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Microbes & Immunity Hyphae and healthspan

Figure 4. The MTHFR variant allele, present in the majority of Americans, and methionine synthetase (MS), suppressed by acetaldehyde, both highlighted
in red, contribute to impair methylation.
Notes: Cofactors are shown in green. Molecules are shown in pink.
Abbreviations: Hcy: Homocysteine; MS: Methionine synthetase; MTHFR: Methylenetetrahydrofolate reductase; SAH: S-Adenosyl homocysteine; SAMe:
S-Adenosyl methionine; THF: Tetrahydrofolate.

increased from 2.6 in 1977 to over 3.0 since 2000. When with short-term effects such as brain fog and fatigue but
this ratio falls outside its recommended range, similar also with cancer and dementia. Alcohol metabolism
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diseases tend to emerge, such as dementia, 145,146 colon elevates homocysteine levels (while reducing B and
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cancer, and ASCVD. 144 B ), which is linked to cancer, dementia, and
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autoimmune disease. The active forms of folate (B ) and
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Candida morphogenesis, virulence, biofilm formation, 9
and dissemination are regulated by fungal histone cyanocobalamin (B ) depend on methylation, a process
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compromised in individuals with the 677T allele. The
deacetylase (HDAC), particularly Sirtuin2. Sirtuin2 is
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NAD -dependent and may be upregulated through the risks of cancer and dementia are further elevated in those
+
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kynurenine pathway (Figure 3). The dietary inclusion of carrying the 677T MTHFR allele. According to the
a pre-biotic (e.g., d-mannose), probiotic (e.g., yogurt), CDC, nearly half of American adults have pre-diabetes
or diabetes, conditions driven by increasing insulin
and post-biotic (e.g., butyrate) can counteract CO. resistance now linked to CO. Recent research indicates
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Bifidobacteria stimulate butyrogenic bacteria, whereas that methylation may play a role in the development of
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lactobacilli enhance butyrate absorption. Both dominate systemic insulin resistance. Consequently, CO, which
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the colony-forming units in probiotics. Lactobacilli is associated with aberrant DNA methylation and histone
significantly inhibit Candida hyphal morphogenesis and deacetylation, may drive disease through dual pathogenic
biofilm formation. Butyrate, a potent HDAC inhibitor, mechanisms involving the epigenome (Figure 4).
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suppresses Candida. 152,153 HDAC also plays a critical role
in carcinogenesis and is associated with dementia, Exercise reversibly enhances gut biodiversity. 174
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autoimmune diseases, and even periodontitis. Autism In summary, achieving an optimal gut microbiome
spectrum disorder should also be considered part through therapeutic approaches involves the following:
of this list. Butyrate immunomodulates IFN-γ and 1) Vitamin D3 supplementation
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transforming growth factor beta, which are cytokine 2) Adequate levels of tryptophan
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reciprocals linked to autoimmune disease and cancer, 3) Maintaining a Ca: Mg ratio close to 2.0
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respectively (Figure 3). In summary, probiotics containing 4) Incorporating pre-biotics, probiotics, and post-biotics
bifidobacteria and lactobacilli may enhance healthspan. 5) Following a diet that moderates the intake of refined
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They work synergistically through butyrate to promote carbohydrates and ethanol
longevity. The HDAC-inhibiting properties of butyrate 6) Engaging in exercise.
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have been directly linked to increased lifespan. 163
11. Conclusion
Candida thrives on a diet high in refined carbohydrates
and alcohol, both of which are metabolized to acetaldehyde The described linkages are thought-provoking but do not
(rate-limiting step). Acetaldehyde is associated not only establish a cause-and-effect relationship. Furthermore,
Volume 2 Issue 3 (2025) 151 doi: 10.36922/mi.4736