Candida

GUT MUCOSAL PERMEABILITY, CANDIDA, FOOD ALLERGY
AUTOIMMUNITY AND IMMUNODEFICIENCY: POSSIBLE LINKS

By Ari Wojdaru, Ph.D.

In recent years there has been increasing interest amongst both members of the medical profession and their patients in the possibility that food may be a cause of unexplained diseases. Unfortunately, this interest has produced more excitement and controversy than scientific research, and although evidence is now accumulating to support a role for diet in the management of conditions as diverse as migraine, eczema and Crohn’s disease, the mechanisms of the relationship between food and disease remain poorly understood.

The purpose of this series of three articles is to clarify the present state of our knowledge in gastro-intestinal integrity and its relation to chronic Candidiasis, food allergy, autoimmunity and immunodeficiency.

The present article covers gut mucosa permeability as the origin of the problem, which will be followed in the next issues by Candida, food allergy autoimmunity and immunodeficiencies.

Assessment of Intestinal Integrity

Imbalance of Gut Mucosal Permeability is the Origin of the Problem

The development of the gastro-intestinal tract in mammals is characterized by the integrated maturation of its many functions. Digestion and absorption of nutrients, the critical factor for survival, depends on the state of development of the gastrointestinal tract. As well as digesting, absorbing and eliminating, the gut acts as a barrier between the internal and external environment.1,2

Control of macromolecular uptake is dependent on a number of factors present either within the intestinal lumen or on the intestinal mucosal surface.3 These factors include both nonimmunological and immunological processes. Nonimmunological factors (intestinal flora, secretion, gastric barrier, peristaltic movement and liver filtration) help to control the proliferation of microorganisms present in the gastrointestinal tract, aid in decreasing adherence of organisms to the gut surface and are important in limiting the available antigen mass that may otherwise overwhelm local immunological defense mechanism and penetrate the mucosal barrier or enter the systemic circulation.4-8 Mucosal immunological factors (secretory IgA, cell mediated immunity, other immunoglobulins), especially the common mucosal associated Lymphoid tissue (MALT), is present at all epithelial surfaces that are in contact with the external environment, is largely independent of the systemic immune response and is governed by antigenic stimuli at epithelial surfaces. A failure or abnormality in one of these mechanisms can result in symptoms such as anaphylaxis, rhinitis and skin rashes, classified as food allergy.2

In normal conditions, factors within the intestinal lumen of the surface of epithelial cells and within the lamina propria combine to limit the access of antigens to systemic circulation. After macromolecular ingestion by the intestinal absorptive cells, most of the ingested material is broken down by lysosomal enzymes in digestive vacuoles9. That portion which escapes breakdown is transported out of the cell by an exocytotic mechanism. Any interference with intracellular capacity to digest macromolecules could therefore result in an increased intestinal transport of molecules.10 A number of factors can affect the stability and lability of lysosomes.11

For example, high concentration of vitamin A, radiation, bacterial and fungal endotoxins and exotoxins can increase the lability of lysosomes, causing the rupture of lysosomal membranes in various cellular systems. On the other hand corticosteroids stabilize the lysosomal membrane and can interfere with the normal digestive function of these intracellular organelles. Thus, inhibition of lysosomal function could in turn result in enhanced transport of intestinal antigens, by decreasing intracellular breakdown.

Mucosal immunodeficiency is another factor which may contribute to an enhanced macromolecular absorption. Secretory IgA is the predominant immunoglobulin present in intestinal secretions. This class of immunoglobulin acts to protect the intestinal epithelium from the uptake of intestinal bacteria, fungi and viruses, as well as of antigenic and toxic macromolecules.12.13 It is possible, therefore, that in the absence of secretory IgA, ingested proteins are absorbed from the gut in increased amounts and can stimulate a systemic immune response. The basis for possible immune-mediated disease in these cases may be the increased uptake of intestinal pathogens or macromolecules, which can interact with the circulating antibody and complement a target organ to produce characteristic autoimmune response.14 Furthermore, patients with selective IgA deficiency have a greatly increased incidence of Coeliac disease compared with the normal population. This is undoubtedly due to an increased uptake of gluten or its breakdown products.15 In a similar manner, intestinal pathogens or their byproducts can penetrate the intestinal mucosa, resulting in a generalized malabsorption.16

The proposed mechanisms by which viruses or bacteria may initiate autoimmunity is through sharing of a common antigenic determinant between a virus or other microorganism and a host cell component. Such shared epitomes can be though of as a three dimensional conformation site or a stretch of amino acids forming a peptide. Thus, an antiviral or bacterial immune response would recognize both the microorganism determinant and the shared host self antigen. These cross-reacting antibodies and immune cells generated by molecular mimicry may in large part be responsible for the presence of autoreactive antibodies and cells found in many infections in humans.17

Recently, there is considerable interest in the concept of enhanced intestinal permeability and its possible role in the pathogenesis and pathophysiology of a variety of intestinal and extraintestinal disorders.18 Bacterial flora is greatly influenced by eating habits, and chemical contamination of the foods plays a significant role in the integrity of intestinal mucosa.

There are over 100 different microorganisms present in the digestive system. Most important are:

• Candida,
• Lactobacilli,
• Enterococci,
• Enterobacteria,
• Streptococci,
• Staphylococci,
• Bifidobacterium,
• Bacteroides,
• Clostridum, and
• Peptococci.

Under normal conditions these bacteria produce a variety of vitamins which are necessary for the human development and function.19 But due to the typical western diet (increased dietary carbohydrates) and usage of broad spectrum antibiotics, corticosteroid hormones and birth control pills, the internal environment has become “polluted” and the balance between humans and their microflora has changed significantly.20 This change in indigenous intestinal flora is mainly an overgrowth of Candida Albicans.

Drug resistant aerobic and anaerobic bacteria or their toxins through one of the above mentioned mechanisms (effect on lysosomal enzymes, induction of IgA deficiency) can increase the permeability of gut mucosa. This observation could mean that the intestinal tract represents a potential site for the absorption of bacterial breakdown products, such as endotoxins and enterotoxins of proteolytic and hydrolytic enzymes or of ingested food antigen that normally exists in the intestinal lume.23 Excessive uptake of food, bacterial, fungal and viral antigens into the circulation can induce immune response in the form of IgG, IgM, IgA and IgE and may contribute to adverse reactions such as allergies and autoimmunities, which are manifested as clinical disease states.23 Therefore, the measurement of circulating antibodies against specified antigens of intestinal bacterial and fungal flora is of considerable importance in the pathogenesis of immunologically mediated diseases, including food allergies and autoimmunities.

References

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