<P>Spring 2014 | UCSF MAGAZINE15 You used to have to travel to the coast of Palau to mine the ocean sediment for drugs. Now we can just check our gut! – Michael Fischbach BACTERIA BY PRESCRIPTION Clearly, Lactobacillus johnsonii has a long and proven history of having a positive therapeutic effect on the body. But what might a microbial agent look like if it were crafted specifically as an asthma drug? The first consideration would be when to intervene. Though diseases such as childhood allergic asthma do not manifest clinically until a child is about 6 years old, Lynch believes that their genesis lies in events that occur very early in life. Essentially, we are trying to build and sustain an appropriate microbial bioreactor in the infant gut, says Lynch. We would likely begin in early life, from birth, with supplementation strategies that manipulate the microbial community in a way that benefits the child. Such a therapeutic might take the form of a dehydrated but viable microbial species mix, not unlike current probiotic supplements, which would be added daily to the infants diet. It would be given from birth through the first few months of life, since that seems to be the critical period in the assembly of a hardy, healthy microbial community. Even after the right microbes are introduced, they would have to be maintained to give them staying power. We also need to investigate nutritional interventions to promote the longevity of these organisms that we are introducing into the system, explains Lynch. These are known as prebiotics – the complex carbohydrates and fibers that fermentative organisms, like the Lactobacilli, prefer to gnaw on. There are prebiotics on store shelves right now, but, like the probiotics next to them, they are fairly blunt tools. The prebiotics of the future will be specifically tailored to the nutritional preferences of the bacteria that are being used as therapeutic agents. Right now, prebiotics are typically broad-spectrum complex carbs that increase the presence of certain beneficial organisms that readily metabolize them, says Lynch. But this will only occur if those organisms are present in the first place; many good bacteria are depleted with dis- ease and inflammation. BEST BET The treatment from the human microbiome thats closest to being realized is for a condition caused by a bacterium called Clostridium dif?cile. Its a rare and painful affliction of the bowels that typically occurs as a result of antibiotic treatment. Antibiotic use depletes the gut of some of the important components of its community and allows for overgrowth of C. dif?cile, a pathogenic bacterium, explains Andrew Goldberg. This causes gastrointestinal distress, diarrhea, and fluid loss – and can be fatal. The current protocol calls for still more antibiotics. However, recent research done in the Netherlands may ultimately change that. In a well- controlled trial of patients with C. dif?cile, half were given antibiotics and the other half received fecal transplants from a healthy individual, typically someone in the same household who had been exposed to the same environmental bacteria. The study was stopped before comple- tion, says Goldberg, because the effectiveness of the fecal transplant was so high that it was felt to be unethical to continue the standard treat- ment in those patients. Physicians believe that this finding will also have very positive implications for patients with other gastrointestinal diseases, such as inflammatory bowel disease. There are currently several ongoing trials of fecal transplantation in the United States. If the efficacy of the treatment proves to be as good as or better than the current protocol for patients with recurrent C. dif?cile, the FDA would likely fast-track the fecal transplant, says Lynch, making it immediately available. Until other treatments derived from the human microbiome are honed into viable therapeutics, antibiotics will likely remain the treat- ment of choice for many of the illnesses that plague us. At first glance, the two strategies appear to approach such illnesses from opposite directions: Antibiotics kill the bad actors, while probiotics and prebiot- ics bolster defenses to restore order. And some argue that antibiotics take out the good with the bad, potentially pushing a microbial community further off kilter, as is the case with C. dif?cile. We found in mice that antibiotics actually made it easier for a pathogen to grab hold and to create a disease state, says Goldberg, primarily because the good actors hadnt survived to intervene. Yet Fischbach predicts that, ultimately, the two approaches will be combined. In the future, he believes, antibiotics will likely be followed by what he calls a probiotic-chaser, to help re- assemble the microbial community, while prebiotics may be used for health maintenance. In the meantime, the field needs to figure out exactly how microbes engage our immune system to make us well, according to Fischbach. Only then will we be able to make effective use of a resource that has been, quite literally, under our noses as long as we have walked the planet. Drug companies spend an enormous amount of time and money trying to develop a single drug and get it into your gut at an appre- ciable concentration, observes Fischbach. Yet we have bacteria already in our gut, probably producing dozens of drugs and affecting our biology and health in profound, very specific ways. Understanding how that works, I hope, is the legacy of what we are doing in this field right now.</p> <UL><LI><a href="http://www.mzines.net/publication/618/aelvmorax/1/1/">Front-Cover</a></LI> <LI><a href="http://www.mzines.net/publication/618/aelvmorax/2/2/">Inside-Front-Cover</a></LI> <LI><a href="http://www.mzines.net/publication/618/aelvmorax/3/3/">Page-1</a></LI> <LI><a href="http://www.mzines.net/publication/618/aelvmorax/4/4/">Page-2</a></LI> <LI><a href="http://www.mzines.net/publication/618/aelvmorax/5/5/">Page-3</a></LI> <LI><a href="http://www.mzines.net/publication/618/aelvmorax/6/6/">Page-4</a></LI> <LI><a href="http://www.mzines.net/publication/618/aelvmorax/7/7/">Page-5</a></LI> <LI><a href="http://www.mzines.net/publication/618/aelvmorax/8/8/">Page-6</a></LI> <LI><a href="http://www.mzines.net/publication/618/aelvmorax/9/9/">Page-7</a></LI> <LI><a href="http://www.mzines.net/publication/618/aelvmorax/10/10/">Page-8</a></LI> <LI><a href="http://www.mzines.net/publication/618/aelvmorax/11/11/">Page-9</a></LI> <LI><a href="http://www.mzines.net/publication/618/aelvmorax/12/12/">Page-10</a></LI> <LI><a href="http://www.mzines.net/publication/618/aelvmorax/13/13/">Page-11</a></LI> <LI><a href="http://www.mzines.net/publication/618/aelvmorax/14/14/">Page-12</a></LI> <LI><a href="http://www.mzines.net/publication/618/aelvmorax/15/15/">Page-13</a></LI> <LI><a href="http://www.mzines.net/publication/618/aelvmorax/16/16/">Page-14</a></LI> <LI><a href="http://www.mzines.net/publication/618/aelvmorax/17/17/">Page-15</a></LI> <LI><a href="http://www.mzines.net/publication/618/aelvmorax/18/18/">Page-16</a></LI> <LI><a href="http://www.mzines.net/publication/618/aelvmorax/19/19/">Page-17</a></LI> <LI><a href="http://www.mzines.net/publication/618/aelvmorax/20/20/">Page-18</a></LI> <LI><a href="http://www.mzines.net/publication/618/aelvmorax/21/21/">Page-19</a></LI> <LI><a href="http://www.mzines.net/publication/618/aelvmorax/22/22/">Page-20</a></LI> <LI><a href="http://www.mzines.net/publication/618/aelvmorax/23/23/">Page-21</a></LI> <LI><a href="http://www.mzines.net/publication/618/aelvmorax/24/24/">Page-22</a></LI> <LI><a href="http://www.mzines.net/publication/618/aelvmorax/25/25/">Page-23</a></LI> <LI><a href="http://www.mzines.net/publication/618/aelvmorax/26/26/">Page-24</a></LI> <LI><a href="http://www.mzines.net/publication/618/aelvmorax/27/27/">Page-25</a></LI> <LI><a href="http://www.mzines.net/publication/618/aelvmorax/28/28/">Page-26</a></LI> <LI><a href="http://www.mzines.net/publication/618/aelvmorax/29/29/">Page-27</a></LI> <LI><a href="http://www.mzines.net/publication/618/aelvmorax/30/30/">Page-28</a></LI> <LI><a href="http://www.mzines.net/publication/618/aelvmorax/31/31/">Page-29</a></LI> <LI><a href="http://www.mzines.net/publication/618/aelvmorax/32/32/">Page-30</a></LI> <LI><a href="http://www.mzines.net/publication/618/aelvmorax/33/33/">Page-31</a></LI> <LI><a href="http://www.mzines.net/publication/618/aelvmorax/34/34/">Page-32</a></LI> <LI><a href="http://www.mzines.net/publication/618/aelvmorax/35/35/">Page-33</a></LI> <LI><a href="http://www.mzines.net/publication/618/aelvmorax/36/36/">Page-34</a></LI> <LI><a href="http://www.mzines.net/publication/618/aelvmorax/37/37/">Page-35</a></LI> <LI><a href="http://www.mzines.net/publication/618/aelvmorax/38/38/">Page-36</a></LI> <LI><a href="http://www.mzines.net/publication/618/aelvmorax/39/39/">Page-37</a></LI> <LI><a href="http://www.mzines.net/publication/618/aelvmorax/40/40/">Page-38</a></LI> <LI><a href="http://www.mzines.net/publication/618/aelvmorax/41/41/">Page-39</a></LI> <LI><a href="http://www.mzines.net/publication/618/aelvmorax/42/42/">Page-40</a></LI> <LI><a href="http://www.mzines.net/publication/618/aelvmorax/43/43/">Page-41</a></LI> <LI><a href="http://www.mzines.net/publication/618/aelvmorax/44/44/">Page-42</a></LI> <LI><a href="http://www.mzines.net/publication/618/aelvmorax/45/45/">Page-43</a></LI> <LI><a href="http://www.mzines.net/publication/618/aelvmorax/46/46/">Page-44</a></LI> <LI><a href="http://www.mzines.net/publication/618/aelvmorax/47/47/">Page-45</a></LI> <LI><a href="http://www.mzines.net/publication/618/aelvmorax/48/48/">Page-46</a></LI> <LI><a href="http://www.mzines.net/publication/618/aelvmorax/49/49/">Page-47</a></LI> <LI><a href="http://www.mzines.net/publication/618/aelvmorax/50/50/">Page-48</a></LI> <LI><a href="http://www.mzines.net/publication/618/aelvmorax/51/51/">Page-49</a></LI> <LI><a href="http://www.mzines.net/publication/618/aelvmorax/52/52/">Back-Cover</a></LI> <LI><a href="http://www.mzines.net/publications/618/x/sitemap.xml" target="_blank">site map</a></LI> </UL>


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