A NAMe-tag for ALS

Nature 572, 474–480 (2019)

The neurodegenerative disease ALS has been shown to be modulated by environmental factors, which could include gut bacteria. Given that gut bacteria are known to affect the pathogenesis of other neurological disorders, Blacher et al. tested the interface between the gut microbiome and the host in the context of ALS. They used mouse models of ALS and found that antibiotic treatment exacerbated the motor-function defects associated with the disease and led to increased motor-neuron cell death and brain atrophy. There were significant differences in compositions of the fecal microbiome of ALS mice compared to those of wild-type (WT) mice even before the appearance of motor-neuron dysfunction. In particular, they identified four strains that exacerbated ALS disease, survival, and brain atrophy, and one, Akkermansia muciniphila (AM), that improved them. Untargeted metabolomics and a scoring algorithm identified AM-induced nicotinamide (NAM) as being synthesized by the WT, but not the ALS microbiota. NAM supplementation mimicked the effects of AM on motor function. Finally, results from a small human study suggested different AM levels and aberrant metabolism of NAM in some patients with ALS, highlighting the involvement of the microbiota in modulating ALS.

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Correspondence to Mirella Bucci.

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Bucci, M. A NAMe-tag for ALS. Nat Chem Biol 15, 933 (2019).

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