Abstract
Candida overgrowth (CO) can induce an avalanche of health problems. Its hyphal wall contains epitopes that can trigger not only gluten type antibodies (celiac disease) but also a plethora of mannan related antibodies targeting Gq coupled GPCRs. These latter can disrupt autonomic receptors, inducing POTS, loss of taste and smell, and many other symptoms. These mannan auto-antibodies also disrupt chemotactic cytokine receptors (CCRs) that can induce pain, psoriasis, alopecia areata, vitiligo and many other maladies. They also target T cells that otherwise suppress latent viruses, e.g., EBV. Hyphae also release candidalysin, a toxin that suppresses growth of competing intestinal bacteria, triggers inflammasomes, and causes hypercitrullination. Anti-citrullinated peptide antibodies (ACPAs) are produced. B cells exposed to hyper citrullination develop citrullinated receptors. ACPAs and CCRs may jointly induce viral reactivation from infected B cells. EBV, latent in virtually all humans and now free to circulate, is targeted by these same ACPAs. EBV nuclear material is released and antinuclear antibodies (ANAs) may emerge. Hyphae also trigger the release of histamine and tryptase from mast cells. Tryptase and mast cells have been tightly linked to the trifecta of mast cell activation syndrome (MCAS), hypermobility spectrum disorder (HSD), and POTS in addition to long Covid (LC) and probably anti-phospholipid syndrome (APS). Hyphae are also linked to periodontitis. Bacteria are generally considered to be the culprits, but Candida hyphae and its biofilm facilitate their pathogenesis. Periodontitis is linked with and may be a sentinel risk indicator for cancer, dementia, autoimmune disease, ASCVD and chronic disease in general. D3 and tryptophan oppose the invasive hyphal transition of Candida, which responds by releasing indoleamine dioxygenase that degrades tryptophan. This altered tryptophan metabolism is characteristic of all of these. Ultimately hyphae may be directly or indirectly involved in gut dysbiosis, including periodontitis, to the detriment of healthspan. The approach is conceptual not empirical.