From: sheriffcoltrane23x@gmail.com   
      
   A cultural revolution in the study of the gut microbiome   
      
      
   posted by news on december 14, 2015 - 9:00pm   
          
   (BOSTON) - It's estimated that as many as 1,000,000 Americans suffer from   
   inflammatory bowel diseases (IBD), such as ulcerative colitis and Crohn's   
   disease, which cause mild to severe symptoms that at best can be managed and   
   at worst can lead to life-   
   threatening complications. While abnormal immune responses are largely   
   responsible for these diseases, issues relating to gut microbiome, intestinal   
   epithelial cells, immune components and the gut's rhythmic peristalsis motions   
   can also contribute to and    
   exacerbate symptoms. But until now, scientists have been hard-pressed to   
   develop new therapies for treating IBDs due to their inability to replicate   
   the human gut microenvironment in the laboratory.   
   Now, a team at the Wyss Institute for Biologically Inspired Engineering at   
   Harvard University co-led by Wyss Institute Founding Director Donald Ingber,   
   M.D., Ph.D., and Wyss Core Faculty member James Collins, Ph.D., has leveraged   
   the Institute's    
   proprietary human-organs-on-chips technology to microengineer a model of human   
   intestinal inflammation and bacterial overgrowth in a human-gut-on-a-chip. The   
   advance, reported in Proceedings of the National Academy of Sciences (PNAS)   
   journal, for the    
   first time allows scientists to analyze how normal gut microbes and pathogenic   
   bacteria contribute to immune responses, and to investigate IBD mechanisms in   
   a controlled model that recapitulates human intestinal physiology.   
   "Chronic inflammation of the intestine is thought to be caused by abnormal   
   interactions between gut microbes, intestinal epithelial cells and the immune   
   system, but so far it has been impossible to determine how each of these   
   factors contribute to the    
   development of intestinal bowel disease," said Hyun Jung Kim, Ph.D., former   
   Wyss Technology Development Fellow and first author on the study, speaking   
   about the limitations of conventional in vitro and animal models of bacterial   
   overgrowth and    
   inflammation of the intestines.   
   The human gut-on-a-chip technology, however, provides an ideal m   
   croenvironment for mimicking the natural conditions of the human intestines in   
   a small-scaled, controllable in vitro platform. The human gut-on-a-chip was   
   first invented at the Wyss    
   Institute in 2012. Made of a clear flexible polymer about the size of a   
   computer memory stick, the hollow-channeled microfluidic device simulates the   
   physical structure, microenvironment, peristalsis-like motion waves and fluid   
   flow of the human    
   intestine.   
   In this latest advance reported in PNAS, the Wyss team showed that the human   
   gut-on-a-chip's unique ability to co-culture intestinal cells with living   
   microbes from the normal gut microbiome for an extended period of time, up to   
   two weeks, could allow    
   breakthrough insights into how the microbial communities that flourish inside   
   our GI tracts contribute to human health and disease.   
   "The discovery of the microbiome and its significance represents a huge   
   paradigm shift in our understanding of human health - there are more microbes   
   living on us and in us than our own cells," said Ingber, who is also the Judah   
   Folkman Professor of    
   Vascular Biology at Harvard Medical School and the Vascular Biology Program at   
   Boston Children's Hospital, and Professor of Bioengineering at the Harvard   
   John A. Paulson School of Engineering and Applied Science. "Until now, use of   
   traditional culture    
   methods and even more sophisticated organoid cultures have prevented the   
   microbiome from being studied beyond one or two days. With our human   
   gut-on-a-chip, we can not only culture the normal gut microbiome for extended   
   times, but we can also analyze    
   contributions of pathogens, immune cells, and vascular and lymphatic   
   endothelium, as well as model specific diseases to understand complex   
   pathophysiological responses of the intestinal tract."   
   "There is much to be learned about IBD, as well as how antibiotics impact the   
   microbiome," said Collins, who is also Termeer Profesor of Medical Engineering   
   and Science at the Massachusetts Institute of Technology. "This technology   
   enables one to study    
   in an isolated and controlled manner the complexity of the microbiome and the   
   role different microbial species play in health and disease. It is therefore a   
   highly valuable platform for discovery and clinical translation efforts."   
   Already the advance has revealed new discoveries into the inner workings of   
   the human intestinal tract and its immune responses. Four small proteins that   
   stimulate inflammation (called cytokines) were found to work in tandem to   
   trigger inflammatory    
   immune responses that damage and irritate the bowel. This discovery could open   
   a new potential therapeutic pathway to treating IBD by "blocking" these   
   cytokine proteins simultaneously.   
   The Wyss team also studied the role fluid flow and the wave-like peristaltic   
   movement of the gut plays in maintaining a dynamic equilibrium of the gut   
   microbiome, finding that absence of peristaltic movement can lead to rampant   
   overgrowth of bacteria    
   completely independent of changes in fluid flow. This could help explain why   
   some patients with IBD and other conditions develop bacterial overgrowth, such   
   as patients who develop ileus, which is a syndrome that can occur following   
   intestinal surgery    
   when there is a prolonged delay in the body's ability to resume normal   
   peristaltic motions.   
   The Wyss team believes the ability of the human gut-on-a-chip to culture the   
   microbiome with human gut cells also holds promise for the field of precision   
   medicine, where a patient's own cells and gut microbiota could one day be   
   cultured inside a gut-on-   
   a-chip for testing different therapies and identifying an individualized   
   treatment strategy.   
   "Previously the microbiome and its role in human health were largely defined   
   through study of their gene expression, but now, by being able to carry out   
   human experimentation in vitro relating to how the microbiome, human   
   intestinal cells and human    
   immune components interplay, we hope to gain a much deeper understanding of   
   underlying pathophysiological mechanisms that will hopefully lead to   
   development of new and more effective therapies," said Ingber.   
   Source: Wyss Institute for Biologically Inspired Engineering at Harvard   
      
      
      
   http://www.sciencecodex.com/a_cultural_revolution_in_the_study_o   
   _the_gut_microbiome-171804   
      
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