A recent study published in Nature may give ALS patients some insight into how gut microbes affect the progression of ALS.
What are microbes?
Inside every person is a microbiome, a community of microorganisms that are also known as microbes. Microbes inhabit a person skin, mucosa, and gastrointestinal tract, but also live in plants, animals, and dirt. These communities are more beneficial to their host than they are harmful.
Some of the many benefits that these microbiomes bring to their host are:
- the production of vitamins and other essential nutrients
- the metabolization of food that humans can’t normally digest on their own
- the breaking down of drugs and toxins
- protection from infections and chronic inflammation
One essential part of the makeup of a microbiome is the environment in which we live. It is important to have variety in one’s microbiome, keeping us open to the many benefits different microbes can bring.
Although most environments promote microbe growth and variety, some are more detrimental than beneficial. In particular, a sterile environment can negatively affect a person’s microbiome. A phenomenon called the Hygiene Hypothesis describes the effects of a sterile environment on a person’s microbiome. The hypothesis states that the cleaner an area is, the less exposure a person has to different – potentially beneficial – microbiomes.
How can mice give insight into ALS progression?
A team of researchers, led by Professor Eran Elinav and Professor Eran Segal of the Weizmann Institute of Science, conducted an experiment that looked at the relationship between a person’s gut microbes and the progression of their ALS.
The team started their study by conducting a series of experiments on mice that showed symptoms of an ALS-like disease. After giving the mice broad-spectrum antibiotics, the researchers recorded that the mice’s ALS symptoms seemed to get worse. These antibiotics were given to wipe out a substantial portion of the mice’s microbiome.
These ALS-prone mice were also observed to have a difficult time surviving in sterile environments. As stated previously, the more sterile an environment is, the less likely a person is exposed to different microbiomes – also known as the Hygiene Hypothesis. This hypothesis goes for any host of microbiomes, including animals.
Researchers concluded that both of the previous tests results hinted at a potential link between changes in the microbiome and accelerated disease progression in ALS-prone mice.
With the use of computational methods, the researchers characterized the composition and function of the microbiome in genetically susceptible ALS mice. They compared the ALS-prone mice to normal mice and identified 11 microbial strains that were altered in the ALS prone mice. These strains were changed as the disease progressed, and even before the mice developed ALS symptoms.
The researchers isolated these 11 strains and tested them one by one in the form of probiotic-like supplements on ALS-prone mice. They found that some of the strains had a clear negative impact on the ALS-like disease. However, they were able to identify one strain, Akkermansia Muciniphila, that significantly slowed disease progression.
To figure out how Akkermansia was able to produce this effect, the researchers examined thousands of small molecules that are secreted by gut microbes. They were able to zero in on a molecule called nicotinamide (NAM). They found that there seemed to be a decrease in the levels of NAM in ALS-prone mice following antibiotic treatment. Alternatively, the levels of NAM would increase if the mice were given a dose of Akkermansia.
In order to confirm that NAM could hinder the course of ALS, the scientists continuously infused ALS prone mice with NAM. After that, they conducted a detailed study of gene expression in the brains of the mice. This study suggested that NAM improved the functioning of the mice’s motor neurons.
What does this mean for human ALS patients?
To see the application of this experiment on human patients, researchers observed 37 human ALS patients. They examined the microbiome profiles of each patient and compared them to family members of these patients. A genomic analysis of the patients suggested that the gut microbes of ALS patients were distinct in functional features and makeup, compared to their family members.
Through this analysis, they were able to see that numerous microbial genes that were involved in the synthesis of NAM were suppressed in ALS patients. They also stated that levels of NAM were reduced significantly in both the blood and brain of 60 human ALS patients. There was also a correlation between reduced NAM levels and the degree of muscle weakness in the patients.
This experiment is just one step toward the understanding of ALS. It shows potential in future advancements in therapeutic options of ALS. The study also provides all those affected by ALS, insight into what affects the disease, and how we can slow its progression.