Comment; Another great article by Dr. Jill reviewing mycotoxins & their effects on the gut & the 4 major gut defensive systems.
- Mechanical: Maintains integrity of the mucosal barrier’s structure and normal function.
- Chemical: Inhibits invasion of pathogenic bacteria using chemicals such as digestive acid.
- Immune: Gut-associated proteins and special cells (such as macrophages, natural killer cells, etc.) guarantee intestinal homeostasis by regulating the immune response against harmful substances.
- Biological: A microecosystem mainly composed of intestinal flora.
Toxin: | Source: | Toxin Subtypes: | Toxin Effects: | Notes: |
Aflatoxins | Aspergillus flavus | B1 (AFB1), B2 (AFB2), G1 (AFG1) & G2 (AFG2) | Most toxic, damages DNA, carcinogenic to humans | Often contaminates foods and animal feed |
A. parasiticus | Reduced gut microbiota diversity | |||
Increase expression of certain microbiome species | ||||
Zearalenone (ZEA) | Fusarium graminearum | Reproductive System | ZEA often co-occurs with DeOxyNivalenol (DON) & Fumonisins suggesting synergy | |
Reduced gut microbiota diversity | ||||
Increase expression of certain microbiome species | ||||
Fusarium culmorum | Intestinal apoptosis | |||
Reduces level of tumor-suppressor genes in intestinal cells which may promote carcinogenesis | ||||
Ochratoxin A (OTA) | Aspergillus | Nephrotoxic | ||
Penicillium | Hepatotoxic | |||
Enterotoxic (mucosal permeability, reduced tight junction protein expression) | ||||
Induces oxidative stress | ||||
Reduces levels of anti-inflammatory cytokines | ||||
Altered gut immunity | ||||
Reduced microbiota diversity | ||||
Increase expression of certain microbiome species | ||||
Trichothecenes | Fusarium graminearum | T-2 Toxins (Type A) | Decreased glucose absorption | |
Stachybotrus chartarum | DeOxyNivalenol (DON), (Type B) | Weight loss | DON completely disrupts abundance of several microbiotal species | |
Necrotic gut lesions | ||||
Increased gut permeability/less tight junction protein expression | ||||
Decreased cytokines for pathogen removal | ||||
Reduced Absorption, ntegrity & Immunity | ||||
Fumosins | Fusarium verticillioides | Fumosin B1 (FB1) | Birth defects of Brain, Spine, Spinal Cord | Abudant in nature |
Neurological disease | ||||
Immunological Disease | ||||
Decreased enterocyte viability & proliferation | ||||
Enterocyte apoptysis | ||||
Decreased tight junction protein expression | Increased gut permeability & microbe movement to circulation | |||
Patulin (PAT) | Aspergillus | Impairs inestinal integrity–>leaky gut | Group 3 Carcinogen–not carcinogenic to humans | |
Byssochylamys | Increased gut permeability & microbe movement to circulation | Fruit-spoiling fungi | ||
0 | Penicillium | Affects distribution pattern of different types of tight junction proteins |
We’ve come a long way in understanding mycotoxins and their effects on our health. Since the identification of the first mycotoxin (aflatoxin) in 1965,1 scientists have identified more than 400 of them produced by hundreds of different fungi under various environmental conditions. I’ve written extensively about the effects of mycotoxins on the body (for examples, see Mycotoxins and Your Brain: How Invisible Fungus Can cause Brain Fog and More and Is Toxic Mold Exposure the Cause of Your Symptoms?). But new research suggests there’s another target for mycotoxins: the gut.
What are Mycotoxins?
Mycotoxins are toxic compounds that arise naturally in mold and fungi due to environmental factors. An estimated 25 percent of the world’s crops are contaminated by mold and fungal growth,1 making them most frequently occurring natural contaminants in human and animal food. However, they can also grow due to poor harvesting practices, improper storage, and less-than-optimal conditions during processing and transportation.
Chronic exposure to mycotoxins is known to have a diverse and powerful impact on human health. The toxic effect of mycotoxins is referred to as mycotoxicosis, the severity of which depends on various factors such as the individual’s age, nutritional status, and extent of exposure. Symptoms of mycotoxicoses include:2
- Abdominal pain
- Nausea and vomiting
- Anorexia
- Jaundice
- Gastrointestinal bleeding
- Fever
- Palpable liver
- Swollen legs
Mycotoxins have also been shown to:3
- Cause cancer
- Cause DNA mutations
- Disturb the development of the embryo or fetus
- Behave like estrogen
- Contribute to hemorrhages
- Damage the immune system
- Cause kidney damage
- Cause liver damage
- Cause skin damage
- Cause brain damage
Looking at these potential effects, it’s easy to see why dietary exposure to mycotoxins is of growing concern.
The Intestinal Mucosal Barrier
The gastrointestinal (GI) tract has multiple functions starting from food ingestion to nutrient absorption to elimination of waste. The architecture of the organ, which can be divided into four layers — mucosa, submucosa, muscularis propria, and serosa — serves to facilitate these responsibilities.
Let’s focus on the mucosa layer, which has an immense surface area for efficient nutrient absorption. The innermost layer of the mucosa, the epithelium layer, is a single layer of thin cells lining the gut lumen. The epithelial cells are connected by large multiprotein complexes called tight junctions, which play an important part in maintaining the integrity of the barrier. The tight junctions control the space between cells and regulate the transport of different substances.
In other words, think of the intestinal mucosal barrier as a defensive barrier that prevents toxins from infiltrating internal systems, where they interact with tissues and cause damage.
Under normal circumstances, the intestinal mucosal barrier is equipped to handle mycotoxins without incurring damage. The intestinal mucosal barrier is composed of four types of barriers, including:
- Mechanical: Maintains integrity of the mucosal barrier’s structure and normal function.
- Chemical: Inhibits invasion of pathogenic bacteria using chemicals such as digestive acid.
- Immune: Gut-associated proteins and special cells (such as macrophages, natural killer cells, etc.) guarantee intestinal homeostasis by regulating the immune response against harmful substances.
- Biological: A microecosystem mainly composed of intestinal flora.
Together, these barriers can maintain the balance between pro- and anti-inflammatory factors. They are also the key to not only maintaining the integrity of the intestinal mucosal barrier’s structure and normal function, but to also prevent pathogens and harmful substances from entering into the rest of the body.4
Mycotoxins and Gut Health
In general, mycotoxins can change the morphology and the structure of the intestinal epithelium, increasing its permeability and reducing the expression levels of tight junction proteins. They have also been shown to be able to reduce mucus and change the diversity and abundance of intestinal microflora. Here, we’ll look at some of the most common mycotoxins and how they affect gut health.
Aflatoxins
Aflatoxins are produced by Aspergillus flavus and Aspergillus parasiticus. The major aflatoxins found in human foods and animal feed are aflatoxins B1, B2, G1, and G2.5 Among them, aflatoxin B1 (AFB1) is considered the most toxic, as it can cause damage to DNA that often lead to cancer. In fact, AFB1 is classified as a group 1 carcinogen by the International Agency for Research on Cancer (IARC), indicating that it is carcinogenic to humans.6
Contamination of aflatoxins is a major concern on foods and animal feeds. Like most mycotoxins, toxicity from AFB1 has been shown to disturb the normal activities and diversity of the intestinal microflora.
Zearalenone (ZEA)
Zearalenone (ZEA) is a mycotoxin produced primarily by Fusarium graminearum and Fusarium culmorum in human foods and animal feeds. ZEA has a high rate of co-occurrence with fumonisins and DON, which suggests that these mycotoxins may be involved in synergistic and/or additive interactions.
While the reproductive system is the main target of ZEA, it can induce cell death in the intestine, although its effects do not seem to be as detrimental compared to those of other mycotoxins.7 One study also showed that ZEA reduced the level of tumor-suppressor genes in intestinal cells, which may be responsible for the carcinogenic effects of the mycotoxin.8
Ochratoxin A (OTA)
Ochratoxin A (OTA) is a mycotoxin produced by Penicillium and Aspergillus species. Exposure to OTA has been shown to be a worldwide phenomenon, with a majority of human blood samples taken from various countries showing the presence of the mycotoxin.9,10,11 Although researchers believe kidneys are the main targets of OTA, some studies suggest that the liver and the GI tract are possible targets as well.12
When animals were fed food treated with OTA, they had more lesions in their intestines and more damage in their mucosa. This can be explained by increased permeability, which is supported by the reduced level of tight junction protein expression.
Studies have also found that OTA induces oxidative stress and a significant decrease in the levels of anti-inflammatory cytokines.13 This alteration of the immune barrier renders the gut vulnerable to infection. Furthermore, like ZEA and AFB1, OTA can reduce the diversity of gut microbiota and significantly increasing the abundance of certain species.14
Trichothecenes
Trichothecenes is mainly produced by the fungi species Fusarium graminearum. There are two major types of trichothecenes that cause toxicity to humans and animals: T-2 toxins (Type A) and deoxynivalenol (DON, also known as Type B). One interaction with the GI tract, T-2 and DON can result in:
- Decreased glucose absorption
- Weight loss
- Necrotic lesions
- Increased intestinal permeability by lowering tight junction proteins expression
- Decreasing the level of chemical signals responsible for pathogen removal
- Reducing gut absorption, integrity, and immunity
When it comes to intestinal microorganisms, studies have shown that DON completely disrupts the abundance of several bacterial species, leading to an imbalance of the microbiota.15
Fumonisins
Fumonisin B1 (FB1) is abundantly found in nature, where it is produced by Fusarium verticillioides. Foods contaminated with FB1 have been shown to cause birth defects of the brain, spine, or spinal cord, as well as other types of neurological and immunological diseases.
In the intestine, FB1 decreases cell viability and proliferation, leading to cell death. Additionally, FB1 decreases the expression level of tight junction proteins, thereby increasing intestinal permeability and promoting the movement of bacteria across the barrier.
Patulin (PAT)
Patulin (PAT) is a group 3 carcinogen (not carcinogenic to humans) produced by various species of Penicillium, Aspergillus, and Byssochylamys known as fruit-spoiling fungi. The classification merely suggests that there is insufficient evidence for the carcinogenicity of PAT and may change with more research. Like other mycotoxins we’ve discussed so far, PAT targets the GI tract by impairing the intestinal barrier integrity, which allows for increased movement of bacteria like E. coli across the cell layers. Studies have also shown that PAT can affect the distribution pattern of different type junction proteins.16,17
Protecting Your Gut From Mycotoxins
The GI tract is quickly emerging as a target of mycotoxins. Although they have not been associated with specific intestinal diseases, their high prevalence in foods and animal feeds as well as the increasing amount of evidence of their deleterious effects show that there is reason for concern.
But there’s good news. I frequently prescribe products, such as Gut Immune powder and probiotics, like Probiotic Essentials with Saccharo or Megasporebiotic to improve the mycotoxin-induced gut barrier dysfunction and significantly reduce their toxicity.18,19 Animal studies have also shown that probiotics may help prevent genetic damage. In addition, you can take the products in the brand new Dr. Jill Miracle Mold Detox Box (more below).
To date, most of the research on the effects of mycotoxins has been focused on the mechanical, chemical, and immune barriers. This could be due to the technical difficulties of simulating the intestinal microbial community. Therefore, more research is needed to understand the interactions between mycotoxins and the gut microbiota for mycotoxicosis prevention and treatment.
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Now it’s time to hear from you. Are you surprised to learn about the effects of mycotoxins on gut health? What steps have you taken to reduce your exposure to mycotoxins? Share your thoughts in the comments below!
References:
1) https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5834427/
2) https://www.who.int/bulletin/archives/77(9)754.pdf
3) https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3153222/
4) https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5019909/
5) https://link.springer.com/article/10.1007%2Fs12550-012-0129-8
6) https://link.springer.com/article/10.1007%2Fs00204-016-1794-8
7) https://www.mdpi.com/2072-6651/7/6/1979
8) https://www.sciencedirect.com/science/article/abs/pii/S0378427414013952?via%3Dihub
9) https://link.springer.com/article/10.1007%2Fs002040100258
10) https://onlinelibrary.wiley.com/doi/abs/10.1002/mnfr.200600137
11) https://link.springer.com/article/10.1007%2Fs002040000157
12) https://www.sciencedirect.com/science/article/abs/pii/S0165242705002485?via%3Dihub
13) https://www.sciencedirect.com/science/article/abs/pii/S0273230017302271?via%3Dihub
14) https://academic.oup.com/toxsci/article/141/1/314/2338291
15) https://www.frontiersin.org/articles/10.3389/fmicb.2018.00804/full
16) https://www.jstage.jst.go.jp/article/tjem/233/4/233_265/_article
17) https://www.sciencedirect.com/science/article/abs/pii/S0378427411012707?via%3Dihub
18) https://pubs.rsc.org/en/content/articlelanding/2019/fo/c8fo02292e#!divAbstract
19) http://www.ccsenet.org/journal/index.php/jfr/article/view/37888
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