From: hound23x@gmail.com   
      
   This article is from the In-Depth Report Innovations in the Microbiome   
      
      
   New Drugs May Come from Microbes in Our Guts   
      
      
   The microbes that live in our gut could prove to be a fertile source for new   
   antibiotics and other useful drugs   
      
   Feb 17, 2015 |By Michael Fischbach   
   **   
      
   One third of the drugs used in the clinic today were synthesized not by   
   chemists or biotechnologists but by plants or microorganisms. Most of these   
   "natural products" come from a few genera of soil and marine bacteria that   
   have long been known for their    
   prolific chemistry. In addition to antibiotics, that group includes compactin,   
   the grandfather of the entire drug class of statins, which Japanese   
   microbiologists cultured from mold in rice sampled from a grain shop in Kyoto;   
   sirolimus, an    
   immunosuppressant used to prevent organ rejection following transplants, which   
   Brazilian scientists uncovered in soil samples from Easter Island; and   
   doxorubicin, a widely used anticancer drug, which Italian researchers isolated   
   from the soil that    
   surrounds Castel del Monte, a 13th-century castle.   
   The classical process of discovering drugs from microorganisms suffers from   
   two challenges: it is slow--microbial isolates are painstakingly cultivated   
   and tested one by one--and it yields limited possibilities for new drugs. We   
   know about the limits    
   from pioneering efforts to sequence the genomes of a few well-known   
   drug-producing bacteria. These efforts reveal a gap between the small number   
   of natural products each strain makes when cultured in the laboratory and the   
   large number of drug-producing    
   genes in each genome (enough to make three dozen or more molecules). The   
   reasons for this deficit are not well understood but probably have something   
   to do with the artificial conditions of lab culture, in which each species is   
   typically cultivated in    
   isolation.   
   Recent advances have raised the prospect of a resurgence in natural-product   
   discovery, albeit from an unanticipated source. Our lab has developed a new   
   algorithm to scan bacterial genome sequences for drug-producing genes. This   
   tool accelerates the    
   process of natural-product discovery by making it possible to perform the   
   hardest step on the computer: prioritizing bacterial species and even specific   
   gene clusters that are most likely to encode a novel drug. Using this   
   approach, we found, to our    
   surprise, a large number of drug-producing genes in the human microbiota, a   
   group of organisms that has not previously been mined for biologically active   
   small molecules. Other labs have developed complementary techniques based on   
   recent advances in    
   synthetic biology. A set of drug-producing genes can now be "refactored" in a   
   way that greatly increases the likelihood that the genes can be expressed in   
   an alternative, lab-friendly host.   
   These advances suggest two tantalizing prospects for developing drugs from the   
   microbiome. The first would be to systematically mine the microbiome for new   
   medicines, building on our unanticipated finding that gut, skin, oral and   
   urogenital bacteria may    
   be prolific producers of natural products. The second possibility is to use   
   the microbes themselves as drugs--most likely in the form of an artificial   
   bacterial community. Recent clinical efforts have shown that fecal   
   transplantation is remarkably safe    
   and engraftment of the new community surprisingly common, suggesting that a   
   single consortium might engraft and function in a large subset of the human   
   population. If a well-studied community of bacteria were used instead of a   
   fecal sample, however, the    
   cocktail of small molecules it produces could be optimized for a specific   
   condition. Research suggests that such an approach might hold particular   
   promise for the treatment of inflammatory bowel disease and perhaps metabolic   
   disorders.   
   Small molecules that mediate many of the biological effects of the microbiota   
   on the host could ultimately prove to be one of the richest sources for new   
   drugs.   
      
   ABOUT THE AUTHOR(S)   
   Michael Fischbach is an assistant professor in the department of   
   bioengineering and therapeutic sciences at the University of California, San   
   Francisco.   
   This article was originally published with the title "Treasure Trove."   
      
   http://www.scientificamerican.com/article/new-drugs-may-come-fro   
   -microbes-in-our-guts/?WT.mc_id=SA_HLTH_20150317   
      
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