Can Microbes Combat Neurodegeneration? (Neuroscience)

Eran Blacher is the 2021 winner of the NOSTER & Science Microbiome Prize for his work in illuminating the relationship between the microbiome and neurodegenerative diseases such as Alzheimer’s disease (AD) and Amyotrophic Lateral Sclerosis (ALS).

The findings reveal new insights into the “gut-brain axis” and demonstrate that harnessing the microbiome and its associated metabolic pathways could provide a valuable approach to treating these and potentially other devastating neurological disorders.

Although millions of people worldwide suffer from neurodegenerative disorders, the roots of neurodegeneration remain unclear. A growing body of research consistently demonstrates that the human brain is inextricably linked to the gut microbiome, influencing brain activity in several ways. For example, small molecule metabolites produced by commensal bacteria can be absorbed into the bloodstream and reach the brain, where they can modulate the activity of brain cells, including neurons, astrocytes, and microglia.

In a mouse model, Blacher and colleagues investigated the role of the microbiome and its metabolites in ALS – a progressive neurodegenerative neuromuscular disease that affects nerve cells in the brain and spinal cord.

Blacher and the researchers depleted the microbiome of ALS-prone Sod1-Transgenic (Sod1-Tg) mice through wide-spectrum antibiotic treatment, discovering dysbiosis and microbiome-driven alterations in metabolite configuration preceding clinical ALS motor symptoms, as well as 11 distinct microbial strains correlated with disease severity.

Probiotic treatment of Sod1-Tg mice with either the gut microbe Akkermansia muciniphila or its associated metabolite, nicotinamide, improved ALS symptoms by significantly improving motor function and restored disrupted spinal cord gene expression patterns.

What’s more, in a preliminary observational study in humans, the researchers found similar, significant changes in the microbiome composition and function of ALS patients, associated with reduced nicotinamide levels in serum and cerebrospinal fluid.

“We posit that these findings are linked to our previous observations in mice and may lay the foundation of a larger clinical study in the future,” writes Blacher.

Finalists for the prize were Maria Zimmermann-Kogadeeva for her essay “Putting host-microbiota interactions in numbers,” and Erez Baruch for his essay “Gut microbiota modulation promotes response in immunotherapy-refractory melanoma patients.”


Reference: Eran Blacher, “Can microbes combat neurodegeneration?”, Science  09 Jul 2021: Vol. 373, Issue 6551, pp. 172-173. DOI: https://doi.org/10.1126/science.abi9353


Provided by AAAS

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