Amyotrophic lateral sclerosis (ALS), also known as motor neurone disease, is thought to be caused by a relatively equal balance of genetic and environmental factors. A new study, led by scientists from the Weizmann Institute of Science, has discovered a molecule secreted by certain gut bacteria could protect against the disease, while other species of gut bacteria can exacerbate the onset of symptoms.
The impressively thorough study began by examining the effect of microbiome disruptions on a mouse model engineered to resemble the symptoms of ALS. After discovering the animal's symptoms rapidly worsened after their microbiomes were eliminated, the researchers homed in on 11 specific bacterial species that seemed to be playing a part in either increasing or decreasing the progression of the disease.
Two particular gut bacteria species, Ruminococcus torques & Parabacteroides distasonis, seemed to rapidly exacerbate ALS symptoms. But, even more interestingly, one species called Akkermansia muciniphila slowed the onset of the symptoms.
To understand exactly how A. muciniphila could be exerting this potentially protective effect the researchers looked at one particular molecule secreted by the bacteria, nicotinamide (NAM). Directly supplementing the ALS-prone mice with NAM resulted in notable reductions to their clinical symptoms.
Translating these results to human subjects, the researchers conducted metabolic and micriobiome profiles in a number of ALS patients. As well as discovering significantly low blood and brain NAM levels in ALS patients, compared to a healthy control control group, a number of microbiome differences were noted, including low levels of microbial genes related to NAM synthesis.
"These findings are only a first step towards achieving a comprehensive understanding of the potential impact of the microbiome on ALS, but they suggest that in the future, various means of altering the microbiome may be harnessed for developing new therapeutic options for ALS," says Eran Elinav, one of the lead scientists on the project.
The researchers do explicitly stress these results are preliminary, and do not imply or suggest any specific human treatment at this stage. Experts not involved in this particular study are quick to note the ALS mouse model used in the new research isn't widely representative of how the disease plays out in humans.
Called a SOD1 model, this transgenic mouse model hinges on a specific gene that triggers the onset of the disease. This particular gene is only responsible for three percent of ALS cases in humans. Brian Dickie, from the Motor Neurone Disease Association says follow-up work in other ALS mouse models is vital before these conclusions are widely accepted.
"Many compounds have been shown to limit disease progression in the SOD1 mouse model, but none have yet shown the same effectiveness in ALS patients, so researchers will be cautious when extending these findings to the human disease," says Dickie.
The research certainly raises more questions than it answers, pointing to the microbiome as potentially modulating the progression of ALS. However, so far there is no clear evidence that NAM in particular can help prevent the progression of ALS. Luis Emiliano Pena Altamira, a research associate from King's College London, suggests A. muciniphila may be doing more in relation to slowing ALS that just producing NAM.
Pena Altamira, who did not work on this new study, points out A. muciniphila has recently been implicated in everything from immune system function to obesity, and there may be more general connections between, "aging, ALS and reduced numbers of this bacterium." A. muciniphila is one of the single most abundant gut bacteria species in the human microbiome, and low levels have recently been associated with inflammatory bowel disease, as well as the efficacy of certain cancer treatments.
Dickie also adds that this new discovery is only a small piece in the greater puzzle that is ALS. While this study certainly suggests the microbiome can play a part in the progression of ALS, it is not hypothesized to be the sole trigger.
"This adds to an emerging, but still fuzzy, picture of a different metabolism that seems to occur in people with ALS," says Dickie. "Diet and exercise are also being studied as potential factors associated with the disease."
The new research was published in the journal Nature.
Source: Weizmann Institute of Science
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