What is a fungus?
Fungi are eukaryotic, heterotrophic, mainly aerobic organisms,
possessing chitin in their cell walls, ergosterol in their plasma
membranes, typical eukaryotic 80S ribosomes, and can produce lysine, for
some of them, exhibiting a dual state as either yeast or mold (13).
Regarding microscopic fungi, yeasts are unicellular forms that reproduce
through budding, while molds are multicellular forms displaying hyphae
in a mycelium (13). Fungi that present as yeast-like or molds, depending
on physicochemical conditions and nutrient availability, are called
“dimorphic” (13).
Before 2011, the taxonomy of fungi was blurred by the co-existence of
distinct names for the sexual (teleomorph) and asexual (anamorph) states
of the same fungus. This dual nomenclature of fungi has hampered
research on fungi for decades. Since 2011, and as a fortunate sequel to
the advent of DNA-base taxonomy genome, an initiative explicitly called
“One fungus, one name” of the International Mycological Association
resolved to use only one name per species (14). To date, the fungal
taxonomy is still in progress and remains relatively unstable.
As stressed above, fungi are ubiquitous in the environment. Humans are
exposed to fungi via inhalation in indoor and outdoor environments; they
are also exposed via ingestion through the digestive tract and via
contact with the skin and eyes. Exposure to fungi may cause a vast
variety of diseases, mainly allergic (such as conjunctivitis, asthma,
hypersensitivity pneumonitis, rhinitis, and allergic broncho-pulmonary
aspergillosis) or infectious (e.g., mucormycoses, invasive
aspergillosis, or fusariosis). Fungal hypersensitivity is often found in
patients with asthma, chronic obstructive pulmonary disease, cystic
fibrosis, and bronchiectasis, ranking among the most prevalent diseases
worldwide (4,15). Fungal infections develop predominantly in
immunocompromised hosts and may exceed 50% case-fatality rates (4,16).
Hypersensitivity pneumonitis (HSP) may occur in subjects without a
previous condition (17).
Moreover, fungi release mycotoxins and volatile organic compounds (VOC).
Mycotoxin production aims to secure fungal nutrients, while VOC is
defined as small molecules containing carbon and able to evaporate under
ambient conditions, such as 0.01 kPa and 20°C (18–20). Exposure to
mycotoxins may occur through inhalation of airborne mycotoxins or
ingestion of contaminated foods, giving rise to mycotoxicosis (19,21).
Fungal VOC are produced by primary and/or secondary metabolism pathways
as a species-specific profile subject to environmental changes. To date,
more than 400 fungal VOC have been described encompassing a wide variety
of chemical compounds: simple hydrocarbons, heterocycles, aldehydes,
ketones, alcohols, phenols, thioalcohols, thioesters and their
derivatives, benzene derivatives, and cyclohexanes (20,21). Although
some fungal VOC have been shown to induce symptoms (fatigue, lethargy,
headache, irritation of ocular and upper airway mucosae, wheezing) and
upregulate biomarkers of inflammation in healthy volunteers (20,22)
their impact on human health is still controversial (18–20). Given
their characteristics mentioned above, fungi are key constituents of the
human exposome and further research is needed to evaluate and
characterize the impact of fungal exposome on human health and use the
data for risk assessment.
Fungal exposome
Worldwide, molds are an increasingly acknowledged part of the human
exposome, both external (23) and internal as microbiome components
collectively named mycobiota (24) (Figure 1) . The external, or
environmental, part of the fungal exposome may be divided into outdoor
and indoor categories, with many shared features but also with many
differences in terms of composition, variation, and potential
interventions.
Indoor and outdoor mold exposure shows geographical, seasonal, and urbanversus rural variability (25–27) and induces immune responses
and health effects, often respiratory and allergic, that may start in
infancy (28–31). In fact, human-fungus interactions extend from
medicine and pharmacy to leisure activities, agriculture, food
processing, industry, and even interplanetary travels (13,32,33).
Currently, allergenic molecules from more than 40 fungal genera have
been characterized
(www.allergen.org, accessed March
8th, 2022), but molecular data are still lacking for
many environmental fungi (Table 2) . Cross-reactivity between
fungal allergens may help to identify some, but not all, fungal
sensitization outside of the available extracts and molecules (34,35).