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   Neuroscientist News    
      
        
   Microbes, mood, and mental health    
      
      
   neuroinsights   
      
   SEPTEMBER 24, 2015    
      
      
   sp24 clostgut.jpg    
   gut microbes    
   Clostridium on gut lining. Color-enhanced scanning electon micrograph. Credit:   
   Med. Mic. Sciences Cardiff University / Wellcome Images    
      
      
      
      
   Everyone has had a "gut feeling"--some liken it to "butterflies" in the   
   stomach before a stressful event, while others deem it a type of   
   intuition--and scientists are bringing this age-old phenomenon into the   
   present-day lab in order to better understand    
   how mental health disorders arise and how they might be treated better.    
      
      
        
      
        
   Studies borne out of the Human Microbiome Project (HMP) have begun to tease   
   out the role the human gut microbiome plays in the development of a host of   
   diseases, including mental health disorders like anxiety and depression,   
   autism spectrum disorders,    
   and schizophrenia. While millions of Americans ----live with a mental health   
   disorder, treatment is often partial at best, ineffective at worst.   
   Understanding what causes these diseases in order to find more effective   
   treatments is a top priority for    
   researchers, doctors, and patients alike.    
      
   Begun in 2008, the HMP is a United States NIH-sponsored, nationwide endeavor   
   to categorize the trillions of microbes that live on and in the human body.   
   Made possible by advances in next-generation sequencing technologies,   
   metagenomics has allowed    
   researchers to sequence the bacterial strains that make their home in our   
   mouths, noses, skin, guts, and private parts. It turns out that bacterial   
   cells are 10 times more prevalent than our own bodily cells, and that there   
   are 100 times more bacterial    
   genes than human genes.1,2,3    
      
   Gastroenterologists have known for decades that the gut microbiome plays a   
   large role in maintaining our bodily functions through its secretions and   
   metabolites, mainly via immune signaling, endocrine signaling, and the enteric   
   nervous system--    
   neurotransmitters produced by gut bacteria.4 This cross-talk between gut and   
   brain takes place through the vagus nerve, a cranial nerve that conducts a   
   long and winding path from the brain to many different organs, including the   
   gut. This system enables    
   the parasympathetic nervous system to maintain homeostasis.    
      
      
        
      
        
   In the past 10 years, a growing number of preclinical (mice) studies have   
   demonstrated that "bidirectional signaling" between the brain and the gut   
   microbiome can actually affect the brain's neurochemistry and subsequently,   
   our emotions and behavior. To    
   be sure, it's a paradigm shift in neuroscience, and some believe it will   
   change the way psychiatrists ultimately treat mental health disorders, says   
   Dr. John Cryan, a leading researcher in the field. Disorders once believed to   
   be conditions of the brain    
   might actually be linked to--maybe even exacerbated by--an imbalance in the   
   microbial community of the gut.    
      
   "We've known for a long time that the gut-brain axis is very important for   
   regulating homeostasis," Cryan, a neuroscientist at the University College   
   Cork in Ireland, says. So, why wouldn't it be possible for the gut microbiome   
   to influence    
   neurochemistry? While "psychobiotics," a term coined by Cryan and Dr. Ted   
   Dinan,5 "is still very much [in] its infancy," Cryan believes it will have an   
   impact on how psychiatrists treat these diseases in the future. Psychobiotics   
   harness the idea that    
   when administered in the right amount, certain bacteria that normally colonize   
   the gut will have a positive effect on mental health, he says. "You look at   
   the last time you had food poisoning, you felt malaise. All of the symptoms   
   apply in mood disorders    
   like depression, all the same physical symptoms are analogous--and that's   
   driven by bacteria."    
      
   Bidirectional signaling    
      
   The blood-brain barrier (BBB) separates the blood circulating throughout the   
   body from the brain, allowing only certain molecules to cross. While more   
   studies are showing a link between the presence of certain bacteria and   
   altered gene expression in the    
   brain, the mechanisms are still unknown. In other words, we don't know yet how   
   gut bacteria communicate with the brain. Is it directly through metabolites   
   that cross the BBB? Through downstream signaling? Both?    
      
   Bidirectional signaling, says Dr. Christopher Lowry, an associate professor in   
   the Department of Integrative Physiology at the University of Colorado   
   Boulder, means that the "brain can influence the gut microbiota, and that,   
   conversely, the gut    
   microbiota can influence the brain." Gut microbiota secrete neuroactive   
   metabolites, including the neurotransmitters dopamine, serotonin, and   
   gamma-aminobutyric acid, or GABA. These microbes also release molecules that   
   can change neurochemistry.    
   Additionally, they can cause localized inflammation, whereby immune cells   
   release immune signaling molecules--another way to alter downstream signaling   
   and host immunity. "These immune signaling molecules can then alter brain   
   function, either through    
   influence on sensory nerves, or through accessing the brain directly," Lowry   
   says.    
      
   Mental health and gut microbes    
      
   Up until recently, the vagus nerve was known only as the "parasympathetic   
   highway." However, more studies are showing a link between an altered   
   microbial community and changes in mental health, like anxiety and depression.   
   While it has been known for a    
   long time that a large proportion of our neurotransmitters like dopamine and   
   serotonin are created in the intestines, neuroscientists are just beginning to   
   learn how our microbiota actually use these molecules to communicate with the   
   brain.    
      
   Cryan's groundbreaking paper appearing in PNAS in 2011 showed that indeed,   
   there was bidirectional signaling between the gut and the brain via the vagus   
   nerve that could lead to changes in mental health. 6 In the animal study, he   
   and his collaborators    
   showed that chronic treatment with Lactobacillus rhamnosus (bacteria normally   
   found in the gut) caused changes in GABA expression in the brain compared to   
   control mice. GABA acts as a major inhibitory, or calming, neurotransmitter.   
   L. rhamnosus, they    
   found, "reduced stress-induced corticosterone and anxiety- and d   
   pression-related behavior" in the mice. Importantly, the behavioral effects   
   were absent in mice whose vagus nerve had been cut.    
      
      
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