Imbalances in Brain Microbiota May Be Behind Demyelination in MS, Study Says

Alterations in microorganisms in the brains of multiple sclerosis (MS) patients could contribute to underlying disease mechanisms, including demyelination, according to researchers.

The study, “Brain microbiota disruption within inflammatory demyelinating lesions in multiple sclerosis,” was published in the journal Scientific Reports.

It is widely recognized that the balance of resident microorganisms (the microbiota) in different tissues is important to both health and disease. Imbalances in organ-specific microbiota are commonly associated with disease.

In MS, inflammatory damage to myelin, the protective layer covering nerve fibers in the brain and spinal cord, affects the white matter, inducing characteristic MS symptoms. But it is still not clear why such demyelination happens. Some studies have shown that, in part, bacteria may cause this process.

Researchers here investigated bacterial quantity and genetic diversity in autopsy brain samples from patients with MS, and compared them with age- and sex-matched samples from people without MS, which served as controls.

Tested samples of cerebral white matter presented low bacterial burden and replication, compared to active bacterial infections in other tissues, they reported. This is, however, not surprising given the sensitivity of the brain to invaders like bacteria and its defenses.

After identifying the microbiota present in all samples, researchers found that a particular group of bacteria, known as Proteobacteria, was more common in white matter samples from MS patients compared to those from non-MS individuals.

In-depth analysis of the bacterial genetic information revealed a “restricted diversity” of Proteobacteria in white matter samples of progressive MS patients, that was linked with increased inflammatory gene expression. Samples from relapsing-remitting MS patients showed a relatively broader range of bacterial species.

Researchers also found that the presence and type of bacteria in the brain was associated with host immune response. Importantly, the detection of a specific bacterial protein, called bacterial peptidoglycan (PGN), correlated with demyelination and neuroinflammation in MS brain samples, which may help to explain disease development and progression.

The team also found that PGN accumulated within demyelinating MS lesions in response to the host immune system. Inflammatory demyelination, they concluded, can be associated to a tissue-specific dysbiosis (microbiota imbalance) in MS.

“Principal component analysis revealed that demyelination, PGN and inflammatory gene expression accounted for 86% of the observed variance,” the researchers wrote. “Thus, inflammatory demyelination is linked to an organ-specific dysbiosis in MS that could contribute to underlying disease mechanisms.”