Gut Microbiome

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.

MICROBIOME STATS
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.

CO-EVOLUTION
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.

RESISTANT STARCH
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:

  1. 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.
  2. 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.
  3. 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
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.

MICROBIOME SUPPLEMENTS

  • 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.

FUTURE THERAPIES
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.

Conclusion
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

FODMAPs

FODMAPs is an acronym for Fermentable Oligo-saccharides, Di-saccharides, Mono-saccharides And Polyols.

FODMAPs are a group of sugars and short chain carbohydrates that are not absorbed in the small intestine (like dietary fibre and resistant starch). Bacteria in the large intestine (or even in the small intestine) ferment FODMAPs to produce large amounts of gas (hydrogen and methane), which can be very uncomfortable, particularly to those with irritable bowel syndrome. They can also act as a laxative by preventing excess water from being absorbed by the intestine

Irritable Bowel Syndrome is a common gastro-intestinal disorder characterized by abdominal bloating, excess gas, crampy pain and diarrhoea and/or constipation. Diagnosis is made on the basis of long-term symptoms and the exclusion of other causes such as inflammatory bowel disease (Crohn’s disease and Ulcerative colitis), Coeliac disease (caused by gluten in wheat and related grains) and other diseases. If you have Irritable Bowel Syndrome, a whole foods plant based diet will provide the high fibre diet that is recommended, but you may need to limit the quantities of some foods. As your gut health improves on a whole foods plant based diet you may find that you are better able to tolerate high FODMAP foods.

FODMAPs are comprised of several groups:

  1. Fructose
  2. Lactose
  3. Sugar polyols – sorbitol and mannitol
  4. Fructans and GOS (galacto-oligosaccharides).

Fructose and lactose are only a problem to individuals who lack the capacity to absorb them from the small intestine. Most non-European adults cannot absorb lactose but this is not an issue on a plant-based diet because lactose is only found in dairy products, not plants. There seems to be an epidemic of fructose intolerance. We suspect that this is related to the gut inflammation and gut bacteria imbalance that we discussed on the Gut Health page. Fructose absorption is assisted by glucose so it is really the excess fructose relative to glucose that causes problems. (Cane sugar is a di-saccharide of fructose and glucose so it’s not a FODMAP, just a concentrated carbohydrate devoid of any other nutrients). For more troublesome symptoms, you may consider taking a hydrogen breath test for fructose intolerance. Your doctor can request this test. The result may then guide you as to whether you may benefit by limiting high fructose foods, or conversely avoid unnecessary restriction of otherwise healthy fruits and vegetables.

The low FODMAP diet is not a total exclusion diet. It’s not like peanut allergy or gluten intolerance. Bacterial fermentation of undigested carbohydrate is part of the normal function of the human gut, and it only becomes a problem when there is too much gas produced too quickly, or that your gut is abnormally sensitive to distension. You can reduce the FODMAP content of your diet without compromising nutrient intake and variety simply by using smaller quantities of high FODMAP fruits and vegetables and increasing the quantities of low FODMAP ingredients. You may find that some classes of FODMAPs cause you more problems than other types. It is also probable that you will not get the same reaction on each occasion that you consume the same food items. There may be some days when you might consider a stricter low FODMAP diet such as before an important event or at times of greater stress.

Intolerance to bread and other foods containing wheat is common. This can be from the FODMAPs in whole wheat, allergy to yeast or wheat proteins, or coeliac disease. Coeliac disease is caused by an immune reaction to some of the proteins in the gluten and results in the gut lining becoming seriously damaged. Symptoms include pain, diarrhea, and malnutrition.  Gluten is present in wheat, barley and rye. Most individuals with coeliac disease can tolerate oats. Your doctor can order a blood test as an initial test for coeliac disease (NB It is important you are tested whilst still consuming gluten). Coeliac disease seems to becoming more common which may in part reflect greater community awareness and increased testing. We speculate that dietary factors may be responsible for some of the increase (see Gut Health page). Wheat products can be replaced with brown rice, oats, potatoes, sweet potatoes, brown rice pasta, buckwheat pasta, quinoa and other high fibre gluten free products.

The reputation of beans for increasing flatulence and gastrointestinal discomfort is overstated. One study of perceived flatulence found that most subjects reported no change when eating half a cup beans per day. But if this food group seems to cause you problems then there are low FODMAP options such as tofu and cooking methods that leach much of the FODMAPs out of the beans.

For more information on which foods to include in a low FODMAP diet see The Monash University Low FODMAP diet – Examples of low and high FODMAP foods. There is also an iPhone App which gives you a filter option for selecting which particular FODMAP classes you wish to restrict. This could be a very useful tool to use while shopping. Download from the App store, or see The Monash University Low FODMAP diet page. See also our Elimination diets page.

Related pages:

Resources

Gut Health

The number of Australians with gut problems seems to have increased in recent years. Most of these individuals do not have Coeliac disease, proven food allergies or inflammatory bowel disease but suffer frequent abdominal pain, bloating and bowel disturbances. Emerging research is pulling together an understanding of the complex interaction between the gut, the food we eat and the role of the gut bacteria. We share with you some ideas on why there has been a rise in gut problems and offer some possible solutions.

Note: If you have persistent gut symptoms, please seek medical advice.

In recent years there has been a great deal of speculation about the pre-agricultural diet and what type of diet is best for the genetic heritage that evolution has given us. What we can tell you is that the humans have a herbivore type gut, very similar to that of apes and monkeys. The relatively smaller size of the human gut can be attributed to our long evolutionary history of cooking food, which reduces the digestive work required. More in Humans are Herbivores.

We evolved in tandem with our gut microbiome, the bacteria and other microbes that inhabit our gut. They are just as much a part of our digestive system as our own cells. They feed on dietary components that are not absorbed in the small intestine, such as dietary fibre and resistant starch. The microbiome pays its fare by providing us with energy and nutrients that would otherwise have been lost. The large bowel or colon is essentially a fermentation vat. This explains the gas.

We have all heard of “good bugs” and “bad bugs” thanks largely to the marketing of probiotic supplements. Recent medical research is finding links between the type of gut bacteria present and certain diseases such as Crohn’s disease. More recently Faecal Transplants have been successfully used to eradicate clostridium difficile infection. However, the current paradigm is still very much about putting the right kind of bacteria into the gut with little consideration of the type of growth medium, the food. This is like planting rice seeds in a wheat paddock with no irrigation and expecting to grow a crop of rice. “Good bugs” can only thrive and persist on the right food mix, the “pre-biotic”. A recent study (David et al 2014) found that it only takes three days of an all plant based diet vs an all animal product diet to produce a completely different balance of gut bacteria. More in Gut Microbiome.

Animal protein foods not only lead to a less favourable gut microbiome but their constituents can also damage the gut lining. Some of these such as saturated fat and endotoxins have a direct inflammatory effect while other such as methionine and carnitine produce inflammatory bacterial products. The loss of the bulking effect of dietary fibre further contributes to these effects. When the gut lining, which is only one cell thick, is damaged by this combination of “bad” gut microbiome and animal protein foods it loses it integrity and leaks like a sieve. Potential allergens and proteins that may trigger autoimmune disease are then able to pass into the blood stream. This state is known as “Leaky gut syndrome” and is thought by some to be responsible for many diseases including auto-immune diseases. Note the correct medical term for ‘leaky gut’ is ‘increased intestinal permeability’, a recognised feature of inflammatory bowel and coeliac disease. More in Leaky gut syndrome (under construction).

Dietary fibre is essential to gut health and is protective against other diseases such as heart disease, diabetes and breast cancer. Our page, Nutrient Density explains that adequate dietary fibre cannot be obtained by simply adding a supplement or particular food to an otherwise low fibre diet. Many gut problems are simply symptoms of inadequate dietary fibre. Constipation is not always apparent as one can have a transit time, from eating to elimination, of 5 days but still be “regular”. There is a group of NutritionFacts videos in the Resources section below which covers this in more detail. More in Fibre (under construction).

There is a group of carbohydrates known as FODMAPs which can ferment too quickly and produce large amounts of gas leading to abdominal pain and distension. A low FODMAP diet can often reduce these symptoms but may not be addressing the underlying cause of why the gut is so sensitive to gas. An inflamed gut lining, a “bad” mix of gut bugs and inadequate dietary fibre may be behind many FODMAP intolerances including whole wheat. Avoiding wheat, other whole grains, or even all starches, will reduce gas production and relieve symptoms for some people but it will not cure the unhealthy gut situation. In fact, the gut health is likely to be worse as fibre intake is further reduced and “good” gut bacteria are starved of fermentable carbohydrates. See FODMAPs.

Many individuals suffering from gut problems protest at the suggestion that their overall diet could be causing the problem. After all, they may be lean and healthy and following the advice of experts to eat more fish, chicken, yoghurt and olive oil, whilst restricting carbohydrates. What’s more, the gut problems may not have followed a change in diet. The onset of gut problems may be delayed for months or years following a change in diet or a habitual low starch diet. There may be a tipping point, an irreversible shift to one side of a precarious balance in an already stressed system that follows some event such a course of antibiotics (see Blaser 2011) or an episode of gastroenteritis. Once the gut bacteria and gut lining have gone past this tipping point they may not readily recover due to positive feedback mechanisms which maintain the new dysfunctional state.

A whole foods plant based diet is part of the solution for most gut problems. Having said this, we wish to make it clear that none of the information we provide is intended to be taken as medical advice and that persistent gut symptoms should be assessed by a qualified health practitioner. If you have Crohn’s disease, Diverticular disease or Ulcerative colitis you might find it interesting to look at the resources, including Success Stories on our page Inflammatory Bowel Disease – Ulcerative Colitis and Crohn’s Disease.

The transition to a whole foods plant based diet may be problematic for some. It can take several months to adapt to the higher dietary fibre content and greater bulk of whole plant foods. Focusing on increasing the intake of starchy foods (eg grains, potatoes) may be better tolerated than trying to eat large amounts of fruits and raw vegetables. The FODMAP information may assist in choosing a less gassy range of whole plant foods during this transition phase. Legumes, for example, may need to be introduced gradually – which may mean abandoning the standard plate model of a “protein” food comprising a quarter of the plate. There is plenty of protein in the food on the rest of the plate.

While there is no question that those with Coeliac disease must avoid all gluten containing grains, wheat, barley and rye, the evidence does not support the avoidance of wheat as a general health measure. Gluten free diets are associated with worse health outcomes (see Lebwohl et al 2017), probably because of the lack of whole grains. This need not be so as there are many other whole grains to choose from and no one is intolerant to all of them.

Plant-based practitioners often prescribe an elimination diet to treat flare ups of ulcerative colitis, Crohn’s disease and autoimmune diseases such as rheumatoid arthritis. A regular whole foods, plant-based diet may not be enough to bring severe gut inflammation under control. Elimination diets are also used to diagnose and treat suspected food intolerances that are not resolved by following a low fat, whole foods, plant-based diet. See our page on Elimination Diets.

Related pages:

Resources

General digestion

Gut flora:

Dietary Fibre:

Gluten, wheat & grains:

Inflammation:

Success stories

Page created 5 October 2013
Page last updated 26 June 2017