Science

ALS and gut bacteria linked in “remarkable” new Harvard study

ALS and gut bacteria linked in...
After discovering genetically identical mice displaying dramatically different health outcomes between two different research facilities, scientists found gut bacteria to be a main influencing factor
After discovering genetically identical mice displaying dramatically different health outcomes between two different research facilities, scientists found gut bacteria to be a main influencing factor
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After discovering genetically identical mice displaying dramatically different health outcomes between two different research facilities, scientists found gut bacteria to be a main influencing factor
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After discovering genetically identical mice displaying dramatically different health outcomes between two different research facilities, scientists found gut bacteria to be a main influencing factor

A new study, led by scientists from Harvard University, is offering more compelling evidence of a link between the development of amyotrophic lateral sclerosis (ALS) and the gut microbiome. One researcher described the discovery as “remarkable”, after finding genetically identical mice displayed different health outcomes determined by their specific gut bacteria communities.

Mutations in a gene called C9orf72 account for more familial cases of ALS than any other genetic variant. ALS is generally thought to be caused by a relatively equal balance of genetic and environmental factors and, although researchers have homed in on a number of particular genetic variants that can be associated with the disease, it is still unknown what particular environmental elements play a role.

This new research stemmed from an initial unexpected observation. Mice bred with C9orf72 mutations designed to model ALS displayed significantly different health effects at two separate locations.

“Many of the inflammatory characteristics that we observed consistently and repeatedly in our Harvard facility mice weren’t present in the Broad facility mice,” explains lead author of the new study, Aaron Burberry. “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.”

After investigating a number of potential variables that could account for these substantially different health outcomes, the researchers focused in on differences in the animal’s microbial flora as the possible primary factor. DNA sequencing indeed confirmed a number of microbial differences between the two cohorts of mice, despite similar lab 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,” says Burberry. “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.”

Finally, the researchers experimented with altering the microbiome of the original ALS mice at the Harvard facility, to see whether this would modify the inflammatory responses normally seen in the animals. Antibiotics, disrupting microbial populations in the gut of the ALS mice, successfully decreased inflammation. Fecal transplants from the healthy mice with the ALS genetic mutation to the unhealthy mice also generated immune improvements and increased lifespan.

Last year a study led by scientists from the Weizmann Institute of Science homed in on several specific gut bacteria species that seemed to play a role in the onset of ALS symptoms. That study worked with a different ALS mouse model, focusing on mutations in the SOD1 gene, another genetic variant linked with familial ALS.

This new study examined a different genetic animal model, and identified different gut bacteria species. The fundamental hypothesis building from this growing body of research suggests, not that gut bacteria is a sole cause of ALS, but it instead plays a role alongside genetic predispositions in triggering the development of the disease.

“Our study focused on the most commonly mutated gene in patients with ALS," says Kevin Eggan, corresponding author on the new study and professor of stem cell and regenerative biology at Harvard. "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.”

The new research was published in the journal Nature.

Source: Harvard University

5 comments
Nobody
Gut bacteria has become one of the most promising fields in medicine. Autoimmune diseases in humans have been linked for some time to gut bacteria and a condition called leaky gut.
Douglas Bennett Rogers
The great thing about autoimmune diseases is many of them can be easily tested for and cured with an elimination diet.
guzmanchinky
Astonishing how the two are linked.
Nobody
@Douglas Bennett Rogers I'm afraid it is not that simple. Elimination diets(such as gluten free) have worked for a few with Hashimoto's thyroid disease or celiac disease but autoimmune is genetic and very often extremely difficult to diagnose. Two members of my family died when their immune systems attacked their red blood cells. My cousin only lived 13 days after the first day he showed symptoms. My Father had to go to Mayo clinic and then it took a week of tests to find the cause. They too were stumped until I told them about my autoimmune problems. With powerful immune suppressing drugs he lived another six years. I also have autoimmune as does my youngest son. I first had sarcoidosis in my lungs and then Hashimoto's that destroyed my thyroid and now rheumatoid arthritis. My son has Hashimoto's but elimination diets have done nothing for us nor has it done anything for a friend with Multiple sclerosis which is also an autoimmune disease. Sorry but your statement that autoimmune can easily be tested and cured shows you need to research this subject much more. Unfortunately, I know far more about it and its variations than I ever wanted to know. Even worse most medical doctors know less than I do and are not even qualified to treat it. If you have autoimmune symptoms, you will probably have to go to four or more doctors to find one with any real expertise and experience to identify and treat your disease. It took me five years and five doctors to find relief. Worse yet, there are a lot of quacks out there selling miracle cures that don't work. That is why you will have to study medical journals yourself to separate the scams from real help.
ALS sufferer
As a very much lay person, have any studies been done with faecal transplants from healthy individuals to existing ALS sufferers? It would seem to be a low risk procedure with much to gain. I for one would be glad to volunteer, and I’m sure there would be many others who with no other positive alternatives would be keen to submit.