RealTime Laboratories

Gliotoxin Derivative

Optimal Result: 0 - 0.5 ppb.

Fungal toxins are considered secondary metabolites which may provide selective advantage under particular conditons.

Gliotoxin belongs to the epipolythiodioxopiperazine class of secondary metabolites (=ETPs). 

The ETPs are produced by a wide variety of fungi, e.g., Aspergillus spp, Chaetomium spp, Penicillium spp, to mention a few. However, Gliotoxin produced by Aspergillus fumigatus has received wide attention because it is considered a virulence factor for A. fumigatus, as well as being present in the sera of cancer patients with aspergillosis (Sugui et al, 2007; Sugui et al, 2007; Bok et al, 2006).

Gliotoxin has been detected in the lung tissue and sera of mice with invasive aspergillosis and sera of cancer patients (Lewis et al, 2005a). The percentage of Aspergillus isolates from cancer patients produced gliotoxin as follows: fumigatus (93 %), niger (75 %), terreus (25 %) and flavus (4 %). (Lewis et al, 2005b). However, only 18 % of A. fumigatus in European patients produce gliotoxin, while 23 % of A. flavus isolates produced aflatoxin B1 (Kosalec and Pepeljnjak, 2005). The difference between the two reports may result from differences in strains of A. fumigatus in culture media and temperature (Kosalec et al, 2005).

The pathobiology of gliotoxin is multi-faceted (Kwon-Chung and Sugui, 2009). These are: 1) the S-S group in the ring forms adducts with cysteine residues of proteins; 2) The S-S group readily goes through a redox cycle production reactive oxygen species (ROS); 3) gliotoxin is immunosuppressive inhibiting phagocytosis; blocking NF-kB transcription factor, inhibiting proinflammatory response and cytokine production; 4) causes mitochondrial directed apoptosis ; 5) induces PM-mediated inflammation in organ transplant patients treated with corticosteroids.; and 6) the mycotoxin probably inhibits normal neutrophil functions in healthy subjects.

Finally, it was believed that gliotoxin was produced by the yeast Candida albicans. However, this observation has recently been questioned (Kupfahl et al 2007).

In conclusion, several species of Aspergillus and other fungi, as well as possibly yeast, produced gliotoxin both in vitro and in vivo. More attention should be paid to this mycotoxin because of its multi-faceted toxic properties.

What is Aspergillus?

Aspergillus spreads in the environment by releasing conidia which are capable of infiltrating the small alveolar airways of individuals. 

In order to evade the body’s defenses Aspergillus releases Gliotoxin to inhibit the immune system (=prevent the immune system from reacting). 

- Gliotoxin impairs the activation of T-cells. T-Cells are immune cells that protect the body from pathogens. 

- Gliotoxin also induces apoptosis (=a form of programmed cell death) in monocytes (=a type of white blood cell) and in monocyte-derived dendritic cells (=T-cell helpers). 

These impairments can lead to multiple neurological syndromes.

What is Invasive Aspergillosis?

Aspergillus fumigatus is responsible for a life-threatening systemic disease called “invasive aspergillosis” (IA) in immunocompromised individuals where mold actually grows inside the lungs but can invade other areas as well. Insufficient immune defense mechanisms result in high IA mortality rates in neutropenic (low white blood cell count) and immunosuppressed patients. 

Connection to Multiple Sclerosis:

Recent research has implicated the mold produced immunosuppressive Gliotoxin as a likely cause of Multiple Sclerosis in people that have a genetic disposition for MS. The frequency of MS has been increasing. [L]

References:

http://www.ncbi.nlm.nih.gov/pubmed/19843884

http://www.ncbi.nlm.nih.gov/pubmed/17030582

http://www.ncbi.nlm.nih.gov/pubmed/20645385

http://www.ncbi.nlm.nih.gov/pubmed/15817772

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2729542/

http://www.ncbi.nlm.nih.gov/pubmed/8777967

http://www.ncbi.nlm.nih.gov/pubmed/8666939

http://www.ncbi.nlm.nih.gov/pubmed/17626149

https://www.clinicaltherapeutics.com/article/S0149-2918(18)30189-9/pdf

https://globaljournals.org/GJMR_Volume14/1-Family-of-Six-their-Health.pdf

What does it mean if your Gliotoxin Derivative result is too high?

Aspergillus fumigatus produces the immunosuppressive agent Gliotoxin. Gliotoxin is a well studied mold toxin and has long been fingered as the main chemical player contributing to the virulence of A. fumigatus. 

Gliotoxin is hypothesized to be an important virulence factor in Aspergillus fumigatus. Experiments have demonstrated that gliotoxin is isolated in the highest concentrations from Aspergillus fumigatus in comparison to other Aspergillus species. This species of fungi is the most common cause of aspergillosis in humans. Gliotoxin is also the only toxin that has been isolated from the sera of patients suffering from invasive aspergillosis. These results suggest a link between gliotoxin secretion and fungal pathogenicity.

Exposure to fungal species that secrete gliotoxin is common because airborne Aspergillus fungal spores are ubiquitous in many environments. Regular environmental exposure does not typically cause illness, but can cause serious infections in immunosuppressed individuals or those suffering from chronic respiratory illnesses. Infections caused by Aspergillus fungus are called aspergillosis. There are many types of aspergillosis, but infections typically affect the lungs or the sinuses.

While not enough data exists to definitively tie chronic gliotoxin exposure to the development of cancer, chronic exposure to other immunosuppressive agents has been linked to the development of lymphomas and mammary tumors. Individuals taking immunosuppressive medications or with previous or current exposure to chemotherapy radiation are at higher risk for the development of these tumors.

The treatment approach should include:

- Educational counseling regarding environmental control and incitant avoidance.

- Neutralization antigen therapy for molds and mycotoxins for increased tolerance and effective mycotoxin detoxification.

- Intravenous and oral supplement nutrition therapy.

- Immunotherapy

- Deep heat depuration therapy (sauna detoxification).

How to inspect one's environment?

Molds and mycotoxins have been increasingly associated with illnesses due to faulty construction, water leaks, floods, and other forms of moisture accumulation that allow them to grow indoors. Visual and odor inspections, as well as spore counts and culture plates, can be used to determine the level of contamination in a building.

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