What Are the Causes of CIRS? Understanding the Full Biotoxin Burden
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 left, cleaned, or remediated, and expected to feel better. But you didn’t.
You’ve heard of Chronic Inflammatory Response Syndrome (CIRS). Maybe you’ve even been diagnosed. You know it has something to do with mold and inflammation. But what if you’ve left the mold behind and are still reacting? What if mold is only part of the picture?
The truth is, CIRS isn’t just a mold illness. 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. About 24% of the population carries HLA genes that impair their 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.
Mold (Mycotoxins and Fungal Fragments)
Yes, mold is a big one. Specifically, mycotoxins (toxic secondary metabolites produced by mold) and fungal fragmentsare 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.
What most websites miss?
Mycotoxins aren’t the only issue. Beta glucans, cell wall fragments from fungi, and volatile organic compounds (VOCs) released by molds can also trigger immune responses—even after active growth is gone.
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.
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.
Fun fact: Actinobacteria are a natural part of soil microbiomes. So if your building has poor drainage or sits on wet ground, it’s more likely to become colonized by these organisms.
Endotoxins (From Gram-Negative Bacteria)
Endotoxins are released by the breakdown of gram-negative bacteria. They’re especially common in buildings with HVAC systems, standing water, or bacterial contamination. Endotoxins can remain in the air and on dust particles long after the initial water 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.
In CIRS, endotoxins can amplify inflammation even after mold and actinobacteria have been cleared—making them a key, but often missed, contributor.
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.
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-like 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 mold 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-\u03b21, and VCS) to diagnose and track recovery.
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.
- Not all CIRS is caused by mold; Lyme and bacteria can 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.
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.
What if your symptoms aren’t just mold-related after all?
