Poisoning The Mitochondria part 2


Senior Member
Toxic Fermentation in CFS

Dr Myhills,

The human gut is almost unique amongst mammals - the upper gut is a near-sterile, digesting carniverous gut (like a dog's or a cat's) to deal with meat and fat, whilst the lower gut (large bowel or colon) is full of bacteria and is a fermenting, vegetarian gut (like a horse's or cow's) to digest vegetables and fibre. From an evolutionary perspective this has been a highly successful strategy - it allows Eskimos to live on fat and protein and other people to survive on pure vegan diets.

Problems arose when humans learned to cook and to farm. This allowed them to access new foods namely pulses, grains and root vegetables - these need cooking to be digestable. From an evolutionary perspective this have been highly successful and allowed the population of humans to increase at a great rate. However carbohydrates have the potential to be fermented in the upper gut with problems arising as detailed below. ME sufferers are evolutionary carnivorous relics!

I suspect allergy to gut flora may be responsible, or part responsible, for many conditions such as irritable bowel, irritable bladder, arthritis, muscle pain (fibromyalgia), so-called intrinsic asthma, urticaria, tinnitus, venous leg ulcers and possibly age related deafness. It is possible that some psychiatric conditions are caused by gut microbes fermenting neurotransmitters to create amphetamine and LSD like substances - not my idea but a Japanese researcher Nishihara.

The stomach, duodenum and small intestine should be free from micro-organisms (bacteria, yeast and parasites - hereon called microbes). This is normally achieved by eating a Stone Age Diet, having an acidic stomach which digests protein efficiently and kills the acid sensitive microbes; then an alkali duodenum, which kills the alkali sensitive microbes with bicarbonate; then bile salts (which are also toxic to microbes) 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.

Anaerobic bacteria, largely bacteroides, flourish in the large bowel, where foods that cannot be digested upstream are then fermented to produce many substances highly beneficial to the body. Bacteroides ferment soluble fibre to produce short chain fatty acids - over 500kcals of energy a day can be generated. This also creates heat to help keep us warm. The human body is made up of 10 trillion cells, in our gut we have 100 trillion microbes or more, i.e. ten times as many! Bacteria 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 bacteroides that make up 90% with E. coli, lactobacilli and bifidobacteria laregly making up the rest.


  • Bacteroides. These are by far and away the most abundant bacteria. 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 over 500Kcal 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 simply because bacteroides cannot exist outside the human gut - oxygen kills it quickly. 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 may give 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. One can measure D lactate in the blood stream.
  • Prevotella (bacteroides in the upper gut). It is thought these ferment to produce http://www.drmyhill.co.uk/wiki/Fermentation_in_the_gut_and_CFS Hydrogen sulphide inhibits mitochondrial function directly. So a positive hydrogen sulphide urine test shows there is a severe gut dysbiosis probably due to overgrowth of prevotella.
Bacteria and yeast 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 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 by enhancing their absorption.
  • 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.

I was fascinated to discover that at rest the liver uses up 27% of all the energy available to the body (compared with the brain at 19% and the heart at 7%). Much of this energy is for detoxification! In ME where energy delivery is impaired, one may expect detoxification to also be impaired!

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,. Perhaps what mitochondria like bacteria will also thrive on.
  • Allergy to microbes - resulting in unecessary inflammation and wasting of immune energy. See Energy Expenditure in ME/CFS: Immune wastage of energy and Rituximab
  • 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 in the gut hydrogen sulphide is produced giving the rotten eggs smell and a positive hydrogen sulphide in urine test. This test is called the "Neurotoxic metabolite test" and can be ordered online directly from Protea Biopharma in Belgium.

Tests for microbes in the upper gut - gut fermentation
  • 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
  • Diet
    • 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
  • Modern medication
    • 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.

  1. 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.
  2. 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.
  3. Toxins produced from normal metabolism e.g. detoxifying neurotransmitters, products from immune activity, breakdown products from damaged tissues etc
  4. 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.
  5. Intoxicants arising as a result of fermentation from the upper gut.
Tests for liver detox ability
We can do a Detoxification Profile at Genova Diagnostics in the USA. This is a functional test to 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. Bacteroides ferment vegetable fibre. The diet needs to be low glycaemic index (see Hypoglycaemia) and rich in raw or lightly cooked vegetables. However some people may also have to avoid vegetable fibre initially to starve out fermenting anaerobes in the upper gut. Indeed this is the basis of the GAPS diet developed by Dr Natasha Campbell McBride. Subsequently these foods can be reintroduced once the upper gut is healed. 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. This helps restore normal function. With fruit, some people will tolerate fructose because this is a monosaccharide and rapidy absorbed. Broadly speaking anaerobic bacteria ferment soluble fibre, aerobic bacteria ferment disaccharides, polysaccharides and starches (ripe fruit OK to eat because fructose is a monosaccharide) and yeast ferment mono-saccharides (ripe fruit not OK to eat!). The GAPS diet adresses fermentation by all three, the specific carbohydrate diet adresses fermetnation by aerobic bacteria [2]. Anti candida diets adddress fermetnation by yeast. If in doubt suggest starting off with a protein fat diet for all the reasons given by Barry Groves in his lovely presentation [[3]]. The only way to really find out is trial and error.
  • Once the upper gut is sterile (additional antibiotics and/or antifungals may be needed), then aim to feed bacteroides in the lower gut- eat pulses, nuts, seeds and vegetables, i.e. foods rich in prebiotics and soluble fibre. 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. 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:
  1. Take high dose ascorbic acid or magnesium ascorbate between and during meals. The acid and the ascorbate both kill microbes. In the right dose they can sterilise the upper gut. If very high doses of vitamin C are taken it will spill over into the large bowel and cause diarrhoea - this is called taking vitamin C to bowel tolerance and is useful in getting rid of gut infections in a gastroenteritis.
  2. Take minerals through the skin by using transdermal micronutrients. This may explain why the tiny amounts of magnesium in injections is so effective!
  3. 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!
  4. Broadly speaking it is yeast that ferment monosaccharides and disaccharides (sugar and fruit sugar), aerobic bacteria that ferment disaccharides and polysaccharides(grain and potato starches) and anaerobic bacteria that ferment soluble fibre.
Improve digestion
Quick efficient digestion of food upstream 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 most 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/or diluted so has a minimal 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. 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! One preparation containing xylitol seems sensible because xylitol further helps kill microbes.
  • 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
  • antibiotics,
  • the Pill and HRT,
  • acid blocking drugs especially proton pump inhibitors,
  • some antidepressants which cause dry mouth.
Change the bugs in the gut
Probiotics have not lived up to their therapeutic potential. I suspect this is because the single most important probiotic is bacteroides and this cannot exist outside the human gut. Oxygen kills it within minutes. There is no probiotic on the market which contains bacteroides. We acquire bacteroides at birth and retain those bacteria for life. Aerobic bacteria may be helpful and are present in many naturally fermented foods - details of how to prepare these can be found in "Gut and Psychology Syndrome".

Kefir is useful because it contains a combination of bacteria that produces a toxin that kills yeast.

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. A patient of mine has a recipe for Growing Mutaflor so that one batch lasts a long time!
  • .
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 sugar 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!
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.
Bacteroides including Prevotella species
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! I am currently trying rifaxamin 400mgs tds for 14 days (perhaps longer) to tackle upper fermenting gut by anaerobes. The idea here is to use a dose of rifaxamin sufficient to kill the billions of bacteria in th eupper gut but not the trillions in the lower gut. Initially this must be done with a protein fat only diet (no carbs or vegetable fibre). See GAPS diet for details. Ideas at [[4]]

Replete with probiotics
Because of the above problems choose your probiotic strategy carefully! The strategies I use are:

Naturally fermented foods - as detailed in the GAPS diet.

Prebiotics provide fermentable substrate for bacteroides. Foods naturally rich in prebiotics are pulses, onions and leeks (if they make you fart, they are full of prebiotics!). See Wikipedia: Prebiotic (nutrition). One can purchase fructo-oligosaccharides, which are a prebiotic.

Kefir - because it kills yeast. It also supplies a safe bacteria for bulking stools and preventing constipation. It 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 to avoid sugar being fermented to D-lactate. Kefir is rich in lactobacillus.

Mutaflor - see Growing Mutaflor if E. coli is low.

Faecal bacteriotherapy is the only way to replace bacteroides.

See also Yeast problems and candida

See also Ulcerative colitis and phosphatidylcholine (PC) in the gut, which explains the importance of the right fats and oils in the diet for normal gut function and flora.

This may prove to be a very useful treatment. Neem is extremely safe. It seems to work by making microbes less sticky so they do not stick to the lining of the gut. This may explain its broad spectrum of action. It works well as a mouth wash for the same reason. I suggest 10mls of neem multiguard after food.

Overview of advice in 500 words - Fermenting gut - the Full Monty
Now that you have digested all the evidence for, all the thinking about, and many treatment ideas for the fermenting gut, here is your reward - a short summary of the approach which can be used by anyone with suspected gut fermentation problems or, indeed, anyone with gut problems and/or diagnosis of IBS. Have a look at Fermenting gut - the Full Monty.

Related Tests
Related Articles
External links
  • Badbugs - a website/resource/forum set up by a sufferer infected with Blastocystis hominis and Dientamoeba fragilis who is dedicated to sharing the results of her extensive reseach into diagnosing and treating these "bad bugs".
  • Lemle MD.Hypothesis: Chronic fatigue syndrome is caused by dysregulation of hydrogen sulfide metabolism. Medical Hypotheses 2009;72(1):108-9. Epub 2008 Sep 16. mdlemle@yahoo.com
  • Protea Biopharma Press Conference, London 28.5.09. Prof K de Meileir, Chris Roelant, Marc Fremont.
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Senior Member
  • Urinary hydrogen sulphide test for dysbiosis; a simple, at-home test you can order through www.proteabiopharma.com. Here is some rationale for the test by Dr. Myhill:

We have good evidence that the fatigue in chronic fatigue syndrome is caused by poor mitochondrial function. We have a test to measure this - the Mitochondrial Function Profile blood test(1) - and we can see if this dysfunction occurs because of micronutrient deficiency, or something which is blocking mitochondria.

Hydrogensulfide (H2S) fits into this picture because it inhibits mitochondrial function, and this provides a nice explanation as to why the abnormal gut flora can cause fatigue.

Work done by Professor Kenny De Meirleir has shown that people with chronic fatigue syndrome consistently have higher levels of hydrogen sulfide in their urine compared to normal controls. Furthermore, this is associated with high levels of bacteria which are not normally found in the gut flora.

He has identified bacteria in the gut responsible for this. The idea is that an overgrowth of Streptococcus, Enterococcus and Prevotella bacteria results in foods being fermented to produce hydrogen sulfide, and it is this which causes the problems.

He further noted that overgrowth of these different bacteria correlated with symptoms.

In particular, Enterococcus is associated with:

  • Headache
  • Arm pain
  • Shoulder pain
  • Myalgia
  • Palpitations
  • And sleep disturbance

Streptococcus correlated with:

  • Post-exertional fatigue
  • Photophobia
  • Mind going blank
  • Cervical gland lymphodynia [swollen lymph nodes in the neck]
  • Palpitations, dizziness and faintness


Hydrogen sulfide (H2S) is produced by normal cells and is an important gaseous signal molecule a little bit like carbon monoxide and nitrous oxide. It is involved in regulation of blood pressure, neuro-transmission, muscle relaxation and the regulation of inflammation.

  • Endogenous hydrogen sulfide [produced in the body] plays a role in regulating blood pressure, body temperature, vascular smooth muscle, cardiac function, blood flow to the brain, and is an important modulator of the hypothalamus-pituitary-adrenal axis.
  • At low dose levels exogenous H2S [from sources outside the body] produces a hibernation like state in mice with a decreasing core body temperature, apnea-like sleep, reduced heart and respiratory rates and a marked metabolic drop.
These symptoms are often experienced by CFS/ME sufferers.

In excess, H2S acts as a mitochondrial poison inhibiting many enzymes involved in oxidative phosphorylation [manufacture by the mitochondria of energy in the form of ATP]. It also interferes with oxygen transport in red blood cells, a little bit like carbon monoxide. Almost always we see low levels of glutathione in CFS, which is a sulfur containing molecule.

From an evolutionary perspective, mitochondria are organelles descended from ancient eukaryotic sulfur-using microbes, and so it is not surprising that H2S targets mitochondria. H2S inhibits immune cells such as CD8, T cells, and Natural Killer cells, so contributing to the immune dysfunction. It also impacts on the hypothalamic-pituitary-adrenal axis. It regulates the use of oxygen by mitochondria.

When gut bacteria or fungi are attacked by something like a heavy metal molecule (e.g. mercury), they have a special defense mechanism (called a "resistance gene") that produces Hydrogen Sulfide (H2S) gas, which binds to the attacker and neutralizes it. Subsequently this highly toxic and poisonous H2S gas is created in the gut. H2S can impair the immunity system, especially in the area of neutrophil function, which is used to fight the original yeast in the gut, and hence one can hit a vicious cycle. H2S is very similar to mercury, in that it can bind to many of the things that mercury binds to and inactivate them. In other words, all the bad things that mercury can do, as described here, H2S can do. H2S can also convert the safer Inorganic mercury to the more dangerous Organic mercury, as described here. H2S has a very special circular relationship with the heavy metals; and therefore, it is a very special gas.
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Senior Member

"Hydrogen sulfide (H2S) has been getting more attention lately in connection with

As I think many of you know, the methylation cycle and glutathione are both parts of the overall sulfur metabolism in the body, as is the production of H2S.

The various reactions that can produce H2S in the body include parts of the
human metabolism, and also the metabolism of certain bacteria in the gut.

The first place I heard about H2S in connection with CFS was from Dr. Amy Yasko, who
emphasizes that people who have genetic polymorphisms in their cystathionine beta synthase (CBS) enzyme, along with a methylation cycle block, will tend to generate more H2S.

I also heard about sulfur-related topics from Susan Owens, who runs the Yahoo
sulfurstories group and the group about trouble with Epsom salts. On the latter
topic, I have speculated that people who don't tolerate Epsom salts well may
have sulfate-reducing bacteria (SRBs) in their gut, which convert sulfate to
hydrogen sulfide. SRBs have been found in the gut in some people. As far as I
know, the human metabolism does not have a pathway for chemically reducing
sulfate, so I think the bacteria must be responsible for converting the sulfate to more chemically reduced species, such as H2S and eventually sulfite, and thus producing the sulfate intolerance in these people. Sulfate is the main form of sulfur normally excreted in the urine.

In the human metabolism, the two enzymes of the transsulfuration pathway, i.e.
cystathionine beta synthase (CBS) and cystathionine gamma lyase (CGL), aka
cystathionase, are capable of producing H2S from cysteine or homocysteine.

In my 2008 revision of the Glutathione Depletion--Methylation Cycle Block
hypothesis, described in the set of PowerPoint slides in the files section of
the cfs-yasko group's website, I proposed that cysteine becomes oxidized to cystine in
the oxidative stress condition present in CFS, and that CGL then catalyzes a pathway
starting with cystine that produces hydrogen sulfide and thiosulfate. I based
this on research summarized by Martha Stipanuk, who has worked a lot in this
area with rats.

I just heard a few days ago from Prof. Ruma Banerjee, who is probably the
leading researcher in the area involving the human sulfur metabolism and vitamin
B12, that the human version of CGL does not use cystine as a substrate under
normal conditions, which the rat version does. I'm not sure yet whether it
would do so under oxidizing conditions, so this aspect of my hypothesis is still
a little "up in the air" at this point. It is clear from our clinical study (also
in the files section of the cfs-yasko website) that the methylation cycle block in CFS is linked to
glutathione depletion, so there has to be a way to explain where the sulfur
metabolites that are dumped down the transsulfuration pathway when there is a
methylation cycle block actually go, since they don't go into making more
glutathione. This aspect needs more research.

Marian Lemle has proposed that hydrogen sulfide is involved in CFS. I had the privilege of meeting her at the
Reno conference in March, where we both presented poster papers. She is also a
friend of Prof. Dick Deth, who works primarily on autism, and who is very knowledgeable about the sulfur metabolism. Marian got
her paper published in the journal Medical Hypotheses, and she also presented
her hypothesis to the federal CFS Advisory Committee last October. Marian didn't
get into the biochemistry of how H2S is produced (she is a science writer, not a
scientist per se), but she noted that the symptoms of H2S poisoning are similar
to those of CFS, and that was the basis for her hypothesis that H2S is involved
in CFS. I thought this was interesting work, and I have interacted with her
concerning how her work and mine might be connected.

Dr. de Meirleir and his group have found that hydrogen sulfide is elevated in
the urine in the most severely ill M.E. patients, and his company is now
offering a qualitative urine test for H2S. His view seems to be that the H2S is
being produced by bacteria in the gut in the severely ill patients, and I think
he is probably right about that.

I think that we will eventually be able to tie all of this together, but it will
take some careful lab work to nail it down.

Here are some speculations about what goes on: First, the sulfur in the human
body originates in the diet (and supplements, if they are used). It comes in as
sulfur-containing amino acids (methionine, cysteine, cystine, and taurine), and
also in the form of sulfate and a few other sulfur-containing species. The
sulfur in whatever amount of H2S is produced, by either the human metabolism or
the bacteria in the gut, must originate in the diet (and supplements) People who bathe in Epsom salts will absorb some sulfate through their skin.

In a normal, healthy person, a lot of the sulfur-containing substances are
digested in the gut and are absorbed into the blood, while some remain in the
gut. Also, some are transported into the gut via the bile, from the liver.
Bacteria in the gut therefore have access to some of it, and I think we are all
familiar with the rotten egg smell that can be associated with flatus, which
comes from hydrogen sulfide. So it is not unusual for bacteria in the gut to be
producing hydrogen sulfide.

It is quite common in CFS that there is dysfunction in the digestive system.
This can include low stomach acid, slow gastric motility, insufficient secretion
of pancreatic enzymes, insufficient secretion of bile, gluten or casein
sensitivity, fructose or lactose intolerance, candidiasis, dysbiotic bacteria,
intestinal permeability (leaky gut), a variety of other food sensitivities,
secretory IgA deficiency, protozoal or helminthic parasites, and others.

Under these circumstances, I think it is quite likely that less of the
sulfur-containing substances will be absorbed into the blood, and more will be
metabolized by bacteria in the gut. The results would likely be less methionine
available for the body's use (including for the methylation cycle), and more
hydrogen sulfide produced by bacteria in the gut, which can be absorbed into the blood, have
toxic effects on the cells of the body, and be excreted in the urine.

As I noted in a recent post, some of the people who have not responded to the
simplfied treatment approach for lifting the methylation cycle block appear to
be low in methionine. If there is not enough methionine available, the
methylation cycle will operate slowly, even if the partial block has been
lifted, because there is not enough "cargo" to be carried around this cycle or
to feed the transsulfuration pathway.

I think this fits in well with what Dr. de Meirleir has reported. If
sulfur-containing substances aren't being absorbed into the body, they would be
available to feed the bacteria in the gut.

I've also noted that in some of the most severely ill PWCs, the condition of the
gut is so dysfunctional that they are not able to derive much nutrition from
their food. Again, I think this is consistent.

So what does this mean for treatment? I think it means that if a person is
treated early enough in their illness, when their gut is still functioning
relatively well, the simplified treatment approach is likely to work. If their
methionine is low, they may also need to supplement it, or to increase their
protein intake in general, perhaps together with betaine HCl to augment stomach
acid and digestive enzymes to help break down the protein in the gut, so that
the amino acids can be absorbed.

If a person is severely ill, so that the digestive system is no longer able to
deliver much nutrition to their body, then I think it is likely that the
hydrogen sulfide level in their urine will be elevated, as Dr. de Meirleir has
reported, because the absorption of the sulfur-containing substances will be
lowered. In these cases, it seems reasonable to suspect that many of the
serious symptoms that are experienced are effects of hydrogen sulfide. Also in
these cases, there may need to be intravenous feeding until the gut is in better
condition, and the simplified treatment approach may not help until the gut is
in condition to absorb nutrients, and the methionine level is high enough that
the methylation cycle is being fed with it.

So how do we know where to draw the line between cases in which the simplified
treatment will work, and cases that will require additional efforts? I think
that measuring the methionine level in a urine amino acids test is one thing
that can be done, and perhaps the H2S test being offered by Dr. de Meirleir's
company would be another way to gauge this. This is all very new, so we don't
have experience to go on yet, but I do think all of this will fit together."

Best regards,

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Senior Member
Mitochondria link

Hydrogen sulfide is produced in small amounts by some cells of the mammalian body and has a number of biological signaling functions. (Only two other such gases are currently known: nitric oxide (NO) and carbon monoxide (CO).

The gas is produced from cysteine by the enzymes cystathionine beta-synthase and cystathionine gamma-lyase. It acts as a relaxant of smooth muscle and as a vasodilator. Eventually the gas is converted to sulfite in the mitochondria by thiosulfate reductase, and the sulfite is further oxidized to thiosulfate and sulfate by sulfite oxidase. The sulfates are excreted in the urine. Due to its effects similar to nitric oxide (without its potential to form peroxides by interacting with superoxide), hydrogen sulfide is now recognized as potentially protecting against cardiovascular disease. The cardioprotective role effect of garlic is caused by catabolism of the polysulfide group in allicin to H 2S, a reaction that could depend on reduction mediated by glutathione.

Though both nitric oxide (NO) and hydrogen sulfide have been shown to relax blood vessels, their mechanisms of action are different: while NO activates the enzyme guanylyl cyclase, H2S activates ATP-sensitive potassium channels in smooth muscle cells. Researchers are not clear how the vessel-relaxing responsibilities are shared between nitric oxide and hydrogen sulfide. However there exists some evidence to suggest that nitric oxide does most of the vessel-relaxing work in large vessels and hydrogen sulfide is responsible for similar action in smaller blood vessels.

Cytochrome c oxidase, also known as complex IV, is the final protein complex in the electron transport chain. The mammalian enzyme has an extremely complicated structure and contains 13 subunits, two heme groups, as well as multiple metal ion cofactors – in all, three atoms of copper, one of magnesium and one of zinc.

This enzyme mediates the final reaction in the electron transport chain and transfers electrons to oxygen, while pumping protons across the membrane. The final electron acceptor oxygen, which is also called the terminal electron acceptor, is reduced to water in this step. Both the direct pumping of protons and the consumption of matrix protons in the reduction of oxygen contribute to the proton gradient. The reaction catalyzed is the oxidation of cytochrome c and the reduction of oxygen.

Cyanide, sulfide, azide, and carbon monoxide all bind to cytochrome c oxidase, thus competitively inhibiting the protein from functioning, which results in chemical asphyxiation of cells. Methanol in methylated spirits is converted into formic acid, which also inhibits the same oxidase system.

"The myelin sheath is made of phospholipids whose synthesis depends on cytochrome c oxidase activity"

Histotoxic hypoxia
is the inability of cells to take up or utilize oxygen from the bloodstream, despite physiologically normal delivery of oxygen to such cells and tissues. Histotoxic hypoxia results from tissue poisoning, such as that caused by alcohol, narcotics, cyanide (which acts by inhibiting cytochrome oxidase), and certain other poisons like hydrogen sulfide (byproduct of sewage and used in leather tanning).

Histotoxic hypoxia refers to a reduction in ATP production by the mitochondria due to a defect in the cellular usage of oxygen. An example of histotoxic hypoxia is cyanide poisoning. There is a profound drop in tissue oxygen consumption since the reaction of oxygen with cytochrome c oxidase is blocked by the presence of cyanide

Histotoxic literally means that the cells have been poisoned. There is no problem getting the oxygen to the tissue - the lungs, blood and circulatory system are all working just fine. However, the tissue is unable to use the oxygen. Cyanide leads to histotoxic hypoxia by poisoning the systems that utilize oxygen to create energy and preventing them from using the oxygen. Even though there is plenty of oxygen there, the cells experience a lack of oxygen and are affected as if there was too little/no oxygen available.

Oxidative phosphorylation

Cytochrome c oxidase
Histotoxic Hypoxia
Hydrogen sulfide
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Senior Member
Treatment of a Positive H2S Test Result

Dr Myhills,

If one has the wrong bacteria in the upper gut, then H2S could be produced as a result of this fermentation process. So, improving gut function and restoring the normal gut flora will be centrally important to tackling gut fermentation producing hydrogen sulfide.

What we need, is an antibiotic which is not absorbed systemically and is specific to those hydrogen sulfide-producing bacteria.

This could be a prescription drug, or a herbal preparation. Initially, I would suggest rifaximin, which is a non-absorbable antibiotic passes through stomach and into intestines without being absorbed into the blood stream], widely used for travelers' diarrhea with very few side effects and low risk of antibiotic resistance. It must be taken with high dose actively fermenting probiotics such as Kefir.

The joy of the urine test for hydrogen sulfide is that we have a way of checking as to whether or not we are making progress with the gut. My view at this stage therefore is to put in place as many of the above interventions as is reasonably possible to do, and take rifaximin 200mg three times daily for three days, then a maintenance dose of 200 mg daily and then re-check a urine test to see if we are making progress.

It may be that eating foods low in sulfur could be helpful, but sulfur is also essential for normal body biochemistry, and my view is that one should concentrate on gut function to ensure quick and efficient digestion into desirable end products rather than further food avoidance.

One could go on further to do more detailed analysis of gut flora to see which bacteria are present and, again, I will try to make this test available.** However, my guess is that this will not affect treatment, at least in the early stages when the aim is to restore gut function.

Probiotics - essential to introduce the friendly bacteria to the gut. Kefir is an excellent cheap source of friendly bacteria.

Professor De Meirleir's treatment regime includes all the above factors, but he believes that heavy metals may also be implicated here because they have a synergistic effect with H2S to make it more toxic.

Indeed, we know already that mercury vapor from dental amalgam can have a profound effect on gut flora. He suggests that H2S may combine with heavy metals, and the resultant compound distorts proteins to form prions. These prions then distort other normal proteins in what is known as the "rotten apple" effect. This magnifies the underlying poisoning by heavy metals and H2S.

So, heavy metal detoxification is likely to be an important part of the treatment program.


  1. Try using Bismuth subsalicylate (BSS). This is commonly known as Pepto Bismol. Each tablespoon or chewable tablet contains 262 mg, and it aggressively soaks up hydrogen sulfide and pulls it out of your body (by turning the hydrogen sulfide into bismuth sulfide). At the same time, it has antibacterial activity that may kill off both the unfriendly bacteria and the biofilms they live in. One to two tablets 3 to 4 times a day will be enough (adjust the dose so that the gas is not too stinky). Give it a 3 to 4 week trial and see if it helps. Then post your results on our community bulletin board and let us know if it helps you. The concern is that the Pepto Bismol may also kill off some of the healthy bacteria, so I would stop it after 3 to 4 weeks. Warning — it is normal for Pepto-Bismol to turn your stools a black color. There appears to be a striking dose-dependent response with BSS: 400 mg / 100 g of dry food completely suppresses cecal hydrogen sulfide release in rats, whereas one fifth of this concentration has no demonstrable effect. What this means in English is just taken enough Pepto-Bismol to keep the flatulence from having a nasty smell.
  2. Similar to bismuth, zinc acetate binds hydrogen sulfide. Zinc deficiency is common and causes immune dysfunction in CFS and fibromyalgia, so taking 25 mg a day of zinc is helpful overall. More than this can be toxic when taken long-term however.

The following foods are helpful when one has a fermentation problem: Complex carbohydrates (e.g. brown rice, buckwheat, rice cakes), vegetables, cranberries and blueberries (non-sweet fruit).

Healing The Gut


Disclaimer, The information in this thread is not intended to be medical advice. The information is meant to inspire and motivate you to make your own decisions surrounding your health care and dietary needs. It is intended for educational and informational purposes only. You should not rely upon any information found on this thread to determine dietary changes, a medical diagnosis or course of treatment. Readers should perform their own research and make decisions in partnership with their own health care providers. Any statements or claims about the possible health benefits obtained from any foods or supplements mentioned on this thread have not been evaluated by the Food & Drug Administration and are not intended to diagnose, treat, cure or prevent any disease. This thread is for educational purposes only to document that recovery is possible.
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Donate Advocate Demonstrate
great posts - too much for me to read as I'm already feeling sick but we really should archive it somewhere so much good information.
Most of the first posts are taken directly from Dr Myhills' excellent, but massive website.


Senior Member
Thanks for all your hard work, Radio! I'm trying your recommendations (and Dr. Myhill's) for mitochondria repair.

But I have to take issue with this: "A traditional Chinese diet does not include dairy products, gluten grains, alcohol and very modest amounts of fruit!"

Southern Chinese eat a lot of rice but Northern Chinese eat wheat in the form of noodles. This is how pasta got to Italy -- via the Italian explorers (was it Marco Polo??).

Chinese also eat fruits, just not the ones Westerners are familiar with. Lychee, for instance. And they, like all other cultures, have long had fermented drinks containing alcohol, some of them fermented from grains. And Mongolians do eat dairy products such as the kefir of mare's milk.

China has a lot of different "ethnic" groups so sweeping statements about what "they" do or don't do probably won't be accurate.


Senior Member
Thanks for all your hard work, Radio! I'm trying your recommendations (and Dr. Myhill's) for mitochondria repair.

But I have to take issue with this: "A traditional Chinese diet does not include dairy products, gluten grains, alcohol and very modest amounts of fruit!"

Chinese also eat fruits, just not the ones Westerners are familiar with. Lychee, for instance. And they, like all other cultures, have long had fermented drinks containing alcohol, some of them fermented from grains. And Mongolians do eat dairy products such as the kefir of mare's milk.
"A traditional Chinese diet does not include dairy products, gluten grains, alcohol and very modest amounts of fruit!"

Yes, One of the first steps in my healing journey was eliminating dairy and gluten from my diet. Also, I have added many traditional Chinese foods to my recovery plan. :thumbsup:

Question : What is the key to nutritional healing?

A diet that complements are genetic weakness and toxic micro-organism imbalances.
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Senior Member
@Radio I am actually thinking Oregano Oil. I did 2 weeks and did wonders. Would that work??
Hey lnester7,

We need to test urinary hydrogen sulphide to see if in fact we do have dysbiosis. Then we can try different treatment options. Oregano oil is very powerful and could be strategy in obliterating these toxic micro-organisms.