Eran Blacher is the 2021 winner of the NOSTER & Science Microbiome Prize for his work in exploring 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 their associated metabolic pathways could provide a useful 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 and the vast majority of AD and ALS cases stem from unknown causes.
"I believe that some answers may lie in the gut and that studying the biological processes occurring outside the brain might shed a new light on some old questions in the field and maybe even revolutionize neuroscience," said Blacher, a senior postdoctoral fellow at Stanford School of Medicine.
Blacher's prize-winning essay," In search of the missing link between microbiome, metabolites and neurodegeneration," will be published in the July 9 issue of Science.
"Despite the challenges created by the pandemic, the NOSTER/Science Prize in 2021 continues in attracting highly competitive submissions from talented young scientists with a selection of great essays highlighting the translational potential of microbiome research to unexpected aspects of human health," said Caroline Ash, senior editor at Science.
"The main, very important takeaway of the essay is that the gut microbiome and its metabolites greatly impact human health and disease, with the brain being a fascinating new frontier," said Blacher.
At any given time, trillions of tiny microorganisms reside within the human body. The many thousands of distinct species that live within the gastrointestinal tract are collectively known as the gut microbiome.
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 blood stream and reach the brain where they can modulate the activity of brain cells, including neurons, astrocytes, and microglia.
However, the gut microbiome is highly sensitive to several environmental factors. Nutrition, circadian rhythms, physical activity, hygiene, and exposure to drugs or pollutants can result in the microbiome rapidly changing its composition and/or function and have a significant impact on the host's health and physiology.
While this type of gut-brain crosstalk has been linked to neurological disorders, including autism spectrum disorder and Parkinson's disease, the role of the microbiome-microbolome in other neurodegenerative diseases is rapidly evolving.
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.
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.
"Unfortunately, ALS is still an incurable and devastating disease, and the findings of the research are very far from suggesting any treatment," said Blacher. "However, the results of this study merit a larger, interventional clinical study that may take a few years and hopefully would allow appreciating the potential of nicotinamide as a possible disease-modifying drug in human ALS."
None-the-less, the study exemplifies how microbiome profiling can be utilized to identify disease-modifying gut microbiota or metabolites and offer new insights into ways to combat neurological diseases.
"We are proud to announce the award for the 2nd NOSTER & Science Microbiome Prize, even despite the worldwide turmoil; caused by COVID-19," said NOSTER Inc. CEO, Kohey Kitao. "I truly hope that the prize will motivate young scientists to passionately pursue their research to develop microbiome-based therapeutic drugs for the benefit of the world."
The NOSTER Science Microbiome Prize rewards young scientists pursuing innovative research on the functional attributes of the microbiota that have potential to contribute to the understanding of human or veterinary health and disease or to guide therapeutic inventions. The Grand Prize winner is awarded $25,000 and the publication of their essay in Science. The winner will also receive a free five-year digital subscription to Science.
Maria Zimmermann-Kogadeeva, for her essay "Putting host-microbiota interactions in numbers." Zimmermann-Kogadeva received undergraduate degrees from Lomonosov Moscow State University in Russia and a Ph.D. from ETH Zürich, Switzerland. Her research aims to understand how microbes adapt to their surrounding, and how these adaptations shape the functional outcome of microbial communities and their interactions with the host and the environment.
Erez Baruch, for his essay "Gut microbiota modulation promotes response in immunotherapy-refectory melanoma patients." Baruch received undergraduate, M.D., and Ph.D. degrees from Tel Aviv University, Israel. His research is focused on mechanisms of immunotherapy resistance and toxicity, modulation of the gut microbiota, and interaction between innate and adaptive immune cells.
The American Association for the Advancement of Science (AAAS) is the world's largest general scientific society and publisher of the journal Science, as well as Science Translational Medicine; Science Signaling; a digital, open-access journal, Science Advances; Science Immunology; and Science Robotics. AAAS was founded in 1848 and includes more than 250 affiliated societies and academies of science, serving 10 million individuals. Science has the largest paid circulation of any peer-reviewed general science journal in the world. The nonprofit AAAS is open to all and fulfills its mission to "advance science and serve society" through initiatives in science policy, international programs, science education, public engagement and more.
Noster was incorporated on May 15, 2020, in Kyoto, Japan, specializing in the research and development of gut microbiome-based treatments with the vision of "connecting life and gut microbiome." The company's mission is to elucidate the functions of over 1,000 species of human gut microorganisms--numbering over 100 trillion--that exist symbiotically with humans, and to contribute to scientific advances in microbiotics to improve the health of people worldwide. Recent research shows that immune and digestive diseases as well as certain cancers are linked to the gut microbiome, making it an obvious target for the development of new biotherapy treatments based on manipulating the abundance and biology of gut microorganisms. To solidify its future, Noster is exploiting its deep understanding of the gut microbiome by building a unique library of intestinal microbes and their metabolites, referred to as "postbiotics." Using this library, company scientists are working passionately to realize breakthroughs in drug discovery and to develop innovative therapeutic treatments targeting the gut microbiome.