Fermentation in the gut and CFS

From DoctorMyhill

1 The normal state of affairs
2 Bugs in the upper gut
3 Other problems caused by upper gut fermentation
4 Tests of bugs in the upper gut - gut fermentation
5 What causes upper gut fermentation?
6 Why a fermenting gut can cause fatigue
7 Tests for liver detox ability
8 Treatment of the fermenting gut
9 Related Tests
10 Related Articles
11 References

I am most grateful to Dr Henry Butt from Australia for providing essential information!

The normal state of affairs

The stomach, duodenum and small intestine should be free from micro-organisms (bacteria, yeast and parasites - hereon called bugs). This is normally achieved by eating a Stone Age Diet, having an acidic stomach which digests protein efficiently and kills the acid sensitive bugs; then an alkali duodenum, which kills the alkali sensitive bugs with bicarbonate; then bile salts (which are also toxic to bugs) and pancreatic enzymes to further digest protein, fats and carbohydrates. The small intestine does more digesting and also absorbs the amino acids, fatty acids, glycerol and simple sugars that result.

Bugs flourish in the large bowel, where foods that cannot be digested upstream are then fermented to produce many substances highly beneficial to the body. This also generates heat to help keep us warm. The human body is made up of 10 million million cells, in our gut we have 100 million million bugs or more, i.e. ten times as many! Bugs make up 60% of dry stool weight, there are over 500 different species, but 99% of bugs are from 30-40 species.

R.E.D. Laboratories in Belgium offer the Faecal microbial analysis, in which they can measure the amount of different bacteria in a stool sample. Per gram of stool we should have:

Total bacterial count between 10 thousand million (10 billion) and 1 million million (1 trillion).
Total anaerobe (oxygen hating) count between 1 hundred million and 1 million million
Bacteroides (fragilis and urealyticus) 90 million to 950 thousand million ie most!
Bifidobacterium between 5 million and 500 million
Lactobacillus between 500 thousand and 10 million

And extras:

Eubacterium less than a thousand million
Prevotella less than 500 million (a member of bacteroides which has specialised to live in the upper gut)
Porphyromonas less than 500 million
Clostridium less than 500 million
Peptococcus less than 100 thousand.
Others
Total aerobe count between 10 million and 100 million
E-coli between 7 million and 90 million

And extras:

Enterococcus less than 500 thousand
Staphylococcus less than 200 thousand
Streptococcus less than 300 thousand
Yeasts less than 10 thousand
Others

So:

Bacteroides. These are by far and away the most abundant bugs. It is bacteroides which allow us to digest cellulose and make short chain fatty acids. This is the main source of food for the colonocytes, the cells lining the bowel and if this is low, then it will result in atrophy of the colon. Short chain fatty acids also protect us from hypoglycaemia. Indeed, it is estimated that up to 540Kcal per day may be generated - a very significant source of energy! They are essential for recycling of bile acids, so low levels of bile acids would indicate poor levels of bacteroides. They occupy the surface of the gut so preventing pathogenic species (such as salmonella, shigella and clostridia) from adhering and causing infection. There is no probiotic which contains bacteroides. This is because it is also a potential pathogen! We just have to feed the gut with the right food (prebiotics) found in pulses, nuts, seeds and vegetables.
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.
Streptococcus. This ferments to produce large amounts of lactic acid. This gives a tendency to acidosis. Lactic acid is metabolised in the liver by lactate dehydrogenase, so high levels of this may indicate bowel overgrowth with streptococcus. Fermentation produces two isomers of lactic acid, namely L-lactate and D-lactate. It is D-lactate which is the problem, the body cannot metabolise this, it accumulates in mitochondria and inhibits them.
Prevotella (bacteroides in the upper gut). These ferment to produce hydrogen sulphide. Hydrogen sulphide inhibits mitochondrial function directly.

Problems could arise either from having the wrong bugs in the lower gut (large intestine), or having any bugs in the upper gut (stomach, duodenum, jejunum, small intestine).

Bugs in the upper gut

In some patients we can see bacteria, yeasts and possibly other parasites existing in the upper gut, which means that foods are fermented there instead of and before being digested. When foods get fermented they produce all sorts of unwanted products which have to be detoxified by the liver cytochrome P450 detox system. These products include:

Alcohols such as ethyl alcohol, propyl alcohol, butyl alcohol and possibly methyl alcohol. These would be metabolised by stage one into acetaldehyde, propylaldehyde, butylaldehyde and possibly formaldehyde. Alcohol and acetaldehydes result in foggy brain, "toxic brain", feeling "poisoned" and so on. Alcohol also upsets blood sugar levels. This makes the sufferer crave sugar and refined carbohydrates - the very foods bugs need in the upper gut to ensure their own survival. This is arguably a clever evolutionary ploy by bugs to ensure their own survival!
Noxious gases such as hydrogen sulphide, nitric oxide, ammonia and possibly others. Hydrogen sulphide is known to inhibit mitochondria and block the oxygen carrying capacity of haemoglobin. It also greatly increases the toxicity of heavy metals.
Odd sugars such as D-lactate. This right handed sugar cannot be detoxified by lactate dehydrogenase, a liver enzyme. If D-lactate is present, then it could point to a problem with gut fermentation. It may result in lactic acidosis. These patients typically present with episodic metabolic acidosis (usually occurring after high carbohydrate meals) and characteristic neurological abnormalities including confusion, cerebellar ataxia, slurred speech, and loss of memory. In a review of 29 reported cases, for example, all patients exhibited some degree of altered mental status. They may complain of or appear to be drunk in the absence of ethanol intake. Indeed, this phenomenon is much better described in the vet world. D-lactate is a recognised cause in cattle of neurological manifestations. Furthermore, products of fermentation are thought to be a cause of laminitis in horses. Indeed, the encephalopathy of liver failure can be treated by gut only antibiotics to wipe out unwelcome overgrowth of fermenting gut flora. D-lactate is fermented from sugars, including fruit sugars. This is a further reason to cut out sugar and fruit strictly from the diet! One molecule of sugar generates two molecules of D-lactate.
Other things I don't yet know about!

In theory the above toxins should all be detoxified by the P450 cytochrome system, but in practice some of these can spill over into the systemic circulation with a simple poisoning effect and resultant production of free radicals and inhibition of mitochondria.

Tests of bugs in the upper gut - gut fermentation

Biolab Gut fermentation profile measures levels of alcohol in the blood. It also looks for short chain fatty acids, which are desirable products of fermentation by friendly bacteria in the large bowel.
D-lactate can be measured by a simple blood test following a carbohydrate meal.
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 Faecal microbial analysis.

What causes upper gut fermentation?

A long history of:

Western lifestyles! The Chinese do not eat dairy products, fruit, gluten, grains or alcohol!
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
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.

Genetic: some people simply have genetically poor detox ability. One example of this, of course, is Gilbert's syndrome, where conjugation with glucuronide (stage 2 detox) is lacking. There are two steps to detoxification: the first is an oxidation reaction which may make some toxins more toxic! Many CFS sufferers have fast stage one and slow stage two metabolism, which means they have a P450 system which initially produces more rather than less toxic stress! So, for example, over 80% of Gilbert's sufferers complain of fatigue. One example is alcohol. This is metabolised initially into acetaldehyde, which is a nasty toxic compound responsible for hangovers! Alcohol intolerance is almost universal in CFS sufferers.
An acquired metabolic lesion as a result of nutritional deficiency. For example, many of these P450 cytochrome enzymes are highly dependent on metal co-factors such as zinc, magnesium, or selenium, B vitamins and essential fatty acids.
Toxins produced from normal metabolism e.g. detoxifying neurotransmitters, products from immune activity, breakdown products from damaged tissues etc
Overwhelming toxins from the outside world, such as persistent organic pollutants, or of course prescribed drug medication or social drugs of addiction (caffeine, alcohol). This probably explains why so many CFSs do not tolerate prescription medication. They then get labelled as unco-operative and are dropped from medical care.
Intoxicants arising as a result of fermentation from the upper gut.

Tests for liver detox ability

We can do genetic tests (such as single nucleotide polymorphisms or SNIPs) through Genova laboratories.Genova also offer functional teststo look at stage one and stage two detoxification.

Treatment of the fermenting gut

The definitive treatment has yet to be established. We are all on a sharp learning curve here! 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 bugs most love to ferment. The diet needs to be low glycaemic index (see Hypoglycaemia) and rich in raw or lightly cooked vegetables. This is because these foods contain a range of natural antimicrobials to inhibit bacterial overgrowth in the upper gut, together with many enzymes essential for their own digestion and fibre for fermentation in the large bowel by friendly bacteria into short chain fatty acids. With fruit, only berries permitted!
Eat pulses, nuts, seeds and vegetables, i.e. foods rich in probiotics. These provide food for bacteroides in the large bowel which ferment them to short chain fatty acids. This is the fuel for the cells lining the gut, without which they atrophy. It is also the fuel which mitochondria can switch to when blood sugar levels fall low (for example during sleep). The best sources are in pulses, vegetables, nuts and seeds.
Acid stomach and alkali duodenum - An acid stomach helps to kill bugs which are acid sensitive, whilst an alkali duodenum helps to kill bugs 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 (Hypochlorhydria) by a simple saliva test. 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.

Improve digestion

Quick efficient digestion of food means that there is less available to be fermented downstream. One may need:

Acid supplements: Indeed, there may be a role for vitamin C as ascorbic acid. Ascorbic acid is acid and so improves digestion of protein. It is also toxic to all microbes including bacteria, yeast and viruses as well as being an important anti-oxidant - indeed the eventual receiver of all electrons from free radicals. Humans, guinea pigs and fruit bats are the only mammal species which cannot make their own vitamin C and we have to get it in food. Scaling up from other mammals we should be consuming 2-6 grams daily (a hundred fold more than the government RDA of 30mgs daily!). One could get the dose just right so that ascorbic acid with food sterilises the upper gut, but is absorbed and has no effect on the lower gut. If one takes excessive vitamin C it will cause diarrhoea as too much gets into the lower gut, kills off the bugs there and empties the gut completely!
Pancreatic enzymes see Pancreatic exocrine function. The need for these could be tested by doing a Comprehensive digestive stool analysis (CDSA). A dose would be 1-3 capsules of Polyzyme Forte (BioCare) with meals depending on the size of the meal, or creon 10,000iu 1-2 with meals.
Magnesium carbonate as above
or Bile acids. These can be measured as part of a CDSA but ask specificially for them as they are not a part of the basic package. Take 150mgs with meals. Apparently prevotella, the bug shown by Kenny de Meirleir to be a major fermenter, is susceptible to bile acids.

Improve the lining of the gut:

Chewing gum. The parotid salivary gland provides a rich source of endothelial growth factor (indeed, this is what John McLaren Howard measures in his hypochlorhydria test) which stimulates growth of the lining of the gut. Chew, because this stimulates flow of saliva. Sugar-free, additive-free gum please!
Dr Butt recommends the intake of red meat and soya bean protein for vegetarians (although he considers this very much "second best").
Dr Butt recommends glutamine in a slow release capsule in order to bypass stomach acidity, correcting antioxidant status (superoxide dismutase, Co-enzyme Q10 and glutathione peroxidase).

Avoid

antibiotics,
the Pill and HRT,
acid blocking drugs especially proton pump inhibitors,
some antidepressants which cause dry mouth.

Change the bugs in the gut

Having done all the above, one can then consider direct action to change the bugs in the gut.

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.
Prebiotics. It is vital that E-coli is given with the prebiotic galactose (galactose oligosaccharides) mainly found in pulses and nuts. These will ferment in the large bowel to produce wind (hydrogen and carbon dioxide) – this only becomes foul smelling if other foods are poorly digested.

Treatment of low numbers of Bacteroides

All the above, especially prebiotics
Dr Butt recommends looking for a probiotics which contain high amounts of Bifido and Lactobacillus including Lactobacillus casei and Lactobacillus rhamnosus because these lactobacilli do not ferment to make D-lactate. OR avoid sugar strictly!

Progress can be monitored by cognitive function – that is to say the symptom of foggy brain should improve.

Treatment of high Streptococcus levels:

All the above
Avoid glucose and fructose strictly – each molecule of glucose and fructose will produce two molecules of lactic acid and create a marked tendency to acidosis. Dr Butt is Chinese and he points out that Chinese people do not eat fruit at all. Only the wealthy Chinese do and then very occasionally. Glucose and fructose is potentially very damaging to the body because it gets fermented by streptococcus into D-lactate. This is another mechanism by which sugars can result in foggy brain.
Erythromycin 500mg twice daily for 7 days or any such macrolide. Perhaps longer. Happily bacteroides, the most abundant probiotic is largely resistant to erythromycin!
Magnesium carbonate and pancreatic enzymes. One can monitor progress through the foggy brain symptom – this should improve and as it does so one can tail off the Erythromycin, but continue with an E-coli probiotic.

Treatment of High Enterococcus

All the above
Kefir contains bacteriocins which inhibit streptococcus. But it also contains lactobacillus plantarum, which can ferment sugar to D-lactate, so avoid sugar strictly if this is your problem! L. Plantarum has good anti-inflammatory action which makes it a desirable probiotic in inflammatory bowel disease.

Prevotella species

There does not appear to be an antibiotic that Prevotella is sensitive to, but it can be reduced by taking bile salts. These are also available on prescription as Ursodeoxycholic acid and I would suggest 150mg with meals, perhaps more!

Replete with probiotics

For this to be effective one should take high doses of actively fermenting probiotics. I like to use Kefir, which is easily grown on many substrates (I use soya milk) and one sachet lasts a lifetime since a new culture can be grown from the previous. See Probiotics and Kefir. I suggest one cupful after meals. Avoid sugar and fruit when using Kefir. This is rich in lactobacillus. For E coli use mutaflor – I have not yet tried culturing mutaflor but it should be possible in theory.

Related Tests

References

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