Fermentation in the gut and CFS
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I am most grateful to Dr Henry Butt from Australia for providing essential information! I spent a day with him in January 2015 and new information has been added to this webpage as a result of our discussions. Please see below for full details.
The normal state of affairs
The human gut is almost unique amongst mammals - the upper gut is a near-sterile, digesting carnivorous gut (like a dog's or a cat's) evolved 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) evolved to digest vegetables and fibre. From an evolutionary perspective this has been a highly successful strategy - it allows people who live in Northern Canada such as Inuits and Yupiks 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, all of which need cooking to be digestible. From an evolutionary perspective this has, again, been a highly successful strategy and has 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. CFS sufferers can be viewed as 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 - this is not my idea but that of a Japanese researcher Katsunari Nishihara, presented in his paper "Disclosure of the major causes of mental illness—mitochondrial deterioration in brain neurons via opportunistic infection" published in the Journal of Biological Physics and Chemistry 12 (2012) 11–18.
The stomach, duodenum and small intestine should be free from micro-organisms (bacteria, yeast and parasites - collectively referred to as microbes hereinafter). This is normally achieved by eating a Ketogenic diet - the practical details; having an acidic stomach which digests protein efficiently and kills the acid sensitive microbes; then by an alkali duodenum, which kills the alkali sensitive microbes with bicarbonate; then via 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. Please see Stomach, duodenum, small intestine and colon for a diagrammatic representation of the gut and its various constituent parts.
Anaerobic bacteria, largely bacteroides, flourish in the large bowel (or colon), where foods that cannot be digested upstream are then fermented to produce many substances highly beneficial to the body. For example, bacteroides ferment soluble fibre to produce short chain fatty acids - over 500kcals of energy a day can be generated in this way. This also creates heat to help keep us warm. The human body is made up of 10 trillion cells, whereas in our gut we have 100 trillion microbes or more, i.e. ten times as many microbes as cells! Bacteria make up 60% of dry stool weight and comprise over 500 different species. However, 99% of the bacteria are from 30-40 species.
Genova laboratories offer stool tests (please see below for Related Tests) which give us a useful handle on the digestive efficiency of the gut and the microbes present. The most important are bacteroides which are a group of anaerobic bacteria - these anaerobic bacteria outnumber aerobes by a factor of 1,000 to 1. It should be remembered that some anaerobic microbes can tolerate some oxygen - the most important of these is E coli.
So, the main types of microbes that we need to be aware of are:
- 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, as previously noted, it is estimated that over 500Kcal per day may be generated via the production of short chain fatty acids by bacteriodes fermenting soluble fibre - a very significant source of energy! They are essential for recycling of bile acids and so low levels of bile acids may indicate poor levels of bacteroides. They occupy the surface of the gut, thus preventing pathogenic species (such as salmonella, shigella and clostridia) from adhering to it and causing infection. There is no probiotic which contains bacteroides, simply because bacteroides cannot exist outside the human gut - oxygen kills bacteroides quickly. We just have to feed the gut with the right food (prebiotics) found in pulses, nuts, seeds and vegetables. If numbers of bacteroides are low then meat and meat broth provides essential building block nutrients. Also see Faecal bacteriotherapy
- E-coli. One gram of stool should contain between 7 million and 90 million E-coli microbes. 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 - please see Growing Mutaflor and also Mutaflor - description and efficacy of treatment of certain indications for further details, and in particular see page 7 of the second link for details of the studies that Dr Butt was referring to.
- Lactobacilli. These ferment sugars to lactic acid - this can be a problem for some patients because two forms are produced namely L lactate, which can be broken down and D lactate, which is the problem! Humans do not have the enzymes to break down D lactate. In cattle, D lactate acidosis can not be distinguished clinically from BSE! Lactobacilli have the potential to do good but if there is too much sugar and fruit sugar in the diet then there is potential for great harm.
- Bifidobacteria. These assist digestion and 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, as below, will flourish if numbers of the above decline for whatever reason - Nature abhors a vacuum!
- Streptococcus. This also ferments sugars 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. Again it is D-lactate which is the problem, the body cannot metabolise this, it accumulates in mitochondria and inhibits them, thus producing all the symptoms of CFS, including foggy brain. One can measure D lactate in the blood stream. Streptococcus over-growth treated with erythromycin has been shown to improve sleep quality.
- Prevotella (bacteroides in the upper gut). It is thought that these ferment to produce hydrogen sulphide. Hydrogen sulphide inhibits mitochondrial function directly. So a positive hydrogen sulphide urine test shows that 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. A brief summary of this system can be seen at Phase 1 and 2 Liver Detoxification Pathways. In summary, these phases, or stages, comprise: Stage 1 - conversion of a toxic chemical into a less toxic one, although this stage may sometimes result in a more toxic chemical, and Stage 2 - the adding of a substance to render toxins less harmful. Please see the section The liver P450 detoxification system is a major source of free radicals below. These products, caused by the fermentation of food in the upper gut, and, which have to be detoxified, 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! Please also see Alcohol intolerance in CFS - gives us a clue as to the mechanisms of fatigue.
- 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. Please see Regulation of mitochondrial bioenergetic function by hydrogen sulfide.
- Odd sugars such as D-lactate. This right handed sugar cannot be detoxified by lactate dehydrogenase, a liver enzyme. For those interested in right-handedness and left-handedness, please see Chirality (chemistry).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. Please see D-Lactic Acidosis- A Review of Clinical Presentation, Biochemical Features, and Pathophysiologic Mechanisms for further details of this review. 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 CFS, where energy delivery is impaired, one may expect detoxification to also be impaired!
Other problems caused by upper gut fermentation
- 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 - the idea here is that microbes are miniscule compared to human cells and so easily spill over into the blood stream. This is called bacterial translocation - see PubMed article on Bacterial translocation from the gastrointestinal tract. Numbers are not sufficient to cause septicaemia, but the immune system could sensitise to them, especially if they get stuck elsewhere in the body. I suspect many modern diseases can be explained by allergy to gut flora namely irritable bladder, (interstitial cystitis), prostatitis, arthritis, asthma, temporal arteritis, polymyalgia rheumatica, skin problems (urticarial, venous ulcers, rosacea, psoriasis etc), psychiatric and psychological reactions (see Nishihara's work, as linked above) and many other possibilities. Furthermore this unnecessary inflammation is wasteful of immune energy, thereby causing fatigue. See Energy Expenditure in ME/CFS: Immune wastage of energy and Rituximab
- Wind, gas, bloating from physical distension
- Foul smelling breath and hallitosis - the products of bacteria fermenting include hydrogen sulphide (stink bomb material!)
- Disturbances of normal gut movement - constipation or diarrhoea - this seems to be a feature of low E coli perhaps because E coli produces tryptophan - a precursor to serotonin which is responsible for gut motility.
- Susceptibility to infections
- Leaky gut - with leaky gut, short chain polypeptides 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 amino 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", this, therefore, makes it much more likely that these heavy metals enter the body and bioaccumulate.
- Foggy brain - the ferments such as alcohol, esters, aldehydes and other lipid soluble substances have a general anaesthetic like effect on membranes on the brain. This probably manifests by inhibiting energy delivery mechanisms to the brain. See Theories of general anaesthetic action.
- Night sweats Dr Butt suggests these may result from microbes spilling over into the blood stream to trigger such.
- 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 in the gut. If you have a clean tongue and no dental plaque then you are likely to have good gut flora. Indeed when the ketogenic diet is done well the teeth should feel glassy smooth.
- Cancer - I suspect upper fermenting gut is a risk factor for cancers of the oesophagus, stomach and large bowel - this is biologically plausible - many tumours are driven by inflammation. H.pylori infection is a known risk factor for stomach cancer as is hypochlorhydria - also a risk factor for fermenting upper gut. Barrett's oesophagus is a pre-malignant condition - I have had several patients who have got rid of their Barrett's through interventions to tackle their upper fermenting gut.
- Constellations of symptoms - for example, Drs De Meileir and Butt have shown that:
- high levels of enterococcus (a form of Lactobacillales or lactic acid bacterium - please see Wikipedia entry on Lactobacillales) are associated with symptoms of headache, arm pain, shoulder pain, myalgia, palpitations and sleep disturbance.
- high levels of streptococcus are also associated with post exertional fatigue, photo-phobia, mind going blank, palpitations, dizziness, faintness.
- low levels of E coli result in foggy brain, fatigue, constipation, food intolerance, food cravings and fatigue.
Tests for microbes in the upper gut - gut fermentation
- Look at the tongue - the tongue should be clean and pink with no fuzz or fur - this would represent colonies of bacteria and yeast.
- Feel your teeth - your teeth should feel like they do after a polish at the dentist - glassy smooth. Any roughness results from bacterial colonies called dental plaque.
- Bicarbonate challenge test - hypochlorhydria is a major risk factor for upper fermenting gut. See Tests for low stomach acid
- 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!
- Tenderness in the right iliac fossa - reflects inflammation in the lower ileum where microbial numbers start to rise exponentially. Please see Wikipedia entry on Right Iliac Fossa and also a diagrammatic view - Right Iliac Fossa
- Burning sensation in the rectum or on passing a stool reflects acidity of the stool as a result of abnormal fermentation.
- Use your nose - 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" - inflammables. I would not like to recommend this as a routine clinical test! Normal fermentation should be odourless. However, 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 situation (ie "smellies") indicates abnormal gut fermentation. The test is called the "Neurotoxic metabolite test" and can be ordered online directly from Protea Biopharma in Belgium. Please also see Professor Glenn Gibson Profile, Reading University
- Salivary VEGF - see Vascular endothelial growth factor (VEGF)- salivary test for hypochlorhydria and Heartburn
- 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. Please refer to Biolab D Lactate Test
- Hydrogen sulphide can be tested for with a urine test. Please see the Related Tests section below.
- Which bugs are there? One can look at stool samples to ascertain this. This does not tell us where microbes are living in the gut but it's a good start. The Comprehensive Digestive Stool Analysis or the Comprehensive Digestive Stool Analysis with parasitology are both helpful tests. The microbes which are thought to be the main cause of abnormal fermentation are lactobacilli (only a problem with high sugar diets), streptococcus and prevotella (bacteria) and candida (yeast). Conversely, in the fermenting gut there may be low levels of bacteroides, E coli and bifidobacteria. This is because if there is fermentation upstream, substrate is "used up" and so there is little substrate left for fermentation downstream and so the bacteroides, E coli and bifidobacteria "miss out"! A more detailed test of the actual bugs present, which includes bacteroides, is the Microbial ecology profile.
- Calculate the anion gap - this can be done from a blood test for urea and electrolytes, which is a routine blood test. It is the difference between the total of sodium plus potassium, compared to chloride and bicarbonate. The idea is that the difference is accounted for by hydrogen ions ie this is a measure of the acidity or pH of the blood. If the result is above 14 Milliequivalents per litre this suggests acidity - fermenting gut is just one cause of this. Please see Wikipedia entry on Anion Gap
What causes upper gut fermentation?
A long history of:
- Western lifestyles! A traditional Chinese diet, for example, 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
- A poor 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
- An acid gut either because of fermentation of sugars or lack of bicarbonate from the pancreas
- Modern medication
- Antibiotics which kill bacteroides - especial care is needed with metronidazole. Other antibiotics are relatively benign and probably over-maligned as a cause of gut problems. Diet is a much bigger player.
- Pill and HRT, which both suppress the immune system, encourage metabolic syndrome and are conducive to 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.
A fermenting gut may result in many problems....
....including fatigue, arthritis, urticaria, dementia, venous ulcers, chronic cystitis, asthma, immune suppression, tinnitus
Many of the above problems can be explained by allergy to fermenting microbes that spill over from the gut into the blood stream to drive allergic/inflammatory reactions at distal sites.
Mitochondrial failure results in fatigue
There is good evidence that the central pathological lesion in CFS is mitochondrial failure (CFS - The Central Cause: 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 and so the mitochondria "go slow". But we can put into place a system of anti-oxidants in order 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, as noted above. 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 of another molecule allows the toxin to become less active and more water soluble so that 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, because of poor stage 2 detox status, over 80% of Gilbert's sufferers complain of fatigue. One example of how this faulty P450 detox system, in CFS sufferers, may manifest itself is in the detoxing of alcohol. Alcohol is metabolised initially into acetaldehyde, which is a nasty toxic compound responsible for hangovers! If one has a fast stage 1 but slow stage 2 metabolism, as CFS sufferers may have, then this will be problematic because large amounts of acetaldehyde will build up. Therefore, it comes as no surprise that alcohol intolerance is almost universal in CFS sufferers - see Alcohol intolerance in CFS - gives us a clue as to the mechanisms of fatigue.
- 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 as to why so many CFSs do not tolerate prescription medication. Other reasons are that many drugs inhibit mitochondria directly, or destabilise membranes in the brain resulting in poor energy delivery to brain cells see Brain fog - poor memory, difficulty thinking clearly etc. Patients refusing medication are then often labelled as unco-operative and are dropped from medical care.
- Intoxicants arising as a result of fermentation from the upper gut.
Treatment of the fermenting gut
The definitive treatment has yet to be established. We are all on a steep learning curve here! The key thing is to sterilise the upper gut (actually it cannot be sterilized completely, but numbers kept as low as possible!) 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 a Diet of low fermentable substrate- it is sugar and refined carbohydrate that 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. Indeed, increasingly I find myself putting people on the ketogenic diet - this is additionally helpful to improve mitochondrial function - see Ketogenic diet - a connection between mitochondria and diet .
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 (Please see the External Links below). 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. They also contain fibre used 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 monosaccharides and disaccharides (ripe fruit not OK to eat!). The GAPS diet addresses fermentation by all three (i.e. anaerobic bacteria, aerobic bacteria and yeast) , the specific carbohydrate diet addresses fermentation by aerobic bacteria - please see here for details of the Specific Carbohydrate Diet - Amazon Link for 'Breaking the Vicious Cycle: Intestinal Health Through Diet' by Elaine Gottschall, MSc. See 'What Is the Specific Carbohydrate Diet?' for a brief summary. Anti candida diets address fermentation by yeast. If in doubt, I suggest starting off with a protein/fat diet for all the reasons given by Barry Groves in his lovely presentation Homo Carnivorous. The only way to really find out is trial and error.
- Once the upper gut is sterile (additional antibiotics and/or anti-fungals 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 pH 8 or above. The pH scale is a logarithmic one and so these figures represent a 10,000 fold difference in acidity.
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:
- 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.
- Take minerals through the skin by using transdermal micronutrients. 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!
- 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.
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 it is 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 and 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) - see Related Tests below. 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. There may be a role for super high doses of pancreatic enzymes - this is because where there is long standing microbial overgrowth, microbes may hide themselves under a muco-polysaccharide body armour! We call these biofilms. Indeed the management of cystic fibrosis has been revolutionised by the use of high dose pancreatic enzymes. Please see Lyme Disease and other Co-infections for further discussion on biofilms.
- Magnesium carbonate as above. Do not take this at mealtimes or stomach acidity will be neutralized - take at least 90 mins after food.
- Bile acids. Take 1 gram of bile salts with meals. Be careful - they can be irritant. 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 may 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
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 the book, "Gut and Psychology Syndrome". Please see Amazon link to "Gut and Psychology Syndrome" book
Treatment of low E-coli:
- All the above
- Feed them with prebiotics given the right substrate microbes double their numbers every 20 minutes.
- 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! It seems that once inoculated E coli will survive given enough galactose and fucose. .
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. The Taymount Clinic offers this technique in UK- see Taymount Clinic
Treatment of high Streptococcus levels:
- All the above
- Avoid all sugars 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 only 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. Streptococci are the most abundant bacteria in the mouth and strep mutans (Please see Streptococcus mutans) is largely responsible for dental plaque, tooth decay and dental abscesses. Teeth should feel glassy smooth!
- Erythromycin 500mg twice daily for 7 days or use any such antibiotic from the macrolide group of drugs. Perhaps longer than 7 days will be needed. Happily bacteroides, the most abundant probiotic, is resistant to erythromycin!
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 the upper 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 (External Links) for details. Ideas can be found in the video of Dr. Mercola interviewing Dr. Natasha Campbell-McBride
Replete with probiotics
The most important factor is to feed them correctly - see above. The single biggest problem is sugar and fruit sugar.
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 but in my practice I very rarely recommend this. It is a procedure for serious bowel pathology such as ulcerative colitis, pseudomembranous colitis or clostridium difficile.
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 that 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.
- Microbial ecology profile
- Comprehensive Digestive Stool Analysis
- Comprehensive Digestive Stool Analysis with parasitology
- Vascular endothelial growth factor (VEGF)- salivary test for hypochlorhydria
- Fermenting gut - the Full Monty
- Yeast problems and candida
- CFS - The Methylation Cycle
- Faecal bacteriotherapy
- Growing Mutaflor
- Alcohol intolerance in CFS - gives us a clue as to the mechanisms of fatigue
- Energy Expenditure in ME/CFS: Immune wastage of energy and Rituximab
- Transdermal micronutrients
- Hypochlorhydria - lack of stomach acid - can cause lots of problems
- Pancreatic exocrine function
- CFS - The Central Cause: Mitochondrial Failure
- Brain fog
- Hypoglycaemia - the full story
- Ketogenic diet - a connection between mitochondria and diet
- Phospholipid exchange
- Yeast problems and candida
- Ulcerative colitis and phosphatidylcholine (PC) in the gut
- Lyme Disease and other Co-infections
- Ketogenic diet - the practical details
- My book The PK Cookbook - Go Paleo-ketogenic and get the best of both worlds.
- 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". The abbreviation "CDD" in his text on treating Blastocystis hominis stands for the Centre for Digestive Diseases in New South Wales, Australia.
- With respect to these matters, a patient of mine, Debbie Williams, has linked me to this very useful file - First Line Treatment Protocol for resistant Blastocystis Hominis infection.
- The GAPS diet
- Gut bacteria and Mind control - fix your brain, fix your gut - Prof. Simon Carding, Leader of the Gut Health and Food Safety Research Programme, Institute of Food Research and Norwich Medical School at the University of East Anglia, describes our current understanding of the human gut and its relationship with its human host and introduces the provocative proposal that gut microbes influence when, what and how often we eat and whether we stay healthy or succumb to disease. The information is presented in the form of a video.
- Amazon Link for 'Breaking the Vicious Cycle: Intestinal Health Through Diet'
- 'What Is the Specific Carbohydrate Diet?'
- 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. firstname.lastname@example.org
- Protea Biopharma Press Conference, London 28.5.09. Prof K de Meileir, Chris Roelant, Marc Fremont.
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