Amyotrophic lateral sclerosis and intestinal microbiota-toward establishing cause and effect - PubMed (original) (raw)

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Amyotrophic lateral sclerosis and intestinal microbiota-toward establishing cause and effect

Marc Gotkine et al. Gut Microbes. 2020.

Abstract

The intestinal microbiota may be involved, through metabolic gut-brain interactions, in a variety of neurological conditions. In this addendum, we summarize the findings of our recent study investigating the potentially modulatory influence of the microbiome in a transgenic ALS mouse model, and the possible application to human disease. We found that transgenic mice show evidence of dysbiosis, even at the pre-symptomatic stage, and have a more severe disease course under germ-free conditions or after receiving broad-spectrum antibiotics. We demonstrated that Akkermansia muciniphila ameliorated the disease in mice and that this may be due to the production of nicotinamide. We then conducted a preliminary study in human ALS and identified functionally similar alterations within the metagenome. Furthermore, we found that patients with ALS had lower systemic and CSF levels of nicotinamide, suggesting that the changes observed in the mouse model may be relevant to human disease.

Keywords: Akkermansia; Amyotrophic lateral sclerosis; als; microbiome; motor neuron disease; nicotinamide; sod1.

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Figures

Figure 1.

Figure 1.

The role of the gut microbiome and its metabolites in an ALS mouse model. (a) SOD-1 transgenic (SOD1-Tg) mouse model of ALS present a distinctly different microbiome composition, even before the onset of any motor impairment and altered metabolites configuration, leading to the deterioration of motor functions after 140 d. (b) Depletion of the gut microbiome by administration of broad-spectrum antibiotics in the drinking water or using germ-free SOD1-Tg mice induces a rapid exacerbation of the clinical symptoms of the disease. (c) Oral administration of Akkermansia muciniphila (AM), a specific commensal bacterium, has beneficial effects on the ALS clinical outcomes, slowing down its progression in SOD1-Tg mice. On the other hand, AM is able to produce metabolites which in turn reach the nervous system through the bloodstream and therefore could impact the course of the disease. Thus, systemic administration of nicotinamide (NAM) via osmotic pumps significantly improved motor functions in the SOD1-Tg treated mice.

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