A study in Nature suggests that the gut microbiome could affect amyotrophic lateral sclerosis in humans, according to research conducted at Israel's Weizmann Institute of Science. Researchers found that symptoms of an ALS-like disease worsened in transgenic mice after they received broad-spectrum antibiotics to wipe out substantial portions of their microbiome.

The findings "suggest that in the future, various means of altering the microbiome may be harnessed for developing new therapeutic options for ALS," said immunology professor Eran Elinav, who led the study.

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Affected mice struggled to survive in germ-free conditions, in which they carried no microbiome. Results hinted at a link between microbiome alterations and disease progression in mice created to be genetically susceptible to ALS, which is also known as Lou Gehrig's Disease.

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Step by step

The scientists characterized the composition and function of the microbiome in the mice who were engineered to be susceptible to ALS, comparing them against mice who had not been genetically tampered with. They identified 11 microbial strains that became altered in the mice made prone to ALS as the disease progressed — or even before they developed overt symptoms of it.

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Scientists administered strains individually in probioticlike supplements to susceptible mice following antibiotics and found that some strains had a negative impact on ALS. One strain, Akkermansia muciniphila, significantly slowed disease progression in the mice and prolonged their survival.

Scientists then examined molecules secreted by gut microbes, zeroing in on nicotinamide (NAM). NAM levels in the mice's blood and in cerebrospinal fluid dipped following antibiotic treatment and increased after scientists administered them Akkermansia, which could secrete this molecule.

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Finally, the researchers examined the microbiome and metabolite profiles of 37 human ALS patients and compared them with those of family members sharing the same household. A detailed genomic analysis suggested that the ALS patients had distinct gut microbiomes in composition and functional features from those of healthy controls.

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When the researchers tested the levels of NAM itself, they found them significantly reduced in both the blood and the brains of 60 human ALS patients when compared with the control group. Moreover, they found a correlation between reduced NAM levels and the degree of muscle weakness in the patients.

mkg/jm (Weizmann Institute of Science)

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