Gut Microbiome Could Play a Role in Multiple Sclerosis

Research shows that gut flora may be involved with the progression of many infections and diseases. Findings from a new study published by the National Academy of Sciences suggests that specific gut microbes are linked to multiple sclerosis (MS) in humans.

Specifically, the study authors hypothesize that gut microbes play a role in neurodegeneration that leads to severe disability and death among patients with MS. They hope that these findings will further understanding of the causes of MS and implement changes to the gut microbiome.

Although much information about MS has come to light in the past few years, it is still largely unclear why the immune system attacks myelin.

“The field has been very successful in identifying genes associated with susceptibility to MS, but I’ve never been satisfied with amount of risk that we’ll be able to explain with just genetics,” said senior author Sergio Baranzini, PhD. “Even identical twins, who share the same genetic inheritance, only share an MS diagnosis about 35% of the time. It’s clear the genome is important, but environmental factors must also play a major role.”

Previous studies have suggested environmental factors can contribute to MS, including smoking, diet, and environmental exposure; however, the biological impact of these factors is hard to prove, according to the authors.

Numerous studies have shown that the gut microbiome can influence the immune system, suggesting that it may also play a role in MS. The authors hypothesize that since the intestine is a significant link between the immune system and outside factors, it may affect the onset and progression of MS.

“This was such a novel question, especially at that time,” said researcher Egle Cekanaviciute, PhD. “No one had looked at the microbiome in MS — almost no one had looked at the role of gut microbes beyond digestive diseases.”

In the study, the authors analyzed the gut microbiome of 71 patients with MS and 71 control patients. The investigators tracked which bacteria were more common or less common in patients with MS compared with the controls. Then, they looked closely at how the differences may affect the immune system’s attack on myelin, according to the study.

The investigators took a multi-pronged approach to testing the function of various gut bacteria among patients with MS.

The researchers first analyzed whether bacteria could change immune cell functions to make them pro- or anti-inflammatory. In vitro experiments showed that 2 bacteria common among patients with MS caused the immune cells to become pro-inflammatory, while a species of bacteria that triggers immune-regulatory responses was reduced in this population, according to the study.

The authors introduced the 3 species of bacteria into mice who lacked a microbiome and discovered similar effects.

To explore how a complex microbial ecosystem may influence neurodegeneration among patients with MS, the investigators performed fecal transplants on mice models of MS. Replacing the microbiome of the mice with the microbiome of human patients with MS resulted in the animals losing immune-regulatory cells. These mice developed severe neurodegeneration.

The authors note that these findings suggest that the microbiome could contribute to MS progression, according to the study. They hypothesize that particular gut microbes can result in high levels of inflammation that can heighten the immune attack on myelin.

“To be clear, we don’t think the microbiome is the only trigger of MS,” Dr Cekanaviciute said. “But it looks like these microbes could be making the disease progression worse or better — pushing someone with genetic predisposition across the threshold into disease or keeping them safe.”

Since the microbiome can be easily altered, researchers may be able to develop new, non-invasive therapies for patients with MS.

“The microbiome is very malleable,” Dr Baranzini said. “You could relatively easily change it in an adult who has MS or is susceptible — something you cannot do with their genetics. This is not a magical approach, but it is hopeful.”