Gut Microbiome Provides New Therapeutic Target for ALS

Brain, one of the top academic journals, published groundbreaking new research by Dr. Feldman et al. that looked at the connection between the microbiome, fatty acids in the blood, and ALS.

In the gut microbiome are a million plus microbes—diverse bacteria species in the gastrointestinal tract. Everybody has them. These bacteria produce metabolites from your diet that enter your bloodstream and provide energy to the cells throughout your body.

In healthy humans, the gut microbiome has coevolved to exist in a state of mutually beneficial symbiosis, contributing to equilibrium in the body and regulating immune function, among other benefits. However, dysbiosis, or an imbalance, in the microbiome can lead to various problems, including cardiovascular disease, respiratory disease, cancer, and neurologic disease.

The latter led Eva Feldman, M.D., Ph.D., et al. to the research published in Brain that honed in specifically on amyotrophic lateral sclerosis (ALS).

Researchers have previously found that the microbiome in the gut of people with ALS is different from those who do not have the disease. But what does this mean?

Dr. Feldman’s team compared the metabolite in the blood of ALS patients with healthy controls and found something exciting and novel. Patients with ALS have a specific microbiome in their gut that pushes out certain toxic metabolites in the class of fatty acids that have separately been associated with ALS. So, it was the first time researchers established that the microbiome may be partly responsible for these problematic fatty acids known to be related to ALS.

And so what we found, which was very interesting and had never been shown before, is that patients with ALS have a specific metabolite, a microbial, a distinct microbiome of microbial communities in their gut that push out metabolites, particularly in classes of lipids. These lipid classes we have shown separately in other papers correlate with disease progression.

The research team then used Mendelian Randomization, a complex statistical model, to see if this was a casual association or if the unique gut microbiome in ALS patients did cause these toxic fatty acid metabolites to be present in the bloodstream, leading to ALS. And it did.

These new findings offer two new paths of study. First, into therapeutics, like fecal transplants that have been proven effective, to bring the microbiome of ALS patients back into balance. The second is in biomarkers, which allow for better disease testing. This paper establishes the presence of these toxic fatty acids that could be used as disease-risk biomarkers.