Chronic Candidiasis Sensitivity Syndrome

and

Biofilm

Since first described by Truss in 1980, chronic candidiasis sensitivity syndrome, also called yeast syndrome, has been controversial. The basis for the syndrome is that a subset of people with nonspecific somatic and neuropsychiatric symptoms may respond to antifungal preparations along with dietary restriction of refined carbohydrates and yeast-fermented foods. Although the term “yeast overgrowth” is commonly used, Candida overgrowth on mucosal surfaces is uncommonly documented. Relapse following successful therapy is the rule. One possible explanation for decades of experience and observation is that sensitive individuals may be reacting immunologically to gastrointestinal and/or vaginal Candida biofilm. Candida albicans and other Candida species are known to be highly immunogenic. C. albicans contains at least 178 antigens, mostly mannoproteins. One antigen, hyphal wall protein 1, is homologous to α- and γ-gliadin. Candida mannoproteins are well documented to stimulate histamine and prostaglandin E2 release. Immunological abnormalities common in chronic fatigue syndrome (which overlaps with chronic candidiasis sensitivity syndrome), such as reduced numbers of natural killer cells and an increased Th2 cytokine profile, are common in candidiasis.

Biofilm formation by C. albicans and other Candida species is universal. Candida biofilms on implanted medical devices and on the oral, esophageal, and vaginal mucosa are well documented. When Candida quorum sensing detects enough organisms to initiate biofilm mode, antifungal resistance genes are activated and drug efflux pumps are upregulated. This provides Candida with heightened levels of defense within biofilm, where they are also resistant to host cell-mediated and antibody immune responses. Among the other mechanisms of resistance to antifungal drugs by Candida biofilms are diminished diffusion of antifungals into biofilm matrix, binding of antifungals by β-glucan in the matrix, reduced metabolic rates, and the presence of persister cells.

The presence of Candida biofilm communities evokes powerful local and systemic host immune responses in sensitive individuals. Candida biofilm communities may explain why certain people respond to antifungal and diet without evidence of thrush, Candida vaginitis, or other forms of Candida overgrowth. Candida biofilm would also explain the frequent relapses seen in these patients, as therapeutic relapse and refractoriness are hallmarks of biofilm infections. Sensitivity to Candida has even been proposed as the cause of the increasing prevalence of celiac disease.

Clinical strategies to chronic candidiasis sensitivity syndrome that include biofilm disruption may hold the key to therapeutic success. Candida biofilm matrices include high amounts of β-(1-3)-glucan and cellulose; β-glucanase and cellulase have been shown to disrupt Candida biofilms. Serratia pepetidase has also been shown to reduce Candida biofilm populations. The use of a hydrolytic enzyme formulation developed by Dr. Stephen Olmstead has been shown in the laboratory to disrupt Candida biofilms and improve sensitivities to antifungal agents. When this enzyme formulation is incorporated into a program of 2 or more antifungal agents, Saccharomyces boulardii, an anti-Candida diet, probiotics, and prebiotics, clinicians may be able to offer patients more effective therapy and longer-lasting clinical results than have previously been possible. More research into the nature of and host immune responses to gastrointestinal Candida biofilms is needed.