From: drarwingnuttephd@gmail.com   
      
   Gut Bacteria Play Key Role in Immune System   
   Published: Oct 16, 2008   
      
   Download Complimentary Source PDF    
      
   By  Michael Smith , North American Correspondent, MedPage Today   
   Reviewed by Dori F. Zaleznik, MD; Associate Clinical Professor of Medicine,   
   Harvard Medical School, Boston   
   save|AA   
   Dan Littman, M.D., Ph.D.   
   Professor of Molecular Immunology NYU School of Medicine   
   Action Points   
   Explain to interested patients that commensal intestinal bacteria play   
   important roles in maintaining health by aiding in digestion and helping to   
   ward off pathogens, among other things.   
   Note that this study suggests that specific types of commensal bacteria also   
   play a role in stimulating production of cells of the immune system, which may   
   open the door to new ways to treat inflammatory diseases.   
   NEW YORK, Oct. 16 -- The development of key immune cells is triggered by   
   specific types of bacteria in the gut, a finding that could lead to new   
   therapies for diseases of inflammation, researchers here said.    
      
   In the absence of bacteria from the cytophaga-flavobacter-bacteroidetes phylum   
   -- or CFB, for short -- the immune cells are also not present, at least in   
   mice, according to Dan Littman, M.D., Ph.D., of New York University, and   
   colleagues.    
      
   On the other hand, when bacteria from that phylum are introduced into animals   
   lacking them, the result is a restoration of Th17 immune cells, Dr. Littman   
   and colleagues said in the Oct. 16 issue of Cell Host & Microbe.   
      
   Th17 cells -- CD4-positive cells that have a potent pro-inflammatory effect--   
   are normally in a balance with another population of CD4-positive cells,   
   dubbed Foxp3-positive cells, which play a regulatory role in the immune system.   
      
   The finding that different populations of gut bacteria influence the   
   development of the Th17 cells could open the door to new treatments for   
   inflammatory bowel disease and other illnesses of the immune system, Dr.   
   Littman said.   
      
   "The number of inflammatory diseases known to involve T helper 17 cells seems   
   to be growing every week," Dr. Littman said. For that reason, he and   
   colleagues have been studying the development of the cells.   
      
   In a series of experiments in mice, he and colleagues showed that a complete   
   absence of so-called commensal bacteria in the small intestine leads to a lack   
   of Th17 cells. Commensal bacteria are the useful organisms that help in   
   digestion and aid in    
   protecting against pathogens.   
      
   In commercially available germ-free mice -- which have a complete lack of   
   bacteria and fungi -- Th17 cells were not detectable and the presence of   
   interleukin-17 secreted by the cells was at the limit of detectability.   
      
   On the other hand, Foxp3-positive cells were increased, even though the total   
   number of CD4-positive cells was two- to three-fold lower than normal.   
      
   When the researchers used a cocktail of antibiotics to destroy the commensal   
   bacteria, they found that the proportion of Th17 cells fell by half after four   
   weeks of treatment. In mice given the cocktail from birth, the proportion of   
   Th17 cells was 80%    
   lower than in control animals by six to eight weeks of age.   
      
   Dr. Littman and colleagues then broke out individual antibiotics to see if   
   they influenced the number of Th17 cells. Vancomycin (Vancocin) -- which   
   mainly attacks Gram-positive bacteria -- had a similar effect to the whole   
   cocktail.   
      
   On the other hand, antibiotics that attack anaerobic and Gram-negative   
   bacteria had little effect.   
      
   More than 90% of the commensal intestinal bacteria -- in both mice and humans   
   -- are either members of the Gram-negative CFB phylum or the Gram-positive   
   Firmicutes phylum, the researchers noted.   
      
   A series of experiments showed that members of the CFB phylum are not present   
   in animals that lack Th17 cells, Dr. Littman and colleagues said, although   
   those from the Firmicutes phylum remain.   
      
   The researchers found that some strains of experimental mice have intestinal   
   bacteria but no Th17 cells. Comparing those animals with other strains, Dr.   
   Littman and colleagues discovered that CFB bacteria were associated with the   
   creation of Th17 cells.   
      
   Exactly which members of the CFB phylum induce the cells is currently under   
   study, the researchers said.   
      
   "It's not the amount of microbial flora but the kind of microbial flora that   
   seems to count," Dr. Littman said.   
      
   The findings point to ways of manipulating the immune system, commented   
   Yasmine Belkaid, Ph.D., of the National Institutes of Health, one of the   
   sponsors of the study.   
      
   "There is more and more evidence that gut flora have a tremendously important   
   influence on human health," Dr. Belkaid said in a statement. "This new study   
   is the first report that has associated a defined set of gut flora with the   
   induction of specific    
   immune cells."   
      
   The study was supported by the Howard Hughes Medical Institute, the Helen and   
   Martin Kimmel Center for Biology and Medicine, the Sandler Program for Asthma   
   Research, the National Gnotobiotic Rodent Resource Center, the NIH, the   
   Phillip Morris Foundation,    
   and the Canadian Institutes of Health Research. The researchers did not report   
   any conflicts.   
      
      
   http://www.medpagetoday.com/InfectiousDisease/GeneralInfectiousDisease/11343   
      
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