Normal Human Mycobiota and Environmental Fungi

The human mycobiota is the fungal component of the microbiota. It is small in biomass and low in diversity compared with the bacterial community. In the gut, fungi account for roughly 0.1 percent of microbial cells. Composition differs widely between individuals and varies over time within one person.

Culture recovers only a minority of what sequencing detects. Sequencing of the internal transcribed spacer region shows that a large share of the fungal DNA in the mouth, gut and airway originates from food, inhaled spores and the environment. These are transient passengers rather than residents. Three genera form the consistent resident core: Candida, Malassezia and Saccharomyces.

• Bacterial competitors: anaerobic gut bacteria and vaginal lactobacilli restrict Candida growth through competition for niches, short chain fatty acids, lactic acid and induction of host antimicrobial peptides. Antibacterial therapy that depletes these species permits fungal expansion.
• Host immune tone: mucosal Th17 responses, interleukin 17 and interleukin 22 signalling, secretory immunoglobulin A and antimicrobial peptides hold commensal Candida in check. Failure of these pathways (for example CARD9 deficiency or STAT3 deficiency) allows overgrowth.
• Diet and glycaemia: high carbohydrate intake and glycosuria favour yeast growth in the mouth, gut and genital tract.
• Hormones: oestrogen raises vaginal glycogen and Candida adherence during pregnancy and with some hormonal preparations.
• Drugs: broad spectrum antibacterials, inhaled and systemic corticosteroids, and cytotoxic chemotherapy.
• Devices and hospitalisation: dentures, catheters, tracheal tubes and ICU stay increase the proportion of colonised body sites and shift carriage towards Candida glabrata, Candida parapsilosis and Candida auris.
• Age: neonates and the elderly carry higher fungal loads.
• Sebum and humidity: lipid rich, humid skin sustains Malassezia.

Commensal fungi cause disease only when one of three things changes: the barrier is breached, competing bacteria are lost, or the immune response fails. The commensal state is the starting point for most invasive candidiasis, and the isolate in the bloodstream usually matches the organism previously colonising the gut or skin.

Heavy multisite Candida colonisation in critically ill patients predicts a higher risk of later invasive candidiasis, but its positive predictive value is poor. Colonisation alone does not justify antifungal therapy.

• Air: Aspergillus conidia in hospital air rise with construction, demolition, renovation and failures of ventilation. High efficiency particulate air filtration with positive pressure rooms reduces exposure of neutropenic patients and transplant recipients.
• Water: biofilm in pipes, shower heads and sink drains harbours Fusarium, Exophiala and Candida, and outbreaks of invasive mould disease have been traced to hospital water.
• Surfaces and equipment: Candida auris contaminates bed rails, mattresses, thermometers, pulse oximeter probes, blood pressure cuffs and other shared equipment, and survives on dry surfaces for weeks. Chlorine based and other sporicidal disinfectants are used; some quaternary ammonium products have reduced activity.
• Medical products: Mucorales and other moulds have contaminated adhesive bandages, wooden tongue depressors, intravenous preparations and compounded drug products.
• Hands of healthcare workers: the route for Malassezia, Candida parapsilosis and Candida auris between patients.

• Agricultural azole fungicides: azole fungicides used on crops and bulbs select azole resistant Aspergillus fumigatus in compost and soil. The dominant environmental resistance alleles are the TR34/L98H and TR46/Y121F/T289A variants of the cyp51A gene. Patients with no prior azole exposure can therefore present with azole resistant invasive aspergillosis.
• Thermal adaptation: the near simultaneous emergence of genetically distinct Candida auris clades on three continents has been linked to adaptation to higher environmental temperatures, because Candida auris grows at 42 degrees Celsius.
• Range expansion: the range of Coccidioides has extended north in western North America, and Cryptococcus gattii has become established in the Pacific northwest since the late 1990s.
• Natural disasters: tornadoes, tsunamis and floods produce wound infections with Mucorales, Scedosporium and dematiaceous fungi through contaminated soil and water.
• Land disturbance: excavation, deforestation and mining release soil dwelling dimorphic fungi.
• Pandemic related exposure: invasive aspergillosis followed severe influenza and severe COVID-19, and mucormycosis rose in association with uncontrolled diabetes and corticosteroid use during the COVID-19 pandemic.

Fungal exposure also harms without infection.

• Aflatoxins from Aspergillus flavus and Aspergillus parasiticus contaminate stored maize and groundnuts. Chronic exposure causes hepatocellular carcinoma, especially with chronic hepatitis B infection, and growth impairment in children. Acute aflatoxicosis produces jaundice and acute liver failure with high mortality, and an outbreak in eastern Kenya in 2004 caused over 300 cases and over 100 deaths.
• Ochratoxin A from Aspergillus and Penicillium is nephrotoxic.
• Fumonisins from Fusarium verticillioides in maize are associated with oesophageal cancer and neural tube defects.
• Ergot alkaloids from Claviceps purpurea on rye and other cereals cause ergotism with vasoconstriction and gangrene, or neurological disease.
• Spores and antigens in damp buildings, hay and compost cause hypersensitivity pneumonitis, allergic asthma and allergic bronchopulmonary aspergillosis in susceptible hosts.

Common airborne contaminants are Penicillium, Cladosporium, Alternaria, non pathogenic Aspergillus species, Rhizopus and Mucor on open plates, Epicoccum and Aureobasidium. Features favouring contamination: single colony growth, growth away from the inoculation streak, growth on one plate only, a fungus not seen on direct microscopy, and an isolate from a person with normal immunity and no tissue evidence.

These features lose weight in profoundly immunocompromised patients, in whom Aspergillus, Fusarium and Mucorales from respiratory samples can be genuine. A mould from a sterile site, or a mould seen invading tissue, is always clinically significant.