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   Gut–brain link grabs neuroscientists   
   Idea that intestinal bacteria affect mental health gains ground.   
      
   Sara Reardon   
   12 November 2014   
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   Lester V. Bergman/Corbis   
   Feeding mice the bacterium Bacteroides fragilis can reverse autism-like   
   symptoms.   
   Companies selling ‘probiotic’ foods have long claimed that cultivating the   
   right gut bacteria can benefit mental well-being, but neuroscientists have   
   generally been sceptical. Now there is hard evidence linking conditions such   
   as autism and    
   depression to the gut’s microbial residents, known as the microbiome. And   
   neuroscientists are taking notice — not just of the clinical implications   
   but also of what the link could mean for experimental design.   
      
      
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   “The field is going to another level of sophistication,” says Sarkis   
   Mazmanian, a microbiologist at the California Institute of Technology in   
   Pasadena. “Hopefully this will shift this image that there’s too much   
   commercial interest and data from    
   too few labs.”   
      
   This year, the US National Institute of Mental Health spent more than US$1   
   million on a new research programme aimed at the microbiome–brain   
   connection. And on 19 November, neuroscientists will present evidence for the   
   link in a symposium at the annual    
   Society for Neuroscience meeting in Washington DC called ‘Gut Microbes and   
   the Brain: Paradigm Shift in Neuroscience’.   
      
   Although correlations have been noted between the composition of the gut   
   microbiome and behavioural conditions, especially autism1, neuroscientists are   
   only now starting to understand how gut bacteria may influence the brain. The   
   immune system almost    
   certainly plays a part, Mazmanian says, as does the vagus nerve, which   
   connects the brain to the digestive tract. Bacterial waste products can also   
   influence the brain — for example, at least two types of intestinal   
   bacterium produce the    
   neurotransmitter γ-aminobutyric acid (GABA)2.   
      
   The microbiome is likely to have its greatest impact on the brain early in   
   life, says pharmacologist John Cryan at University College Cork in Ireland. In   
   a study to be presented at the neuroscience meeting, his group found that mice   
   born by caesarean    
   section, which hosted different microbes from mice born vaginally, were   
   significantly more anxious and had symptoms of depression. The animals’   
   inability to pick up their mothers’ vaginal microbes during birth — the   
   first bacteria that they would    
   normally encounter — may cause lifelong changes in mental health, he says.   
      
   Similarly, a 2013 study from Mazmanian’s lab found that a mouse model with   
   some features of autism had much lower levels of a common gut bacterium called   
   Bacteroides fragilis than did normal mice3. The animals were also stressed,   
   antisocial and had    
   gastrointestinal symptoms often seen in autism. Feeding B. fragilis to the   
   mice reversed the symptoms. The group also found that the mice with these   
   symptoms had higher levels of a bacterial metabolite called 4-et   
   ylphenylsulphate (4EPS) in their blood,    
   and that injecting that chemical into normal mice caused the same behavioural   
   problems.   
      
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   The mechanism for these effects is still unclear. At the meeting, Mazmanian   
   will present data showing that feeding 4EPS to mice causes behavioural   
   problems only if the gut is leaky, presumably because that allows the chemical   
   to seep into the body    
   through the intestinal wall. That observation raises the possibility that some   
   people with autism could be supported with therapies, such as probiotics, that   
   target the gut instead of the brain, which is a much more complex and   
   inaccessible organ.   
      
   Yet even those at the forefront of the research remain sceptical that the   
   findings will translate into treatments for humans. The evidence that   
   probiotics affect human behaviour “is minimal to say the least”, Mazmanian   
   acknowledges. Still, he says, a    
   growing number of researchers are starting to look at some mental illnesses   
   through a microbial lens.   
      
   There are implications for basic research too. In another study to be   
   presented at the meeting, veterinarian Catherine Hagan at the University of   
   Missouri in Columbia compared the gut bacteria in laboratory mice of the same   
   genetic strain that had been    
   bought from different vendors. Their commensals differed widely, she found:   
   mice from the Jackson Laboratory in Bar Harbor, Maine, for instance, had fewer   
   bacterial types in their guts than did mice from Harlan Laboratories, which is   
   headquartered in    
   Indianapolis, Indiana.   
      
   Such differences could present a major complication for researchers seeking to   
   reproduce another lab’s behavioural experiments, Hagan says. When her team   
   transplanted bacteria from female Harlan mice into female Jackson mice, the   
   animals became less    
   anxious and had lower levels of stress-related chemicals in their blood. Hagan   
   notes that when a lab makes a mouse by in vitro fertilization, the animal will   
   pick up microbes from its surrogate mother, which might differ greatly from   
   those of its genetic    
   mother. “If we’re going to kill animals for research, we want to make sure   
   they’re modelling what we think they’re modelling,” she says.   
      
   Nature 515, 175–177 (13 November 2014) doi:10.1038/515175a   
   References   
      
   Kang, D.-W. et al. PLoS ONE 8, e68322 (2013).   
   ArticlePubMedChemPort   
   Show context   
   Barrett, E. et al. J. Appl. Microbiol. 113, 411–417 (2012).   
   ArticlePubMedChemPort   
   Show context   
   Hsiao, E. Y. et al. Cell 155, 1451–1463 (2013).   
   ArticlePubMedISIChemPort   
   Show context   
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   From nature.com   
   Microbiome therapy gains market traction   
   13 May 2014   
   Bacterium can reverse autism-like behaviour in mice   
   05 December 2013   
   Friendly bacteria cheer up anxious mice   
   30 August 2011   
   From elsewhere   
   Society for Neuroscience Annual Meeting 2014   
      
      
      
   http://www.nature.com/news/gut-brain-link-grabs-neuroscientists-1.16316   
      
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