ALS and the Microbiome: Yet Another Potential Connection

Earlier this year, another study was published showing alterations in the gut microbiomes of patients with ALS (amyotrophic lateral sclerosis).[i]  And,yet again, it shows an imbalance in the ratio of protective microbial species to pro-inflammatory ones.

The study included 50 ALS patients ranging in age from 18 (can you imagine?!) to 75, and 50 age- and sex- matched controls. (20 of the 100 patients did not complete the study, however, including 1 death, so the sample size is still relatively small.) All patients underwent extensive testing at baseline including an in-depth assessment of their ALS symptoms, including lung function.  Stool samples were collected at baseline, 3 months and 6 months. The ALS patients’ had significantly lower levels of Clostridium, as well as yeasts, and a much higher level of Escherichia coli (E.coli) and Enterobacteriaceae.[ii]

I think the most significant finding, in terms of the microbial differences:  a group of bacteria called Cyanobacteria were also significantly higher in the ALS group, to the point where the researchers actually state, “These data support the hypothesis that Cyanobacteria play a fundamental role in the pathogenesis of neurodegenerative diseases and particularly ALS.”  In a study in Guam, an amino acid derived from a tropical plant was shown to induce a sporadic form of ALS combined with Parkinson’s disease and dementia.  This amino acid was found to originate from Cyanobacteria in the roots of the plant, and is “…biomagnified in the food chain through animals up to man.”  Researchers have found that this amino acid is higher in the brains of patients with ALS with PD and dementia:  it’s believed to lead to an abnormal excitatory state in the brain, and neuron death.  Cyanobacteria are also “…responsible for the production of other neurotoxic molecules.”

Overall diversity of the gut bacteria was higher in the control group and there were differences too in the ALS patients with more and less severity of disease.  The ALS patients had higher levels of Lactobacillus, Citrobacter, Coprococcus, and Ruminiclostridium.  This latter species was also found, by the way, at higher levels in the Wiezmann Institute research I reported on back in August of 2019.

A quick reminder:  I am anxiously awaiting the results of the next steps in that remarkable paper out of Harvard which I wrote about back in May of this year.  In that case, the researchers found that two groups of identical mice who carry a gene  making both animals and people more prone to developing ALS are more or less likely to develop the disease based upon their gut microbes.  Their next steps were to look at the specific bacterial species involved.

The researchers in today’s paper didn’t stop with just an analysis of microbiome differences:  this was actually was a 6 month study with 2 experimental groups of people who took a daily probiotic supplement, one for the full 6 months, one group for only 3 of the 6 months.  The probiotic contained The supplement contained Streptococcus thermophiles (5 × 10⁹ CFU/dose), Lactobacillus fermentum (4 × 10⁹ CFU/dose), Lactobacillus delbrueckii subsp. delbrueckii, Lactobacillus plantarum, and Lactobacillus salivarius (2 × 10⁹ CFU/strain/dose); these particular species were selected “… considering the results of previous studies that showed their capabilities to counteract gut pathogens, such as some Candida strains, Enterobacteria, their anti-inflammatory properties and positive influence in restoring the gut physiological barrier.”

Well, that’s fair enough but yet again, what struck me was the incredibly low potency:  by my calculations, the daily dose of probiotics was a mere 16 billion units (5×10.  As I know I have pointed out before, Visbiome and VSL#3, which are the best studied probiotics in the world in clinical trials, contain – at their lowest potency – 110 billion units per capsule.  The dosage used to treat IBD is often close to 2 TRILLION.   Anyway, while the probiotic did affect the composition of the gut microbiome marginally, it did not affect disease progression.  The only real change was an increase in a family of bacteria called Rikenellaceae, which is a bacteria highly represented in the gut.  The levels of Cyanobacteria did decrease in both experimental groups but not significantly.  You do have to wonder what would have happened if they’d used much higher doses.

The main finding really is as I stated in the opening paragraph:  there is a distinct imbalance in ALS patients between protective and neurotoxic/pro-inflammatory species of bacteria.  Their next steps are to run larger clinical trials testing new “microbial strategy” to attempt to ameliorate the condition.

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[i] Di Gioia, D., Bozzi Cionci, N., Baffoni, L. et al. A prospective longitudinal study on the microbiota composition in amyotrophic lateral sclerosis. BMC Med 18, 153 (2020). https://doi.org/10.1186/s12916-020-01607-9

[ii] https://alsnewstoday.com/2020/07/31/study-probes-gut-microbiome-alterations-probiotics-in-als-patients/