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Microbes & Immunity Hyphae and healthspan

EBV-laden B cells, leading to the release of EBV coexistent with SLE were Hashimoto thyroiditis (6%), celiac
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nuclear antigen (ENA) into the general circulation. This disease (3%), Sjögren syndrome (3%), and RA (2%). 100
reactivation correlates with the coincident appearance of
ANAs and ENA. Such CCPAb activity has been observed 8. ATM in cancer, dementia, autoimmunity,
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in RA and SLE. 68,69 ANAs are positive in approximately and ASCVD
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one-fourth of postural orthostatic tachycardia syndrome These diseases collectively contribute to the reduction
(POTS) cases. EBV reactivation has been reported in of both healthspan and lifespan. Their pathogenesis is
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up to 27% of those with COVID-19 and 68% of those complex; however, they appear to be interconnected.
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with LC. The released but viable EBV may not only Autoimmune diseases are associated with cancer,
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generate ANAs against ENA secreted by the virus but also dementia, and ASCVD. Specifically, SLE and RA are
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shuttle between immune and epithelial cells, inducing linked to ASCVD, 106,107 dementia, 108,109 and cancer. 110,111 In
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autoimmune diseases related to intracellular ENA. 112
Examples include SLE, multiple sclerosis, RA, IBD, celiac addition, IBD has been associated with dementia.
disease, type 1 diabetes, and juvenile idiopathic arthritis. Candida may actively contribute to this linkage not only
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Autoantibodies induced by different regions of ENA may through hyphae and candidalysin-induced autoantibodies
cross-react with SLE autoantigens such as SmB, SmD, and but also through yeast/hyphae release of IDO and D
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Ro. 74 deficiency. CO is a growing concern due to the increasing
prevalence of (1) a more sedentary lifestyle with reduced
7. Hyphae and mast cells/histamine/ sunlight exposure and (2) the nutritional decline of the
tryptase Western diet, characterized by higher consumption of
This section explores the connections between hyphae, alcohol, refined sugars, and processed meats. This is
periodontitis, candidalysin-induced antibodies, and the significant because IDO expression has been detected in both
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trifecta of POTS, mast cell activation syndrome (MCAS), the yeast and hyphal forms of Candida. IDO metabolizes
and hypermobility spectrum disorder (HSD). Mast cells are tryptophan, which opposes the transition of commensal
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recognized as biomarkers of periodontitis, 75,76 and hyphae yeast to its pathogenic hyphal form. Pathogenesis seems
associated with periodontitis can activate mast cells. The to proceed through ATM, a physiological abnormality
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incidence of periodontitis is higher in individuals with central to various diseases, including LC. ATM has
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LC compared to controls. Anticardiolipin antibodies also been reported in periodontitis and is a hallmark of
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(antiphospholipid antibodies) are detected in 15 – 20% of most chronic inflammatory diseases. The IDO-releasing
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individuals with periodontitis. Oral symptoms in POTS potential of CO may not only induce ATM but may also
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include refractory periodontitis, xerostomia, dysgeusia, be potentiated by it. Moreover, short-chain fatty acids
and burning mouth. Periodontal disease in HSD is (SCFAs) produced by gut bacteria inhibit Candida hyphal
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primarily genetic in origin, although CO may exacerbate invasion and help prevent ATM. 119
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it. Mast cells are key players in periodontitis and are
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also prominent in dementia, cancer, ASCVD, and 9. Candida and ATM
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autoimmune diseases. Tryptase- and chymase-positive Increasing interest in the gut microbiome and ATM has
mast cells are frequently found in skin biopsies from underscored their underappreciated roles in cancer,
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individuals with systemic and cutaneous lupus. Mast autoimmune disease, dementia, 122,123 and chronic
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cells collaborate with ACPAs in RA and play significant inflammation. CO may potentiate ATM due to the
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roles in Sjögren’s syndrome, Graves’ disease, IBD, and following mechanisms:
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various other autoimmune diseases, including multiple 1) Candida expresses its own IDO, which shares 31%
sclerosis, psoriasis, and atopic dermatitis. Mast cells and homology with mammalian IDO
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tryptase serve as crucial links in the trifecta of HSD, MCAS, 2) Tryptophan inhibits fungal IDO, while fungal IDO
and POTS and may also contribute to antiphospholipid inhibits tryptophan
syndrome (APS) (Figure 2). 3) Interferon-gamma (IFN-γ) drives mammalian IDO
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ACPAs activate mast cells, which are associated with activity
RA, spondyloarthritis, psoriatic arthritis, and HSD, 4) Fungal IDO promotes yeast-to-hyphae morphogenesis
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all observed in LC. MCAS and HSD are linked, as are 5) Tryptophan, mammalian IDO, and IFN-γ inhibit
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POTS/MCAS and POTS/HSD. Nearly 80% of patients yeast-to-hyphae morphogenesis
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with HSD displayed POTS. MCAS, HSD, and POTS 6) Fungal IDO and mammalian IDO are antagonists and
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are all linked to SLE, as is APS. 101,102 In a large community- are typically balanced in individuals with a healthy gut
based survey, the most common autoimmune conditions microbiome.
Volume 2 Issue 3 (2025) 148 doi: 10.36922/mi.4736