Eric Dorninger, ND, Lac

Emerging evidence suggests that Chronic Inflammatory Response Syndrome (CIRS) caused by exposure to water-damaged buildings may contribute to neuroinflammation, Parkinsonian symptoms, and potentially modifiable pathways of neurodegeneration in susceptible individuals.

Could some cases of Parkinson’s disease have an environmental origin? This article examines the growing evidence linking Chronic Inflammatory Response Syndrome (CIRS), biotoxin exposure from water-damaged buildings, and chronic neuroinflammation, while exploring emerging diagnostic biomarkers and therapeutic implications for clinicians.

When Parkinson’s Isn’t Idiopathic

Parkinson’s disease (PD) is classically defined by dopaminergic neuron loss in the substantia nigra, α-synuclein aggregation, and progressive motor decline. Yet despite decades of research, most cases remain labeled “idiopathic.”

But what if a subset of Parkinson’s disease is not idiopathic at all?

Emerging evidence suggests that environmental exposures—particularly those associated with water-damaged buildings (WDBs)—may serve as upstream drivers of chronic neuroinflammation. In patients with Chronic Inflammatory Response Syndrome (CIRS), a multisystem illness triggered by biotoxins, we observe a convergence of clinical symptoms, imaging findings, and genomic signatures that overlap strikingly with Parkinson’s disease.1

This raises a critical question:
Could Parkinson’s disease, in some patients, represent a downstream manifestation of untreated CIRS?

CIRS: A Neuroinflammatory Illness

CIRS is a chronic, innate immune-mediated condition triggered by exposure to biotoxins commonly found in water-damaged indoor environments, including endotoxins (lipopolysaccharides), Actinobacteria, and fungal fragments.2 In genetically susceptible individuals, these exposures lead to persistent immune activation and failure of normal inflammatory resolution.

While often described as systemic, CIRS is fundamentally brain-active inflammation. Patients commonly present with:

• Cognitive impairment
• Memory and executive dysfunction
• Neuropathic symptoms
• Dysautonomia
• Movement abnormalities
• Mood Phenomena (e.g. anxiety)

These findings are supported by objective data. Advanced imaging has demonstrated measurable structural brain changes in WDB-exposed patients, including alterations in cortical gray matter, ventricular size, and deep brain structures.

Importantly, these changes are not static. With appropriate treatment, including removal from exposure and targeted therapy (the CIRS Protocol), brain abnormalities have been shown to improve, establishing CIRS as a model of potentially reversible neurodegeneration.

Parkinson’s Disease as an Inflammatory Disorder

The modern understanding of Parkinson’s disease has evolved beyond a purely degenerative model. PD is now recognized to involve:

• Chronic neuroinflammation
• Microglial activation
• Mitochondrial dysfunction (Molecular Hypometabolism) 
• Immune dysregulation

Activation of inflammatory pathways—particularly NF-κB signaling and microglial cascades—contributes directly to neuronal injury and α-synuclein pathology. Environmental contributions are also increasingly recognized, with infectious and toxic exposures implicated in disease initiation and progression.

Parkinson’s disease, therefore, is not simply degenerative—it is inflammatory, environmentally influenced, and potentially modifiable.

Biotoxins and the Innate Immune Response (CIRS)

A key mechanistic bridge between CIRS and Parkinson’s disease lies in exposure to lipopolysaccharides (LPS) and other microbial fragments found in water-damaged buildings.

LPS (endotoxins) are potent activators of the innate immune system through Toll-like receptor pathways (TLR2 and TLR4) and CD14 (Cluster of Differentiation 14). Activation of these receptors drives downstream signaling via NF-κB and other inflammatory mediators, resulting in sustained immune activation.2,3,4

Experimental models have demonstrated that systemic LPS exposure can induce:

• Microglial activation
• α-synuclein aggregation
• Progressive neurodegeneration

In patients with CIRS, chronic exposure to these biotoxins leads to persistent immune signaling, impaired resolution of inflammation, and ongoing neuronal stress—conditions that closely mirror the pathophysiologic environment observed in Parkinson’s disease.

A Transcriptomic Signature Linking CIRS and Parkinson’s

Recent advances in transcriptomic analysis have provided further evidence of a connection between CIRS and Parkinson’s disease.

Using gene expression profiling, a distinct molecular signature has been identified in patients with CIRS and Parkinsonian features. This includes dysregulation in:

• Clusterin (CLU)
• Coagulation pathway genes (COAG)
• Cytoskeletal tubulin genes (TUB)

These markers—referred to as “Triple Positives”—represent a reproducible genomic fingerprint associated with Parkinson’s-like illness.

Additional findings include:

• Elevated TLR2 signaling
• Increased RELA (NF-κB pathway) activation
• Dysregulation of Akt/autophagy pathways

Together, these changes link environmental exposure to disruptions in immune signaling, cellular repair, and neuronal integrity. Notably, these abnormalities may be detectable prior to advanced clinical disease, suggesting a potential role in identifying patients in a prodromal phase of Parkinson’s.

Clinical Overlap: CIRS and Parkinsonian Features

The clinical overlap between CIRS and Parkinson’s disease is substantial. Patients with CIRS frequently exhibit:

• Tremor
• Motor slowing
• Balance disturbances
• Cognitive decline
• Autonomic dysfunction

These features closely resemble early Parkinsonian presentations. In this context, what is often labeled as “idiopathic” Parkinson’s disease may, in some cases, represent a later-stage manifestation of chronic inflammatory illness.

This perspective reframes Parkinson’s disease as a final common pathway of multiple upstream insults, including environmental biotoxin exposure.

Imaging Correlates and Reversibility

Neuroimaging findings further support this connection. In CIRS, volumetric MRI studies have demonstrated abnormalities in regions directly relevant to Parkinson’s disease, including:

• Caudate
• Putamen
• Cortical gray matter
• Ventricular structures

These areas are integral to motor control and basal ganglia function.

The critical distinction is that, in CIRS, these structural abnormalities have demonstrated partial reversibility with treatment. This challenges the assumption that neurodegenerative changes are uniformly irreversible and suggests that, when identified early, inflammatory drivers of neuronal dysfunction may be modifiable.

Treatment Implications

If a subset of Parkinson’s disease arises from chronic inflammatory activation driven by environmental exposure, early identification becomes essential.

The treatment model for CIRS includes:

1. Removal from exposure
2. Binding and elimination of biotoxins (e.g., cholestyramine)
3. Correction of inflammatory and hormonal dysregulation
4. Restoration of normal immune signaling and neuroendocrine hormones
5. Use of vasoactive intestinal peptide (VIP) to support neurorepair

Transcriptomic studies have demonstrated that treatment can be associated with normalization of gene expression patterns and clinical improvement. These findings suggest that, in select patients, addressing the upstream inflammatory driver may help stabilize—or potentially improve—neurologic function.

Clinical Screening

Clinicians should consider evaluating for CIRS in patients with:

• “Idiopathic” Parkinson’s disease
• Early or atypical Parkinsonian symptoms
• Cognitive decline without clear etiology
• Known or suspected exposure to water-damaged environments
• Treatment-resistant neurologic symptoms

Screening tools may include:

• Visual Contrast Sensitivity (VCS) testing
• Inflammatory biomarkers (C4a, TGF-β1, MMP-9)
• Transcriptomic analysis (when available)
• Environmental assessment of indoor spaces

Reframing Parkinson’s Disease

The traditional view of Parkinson’s disease as an inevitable, progressive neurodegenerative disorder is being challenged by emerging insights into inflammation, immunity, and environmental exposure.5 

While not all Parkinson’s disease can be attributed to CIRS, current evidence suggests:

For a subset of patients, Parkinson’s disease may represent a downstream manifestation of chronic innate immune activation triggered by exposure to water-damaged buildings.

Recognizing this possibility expands both diagnostic and therapeutic frameworks and introduces the potential for earlier, more targeted intervention.

Conclusion

The intersection of CIRS and Parkinson’s disease represents a meaningful shift in our understanding of neurodegeneration. By identifying environmental triggers, defining objective biomarkers, and demonstrating reversibility of brain changes, we move toward a model of care that is not only descriptive—but interventional.

For clinicians willing to look upstream, Parkinson’s disease may not be the beginning of the story—but the consequence of one that began years earlier.

References (AMA Style – Key Selections)

1. Shoemaker R, et al. Transcriptomic fingerprint for Parkinson’s disease in CIRS. Med Res Arch. 2024.
2. Shoemaker R, et al. Novel therapeutic approach to Parkinson’s disease: endotoxin, Toll receptors, and transcriptomics. Med Res Arch. 2025.
3. Dutta D, et al. TLR2/MyD88/NF-κB pathway in Parkinson’s disease. Nat Commun. 2021.
4. Wu L, et al. Systemic LPS exposure induces neurodegeneration. Glia. 2007.
5. Standaert DG, et al. Neuroinflammation in Parkinson’s disease. J Neurosci. 2016.

Eric Dorninger, ND, LAc, is a naturopathic physician, licensed acupuncturist, and founder of Roots and Branches Integrative Health Care in Louisville, Colorado. A graduate of Bastyr University with a Doctor of Naturopathic Medicine and a Master of Science in Acupuncture, he completed a two-year residency in naturopathic primary care after earning his undergraduate degree in kinesiology from the University of Colorado Boulder. Dr. Dorninger specializes in complex chronic illness, including Chronic Inflammatory Response Syndrome (CIRS), autoimmune disease, biotoxin illness, chronic fatigue, and neuroinflammatory disorders. He is a Shoemaker-certified practitioner, teaches functional medicine, and is dedicated to evidence-informed, root-cause approaches that identify and address the underlying drivers of chronic disease.