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Microbes & Immunity Hyphae and healthspan

morphogenesis and fungal IDO. This is especially (Figure 3), which enhances the integrity of both intestinal
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critical for individuals with COVID-19 and LC. Intestinal and brain barriers. All CYP450 enzymes require Mg 2+140 ,
epithelial cells are rich in ACE2 receptors, which must form highlighting its critical role and the importance of the
a complex with B AT, a neutral amino acid transporter, Ca: Mg ratio. Dietary calcium and magnesium compete for
0
to enable tryptophan absorption. The loss of ACE2 absorption through the calcium-sensing receptor. Mg is
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2+
receptor-bearing cells due to SARS-CoV-2 invasion may also necessary for converting tryptophan to serotonin (for
explain the low levels of tryptophan and serotonin reported mood regulation) and serotonin to melatonin (for sleep).
in COVID-19 and LC. (Figure 3). This leaves fungal It serves as a required cofactor for multiple steps in the
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IDO unopposed and suggests that Candida might act as synthesis of the active form of vitamin D from D and is
3
a collaborator with SARS-CoV-2. Methionine, another essential for its transport by the vitamin D-binding protein.
essential neutral amino acid, is critical for methylation In addition, Mg is required for methylation (Figure 4),
2+
(Figure 4). Aberrant methylation, which is linked to exacerbating risks associated with CO and the 677T allele.
cancer, dementia, and autoimmune disease, is facilitated by Magnesium exhibits fungicidal properties in vitro. In
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the 677T methylenetetrahydrofolate reductase (MTHFR) 1989, Jean Durlach, founder of the International Society
variant allele. According to the Centers for Disease for Development of Research on Magnesium, reported
Control and Prevention (CDC), most Americans carry this that a ratio of 2.0 (cation concentrations in mmol/volume)
allele. Acetaldehyde, elevated in CO, inhibits methionine was the ideal target. A high Ca: Mg ratio is characteristic
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synthase, further compromising methylation in such of conditions such as cancer, autoimmune diseases, and
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individuals (Figure 4). This methylation deficiency may ASCVD, with the optimal ratio being between 1.7 and
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pre-dispose them to COVID-19 and LC. Furthermore, 2.8. The Asian diet is typically low in calcium, whereas the
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CO may exacerbate this vulnerability. Western diet is often deficient in magnesium. According
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Intestinal bacterial cytochrome P450 enzymes to the National Health and Nutrition Examination Survey,
metabolize tryptophan into its indole derivatives the mean dietary Ca: Mg intake ratio for Americans has

Figure 3. Altered tryptophan metabolism (ATM) characterizes long COVID, autoimmunity, cancer, dementia, and other diseases. Interferon-gamma
(IFN-γ) and transforming growth factor beta (TGF-β) counterbalance each other: TGF-β governs tolerogenesis, with excessive levels leading to tolerance of
cancer antigens and insufficient levels resulting in intolerance of host antigens. Candida can release its own indoleamine dioxygenase (IDO), contributing
to ATM and potentiating cancer and dementia.
Notes: Numbers indicate references. Arrow thickness denotes pathway preference.
Abbreviations: AhR: Aryl hydrocarbon receptor; NAD : Oxidized nicotinamide adenine dinucleotide.
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Volume 2 Issue 3 (2025) 150 doi: 10.36922/mi.4736