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Evidence has been building in recent years that the microbes in our guts influence neurological diseases such as Parkinson's disease and motor neurone disease (MND, also known as ALS). A new announcement not only strengthens that connection, it offers perhaps the clearest path yet to treatments, despite the early stage the work is at.
A team led by Professor Eran Elinav of Israel's Weizmann Institute gave broad-spectrum antibiotics to mice with a genetic condition similar to MND. Their symptoms got considerably worse compared to a control population. Moreover, when the mice were raised in sterile environments, giving them no opportunity to replenish their gut bacteria, most of them died very quickly.
This turns on its head some previous thinking about the gut-brain connection. Instead of some gut bacteria causing, or at least accelerating, neurological diseases it looks like the microbiome may act as a shield, and the absence of beneficial strains contributes to the problems.
In Nature, the team reports evidence the effects run both ways and provides tentative indications this applies to humans as well as mice.
The ecosystem of the gut (also known as the microbiome) is so complex that identifying the beneficial strains is a challenge. The Weizmann researchers compared the microbiomes of healthy mice with those developing MND and found 11 strains that showed differences. They tested each by giving these strains from healthy mice one at a time to mice with MND previously treated with antibiotics.
Most introduced bacteria had no measurable effect, two worsened the disease, and another two appeared to intensify some symptoms but not others. None of these bacteria had any detectable effect on mice without a genetic susceptibility to MND.
On the other hand, mice given Akkermansia muciniphila lived longer and experienced slower progression of MND. Akkermanisa produces thousands of molecules, but after screening Elinav identified nicotinamide as the most likely vehicle for its effects. Mice given nicotinamide infusions showed the same benefits as those given Akkermanisa probiotics.
Neurodegenerative research is littered with examples of treatments that show promise in rodents but have not translated to humans. It's too early to tell if nicotinamide will join them, but Elinav found 37 patients with MND had distinctly different gut microbiomes from their own family members, with genes involved in nicotinamide suppressed and precursor molecules altered or rare.
The paper notes: “Our human data is preliminary and observational, and is not aimed or sufficient to constitute a treatment recommendation of any sort in this devastating disease.” Nevertheless, these observations include the very suggestive finding that the lower the nicotinamide levels in 60 people with MND, the more their muscles had degenerated.
