The microbes that inhabit the human gut are an essential part of the digestive system. Their influence on health and disease extends beyond digestion and gut health to have effects on heart health, the immune system, and the brain. We are on the cusp of a research and knowledge explosion in this area of health sciences with some ground breaking research being published in 2013. We can only hope that the reductionist research will give us a better understanding of the effect of the whole diet on gut microbiome and not just a new supplement and a pharmaceutical industry offering quick fixes to lifestyle diseases.
Our microbiome, which includes bacteria, fungi and their viruses, has impressive stats – more cells than the entire human body, more genes than the human genome, and a combined weight of over a kilogram. We are part microbe, a symbiosis of human and non-human cells, part of an ecosystem rather than a stand-alone organism. Identifying all of the microbes in and on the human body is a massive task and just as we had The Human Genome Project, we now have The Human Microbiome Project which has been underway for 6 years.
Gut microbes did not just turn up one day and set up camp in the human gut. We evolved in tandem with our gut microbes, with natural selection favouring those individuals whose gut physiology supported the growth of microbes which were beneficial to health and survival. It has been suggested that the capacity of gut microbiome to change rapidly in response to diet, which we shall mention later, may be an evolutionary adaption that assisted us to survive on a variety of diets.
MICROBES ASSIST DIGESTION
Many animals are dependent on gut bacteria to break down plant molecules into useable pieces. Cows and other ruminants, for example, have a fermentation sac at the top end of the gut in which bacteria break down cellulose before it enters the intestine. While in humans and other primates most of the nutrients are absorbed in the small intestine before the residue is fermented in the colon (the large bowel and rectum) enabling us to extract additional nutrients that would otherwise be wasted. One group of gut microbes, Bacteroides, synthesizes enough vitamin K to meet our daily needs.
OTHER GUT MICROBE ROLES
Gut microbes have many roles other than breaking down hard to digest food components. A health-supporting set of gut microbes wards off disease causing microbes: they fill the available micro-habitats and discourage the growth of pathogens by producing antimicrobial substances and altering the pH and other chemical features of the environment. Gut bacteria are thought to have an important role in modulating the immune system and food allergies and asthma may be the result of this process failing early in life. It is likely that the gut microbiome alters the levels of the many local hormones that regulate gut function. It has even been proposed that the effect on these gut hormones may have a role in obesity. Even if this is so, it’s still the food that is causing the problem.
Gut microbes “eat” the left overs after food has been through the stomach and small intestine. This of course includes dietary fibre – polysaccharides which our digestive enzymes cannot break down as well as various indigestible sugars and oligosaccharides. However, the digestive system is not 100% efficient, and despite chewing, stomach acid, detergent-like bile, powerful digestive enzymes and a vast expanse of folded absorptive gut surface, the colon takes delivery of a considerable quantity of carbohydrates and proteins that have escaped the digestive enzymes in the small intestine by way of their physical form. One of these is resistant starch, now considered to one of the most health supporting components of dietary fibre (although it is not officially dietary fibre). Resistant starch encourages the growth of “good” gut microbes. It is one a group of food substances that have been called “pre-biotics”, food substances which encourage the growth of “good” microbes.
Nature does not design a colonic fermentation unit as a wildlife reserve for microbes – the farmed microbes must pay their way. And they do this by providing us with significant extra calories and nutrients from the food we eat, particularly from the high fibre and starchy foods to which we seem to be well adapted to eating. The gut bacteria need calories too, and they use some of the 4 cal/g contained in resistant starch, leaving us with 2-3 cal/g. The reduced calorie contribution of these carbohydrates is one of the reasons why people on plant based diet can eat more calories without gaining weight.
The butyrate which gut microbes produce from resistant starch could be considered an essential nutrient for the gut health and perhaps the whole body. Butyrate is the preferred energy substrate for the enterocyte cells which line the colon. Keeping the enterocytes healthy with butyrate may be one of the mechanisms by which plant based diets prevent bowel cancer and inflammatory bowel disease. The butyrate “deficiency” of low carb diets may be a major contributor to gut problem, both benign and serious. The butyrate (and propionate) are absorbed into the portal circulation, drip feeding the liver with a continuous energy supply or “tonic”. This is believed to be beneficial in regulating metabolic disorders such as insulin resistance and high cholesterol. More on Resistant starch
TOXIC SUBSTANCES PRODUCED BY MICROBES
The TMAO – gut microbiome story was one of the medical science breakthroughs of 2013. Carnitine, found in meat, and choline, found mainly in animal products (especially eggs), are metabolized by gut microbes to TMA (trimethylamine) which is then oxidized by liver enzymes and released into the blood stream as TMAO (trimethylamine-oxide). TMAO is toxic to the lining of arteries and promotes the progression of atherosclerosis. It has also been associated with prostate cancer. Perhaps the most intriguing part of the story is that the gut microbiome of vegans does not produce TMAO when presented with a single meal of meat.
Gut microbes may generate other toxic substances. Bile acid breaking down microbes may produce carcinogens. Other microbes break down sulphur containing amino acids, producing sulphur containing metabolites toxic to the gut lining as well as volatile compounds that contribute to bad breath and body odour. Animal proteins are characteristically high in sulphur containing amino acids.
Neu5Gc is a sialic acid that humans don’t produce, but when we obtain it from the flesh and meat of other animals it becomes incorporated into our body chemistry and promotes inflammation. Its relevance to gut microbes is that it enhances the absorption of the toxin produced by some pathogenic E.coli. Those travelling to developing countries might reduce their susceptibility to this type of travelers diarrhea by avoiding meat and dairy before and during travel.
NON-COLON GUT MICROBIOME
Although the focus of this discussion is on the microbiome of the colon, there are microbes throughout the gastrointestinal tract. There are microbes on and around the teeth including those that contribute to dental decay and periodontitis. The tongue has crypts which harbor bacteria and there is a video? below which suggests that they may have a role in promoting artery health. Even in the inhospitable acid bath of the stomach, Helicobacter pylori, a bacteria that causes peptic ulcers and stomach cancer, thrives. The small intestine too is not bacteria free, and some people suffer pain when bacteria here produce gas as they ferment the indigestible sugars known as FODMAPs. It is probable that the junction of the small intestine and the colon is not a one way valve and that there is some reflux of colon material into the small intestine. The vitamin B12 produced by these upper gut bacteria may explain why not all long term vegans become depleted of this vitamin.
DENTAL MICROBIOMES OF THE PAST
Unlike other body tissues, the dental calculus (calcified plaque) on the skeletal remains of ancient people preserves the DNA of their dental microbiome. The Australian Centre for Ancient DNA has developed techniques to probe oral microbiome of people who died thousands of year ago. These and other research finding suggest that the modern oral microbiome contains an unfavourable balance of bacteria, both in respect to dental decay and periodontal disease. While there some who blame the imbalance on a more carbohydrate rich diet, we think that this is based somewhat on the paleofantasy that our ancestors ate very little carbohydrate food until the agricultural revolution. Interestingly regional differences in the Neanderthal diets, including some who ate sugary dates, did not find a variance in dental decay. One explanation for this is that the decay causing bacteria, Streptococcus mutans may only have taken up residence in our mouths in the last 10 000 years. Following the industrial revolution there was a major shift in dental microbiome towards the streptococci and lactobacilli species which feed on sugar and produce decay causing acids. The microbes which cause periodontitis do so by promoting inflammation, which may worsen other whole body diseases such as diabetes and artery disease.
DIET AND MICROBIOME POPULATION
A landmark study on the effect of diet on gut microbiome was published in Nature Journal in 2013/2014 (David, L.A. et al. 2014). The authors found that feeding subjects either an all animal product or all plant based diet for only 3 days produced a dramatic shift in the predominant species in the gut microbiome of all subjects. This occurred regardless of the subjects’ individual microbiomes at the beginning of the experiment. The plant fuelled microbiome had more organisms that digest plant polysaccharides and resembled that of herbivores. This type of microbiome had high numbers of bacteria that are associated with good gut health. In contrast, the animal fuelled microbiome had bile-tolerant organisms and resembled that of carnivores. Bacteria that are associated with inflammation and disease thrived in this environment. This remarkable shift in balance from beneficial bacteria to disease promoting bacteria took only three days. The authors commented that the outgrowth of microorganisms capable of triggering inflammatory bowel disease in those fed the animal rich diet supported the link between dietary fat, bile acids and these diseases. The authors concluded with the interesting suggestion that the ability of gut microbiome to change rapidly may assist us to survive on a diverse range of diets.
This research led us to the following conclusions:
- Diet determines the type of gut microbiome so we should abandon the concept of fixing gut problems by simply putting “good” microbes into the gut without changing the diet.
- The gut microbiome changes so rapidly with the food we eat, that it is likely that a single day or even a single meal has some effect, so that we may need to eat mostly plants most of the time to maintain a healthy gut microbiome.
- The strength of the dietary effect and its reproducibility supports the idea that diet can be used to prevent or treat diseases in which we suspect that microbiome plays a major role.
The gut microbiome patterns associated with dietary habits are maintained over time. Rural people, eating more minimally processed plant foods have more Treponema and Prevotella bacteria which may protect against inflammatory diseases of the colon. The correlation between gut microbiome pattern and diet is reliable enough to determine the predominant diet of ancient peoples from their faeces. One such specimen from a cave in Mexico revealed that the person who left it there 1400 years ago most likely had a diet rich in maize.
Antibiotics destroy friendly gut bacteria as well as pathogens. This collateral damage can result in serious gut infection with antibiotic resistant ‘bad’ bacteria such as clostridium difficile. It was previously assumed that a normal healthy gut microbiome would rebound following the cessation of antibiotics. However, there is now some evidence that gut microbiome may be permanently damaged by repeated courses of antibiotics, particularly in children (Blaser 2011). Typically a child in the developed world will receive 10-20 courses of antibiotics before they turn 18 yr. The more courses of antibiotics a child receives, the more likely he or she is to develop inflammatory bowel disease. This correlation may also extend to type 1 diabetes, allergies and asthma.
- Probiotics have been around for years, first as yoghurt and other fermented products containing live bacteria and now also as capsules. Despite all the industry hype, the evidence for the benefits of these is sketchy. Most are based on varieties of lactobacillus which are not the dominant “good” bacteria in the adult gut.
- Ecobiotics is a term used to describe a more purposefully designed blend of gut microbe supplement. They are designed to bypass the acid environment of the stomach and deliver a disease modifying blend of bacteria to the colon. These microbes might include some of those that predominate in a healthy plant fed gut.
- Faecal transplants (or faecal microbiota transplantation – FMT) is as the name suggests, a pooh transplant, in which a sample of colon contents from someone with a healthy gut (and no infectious diseases) is blended and infused through a tube upwards or downwards into the recipients colon.
- Pre-biotics are supplements containing substances which encourage the growth of “good” bacteria. They may contain substances found in whole plant foods, such as resistant starch and oligosaccharides.
Life is not sterile, and we are constantly ingesting microorganisms. The Nature Journal study found that organisms in meat and plants transiently colonized the gut of the recipients. The NutritionFacts video Chicken Out of UTIs describes research which suggests that some UTIs are caused by E.coli that find their way into our bodies from raw chicken. It is possible that we exchange gut microbes with each other more often than we might like to think, particularly when we live together.
We expect that the increasing public and medical appreciation of the importance of gut microbes will bring a huge profit driven industry offering quick fixes to “bad” gut microbiomes. We should remember the Nature Journal study (David, L.A. et al. 2014) – you can’t grow good gut bugs on meat, eggs and cheese. This is not to say that these advanced probiotic approaches won’t be useful in medicine, but that their effectiveness will be limited if we don’t also address the pre-biotic, which usually means the food. Some possible roles for microbiome supplements are: infants born by caesarean section, following gut surgery, severe inflammatory bowel disease, after very broad spectrum antibiotic treatment, and in the treatment of infections such as clostridium. More research will be needed to develop a microbiome supplement evidence base.
MICROBIOME MODIFICATION IN THE TREATMENT OF DISEASE
Recent research has found an inflammation promoting microbiome in Crohns disease affected tissue. However it is uncertain whether the microbes caused the inflammation or are there because the tissue was already diseased. Prof Tom Borody is not waiting for further evidence. He is already performing faecal transplants in his Sydney clinic and claims to have cured people of Crohns disease and ulcerative colitis. It is of note that Ulcerative Colitis is a disease in countries where the diet is high in meat and dairy foods, and was completely absent in plant eating populations such as those in central Africa. Apart from numerous case reports of resolution of Crohns disease and ulcerative colitis on a WFPB, there is a Japanese study in which long term remission of Crohns disease was induced with a plant based diet. Faecal transplants are now recognized in the USA as an effective treatment for anti-biotic resistant Clostridum Difficile infection. This infection can be life threatening in debilitated patients and often follows antibiotic courses; and there is a new, more infectious strain, sweeping the world. It is possible that many of these infections could be avoided if more people consumed a WFPB diet.
MICROBIOME AND THE BRAIN
A microbiome-gut-brain connection has been proposed, and the term psychobiotics coined for microbiome supplements that may improve mood disorders and other brain disorders. We already know that the brain is influenced by the gut via the vagus nerve, hormones released by the gut and by substances absorbed through the gut (perhaps including TMAO and Neu5Gc). There has been some research on mice demonstrating that transplanting faeces from an anxious strain of mice to normal mice results in a transfer of anxious behavior. There is some evidence suggesting that a healthier more plant based diet improves mood. It is worth considering the impact on society of the current trend towards more animal ‘protein’ foods and less carbohydrate ‘fibre’ foods if this were to tip the psychology of the whole population towards depression, anxiety and aggression.
A whole foods plant based diet has an extraordinary breadth of effect in that it is beneficial to a wide range of diseases. It does this through its positive effect on a number of known disease mechanisms including vascular health, inflammation, insulin sensitivity and angiogenesis. It now seems without doubt that we can add “supports a favourable gut microbiome” to that list. We expect that nutrition will remain the mainstay of gut microbiome therapy and that probiotics, ecobiotics, psychobiotics and faecal transplants will have a secondary role in particular circumstances.
See also: Resistant Starch
Resources – see Gut Health page
Page created 10 May 2014
Page last updated 5 October 2014