Homing in on a Microbiome Culprit in ALS

And just like last week, the Weizmann Institute in Israel strikes again.  So much cutting edge research out of one place!

As many of you may know from previous posts on this blog (look here and here, as just two of many examples), over the last number of years, more and more research points to a connection between the gut biome and neurodegenerative diseases like Alzheimer’s, Parkinson’s, and  ALS (Amyotrophic Lateral Sclerosis).  The winner of the 2021 NOSTER & Science Microbiome Prize is Dr. Eran Blacher, whose research into the connection may have brought us one step closer to figuring out the mechanism of action.  Talking about research that is desperately needed! – millions of people worldwide are suffering from these types of diseases which, “By gradually destroying motor abilities, communication skills, memory, and clear thinking, these devastating diseases rob patients of their independence and take a heavy toll on family members and caregivers.”[i]

Blacher and colleagues, working at the Weizmann Institute of Science, depleted the microbiomes of a specific type of genetically engineered mice using a broad spectrum antibiotic.  Alterations to the microbiome led to subsequent changes in the metabolites normally produced by gut bacteria.  In turn, this led to a progressive neurodegenerative disease that greatly resembles ALS. Remember that small molecules produced by gut bacteria can cross through the epithelial barrier and make their way into the blood stream, allowing the gut to communicate with the brain.

11 distinct microbial strains correlated to disease severity.  Most exciting though is that probiotic treatment of the mice with either  our old friend, Akkermansia muciniphila, or its associated metabolite (nicotinamide, which is a form of vitamin B3) improved these ALS-like symptoms by significantly improving motor function and restoring normal spinal cord gene expression patterns.

A preliminary study was also performed in humans, and the researchers found a similar pattern of changes in microbiome composition and function (i.e. metabolite production) in patients with ALS.  Just like they found in the mice, they found reduced levels of nicotinamide in serum and cerebrospinal fluid:  the “…study showed that the composition and function of the microbiome of ALS patients substantially differed from that of healthy family members. Moreover, we found a significant reduction in nicotinamide concentrations in both sera and cerebrospinal fluids of ALS patients.”

There was a very interesting note in the article concerning prior research which showed that inhibiting the glycoprotein, CD38, which is an efficient NAD+-consuming enzyme  (i.e. it very efficiently metabolizes nicotinamide) is also a “…promising strategy to treat brain pathologies.” A quick search led me to a 2019 article which states, “In the central nervous system, vitamin B3 has long been recognized as a key mediator of neuronal development and survival.”[ii]  This article concludes, “A growing body of evidence highlights the key role of vitamin B3 in neuronal health. What is emerging is that niacin bioavailability is crucial for neuronsurvival and functions: indeed, vitamin deficiency has been recognized as a pathogenic factor for neurological deficits and dementia, as well as for neuronal injury and psychiatric disorders.”

I will definitely be keeping a look out for more on this line of research.  It really does look promising!

p.s.  By the way, an aside for any of you who suffer – as I do – from migraines.  From this 2nd article on nicotinamide:  “When orally, intramuscularly or intravenously administrated, vitamin B3 (especially, nicotinic acid) has therapeutic effects in headache management.”  Daily, I take a vitamin B complex, but I think I’ll be adding extra vitamin B3 going forward!


[i] https://science.sciencemag.org/content/373/6551/172.full

[ii] Gasperi V, Sibilano M, Savini I, Catani MV. Niacin in the Central Nervous System: An Update of Biological Aspects and Clinical Applications. Int J Mol Sci. 2019;20(4):974. Published 2019 Feb 23. doi:10.3390/ijms20040974

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