(Or It Takes Guts to Alter a Brain Part II)
The term gut microbiota-brain axis describes the multiple mechanisms involved in microbe-to-brain interactions. These mechanisms include endocrine, immune, and neural signaling. Last year I wrote a post entitled “The Vagus Nerve”, which examined the role of the vagus nerve (neural pathway!) in the gut microbiota-brain axis. To re-cap, researchers from the University of College Cork and McMaster University found that an anxiety-reducing probiotic failed to impact the behavior of mice lacking a functional vagus nerve. No vagus nerve = no microbe-brain regulation. While the vagus nerve serves as an important component of the gut microbiota-brain axis, this post highlights an interesting story regarding vagus-independent mechanisms.
Chronic gut inflammation has increasingly been linked with psychiatric disorders. Indeed, people diagnosed with inflammatory bowel disease have a much higher risk of depression and anxiety. For more information, check out the link to Foster and Neufeld’s Gut–brain axis: how the microbiome influences anxiety and depression (see below). In 2010, Premysl Bercik and colleagues reported that chronic gut inflammation increased anxiety-like behavior in mice. Mice with gastric inflammation had increased levels of cytokines. Produced by immune cells, cytokines are small proteins that drive inflammatory responses. In addition, these mice had decreased levels of brain-derived neurotropic factor (BDNF). BDNF is an abundant protein found within the brain that protects and maintains neurons. In addition, alterations of BDNF levels have been linked with depression. To examine how the inflamed gut microbiota impacted behavior, a subset of mice received a vagotomy (snipped vagus nerve). However, the vagotomy did not impact anxiety-like behavior! Next, researchers treated the “anxious” mice with anti-inflammatory drugs. Drug treatment reduced anxiety-like behavior and decreased levels of pro-inflammatory cytokines, but did not impact BDNF levels. Surprisingly, treatment with the probiotic Bifidobacterium longum also decreased anxiety-like behavior and normalized BDNF levels. This microbial therapy, however, did not impact cytokine levels. Weird, right?! So how does the inflamed gut microbiota impact the brain? And how did the bacteria B. longum change behavior and neural chemistry? Short answer—we don’t know the exact mechanisms and there are probably many mechanisms involved (immune—cytokines, neural—BDNF, and more…). Researchers are continuing to discover the ways that microbes impact our mental health. I’m excited to learn more.
Stay tuned: in Part III, I’ll continue discussing the microbe/brain connection. Happy Exploring!
Microbes and Depression: http://www.psych.ufl.edu/~dpdevine/bb/pelham.pdf