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 a problem?
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.

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