The clue that gut bacteria could contribute to Amyotrophic Lateral Sclerosis — commonly known as ALS or Lou Gehrig’s Disease — came when Aaron Burberry moved genetically altered mice from one lab to another.
“Same cages, same food, but we learned that the gut microbiome differed between these environments,” said Burberry, a professor and researcher at Case Western Reserve University's School of Medicine.
Burberry said changes in the intestinal flora in the relocated mice altered concentrations of inflammatory chemicals in the animals’ nervous systems.
“And we showed that if we made the gut microbiome more similar to the environment where the mice were protected, we could dial down the inflammation in their brains of those animals," he said.
Those findings could lead to breakthroughs in the way ALS is treated in people, Burberry said. The disease causes nerve cells to break down in the brain, leading to muscle weakness. It can progress to affect walking, talking and chewing.
In Burberry's research, the mice were engineered to have mutations in a gene known as C9ORF72, which is believed to be involved in around 10% of human cases of ALS. But no one knew how aberrations in this gene contribute to the disease.
That is until Burberry, formerly of Harvard University, published his new work in the Science Translational Medicine journal.
Burberry showed that a protein produced in the gut that activates certain immune cells was present in the central nervous system of ALS patients.
“It's called CD80 and people hadn't seen elevation of CD80 in ALS patients before," Burberry said.
The question for Burberry was, why was this happening?
“People have known for a long time that the brains of people who are experiencing ALS are inflamed,” he noted.
He said the CD80 protein was influencing the production of another immune factor, Interleukin 17A — or IL-17A — which led to inflammation in the brains of mice with the C9ORF72 mutation.
In a series of experiments, including fecal transplants in mice, he showed that blocking IL-17A in mice with ALS improved their symptoms. Crucially, Burberry showed that “by generally suppressing gut microbes, the animals performed better, they could run longer and they had less inflammation on the brain.”
He said this explains the differences researchers were seeing in the mice that had been moved between labs.
“The gut microbiome was different between these different environments, and that was driving these changes in the outcome,” Burberry said.
Burberry added drugs currently used to treat autoimmune diseases like psoriasis and rheumatoid arthritis that block production of IL-17A could be repurposed to treat ALS.
He’s also taking a look at how altering gut bacteria can improve brain health.
“It's very interesting to understand what components of our environment might be shaping our gut microbiota that might influence our peripheral immune system and our brain,” Burberry said.
His team is developing probiotics to see if they could be used to treat or prevent ALS in human patients.
“We can leverage the gut microbiome to change our susceptibility to brain diseases,” he said.
