ALS or no ALS? The Bacterial Microbiome May the Key

Those who read this blog regularly know that there are some topics that particularly interest me:  autism, Parkinson’s, the obesity epidemic, so-called mental illnesses, dementia, to name just a few.  Another obsession of mine is ALS (amyotrophic lateral sclerosis) which, for all my life up – until 5 years ago or so – I mistakenly thought was unbelievably rare.  Thus, I am always exceptionally happy to read of any progress being made as it seems there’s precious little.

Today, I’m reporting to you that new research out of Harvard provides yet more “compelling evidence” of a link between the gut biome and the development of ALS.[i]  I have written a little about this before (here, for example), but the latest news is, I believe, a big leap forward.

The gene C9orf72 is the most common genetic variant leading to familial ALS.  To date, the development of ALS is thought to be a combination of genes and environment. After all, not everyone who carries the genetic marker develops the disease – they are just more prone to do so. In this research, genetically identical mice with C9orf72 mutations, raised in two different facilities (one group at Harvard, one group at separate location), showed radically different outcomes.  The latter group lived to a ripe and healthy old age.  The Harvard mice did not.  Why?

The scientists looked at many variables that could have led to the different outcomes, and ended up zeroing in on the gut microbes (no surprise!) of the two groups:  “At institutions hundreds of miles apart, very similar gut microbes correlated with the extent of disease in these mice.” What they were able to ascertain is that the mice housed in the remote facility had fewer pro-inflammatory species of gut bacteria:  “Here we report that an environment with reduced abundance of immune-stimulating bacteria protects C9orf72-mutant mice from premature mortality and significantly ameliorates their underlying systemic inflammation and autoimmunity.” [ii]

Once they recognized this, they tested to see if altering the microbiota of the Harvard mice would change their health outcomes.  Antibiotics and fecal transplants from healthy mice did indeed improve their immune status and increase their lifespans.

They conclude, “…our studies suggests that the microbiome may be an important governor of the onset and progression of neurological disease in patients with C9ORF72 mutations, including those experiencing autoimmune and inflammatory conditions before a diagnosis of ALS…”  The next step in their research is to look at the gut microbiomes of humans within families carrying this genetic mutation to see whether or not “… the gut microbiota differs between individuals that remain healthy and those that acquire the conditions.”

By the way, I want to remind you that  a study done last year by the Weizmann Institute, looked at specific species that seem to be associated with the development of ALS.  I wrote about this at the time the paper came out.  (These mice had a different gene variant, also linked with familial ALS.)  The two suspect species are Ruminococcus torques and Parabacteroides distasonis  which rapidly exacerbated ALS development.  As I wrote about in that post, Akkermansia muciniphila, markedly slowed the development of symptoms.[iii]

I’ve written many times about potential ways to promote the growth of Akkermansia, which unfortunately is still not available as an OTC probiotic.  To name just a few: prebiotics, like FOS; other probiotic species, like L. rhamnosus and B. animalis; cranberries, black tea, grape extract; the medicine, Metformin, which I have written about before; and caloric restriction.  Some day soon, I suspect, we’ll also be able to supplement with it as a store-bought probiotic.  Oh, yeah!  – and add Akkermansia research to that list of my personal obsessions!

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[i] https://newatlas.com/science/als-gut-bacteria-microbiome-harvard-study/

[ii] Burberry, A., Wells, M.F., Limone, F. et al. C9orf72 suppresses systemic and neural inflammation induced by gut bacteria. Nature (2020). https://doi.org/10.1038/s41586-020-2288-7

[iii] https://newatlas.com/als-gut-bacteria-microbiome-motor-neurone-disease/60699/