In Honor of Ice Bucket Challenge Month: ALS and Akkermansia (yet again)

You know how it’s inevitable that when you learn something new, suddenly you see it everywhere?  Akkermansia muciniphila…I first mentioned it in a post back in May 2017, and things kind of revved up from there.  These days, it feels like it’s taking the microbiome world by storm.

I’ll come back to that in a moment.

August is ALS (Amyotrophic lateral sclerosis) fund-raising month.  In the USA, we often call ALS Lou Gehrig’s Disease, after one of the greatest baseball players ever, who died of ALS in 1941, days before his 38th birthday.  ALS used to be something that Lou Gerhig had, and then the great physicist, Stephen Hawking…but it seemed so very, very rare.  Not anymore…at least to me.  I already know 3 people with it, 2 whom have already died.  Like every other chronic disease, it feels like it is starting to become more and more common, appearing everywhere.  So at the moment, as a good friend battles this awful, awful disease, any good news is more than welcome.

Yesterday morning, I spotted an article on an ALS devoted site about research showing that the microbiome may influence the progression of the illness.[i]  It turns out that in a mouse model, a metabolite called nicotinamide (which is simply a form of Vitamin B3, niacin) produced by none other than our old friend, Akkermansia muciniphila, slowed the disease’s progression.  (They also found that 2 species, both of which are unfamiliar to me, worsened ALS symptoms:  Ruminococcus torques and Parabacteroides distasonis.)

Scientists at the Weizmann Institute of Science, in Israel (I can’t believe how many times I find myself writing about work coming out of this place!), are exploring how gut metabolites, which can cross the blood-brain barrier, may be used in the treatment of neurodegenerative illnesses.  In this study, they began by wiping out the gut flora of mice with ALS to see what would happen.  Doing so exacerbated the ALS, in terms of both symptom severity and decreased motor neurons in the brain, which had actually shrunk.

They then compared the gut bacteria of the ALS mice with healthy controls and found 11 potential organisms that could be factors.  They tested each, one by one, as oral supplements, giving them to the ALS mice who’d first had their microbiomes wiped out with major antibiotics.

Sure enough, 1 strain stood out:  Akkermansia muciniphila.  In the healthy controls, they discovered the nicotinamide produced by the bacteria in the blood and brain (cerebrospinal fluid), which was not there in mice treated with antibiotics.  To ensure that it was the nicotinamide having the palliative effect, they continuously administered it to the ALS mice and saw significant improvement.  They believe it could be because this vitamin B3 improved mitochondrial function.  (Mitochondria are the powerhouse of each cell in the body.)

The final step in their research was to figure out whether or not this applies to humans as well.  To determine this, they analyzed the microbiomes of 37 patients with ALS and 29 controls who live in the same households as the patients (as their microbiomes should, theoretically, be similar).  Not unexpectedly, they found that the humans with ALS had significantly different gut bacterial profiles.  More than that, they found that genes involved in producing nicotinamide were less active in the ALS patient  microbiomes and yes, nicotinamide levels were decreased in the brains of 60 patients with ALS studied, which was associated with more severe muscle weakness.  (By the way, I first wrote about microbiome differences in those with ALS back in March, 2017.  In that case, researchers found that giving the short chain fatty acid, butyrate, helped improve the quality of the microbiome, alleviating symptoms of ALS in  mice.)

This research did not involve giving human ALS patients nicotinamide so we don’t yet know if this will have any effect on people.  They write, “We suggest that environmentally driven microbiome–brain interactions may modulate ALS in mice, and we call for similar investigations in the human form of the disease.”[ii]  Unfortunately, as you know, human trials can take years to happen…assuming  the millions of dollars necessary can even be raised.

Still, trying to look for a little ray of light:  this is a pretty remarkable finding, I think.  And once again…it leads me to wonder if and when Akkermansia will be available for purchase as a probiotic.

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[i] https://alsnewstoday.com/2019/07/25/gut-microbiome-slow-als-progression-study/

[ii] Blacher, E, et. al. Potential roles of gut microbiome and metabolites in modulating ALS in mice.  Nature. 2019. doi: 10.1038/s41586-019-1443-5.

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