New Research Finds Link Between ALS Progression and the Microbiome
The microbiome is the trillions of bacteria, viruses and fungi that live in the human body. It is increasingly being investigated for its role in numerous diseases, not just gastrointestinal diseases, but psychiatric and central nervous system disorders. New research shows that the gut microbiome appears to play a role in the course of amyotrophic lateral sclerosis (ALS), also known as Lou Gehrig’s disease.
Researchers with the Weizmann Institute of Science worked with mice with an ALS-like disease. They found that the course of the disease slowed after the mice received specific strains of gut microbes or substances that were secreted by the microbes. The results suggest that the microbiome may play a regulatory role in people with ALS.
The research was published in the journal Nature.
“Our long-standing scientific and medical goal is to elucidate the impact of the microbiome on human health and disease, with the brain being a fascinating new frontier,” stated Eran Elinav, professor of the Immunology Department, who led the research with Eran Segal of the Computer Science and Applied Mathematics Department at Weizmann.
Elinav went on to say, “Given increasing evidence that microbiome affects brain function and disease, we wanted to study its potential role in ALS.”
First, studying the mice with the ALS-like disease, they gave them broad-spectrum antibiotics that killed off most of the mice’s microbiome. This caused the symptoms of the ALS-like disease to become worse. They also found that when they induced mice to live in a germ-free situation, i.e., having no microbiome, the mice struggled to live under that environment. The researchers believe this suggests a possible link between changes in the microbiome and accelerated disease progression, at least in mice genetically susceptible to ALS.
Using advanced computation, the analyzed the composition and function of the ALS-prone mice’s microbiome, comparing them to normal mice. They found 11 strains of microbes that were altered in ALS-prone mice as the disease progressed or even before they developed ALS symptoms.
They then isolated the microbes and fed them to the mice one at a time. Some of the strains had a significant impact on the ALS-like disease. One in particular, Akkermansia muciniphila actually slowed disease progression in the mice and prolonged their survival. This mucin-degrading bacterium is found in the GI tracts of numerous animals, including humans, and is being investigated for its role in a number of conditions, including obesity, diabetes and inflammation, as well as cancer.
In an attempt to determine why Akkermansia might have this effect, the researchers analyzed thousands of small molecules secreted by the microbes, focusing on one called nicotinamide (NAM). In ALS-prone mice, the blood levels of NAM and in the cerebrospinal fluid was decreased after antibiotic treatment and increased after the mice were given Akkermansia. They then continuously infused the ALS-prone mice with ALS, which improved the clinical condition of the mice. Gene expression studies in the brains of the mice suggested NAM improved motor neuron function.
Interestingly, research is being conducted on the role of another nicotinamide called nicotinamide adenine dinucleotide (NAD+) in Alzheimer’s disease. NAD+ is essential to cellular energy generation and metabolism. As we age, NAD levels decrease, and there appear to be linked to neuroinflammation and the brain’s immune response to damage being impaired by this decrease in energy.
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