A new study led by scientists at Harvard University provides more convincing evidence of the link between the development of amyotrophic lateral sclerosis (ALS, or metastasis) and the gut microbiome. The researchers described the findings as “extraordinary” after mice with the same genes showed different health outcomes determined by their specific gut bacterial communities.
Mutations in a gene called C9orf72 have led to more familial cases of ALS than any other genetic variant. ALS is often thought to be caused by a relative balance of genetic and environmental factors, and while researchers have found a homeine in some specific genetic variants associated with the disease, they still don’t know what specific environmental factors play a role.
The new study stems from an initial surprise observation. Mice bred with the C9orf72 gene mutation designed for the ALS model showed significantly different health effects in two different locations. “Many of the inflammatory characteristics we consistently and repeatedly observed in Harvard facility mice did not exist in Broad facility mice,” explained Aaron Burberry, lead author of the new study. “What’s even more shocking is that the Broad facility mice live to old age. These observations have inspired our efforts to understand what these two different environments may have contributed to these different outcomes. “
After examining a number of potential variables that could explain these substantial different health outcomes, the researchers focused on differences in the microbiome in animals as a possible factor. DNA sequencing did confirm some microbial differences between the two cohort mice, although laboratory conditions were similar.
“At this point, we reached out to the wider scientific community because many different groups studied the same genetic mouse models and observed different results,” Burberry said. “We collected microbiome samples from different laboratories and sequenced them. In the institutions hundreds of miles apart, very similar gut microbes were associated with the extent of the disease in these mice. “
Finally, in a Harvard experiment, the researchers altered the microbiome of ALS primitive mice to see if it could alter normal inflammatory responses in animals. Antibiotics destroyed the microbiome in the guts of ALS mice, successfully reducing the inflammatory response. Transplanting the feces of healthy mice with MUTATIONs in the ALS gene into unhealthy mice also produced improved immunity and longer life.
A study last year led by scientists at the Weizmann Institute of Science found that several specific species of gut bacteria appear to play a role in the onset of ALS symptoms. The study worked with different ALS mouse models, focusing on mutations in the SOD1 gene, another genetic mutation associated with familial ALS.
The new study looked at different genetic animal models and identified different types of gut bacteria. The basic hypothesis of the study suggests that not that gut bacteria are the only cause of ALS, but that it works with genetic predispositions that trigger disease development.
“Our study focused on the most common mutant genes in ALS patients,” said Kevin Eggan, lead author of the new study and a professor of stem cell and regenerative biology at Harvard University. “One notable finding is that the same mouse model — with the same genetic properties — has very different health outcomes in our different laboratory facilities. We trace the different results back to the different gut microbiomes in these mice, and now we have an intriguing assumption as to why some individuals who carry this mutation develop into ALS, while others don’t develop als. “
The new study was published in the journal Nature.