A Study on the Overreactive Immune System After Mold and Mycotoxin Exposure

by Dr. Susan Tanner, MD

Mold and mycotoxin exposure results primarily from the inhalation of spores, but also from ingestion of mold-contaminated food sources.  Spores serve as vectors for mycotoxins and are pathogenic due to allergenic and infectious properties. However one is exposed, mycotoxins are systematically absorbed,  affecting many different body systems and organs.  According to critical opinions, there is not sufficient evidence that mold/mycotoxin exposure might directly cause autoimmune diseases, but I think what may not be taken into consideration is genetic susceptibility, which varies widely.

The situation appears different considering the role of mold and, in particular, of mycotoxins as risk factors in the onset and severity of various diseases in individuals with already impaired immune systems. Asthma exacerbation is an example.  Although there seems to be an association between mold/mycotoxin exposure and exacerbation of other dysregulated immune conditions like inflammatory bowel diseases, autoimmune diseases, or disease progression in HIV-positive patients, there is not yet published data that is universally accepted.

Any time I get into the realm of immunology I tend to get overwhelmed.  The subject is very complex, and the diagrams of how everything works with all their moving parts could cover an entire wall and still be lacking. Thus, the overall effects and impacts that mold has on the immune system, in general, is a large topic to conquer concisely. What I do hope to point out in this article, however, is that mold and mycotoxins have, by various pathways, the ability to inflame, aggravate, and possibly cause a number of illnesses and infections.

Immune System Activation by Mold Exposure

Many practitioners who have treated mold-injured patients also have to consider complications, such as the reactivation of chronic viruses such as Epstein Barr, the development of other infections in the gut including Clostridium Difficile (C. Diff), and the overgrowth of other pathogenic bacteria including species of staph.  Additionally, the onset of autoimmune conditions such as Hashimoto’s thyroiditis and other arthritic conditions have been presented after a time of mold exposure.   The question has arisen as to what happens in the immune system such that these infections and illnesses occur.

It has been long suspected that an overall toxic burden, for a variety of reasons, puts more pressure on the immune system to both underperform in protecting against certain infections and to become overactive and reactive to some of the body’s own tissues.  A study in the International Journal of Molecular Sciences published on November 12, 2021, by Kraft, Buchenanaur, and Polte, really helps us understand what is happening on a cellular level in the immune system.  Observations outlined in the study indicate the importance of mold/mycotoxin exposure in individuals with pre-existing dysregulation of the immune system due to exacerbation of underlying pathophysiology including allergic and non-allergic chronic inflammatory diseases, autoimmune disorders, and immune deficiency syndromes. The study explains the presentation of its findings as follows:

“. . . next to direct effects of mold and mycotoxin exposure in immunocompetent individuals, exposure in the presence of pre-existing immune dysregulation is of particular concern. First, we briefly describe how mycotoxins directly exert immunomodulatory effects. Next, we illustrate how mycotoxins might trigger the onset or exacerbation of chronic inflammatory diseases, autoimmune disorders, and the progression of HIV disease. Furthermore, cellular, and molecular key mechanisms of these exacerbating effects in the progression of the underlying diseases are discussed.”

In the paragraphs that follow, I will touch on many aspects of immunology that the study discusses. Th goal is to understand how mold and mycotoxin exposure impact the immune system and why that could these “natural” substances seem to make the immune system go off the rails.

Mold and Allergic Reactions

Mold can cause different hypersensitivity reactions. Hypersensitivity reactions are exaggerated or inappropriate immunologic responses that occur in response to an allergen. Allergens, like mold, also act as antigens resulting in a strong immune response.  For example, the four genera of Alternaria mold species produce allergens including enolase, heat shock proteins, cyclophilins, proteases, redoxins, and disulfide isomerases. According to the research by these authors, there is no evidence that mycotoxins themselves function as allergens.

Type 1 allergies are characterized by antigen-specific IgE-antibodies which are produced shortly after exposure to already sensitized mold antigens. Even if the prevalence of sensitization can only be estimated, there are multiple studies indicating that mold is considered an important allergen source for allergic asthma. Additionally, studies show that children who live in water-damaged homes with high mold counts are much more likely to develop and suffer from asthma.

Several outdoor and indoor mold species exert strong inflammatory and allergenic properties in asthmatics with mold sensitization. Next to allergic asthma, fungal rhinosinusitis, a subset of chronic rhinosinusitis with nasal polyps, has also been classified as a type 1 allergy with elevated levels of mold-specific IgE.

In addition to type 1 allergies, mold can also induce type 3 and 4 hypersensitive reactions, known as hypersensitivity pneumonitis. These reactions are mediated by immune complexes and T helper cells, and hypersensitivity pneumonitis has been associated with airway exposure to high concentrations of mold spores, especially due to occupational conditions like in cases of Farmer’s Lung–where an inflammatory respiratory disease is caused by the frequent inhalation of mold spores present on hay or crops.

Mold and Autoimmune Diseases

The association with the development of autoimmune diseases is multifactorial with both genetic and environmental factors playing a role.  As we have said many times, genetics loads the gun, environment pulls the trigger. To further complicate matters, epigenetic modifications can be triggered by environmental exposures to cause aberrant expression of genes and induce autoimmune diseases.

Multiple sclerosis (MS) is characterized by neuroinflammation and axonal demyelination of neurons in the central nervous system and spinal cord. A correlation between fungal infection and MS has been described for candidal yeast. Even without a diagnosis of MS, neural protein autoantibodies were increased in several individuals who were exposed to mold. Similarly, a conducted cohort study of 8 females with known exposure to water-damaged or mold-contaminated buildings tested positive for IgG neuronal antibodies against microtubule-associated protein-2, myelin basic protein, tau, glial fibrillary acidic protein, tubulin, and S-100B.  It must be noted, however, that an increase in autoantibodies may be caused by multiple factors including environmental triggers such as a viral illness or prolonged exposure to certain toxic chemicals.

Additional observations regarding autoimmune abnormality have also been seen regarding fungal and mycotoxin exposure: In a small case-control study there were elevated levels of reactivity for antimitochondrial antibodies in 6 patients all associated with mold and moisture exposure. Mold-derived mycotoxins might induce mitochondria damage and trigger autoimmunity via anti-mitochondrial antibodies, which are also detected in more than 90% of patients with primary biliary cirrhosis without alcoholism.

For rheumatoid arthritis (RA), another autoimmune disease, only limited data are available analyzing the effect of mold exposure in humans, but a case study published in the 80s with only a small cohort of patients described a tendency of stronger sensitization to Aspergillus antigens in RA patients compared to controls. There are currently no further human data available for a decent assessment of a potential relationship between RA and mold exposure. However, in an experimental Rheumatoid arthritis model mycotoxins that were examined have the potential to increase the susceptibility and severity of RA in mice. The exposed mice showed an increased amount of impact on paw joints with inflammatory white blood cells, synovial hyperplasia, cartilage destruction, and bone erosion.

In patient studies involving colitis, there were several incidences of worsening of this condition when patients had mycotoxin exposure. In this particular study, the mycotoxin was trichothecene from black mold (Stachybotrys) but it is thought that other molds and mycotoxins, most notable zearalenone, contribute to this as well.   The cause of colitis could also have been from mycotoxins but that was not part of this study.

Mold and Inflammation

Molds and their components including mold spores and hyphal fragments are known to be involved in inflammation and as allergens that can cause different diseases. The immune system is often triggered by several mycelium molecules of molds. β-1,3 glucans are naturally occurring in the cell walls of fungi and are recognized by host phagocytic cells, dendritic cells, neutrophils, and epithelial cells via C-type lectin receptors. Additionally, the mold cell wall is composed of glycoproteins with allergenic properties and further, mold allergens are also found in enzymes released in the external environment during the germination process. The lung epithelium and the dendritic cells present in the lung can recognize these allergens which initiate the allergenic process. Findings show that mold spores can activate innate immune cells, the first line of defense, and modulate the development of adaptive immunity through the differentiation of T-helper 1 (Th1) and T-helper 17 (Th17) cells, critical cells needed to mount a protective immune response against pathogenic fungi. These responses have been widely investigated with candida yeast and Aspergillus mold.  Moreover, the engagement of C-type lectin receptors triggers the activation of intracellular signaling pathways leading to the activation of inflammasomes and promoting inflammatory responses critically required to control fungal infections, including mold. Thus, one can then understand why living in indoor spaces with high levels of mold spores may lead to chronic or recurring fungal infections for the inhabitants.

Mold and Barrier Function

Further findings in this fascinating study have to do with the impacts on barrier function.  I am referring both to the mucosal lining of the respiratory tract as well as the endothelial layer of the gut, the immune-rich layer of the small intestine. It has been demonstrated that mycotoxins can influence the gastrointestinal microbiome directly through antimicrobial activity and through secondary mechanisms involving the release of antimicrobial compounds from mycotoxin-damaged host cells. So far, it has been identified that the interaction between the gut microbiome and mycotoxins plays a significant role in the development of mycotoxicosis and overall illness from mold exposure.

Helping the Immune System After Exposure

This brings us then, to what to do.

Step one, as we have said over and over, is the elimination of the toxins from your air and food sources.  You cannot get better if the influx of mold continues to keep your immune system dysregulated.

Other steps, such as the re-establishment of a good gut microbiome, detoxification of a burdened system, and continual clearing and removal of spores from the respiratory passages by gentle irrigation may come next.

Specific immune regulation either by allergy therapies or other modulation may be helpful as well.  Sinus Defense is easy, homeopathic, and affordable.  As always, however, guidance by a mold-literate practitioner to help you navigate this is always recommended!