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Creative Minds: Can Microbes Influence Mental Health?

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While sitting in microbiology class as a college sophomore, Elaine Hsiao was stunned to learn that the human gut held between as much as 6 pounds of bacteria -- twice the weight of an adult human brain. She went on to learn during her graduate studies in neurobiology that these microbes had co-evolved with humans and played important roles in our bodies, aiding digestion and immune function, for example. But more intriguing to her, by far, was new research that suggested that gut bacteria might even be influencing our thoughts, moods and behavior.

Now a senior research fellow at the California Institute of Technology, Hsiao is launching her own effort to explore how these microbes can affect brain function -- a very creative endeavor made possible through the National Institutes of Health’s Early Independence Award program -- also known as the “skip the post-doc” award.

So, how might a bunch of bacteria living in your intestines, which are located a good distance away from your brain, play a role in your mental well-being? Well, it turns out that there are several different avenues through which microbes can exert what may amount to a type of mind control.

First of all, and perhaps most obviously, gut bacteria are engaged in a wide range of biochemical activities, producing metabolites that are absorbed into the human bloodstream. But there are other connections. One species of bacterium, for example, sends messages that are carried via the vagus nerve, which links the intestinal lining to the brain. When this species is present, the mice demonstrate fewer depressive behaviors than when it’s absent. Another bacterium plays an enormous role in shaping the immune system, which goes awry in many neurological diseases. This species of bacterium interacts directly with the immune system’s regulatory T-cells to provide resistance against a mouse version of multiple sclerosis, a progressive disease in which the immune cells damage the central nervous system by stripping away the insulating covers of nerve cells.

In work conducted during graduate school and a brief postdoctoral fellowship, Hsiao laid an impressive foundation for her latest research efforts. Using mice as her model system, she studied how activating the mother’s immune system during pregnancy may raise her offspring’s risk of schizophrenia and autism. As part of this work, she looked at how inflammatory signals are relayed to the placenta and how prenatal insults, such as maternal infections, can affect embryonic brain development. She also examined how maternal immune activation shapes immune systems of offspring -- a concept called prenatal programming.

Realizing that the immune system interacts closely with normal microbes, Hsiao is now focused on how gut bacteria influence immunity, brain function, and behaviors in mouse models of neurodevelopmental disorders. In a just-published study, she reveals that when mice that display core symptoms of autism spectrum disorder are given bacteria-laden treatments called probiotics, many of the mice’s behavioral abnormalities disappear.

To expand this research, Hsiao will use her 2013 NIH Early Independence Award to explore how microbes in the gut influence levels of the neurotransmitter serotonin. You may have heard of serotonin in the context of its effects on the brain, particularly its role in depression. However, this molecule also helps to regulate heart function, constriction of blood vessels, and differentiation of red blood cells. Hsiao plans to identify specific types of bacteria that modulate human serotonin levels, figure out the biochemical pathways they use, and understand the links to human disease.

Ultimately, Hsiao hopes that her work will translate into microbe-based therapies. Who knows? Perhaps someday one key to better mental health might be an extra dose of some of the trillions of microbes that hang out in our guts.

And Hsiao’s not the only creative mind whom I’d like to salute today. She’s among at least nine young researchers supported by NIH named to Forbes magazine’s annual “30 Under 30” list. The other up-and-coming scientists are: NIH intramural researchers Greg Alshuin (National Heart, Lung, and Blood Institute) and Anna F. Lau (NIH Clinical Center); NIH Early Independence Award winners Adam de la Zerda (Stanford University School of Medicine), Mitchell Guttman (California Institute of Technology), David Weinberg (University of California, San Francisco), and Daniela Witten (University of Washington); NIH Small Business Innovation Research awardee Rachel Haurwitz (Caribou Biosciences); and NIH-funded Graduate Student Fellow Zirui Song (Harvard Medical School).

Congratulations to all! I look forward to seeing how your work will help to shape the future of science and medicine.

(Image via Triff/Shutterstock.com)

Francis S. Collins, M.D., Ph.D. is the Director of the National Institutes of Health (NIH). In that role he oversees the work of the largest supporter of biomedical research in the world, spanning the spectrum from basic to clinical research. Dr. Collins is a physician-geneticist noted for his landmark discoveries of disease genes and his leadership of the international Human Genome Project, which culminated in April 2003 with the completion of a finished sequence of the human DNA instruction book. He served as director of the National Human Genome Research Institute at the NIH from 1993-2008.

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