Study identifies link between gut microbiome and neurodegenerative disease

Researchers from Harvard University have discovered a new link between the gut and the brain in amyotrophic lateral sclerosis (ALS), a neurodegenerative disease.

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They discovered that in mice with a common ALS genetic mutation, altering the gut microbiome using fecal transplants or antibiotics could inhibit or enhance the symptoms of the disease.

The study outcomes offer a possible explanation for why ALS is manifested only in certain individuals carrying the mutation.

The researchers also underpinned a potential therapeutic approach depending on the microbiome. The study was published in the Nature journal.

Our study focused on the most commonly mutated gene in patients with ALS. We made the remarkable discovery that the same mouse model—with identical genetics—had substantially different health outcomes at our different lab facilities. We traced the different outcomes to distinct gut microbial communities in these mice, and now have an intriguing hypothesis for why some individuals carrying this mutation develop ALS while others do not.”

Kevin Eggan, Professor, Department of Stem Cell and Regenerative Biology, Harvard University

Different facilities, different outcomes

Initially, the researchers examined the genetic mutation of ALS by creating a mouse model in their lab facility at Harvard University. The mice showed an overactive immune response such as inflammation in the nervous system, as well as in the rest of the body, which reduced their lifespan.

The scientists also created the mouse model in their laboratory at the Broad Institute, where Eggan serves as the director of stem cell biology at the Stanley Center for Psychiatric Research, for conducting experiments that are more detailed.

Surprisingly, the mice displayed the same genetic mutation but their health outcomes appeared to be very different.

Many of the inflammatory characteristics that we observed consistently and repeatedly in our Harvard facility mice weren’t present in the Broad facility mice. Even more strikingly, the Broad facility mice survived into old age. These observations sparked our endeavor to understand what about the two different environments could be contributing to these different outcomes.”

Aaron Burberry, Study Lead Author, Harvard University

Burberry is also a postdoctoral fellow in Eggan’s laboratory.

Searching the gut microbiome

The researchers looked for the environmental changes between the mice by focusing on the gut microbiome.

They used the DNA sequencing technique to detect the gut bacteria and discovered particular microbes that were present in the Harvard facility mice but not in the Broad facility mice, although both facilities had standardized laboratory conditions.

At this point, we reached out to the broader scientific community, because many different groups have studied the same genetic mouse model and observed different outcomes. We collected microbiome samples from different labs and sequenced them. At institutions hundreds of miles apart, very similar gut microbes correlated with the extent of disease in these mice.”

Aaron Burberry, Study Lead Author, Harvard University

The scientists then experimented with a number of methods to modify the microbiome and enhance the outcomes for the Harvard facility mice. The researchers effectively reduced the inflammation by treating the Harvard facility mice with fecal transplants or antibiotics from the Broad facility mice.

Gut-brain connection

The researchers also discovered a crucial link between the gut and the brain by investigating the association between environmental and genetic factors in ALS.

The gut microbiome can potentially impact the disease severity, whether the persons with the genetic mutation develop ALS, the associated condition frontotemporal dementia, or no symptoms at all, and can be a promising target for treatment.

“Our study provides new insights into the mechanisms underlying ALS, including how the most common ALS genetic mutation contributes to neural inflammation. 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,” Eggan concluded.