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Leaky gut

MagazineSeptember 1997 (Vol. 8 Issue 6)Leaky gut

One of the most overlooked causes of disease is not just what we eat but how well we digest it, particularly in our small intestine

One of the most overlooked causes of disease is not just what we eat but how well we digest it, particularly in our small intestine.

Think of your gut as a one way fence. The lining of the gut is permeable that is, small particles of food are able to pass through it into the other cells of our body but in a healthy body, these "holes" are small enough to keep contained molecules which might otherwise cause harm.

Beside containing the nutrients we need and which will pass through our permeable gut, food contains a toxic load the body needs to be protected from. This protection is supplied by complex mechanisms which support one another: intestinal secretions, the lining of the intestine and certain white blood cells (J Intern Med Suppl, 1990; 732: 145-54). It is through this complex system that the digested, important portions of food are able to pass through to the body, while toxins are barricaded out.

This intestinal barrier is supported by the liver, through which all food substances must pass before entering our circulatory system to be carried to other tissues and organs. Certain cells in the liver remove absorbed molecules which are too large to pass through the gut. Liver enzymes also transform certain chemicals produced in the gut by oxidation and with such substances as the amino acid glutathione (GSH) for excretion into bile and for circulation to the kidneys.

Nevertheless, the cost of this detoxification is high; free radicals are generated, and antioxidants like GSH are consumed in large quantities (Ann Rev Nutr, 1991; 11: 141-157; Biochem Pharmacol, 1978; 27: 1805-13).

Whenever this intestinal barrier is damaged in any way, the number of free radicals and carcinogens in the liver's oxidase system are increased. In fact, this sort of toxic overload, where extra "toxic" bile is produced and backs up into the pancreatic ducts, may be the major cause of chronic pancreatic disease (Lancet, 1983; ii: 375-8).

A damaged intestinal barrier function can also cause disease directly. Whenever this natural permeability of the gut is increased, it stimulates allergic type responses to foods and components of normal gut flora.

Leaky gut syndrome is one of a number of disorders associated with increased intestinal permeability, where the one way gates of the gut, in effect, open too wide. A number of conditions have been shown to be accompanied by a leaky gut. These include inflammatory and infectious bowel diseases (Gastroenterology, 1989; 97: 927-31), chronic inflammatory joint diseases (Clin Exp Rheumatol, 1990; 8: 75-83), skin conditions like acne, psoriasis and dermatitis (Br J Dermatol, 1983; 108: 33-7), and many diseases triggered by food allergy or specific food intolerance, including eczema, urticaria, and irritable bowel syndrome (Lancet, 1981; i: 1285-6), chronic fatigue syndromes (Ridgen, Cheney, Lapp, Galland, unpublished results), and even chronic hepatitis (Gastroenterology, 1991; 100: 513-9).

Increased gut permeability may play a primary role in causing these diseases, or it may be a consequence of it, but by causing immune system reaction, liver dysfunction and pancreatic insufficiency, it creates a vicious cycle. In most cases, the role of increased intestinal permeability in these sorts of patients often goes unrecognized.

Causes of leaky gut

A leaky gut is caused by exposure to substances which damage the lining of the intestine. The commonest causes of damage are infectious agents (viral, bacterial and protozoan) (Scand J Infect Dis, 1984; 16: 339-44; Ann Rheum Dis, 1991; 50: 91-4), alcohol (Lancet, 1984; i: 79-82), and non steroidal anti inflammatory drugs (Br J Rheumatol, 1987; 26: 103-7). Other causes include hypoxia (too little oxygen) of the bowel (such as occurs during open heart surgery or shock) (Ann Thorac Surg, 1993; 55: 1080-6) and chemotherapy drugs (J Pediatr Gastroenterol Nutr, 1989; 9: 301-6).

Whatever causes leaky gut, once the condition has developed, it can be self perpetuating.

Allergy

The relationship between food sensitivities and the leaky gut is complex and circular. In experimental trials, children and adults with eczema, urticaria or asthma triggered by food allergy show that they have higher gut permeability than those of who don't have these conditions (Allergy, 1989; 9: 47-51). This may indicate that allergies and food sensitivities may be caused by a leaky gut. But by the same token, whenever allergic subjects are exposed to allergenic foods, gut permeability sharply increases. What this probably means is that an increase in intestinal permeability is both important as a cause of food allergy and also the result of food allergy.

Malnutrition

Nutrients are ordinarily absorbed through the cells. If the lining of the gut is damaged, this absorption decreases, possibly causing malnutrition, which only makes other problems worse (Am J Med, 1979; 67: 1077-84). Under normal conditions, the lining of the intestine has the fastest production of new cells of any tissue in the body; old cells slough and a new lining is generated every three to six days (N Eng J Med, 1978; 298: 1393-402). That's why its important for the metabolic demands of this normally rapid cell turnover to be met if a damaged gut lining is to be able to heal. If they aren't, the gut becomes even more permeable and you become even more malnourished.

Bacterial Dysfunction

A kind of low level dysfunction, called dysbiosis, is caused by ordinarily unvirulent organisms which mainly do their damage by altering the metabolic or immune responses of the body (J Advancement Med, 1993; 6: 67-82). The situation where the immune system begins to react to (and destroy) normal gut flora is one example that has been implicated in the development of conditions such as Crohn's disease and ankylosing spondylitis (Br J Exp Pathol, 1980; 61: 92-6). Recent research suggests that this kind of gut bacterial sensitization is an early complication of altered permeability (Baillieres Clin Rheumatol, 1989; 3: 271-84).

This phenomenon is a well known and studied side effect of non steroidal anti inflammatory drugs (NSAIDs). Single doses of aspirin or of indomethacin increase cellular permeability, in part by inhibiting the synthesis of the protective fatty acid prostaglandin (Br J Rheumatol, 1987; 26: 103-7). Long term exposure to NSAIDs leaves the gut highly inflamed and highly permeable. This condition can only be prevented or reversed by the antibiotic metronidazole (Dig Dis Sci, 1993; 38: 417-25; Gut; 1992; 33: 1204-8). This is significant because it demonstrates the involvement of bacterial toxins in causing this vicious cycle. Patients with rheumatoid arthritis receiving NSAIDs have been shown to have increased antibody levels to the bacteria Clostridium perfringens (Br J Rheumatol, 1992; 31: 443-7).

Changing the flora of the gut through the use of antibiotics, synthetic and natural, probiotics such as acidophilus (the "friendly bacteria"), and diet is one strategy for breaking the vicious cycle in leaky gut syndromes. Usually, patients whose arthritis is alleviated by a vegetarian diet are those where the diet alters gut ecology; if the diet doesn't do this in a particular case, the arthritis usually isn't improved (Br J Rheumatol, 1994; 33: 638-43).

Stress on the liver

The liver of leaky gut patients works overtime to remove oversized food molecules and to oxidize gut toxins, causing increased production of free radicals. This, in turn, causes damage to liver cells and sends by products into bile, producing a toxic bile capable of damaging bile ducts and backing up into the pancreas (Lancet, 1983; ii: 375-8). In attempting to rectify all this, the liver depletes its reserves of certain amino acids (JAMA, 1994; 272: 1845-50). We know that this happens in liver diseases caused by alcohol (Lancet, 1984; i: 79-82).

Diagnosing a leaky gut

You should suspect that you have a leaky gut if you have any of the conditions listed in the box right. Your practitioner can measure your gut permeabily through the lactulose/mannitol challenge test (box, p 2) .

If you come up with a normal lactulose/mannitol test result, repeat it after you've eaten a meal of your most common foods. If the test meal produces an increase in lactulose excretion (which signifies a leaky gut) or a decrease in mannitol excretion (signifying malabsorption of food), it's likely that you have specific food intolerances. Further testing for food allergy is then warranted. Once you've been maintained on a stable elimination diet for four weeks, you should repeat the lactulose/mannitol challenge after a test meal with the foods permitted on the elimination diet. A normal result will assure you that all major allergens have been identified. An abnormal result indicates that more detective work is needed.

If the initial fasting mannitol absorption is low, your doctor should suspect that you aren't absorbing food well. Look for evidence of celiac disease, intestinal parasites, ileitis (inflammation of the intestine), small bowel bacterial overgrowth and other disorders classically associated with intestinal malabsorption and have them treated. After eight weeks of therapy, have the the lactulose/mannitol challenge repeated. If you are excreting more mannitol, it shows your absorption has improved. The lactulose/mannitol test may be used to detect celiac disease or intolerance to gluten (J Clin Gastroenterol, 1985; 7: 232-6), particularly in patients where allergy to gluten doesn't cause diarrhea but failure to thrive, schizophrenia or inflammatory arthritis.

In the case of relatively mild celiac disease or inflammatory bowel disease, your mannitol absorption may not be affected but the lactulose absorption will be elevated. A recent study published in the Lancet found that the lactulose/ mannitol ratio was an accurate predictor of a relapse in patients who'd previously suffered from Crohn's disease (Lancet, 1993; 341: 1437-9).

If your initial fasting lactulose is elevated, or if the initial fasting lactulose/mannitol ratio is elevated, your practitioner should also consider the possibility of mild bowel disease or gluten allergy.

Other factors

l What drugs are you taking (particularly chemotherapy that is, cell killing drugs like methotrexate or NSAIDs)? Do you drink alcohol? If so, stop and have the lactulose/mannitol challenge repeated three weeks later. If the result has become normal, you will have identified the likely cause of leaky gut. If it is not, bacterial sensitization may have occurred. This may be treated with antimicrobial drugs and probiotics.

My preference is a combination of citrus seed extract, berberine and artemisinin (the active alkaloid in the herb Artemisia annua), which attacks enterobacteriaceae, bacteroides, protozoa and yeasts (Tokai J Exp Clin Med, 1990; 15: 417-23; Am J Dis Child, 1975; 129: 866; J Infec Dis, 1987; 155: 979-84; Nature; 1967; 215: 527-8).

If you don't drink or take these drugs, look into your diet. Recent fasting or crash dieting may increase permeability. Eat a nutritionally sound diet for three weeks and repeat the test.

If you have chronic arthritis, it may be difficult to stop NSAIDs. But there are many other alternative anti inflammatory therapies, including essential fatty acids and antioxidants (WDDTY vol 2 no 12 and vol 5 no 5). Changing the NSAID used may also be helpful. NSAIDs like indomethacin, which recirculate in the liver and the gut, are more likely to damage the small intestine than are NSAIDs that are not excreted in bile. Nabumetone is the only presently available NSAID that does not increase small intestinal permeability.

Do you have any hidden infections? The possibilities include recent acute viral or bacterial enteritis, intestinal parasites, HIV infection and infection with the candida albicans yeast. Stool testing is useful in identifying these. Have your gut permeability test six weeks after starting your appropriate therapy.

Do you have any food allergies? Take the lactulose/mannitol challenge test fasting and again after eating a test meal. At the Hospital St Vincent de Paul in Paris, permeability testing has been effectively used with allergic infants to determine which dietary modifications their mothers need to make while breast feeding and which of the "hypoallergenic" infant formulas they needed to avoid in order to relieve their symptoms (Allergy, 1994; 49: 295-8).

If your test shows you have abnormal fasting permeability, you have more gut lining damage than patients with normal fasting permeability and will take longer to heal.

Do you have gut bacterial overgrowth? This can be caused by too low stomach acid (hypochlorhydria) or maldigestion (Am J Gastroenterol, 1990; 85: 231-7). You can have this confirmed by a hydrogen breath test. Most of the damage resulting from bacterial overgrowth is caused by bacterial enzyme activity, which destroys the protective mucus coat of the gut. If you haven't had intestinal surgery or blockages, but test positively for bacterial overgrowth, it's likely that you have hypochlorhydria, which could be due to chronic gastritis (inflammation of the stomach lining) from infection with the Helicobacter pylori bug. Triple therapy with the drug bismuth and antibiotics may be needed, but it is not presently known whether such treatment can reverse atrophic gastritis or whether natural, plant derived antimicrobials can achieve the same results.

Bacterial overgrowth due to hypo chlorhydria tends to be a chronic problem that recurs within days or weeks after antimicrobials are discontinued. Keith Eaton, a British allergist who has worked extensively with the gut fermentation syndrome, finds that taking 500 mg of L-histidine, twice daily, improves gastric acid production in allergic patients with hypochlorhydria, probably by increasing gastric histamine levels.

Supplementing your diet with the stomach acid betaine hydrochloride is usually helpful, but intermittent short courses of bismuth, citrus seed extract, Artemesia, colloidal silver and other natural antimicrobials are often needed. Your treatment needs to go on for a least 12 weeks, for complete healing. Then repeat the lactulose/mannitol test at the end of 12 weeks (while you are taking the antimicrobials) to see if you are better. The most sensitive test for recurrence of bacterial overgrowth is not the lactulose/mannitol assay but the breath hydrogen analysis.

!ALeo Galland

This article was adapted from a paper which first appeared in Townsend Letter for Doctors and Patients, (911 Tyler Street, Port Townsend, WA 98368-6541 Tel: 360-385-6021).


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