We've come a long way in the five years since the ice bucket challenge drew attention to amyotrophic lateral sclerosis (ALS), also called Lou Gehrig's disease. During that time, scientists have been learning more about the microbes we carry in our gastrointestinal tracts, and the powerful impact they seem to have on our health. Changes in the gut microbiome have been linked to many disorders, including inflammatory bowel disease, fibromyalgia, and colorectal cancer. Now scientists have found that the microbes in the gut may influence the course of ALS.
Reporting in Nature, the investigators from the Weizmann Institute of Science and their collaborators determined that in a mouse model, ALS got worse when they were exposed to broad-spectrum antibiotics that eliminated most of their gut microbiome. The scientists also observed that a specific type of gut bacteria can slow the progression of ALS through a compound it produces. These findings have to be confirmed in people, but research suggests that they will apply to ALS patients.
"Our long-standing scientific and medical goal is to elucidate the impact of the microbiome on human health and disease, with the brain being a fascinating new frontier," noted Immunology Professor Eran Elinav. "Given increasing evidence that microbiome affects brain function and disease, we wanted to study its potential role in ALS."
In this study, the researchers utilized mice that are likely to develop ALS, rearing them in sterile conditions, which prevented them from developing a microbiome. The mice had difficulty surviving the process, indicating to the researchers that the gut microbes were playing a role in the disease.
With cutting-edge computational tools, the scientists were able to characterize the microbiomes in these mice and compare them with healthy mice. There were eleven strains of bacteria that were changed in the mice prone to ALS, with the changes occurring before symptoms appeared. After exposing the ALS-prone mice to probiotics, including these microbial strains, one particular strain, Akkermansia muciniphila, significantly slowed the progression of the disorder in the mice, and increased their lifespan.
The investigators wanted to know how the microbe had this impact and found the molecules that Akkermansia generates and releases. One compound, nicotinamide (NAM), was found at lower levels in ALS-prone mice after exposure to antibiotics, but went up after the mice received NAM-producing Akkermansia. NAM was confirmed to be responsible for the microbe's effects on ALS after the researchers exposed mice prone to ALS to the NAM directly. These mice had significantly improved health outcomes. NAM appeared to be changing gene expression so that motor neuron function was improved.
The study authors want to investigate these findings in humans.
In the video above, the ALS association looks back on the ice bucket challenge.
Sources: AAAS/Eurekalert! via Weizmann Institute of Science, Nature