigorous nature. Other studies have shown that colorectal cancer is associated with a loss of diversity amongst the gut bacteria, not just volume.
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.
So have can you get your gut straight again?
In the short term, taking Lactic Acid Bacteria (LAB) can have some extremely beneficial results. Such bacteria (for example, strains of acidophilus such as Lactobacillus acidophilus) can change the acidity of the gut stopping ´bad´ bacteria thriving - producing toxins, causing inflammation, even causing an immune response. Bifidobacterium lactis also has an inhibiting effect on pathogens in the gut. Both types of bacteria can also bind to dangerous bile acids, repair the gut wall and reduce DNA damage. Some LABs can produce anti-inflammatory compounds. One, sodium butyrate, has even been shown to kill colorectal cancer cells.
But in the longer-term, however, diversity is crucial. Multi-strain probiotics do exist, each with 7 or 8 different strains. Some in America can have 25 different strains. But be wary of the volume claims - 40 billion per pill is ridiculous. You only need a few billion - it´s what you eat that matters. Feed them the right foods and they will thrive and become trillions. By feeding them the foods they love (whole foods, fibrous foods like pectins and inulin) their levels will soon multiply. In fact research showed it was pointless taking probiotics if you didn´t also eat the apples and carrots for pectins, and endive and onions for inulin.
The road to full diversity is linked to the foods you eat - raw unpasteurised milk contains over 150 strains of bacteria and immune boosting compounds; or sauerkraut - indeed any fermented vegetables, miso soup, kefir, kombucha and tempeh.
Research is quite clear on beneficial bacteria (or ´commensal´ or Probiotics) in the gut: They enhance your immune system, are essential in releasing vitamins and important health compounds from your food, they help to excrete toxic chemicals from the body, and even produce a cancer-killing chemical.
They can also consume over 2.2 kilograms of yeasts and microbes every night while you sleep - external ´forces´ you really must keep under control! Over 4000 research studies exist providing clues as to how they not only prevent cancer, but can help you beat it if you already have it.
So that´s the up to date knowledge. Interestingly, research covered in Cancer Watch last year showed three areas of the colon, each protected by different coloured foods. It pays to eat a Rainbow diet!
The bottom line - the symptoms of colorectal cancer are most usually the symptoms of a damaged microbiome.
Fighting the microbes and yeasts in your gut
In icon Issue 3 2006 we first covered the general benefits of probiotics and, in researching the article, we can genuinely say how surprised we were: The amount of top quality research including well-planned and executed clinical trials that indicates beneficial bacteria are crucial to very many aspects of our health - was simply amazing. We were not aware of the serious benefits these bacteria bring to our health, and we doubt whether most of our readers - including not just patients but Doctors, nurses and oncologists - have much idea either. This article is, however, specifically about ........
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 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. Even more depressing is the fact that mortality from this cancer is rising (Boyle & Langman 2000). One estimate puts the lifetime risk for Europeans of developing this disease at 2% (Cappocaccia et al 2002). In the EU, 6% of men and women may be affected by the age of 75. 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 affect the 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.
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 herefor 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 Caprylic acid toOregano oil and Pau D´Arco along 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.
This article was written in 2006: Diet and CRC
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
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 manyLactobacillus 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:
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
 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
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 andBifidobacterium 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:
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:
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:
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
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