Candidiasis Part I: Pathogenicity Mechanisms

Candidiasis is a fungal infection linked to any form of Candida species (1). These infections can occur in various places on or inside the body, e.g. esophagus, genitals, intestines, mouth, scalp, skin. For example, oral thrush, evidenced by white patches on the tongue or other areas in the mouth are common in infants, as well as the elderly and people with compromised immune function, e.g. HIV, cancer (2). Oral thrush can cause mouth sores and make it difficult to swallow (3). This type of candidiasis can also reach down into the esophagus making swallowing even more painful. At times, candida can be become systemically invasive leading to candidemia which is defined as candida infection within the bloodstream. Candida albicans is the most common form of candida organism causing candidiasis, but there are multiple types in existence known to cause problems (4).

Gastrointestinal candidiasis (GC) is a well-known problem amongst functional and integrative medicine providers, but is an underappreciated condition in conventional medicine, despite decades of clinical research (5). In autism, for example, GC commonly causes or contributes to digestive symptoms, e.g. bloating, flatulence. GC also can contribute to the accumulation of various toxic compounds such as arabinose known to alter neural function and other biochemical imbalances (6).

This article series discusses various aspects of chronic candidiasis as it relates to different health conditions and explores different mechanisms of pathogenicity, laboratory testing and treatment intervention. In part #1, we begin with examples of pathogenicity mechanisms of candida: arabinose toxicity, leaky gut (intestinal permeability), invasive protein and immune deficiency.

Arabinose Toxicity

Arabinose, a sugar aldehyde, closely related to a sugar alcohol known as arabinitol, has been used for years as an indicator of invasive candidiasis (7). An article in 1995 by W. Shaw, Ph.D. (8) detailing high levels of arabinose in twins with autism 1 eventually led to further research into this compound and its prevalence to various health disorders such as Alzheimer’s disease. Arabinose can bind with the amino acid lysine found in various proteins which then cross-links with arginine that exists in adjoining proteins (9). This interaction can alter normal biological function throughout the body, including neuronal structures through the development of a glycation end-product called Pentosidine. This structure (complex of arabinose-lysine-arginine) has been linked to various adverse neurological reactions, including myelin damage, neurofibrillary tangle development and Alzheimer’s disease (10).

Finally, the epsilon amino group of lysine is a functional component of many enzyme systems that also depend on cofactor binding from vitamin B6, lipoic acid and biotin (11). High amounts of pentosidine, which block these binding sites, may lead to functional deficiencies even when nutritional intake of these nutrients is adequate.

Leaky Gut (Intestinal Permeability)

Invasive candida can also play a role in leaky gut (LG), also known as increased intestinal permeability, by piercing either through the apical membrane of an epithelial cell or damaging the tight junctions. It does this through an invasive protein described below.

The lining of the digestive system is a complex network of epithelial structures, cells and immune globulins that are all involved in absorption of nutrients, neutralization of toxins and immune function. This complex network is often referred to as the mucosal barrier. When aspects of the barrier are disturbed a leaky gut can develop.

LG is a disorder of the digestive system where there is a loss of the integrity of the intestinal lining that normally prevents toxins from crossing over into the blood stream. LG is known as a causative or contributing factor in various health conditions such as chronic fatigue, allergies, arthritis, autoimmune

diseases/disorders and other inflammatory diseases (12). The idea that various substances can breach the boundary between cells in the intestinal system gaining access to the bloodstream and eliciting an immune response is well known in the study of diarrheal-based disorders and celiac disease (13).

The basic structure of the intestinal lining is represented by villi (greater surface area capacity), microvilli (made up of epithelial cells that compose the function of digestion) and smaller structures, called the ‘tight junctions (TJ),’ which keep the intestinal lining functional and intact. TJs help to maintain the cohesiveness of epithelial cells. They are made up of various proteins such as zonulin and occludin, which are linked to actin fibers. This complex of cellular structures aides in maintenance of muscular contraction, movement and shape (14). The function of the TJs is to keep large macromolecules from crossing the digestive lining which can trigger adverse immune reactions causing inflammation, autoantibody responses and tissue damage.

Invasive candida can produce tentacle structures called hyphae that pierce through the epithelial cell lining in the area of the tight junction. These hyphae are induced from a candida specific protein called invasin (15). This invasin protein allows the candida organism to directly pierce through the surface lining of the digestive tract either through the apical membrane or between epithelial cells at the tight junction.

Immune Dysfunction

The immune suppressant chemical gliotoxin is most often linked to Aspergillus fungus where it is known to inhibit various aspects of immune function such as depletion of neutrophils, eosinophils and macrophages (16). Gliotoxin can also indirectly lead to systemic inflammation (17) and mitochondrial damage (18).

Candida organisms have been researched in their production of various compounds too which can damage the immune system, including immunotoxins like cell-wall mannan catabolites (19) and a gliotoxin-like compound (20). The gliotoxin link to candida has been controversial (21), but various fungal compounds like those described here and others are important factors to consider in all cases of chronic candidiasis.

Conclusion

There are many other pathogenicity mechanism linked to candida infections, but those discussed in this article are important when evaluating a patient suffering with various chronic health issues, whether it is autism, autoimmune disorders, chronic digestive disorders, dementia, immune deficiency, food allergies or fatigue.

In part 2 of this article series we will explore the various laboratory testing options for chronic candidiasis, both from a conventional medicine and integrative medicine standpoint, as it is important to understand the pros and cons of each.

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