Is Inflammatory Bowel Disease Mold Toxicity?

Written by Guest Author: Alli Manzella

 

For many, the concept of exposure to indoor mold impacting the gut is unfathomable. Doctors acknowledge that mold causes sinus issues, asthma, aspergillosis, and allergies but anything outside of that is often considered pseudoscience. 

 

Mold illness, also known as Chronic Inflammatory Response Syndrome (CIRS), resulting from prolonged exposure to water-damaged buildings, is a multi-symptom, multi-system illness. [1,2,3,4,5] Mold exposure has been linked to various chronic and systemic conditions, including cancer and autoimmune diseases. [6,7,8]

 

Disclaimer: The following introductory content is an NwJ addition for additional reader context.  

 

What Is Inflammatory Bowel Disease?

Inflammatory Bowel Disease (IBD) is a term that encompasses chronic inflammatory conditions of the gastrointestinal (GI) tract. The primary types of IBD are Crohn’s disease and ulcerative colitis. These conditions are characterized by periods of active disease, known as flare-ups, and periods of remission. IBD can significantly impact a person’s quality of life, causing symptoms such as abdominal pain, diarrhea, weight loss, and fatigue.

 

Types of IBD

1. Crohn’s Disease: This type of IBD can affect any part of the GI tract, from the mouth to the anus, but most commonly affects the end of the small intestine (ileum) and the beginning of the colon. Inflammation can occur in patches and penetrate multiple layers of the bowel walls.

 

2. Ulcerative Colitis: This condition is limited to the colon (large intestine) and rectum. The inflammation is continuous, usually starting from the rectum and extending proximally. It affects only the innermost lining of the colon.

 

What Are the Distinctions Between IBD, IBS, and Leaky Gut Syndrome?

 

 

You may have heard of Irritable Bowel Syndrome (IBS), which is actually not classified as an IBD. IBD involves chronic inflammation and can cause permanent damage to the GI tract, whereas IBS is a functional disorder that does not cause inflammation, ulcers, or other damage to the bowel.

 

Both conditions can cause abdominal pain and changes in bowel habits, but IBS often includes bloating and is usually relieved by bowel movements, whereas IBD includes severe symptoms such as rectal bleeding, weight loss, and persistent diarrhea.

 

IBD is also diagnosed through a combination of endoscopic procedures, imaging studies, and biopsy, while IBS is diagnosed based on symptoms and exclusion of other conditions. Standard care for IBD treatment may include anti-inflammatory drugs, immune system suppressors, and surgery, whereas IBS is managed with dietary changes, medications to relieve symptoms, and stress management.

 

And while we’re at it, let’s define leaky gut. Leaky gut syndrome, also known as increased intestinal permeability, is a condition where the lining of the small intestine becomes damaged, allowing undigested food particles, toxins, and bacteria to pass through the intestinal wall and enter the bloodstream. 

 

This leakage can trigger an immune response and inflammation throughout the body, potentially leading to a variety of health issues such as food sensitivities, digestive disturbances, and autoimmune conditions. Factors contributing to leaky gut include chronic inflammation, infections, poor diet, chronic stress, and toxin exposure. 

 

The key takeaway is that while these gut illnesses are related, they are not the same (and the root cause is not always the same). 

 

Is IBD an Autoimmune Disease?

The exact cause of IBD remains unknown (but consider the powerful case presented in the remaining part of this article). It is understood that a malfunctioning immune response contributes to heightened inflammation in the gastrointestinal (GI) tract.

 

While IBD shares characteristics with autoimmune diseases, it is distinct and falls under the category of immune-mediated inflammatory diseases (IMIDs). IMIDs are conditions where chronic inflammation occurs due to an abnormal immune response. 

 

IBD is not an autoimmune illness. Crohn’s and ulcerative colitis are not autoimmune illnesses. As mentioned later in this article, these GI illnesses cannot be tested for antibodies. 

 

Autoimmune diseases are marked by an inappropriate immune response against healthy tissues and organs. For instance, rheumatoid arthritis (RA) patients often have autoantibodies targeting healthy joint tissue. IBD, however, is different.

 

Mold Illness and Gastrointestinal Symptoms

 

 

 

It is extremely common for mold-sick patients to present with gastrointestinal-related symptoms, including IBS, food intolerances, bloating, nausea, secretory diarrhea as well as alternating constipation with diarrhea. [9,10] Ulceration and rectal bleeding have been reported in human cases of mold illness and in animal studies where subjects were exposed to mycotoxins. [11,12]

 

Roughly 75% of the population will not be impacted systemically by mold, making it incredibly challenging to accept the possibility that mold can dramatically affect the health of others. 

 

Chronic illness due to mold exposure predominantly occurs within a subset of the population who have variants in Human Leukocyte Antigen (HLA) Immune Response Genes that regulate immune and inflammatory processes. [13,14] In those who carry specific HLA DR/DQ haplotypes, many biotoxins are not recognized by the body as foreign, which leads to an accumulation of mycotoxins within tissues and organs. [15,16] Moreover, these individuals will continue to retain mycotoxins from current and past exposures throughout their lifetime— resulting in an ongoing cycle of inflammation, immune dysregulation, and weakened or inappropriate immune responses. [17,18]

 

The Connection Between IBD and Mold Illness

Inflammatory Bowel Disease (IBD) refers to two conditions characterized by chronic inflammation of the gastrointestinal (GI) tract: ulcerative colitis and Crohn’s disease.   

 

Individuals diagnosed with IBD carry these specific HLA DR/DQ variants. [19] Multiple studies have confirmed associations between the HLA-DR/DQ haplotypes in both ulcerative colitis and Crohn’s disease. [20,21,22] HLA DR/DQ genes are candidates for genetic susceptibility to IBD because their products play a central role in the immune response. Intestinal epithelia of patients with IBD have increased proliferation rates and expression of HLA-DR compared to healthy controls. [23]

 

How Mold Impacts the Gastrointestinal Tract

 

 

Mycotoxins, produced by mold, can be as small as 0.1 microns, when inhaled into the lungs, they pass through alveoli directly into the bloodstream. [24] Mycotoxins are either stored away in tissues or shuttled to the liver and kidneys for excretion into bile and urine. [25,26,27,28,29,30] 

 

The gallbladder dumps bile containing mycotoxins into the duodenum, the first portion of the small intestine. Roughly 95% of bile-containing mycotoxins will be reabsorbed via the enterohepatic circulation (recycling of bile acids and other substances between the liver and small intestine), mostly through the terminal ileum, the last portion of the small intestine. Mycotoxins that are not reabsorbed will be removed through defecation. [31,32,33] While in transit out with the stool, mycotoxins have the potential to cause inflammation and ulceration throughout the entire gastrointestinal system—including the liver, gallbladder, biliary tract, and pancreas. [34,35,36,37,38,39,40,41]

 

Continued exposure to mycotoxins from water-damaged buildings and via enterohepatic circulation, where mycotoxins persist in the gastrointestinal tract, will have direct detrimental impacts on the gut microbiome. For one, mycotoxins induce an antibiotic effect on the gut microbiota and negatively impact microbial diversity. Mycotoxins also kill beneficial microbes and trigger bacteria to act pathologically by releasing highly inflammatory endotoxins and lipopolysaccharides. [42,43,44]

 

Mycotoxins impair gut-immune responses by down-regulating the expression of mucin, hindering cell responses, and preventing secretory IgA from exiting epithelial cells into the mucus layers. Secretory IgA is an innate immune component that is found on mucosal surfaces and is the first line of defense against adhesion and colonization of the intestinal linings. Research has demonstrated that mycotoxins hinder both humoral and cellular immunity of the intestinal mucosa. This includes the primary functions of the gut and mucosa-associated lymphoid tissue. The gut-associated lymphoid tissue (or GALT) is responsible for secreting glycoproteins which contain oligosaccharides that feed native strains of bacteria. [45]  

 

When these essential gut-immune functions are disordered due to mold toxicity, we see a persistent decline in microbial diversity, bacterial translocation, and a rise in recurrent bacterial infections. Including an inability to resist and clear Salmonella, Clostridium, and E.Coli, amongst many other lesser-known pathogenic bacterial infections. [46,47,48,49,50,51,52]

 

By decreasing gastrointestinal immunity, mycotoxins directly increase susceptibility to fungal, viral, and parasitic infections. [53,54,55,56] As an example, mycotoxins suppress various immune responses following Cytomegalovirus infection. [57] Non-resolving cytomegalovirus presents in features of ulcerative colitis such as diarrhea, abdominal pain, rectal bleeding, and weight loss. [58]

 

The Consequence of Compromised Gut-Immune Barriers

 

 

When these protective gut-immune barriers are compromised, antigens (including mycotoxins) can now interact with the intestinal surface. Studies have demonstrated that mycotoxins directly inhibit normal division and proliferation of intestinal epithelial cells. Mycotoxins damage intestinal villi and increase intestinal permeability. Mycotoxins also activate immune pathways and induce inflammatory responses in the intestinal epithelium. 

 

They activate lysosomes to engulf connections between intestinal epithelial cells, resulting in structural collapse. In addition, mycotoxins inhibit the self-repair processes of the intestine, eventually leading to the death and autophagy of intestinal epithelial cells. [59] This loss of gastrointestinal lining integrity and activation of localized immune-inflammatory responses has been linked to the pathogenesis of various chronic intestinal inflammatory diseases, including Crohn’s and ulcerative colitis. [60 61,62,63,64,65]

 

It is not a coincidence that in IBD, we commonly find a variety of pathogenic organisms, including bacterial or fungal overgrowth, viruses, and parasites. [66,67,68,69,70,71] While addressing pathogen load via conventional and integrative therapies helps reduce symptoms, this does not correct the underlying gut-immune deficiency. 

 

Until therapies become available that resolve gut-immune suppression, it is important to target these infections. However, this anti-pathogen approach may have long-term detrimental impacts as the association of commensal fungi, viruses, and parasites with the host is still not fully recognized in healthy versus disease states. [72] 

 

The Importance of Root-Cause Healing for Mold Illness

 

 

In recent years, there has been growing interest in the “mycobiome” and fungal overgrowth as playing a role in the pathology of IBD. [73] Research has concluded that fungal overgrowth in IBD is the result of suppression of mucosal immunity. [74] 

 

It is important to note that while mycotoxin exposures can come from endogenous sources, such as the colonization of mold and/or fungus within the sinus cavities, lungs, and gastrointestinal tract, these infections are opportunistic in nature. [75,76,77,78] Continued exposure to mycotoxins from water-damaged and endogenous sources will result in increased toxicity and further disease progression.[79,80,81]

 

Further Implications of IBD and Immune System Dysregulation

The CDC has recently changed the definition of IBD to state, “The exact cause of IBD is unknown, but IBD is the result of a weakened immune system.” [82] As there are no autoantibodies in Crohn’s or colitis, IBD is no longer thought of as an autoimmune disease. [83,84] According to the Lancet, “Ulcerative colitis is thought to occur in people with a genetic predisposition following environmental exposures; gut epithelial barrier defects, the microbiota, and a dysregulated immune response are strongly implicated.” [85]

 

It is interesting to note that those living with a genetic condition known as ‘Primary Immunodeficiency’ suffer from far greater rates of Crohn’s and colitis compared to the general public. [86,87,88] People with conditions related to immunodeficiency share a similar dysbiotic microbiota observed in IBD—demonstrating that weakened immune responses heavily impact gut function and microbiota composition. [89,90,91]

 

The concept of IBD resulting from an immune deficient state has revolutionized treatment in recent years. [92,93,94,95] Instead of focusing solely on medications that suppress downstream inflammatory responses, new therapies that seek to stimulate the immune system to adequately respond to pathogen load, dysbiosis, and barrier defects are proving to induce sustained unmedicated remission. [96,97,98]

 

Mycotoxins and Immune Dysfunction

As far as environmental factors go, mycotoxins are truly unique in how they impact the gut immune system. Mycotoxins have been proven in peer-reviewed research to cause epithelial barrier defects, gastrointestinal lining permeability, and dysbiotic changes to the microbiome. Mycotoxins dysregulate the immune system by inciting both immunostimulatory and immunosuppressive effects. [99,100,101,102,103,104,105,106,107,108,109,110] These factors combined are the fundamental basis for diagnosing IBD. [111] 

 

Mold exposure causes bidirectional immunotoxicity, harming both innate immunity, which provides the body’s first line of defense through general, non-specific mechanisms, and adaptive immunity, which involves a targeted response to specific pathogens developed over time. Mold exposure affects the proliferation, differentiation, or maturation of immune cells, such as lymphocytes, dendritic cells, and macrophages. Mycotoxin exposure increases the expression of various interleukins, chemokines, and cytokines. Including TNF-α and NF-κB pathways, all of which have been well studied and modulated in the management of IBD. [112,113,114,115]

 

Mold Illness and Mast Cell Activation Syndrome

Increased numbers of mast cells are present in the ileum and colon of patients with IBD. The release of proinflammatory mediators from activated mast cells in the intestines of patients with IBD is the result of a loss of mucosal barrier function. A fully functional mucosal lining will prevent epithelial contact with pathogens and immune-activating antigens in the gastrointestinal tract. [116,117,118] 

 

Mold exposure is implicated as a key player in the development of mast cell activation syndrome (MCAS). The resulting loss of mucosal barrier function allows antigens from the environment, food, chronic infections, and dysbiosis to chronically activate the mast cells.

 

 

Exposure to mold spores, mycotoxins, and volatile organic compounds (VOCs) will stimulate mast cells to secrete proinflammatory cytokines, histamine, prostaglandins, interleukins, and chemokines. Symptoms of MCAS are multi-system and include fatigue, poor memory, brain fog, inability to focus or have continuous sleep, anxiety, mood disorders, migraines, rashes, hives, low blood pressure, racing heart, lightheadedness, diarrhea, abdominal pain, constipation, nausea, bloating, strong PMS or Mittelschmerz symptoms, allergy-like symptoms, asthma, wheezing and shortness of breath, joint damage and pain. [119,120,121]

 

Mycotoxins from indoor mold can disrupt important cellular processes in the body. Specifically, these toxins interfere with the Janus kinase (JAK) pathway, which is crucial for transmitting signals inside cells. This pathway involves proteins called signal transducers and activators of transcription (STATs) that help regulate gene expression and immune responses. When mycotoxins hijack this pathway, they can trigger the programmed death (apoptosis) of intestinal epithelial cells, which are the cells lining the gut. This damage can contribute to various gastrointestinal issues. [122] 

 

Researchers are currently studying drugs known as Janus kinase inhibitors as potential treatments for inflammatory bowel disease (IBD). These inhibitors aim to block the harmful effects of the JAK-STAT pathway activation, thereby reducing inflammation and preventing cell death in the intestines. This research is ongoing, but it holds promise for new therapies that could help manage IBD more effectively. [123]

 

Mitochondria, the powerhouses of the cell, are essential for maintaining the health and balance (homeostasis) of the intestines. They produce adenosine triphosphate (ATP), the energy currency of the cell, which is vital for various cellular functions. Besides energy production, mitochondria play key roles in managing energy metabolism and maintaining redox homeostasis, which involves balancing the production and detoxification of reactive oxygen species to prevent cellular damage. They are also involved in regulating apoptosis, the process of programmed cell death, which is important for removing damaged cells and ensuring healthy cell turnover. Additionally, mitochondria influence intestinal immune responses, helping to protect the gut from infections and maintaining overall intestinal health.

 

Interaction between the gut microbiota and mitochondria is critically important for intestinal barrier function. [124] Mitochondrial damage caused by mycotoxins has been well studied for its relationship to many chronic diseases, including IBD. [125,126]

 

Mycotoxins, toxic compounds produced by certain molds, induce oxidative stress in the body, leading to various harmful effects. They are linked to cytotoxicity, which is the damaging or killing of cells, and can trigger apoptosis, which is programmed cell death. Mycotoxins also promote the expression of pro-inflammatory cytokines, which are signaling molecules that drive inflammation. Additionally, they can cause DNA damage, compromising genetic integrity, and reduce the capacity of phagocytes, the cells responsible for engulfing and destroying pathogens. These detrimental effects are also part of the disease presentation of Crohn’s disease and colitis. [127,128,129]

 

Mold Exposure and Nitric Oxide

Nitric oxide is one of the main signaling molecules of the immune system. Nitric oxide protects the gastrointestinal lining from a variety of stimuli, maintains mucosal perfusion, regulates peristalsis, and prevents the development of mast cell activation. [130] Exposure to mycotoxins and VOCs produced by mold ramps up a nitric oxide-mediated inflammatory response by stimulating iNOS as a defense mechanism. [131,132] This is helpful in acute situations but not when the response becomes an ongoing inflammatory process driven by mycotoxin exposure while living in a water-damaged home. The up-regulation of iNOS has been shown to correlate with prolonged colonic inflammation, especially within epithelial cells. [133]

 

Conversely, extended periods of mycotoxin exposure will deplete nitric oxide production, which can modify gastrointestinal functions. [134] Mycotoxins stimulate the production of reactive oxygen species (ROS), including harmful molecules like peroxynitrite. These reactive molecules can cause significant oxidative damage to cells and tissues, contributing to various health issues and exacerbating conditions such as inflammation and cellular injury. [135,136] 

 

Peroxynitrite is associated with the trigger of cytotoxic processes, including lipid peroxidation, where peroxynitrite reacts with lipids in cell membranes, causing oxidative damage. This damage weakens the cell membranes, making them less effective at protecting the cell. Additionally, peroxynitrite can cause DNA damage, compromising the cell’s genetic material. Both lead to increased permeability in epithelial cells, ultimately making the cell lining in the gut more susceptible to allowing harmful substances to pass through. 

 

There have been many studies looking at iNos and Peroxynitrite in IBD. [137] Scientists have learned that Mesalamine, a medication used in the treatment of IBD, is a potent scavenger of Peroxynitrite. [138] Although the mechanism of action of Mesalamine is multifactorial, one of its therapeutic effects may be the ability to scavenge Peroxynitrite.

 

Mycotoxins also damage the enteric nervous system leading to a multitude of neurological disorders as well as peripheral neuropathy. [139,140,141] Damage to the nerves impacting the GI tract can result in motility disorders, including hypomotility, hyperperistalsis, gastroparesis, and biliary dyskinesia. There is a clear correlation between many chronic digestive issues and peripheral neuropathy. [142]

 

The Role of MSH in Mold Illness and IBD

In mold illness, melanocyte-stimulating hormone (MSH) will be low in over 95% of patients. [143] MSH is a regulatory neuropeptide that controls many other hormones, inflammatory pathways, and basic defenses against invading microbes. [144] MSH is antimicrobial as well as antifungal and protects against cytokine-induced barrier damage of intestinal epithelial monolayers. [145,146] 

 

Without adequate levels of MSH, we see a loosening of tight junctions within epithelial linings. MSH plays an important role in protecting intestinal cells from oxidative damage. Animal studies show MSH prevents the development of IBD, and can be used to modulate disease severity and induce remission. [147]

 

IBD and Mold Illness Biomarkers

 

 

In IBD, we see elevated levels of TGF Beta-1 and MMP-9 as well as deficiencies in VIP, ADH, and VEGF. These biomarkers are part of a series of labs that are diagnostic of mold illness. [148,149] 

 

For some time now, researchers have been attempting to modulate these biomarkers in IBD without being able to clearly identify what actually causes these perturbations. [150, 151, 152, 153, 154, 155, 156, 157, 158, 159, 160, 161, 162] These biomarkers play a significant role in inflammatory processes, immune system activation, and regulation, as well as maintaining colonic epithelial barrier function. [163,164,165,166,167,168,169,170,171,172,173]

 

Mold Toxicity and Food Sensitivities

People suffering from mold toxicity often report an increase in food sensitivities. The most common is gluten intolerance but many react to foods containing dairy, eggs, and yeast. 

 

Foods that are rich in specific carbohydrates, FODMAPS, sulfur, sulfites, oxalates, histamines, and lectins may also cause an uptick in symptoms. Non-allergy-related food intolerances can be caused by cholestasis or a decrease in bile salt excretion, pancreatic insufficiency, MCAS, loss of mucosal barrier function, damage to the gastrointestinal lining, malabsorption, dysbiosis, small intestinal bacterial or fungal overgrowth, and motility disorders. [174,175,176] 

 

All of these are associated with exposure to mycotoxins and have profound impacts on quality of life. [177,178,179,180,181,182,183,184,185,186]

 

Does Mold Illness Cause IBD?

 

 

Multiple studies have implicated mycotoxin exposure to be a factor in the development of IBD. [187, 188, 189, 190, 192, 193, 194, 195, 196, 197, 198, 199, 200] Sadly, no direct causative research has been done looking at indoor environmental mold exposure, as mycotoxins are predominantly studied as food-based toxicants. The disconnect lies in the lack of understanding that, regardless of the route of exposure, mycotoxins will impact the gut in various direct and indirect ways, as outlined in this article. 

 

This begs the question: With all this research, how have we continued to ignore mold as a root cause of gastrointestinal illnesses? especially given the fact that very little is available to truly manage these conditions. Protocols exist now to treat mold toxicity and its downstream effects that could easily be implemented within the field of gastroenterology.  

 

Closing Thoughts

While the supporting evidence and clinical practice strongly suggest that mold illness is more than likely a root cause of IBD and other GI concerns, it’s important to note that there are many other root causes of these conditions as well. From leaky gut syndrome to various lifestyle factors, it’s likely a complex interplay of different factors that trigger the massive inflammatory response within the gut. Working with the right practitioner is essential for discovering your root cause.

 

This guest article was written by Functional Nutrition and Environmental Health Specialist, Alli Manzella. Alli and her team are spearheading a grassroots, volunteer effort to support research and streamline root-cause therapies in gastroenterology. To learn more, please visit their website here or Instagram here. 

 

To learn more about how mold impacts the gut and Alli’s work, click here.

 

Work With Our Trusted Mold Illness Gut Specialist Practitioners

The Nutrition with Judy practice is honored to be trusted CIRS Mold Illness practitioners, having served hundreds of clients and patients from around the globe. We’re passionate about helping our clients achieve root-cause healing in order to lead the best quality of life possible that’s nearly symptom-free. Our team is dedicated to helping CIRS Mold Illness patients navigate this complex illness. If you think you’re suffering from CIRS or mold illness, start with our White Glove Service for comprehensive care.