Leaky gut syndrome (LGS) has become a popular diagnosis which has considerable credence in the popular media but has few friends in conventional medical circles. Recent evidence, however, suggests that it does exist and can be easily caused by use of acid-suppressant drug therapy. Its clinical significance is still debated.
The gut – and its wall
The gut is a long, clever tube with the primary function of digesting and absorbing nutrients, which are then absorbed and distributed in the blood stream to nourish the body. It also harbours billions of bacteria and yeasts that perform beneficial, and occasionally potentially harmful, functions and it acts as a conduit for drugs, minerals, hormones and toxins excreted by the liver via the bile. These very different functions require the lining of the gut to differentiate between essential nutrients and unwanted bacteria and toxins, literally separating the ‘wheat from the chaff’. This is achieved in part by an ‘intelligent filtering’ mechanism of the gut wall. But this can break down allowing in undesirable components from the diet or from organisms resident in the gut. This, in turn, can cause ill health.
The gut wall is mainly composed of enterocytes, which are covered, especially in the stomach, a layer of mucus which contains a bacterial soup. Each individual cell is bound to its neighbours by tight junctions which are zinc-rich subcellular structures that some
researchers think become disrupted in leaky gut syndrome.
Absorption through the wall
Throughout most of the gut water and dissolved vitamins, many minerals, simple sugars and other small molecules can be absorbed. This mainly occurs in the duodenum and small intestine and to a much lesser degree in the large bowel. The fluid and nutrients are taken by blood vessels to the liver. Fats, fat-soluble vitamins and many drugs are absorbed by a combined action of bile from the liver and pancreatic digestive enzymes and the emulsified complex is taken up into lymphatic vessels that by-pass the liver and trickle into the blood stream.
A healthy gut wall is required to contain this complex chemical mix until the large molecules derived from foods are sufficiently broken down by digestive processes to allow absorption to take place.
Damage to the wall
Damage to the gut wall can occur as a result of anti-inflammatory drugs used in the treatment of arthritis and from powerful drugs that suppress gastric acid output, termed proton pump inhibitors, PPIs.
A recent study on the effect of the PPI drug esomeprazole by doctors in Philadelphia assessed their effect on gut permeability using a concentrated solution of sucrose (ordinary table sugar). Sucrose is a disaccharide (composed of two simple sugar molecules) that has to be broken down before it can be absorbed in the duodenum and small bowel. It is not produced by our own metabolism. Any that is accidentally absorbed intact must pass through the gut wall around the sides of the enterocyte cells and then enter the blood stream. It is then rapidly excreted intact in the urine. Its appearance, intact, in the urine is an indicator of gastrointestinal leakiness.
The researchers found that use of esomeprazole resulted, within days, in an increase in intestinal permeability, which presumably occurred in the upper gastrointestinal tract. This change reversed within days of cessation of the drug reflecting the rapid turnover of cells in the upper gut wall.
Other possible factors causing LGS include antibiotics, environmental toxins, nutritional deficiencies, and gastrointestinal parasitic infections. Damage to the gut wall as a result of an inflammatory disorder such as Crohn’s disease, colitis or as a result of an acute infection can also contribute to the condition.
Other tests of gastrointestinal permeability use other non-digestible sugars of varying molecular size, lactulose, mannitol or radioactive markers.
Can leakiness cause
The important issues are whether the leakiness of the gut is important in the causation of the patient’s problems, and what can, or needs to be, done about it.
Some researchers have theorised that leaky gut syndrome allows the leakage of fragments derived from partially digested proteins termed peptides. These peptides could mimic the effects of some sedating drugs like morphine or trigger inflammation in the gut wall itself.
Some peptides with opioid activity have been identified in the urine of autistic children by researchers from Sunderland. They have proposed that because they are derived from milk and wheat that excluding these foods from their diet can be beneficial. The peptides’ appearance in the urine suggests that they have reached there as a result of LGS and the incomplete digestion of these foods.
However, a recent paper by doctors at Great Ormond Street Children’s Hospital failed to find these peptides in the urine of autistic children. Furthermore a review of gluten- and casein-free diets for autistic spectrum disorder on the Cochrane Database concluded that the evidence for the use of such exclusion diets was poor and that large-scale controlled trials are needed. The author’s own limited experience of such diets is very variable.
Some practitioners argue that LGS is a causative factor in rheumatoid arthritis, asthma, diabetes and MS as well as chronic inflammatory bowel disease and chronic heart failure. It may also be present in patients with small intestinal bacterial overgrowth (SIBO) that, itself, may complicate gastrointestinal conditions including severe irritable bowel syndrome.
The mechanisms behind leaky gut syndrome in these situations may include changes in
intestinal flora, increased adherence of bacteria to the bowel wall, gut wall inflammation, immune deficiency and changes in circulation. However it is unclear whether the increase in intestinal permeability is a primary or secondary event and not all studies have found these associations.
The part played by bowel flora is not at present clear. Changes in flora could alter the function of enterocytes, their adhesion and, of course, gut transit as well as the production of undesirable immune and inflammatory effects.
For nearly twenty years it has been known that patients with Crohn’s disease, but not
ulcerative colitis, often have evidence of IgG antibodies against candida albicans and saccharomyces cerevisiae. However the presence of these antibodies does not automatically mean that they play a causative role in the disease.
As yet there is no specific treatment for LGS but various approaches are considered or are likely to be beneficial:
• Reduce inflammation in the intestinal wall by dietary change and use of anti-
• Avoidance of foods to which the person is allergic or
• Avoidance of drugs and other causative factors (see previous page)
• Improvements in bowel flora by dietary change and use of probiotic preparations
• Avoidance or limitation of alcohol for at least several weeks
• Zinc supplements have been shown to reduce intestinal permeability in patients with Crohn’s disease. In a small Italian study zinc
sulphate 110 mg three times daily for eight weeks was used in patients who were already in remission. This dose exceeds UK/US safety guidelines and should only be taken with expert advice.
• Other supplements might be helpful. Several B vitamins are essential for the health of the metabolically active enterocytes and a diet rich in omega-3 oils or supple-
ments of fish oils might have an anti-inflammatory effect
• Glutamine supplements have a reputation for being beneficial but this amino acid is only likely to be
deficient (and supplements beneficial) in malnourished or very ill patients such as those with pancreatitis.
It does seem that there is
renewed interest in the function of the gut wall in many gastrointestinal and other diseases. LGS may be a reality for some patients but its importance is as yet unclear. Whether adding this diagnosis to an exisiting gastrointestinal one is of benefit to the patient is also unclear. A degree of healthy scepticism should be combined with a little optimistic interest when considering LGS.
1 Millward C. et al. Gluten- and casein-free diets for autistic spectrum disorder. Cochrane Database Syst Rev. 2008 Apr 16;(2):CD0033498.
2 Cass H. et al. Absence of urinary opioid peptides in children with autism. Arch Dis Child. 2008 Sep;93(9):745-50.
3 Mullin J. et al. Esomeprazole Induces Upper Gastrointestinal Tract Transmucosal Permeability Increase. Aliment Pharmacol Ther. 2008;28(11):1317-1325.
4 Bonet A. et al. Glutamine, an almost essential amino acid in the critically ill patient. Med Intensiva. 2007 Oct;31(7):402-6.
5 Huang XX. Et al. Effects of enteral nutrition supplemented with glutamine and arginine on gut barrier in patients with severe acute pancreatitis: a prospective randomized controlled trial. Zhongua Yi Xue Za Zhi. 2008 Sep 9;88(34):2407-9.
6 Bjarnason I. et al. The leaky gut of alcoholism: possible route of entry for toxic compounds. Lancet. 1984 Jan 28;1(8370):179-82.
7 Sandek A. et al. The emerging role of the gut in chronic heart failure. Curr Opin Clin Nutr Metab Care. 2008 Sep;11(5):632-9.
8 Sturniolo GC. Et al. Zinc supplementation tightens “leaky gut” in Crohn’s disease. Inflamm Bowel Dis. 2001 May;7(2):94-8.
Margaret Moss comments:
'Sulphate is needed to make sulphated glycosaminoglycans (GAGS) for the gut wall. Without adequate sulphate the gut wall is leaky. Without adequate sulphate there is a shortage of digestive enzymes. So food is less efficiently broken down, and the holes in the gut are bigger. That leads to partly broken down food, eg peptides reaching the blood. One peptide is beta casomorphine, which affects the brain.'
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First Published in 2009
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