What are All the Causes of CIRS?

It usually starts with mold. Maybe it was a leaky roof or a musty basement you barely noticed. Maybe you were told it couldn’t be mold because it wasn’t visible. So you cleaned, remediated, or moved and expected to feel better. But you didn’t.

In fact, you got worse.

This is a hallmark sign of CIRS, or Chronic Inflammatory Response Syndrome. CIRS is caused by a genetic anomaly that prevents your body from recognizing and expelling mold. Instead, your immune system is in a constant state of inflammation as it continually attacks the mold. Over time, this chronic inflammation starts to show up as mysterious symptoms:

Chronic fatigue
Ongoing pain, sometimes diagnosed as fibromyalgia
IBS
MCAS
MCS
Electronic sensitivities (EMF)
And many other illnesses and symptoms.

However, CIRS isn’t just caused by mold. It’s a chronic immune system disorder caused by biotoxin exposure—and mold is just one of several culprits. Understanding all the potential sources of exposure is the missing link for many patients who still feel sick despite doing “all the right things.”

Let’s explore the full range of CIRS triggers, the science behind them, and what most websites fail to mention.

What Is CIRS, Really?

Chronic Inflammatory Response Syndrome (CIRS) is a multi-system, multi-symptom illness triggered by exposure to biotoxins in genetically susceptible individuals. The gene that causes CIRS is the HLA gene, which is carried by about 24% of the population. This gene impairs the ability to clear these toxins once exposed (Shoemaker et al., 2010).

The immune system, unable to eliminate the biotoxins, stays stuck in a chronic inflammatory loop. This leads to a cascade of symptoms—fatigue, brain fog, muscle pain, sensitivity to chemicals or food, and much more.

Most people think of mold as the only trigger. But mold is just one piece of a much larger biotoxin burden. Below, we’ll go through all of the biotoxins known to cause CIRS.

Understanding the Full Biotoxin Burden

Biotoxin #1: Mold (Mycotoxins and Fungal Fragments)

Although there have been many discoveries of other toxins that cause CIRS, mold is still number one. Specifically, mycotoxins (toxic secondary metabolites produced by mold) and fungal fragments are well-established CIRS triggers.

The Shoemaker Protocol relies on HERTSMI-2 or ERMI testing to quantify mold contamination in buildings using DNA-based methods. This is different from visual inspections or air sampling.

Biotoxin #2: Actinobacteria (Gram-Positive Bacteria)

Found in water-damaged buildings, actinobacteria are a group of gram-positive, filamentous bacteria that release inflammatory exotoxins. These bacteria are small enough to become airborne and are often overlooked in standard mold testing.

Actinobacteria are the most common cause of CIRS.

Dr. Shoemaker’s research has shown that actinobacteria can be just as inflammatory as mold spores. They produce endotoxin-like molecules that can activate the innate immune system, especially in genetically susceptible individuals.

Good to know: these bacteria can colonize more than just your home! If your home testing comes back clean, that doesn’t mean you’re free from exposure. Recent research suggests actinobacteria on your skin can also be an ongoing source of exposure. (source, source)

Biotoxin #3: Endotoxins (From Gram-Negative Bacteria)

Endotoxins are released by the breakdown of gram-negative bacteria. They’re especially common in buildings with sewer lines, sump pumps, or bacterial contamination. Endotoxins can remain in the air and on dust particles long after the initial damage has been addressed.

These molecules bind to Toll-like receptor 4 (TLR4) on immune cells, triggering systemic inflammation. This is why endotoxins are considered among the most potent activators of the innate immune system.

Endotoxins are the second most common cause of CIRS.

In CIRS, endotoxins can amplify inflammation even after mold and actinobacteria have been cleared—making them a key, but often missed, contributor.

Biotoxin #4: Beta Glucans (Fungal Cell Wall Fragments)

Beta glucans deserve a section of their own. These polysaccharides are found in the cell walls of fungi, including non-toxic and dead mold. Think of them as mold residue. Even if the mold is “dead” or cleaned, beta glucans can linger in dust and trigger immune dysregulation.

Why does this matter?

Because many remediated homes still cause symptoms in CIRS patients—not due to active growth, but due to leftover beta glucans that aren’t properly cleaned. These are not detected by typical mold tests, but they can continue to provoke an immune response.

Biotoxin #5 Lyme Disease (Borrelia burgdorferi)

Yes, Lyme disease can cause CIRS.

In fact, one of the original subgroups identified by Dr. Shoemaker as susceptible to CIRS was patients with Borrelia burgdorferi exposure. Unlike traditional Lyme diagnoses that focus on active infection, Shoemaker’s model recognizes that the biotoxins released by Borrelia can also lead to a CIRS-like immune profile.

In genetically susceptible individuals, Lyme disease can trigger a chronic inflammatory response even after the infection is gone. This is why many post-treatment Lyme patients continue to experience debilitating symptoms: their immune system is dysregulated, not just infected.

What most websites get wrong is treating CIRS-Post Lyme with endless antibiotics. But if the problem is immune activation, not ongoing infection, antibiotics won’t help.

How This All Comes Together

Understanding that CIRS is a biotoxin illness—not just a mold illness— is a paradigm shift for many patients. If you’re only treating for mold, but still reacting, it may be because other biotoxins are still in your environment.

Here’s the hard part: these biotoxins can’t be seen or smelled. And standard testing often misses the full picture. That’s why the Shoemaker Protocol uses validated environmental tests (like ERMI/HERTSMI-2) and medical markers (like C4a, TGF-beta 1, and VCS) to diagnose and track recovery.

If your HERTSMI-2 results look good, that’s not enough to confirm that you’re out of biotoxin exposure. You still need to run proper testing for:

Endotoxins
Beta Glucans
Actinomycetes

At Flourish Clinic, we specialize in helping patients identify which specific biotoxins are contributing to their symptoms. Whether it’s mold, Lyme, endotoxins, or bacterial fragments, we’re trained to interpret the labs, assess the environment, and implement the full Shoemaker Protocol.

Things Most Websites Won’t Tell You

Mold plates are useless for diagnosing CIRS triggers.
Clean homes can still harbor actinobacteria, endotoxins, and beta glucans.
You don’t need to see mold for it to make you sick. Spore counts need to be >25,000 to see mold. There can still be a serious mold problem even when it’s not visible.
Not all CIRS is caused by mold; Lyme, actinobacteria, endotoxins, and beta glucans all play a major role.
Some Actinobacteria species can colonize YOU. Making your body the ongoing source of exposure.
Urinary mycotoxin testing is not a valid way to diagnose CIRS.

Does CIRS go away?

The good news is, while it is impossible for CIRS to go away on its own, CIRS can be treated. The Shoemaker Protocol, created by Dr. Ritchie Shoemaker, is the only scientifically proven method of treating CIRS. This groundbreaking 12 step protocol addresses everything that plays a role in CIRS, including:

Environmental remediation
Binding and expelling biotoxins
Treating MARCoNS
Correcting hormonal dysfunction

With the guidance of a trained Shoemaker Protocol practitioner, the protocol takes about a year to complete. However, when done correctly the success rate is upwards of 85%.

FAQs

Is mold the only cause of CIRS?

While mold is the top cause of CIRS, it has many related biotoxins that also cause CIRS. These include:

- Actinobacteria
- Endotoxins
- Beta Glucans
- Lyme Disease (Borrelia burgdorferi)

What are Actinobacteria, or Actinomycetes?

Actinobacteria are a group of gram-positive, filamentous bacteria that release inflammatory exotoxins. These bacteria are small enough to become airborne and are often overlooked in standard mold testing.

What are Endotoxins?

What are Beta Glucans?

Beta Gluons are polysaccharides that are found in the cell walls of fungi, including non-toxic and dead mold. Think of them as mold residue. Even if the mold is “dead” or cleaned, Beta Glucans can linger in dust and trigger immune dysregulation.

Can Lyme Disease cause CIRS?

Yes, the same bacteria that cause Lyme Disease, called Borrelia burgdorferi, release a biotoxin that can cause CIRS.

What is the best way to test for the causes of CIRS?

If your HERTSMI-2 results look good but you’re still sick, you need to run proper testing for:

- Endotoxins
- Beta Glucans
- Actinomycetes

Does CIRS go away?

The good news is, while it is impossible for CIRS to go away on its own, CIRS can be treated. The Shoemaker Protocol, is a groundbreaking 12 step protocol that addresses everything that plays a role in CIRS, including:

- Environmental remediation
- Binding and expelling biotoxins
- Treating MARCoNS
- Correcting hormonal dysfunction

With the guidance of a trained Shoemaker Protocol practitioner, the protocol takes about a year to complete. When done correctly the success rate is upwards of 85%.

Final Thoughts

If you’ve done the mold work but you’re still reacting, it may be time to look deeper. Understanding the full biotoxin burden is essential for true recovery from CIRS.

Do you think you have CIRS? Book a complimentary 15-minute phone chat with one of our Shoemaker practitioners!

Book Here

Mark Volmer has attained the highest level of Shoemaker Protocol certification, and is one of only two of Canada’s Shoemaker Protocol practitioners. The Shoemaker Protocol is the only scientifically proven method of treating CIRS.