Researchers Investigate Novel Paradigm Connecting MS to Hygiene Hypothesis, Microbiome

Researchers recently developed a novel paradigm that connects the pathophysiology of multiple sclerosis (MS) to the hygiene hypothesis and the microbiome, according to a analysis published by Autoimmunity Reviews.

The researchers had hypothesized that the microbiome in MS represents a defective environment that does not provide normal levels of toll-like receptor (TLR2)-tolerizing bacterial products to the systemic immune system.

“Consistent with the hygiene hypothesis, we posit that this defective microbiome function results in abnormally regulated systemic innate immune TLR2 responses that play a critical role in both the inflammatory and defective remyelinative aspects of MS,” the authors said. “We have completed proof of concept studies that support the inflammatory, remyelinating, and human immune response components of this paradigm.”

The review reported that abnormally enhanced TLR2 signaling is a key in both the autoreactive central nervous system (CNS) inflammation and defective remyelination in MS. Additionally, abnormally enhanced TLR2 responsiveness is dependent on both a microbiome that is defective in providing adequate TLR2-tolerizing pathogen-associated molecular patterns (PAMPs) to the systematic immune system and hygiene hypothesis, according to the report.

“In terms of the hygiene hypothesis and MS, the microbiome is the relevant 'environment' and its defective delivery of 'environmental' PAMPs to the systemic immune system makes it functionally 'too clean.' The result is innate immune over-responsiveness that we postulate is critical to the pathophysiology of MS,” noted the authors.

The authors outlined several studies which support the inflammatory component, the remyelinating component, and the human immune response component of the paradigm. The researchers suggest that these studies act as the foundation for futher documentation and the relevance of the paradigm in MS.

The researchers concluded that the induction of TLR2 tolerance may represent a novel 2-pronged approach to treating MS by inhibiting autoimmune inflammation while facilitating myelin repair.

Reference

Wasko N, Nichols F, Clark R. Multiple sclerosis, the microbiome, TLR2, and the hygiene hypothesis [published online November 15, 2019]. Autoimmunity Reviews. doi :10.1016/j.autrev.2019.102430