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Microbes & Immunity

MINI-REVIEW
Candida hyphae and healthspan: Hypothesis

Patrick W. Chambers*
Department of Pathology, Torrance Memorial Medical Center, Torrance, California, United States of
America

Abstract

Candida is traditionally considered an opportunistic pathogen. However, recent
research, accelerated by COVID-19, has raised thought-provoking questions about
the limitations of this view. Dietary carbohydrates and ethanol have been shown to
enable its pathogenic transition. Its hyphae express epitopes that may initiate celiac
and Crohn’s diseases. Hyphal mannan is potentially linked to Gq-coupled G-protein
coupled receptors. Antibodies to these receptors include chemotactic cytokine
receptors, which may mediate the escape of latent Epstein–Barr virus. Candida
hyphae induce mast cells to release histamine and tryptase, which are associated
with paroxysmal orthostatic tachycardia syndrome, mast cell activation syndrome,
and hypermobility spectrum disorder—conditions frequently observed in long
COVID (LC). Hyphae are also implicated in periodontitis, a condition linked to and
potentially serving as a sentinel risk indicator for cancer, dementia, autoimmune
disease, atherosclerotic cardiovascular disease, and chronic diseases in general.
Candida yeast and hyphae can produce their own indoleamine dioxygenase (IDO),
which antagonizes host IDO, impacting tryptophan metabolism. Altered tryptophan
*Corresponding author: metabolism is observed in cancer, dementia, autoimmune diseases, and LC. Candida
Patrick W. Chambers overgrowth (CO) also releases candidalysin, a toxin that suppresses competing
(pwc@gte.net) intestinal bacteria, triggers inflammasomes, and causes hypercitrullination, a process
Citation: Chambers PW. associated with several autoimmune diseases and cancers. In addition, CO produces
Candida hyphae and healthspan: aspartyl protease, leading to the release of zonulin from intestinal epithelial cells,
Hypothesis. Microbes & Immunity. which increase intestinal and endothelial permeability – hallmarks of autoimmune
2025;2(3):145-161.
doi: 10.36922/mi.4736 diseases. Candida-induced acetaldehyde amplifies the harmful effects of a genetic
variant, highly prevalent in Americans, linked to cancer, dementia, and autoimmune
Submitted: September 2, 2024
diseases. The gut microbiome is increasingly recognized as critical to overall health,
Revised: September 9, 2024 and hyphae may play a major role in determining its composition. In this review,
Accepted: November 11, 2024 the roles of cholecalciferol, tryptophan, and magnesium in counteracting the yeast-
to-hyphae transition and invasion are explored. The approach presented here is
Published online: December 12,
2024 conceptual rather than empirical.
Copyright: © 2024 Author(s).
This is an Open-Access article Keywords: Periodontitis; Mast cell; Cancer; Dementia; Zonulin; Candida; Microbiome
distributed under the terms of the
Creative Commons Attribution
License, permitting distribution,
and reproduction in any medium,
provided the original work is 1. Introduction
properly cited.
Publisher’s Note: AccScience The overarching goal for humanity is to enhance both the quality and length
Publishing remains neutral with of life. Although life expectancy has generally increased due to technological
regard to jurisdictional claims in
published maps and institutional advancements, the quality of life has often declined. A growing deficit in proper diet
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Volume 2 Issue 3 (2025) 145 doi: 10.36922/mi.4736