Boosting a gut bacterium helps mice fight an ALS-like disease

A friendly gut bacterium can help lessen ALS symptoms, a study of mice suggests.

Mice that develop a degenerative nerve disease similar to amyotrophic lateral sclerosis (ALS), or Lou Gehrig’s disease, fared better when bacteria making vitamin B3 were living in their intestines, researchers report July 22 in Nature. Those results suggest that gut microbes may make molecules that can slow progression of the deadly disease.

The researchers uncovered clues that the mouse results may also be important for people with ALS. But the results are too preliminary to inform any changes in treating the disease, which at any given time affects about two out of every 100,000 people, or about 16,000 people in the United States, says Eran Elinav, a microbiome researcher at the Weizmann Institute of Science in Rehovot, Israel.

“With respect to ALS, the jury is still out,” says Elinav, also of the German Cancer Research Center in Heidelberg. “We have to prove that what we found in mice is reproducibly found in humans.”

Elinav and his colleagues examined the gut microbiomes — bacteria, archaea and other microbes that live in the colon, or large intestine — of mice that produce large amounts of a mutated form of the SOD1 protein. In the mice, as in human ALS patients, faulty SOD1 proteins clump together and lead to the death of nerve cells.

Microbiomes of ALS mice contained almost no Akkermansia muciniphila bacteria. Restoring A. muciniphila in the ALS mice slowed progression of the disease, and the mice lived longer than untreated rodents. By contrast, greater numbers of two other normal gut bacteria, Ruminococcus torques and Parabacteroides distasonis, were associated with more severe symptoms.

Akkernansia has a mixed record when it comes to human health. It’s been linked to protection against type 2 diabetes that comes with aging (SN:12/22/18, p. 14), and it may help people lose weight (SN: 5/4/13, p. 10) and relieve symptoms of inflammatory bowel diseases. But studies of Alzheimer’s dementia, multiple sclerosis (SN: 12/9/17, p. 20) and Parkinson’s disease have associated increased numbers of Akkermansia with worse symptoms, says Brett Finlay, a microbiologist at the University of British Columbia in Vancouver who was not involved in the study. “So I was surprised to see a beneficial effect of Akkermansia in a brain disease, because, thus far, it’s been associated with poorer outcomes.”

Elinav’s team investigated what Akkermansia does to relieve symptoms that hamper the mice’s ability, for example, to stay on a rotating rod or grip a wire. The researchers focused on molecules, or metabolites, the bacteria produce, including B3.

Giving nicotinamide, a water soluble form of vitamin B3 found in foods and dietary supplements, to ALS mice improved some symptoms. But unlike mice with boosted Akkermansia numbers, the vitamin-supplemented mice didn’t live any longer than untreated mice. That finding may mean that the bacteria produce other substances or work with other microbes to affect symptoms, which wouldn’t be too surprising, says Jun Sun, a medical microbiologist at the University of Illinois in Chicago. “Usually you don’t expect one miracle metabolite can rescue the mice completely,” she says.

Preliminary work suggests Akkermansia may play a role in human ALS, too. In a small study of 37 ALS patients and 29 healthy family members, Elinav’s group found that people with ALS also have lower levels of Akkermansia in their stool. Levels of nicotinamide in ALS patients’ blood and cerebrospinal fluid were also lower than in healthy people. The lower the levels of nicotinamide in the blood, the more severe the patient’s symptoms, the researchers discovered.