Motor neurone disease researchers find link to microbes in gut

https://www.theguardian.com/society/2019/jul/22/motor-neurone-disease-researchers-find-link-to-microbes-in-gut

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Scientists have found tantalising clues that the devastating condition motor neurone disease may be linked to changes in microbes that live in the gut.

Studies in mice revealed that animals bred to develop amyotrophic lateral sclerosis (ALS), a form of the disease that affected the cosmologist Stephen Hawking, improved and lived longer when they were given an organism called Akkermansia muciniphila.

Among other substances, the microbe secretes a molecule called nicotinamide which may slow the course of motor neurone disease by improving the function of muscle-controlling neurons in the brain.

The findings are preliminary, and researchers stress that far more work is needed to confirm the effect. But as the first study to link gut microbes – collectively known as the microbiome – to the neurodegenerative illness, the work raises the possibility of new treatments for the condition.

Eran Elinav at the Weizmann Institute of Science in Israel began by showing that mice with a mutation common in ALS patients fared much worse when their gut microbes were all but wiped out with strong antibiotics. The finding suggested that somehow, microbes in the animals’ guts were involved in how quickly the disease progressed.

To explore further, the researchers analysed the gut microbes in the ALS-prone mice and compared them with normal mice. They spotted 11 strains of microbes that were either more or less common in the ALS-prone animals as the disease progressed and physical symptoms took hold.

Two types of bugs, called Ruminococcus torques and Parabacteroides distasonis, both exacerbated the symptoms of ALS, a disease that kills off motor neurons and tends to be fatal in humans within three to five years of diagnosis. Only Akkermansia muciniphila appeared to improve the animals’ symptoms.

After examining thousands of molecules produced by the gut microbes, the scientists identified nicotinamide as a potentially important one. To test its effects directly, the scientists used tiny pumps to infuse the compound into the animals. “When we gave it to ALS-prone mice it very significantly improved ALS severity in these mice,” Elinav said. It also altered gene expression in the animals’ brains, returning it to a more healthy state, he added.

The researchers went on to look at the microbiomes of 37 human ALS patients and compared the results with healthy family members. They discovered that the patients had low levels of nicotinamide in their blood. In further tests, other ALS patients were found to have low levels of nicotinamide in their blood and the cerebrospinal fluid that bathes the brain. “Interestingly, nicotinamide levels were mildly correlated to the motor function of these ALS patients,” Elinav said.

He also emphasised that the research, although promising, is still at an early stage. “While these human results are interesting and may shed new light on the elusive modulators and causes of human ALS, they are very preliminary,” he said.

“By no means do these preliminary results constitute in any form or shape a recommendation for human treatment, intervention or prevention by patients and their physicians,” he added.

Brian Dickie, director of research development at the Motor Neurone Disease Association, said: “There is increasing evidence from a wide variety of sources that the bacteria in our gut can play a role in a wide range of neurological conditions, though ALS has not been as widely studied as other conditions such as multiple sclerosis, Parkinson’s disease, Alzheimer’s disease and stroke.

“These are important new findings which support the theory that certain bacteria may play a disease-modifying role in ALS and that this may occur though changes in a particular metabolic pathway. This adds to an emerging, but still fuzzy, picture of a different metabolism that seems to occur in people with ALS. Diet and exercise are also being studied as potential factors associated with the disease.”