Dr. Sarah Myhill MB BS
I am most grateful to Dr Henry Butt from Australia for providing essential information!
The normal state of affairs
The stomach, duodenum and small intestine should be free from micro-organisms (bacteria, yeast and parasites - hereon called bugs). This is normally achieved by eating a Stone Age Diet, having an acidic stomach which digests protein efficiently and kills the acid sensitive bugs; then an alkali duodenum, which kills the alkali sensitive bugs with bicarbonate; then bile salts (which are also toxic to bugs) and pancreatic enzymes to further digest protein, fats and carbohydrates. The small intestine does more digesting and also absorbs the amino acids, fatty acids, glycerol and simple sugars that result.
Bugs flourish in the large bowel, where foods that cannot be digested upstream are then fermented to produce many substances highly beneficial to the body. This also generates heat to help keep us warm. The human body is made up of 10 million million cells, in our gut we have 100 million million bugs or more, i.e. ten times as many! Bugs make up 60% of dry stool weight, there are over 500 different species, but 99% of bugs are from 30-40 species.
Metametrix laboratories in USA offer the Microbial Ecology Profile, in which they can measure the amount of different bacteria in a stool sample. This tells us which bugs are present and their numbers. However, the most important are baceroides, E. coli, lactobacilli and bifidobacteria.
Bacteroides. These are by far and away the most abundant bugs. It is bacteroides which allow us to digest soluble fibre and make short chain fatty acids. This is the main source of food for the colonocytes, the cells lining the bowel and if this is low, then it will result in atrophy of the colon. Short chain fatty acids also protect us from hypoglycaemia. Indeed, it is estimated that up to 540Kcal per day may be generated - a very significant source of energy! They are essential for recycling of bile acids, so low levels of bile acids may indicate poor levels of bacteroides. They occupy the surface of the gut so preventing pathogenic species (such as salmonella, shigella and clostridia) from adhering and causing infection. There is no probiotic which contains bacteroides. This is because it is also a potential pathogen! We just have to feed the gut with the right food (prebiotics) found in pulses, nuts, seeds and vegetables. Also see Faecal bacteriotherapy
E-coli. One gram of stool should contain between 7 million and 90 million. E-coli ferments to produce folic acid, vitamin K2 (this protects against osteoporosis), Co-enzyme Q10 (essential for mitochondrial function), together with 3 amino acids, namely tyrosine and phenylalanine (these are pre-cursors of dopamine, lack of which results in low mood) and tryptophan. Tryptophan is a pre-cursor of serotonin, which is responsible for gut motility. So, if there are low counts of E-coli, one can expect problems in all the above areas, i.e. osteoporosis and bone problems, mitochondrial function, low mood and poor gut motility. Dr Butt told me about a study done in Germany where E-coli probiotics were given in the treatment of constipation and there was a dramatic improvement from 1.6 motions a week to 6, illustrating the effects on motility! E-coli is contained in the probiotic Mutaflor produced commercially in Germany.
Lactobacilli. These ferment sugars to lactic acid, which provides an acid environment in the large bowel to protect against infection. Also highly protective against bowel cancer. Abundant in Kefir. '
Bifidobacteria. These assist digestion, protect against development of allergies and cancer.
We need to concentrate our efforts on the above goodies - get these right and all else falls into place! Other bacteria will flourish if numbers of the above decline for whatever reason - Nature abhors a vacuum!
Streptococcus. This ferments to produce large amounts of lactic acid. This gives a tendency to acidosis. Lactic acid is metabolised in the liver by lactate dehydrogenase, so high levels of this may indicate bowel overgrowth with streptococcus. Fermentation produces two isomers of lactic acid, namely L-lactate and D-lactate. It is D-lactate which is the problem, the body cannot metabolise this, it accumulates in mitochondria and inhibits them.
Prevotella (bacteroides in the upper gut). These ferment to produce hydrogen sulphide. Hydrogen sulphide inhibits mitochondrial function directly. So a positive hydrogen sulphide urine test shows there is a severe gut dysbiosis with overgrowth of prevotella secondary to undergrowth of the goodies!
Problems could arise either from having the wrong bugs in the lower gut (large intestine), or having any bugs in the upper gut (stomach, duodenum, jejunum, small intestine).
Bugs in the upper gut
In some patients there are bacteria, yeasts and possibly other parasites existing in the upper gut, which means that foods are fermented there instead of and before being digested. When foods get fermented they produce all sorts of unwanted products which have to be detoxified by the liver cytochrome P450 detox system. These products include:
Alcohols such as ethyl alcohol, propyl alcohol, butyl alcohol and possibly methyl alcohol. These would be metabolised by stage one into acetaldehyde, propylaldehyde, butylaldehyde and possibly formaldehyde. Alcohol and acetaldehydes result in foggy brain, "toxic brain", feeling "poisoned" and so on. Alcohol also upsets blood sugar levels. This makes the sufferer crave sugar and refined carbohydrates - the very foods bugs need in the upper gut to ensure their own survival. This is arguably a clever evolutionary ploy by bugs to ensure their own survival!
Noxious gases such as hydrogen sulphide, nitric oxide, ammonia and possibly others. Hydrogen sulphide is known to inhibit mitochondria and block the oxygen carrying capacity of haemoglobin. It also greatly increases the toxicity of heavy metals.
Odd sugars such as D-lactate. This right handed sugar cannot be detoxified by lactate dehydrogenase, a liver enzyme. If D-lactate is present, then it could point to a problem with gut fermentation. It may result in lactic acidosis. These patients typically present with episodic metabolic acidosis (usually occurring after high carbohydrate meals) and characteristic neurological abnormalities including confusion, cerebellar ataxia, slurred speech, and loss of memory. In a review of 29 reported cases, for example, all patients exhibited some degree of altered mental status. They may complain of or appear to be drunk in the absence of ethanol intake. Indeed, this phenomenon is much better described in the vet world. D-lactate is a recognised cause in cattle of neurological manifestations. Furthermore, products of fermentation are thought to be a cause of laminitis in horses. Indeed, the encephalopathy of liver failure can be treated by gut only antibiotics to wipe out unwelcome overgrowth of fermenting gut flora. D-lactate is fermented from sugars, including fruit sugars. This is a further reason to cut out sugar and fruit strictly from the diet! One molecule of sugar generates two molecules of D-lactate.
Other things I don't yet know about!
In theory the above toxins should all be detoxified by the P450 cytochrome system, but in practice some of these can spill over into the systemic circulation with a simple poisoning effect and resultant production of free radicals and inhibition of mitochondria.
These products of fermentation add to our total chemical load and therefore may worsen an underlying poisoning (such as chronic organophosphate poisoning) by overwhelming our detox defences.
Other problems caused by upper gut fermentation
Symptoms - for example, Drs De Meileir and Butt have shown that high levels of enterococcus are associated with symptoms of headache, arm pain, shoulder pain, myalgia, palpitations and sleep disturbance. High levels of streptococcus are associated with post exertional fatigue, photophobia, mind going blank, palpitations, dizziness, faintness.
Malabsorption of micronutrients;
Nutritional supplements could make things worse. It is possible that the fermenting gut explains this. Instead of nourishing you, supplements nourish the bugs. This encourages their growth and therefore fermentation! This makes sense because from an evolutionary perspective mitochondria are derived from bacteria,. So what mitochondria like bacteria will also thrive on.
Wind, gas, bloating from physical distension
Disturbances of normal gut movement - constipation or diarrhoea;
Susceptibility to infections;
Leaky gut - with leaky gut, short chainpolypeptides may leak into the blood stream and act as hormone mimics. For example, a strip of amino acids Ser-Tyr-Set-Met would mimic ACTH - the hormone which stimulates the adrenal gland. An 8 amimo acid fragment could act like glycogen and so deplete glycogen (sugar) stores in the liver.
Susceptibility to heavy metal poisoning - because hydrogen sulphide binds to heavy metals rendering them "organic" instead of "inorganic" and therefore much more likely to enter the body and bioaccumulate.
Prion disorders - heavy metals in the wrong department can twist normal proteins and convert them into pathogenic prions which are implicated in prion disorders.
Dental, gum and mouth problems - one is likely to have similar bacteria in the mouth as the gut. If you have a clean tongue and no dental plaque then you are likely to have good gut flora.
Gibson, a food microbiologist from Reading, divides people into "smellies" and "inflammables" - normal gut fermentation produces hydrogen and methane which allows one to "light their own flatus". It is also odourless. With sulphate reducing bacteria present hydrogen sulphide is produced - giving the rotten eggs smell and a positive Hydrogen sulphide in urine.
Tests of bugs in the upper gut - gut fermentation
Biolab Gut fermentation profile measures levels of alcohol in the blood. It also looks for short chain fatty acids, which are desirable products of fermentation by friendly bacteria in the large bowel.
D-lactate can be measured by a blood test following a carbohydrate meal. The snag is that postal samples are not completely reliable and in order to have the test, the patient either needs to go to Biolab to have blood taken and processed straight away or he/she has to find a laboratory where they will spin and separate blood immediately and freeze it so that a frozen sample is sent to Biolab. This is quite difficult to organise and I will not be recommending this test, but if anyone can organise it for themselves, please ask for it and I will make a referral to Biolab.
Hydrogen sulphide can be tested for with a urine test.
A good clinical test for upper gut fermentation is whether one produces wind or gas (belching, bloating, feeling full, noisy gut etc) after eating carbohydrates!
Which bugs are there? One can look at stool samples to ascertain that. That does not tell us where the bugs came from but it's a good start. Comprehensive Digestive Stool Analysis or Comprehensive Digestive Stool Analysis with Parasitology is sometimes helpful. The bugs which are thought to be the main fermenters are enterococcus, streptococcus and prevotella (bacteria) and candida (yeast). Conversely, in the fermenting gut there may be low levels of bacteroides, lactobacilli and bifidobacteria. This is because if there is fermentation upstream, there is little substrate for fermentation downstream! A more detailed test of the actual bugs present which includes bacteroides is Microbial Ecology Profile.
What causes upper gut fermentation?
A long history of:
- Western lifestyles! A traditional Chinese diet does not include dairy products, gluten grains, alcohol and very modest amounts of fruit
- Failure to inoculate the gut at birth with the correct friendly bacteria - see Probiotics
- high in sugar and refined carbohydrate
- low in vegetables, pulses, nuts and seeds.
- low in other micronutrients
- Poor digestion of food - see Hypochlorhydria and Pancreatic exocrine function
- Antibiotics, which wipe out the gut flora
- Pill and HRT, which suppress the immune system and encourage yeast overgrowth
- Acid blockers such as antacids, H2 blockers and proton pump inhibitors, which inhibit stomach acid production - see Hypochlorhydria. Allergies to food may also result in this problem.
Why a fermenting gut can cause fatigue
Mitochondrial failure results in fatigue
There is good evidence that the central pathological lesion in CFS is mitochondrial failure. What is critical to the optimal function of mitochondria is good redox state, that is to say the balance between free radical stress and our ability to cope with those free radicals, i.e. the body's antioxidant status. Free radicals damage mitochondria so they go slow, but we have a system of anti-oxidants in place to protect us against this free radical stress. See Antioxidants and CFS - The Methylation Cycle.
Free radicals partly control mitochondrial activity
Excessive free radical production, which cannot be dealt with by antioxidant reserves, will damage and switch off mitochondria. One would think
that the largest source of free radicals comes from mitochondria themselves since here we have large amounts of glucose being oxidised in the presence of oxygen to produce energy with a large potential to produce free radicals, such as superoxide. Whilst this is undoubtedly a major source, even greater than this is the liver P450 cytochrome system. Humans are able to eat a wider variety of foods than any other mammal because of this amazing detoxification system of enzymes. It has resulted in humans becoming the most successful mammal because we can occupy almost any ecological niche. When the P450 detox system is working well, then this has enormous evolutionary advantages. However, if things start to go wrong, excessive amounts of free radicals are produced with the potential to switch on a chronic fatigue syndrome.
At this point it must be emphasised that a chronic fatigue syndrome is a protective adaptive response. If that person did not become acutely fatigued and succeeded in pushing on physically or mentally, then the excessive free radicals so generated would have the potential to cause enormous pathological damage. This is probably why we do not see wild animals with chronic fatigue syndromes. They simply push themselves to destruction because they have to survive.
The liver P450 detoxification system is a major source of free radicals
There are two stages to liver detox. Stage one is an oxidation reaction to make molecules a bit more active in order that stage two can take place, in which another molecule is stuck on. This tacking on allows the toxin to become less active and more water soluble so it can be excreted in urine. The tacking on could be of a sugar (glucuronidation), amino acid, glutathione, sulphate group and so on.
There are many possible ways the liver P450 cytochrome system could be overwhelmed.
- Genetic: some people simply have genetically poor detox ability. One example of this, of course, is Gilbert's syndrome, where conjugation with glucuronide (stage 2 detox) is lacking. There are two steps to detoxification: the first is an oxidation reaction which may make some toxins more toxic! Many CFS sufferers have fast stage one and slow stage two metabolism, which means they have a P450 system which initially produces more rather than less toxic stress! So, for example, over 80% of Gilbert's sufferers complain of fatigue. One example is alcohol. This is metabolised initially into acetaldehyde, which is a nasty toxic compound responsible for hangovers! Alcohol intolerance is almost universal in CFS sufferers.
- An acquired metabolic lesion as a result of nutritional deficiency. For example, many of these P450 cytochrome enzymes are highly dependent on metal co-factors such as zinc, magnesium, or selenium, B vitamins and essential fatty acids.
- Toxins produced from normal metabolism e.g. detoxifying neurotransmitters, products from immune activity, breakdown products from damaged tissues etc
- Overwhelming toxins from the outside world, such as persistent organic pollutants, or of course prescribed drug medication or social drugs of addiction (caffeine, alcohol). This is part of the explanation why so many CFSs do not tolerate prescription medication. Other reasons are that many drugs inhibit mitochondria directly, or destabilse membranes in the brain resulting in poor energy delivery to brain cells see Brain fog - poor memory, difficulty thinking clearly etc. Patients refusing medication then get labelled as unco-operative and are dropped from medical care.
Intoxicants arising as a result of fermentation from the upper gut.
Tests for liver detox ability
We can do genetic tests (such as single nucleotide polymorphisms or SNIPs) through Genova laboratories.Genova also offer functional teststo look at stage one and stage two detoxification.
Treatment of the fermenting gut
The definitive treatment has yet to be established. We are all on a sharp learning curve here! The key thing is to sterilise the upper gut and normalise digestion of food so that only the friendly bugs can grow downstream. But the principles of treatment are:
Try to recreate the ideal environment for digestion of foods
Eat Diet of low fermentable substrate - it is sugar and refined carbohydrate which microbes most love to ferment. The diet needs to be low glycaemic index (see Hypoglycaemia) and rich in raw or lightly cooked vegetables. This is because these foods contain a range of natural antimicrobials to inhibit bacterial overgrowth in the upper gut, together with many enzymes essential for their own digestion and fibre for fermentation in the large bowel by friendly bacteria into short chain fatty acids. With fruit, only berries permitted!
Feed bacteroides - eat pulses, nuts, seeds and vegetables, i.e. foods rich in probiotics. These provide food for bacteroides in the large bowel which ferment them to short chain fatty acids. This is the fuel for the cells lining the gut, without which they atrophy. It is also the fuel which mitochondria can switch to when blood sugar levels fall low (for example during sleep). The best sources are in pulses, vegetables, nuts and seeds.
Acid stomach and alkali duodenum - An acid stomach helps to kill microbes which are acid sensitive, whilst an alkali duodenum helps to kill microbes which are alkali sensitive. A normally acid stomach would be pH 4 or less, whilst the duodenum would be 8 or above. The pH scale is a logarithmic one so these figures represent a 10,000 fold difference in acidity.
One can test for a non-acid stomach by a simple saliva test - see Hypochlorhydria. There is no easy way to test for an alkali duodenum. Where there is hypochlorhydria, take additional acid with food (as ascorbic acid or betaine hydrochloride). The stomach normally takes 1-2 hours to empty; at this point take magnesium carbonate 1-2 grams, which neutralises stomach acid and assists digestion in the duodenum.
Eat smaller meals - lesser amounts of foods are easier to deal with. Anyone who has eaten much too large a meal will recognise the symptoms of fermenting gut - fatigue, bloating, discomfort and, later, foul smelling wind!
Sterilise the upper gut - the key here is to take something which kills bugs in the upper gut but does not upset bacteria in the lower gut. This is why antibiotics are not ideal - they will also upset lower gut flora. Bacteria and yeast are greedy for micronutrients, especially minerals. Indeed, this may explain why some patients worsen when they take micronutrients - these simply feed the upper gut flora so they ferment harder. Ways to tackle this:
- Take high dose ascorbic acid between and during meals. The acid and the ascorbate both kill microbes. In the right dose they can sterilise the upper gut but since most is absorbed the lower gut is not affected. If very high doses of vitamin C are taken it will spill over into tthe large bowel and cause diarrhoea - this is called taking vitamin C to bowel tolerance and is useful in getting rid of gut infections such as viral gastroenteritis.
- Take minerals through the skin by mixing them with aqueous cream - see Minerals and vitamins in creams. This may explain why the tiny amounts of magnesium in injections is so effective!
- Plant tannins (eg viracin) chelate up minerals so they are not available to bugs. This may explain why tea drinking is so popular - the tannin in tea has the same effect. Also spicy foods kill microbes and may explain why the most popular British dish is now curry! Since gut fermentation is a common problem in people eating Western diets perhaps subconciously we have worked out that a good curry with a cup of tea makes us feel better!
Quick efficient digestion of food means that there is less available to be fermented downstream. One may need:
Acid supplements: Indeed, there may be a role for vitamin C as ascorbic acid. Ascorbic acid is acid and so improves digestion of protein. It is also toxic to all microbes including bacteria, yeast and viruses as well as being an important anti-oxidant - indeed the eventual receiver of all electrons from free radicals. Humans, guinea pigs and fruit bats are the only mammal species which cannot make their own vitamin C and we have to get it in food. Scaling up from other mammals we should be consuming 2-6 grams daily (a hundred fold more than the government RDA of 30mgs daily!). One could get the dose just right so that ascorbic acid with food sterilises the upper gut, but is absorbed and has no effect on the lower gut. If one takes excessive vitamin C it will cause diarrhoea as too much gets into the lower gut, kills off the bugs there and empties the gut completely!
Pancreatic enzymes see Pancreatic exocrine function. The need for these could be tested by doing a Comprehensive digestive stool analysis (CDSA). A dose would be 1-3 capsules of Polyzyme Forte (BioCare) with meals depending on the size of the meal. Be aware that many prescribable pancreatic enzymes contain toxic dimethicones or phthalates.
Magnesium carbonate as above
or Bile acids. These can be measured as part of a CDSA but ask specificially for them as they are not a part of the basic package. Take 150mgs with meals. Apparently prevotella, the bug shown by Kenny de Meirleir to be a major fermenter, is susceptible to bile acids. Increasing fats and oils in the diet will improve bile flow and my help flush out unwanted bacteria in the biliary tree. See Phospholipid exchange
Improve the lining of the gut:
Chewing gum. The parotid salivary gland provides a rich source of endothelial growth factor (indeed, this is what John McLaren Howard measures in his hypochlorhydria test) which stimulates growth of the lining of the gut. Chew, because this stimulates flow of saliva. Sugar-free, additive-free gum please!
Dr Butt recommends the intake of red meat and soya bean protein for vegetarians (although he considers this very much "second best").
Dr Butt recommends glutamine in a slow release capsule to nourish the gut lining and also to correct antioxidant status (superoxide dismutase, Co-enzyme Q10 and glutathione peroxidase). See Antioxidants
the Pill and HRT,
acid blocking drugs especially proton pump inhibitors,
some antidepressants which cause dry mouth.
Change the bugs in the gut
Having done all the above, one can then consider direct action to innoculate the gut with desirable bacteria. This is difficult because unless the gut has been programmed at birth to accept a particular bug, it will tend to reject it. This is why probiotics may have to be taken long tern and so it is desirable to grow them yourself.
Treatment of low E-coli:
All the above and
Mutaflor ½ a capsule daily for two days, then 1 capsule daily for seven days then 2 capsules daily for 14 days and adjust the dose subsequently according to response. Julia Oakley has a recipe for Growing Mutaflor so that one sachet lasts a lifetime!
Prebiotics. It is vital that E-coli is given with the prebiotic galactose (galactose oligosaccharides) mainly found in pulses and nuts. These will ferment in the large bowel to produce wind (hydrogen and carbon dioxide) this only becomes foul smelling if other foods are poorly digested.
Treatment of low numbers of Bacteroides
All the above, especially prebiotics
Low numbers of bacteroides should build up easily with above measures
A major problem would arise if there were no bacteroides. There is no probiotic which contains bacteroides because it does not survive outside the human gut. One possibility would be to consider Faecal bacteriotherapy ie use fresh live actively fermenting bugs from another human gut. The main proponent of this therapy is Dr Thomas Borody. See Thomas Borody. I do not know of anyone who does this technique in UK.
Treatment of high Streptococcus levels:
All the above
Avoid glucose and fructose strictly each molecule of glucose and fructose will produce two molecules of lactic acid and create a marked tendency to acidosis. Dr Butt is Chinese and he points out that Chinese people do not eat fruit at all. Only the wealthy Chinese do and then very occasionally. Glucose and fructose are potentially very damaging to the body because they get fermented by streptococcus into D-lactate. This is another mechanism by which sugars can result in foggy brain.
Erythromycin 500mg twice daily for 7 days or any such macrolide. Perhaps longer. Happily bacteroides, the most abundant probiotic is largely resistant to erythromycin!
Magnesium carbonate and pancreatic enzymes. One can monitor progress through the foggy brain symptom this should improve and as it does so one can tail off the Erythromycin, but continue with an E-coli probiotic.
Treatment of High Enterococcus
All the above
Kefir contains bacteriocins which inhibit streptococcus. But it also contains lactobacillus plantarum, which can ferment sugar to D-lactate, so avoid sugar strictly if this is your problem! L. Plantarum has good anti-inflammatory action which makes it a desirable probiotic in inflammatory bowel disease.
There does not appear to be an antibiotic that Prevotella is sensitive to, but apparently it can be reduced by taking bile salts. These are also available on prescription as Ursodeoxycholic acid and I would suggest 150mg with meals, perhaps more!
Replete with probiotics
For this to be effective one should take high doses of actively fermenting probiotics. I like to use Kefir, which is easily grown on many substrates (I use soya milk) and one sachet lasts a lifetime since a new culture can be grown from the previous. See Probiotics and Kefir. I suggest one cupful after meals. Avoid sugar and fruit when using Kefir. This is rich in lactobacillus. For E coli use mutaflor - see Growing Mutaflor
See also Yeast problems and candida
Faecal microbial analysis
Comprehensive Digestive Stool Analysis
Gut fermentation profile
Probiotics - we should all be taking these all the time and double the dose following antibiotics and gastroenteritis
Yeast problems and candida
CFS - The Methylation Cycle