Harvard University scientists identify gut-brain connection in ALS

Researchers from Harvard University in Cambridge, Massachusetts have identified a new gut-brain connection in the neurodegenerative disease amyotrophic lateral sclerosis (ALS), according to a new study published in the journal Nature.

For the study, the researchers initially looked at the ALS genetic mutation by developing a mouse model at their Harvard University lab facility. The mice had an overactive immune response, including inflammation in the nervous system and the rest of the body, which led to a shortened lifespan.

To run more detailed experiments, the researchers also developed the mouse model in their lab facility at the Broad Institute in Cambridge, Massachusetts. Although the mice had the same genetic mutation, their health outcomes were dramatically different.

Looking for environmental differences between the mice, the researchers honed in on the gut microbiome. By using DNA sequencing to identify gut bacteria, the researchers found specific microbes that were present in the Harvard University facility mice but absent in the Broad Institute facility mice, even though the lab conditions were standardized between facilities.

The researchers then tested ways to change the microbiome and improve outcomes for the Harvard facility mice. By treating the Harvard University facility mice with antibiotics or fecal transplants from the Broad Institute facility mice, the researchers successfully decreased inflammation.

The researchers found that in mice with a common ALS genetic mutation, changing the gut microbiome using antibiotics or fecal transplants could prevent or improve disease symptoms. The findings provide a potential explanation for why only some individuals carrying the mutation develop ALS, the researchers said, and point to a possible therapeutic approach based on the microbiome.

"Our study provides new insights into the mechanisms underlying ALS, including how the most common ALS genetic mutation contributes to neural inflammation," said Kevin Eggan, PhD, professor of stem cell and regenerative biology at Harvard University, in a statement. “The gut-brain axis has been implicated in a range of neurological conditions, including Parkinson's disease and Alzheimer's disease. Our results add weight to the importance of this connection."