Mold Genes: How mold and mycotoxins interact with genetics

Key takeaways:
~ Some types of mold produce mycotoxins, which are toxic at very low levels.
~ Our detoxification pathways eliminate many types of mycotoxins that we are exposed to regularly in low levels.
~ Genetic variants in the detoxification genes make some people more susceptible to negative health effects from mold and mycotoxins.
~ Knowing your genetic susceptibility can help you target the right pathways to detoxify mold and mycotoxins.

Mold and Mycotoxins: Health Effects and Sources of Exposure

We are all exposed to mold on a daily basis. Fungi are essential to life: they live on our skin, make our soil fertile, and help decompose organic matter. But… some molds release microscopic toxins that can harm you. And for some people, exposure to certain types of mold can lead to long-term health problems.

Mold is a general term for the types of multicellular fungi that are filamentous. Yeast is also classified as a fungus, but it is single-celled and doesn’t produce filaments.

Exposure to certain types of mold – the kind that produces mycotoxins – can cause chronic health problems, gut health issues, immediate illness, mitochondrial dysfunction, or even death. When people talk about the health effects of mold, they are usually referring to the effects of mycotoxin exposure.

What are mycotoxins?

Mycotoxins are microscopic mold metabolites that can cause harm. They are naturally occurring toxins produced by filamentous fungi (molds). They are classified as toxins because even at very low doses, they can cause illness or even death in humans and other animals.[ref] Mycotoxins are different from the toxins found in poisonous mushrooms, which are the fruiting bodies of fungi.

Mycotoxins are found in trace amounts on moldy nuts, grains, coffee, and dried fruits. The mold that grows in damp places, such as water-damaged building materials, can also produce mycotoxins.

Aflatoxins, ochratoxins, trichothecenes, zearalenone, fumonisins, and ergotamine are more commonly studied mycotoxins, but more than 300 mycotoxins are known to exist. Some of these mycotoxins are produced by more than one type of fungus, while others are specific to a single fungal species.[ref]

The World Health Organization estimates that up to 25% of crops are contaminated with mold or fungal growth at some point in their life cycle. Some grains may have fungal problems in the field, while other products may grow mold during storage.[ref] Food processing methods reduce mold or mycotoxin contamination in foods that are used for human consumption. However, animal feed is more commonly contaminated with mold.

How are we exposed to mycotoxins?

Mycotoxins are produced by different types of fungi that grow on crops, in preserved foods, in damp homes, and in the soil, especially where warm and humid conditions are conducive to fungal growth.

The main routes of exposure to mycotoxins include:[ref]

• Ingestion: Contaminated food and drink (nuts, grains, coffee, dried fruit)
• Inhalation: Airborne spores in damp buildings
• Dermal: Skin contact with moldy materials

Foods can be contaminated by mycotoxins either in the field or during drying, storage, and processing. Contamination with mycotoxins is more of a problem when agricultural processes and food handling procedures are poor.[ref]

Mycotoxins pose a dual problem:[ref]

• They are toxic at extremely low levels
• They are chemically stable, allowing them to survive cooking

Mold Exposure: Acute vs. Chronic

Exposure to mycotoxins can be either acute or chronic:

• Acute exposure will result in rapid and severe symptoms of poisoning for someone who is exposed to higher levels of mycotoxins at one time (e.g., eating a bunch of moldy nuts).
• Chronic exposure is more common. Exposure to very low doses over long periods of time can result in various health effects, including an increased risk of certain cancers.

Acute exposure from eating foods containing mycotoxins can cause symptoms of food poisoning. Researchers believe that a percentage of food poisoning cases each year are actually due to mycotoxins.

Chronic exposure to mycotoxins can come from food or a moldy environment. For example, mycotoxins often contaminate coffee beans and tea leaves at very low levels. Drinking contaminated coffee or tea every morning is one way we can be chronically exposed to trace levels of mycotoxins.[ref]

In addition, mycotoxins can be airborne and enter the lungs or pass through the skin. Homes, schools, and office buildings that have been water damaged by flooding, roof leaks, plumbing drips, or AC condensation can develop mold in hidden places, leading to chronic mycotoxin exposure.

Specific mycotoxins: Dive into the details

Mycotoxin is a general term for many different types of toxins, and people are unique in how their bodies process and eliminate the different types of mycotoxins.

Genetic variants in the detoxification genes mean that some people may have little or no problem with mycotoxin exposure, while others may be very sensitive to low amounts of specific mycotoxins.  Understanding the different types of mycotoxins, along with understanding your genes, may help you to identify what may be a problem for you.

Let’s take a look at several specific mycotoxins and what they do in the body:

1. Ochratoxin A
2. Zearalenone
3. Aflatoxin A and B1
4. Trichothecene
5. Fumonisins
6. Ergot alkaloids
7. Deoxynivalenol
8. Patulin

1) Ochratoxin A is produced by Aspergillus and Penicillium sp. Ochratoxin A is toxic and thought to be carcinogenic, especially in the kidneys and liver.[ref]

Ochratoxin A is found in cereals, coffee, wine, dried fruits, beer, and grape juice. It is also found in animal organs (kidneys, liver) of grain-fed animals. In humans, ochratoxin A can have a severe immunosuppressive effect at low and high exposure doses. Ochratoxin A also alters the absorption of nutrients in the intestines.[ref][ref][ref]

2) Zearalenone is produced by Fusarium species that grow on corn or other grains.[ref] It can bind to estrogen receptors (mimics estrogen) and is a reproductive toxin in animal studies. In addition, zearalenone is toxic to the liver and causes cell death.[ref] One study describes zearalenone as: “a non-steroidal compound that exhibits oestrogen-like activity”.[ref]

3) Aflatoxins are produced by a couple of different Aspergillus species. There are 18 types of aflatoxins, with aflatoxin B1 being one of the most toxic and carcinogenic.[ref]

Aflatoxins are commonly found in peanut products and sometimes in milk from cows fed with contaminated grain. Aflatoxin B1 is also found in cottonseed oil.[ref] Aflatoxicosis is the medical term for acute aflatoxin exposure that leads to liver damage, jaundice, and, in severe cases, death.[ref] Chronic dietary exposure to aflatoxins is one cause of liver cancer.[ref]

Aspergillosis is a lung infection caused by Aspergillus infections in the lung. This mainly occurs in immunocompromised people or people with chronic lung conditions.[ref][ref] Aspergillus infection in the lungs or respiratory tract secrete aflatoxins. These aflatoxins then impair the airway cilia from functioning correctly, leading to reduced mucosal clearance.[ref]

4) Trichothecene mycotoxins encompass about 100 subtypes of metabolites from Fusarium species. Trichothecenes can contaminate corn, wheat, barley, oats, rice, rye, vegetables, and other crops. They are a common cause of poisoning in animals eating contaminated feed. Trichothecenes are easily absorbed and then distributed throughout the animal’s tissues. Human exposure comes from consuming meat, milk, and eggs from animals fed contaminated grains.[ref]

Consumption of trichothecene-contaminated foods can cause gastrointestinal issues. This mycotoxin affects actively dividing cells, such as in the intestinal or oral mucosa, and causes cell death.[ref]

5) Fumonisins are metabolites produced by Fusarium fungal species that can grow on peanuts, corn, and grapes. Certain fumonisin subtypes are linked to an increased risk of esophageal cancer, and in general, fumonisins are considered a WHO class 2B carcinogen.[ref][ref]

An interesting observation by researchers is that fumonisins reduce folate uptake in cells: “Because fumonisin B₁ reduces uptake of folate in different cell lines, fumonisin consumption has been implicated in neural tube defects in human babies”.[ref]

6) Ergot alkaloids are compounds created by Claviceps species, which are fungal pathogens that attack grasses such as rye. Ergot poisoning has been known for centuries. It was described as a “slow nervous fever” that occurred in the summer after a wet winter in the Middle Ages and was called St. Anthony’s fire. The symptoms recorded throughout history include convulsions, sores, hallucinations or mania, headaches, nausea, gangrene, and burning extremities.[ref] Modern grain processing methods eliminate ergot as a problem in human food sources, but it can still affect animals that graze on grasses or contaminated grains.[ref] The neuroactive components in the ergot alkaloids are similar to precursor molecules for LSD. Interestingly, a couple of Parkinson’s drugs are derived from ergot.

7) Deoxynivalenol is a mycotoxin produced by Fusarium species. It is found in wheat, beans, and some spices. Deoxynivalenol causes severe gastrointestinal issues similar to food poisoning when consumed via contaminated foods.[ref]

8) Patulin is a mycotoxin produced by Aspergillus, Penicillium, and Byssochlamys sp. It is most often found on apples, but can also occur on other moldy fruits or grains. The biggest dietary source is apple juice made from apples that aren’t fresh. Patulin can cause gastrointestinal problems and also organ damage.[ref] Patulin binds to thiol groups found in the intracellular antioxidant glutathione, which then causes oxidative stress, mitochondrial dysfunction, and cell death.[ref]

Health Effects of Mycotoxin Exposure: Symptoms from Mold

Exposure to mycotoxins can produce various physical responses — depending on the toxin, exposure route, amount, and individual genetic differences. Here’s what research shows:

Mitochondrial dysfunction:
This mycotoxin can impair mitochondrial function and inhibit the synthesis of certain proteins.[ref] Even at very low levels, mycotoxins, such as aflatoxin, can cause mitochondrial dysfunction and cell death. In the mitochondria, mycotoxins can cause disruption in the respiratory chain, decreasing the production of ATP and leading to chronic diseases.[ref] Some mycotoxins, such as patulin, can bind to thiol groups in glutathione, thus decreasing this essential cellular antioxidant. Without enough glutathione, oxidative stress and mitochondrial dysfunction.[ref]

Lung inflammation: 
An inflammatory response occurs when lung tissue is exposed to airborne trichothecenes. IL-1B increases in a manner dependent on NLRP3 activation.[ref] Aflatoxin G1 airborne exposure significantly increases inflammation in the lung. [ref] Stacchybotry chartarum, also known as black mold, produces trichothecenes that can enter the lungs and cause inflammation and allergic symptoms.[ref]

Organ damage and cell death:
From airborne exposure to fungi, the mycotoxins can travel from the lungs to the liver, kidneys, and spleen. Mycotoxins can cause inflammatory cytokines to increase in all of these organs. Specifically, researchers found higher levels of IL-1B, IL-6, and TNF-alpha.[ref] Genetic variants can influence how strong the inflammatory response may be. For example, TNF-alpha variants may cause some individuals to produce more of this cytokine in response to a mycotoxin. The overactive immune response then causes more cellular damage, exacerbating the problems from the mycotoxins.

Read more about SNPs that cause excessive inflammation

Suppressed immune response:
Zearalenone is a mycotoxin that suppresses the normal inflammatory response that cells should produce against pathogenic bacteria. Zearalenone exposure tamps down the proinflammatory cytokines (TNF-alpha, IL1B, IL6) that should be produced in response to gram-negative bacteria. This ‘tamping down’ suggests a reduction in the innate immune response, which could leave someone vulnerable to infections after exposure to zearalenone.[ref]

Kidney damage:
Oral exposure to ochratoxin A from contaminated food is linked to kidney injury. Animal studies show that ochratoxin A increases inflammatory cytokines and upregulates genes related to fibrosis in the kidneys. Blocking NLRP3, an inflammatory activator, was able to suppress the kidney injury.[ref] Patulin is also known for causing kidney damage. The mechanism of action here seems to be mitochondrial damage and lack of ATP — kidney cells use a lot of ATP. [ref]

Gut microbiome interaction:
Exposure to mycotoxins through foods can impact the gut microbiome in several ways. First, some gut microbes can metabolize mycotoxins, sometimes creating more toxic metabolites. Mycotoxins can also impact the composition of the gut microbiome by killing off some bacteria and affecting gut barrier function. Interestingly, certain mycotoxins affect the way nutrients are absorbed.[ref][ref]

Atopic dermatitis (eczema):
Long-term exposure to visible mold during infancy increases the risk of atopic dermatitis in children.[ref]

Asthma:
Many epidemiological studies link childhood asthma to mold exposure.[ref] One study looked at the interaction between genetic variants linked to asthma and mold exposure. In children exposed to visible mold, such as on the ceiling, there was a three-fold increased risk of asthma when taking into account genetic variants and mold exposure.[ref]

Detoxifying mycotoxins: pathways involved

We are all regularly exposed to mycotoxins at trace levels, and our bodies have ways of getting rid of mycotoxins. The key is to not overwhelm the detoxification system through either an excess of toxins or by not having enough of the cofactors needed for detoxification.

In general, the body breaks down and eliminates toxins in three steps: phase I detoxification (CYP450 genes) makes the substance more polar; phase II detoxification (UGTs, GSTs) makes the metabolite water-soluble; and phase III is the excretion of the metabolite.