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Mold Exposure and Mycotoxicity: On the Path to Precise Science

Mold exposures can be neurotoxic and immunogenic leading to a variety of consequences to the body, in particular the nervous system.  The route of mold exposure occurs through one of several ways: through ingestion, inhalation or direct contact with mycotoxins. The simplest immune responses of mold exposure is a hypersensitivity or allergic reaction causing superficial skin infection or rash, asthma, sinus, and hypersensitivity pneumonitis. Improved understanding of the pathways of myotoxicity has occured over the past decade with appreciation of the innate and adaptive immune systems respectively interacting with both macrophages and other resident cells that recognizing pathogens and signs of cellular damage, and T-cells and B-cells and their respective lymphocyte subsets, sequestered as memory cells.  Mycotoxins originate from metabolism or growth of the fungus from which they originate, appearing as bizarre molecules with molecular weights of scarcely 50 Dalton (Da) to 500 Daltons. The difficulty in detecting them biologically in food and in the atmosphere poses a huge risk.  In its mildest form, acute direct exposure results in topical sensitivity or necrosis of the skin surfaces while chronic systemic absorption interferes with host mechanism of protein synthesis and other metabolic pathways, resulting in depressed hematologic, liver or kidney function, while the long-term immunosuppressive and mutagenic effects of mycotoxins can be associated with the induction of cancer due to its effect on DNA replication.  The symptoms and signs of chronic mold exposure can be as diverse as their structure and effects on the human body.  Many toxigenic fungi are ubiquitous in nature with a strong ecological link to human food supplies where it   poses the greatest risk to populations in conjunction with human food consumption.   

The commonest mycotoxins responsible for human disease are aflatoxins, ochratoxin A, fumonisins, trichlothecenes and zearalenone. Aflatoxins are categorized by their immunofluorescence patterns under ultraviolent light on thin layer chromatography.  Collectively they are potent toxins and carcinogens especially in association with hepatitis B virus (HBV) where they caused outbreaks of hepatitis after consumption of 2 to 6 mg of the aflatoxin of A, Aspergillus flavus, in a single day. Death supervenes after consumption of a lethal dose of 10 to 20 mg. Aflatoxin B is a potent carcinogen leading to human liver cancer in central Africa and parts of Southeast Asia while others associate with hepatitis B virus as co-carcinogens, leading to increased rates of liver cancer. Aflatoxin B1 is a class 1 human carcinogen.  The commonest source of aflatoxins are in stored peanuts, maize, cotton seed and cereals, usually in association with inadequate drying or improper storage.  Ochratoxins are acute hepatic and renal toxins, with immunosuppressive and carcinogenic effects. Like the aflatoxins, they accumulate in fat tissue and not readily excreted from the body. Common sources of ochratoxin A are drying or decaying vegetation, seeds, nuts, and fruits.  Fumonisins have been described in a fatal disease of horses where they present as leukoencephalomalcia due to the competition of the mycotoxin for sphingosine lipids important in normal brain white matter metabolism. While this disease has not been well recognized in humans, the carcinogenic potential of fumonisins have been recognized in humans in association with esophageal cancer in certain parts of the world where the toxin in endemic in certain food sources.  Acute toxic exposure to trichlothecene, causes nausea, vomiting, anorexia, headache, abdominal pain, chills, giddiness and convulsions, while chronic indolent exposure can lead to increased susceptibility to microbial infection. Zearalenone is an estrogenic mycotoxin that causes genital problems in domestic animals, including hyperemia and edematous swelling of the vulvula, prolapse of the vagina and rectum, infertility, fetal loss, testicular atrophy, and hypertrophy of the mammary glands, as well as, precocious puberty in children.  
Numerous investigations have demonstrated the qualitative and quantitative richness of fungal material and their metabolic products inside buildings with moisture damage exposure which can lead to systemic inflammation and a risk for acquired illness .  Among home inspections of exposed children with evidence of subclinical inflammation, there were increased levels of proinflammatory cytokines detected in the blood, particularly when major moisture damage was found in the child’s main living areas such as the living room, kitchen, bedroom and bathroom.  Glucan, a glucose polymer and constituent of the cell wall of certain pathogenic fungi, has been used as a marker for indoor fungal exposure. Children with household mold exposure had higher glucan levels, with two or more positive skin tests, and a 9-fold greater odds of 1 or more visits to an emergency room for asthma. Key determinants of the fungal microbiome in a given home correlates with several quantitative measures include, the age of the home (p=0.002), an Environmental Relative Moldiness Index (ERMI) value (p=0.003), and relative indoor humidity (p=0.015). Dog ownership influences bacterial but not mold microbiome diversity.  Low-income urban home dwellers with the highest index of household mold exposure appeared to cluster by site, with cumulative mold exposures that was associated with the poorest health among those studied.  One meta-analysis and systemic review found that indoor fungal exposure posed a longitudinal respiratory health risk when exposed to certain species, with increased exacerbation of asthmatic symptoms in both children and adults. 
Mold exposure as a cause of human illness has advanced from its early stages of scientific precision. It is likely that with the application of molecular genetic studies to the human microbiome will validate the relation of mycotoxicity to human illness. The microbiome of the home and work environment are areas of intense interest because of the possible impact of the fungal microbiome on the health of its dwellers and workers.  




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