From: mjs23x@gmail.com   
      
   Human Gut Microbe Transplant Alters Mouse Behavior    
   Fecal transplants from humans with irritable bowel syndrome and anxiety into   
   mice lead to similar symptoms and anxiety-like behavior in the rodents,   
   researchers report.      
      
   By Anna Azvolinsky | March 1, 2017    
      
    Image No 1    
   WIKICOMMONS, RAMA    
   Researchers have been unable to pinpoint the causes of irritable bowel   
   syndrome (IBS), a heterogeneous disorder characterized by both diarrhea and   
   constipation. IBS can also be accompanied by symptoms associated with anxiety   
   and depression and, thus, is    
   thought to affect gut-brain communication.    
      
   In a study published today (March 1) in Science Translational Medicine,   
   researchers from McMaster University in Ontario, Canada, and their colleagues   
   demonstrate evidence of a direct link between gut microbes and the symptoms   
   and behaviors of IBS in mice.   
    Germ-free mice that received fecal microbiota from patients with IBS mimicked   
   the symptoms of the disorder, including anxiety-like behaviors, the team   
   reported.    
      
   “This [study] is a wonderful demonstration for the functionality of the   
   microbiota, showing gut bacteria from subjects with irritable bowel syndrome   
   can induce both gastrointestinal issues, as well as the anxiety that is   
   co-morbid with IBS,” Sarkis    
   Mazmanian, a professor of microbiology at Caltech who was not involved in the   
   work, wrote in an email to The Scientist.    
      
   “The field can often get stuck in simply cataloging gut microbes and asking   
   which species are present or absent during a specific condition. However, this   
   study takes the next steps and addresses how distinct populations of bacteria   
   can directly    
   influence a number of physiological outcomes that are pertinent to the   
   illness,” wrote Timothy Sampson, a postdoc in the Mazmanian lab who also was   
   not involved in the work.    
      
   McMaster gastrointestinal disease researcher Premysl Bercik and colleagues   
   used stool samples from eight patients with a history of IBS with diarrhea for   
   at least two years, as well as from five healthy individuals, to colonize the   
   guts of germ-free mice.   
    A portion of each individual’s fecal sample was transplanted into 10   
   different mice. “We know there is a constant communication between the gut   
   and the brain, and in IBS and other functional bowel disorders, this   
   communication is altered,” Bercik    
   told The Scientist. “We wanted to understand how the gut microbiota fits   
   in.”    
      
   After three weeks, the researchers assessed the composition of each rodent’s   
   gut microbiota and compared the bacterial profiles to those obtained directly   
   from the individuals’ fecal samples. The mice that received fecal   
   transplants from people with    
   IBS showed both faster movement of luminal contents through the    
   astrointestinal tract and higher gut permeability compared to mice that   
   received a fecal transplant from a healthy human donor. The team also   
   identified types and levels of seven    
   metabolites that differed between the two groups of mice that received   
   transplants from healthy donors or from people with IBS, including several   
   forms of lysophosphatidylcholine and phosphatidylserine, which were increased   
   and decreased, respectively,    
   in mice colonized with bacteria from IBS patients.    
      
   “The authors’ experimental setup and analyses are really thorough. They   
   included many animals in their experiments to arrive at their conclusions,”   
   said June Round, an assistant professor of pathology at the University of Utah   
   School of Medicine    
   who was not involved in the work.    
      
   The team next examined whether the anxiety-associated behaviors linked to IBS   
   could also be transmitted to the mice via transplanted gut microbes. The   
   researchers used two well-established tests to measure anxiety-like behaviors   
   in the mice: the amount    
   of time it took for an animal to step down from an elevated platform to   
   explore its environment, and the time an animal spent in the dark versus   
   exploring a well-lit chamber.    
      
   Mice colonized with bacteria from patients with IBS who did not have anxiety   
   symptoms and from healthy individuals did not exhibit anxiety-like behaviors,   
   while mice colonized with bacteria from IBS patients with anxiety symptoms   
   showed similar symptoms    
   in both behavioral tests. Those mice colonized with gut bacteria from IBS   
   patients also displayed signs of immune activation associated with low-grade   
   inflammation compared to mice colonized with bacteria from healthy   
   individuals.    
      
   One caveat of the experimental approach, according to Round, is that there are   
   likely organisms that contribute to IBS that are lost during transplantation   
   from human to mouse. These organisms might be under-represented bacterial   
   species not captured by    
   current sequencing technologies.    
      
   Bercik agreed. “Commonly, the organisms we measure are the ones that are   
   most numerous but it may not be the most common ones that are most influential   
   to patients’ symptoms,” he said.    
      
   For Sampson, the behavioral outcomes were not that surprising. “We have   
   known for some time that different populations of gut microbes, derived from   
   mice, can exert differential effects on anxiety phenotypes in those mice.   
   However, this study is able    
   to identify distinct bacterial taxa and even specific bacterial metabolites   
   derived from humans that correlate with how the animals perform in anxiety   
   measures.”    
      
   “Our work shows that the gut microbiota from patients with IBS has the   
   capacity to induce the same gut dysfunction in mice that we see in the   
   patient, suggesting that the gut bacteria are at least one main contributor to   
   IBS,” said Bercik.    
      
   With a list of potential bacterial species—and their associated   
   metabolites—that might contribute to IBS, the team is trying to zero in on   
   causative factors.    
      
   Mazmanian is optimistic about the direction of this research. “This research   
   may lead to identification of bacteria or bacterial products that may mediate   
   gut-brain interactions, and potentially inform novel development of treatment   
   avenues for IBS and    
   its associated symptoms,” he wrote.    
      
   G. De Palma et al., “Transplantation of fecal microbiota from patients with   
   irritable bowel syndrome alters gut function and behavior in recipient   
   mice,” Science Translational Medicine, doi:10.1038/nature21356, 2017.    
      
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